Medicine › Nephrology

Chronic Kidney Disease and Diabetes

Works Count: 32260

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Description

This cluster of papers focuses on chronic kidney disease (CKD) and its various aspects including estimation of glomerular filtration rate, association with cardiovascular disease, diabetic nephropathy, renal insufficiency, albuminuria, fibrosis, TGF-ß signaling, and the global burden of CKD. It covers topics related to diagnosis, management, risk factors, and implications of CKD on mortality and cardiovascular outcomes.

Keywords

Chronic Kidney Disease; Glomerular Filtration Rate; Cardiovascular Disease; Diabetic Nephropathy; Renal Insufficiency; Albuminuria; Fibrosis; TGF-ß; Obesity-related Glomerulopathy; Global Burden

Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis

2010-05-18

Kunihiro Matsushita , Marije van der Velde , Brad C. Astor +7 more

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The Kidney: Structure and Function in Health and Disease

1952-03-01

Homer W. Smith

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The Glomerular Permeability Determined by Dextran Clearance Using Sephadex Gel Filtration

1968-01-01

C. E. Mogensen

A method is described for measuring glomerular permeability by dextran clearance using Sephadex gel filtration technique. Clearance is shown to be a function of molecular size, decreasing with increasing molecular … A method is described for measuring glomerular permeability by dextran clearance using Sephadex gel filtration technique. Clearance is shown to be a function of molecular size, decreasing with increasing molecular weight. At a mol. weight higher than 55,000, the clearance is very low and approximately zero, while it averages 95 ml per minute at a mol. weight of 15,000. If plotted in a log.log. graph, a linear relation is found between clearance and molecular weight. In a semilog. graph, however, with clearance plotted against log. Stokes radius, the relation is also linear, with a slight deflection in the high molecular part, however.

The definition, classification, and prognosis of chronic kidney disease: a KDIGO Controversies Conference report

2010-12-08

Andrew S. Levey , Paul E. de Jong , Josef Coresh +6 more

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Development and progression of nephropathy in type 2 diabetes: The United Kingdom Prospective Diabetes Study (UKPDS 64)

2003-01-01

Amanda Adler , Richard Stevens , Susan E. Manley +4 more

Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third national health and nutrition examination survey

2002-12-24

Josef Coresh , Brad C. Astor , Tom Greene +2 more

Cellular and molecular mechanisms of renal fibrosis

2011-10-18

Youhua Liu

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Definition and classification of chronic kidney disease: A position statement from Kidney Disease: Improving Global Outcomes (KDIGO)

2005-05-06

Andrew S. Levey , Kai‐Uwe Eckardt , Yusuke Tsukamoto +7 more

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Prevalence of Chronic Kidney Disease in the United States

2007-11-06

Josef Coresh , Elizabeth Selvin , Lesley A. Stevens +5 more

ContextThe prevalence and incidence of kidney failure treated by dialysis and transplantation in the United States have increased from 1988 to 2004. Whether there have been changes in the prevalence … ContextThe prevalence and incidence of kidney failure treated by dialysis and transplantation in the United States have increased from 1988 to 2004. Whether there have been changes in the prevalence of earlier stages of chronic kidney disease (CKD) during this period is uncertain.ObjectiveTo update the estimated prevalence of CKD in the United States.Design, Setting, and ParticipantsCross-sectional analysis of the most recent National Health and Nutrition Examination Surveys (NHANES 1988-1994 and NHANES 1999-2004), a nationally representative sample of noninstitutionalized adults aged 20 years or older in 1988-1994 (n = 15 488) and 1999-2004 (n = 13 233).Main Outcome MeasuresChronic kidney disease prevalence was determined based on persistent albuminuria and decreased estimated glomerular filtration rate (GFR). Persistence of microalbuminuria (>30 mg/g) was estimated from repeat visit data in NHANES 1988-1994. The GFR was estimated using the abbreviated Modification of Diet in Renal Disease Study equation reexpressed to standard serum creatinine.ResultsThe prevalence of both albuminuria and decreased GFR increased from 1988-1994 to 1999-2004. The prevalence of CKD stages 1 to 4 increased from 10.0% (95% confidence interval [CI], 9.2%-10.9%) in 1988-1994 to 13.1% (95% CI, 12.0%-14.1%) in 1999-2004 with a prevalence ratio of 1.3 (95% CI, 1.2-1.4). The prevalence estimates of CKD stages in 1988-1994 and 1999-2004, respectively, were 1.7% (95% CI, 1.3%-2.2%) and 1.8% (95% CI, 1.4%-2.3%) for stage 1; 2.7% (95% CI, 2.2%-3.2%) and 3.2% (95% CI, 2.6%-3.9%) for stage 2; 5.4% (95% CI, 4.9%-6.0%) and 7.7% (95% CI, 7.0%-8.4%) for stage 3; and 0.21% (95% CI, 0.15%-0.27%) and 0.35% (0.25%-0.45%) for stage 4. A higher prevalence of diagnosed diabetes and hypertension and higher body mass index explained the entire increase in prevalence of albuminuria but only part of the increase in the prevalence of decreased GFR. Estimation of GFR from serum creatinine has limited precision and a change in mean serum creatinine accounted for some of the increased prevalence of CKD.ConclusionsThe prevalence of CKD in the United States in 1999-2004 is higher than it was in 1988-1994. This increase is partly explained by the increasing prevalence of diabetes and hypertension and raises concerns about future increased incidence of kidney failure and other complications of CKD.

MICROALBUMINURIA AS A PREDICTOR OF CLINICAL NEPHROPATHY IN INSULIN-DEPENDENT DIABETES MELLITUS

1982-06-01

G C Viberti , R. J. Jarrett , U. Mahmud +3 more

Chronic kidney disease as a global public health problem: Approaches and initiatives – a position statement from Kidney Disease Improving Global Outcomes

2007-06-14

Andrew S. Levey , R. C. Atkins , Josef Coresh +7 more

Defective fatty acid oxidation in renal tubular epithelial cells has a key role in kidney fibrosis development

2014-11-24

Hyun Mi Kang , Seon Ho Ahn , Peter S. Choi +7 more

The Metabolic Syndrome and Chronic Kidney Disease in U.S. Adults

2004-02-03

Jing Chen , Paul Muntner , L. Lee Hamm +5 more

Background: The metabolic syndrome is a common risk factor for cardiovascular disease. Objective: To examine the association between the metabolic syndrome and risk for chronic kidney disease and microalbuminuria. Design: … Background: The metabolic syndrome is a common risk factor for cardiovascular disease. Objective: To examine the association between the metabolic syndrome and risk for chronic kidney disease and microalbuminuria. Design: Cross-sectional study. Setting: The Third National Health and Nutrition Examination Survey. Patients: Participants 20 years of age or older were studied in the chronic kidney disease (n = 6217) and microalbuminuria (n = 6125) analyses. Measurements: The metabolic syndrome was defined as the presence of 3 or more of the following risk factors: elevated blood pressure, low high-density lipoprotein cholesterol level, high triglyceride level, elevated glucose level, and abdominal obesity. Chronic kidney disease was defined as a glomerular filtration rate less than 60 mL/min per 1.73 m2, and microalbuminuria was defined as a urinary albumin–creatinine ratio of 30 to 300 mg/g. Results: The multivariate-adjusted odds ratios of chronic kidney disease and microalbuminuria in participants with the metabolic syndrome compared with participants without the metabolic syndrome were 2.60 (95% CI, 1.68 to 4.03) and 1.89 (CI, 1.34 to 2.67), respectively. Compared with participants with 0 or 1 component of the metabolic syndrome, participants with 2, 3, 4, and 5 components of chronic kidney disease had multivariate-adjusted odds ratios of 2.21 (CI, 1.16 to 4.24), 3.38 (CI, 1.48 to 7.69), 4.23 (CI, 2.06 to 8.63), and 5.85 (CI, 3.11 to 11.0), respectively. The corresponding multivariate-adjusted odds ratios of microalbuminuria for participants with 3, 4, and 5 components were 1.62 (CI, 1.10 to 2.38), 2.45 (CI, 1.55 to 3.85), and 3.19 (CI, 1.96 to 5.19), respectively. Conclusions: These findings suggest that the metabolic syndrome might be an important factor in the cause of chronic kidney disease.

A More Accurate Method To Estimate Glomerular Filtration Rate from Serum Creatinine: A New Prediction Equation

1999-03-16

Andrew S. Levey , Juan Bosch , Julia B. Lewis +3 more

Background: Serum creatinine concentration is widely used as an index of renal function, but this concentration is affected by factors other than glomerular filtration rate (GFR). Objective: To develop an … Background: Serum creatinine concentration is widely used as an index of renal function, but this concentration is affected by factors other than glomerular filtration rate (GFR). Objective: To develop an equation to predict GFR from serum creatinine concentration and other factors. Design: Cross-sectional study of GFR, creatinine clearance, serum creatinine concentration, and demographic and clinical characteristics in patients with chronic renal disease. Patients: 1628 patients enrolled in the baseline period of the Modification of Diet in Renal Disease (MDRD) Study, of whom 1070 were randomly selected as the training sample; the remaining 558 patients constituted the validation sample. Methods: The prediction equation was developed by stepwise regression applied to the training sample. The equation was then tested and compared with other prediction equations in the validation sample. Results: To simplify prediction of GFR, the equation included only demographic and serum variables. Independent factors associated with a lower GFR included a higher serum creatinine concentration, older age, female sex, nonblack ethnicity, higher serum urea nitrogen levels, and lower serum albumin levels (P < 0.001 for all factors). The multiple regression model explained 90.3% of the variance in the logarithm of GFR in the validation sample. Measured creatinine clearance overestimated GFR by 19%, and creatinine clearance predicted by the Cockcroft-Gault formula overestimated GFR by 16%. After adjustment for this overestimation, the percentage of variance of the logarithm of GFR predicted by measured creatinine clearance or the Cockcroft-Gault formula was 86.6% and 84.2%, respectively. Conclusion: The equation developed from the MDRD Study provided a more accurate estimate of GFR in our study group than measured creatinine clearance or other commonly used equations. *For members of the Modification of Diet in Renal Disease Study Group, see N Engl J Med. 1994; 330:877-84.

Serum cystatin C is superior to serum creatinine as a marker of kidney function: A meta-analysis

2002-08-01

Vikas R. Dharnidharka , Charles Kwon , Gary Stevens

Using Standardized Serum Creatinine Values in the Modification of Diet in Renal Disease Study Equation for Estimating Glomerular Filtration Rate

2006-08-15

Andrew S. Levey , Josef Coresh , Tom Greene +5 more

Background: Glomerular filtration rate (GFR) estimates facilitate detection of chronic kidney disease but require calibration of the serum creatinine assay to the laboratory that developed the equation. The 4-variable equation … Background: Glomerular filtration rate (GFR) estimates facilitate detection of chronic kidney disease but require calibration of the serum creatinine assay to the laboratory that developed the equation. The 4-variable equation from the Modification of Diet in Renal Disease (MDRD) Study has been reexpressed for use with a standardized assay. Objective: To describe the performance of the revised 4-variable MDRD Study equation and compare it with the performance of the 6-variable MDRD Study and Cockcroft–Gault equations. Design: Comparison of estimated and measured GFR. Setting: 15 clinical centers participating in a randomized, controlled trial. Patients: 1628 patients with chronic kidney disease participating in the MDRD Study. Measurements: Serum creatinine levels were calibrated to an assay traceable to isotope-dilution mass spectrometry. Glomerular filtration rate was measured as urinary clearance of 125I-iothalamate. Results: Mean measured GFR was 39.8 mL/min per 1.73 m2 (SD, 21.2). Accuracy and precision of the revised 4-variable equation were similar to those of the original 6-variable equation and better than in the Cockcroft–Gault equation, even when the latter was corrected for bias, with 90%, 91%, 60%, and 83% of estimates within 30% of measured GFR, respectively. Differences between measured and estimated GFR were greater for all equations when the estimated GFR was 60 mL/min per 1.73 m2 or greater. Limitations: The MDRD Study included few patients with a GFR greater than 90 mL/min per 1.73 m2. Equations were not compared in a separate study sample. Conclusions: The 4-variable MDRD Study equation provides reasonably accurate GFR estimates in patients with chronic kidney disease and a measured GFR of less than 90 mL/min per 1.73 m2. By using the reexpressed MDRD Study equation with the standardized serum creatinine assay, clinical laboratories can report more accurate GFR estimates. *For a list of investigators of the Chronic Kidney Disease Epidemiology Collaboration, see the Appendix.

Body Mass Index and Risk for End-Stage Renal Disease

2006-01-03

Chi‐yuan Hsu , Charles E. McCulloch , Carlos Iribarren +2 more

Background: Although interest in the relationship between obesity and kidney disease is increasing, few epidemiologic studies have examined whether excess weight is an independent risk factor for end-stage renal disease … Background: Although interest in the relationship between obesity and kidney disease is increasing, few epidemiologic studies have examined whether excess weight is an independent risk factor for end-stage renal disease (ESRD). Objective: To determine the association between increased body mass index (BMI) and risk for ESRD. Design: Historical (nonconcurrent) cohort study. Setting: A large integrated health care delivery system in northern California. Participants: 320 252 adult members of Kaiser Permanente who volunteered for screening health checkups between 1964 and 1985 and who had height and weight measured. Measurements: The authors ascertained ESRD cases by matching data with the U.S. Renal Data System registry through 2000. Results: A total of 1471 cases of ESRD occurred during 8 347 955 person-years of follow-up. Higher BMI was a risk factor for ESRD in multivariable models that adjusted for age, sex, race, education level, smoking status, history of myocardial infarction, serum cholesterol level, urinalysis proteinuria, urinalysis hematuria, and serum creatinine level. Compared with persons who had normal weight (BMI, 18.5 to 24.9 kg/m2), the adjusted relative risk for ESRD was 1.87 (95% CI, 1.64 to 2.14) for those who were overweight (BMI, 25.0 to 29.9 kg/m2), 3.57 (CI, 3.05 to 4.18) for those with class I obesity (BMI, 30.0 to 34.9 kg/m2), 6.12 (CI, 4.97 to 7.54) for those with class II obesity (BMI, 35.0 to 39.9 kg/m2), and 7.07 (CI, 5.37 to 9.31) for those with extreme obesity (BMI ≥ 40 kg/m2). Higher baseline BMI remained an independent predictor for ESRD after additional adjustments for baseline blood pressure level and presence or absence of diabetes mellitus. Limitations: Primary analyses were based on single measurements of exposures. Conclusions: High BMI is a common, strong, and potentially modifiable risk factor for ESRD.

Longitudinal Follow-up and Outcomes Among a Population With Chronic Kidney Disease in a Large Managed Care Organization

2004-03-22

Douglas S. Keith , Gregory A. Nichols , Christina M. Gullion +2 more

<h3>Background</h3> Chronic kidney disease is the primary cause of end-stage renal disease in the United States. The purpose of this study was to understand the natural history of chronic kidney … <h3>Background</h3> Chronic kidney disease is the primary cause of end-stage renal disease in the United States. The purpose of this study was to understand the natural history of chronic kidney disease with regard to progression to renal replacement therapy (transplant or dialysis) and death in a representative patient population. <h3>Methods</h3> In 1996 we identified 27 998 patients in our health plan who had estimated glomerular filtration rates of less than 90 mL/min per 1.73 m<sup>2</sup>on 2 separate measurements at least 90 days apart. We followed up patients from the index date of the first glomerular filtration rates of less than 90 mL/min per 1.73 m<sup>2</sup>until renal replacement therapy, death, disenrollment from the health plan, or June 30, 2001. We extracted from the computerized medical records the prevalence of the following comorbidities at the index date and end point: hypertension, diabetes mellitus, coronary artery disease, congestive heart failure, hyperlipidemia, and renal anemia. <h3>Results</h3> Our data showed that the rate of renal replacement therapy over the 5-year observation period was 1.1%, 1.3%, and 19.9%, respectively, for the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI) stages 2, 3, and 4, but that the mortality rate was 19.5%, 24.3%, and 45.7%. Thus, death was far more common than dialysis at all stages. In addition, congestive heart failure, coronary artery disease, diabetes, and anemia were more prevalent in the patients who died but hypertension prevalence was similar across all stages. <h3>Conclusion</h3> Our data suggest that efforts to reduce mortality in this population should be focused on treatment and prevention of coronary artery disease, congestive heart failure, diabetes mellitus, and anemia.

KDOQI US Commentary on the 2012 KDIGO Clinical Practice Guideline for the Evaluation and Management of CKD

2014-03-20

Lesley A. Inker , Brad C. Astor , Chester H. Fox +5 more

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Assessing Kidney Function — Measured and Estimated Glomerular Filtration Rate

2006-06-07

Lesley A. Stevens , Josef Coresh , Tom Greene +1 more

In the coming years, estimates of the glomerular filtration rate (GFR) may replace the measurement of serum creatinine as the primary tool for the assessment of kidney function. Indeed, many … In the coming years, estimates of the glomerular filtration rate (GFR) may replace the measurement of serum creatinine as the primary tool for the assessment of kidney function. Indeed, many clinical laboratories already report estimated GFR values whenever serum creatinine is measured. This review considers current methods of measuring GFR and GFR-estimating equations and their strengths and weaknesses as applied to chronic kidney disease.

Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without diabetes: a meta-analysis

2012-09-24

Caroline S. Fox , Kunihiro Matsushita , Mark Woodward +7 more

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Evaluation and Management of Chronic Kidney Disease: Synopsis of the Kidney Disease: Improving Global Outcomes 2012 Clinical Practice Guideline

2013-06-04

Paul E. Stevens

The Kidney Disease: Improving Global Outcomes (KDIGO) organization developed clinical practice guidelines in 2012 to provide guidance on the evaluation, management, and treatment of chronic kidney disease (CKD) in adults … The Kidney Disease: Improving Global Outcomes (KDIGO) organization developed clinical practice guidelines in 2012 to provide guidance on the evaluation, management, and treatment of chronic kidney disease (CKD) in adults and children who are not receiving renal replacement therapy.The KDIGO CKD Guideline Development Work Group defined the scope of the guideline, gathered evidence, determined topics for systematic review, and graded the quality of evidence that had been summarized by an evidence review team. Searches of the English-language literature were conducted through November 2012. Final modification of the guidelines was informed by the KDIGO Board of Directors and a public review process involving registered stakeholders.The full guideline included 110 recommendations. This synopsis focuses on 10 key recommendations pertinent to definition, classification, monitoring, and management of CKD in adults.

Estimating Glomerular Filtration Rate from Serum Creatinine and Cystatin C

2012-07-05

Lesley A. Inker , Christopher H. Schmid , Hocine Tighiouart +7 more

Estimates of glomerular filtration rate (GFR) that are based on serum creatinine are routinely used; however, they are imprecise, potentially leading to the overdiagnosis of chronic kidney disease. Cystatin C … Estimates of glomerular filtration rate (GFR) that are based on serum creatinine are routinely used; however, they are imprecise, potentially leading to the overdiagnosis of chronic kidney disease. Cystatin C is an alternative filtration marker for estimating GFR.

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New Equations to Estimate GFR in Children with CKD

2009-01-22

George J. Schwartz , Alvaro MunCombining Tildeoz , Michael F. Schneider +4 more

The Schwartz formula was devised in the mid-1970s to estimate GFR in children. Recent data suggest that this formula currently overestimates GFR as measured by plasma disappearance of iohexol, likely … The Schwartz formula was devised in the mid-1970s to estimate GFR in children. Recent data suggest that this formula currently overestimates GFR as measured by plasma disappearance of iohexol, likely a result of a change in methods used to measure creatinine. Here, we developed equations to estimate GFR using data from the baseline visits of 349 children (aged 1 to 16 yr) in the Chronic Kidney Disease in Children (CKiD) cohort. Median iohexol-GFR (iGFR) was 41.3 ml/min per 1.73 m(2) (interquartile range 32.0 to 51.7), and median serum creatinine was 1.3 mg/dl. We performed linear regression analyses assessing precision, goodness of fit, and accuracy to develop improvements in the GFR estimating formula, which was based on height, serum creatinine, cystatin C, blood urea nitrogen, and gender. The best equation was: GFR(ml/min per 1.73 m(2))=39.1[height (m)/Scr (mg/dl)](0.516) x [1.8/cystatin C (mg/L)](0.294)[30/BUN (mg/dl)](0.169)[1.099](male)[height (m)/1.4](0.188). This formula yielded 87.7% of estimated GFR within 30% of the iGFR, and 45.6% within 10%. In a test set of 168 CKiD patients at 1 yr of follow-up, this formula compared favorably with previously published estimating equations for children. Furthermore, with height measured in cm, a bedside calculation of 0.413*(height/serum creatinine), provides a good approximation to the estimated GFR formula. Additional studies of children with higher GFR are needed to validate these formulas for use in screening all children for CKD.

Chronic kidney disease after nephrectomy in patients with renal cortical tumours: a retrospective cohort study

2006-08-18

William C. Huang , Andrew S. Levey , Angel M. Serio +5 more

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Urinary Albumin Excretion Predicts Cardiovascular and Noncardiovascular Mortality in General Population

2002-09-30

Hans L. Hillege , V. Fidler , Gilles F.H. Diercks +7 more

For the general population, the clinical relevance of an increased urinary albumin excretion rate is still debated. Therefore, we examined the relationship between urinary albumin excretion and all-cause mortality and … For the general population, the clinical relevance of an increased urinary albumin excretion rate is still debated. Therefore, we examined the relationship between urinary albumin excretion and all-cause mortality and mortality caused by cardiovascular (CV) disease and non-CV disease in the general population.In the period 1997 to 1998, all inhabitants of the city of Groningen, the Netherlands, aged between 28 and 75 years (n=85 421) were sent a postal questionnaire collecting information about risk factors for CV disease and CV morbidity and a vial to collect an early morning urine sample for measurement of urinary albumin concentration (UAC). The vital status of the cohort was subsequently obtained from the municipal register, and the cause of death was obtained from the Central Bureau of Statistics. Of these 85 421 subjects, 40 856 (47.8%) responded, and 40 548 could be included in the analysis. During a median follow-up period of 961 days (maximum 1139 days), 516 deaths with known cause were recorded. We found a positive dose-response relationship between increasing UAC and mortality. A higher UAC increased the risk of both CV and non-CV death after adjustment for other well-recognized CV risk factors, with the increase being significantly higher for CV mortality than for non-CV mortality (P=0.014). A 2-fold increase in UAC was associated with a relative risk of 1.29 for CV mortality (95% CI 1.18 to 1.40) and 1.12 (95% CI 1.04 to 1.21) for non-CV mortality.Urinary albumin excretion is a predictor of all-cause mortality in the general population. The excess risk was more attributable to death from CV causes, independent of the effects of other CV risk factors, and the relationship was already apparent at levels of albuminuria currently considered to be normal.

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Prevalence of chronic kidney disease in China: a cross-sectional survey

2012-03-01

Luxia Zhang , Fang Wang , Li Wang +7 more

National Kidney Foundation Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification

2003-07-15

Andrew S. Levey , Josef Coresh , Ethan M. Balk +7 more

Chronic kidney disease is a worldwide public health problem with an increasing incidence and prevalence, poor outcomes, and high cost. Outcomes of chronic kidney disease include not only kidney failure … Chronic kidney disease is a worldwide public health problem with an increasing incidence and prevalence, poor outcomes, and high cost. Outcomes of chronic kidney disease include not only kidney failure but also complications of decreased kidney function and cardiovascular disease. Current evidence suggests that some of these adverse outcomes can be prevented or delayed by early detection and treatment. Unfortunately, chronic kidney disease is underdiagnosed and undertreated, in part as a result of lack of agreement on a definition and classification of its stages of progression. Recent clinical practice guidelines by the National Kidney Foundation 1) define chronic kidney disease and classify its stages, regardless of underlying cause, 2) evaluate laboratory measurements for the clinical assessment of kidney disease, 3) associate the level of kidney function with complications of chronic kidney disease, and 4) stratify the risk for loss of kidney function and development of cardiovascular disease. The guidelines were developed by using an approach based on the procedure outlined by the Agency for Healthcare Research and Quality. This paper presents the definition and five-stage classification system of chronic kidney disease and summarizes the major recommendations on early detection in adults. Recommendations include identifying persons at increased risk (those with diabetes, those with hypertension, those with a family history of chronic kidney disease, those older than 60 years of age, or those with U.S. racial or ethnic minority status), detecting kidney damage by measuring the albumin-creatinine ratio in untimed ("spot") urine specimens, and estimating the glomerular filtration rate from serum creatinine measurements by using prediction equations. Because of the high prevalence of early stages of chronic kidney disease in the general population (approximately 11% of adults), this information is particularly important for general internists and specialists.

Chronic Kidney Disease and Mortality Risk

2006-06-01

Marcello Tonelli , Natasha Wiebe , Bruce F. Culleton +5 more

Current guidelines identify people with chronic kidney disease (CKD) as being at high risk for cardiovascular and all-cause mortality. Because as many as 19 million Americans may have CKD, a … Current guidelines identify people with chronic kidney disease (CKD) as being at high risk for cardiovascular and all-cause mortality. Because as many as 19 million Americans may have CKD, a comprehensive summary of this risk would be potentially useful for planning public health policy. A systematic review of the association between non-dialysis-dependent CKD and the risk for all-cause and cardiovascular mortality was conducted. Patient- and study-related characteristics that influenced the magnitude of these associations also were investigated. MEDLINE and EMBASE databases were searched, and reference lists through December 2004 were consulted. Authors of 10 primary studies provided additional data. Cohort studies or cohort analyses of randomized, controlled trials that compared mortality between those with and without chronically reduced kidney function were included. Studies were excluded from review when participants were followed for < 1 yr or had ESRD. Two reviewers independently extracted data on study setting, quality, participant and renal function characteristics, and outcomes. Thirty-nine studies that followed a total of 1,371,990 participants were reviewed. The unadjusted relative risk for mortality in participants with reduced kidney function compared with those without ranged from 0.94 to 5.0 and was significantly more than 1.0 in 93% of cohorts. Among the 16 studies that provided suitable data, the absolute risk for death increased exponentially with decreasing renal function. Fourteen cohorts described the risk for mortality from reduced kidney function, after adjustment for other established risk factors. Although adjusted relative hazards were consistently lower than unadjusted relative risks (median reduction 17%), they remained significantly more than 1.0 in 71% of cohorts. This review supports current guidelines that identify individuals with CKD as being at high risk for cardiovascular mortality. Determining which interventions best offset this risk remains a health priority.

Chronic Kidney Disease and the Risks of Death, Cardiovascular Events, and Hospitalization

2004-09-22

Alan S. Go , Glenn M. Chertow , Dongjie Fan +2 more

End-stage renal disease substantially increases the risks of death, cardiovascular disease, and use of specialized health care, but the effects of less severe kidney dysfunction on these outcomes are less … End-stage renal disease substantially increases the risks of death, cardiovascular disease, and use of specialized health care, but the effects of less severe kidney dysfunction on these outcomes are less well defined.We estimated the longitudinal glomerular filtration rate (GFR) among 1,120,295 adults within a large, integrated system of health care delivery in whom serum creatinine had been measured between 1996 and 2000 and who had not undergone dialysis or kidney transplantation. We examined the multivariable association between the estimated GFR and the risks of death, cardiovascular events, and hospitalization.The median follow-up was 2.84 years, the mean age was 52 years, and 55 percent of the group were women. After adjustment, the risk of death increased as the GFR decreased below 60 ml per minute per 1.73 m2 of body-surface area: the adjusted hazard ratio for death was 1.2 with an estimated GFR of 45 to 59 ml per minute per 1.73 m2 (95 percent confidence interval, 1.1 to 1.2), 1.8 with an estimated GFR of 30 to 44 ml per minute per 1.73 m2 (95 percent confidence interval, 1.7 to 1.9), 3.2 with an estimated GFR of 15 to 29 ml per minute per 1.73 m2 (95 percent confidence interval, 3.1 to 3.4), and 5.9 with an estimated GFR of less than 15 ml per minute per 1.73 m2 (95 percent confidence interval, 5.4 to 6.5). The adjusted hazard ratio for cardiovascular events also increased inversely with the estimated GFR: 1.4 (95 percent confidence interval, 1.4 to 1.5), 2.0 (95 percent confidence interval, 1.9 to 2.1), 2.8 (95 percent confidence interval, 2.6 to 2.9), and 3.4 (95 percent confidence interval, 3.1 to 3.8), respectively. The adjusted risk of hospitalization with a reduced estimated GFR followed a similar pattern.An independent, graded association was observed between a reduced estimated GFR and the risk of death, cardiovascular events, and hospitalization in a large, community-based population. These findings highlight the clinical and public health importance of chronic renal insufficiency.

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Modified Glomerular Filtration Rate Estimating Equation for Chinese Patients with Chronic Kidney Disease

2006-09-21

Yingchun Ma , Li Zuo , Jianghua Chen +7 more

The Modification of Diet in Renal Disease (MDRD) equations provide a rapid method of assessing GFR in patients with chronic kidney disease (CKD). However, previous research indicated that modification of … The Modification of Diet in Renal Disease (MDRD) equations provide a rapid method of assessing GFR in patients with chronic kidney disease (CKD). However, previous research indicated that modification of these equations is necessary for application in Chinese patients with CKD. The objective of this study was to modify MDRD equations on the basis of the data from the Chinese CKD population and compare the diagnostic performance of the modified MDRD equations with that of the original MDRD equations across CKD stages in a multicenter, cross-sectional study of GFR estimation from plasma creatinine, demographic data, and clinical characteristics. A total of 684 adult patients with CKD, from nine geographic regions of China were selected. A random sample of 454 of these patients were included in the training sample set, and the remaining 230 patients were included in the testing sample set. With the use of the dual plasma sampling (99m)Tc-DTPA plasma clearance method as a reference for GFR measurement, the original MDRD equations were modified by two methods: First, by adding a racial factor for Chinese in the original MDRD equations, and, second, by applying multiple linear regression to the training sample and modifying the coefficient that is associated with each variable in the original MDRD equations and then validating in the testing sample and comparing it with the original MDRD equations. All modified MDRD equations showed significant performance improvement in bias, precision, and accuracy compared with the original MDRD equations, and the percentage of estimated GFR that did not deviate >30% from the reference GFR was >75%. The modified MDRD equations that were based on the Chinese patients with CKD offered significant advantages in different CKD stages and could be applied in clinical practice, at least in Chinese patients with CKD.

Expressing the Modification of Diet in Renal Disease Study Equation for Estimating Glomerular Filtration Rate with Standardized Serum Creatinine Values

2007-03-02

Andrew S. Levey , Josef Coresh , Tom Greene +4 more

We sought to reexpress the 4-variable Modification of Diet in Renal Disease (MDRD) Study equation for estimation of glomerular filtration rate (GFR) using serum creatinine (S(cr)) standardized to reference methods.Serum … We sought to reexpress the 4-variable Modification of Diet in Renal Disease (MDRD) Study equation for estimation of glomerular filtration rate (GFR) using serum creatinine (S(cr)) standardized to reference methods.Serum specimens included creatinine reference materials prepared by the College of American Pathologists (CAP), traceable to primary reference material at the NIST, with assigned values traceable to isotope dilution mass spectrometry (IDMS), a calibration panel prepared by the Cleveland Clinic Research Laboratory (CCRL), and frozen samples from the MDRD Study. Split specimens were measured at the CCRL using the Roche enzymatic and Beckman CX3 kinetic alkaline picrate assays.Roche enzymatic assay results on CAP samples were comparable to IDMS-assigned values. Beckman CX3 assay results in 2004-2005 were significantly higher than but highly correlated with simultaneous Roche enzymatic assay results (r(2) = 0.9994 on 40 CCRL samples) and showed minimal but significant upward drift from Beckman CX3 assay results during the MDRD Study in 1989-1991 (r(2) = 0.9987 in 253 samples). Combining these factors, standardized S(cr) = 0.95 x original MDRD Study S(cr). The reexpressed 4-variable MDRD Study equation for S(cr) (mg/dL) is GFR = 175 x standardized S(cr)(-1.154) x age(-0.203) x 1.212 (if black) x 0.742 (if female), and for S(cr) (micromol/L) is GFR = 30849 x standardized S(cr)(-1.154) x age(-0.203) x 1.212 (if black) x 0.742 (if female) [GFR in mL x min(-1) x (1.73 m(2))(-1)].When the calibration of S(cr) methods is traceable to the S(cr) reference system, GFR should be estimated using the MDRD Study equation that has been reexpressed for standardized S(cr).

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Chronic kidney disease and cardiovascular risk: epidemiology, mechanisms, and prevention

2013-05-31

Ron T. Gansevoort , Ricardo Correa‐Rotter , Brenda R. Hemmelgarn +5 more

Revised Equations for Estimated GFR From Serum Creatinine in Japan

2009-04-02

Seiichi Matsuo , Enyu Imai , Masaru Horio +7 more

A New Equation to Estimate Glomerular Filtration Rate

2009-05-05

Andrew S. Levey , Lesley A. Stevens , Christopher H. Schmid +7 more

Background: Equations to estimate glomerular filtration rate (GFR) are routinely used to assess kidney function. Current equations have limited precision and systematically underestimate measured GFR at higher values. Objective: To … Background: Equations to estimate glomerular filtration rate (GFR) are routinely used to assess kidney function. Current equations have limited precision and systematically underestimate measured GFR at higher values. Objective: To develop a new estimating equation for GFR: the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Design: Cross-sectional analysis with separate pooled data sets for equation development and validation and a representative sample of the U.S. population for prevalence estimates. Setting: Research studies and clinical populations (“studies”) with measured GFR and NHANES (National Health and Nutrition Examination Survey), 1999 to 2006. Participants: 8254 participants in 10 studies (equation development data set) and 3896 participants in 16 studies (validation data set). Prevalence estimates were based on 16 032 participants in NHANES. Measurements: GFR, measured as the clearance of exogenous filtration markers (iothalamate in the development data set; iothalamate and other markers in the validation data set), and linear regression to estimate the logarithm of measured GFR from standardized creatinine levels, sex, race, and age. Results: In the validation data set, the CKD-EPI equation performed better than the Modification of Diet in Renal Disease Study equation, especially at higher GFR (P < 0.001 for all subsequent comparisons), with less bias (median difference between measured and estimated GFR, 2.5 vs. 5.5 mL/min per 1.73 m2), improved precision (interquartile range [IQR] of the differences, 16.6 vs. 18.3 mL/min per 1.73 m2), and greater accuracy (percentage of estimated GFR within 30% of measured GFR, 84.1% vs. 80.6%). In NHANES, the median estimated GFR was 94.5 mL/min per 1.73 m2 (IQR, 79.7 to 108.1) vs. 85.0 (IQR, 72.9 to 98.5) mL/min per 1.73 m2, and the prevalence of chronic kidney disease was 11.5% (95% CI, 10.6% to 12.4%) versus 13.1% (CI, 12.1% to 14.0%). Limitation: The sample contained a limited number of elderly people and racial and ethnic minorities with measured GFR. Conclusion: The CKD-EPI creatinine equation is more accurate than the Modification of Diet in Renal Disease Study equation and could replace it for routine clinical use. Primary Funding Source: National Institute of Diabetes and Digestive and Kidney Diseases.

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Diabetic Nephropathy: Diagnosis, Prevention, and Treatment

2005-01-01

Jorge Luiz Gross , Mirela Jobim de Azevedo , Sandra Pinho Silveiro +3 more

Diabetic nephropathy is the leading cause of kidney disease in patients starting renal replacement therapy and affects ∼40% of type 1 and type 2 diabetic patients. It increases the risk … Diabetic nephropathy is the leading cause of kidney disease in patients starting renal replacement therapy and affects ∼40% of type 1 and type 2 diabetic patients. It increases the risk of death, mainly from cardiovascular causes, and is defined by increased urinary albumin excretion (UAE) in the absence of other renal diseases. Diabetic nephropathy is categorized into stages: microalbuminuria (UAE &gt;20 μg/min and ≤199 μg/min) and macroalbuminuria (UAE ≥200 μg/min). Hyperglycemia, increased blood pressure levels, and genetic predisposition are the main risk factors for the development of diabetic nephropathy. Elevated serum lipids, smoking habits, and the amount and origin of dietary protein also seem to play a role as risk factors. Screening for microalbuminuria should be performed yearly, starting 5 years after diagnosis in type 1 diabetes or earlier in the presence of puberty or poor metabolic control. In patients with type 2 diabetes, screening should be performed at diagnosis and yearly thereafter. Patients with micro- and macroalbuminuria should undergo an evaluation regarding the presence of comorbid associations, especially retinopathy and macrovascular disease. Achieving the best metabolic control (A1c &lt;7%), treating hypertension (&lt;130/80 mmHg or &lt;125/75 mmHg if proteinuria &gt;1.0 g/24 h and increased serum creatinine), using drugs with blockade effect on the renin-angiotensin-aldosterone system, and treating dyslipidemia (LDL cholesterol &lt;100 mg/dl) are effective strategies for preventing the development of microalbuminuria, in delaying the progression to more advanced stages of nephropathy and in reducing cardiovascular mortality in patients with type 1 and type 2 diabetes.

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Chronic kidney disease: global dimension and perspectives

2013-05-30

Vivekanand Jha , Guillermo García-García , Kunitoshi Iseki +6 more

Hyperfiltration in remnant nephrons: a potentially adverse response to renal ablation

1981-07-01

Thomas H. Hostetter , Jean L. Olson , Helmut G. Rennke +2 more

Micropuncture studies were performed in three groups of male Munich-Wistar rats 1 wk after surgery: group I, eight control rats that underwent laparotomy and were fed a normal diet; group … Micropuncture studies were performed in three groups of male Munich-Wistar rats 1 wk after surgery: group I, eight control rats that underwent laparotomy and were fed a normal diet; group II, nine rats that underwent right nephrectomy and segmental infarction of five-sixths of the left kidney and were fed a normal diet; and group III, seven rats that underwent the same renal ablative procedure and were fed a low protein diet. Single nephron glomerular filtration rate (SNGFR) was higher in the remnant kidney of group II rats compared with group I rats due to higher average values for mean glomerular transcapillary hydraulic pressure difference (delta P) and initial glomerular plasma flow rate (QA) in group II. Glomeruli in remnant kidneys of group II showed striking alterations in morphology, including epithelial cell protein reabsorption droplets, foot process fusion, and mesangial expansion. Group III rats demonstrated a mean SNGFR not statistically different from that of group I, but significantly less than that of group II rats. This lack of absolute hyperfiltration in remnant glomeruli of group III rats relative to group I obtained because QA and delta P did not increase above values found in group I. The glomerular structural lesions seen in group II were also largely attenuated in group III. These studies demonstrate that alterations in glomerular hemodynamics associated with renal ablation are accompanied by structural lesions and suggest that sustained single nephron hyperfiltration may have maladaptive consequences by damaging remnant glomeruli.

A simplified equation to predict glomerular filtration rate from serum creatinine

2000-09-25

Andrew S. Levey , Juan P. Bosch , J B Lewis +3 more

Pathophysiology of Progressive Nephropathies

1998-11-12

Giuseppe Remuzzi , Tullio Bertani

In patients with renal diseases characterized by proteinuria, the initial insult to the kidney is usually followed by a progressive decline in the glomerular filtration rate. This decline has been … In patients with renal diseases characterized by proteinuria, the initial insult to the kidney is usually followed by a progressive decline in the glomerular filtration rate. This decline has been thought to be due to changes in renal hemodynamics initiated by the loss of nephrons.1 When renal mass is reduced in rats, the remaining nephrons undergo sudden hypertrophy, with a concomitant lowering of arteriolar resistance and an increase in glomerular plasma flow.2,3 Afferent arteriolar tone decreases more than efferent arteriolar tone, and therefore, the hydraulic pressure in glomerular capillaries rises4 and the amount of filtrate formed by each nephron . . .

Microalbuminuria Predicts Clinical Proteinuria and Early Mortality in Maturity-Onset Diabetes

1984-02-09

C. E. Mogensen

We studied whether microalbuminuria (30 to 140 μg of albumin per milliliter) would predict the later development of increased proteinuria and early mortality in Type II diabetics. During 1973, morning … We studied whether microalbuminuria (30 to 140 μg of albumin per milliliter) would predict the later development of increased proteinuria and early mortality in Type II diabetics. During 1973, morning urine specimens of diabetic clinic patients 50 to 75 years of age whose disease had been diagosed after the age of 45 were examined for albumin level by radioimmunoassay. Seventy-six patients with albumin concentrations of 30 to 140 μg per milliliter were identified for long-term follow-up. They were compared with normal controls, diabetic patients with lower albumin concentrations (75 patients with concentrations <15 μg per milliliter and 53 with concentrations of 16 to 29 μg per milliliter), and 28 diabetic patients with higher concentrations (>140). Age, duration of diabetes, treatment method, fasting blood glucose level, blood pressure, height, and weight were determined for the four diabetic groups. After nine years the group with albumin concentrations of 30 to 140 μg per milliliter was more likely to have clinically detectablle 5oteinuria (>400 μg per milliliter) than were the groups with lower concentrations. Mortality was 148 per cent higher in this group than in normal controls — comparable to the increase (116 per cent) in the group with heavy proteinuria (albumin levels >140 μg per milliliter). In addition, mortality was increased 76 per cent in the group with albumin levels of 16 to 29 μg per milliliter and 37 per cent in the group with levels below 15. We conclude that microalbuminuria in patients with Type II diabetes is predictive of clinical proteinuria and increased mortality. (N Engl J Med 1984; 310:356–60.)

Predicting Diabetic Nephropathy in Insulin-Dependent Patients

1984-07-12

Carl Erik Mogensen , Celanie K. Christensen

We studied whether microalbuminuria (urinary albumin excretion rates of 15 to 150 micrograms per minute) would predict the development of increased proteinuria in Type I diabetes. We also studied the … We studied whether microalbuminuria (urinary albumin excretion rates of 15 to 150 micrograms per minute) would predict the development of increased proteinuria in Type I diabetes. We also studied the influence of glomerular filtration rate, renal blood flow, and blood pressure on the later development of proteinuria. Forty-four patients who had had Type I diabetes for at least seven years and who had albumin excretion rates below 150 micrograms per minute were studied from 1969 to 1976, and 43 were restudied in 1983. Of the 14 who initially had albumin excretion rates at or above 15 micrograms per minute, 12 had clinically detectable proteinuria (over 500 mg of protein per 24 hours) or an albumin excretion rate above 150 micrograms per minute at the later examination. Of the 29 who initially had albumin excretion rates below 15 micrograms per minute, none had clinically detectable proteinuria at the later examination, although four had microalbuminuria. Those whose condition progressed to clinically overt proteinuria had elevated glomerular filtration rates and higher blood pressures at the initial examination than did those in whom proteinuria did not develop. Renal blood flow was not elevated in these patients. We conclude that microalbuminuria predicts the development of diabetic nephropathy and that elevated glomerular filtration rates and increased blood pressure may also contribute to this progression.

Global Prevalence of Chronic Kidney Disease – A Systematic Review and Meta-Analysis

2016-07-06

Nathan R. Hill , Samuel Fatoba , Jason Oke +4 more

Chronic kidney disease (CKD) is a global health burden with a high economic cost to health systems and is an independent risk factor for cardiovascular disease (CVD). All stages of … Chronic kidney disease (CKD) is a global health burden with a high economic cost to health systems and is an independent risk factor for cardiovascular disease (CVD). All stages of CKD are associated with increased risks of cardiovascular morbidity, premature mortality, and/or decreased quality of life. CKD is usually asymptomatic until later stages and accurate prevalence data are lacking. Thus we sought to determine the prevalence of CKD globally, by stage, geographical location, gender and age. A systematic review and meta-analysis of observational studies estimating CKD prevalence in general populations was conducted through literature searches in 8 databases. We assessed pooled data using a random effects model. Of 5,842 potential articles, 100 studies of diverse quality were included, comprising 6,908,440 patients. Global mean(95%CI) CKD prevalence of 5 stages 13·4%(11·7–15·1%), and stages 3–5 was 10·6%(9·2–12·2%). Weighting by study quality did not affect prevalence estimates. CKD prevalence by stage was Stage-1 (eGFR>90+ACR>30): 3·5% (2·8–4·2%); Stage-2 (eGFR 60–89+ACR>30): 3·9% (2·7–5·3%); Stage-3 (eGFR 30–59): 7·6% (6·4–8·9%); Stage-4 = (eGFR 29–15): 0·4% (0·3–0·5%); and Stage-5 (eGFR<15): 0·1% (0·1–0·1%). CKD has a high global prevalence with a consistent estimated global CKD prevalence of between 11 to 13% with the majority stage 3. Future research should evaluate intervention strategies deliverable at scale to delay the progression of CKD and improve CVD outcomes.

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Obesity and Kidney Disease: Hidden Consequences of the Epidemic

2017-01-01

Csaba P. Kövesdy , Susan L. Furth , Carmine Zoccali

Obesity has become a worldwide epidemic, and its prevalence has been projected to grow by 40% in the next decade. This increasing prevalence has implications for the risk of diabetes, … Obesity has become a worldwide epidemic, and its prevalence has been projected to grow by 40% in the next decade. This increasing prevalence has implications for the risk of diabetes, cardiovascular disease, and also for chronic kidney disease. A high body mass index is one of the strongest risk factors for new-onset chronic kidney disease. In individuals affected by obesity, a compensatory hyperfiltration occurs to meet the heightened metabolic demands of the increased body weight. The increase in intraglomerular pressure can damage the kidneys and raise the risk of developing chronic kidney disease in the long-term. The incidence of obesity-related glomerulopathy has increased 10-fold in recent years. Obesity has also been shown to be a risk factor for nephrolithiasis, and for a number of malignancies including kidney cancer. This year, the World Kidney Day promotes education on the harmful consequences of obesity and its association with kidney disease, advocating healthy lifestyle and health policy measures that make preventive behaviors an affordable option.

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Diabetic Kidney Disease

2017-05-18

Radica Z. Alicic , Michele T. Rooney , Katherine R. Tuttle

Diabetic kidney disease develops in approximately 40% of patients who are diabetic and is the leading cause of CKD worldwide. Although ESRD may be the most recognizable consequence of diabetic … Diabetic kidney disease develops in approximately 40% of patients who are diabetic and is the leading cause of CKD worldwide. Although ESRD may be the most recognizable consequence of diabetic kidney disease, the majority of patients actually die from cardiovascular diseases and infections before needing kidney replacement therapy. The natural history of diabetic kidney disease includes glomerular hyperfiltration, progressive albuminuria, declining GFR, and ultimately, ESRD. Metabolic changes associated with diabetes lead to glomerular hypertrophy, glomerulosclerosis, and tubulointerstitial inflammation and fibrosis. Despite current therapies, there is large residual risk of diabetic kidney disease onset and progression. Therefore, widespread innovation is urgently needed to improve health outcomes for patients with diabetic kidney disease. Achieving this goal will require characterization of new biomarkers, designing clinical trials that evaluate clinically pertinent end points, and development of therapeutic agents targeting kidney-specific disease mechanisms (e.g., glomerular hyperfiltration, inflammation, and fibrosis). Additionally, greater attention to dissemination and implementation of best practices is needed in both clinical and community settings.

US Renal Data System 2016 Annual Data Report: Epidemiology of Kidney Disease in the United States

2017-02-22

Rajiv Saran , Bruce Robinson , Kevin C. Abbott +7 more

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Chronic Kidney Disease Diagnosis and Management

2019-10-01

Teresa K. Chen , Daphne H. Knicely , Morgan E. Grams

<h3>Importance</h3> Chronic kidney disease (CKD) is the 16th leading cause of years of life lost worldwide. Appropriate screening, diagnosis, and management by primary care clinicians are necessary to prevent adverse … <h3>Importance</h3> Chronic kidney disease (CKD) is the 16th leading cause of years of life lost worldwide. Appropriate screening, diagnosis, and management by primary care clinicians are necessary to prevent adverse CKD-associated outcomes, including cardiovascular disease, end-stage kidney disease, and death. <h3>Observations</h3> Defined as a persistent abnormality in kidney structure or function (eg, glomerular filtration rate [GFR] <60 mL/min/1.73 m<sup>2</sup>or albuminuria ≥30 mg per 24 hours) for more than 3 months, CKD affects 8% to 16% of the population worldwide. In developed countries, CKD is most commonly attributed to diabetes and hypertension. However, less than 5% of patients with early CKD report awareness of their disease. Among individuals diagnosed as having CKD, staging and new risk assessment tools that incorporate GFR and albuminuria can help guide treatment, monitoring, and referral strategies. Optimal management of CKD includes cardiovascular risk reduction (eg, statins and blood pressure management), treatment of albuminuria (eg, angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers), avoidance of potential nephrotoxins (eg, nonsteroidal anti-inflammatory drugs), and adjustments to drug dosing (eg, many antibiotics and oral hypoglycemic agents). Patients also require monitoring for complications of CKD, such as hyperkalemia, metabolic acidosis, hyperphosphatemia, vitamin D deficiency, secondary hyperparathyroidism, and anemia. Those at high risk of CKD progression (eg, estimated GFR <30 mL/min/1.73 m<sup>2</sup>, albuminuria ≥300 mg per 24 hours, or rapid decline in estimated GFR) should be promptly referred to a nephrologist. <h3>Conclusions and Relevance</h3> Diagnosis, staging, and appropriate referral of CKD by primary care clinicians are important in reducing the burden of CKD worldwide.

Global, regional, and national burden of chronic kidney disease, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017

2020-02-01

Boris Bikbov , Caroline Purcell , Andrew S. Levey +7 more

<h2>Summary</h2><h3>Background</h3> Health system planning requires careful assessment of chronic kidney disease (CKD) epidemiology, but data for morbidity and mortality of this disease are scarce or non-existent in many countries. We … <h2>Summary</h2><h3>Background</h3> Health system planning requires careful assessment of chronic kidney disease (CKD) epidemiology, but data for morbidity and mortality of this disease are scarce or non-existent in many countries. We estimated the global, regional, and national burden of CKD, as well as the burden of cardiovascular disease and gout attributable to impaired kidney function, for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017. We use the term CKD to refer to the morbidity and mortality that can be directly attributed to all stages of CKD, and we use the term impaired kidney function to refer to the additional risk of CKD from cardiovascular disease and gout. <h3>Methods</h3> The main data sources we used were published literature, vital registration systems, end-stage kidney disease registries, and household surveys. Estimates of CKD burden were produced using a Cause of Death Ensemble model and a Bayesian meta-regression analytical tool, and included incidence, prevalence, years lived with disability, mortality, years of life lost, and disability-adjusted life-years (DALYs). A comparative risk assessment approach was used to estimate the proportion of cardiovascular diseases and gout burden attributable to impaired kidney function. <h3>Findings</h3> Globally, in 2017, 1·2 million (95% uncertainty interval [UI] 1·2 to 1·3) people died from CKD. The global all-age mortality rate from CKD increased 41·5% (95% UI 35·2 to 46·5) between 1990 and 2017, although there was no significant change in the age-standardised mortality rate (2·8%, −1·5 to 6·3). In 2017, 697·5 million (95% UI 649·2 to 752·0) cases of all-stage CKD were recorded, for a global prevalence of 9·1% (8·5 to 9·8). The global all-age prevalence of CKD increased 29·3% (95% UI 26·4 to 32·6) since 1990, whereas the age-standardised prevalence remained stable (1·2%, −1·1 to 3·5). CKD resulted in 35·8 million (95% UI 33·7 to 38·0) DALYs in 2017, with diabetic nephropathy accounting for almost a third of DALYs. Most of the burden of CKD was concentrated in the three lowest quintiles of Socio-demographic Index (SDI). In several regions, particularly Oceania, sub-Saharan Africa, and Latin America, the burden of CKD was much higher than expected for the level of development, whereas the disease burden in western, eastern, and central sub-Saharan Africa, east Asia, south Asia, central and eastern Europe, Australasia, and western Europe was lower than expected. 1·4 million (95% UI 1·2 to 1·6) cardiovascular disease-related deaths and 25·3 million (22·2 to 28·9) cardiovascular disease DALYs were attributable to impaired kidney function. <h3>Interpretation</h3> Kidney disease has a major effect on global health, both as a direct cause of global morbidity and mortality and as an important risk factor for cardiovascular disease. CKD is largely preventable and treatable and deserves greater attention in global health policy decision making, particularly in locations with low and middle SDI. <h3>Funding</h3> Bill & Melinda Gates Foundation.

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Epidemiology of chronic kidney disease: an update 2022

2022-03-18

Csaba P. Kövesdy

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Chronic Kidney Disease

2016-11-23

Angela C Webster , Evi Nagler , Rachael L. Morton +1 more

Application of serum STIM1, AOPPS, and urinary NGAL, AGT in the diagnosis of hypertensive nephropathy

2025-06-24

Baohua Li , Chunsheng Wang , Dong‐Shen Ou‐Yang +3 more | Renal Failure

We aim to explore the diagnostic value of early detection of serum stromal interaction molecule 1 (STIM1), advanced oxidation protein products (AOPPs), urinary neutrophil gelatinase-associated lipocalin (NGAL), and angiotensinogen (AGT) … We aim to explore the diagnostic value of early detection of serum stromal interaction molecule 1 (STIM1), advanced oxidation protein products (AOPPs), urinary neutrophil gelatinase-associated lipocalin (NGAL), and angiotensinogen (AGT) in hypertensive nephropathy (HN). A retrospective study was conducted on 123 patients with primary hypertension. Based on the diagnostic criteria for HN, patients were divided into the HN group (n = 58) and simple hypertension group (n = 65). Additionally, 60 healthy individuals undergoing routine physical examinations were selected as the control group. The concentrations of serum STIM1, AOPPs, and urinary NGAL and AGT were assessed. The HN group exhibited higher levels of serum STIM1, AOPPs, and urinary NGAL and AGT than the simple hypertension and control groups. Pearson correlation analysis revealed that serum STIM1 and AOPPs were positively correlated with BUN, UN, and SCr and negatively correlated with eGFR; urinary NGAL and AGT were positively correlated with blood urea nitrogen, uric acid, and serum creatinine and negatively correlated with eGFR (all p < 0.05). Logistic regression analysis displayed a correlation between HN and serum STIM1 (OR: 1.019; 95%CI: 1.049-1.148), AOPPs (OR: 1.312; 95%CI: 1.129-1.526), and AGT (OR: 1.436; 95%CI: 1.183-1.742) (p < 0.05). ROC curve analysis demonstrated that the combined detection of serum STIM1, AOPPs, and urinary NGAL, AGT had a higher AUC for predicting HN compared to individual tests. Detection of serum STIM1, AOPPs, and urinary NGAL and AGT has diagnostic value in HN, providing a reference for early diagnosis and timely treatment of HN.

Identification of hub genes involved in the pathogenesis of diabetic nephropathy: A multi‐omics study integrating machine learning, mendelian randomization and mediation analysis

2025-06-24

Kang Li , Huidi Tang , Yanqing Wang +1 more | Diabetes Obesity and Metabolism

Abstract Background Diabetic nephropathy (DN), affecting 30%–40% of diabetic patients, is the leading cause of end‐stage renal disease worldwide. This study aims to identify diagnostic biomarkers and explore potential gene‐metabolite … Abstract Background Diabetic nephropathy (DN), affecting 30%–40% of diabetic patients, is the leading cause of end‐stage renal disease worldwide. This study aims to identify diagnostic biomarkers and explore potential gene‐metabolite interactions in DN pathogenesis through integrated bioinformatics approaches and experimental validation. Methods We analysed Gene Expression Omnibus datasets through differential expression analysis, weighted gene co‐expression network analysis (WGCNA) and machine learning algorithms to identify key DN‐associated genes. The causal relationships between candidate genes and DN were investigated using Mendelian randomization (MR) analysis with cis‐expression quantitative trait loci data, which random‐effects inverse variance weighted (IVW) method was our primary analysis approach. We then employed mediating MR analysis to explore metabolite‐mediated pathways. The expression of identified genes was validated in both human DN kidney samples and diabetic mouse models. Results Our analysis identified seven diagnostic genes (LUM, ESM1, VCAN, LOX, G0S2, THBS2 and UMOD). Through MR analysis, THBS2 showed a significant causal association with DN outcomes (OR = 1.1653, 95% CI [1.0103, 1.3441], p = 0.0357). Subsequent mediation analysis suggested that THBS2 may influence DN development through modulation of N‐acetyl‐beta‐alanine levels (mediating effect = 17.85%, p = 0.02). Importantly, elevated THBS2 expression was confirmed in both DN patient kidney samples and diabetic mouse models, validating our bioinformatics findings. Conclusions Through comprehensive bioinformatics analysis and experimental validation, we identified THBS2 as a potential diagnostic marker for DN. These findings provide new insights into DN pathogenesis and suggest directions for future therapeutic strategies.

KHẢO SÁT NỒNG ĐỘ VÀ XÁC ĐỊNH MỐI TƯƠNG QUAN GIỮA CYSTATIN C VÀ HORMONE TUYẾN GIÁP Ở BỆNH NHÂN CƯỜNG GIÁP

2025-06-23

Huyên Đoàn Duy , Châu Đoàn Thị Kim | Tạp chí Y học Việt Nam

Đặt vấn đề: Nồng độ cystatin C trong huyết thanh được đề xuất có mối liên quan với các thông số chức năng tuyến giáp và có thể sử dụng … Đặt vấn đề: Nồng độ cystatin C trong huyết thanh được đề xuất có mối liên quan với các thông số chức năng tuyến giáp và có thể sử dụng để theo dõi điều trị ở bệnh nhân cường giáp. Tuy nhiên, các dữ liệu hiện có vẫn chưa có sự thống nhất, đặc biệt tại Việt Nam. Mục tiêu: Khảo sát nồng độ và xác định mối tương quan giữa cystatin C và các hormone tuyến giáp trong máu. Đối tượng và phương pháp nghiên cứu: Nghiên cứu mô tả cắt ngang có phân tích trên 63 bệnh nhân đến khám và điều trị cường giáp tại Bệnh viện Đa khoa tỉnh Bình Thuận từ tháng 09 năm 2024 đến tháng 03 năm 2025. Kết quả: Về đặc điểm chung, tỷ lệ nữ/nam = 3,85, độ tuổi trung bình là 44,59 ± 13,08, phần lớn dưới 50 tuổi. Chỉ số khối cơ thể trung bình là 20,0 ± 3,35, tỷ lệ gầy chiếm đến 41,3%. Nồng độ FT3, FT4 và TSH trong máu có trung vị lần lượt là 3,58 pmol/L, 1,38 p/mol/L và 0,215 mUI/L. Nồng độ cystatin C máu trung bình là 0,82 ± 0,19 mg/L. Nồng độ cystatin C có mối tương quan thuận với nồng độ FT3 (r=0,666; p<0,001) và FT4 (r=0,447; p<0,001). Ngược lại, nồng độ cystatin C tương quan nghịch với nồng độ TSH (r=-0,526; p<0,001). Kết luận: Nồng độ cystatin C cho thấy có mối tương quan thuận với nồng độ FT3, FT4 và tương quan nghịch với TSH.

Cross-country inequalities in the epidemiology of chronic kidney disease due to type 2 diabetes mellitus, 1990–2021: findings from the global burden of disease study 2021

2025-06-23

Shiyi Shan , Jiayao Ying , Jiali Zhou +7 more | Diabetology & Metabolic Syndrome

Chronic kidney disease due to type 2 diabetes mellitus (CKD-T2DM) is a predominant and life-threatening complication of T2DM, with significant inequalities in its epidemiological features globally. This study aimed to … Chronic kidney disease due to type 2 diabetes mellitus (CKD-T2DM) is a predominant and life-threatening complication of T2DM, with significant inequalities in its epidemiological features globally. This study aimed to examine cross-country inequalities in the epidemiology of CKD-T2DM from 1990 to 2021. Data were extracted from the Global Burden of Disease (GBD) 2021 study. The epidemiological features of CKD-T2DM included age-standardized prevalence rate (ASPR), incidence rate (ASIR), and death rate (ASDR) from 1990 to 2021. The slope index of inequality (SII) and concentration index were applied to evaluate absolute and relative cross-country inequalities at global and regional scales in 1990 and 2021. Six inequality changing patterns were identified: worsening inequality in lower socio-demographic index (SDI) countries, improving inequality in lower SDI countries, worsening inequality in higher SDI countries, improving inequality in higher SDI countries, shift to higher burden in higher SDI countries, and shift to higher burden in lower SDI countries. Globally, from 1990 to 2021, the inequality in ASPR exhibited a worsening inequality in lower SDI countries pattern, with SII increasing from -161.96 (95% confidence interval [CI]: -292.64, -31.28) to -181.13 (95% CI: -302.25, -60.00) and concentration index from -0.03 (95%CI: -0.05, -0.02) to -0.04 (95%CI: -0.05, -0.02). The SII for ASIR showed a worsening inequality in higher SDI countries pattern, ranging from 9.44 (95% CI: 6.79, 12.08) to 11.65 (95% CI: 8.20, 15.10), while the concentration index exhibited an improving inequality in higher SDI countries pattern, ranging from 0.09 (95% CI: 0.06, 0.12) to 0.09 (95% CI: 0.06, 0.12). The SII for ASDR showed a worsening inequality in lower SDI countries pattern, ranging from -4.46 (95% CI: -6.44, -2.47) to -5.42 (95% CI: -7.92, -2.90), while the concentration index exhibited an improving inequality in lower SDI countries pattern, shifting from -0.13 (95% CI: -0.20, -0.07) in 1990 to -0.11 (95% CI: -0.18, -0.03) in 2021. Inequality patterns also varied across different geographic or socio-economic regions. Our study revealed considerable cross-country inequalities in the epidemiology of CKD-T2DM, underscoring the necessity for tailored health interventions, international cooperation, and adequate healthcare investment across different regions to address these inequalities.

THE EFFECT OF SUBTOTAL NEPHRECTOMY PROCEDURE ON THE GLOMERULOSCLEROSIS INDEX

2025-06-22

I Wayan Yoga Diva Peranawa , Ni Putu Diah Witari , Putu Nita Cahyawati | Meditory The Journal of Medical Laboratory

Background: Chronic kidney disease is one of the kidney disorders with a steadily increasing incidence rate.Objective: This study aims to determine the effect of subtotal nephrectomy on the renal glomerulosclerosis … Background: Chronic kidney disease is one of the kidney disorders with a steadily increasing incidence rate.Objective: This study aims to determine the effect of subtotal nephrectomy on the renal glomerulosclerosis in Mus musculus L. at 7, 14, and 28 days post-operation. Methods: This true-experimental study with a randomized post-test-only control group design used 16 white mice divided into four treatment groups (SO, SN7, SN14, and SN28). Kidney specimens were stained using Hematoxylin-Eosin and imaged to assess the glomerulosclerosis index. The results were analyzed using one-way ANOVA.Results: The findings showed that glomerulosclerosis could be observed as early as 7 days post-procedure. The highest score was found in the SN28 group (3.55 ± 0.129). A significant difference was observed between the SO and SN7, SN14, and SN28 groups (p 0.05). Significant differences were also found between the SN7 and SN14 and SN28 groups (p 0.05), while no significant difference was observed between the SN14 and SN28 groups.Conclusions: These results indicate that subtotal nephrectomy can induce glomerulosclerosis as early as day seven post-operation. The highest glomerulosclerosis index was observed on day 28, although statistically, it did not differ significantly from the index on day 14.

The distal nephron biomarkers associate with diabetic kidney disease progression

2025-06-22

Christina Tamargo , Steven G. Coca , Heather Thiessen‐Philbrook +7 more | JCI Insight

BACKGROUNDWhile urinary biomarkers show promise in predicting diabetic kidney disease (DKD) progression, distal tubular markers remain understudied. We investigated the association of distal tubule markers, epidermal growth factor (EGF) and … BACKGROUNDWhile urinary biomarkers show promise in predicting diabetic kidney disease (DKD) progression, distal tubular markers remain understudied. We investigated the association of distal tubule markers, epidermal growth factor (EGF) and uromodulin (UMOD), with DKD progression in the Veterans Affairs Diabetes in Nephropathy (VA NEPHRON-D) clinical trial. We used Cox regression models to evaluate the association between each biomarker and DKD progression and the relationship between change over time in biomarker and DKD progression. We used mixed models to investigate biomarker levels at baseline, 12 months, and over time and their relationships with longitudinal eGFR change. Participants (n = 1,116) had type 2 diabetes, urine albumin-to-creatinine ratio (UACR) ≥ 300 mg/g, and eGFR 30-89.9 mL/min/1.73 m2. Mean age was 65 years, mean eGFR was 56 (SD 19) mL/min/1.73 m2, and median UACR was 840 (IQR 424-1,780) mg/g. One hundred forty-four participants (13%) had DKD progression over a median follow-up of 2.2 (1.3-3.1) years. Higher baseline EGF and UMOD were independently associated with a lower risk of DKD progression (adjusted HR 0.68, 95% CI 0.47, 0.99 and 0.85, [0.75, 0.98] per 2-fold higher concentration of EGF and UMOD, respectively). Serial biomarker measurements were performed at baseline and 12 months, and a slower decline in biomarkers was associated with a lower risk of DKD progression when adjusted for baseline biomarker levels. Urinary EGF and UMOD may serve as valuable prognostic biomarkers in DKD. gov NCT00555217. NIH U01DK102730, U01DK103225, K23 DK118198, R01DK137087, U01DK103225, R37DK039773, U01DK114866, U01DK106962, U01DK129984, and R01DK093770; National Institute of Diabetes and Digestive and Kidney Diseases contract U01DK106965.

Chronic kidney disease screening in Iran: a cost-effectiveness analysis of different strategies

2025-06-20

Fatemeh Keshvari-Shad , Mahmood Yousefi , Sakineh Haj Ebrahimi +3 more | Renal Replacement Therapy

Abstract Background Chronic kidney disease (CKD) places a significant health burden on developing countries such as Iran. Early diagnosis and management of CKD, even when asymptomatic, can improve patient outcomes. … Abstract Background Chronic kidney disease (CKD) places a significant health burden on developing countries such as Iran. Early diagnosis and management of CKD, even when asymptomatic, can improve patient outcomes. The objective of this study was to evaluate the cost-effectiveness of CKD screening programs in Iran. Methods A decision-analytic Markov model was used to compare five CKD screening strategies, including (1) estimated glomerular filtration rate (eGFR); (2) urine albumin-to-creatinine ratio (ACR); (3) urine albumin concentration (UAC); (4) urine dipstick proteinuria testing; and (5) no screening among the general population aged 40–80 years: The analysis was conducted from the Iranian healthcare system’s perspective over a lifetime horizon, with a 1-year Markov cycle length. Future costs and health outcomes were discounted at an annual rate of 3.5%. Model input parameters were extracted from published literature and local Iranian data where available. The incremental cost-effectiveness ratios (ICERs) were used to compare the cost and outcome of different strategies. Probabilistic sensitivity analysis (PSA) was conducted to assess the impact of total uncertainty on the results. Results Our analysis found that all four screening programs increased quality-adjusted life years (QALYs) compared with no screening. The eGFR screening strategy had the highest QALYs among all strategies, while the no screening strategy had the highest costs. Using a willingness-to-pay threshold of IRR 316,112,349 (US $3276.8) per QALY, the model suggests that the ACR, eGFR, and dipstick screening strategies were superior to no screening, offering lower costs and more QALYs over the 40-year period. Probabilistic sensitivity analysis confirmed the robustness of these base-case findings. Conclusions The current study demonstrated that screening for chronic kidney disease is cost-effective in the Iranian healthcare system while reducing costs and increasing QALYs. This economic analysis provides evidence to support implementing a screening program for chronic kidney disease management in Iran.

Biomarkers of Kidney Failure and All-Cause Mortality in CKD

2025-06-20

Anthony Onoja , Thomas J. McDonnell , Isabelle Annessi +7 more | Journal of the American Society of Nephrology

Background: Chronic kidney disease (CKD) carries a variable risk for multiple adverse outcomes, highlighting the need for a personalised approach. This study evaluated several novel biomarkers linked to key disease … Background: Chronic kidney disease (CKD) carries a variable risk for multiple adverse outcomes, highlighting the need for a personalised approach. This study evaluated several novel biomarkers linked to key disease mechanisms to predict the risk of kidney failure (first event of eGFR <15 ml/min/1.73m 2 or kidney replacement therapy), all-cause mortality, and a composite of both. Methods: We included 2,884 adults with non-dialysis CKD from 16 nephrology centres across the UK. Twenty-one biomarkers associated with kidney damage, fibrosis, inflammation, and cardiovascular disease were analysed in urine, plasma, or serum. Cox proportional hazards models were used to assess biomarker associations and develop risk prediction models. Results: Participants had mean age 63 (15) years, 58% were male and 87% White. Median eGFR 35 (25, 47) ml/min/1.73m 2 , and median urinary albumin-to-creatinine ratio (UACR) 197 (32, 895) mg/g. During median 48 (33, 55) months follow-up, 680 kidney failure events and 414 all-cause mortality events occurred. For kidney failure, a model combining three biomarkers (sTNFR1, sCD40, UCOL1A1) showed good discrimination (c-index 0.86, 95% CI: 0.83–0.89) but was outperformed by a model using established risk factors (age, sex, ethnicity, eGFR, UACR; c-index 0.90, 95% CI: 0.88–0.92). For all-cause mortality, a model using three biomarkers (hs-cTnT, NT-proBNP, suPAR) demonstrated equivalent discrimination (c-index 0.80, 95% CI: 0.75–0.84) to an established risk factor model (c-index 0.80, 95% CI: 0.76–0.84).For the composite outcome, the biomarker model discrimination (C-index 0.78, 95% CI: 0.76, 0.81) was numerically higher than for established risk factors (C-index 0.77, 95% CI: 0.74, 0.80), and the addition of biomarkers to the established risk factors led to a small but statistically significant improvement in discrimination (C-index 0.80, 95% CI: 0.77, 0.82; p value < 0.01) Conclusions: Risk prediction models incorporating novel biomarkers showed comparable discrimination to established risk factors for kidney failure and all-cause mortality.

Mind the Gap: Discordance Between Cystatin C and Creatinine eGFR and Diabetes Complications

2025-06-20

Richard J. MacIsaac | Diabetes Care

Performance of the Kidney Failure Risk Equation according to diabetic status in the CKD-CAREMEAU cohort of patients with chronic kidney disease

2025-06-19

Julien Prouvot , Pascal Reboul , Pedram Ahmadpoor +7 more | Journal of Nephrology

Panaxatriol saponins exert anti-renal fibrosis by suppressing TNF-α mediated inflammation and TGF-β1/Smad3 signaling pathway

2025-06-19

Yi Si , Feiyan Li , Xin Ma +6 more | Renal Failure

Renal fibrosis is a key pathological process in the progression of chronic kidney disease (CKD). Panaxatriol saponins (PTS), the main bioactive compounds extracted from Panax notoginseng (Burk.) F.H. Chen, have … Renal fibrosis is a key pathological process in the progression of chronic kidney disease (CKD). Panaxatriol saponins (PTS), the main bioactive compounds extracted from Panax notoginseng (Burk.) F.H. Chen, have demonstrated antioxidative and anti-inflammatory activities. This study aimed to investigate the potential protective effects of PTS against renal fibrosis and explore the underlying pharmacological mechanisms. A unilateral ureteral obstruction (UUO) model was established in Sprague-Dawley (SD) rats to induce renal fibrosis. Histopathological changes were assessed using hematoxylin and eosin (HE) staining, Masson's trichrome staining, and transmission electron microscopy (TEM). Network pharmacology and molecular docking approaches were employed to identify potential signaling molecules through which PTS may mitigate renal fibrosis. Western blotting, quantitative real-time PCR (qRT-PCR), and immunohistochemistry were utilized to validate the involvement of specific signaling pathways in PTS-mediated anti-fibrotic effects. Our data demonstrated that PTS alleviated renal dysfunction and provided protective effects against renal fibrosis, primarily through the TNF-α and TGF-β1 signaling pathways. Moreover, PTS treatment significantly downregulated pro-inflammatory cytokines such as TNF-α, IL-6, and Smad3 activity. Additionally, PTS inhibited the expression of key fibrosis markers, including α-SMA, collagen I, and fibronectin. Our study suggests that PTS exert a prevention effect in renal fibrosis by blocking the TGF-β1/Smad3 signaling pathway.

Chronic kidney disease of unknown aetiology: a real-world study

2025-06-18

Joshua Storrar , Sayyid Raza , Ivona Baričević-Jones +4 more | Research Square (Research Square)

<title>Abstract</title> <bold>Background</bold> Diagnosis of rare chronic kidney disease (CKD) can be difficult with conventional diagnostic workup. When no diagnosis is identified, this is termed CKD of unknown aetiology (CKDUA). There … <title>Abstract</title> <bold>Background</bold> Diagnosis of rare chronic kidney disease (CKD) can be difficult with conventional diagnostic workup. When no diagnosis is identified, this is termed CKD of unknown aetiology (CKDUA). There are multiple benefits in obtaining a diagnosis in these cases. The advent and increasing availability of genetic testing in recent years has been a welcome additional diagnostic tool. In this study we aimed to determine the demographics, kidney related outcomes and predisposing factors for a cohort of patients with CKDUA within the Salford Kidney Study (SKS).<bold>Methods</bold> The SKS is a single-centre, ongoing, prospective, observational cohort study of adult patients referred to the renal service at Salford Royal Hospital, UK. Within the SKS there are 398 patients with CKDUA. A group with diabetic kidney disease (DKD) was used as a comparator. An analysis was performed comparing these two groups with a particular focus on their demographics and kidney related outcomes.<bold>Results</bold> median age of the CKDUA cohort was 71.4 years, with 60.1% male and 96.2% White. There was advanced CKD at presentation (median eGFR 30ml/min/1.73m<sup>2</sup>), with a 5-year mortality of 27.6%. When compared with the DKD cohort, the CKDUA cohort were older (71.4 years vs 67.3 years, p < 0.001), had more equal sex distribution (male 60.1% vs 68%, p < 0.009), had less advanced renal disease at presentation (eGFR 30ml/min/1.73m<sup>2</sup> vs 26ml/min/1.73m<sup>2</sup>,p < 0.001), and were less likely to progress to renal replacement therapy (14.1% vs 28.2%, p < 0.001).<bold>Conclusions</bold> CKDUA is difficult to manage: other than general supportive measures there is little else that can be offered. This study reports on a real-world cohort of patients with CKDUA and identifies that in comparison to a DKD cohort their outcomes are improved.

Delineating the Metabolic Phenotype of Biopsy-Derived Kidney Cells

2025-06-17

Masataka Kawamura , Catherine Parmentier , Lisa A. Robinson +7 more | Journal of Visualized Experiments

Role of Inflammatory and Hematologic Biomarkers in Predicting Chronic Kidney Disease Progression

2025-06-17

Collince Odiwuor Ogolla , Lucy W. Karani , Stanslaus Musyoki +1 more | Research Square (Research Square)

<title>Abstract</title> <bold>Background</bold> Chronic kidney disease (CKD) is a progressive condition that as such entails huge morbidity and mortality. Identification of dependable biomarkers that could predict the progression of CKD can … <title>Abstract</title> <bold>Background</bold> Chronic kidney disease (CKD) is a progressive condition that as such entails huge morbidity and mortality. Identification of dependable biomarkers that could predict the progression of CKD can provide an opportunity for risk stratification and early intervention. This study evaluates the role of inflammatory and hematologic biomarkers in the 1-year prediction of CKD progression.<bold>Methods</bold> The study was prospective and observational, with 120 adults recruited with CKD stages 1–4, from April 2024 to April 2025. Baseline data including the demographic characteristics, comorbidities, and laboratory parameters were collected. The biomarkers studied included CRP, NLR, PLR, hemoglobin, WBC count, and serum ferritin. CKD progression was defined as a persistent decline of ≥ 25% in eGFR or movement to a higher KDIGO stage. Statistical application included t-tests, coefficients of correlation, multivariate logistic regression, and ROC curve analysis.<bold>Results</bold> Within a 12-month follow-up period, CKD progression was documented in 42 patients (35.0%) and was most frequent among patients in CKD stage 3 at baseline. Progressors recorded significantly higher values of CRP, NLR, PLR, and ferritin and lower values of hemoglobin ((p < 0.05). On multivariate analysis, CRP, NLR, and hemoglobin emerged as independent predictors of progression. ROC analysis was conducted showing good prediction ability for CRP (AUC 0.78), hemoglobin (AUC 0.75), and NLR (AUC 0.72).<bold>Conclusion</bold> Elevated inflammatory and hematologic biomarkers, particularly CRP, NLR, and low hemoglobin, are significantly associated with the progression of CKD. These biomarkers could be employed as cheap and quick differentiating tools for high-risk CKD patients while fostering clinical monitoring documentation.

External validation, recalibration, and clinical utility of the kidney failure risk equation in patients with advanced CKD: a nationwide retrospective cohort analysis in Peru

2025-06-16

Jessica Bravo-Zúñiga , Percy Soto-Becerra , Edgar Coila-Paricahua +5 more | Research Square (Research Square)

<title>Abstract</title> Background The Kidney Failure Risk Equation (KFRE) is widely used for predicting kidney failure, but its external validity in Latin America is limited. A previous study in Peru found … <title>Abstract</title> Background The Kidney Failure Risk Equation (KFRE) is widely used for predicting kidney failure, but its external validity in Latin America is limited. A previous study in Peru found that KFRE was miscalibrated but did not evaluate its recalibration or clinical utility. Methods We conducted a retrospective cohort study using data from EsSalud’s Renal Health Surveillance Program (2013–2022), including 30,031 patients with chronic kidney disease (CKD) stages G3-4. Kidney failure was defined by dialysis initiation or nephrologist-confirmed end-stage renal disease. Calibration was assessed using observed-to-expected (O/E) ratios and differences, calibration slope, and intercept, while discrimination was evaluated using the concordance index (C-index). Recalibrated models were developed, and decision curve analysis (DCA) was performed to evaluate clinical utility. Results The original KFRE demonstrated good discrimination (C-index: 0.88 at 2 years, 0.85 at 5 years) but poor calibration in-the-large: O/E ratios indicated mean underestimation of risk at 2 years (O/E ratio: 1.84) and a slight mean overestimation at 5 years (O/E ratio: 1.06). Original KFRE also had poor weak (slope: 0.58) and poor moderate calibration. Recalibrated models improved calibration in-the-large, but none achieved good weak (all slope < 1) and moderate calibration. However, DCA showed a higher net benefit for KFRE-based nephrology referrals (in original and recalibrated by method D) compared to Peruvian and international guidelines, especially over a 5-year horizon. Conclusions Despite miscalibration, KFRE remains valuable for guiding nephrology referrals in Peru, with recalibrated models offering potential improvements. This is the first study in Latin America to rigorously assess the clinical utility of KFRE.

Proteomic analysis of human kidney biopsies unveils emerging acute kidney injury very early after liver graft reperfusion

2025-06-16

Åsa Norén , Roberto Boi , Rille Pullerits +7 more | Journal of Translational Medicine

Abstract Background Acute kidney injury (AKI) is a frequent complication after liver transplantation (LT) and is associated with morbidity, mortality, and late development of chronic kidney disease. Risk factors for … Abstract Background Acute kidney injury (AKI) is a frequent complication after liver transplantation (LT) and is associated with morbidity, mortality, and late development of chronic kidney disease. Risk factors for AKI after LT include patient, perioperative and graft-related factors. The exact renal molecular mechanisms behind AKI in LT are unclear. Methods Alterations in the proteome were investigated in kidney biopsies from 21 patients undergoing LT using quantitative proteomics. The most upregulated protein was validated using immunohistochemistry. In addition, serum levels of interleukin (IL)-33, insulin-like growth factor binding protein (IGFBP)-7 and high-mobility group box (HMGB)-1 were analyzed. In silico data validation was performed using 14 recently published proteomics and transcriptomics datasets. Results In post-reperfusion biopsies, we identified 731 differentially regulated proteins between patients with and without AKI. The most upregulated pathways were related to inflammation, integrin signaling and extracellular matrix (ECM) remodeling. The most downregulated pathways were traceable to a mitochondrial origin. HMGB-1 was found to be already upregulated (15%) 2 h after LT in patients who later developed AKI. The AKI group also showed upregulation of the alarmin IGFBP-7, caspases 1, 4 and 8, nuclear factor kappa B subunits, and the inflammasome adaptor protein PYCARD. Circulating IL-33 and HMGB-1 (but not IGFBP-7) increased during LT but returned to normal levels within 24 h. Altogether, these findings indicate ongoing inflammatory signaling activity in the kidneys of LT recipients who ultimately develop moderate or severe AKI shortly after liver graft reperfusion. Conclusions LT induces extensive alarmin signaling and ECM remodeling in the kidneys of recipients who develop postoperative AKI. Further strategies to curtail this phenomenon are mandated. Trial registration https://www.researchweb.org/is/en/vgr/project/278585 , Registered 24 May 2022 (Retrospectively registered).

Correction: Current status, trend changes, and future predictions of the disease burden of type 1 diabetes kidney disease in global and China

2025-06-16

Qinghua Yang , Jing Li , Mingwei Luo +1 more | Frontiers in Endocrinology

Can screening for albuminuria detect type 2 diabetes mellitus?

2025-06-13

Mi Kyung Kim | Kidney Research and Clinical Practice

Study of MicroRNA-192 as an Early Biomarker for Diagnosis of Diabetic Nephropathy

2025-06-13

Mohamad Motawea , Mayada S. Khalel , Ismail Kandil +4 more | Diagnostics

Background/Objectives: Diabetic nephropathy (DN) is a serious complication of diabetes mellitus. This clinical condition is diagnosed through the detection of microalbuminuria. Molecular biomarkers such as MicroRNA-192 may play a role … Background/Objectives: Diabetic nephropathy (DN) is a serious complication of diabetes mellitus. This clinical condition is diagnosed through the detection of microalbuminuria. Molecular biomarkers such as MicroRNA-192 may play a role in the early diagnosis of this condition. This study aims to compare the serum concentrations of MicroRNA-192 in diabetic patients with and without DN and in healthy individuals. Methods: This study was a retrospective case-control study that included three groups. Group I included diabetic patients without DN, Group II included patients with DN, and Group III included healthy control subjects. Blood samples were obtained from each participant and subjected to a full biochemical study including creatinine, albumin, and the detection of MicroRNA-192 by real-time polymerase chain reaction. Results: There were significant differences among the MicroRNA-192 levels in the three groups (p-0.001). There was a significant increase in the MicroRNA-192 level in Group I (1.35 ± 7 0.5) compared with Group II (0.65 ± 7 0.2, p3 = 0.001) and Group III (0.83 ± 7 0.3, p1-0.001). There was a significant reduction in the MicroRNA-192 level in Group II compared with Group III (p2-0.001). Conclusions: This study highlights the potential role of serum miR-192 as a noninvasive biomarker for the early detection of DN in patients with type 2 DM. Our findings demonstrated that serum miR-192 levels were significantly reduced in patients with DN compared with diabetic patients without nephropathy and healthy controls, suggesting the possible protective role of miR-192 in early disease stages.

Is cystatin C more accurate in determining GFR than creatinine in adults with suspected chronic kidney disease?

2025-06-13

Christopher Boisselle , Justin Z. Chen | Evidence-Based Practice

Response to Comment on “Establishing discordance rate of estimated glomerular filtration rate between serum creatinine‐based calculations and cystatin‐C‐based calculations in critically ill patients”

2025-06-13

Victoria Williams , Anthony T. Gerlach | Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy

Comment on “Establishing discordance rate of estimated glomerular filtration rate between serum creatinine‐based calculations and cystatin‐C‐based calculations in critically ill patients”

2025-06-13

Rachel W. Khan , Wendy L. St. Peter | Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy

MiR-106b-5p improving the progression of chronic kidney disease by inhibiting the TGF-β/Smad pathway

2025-06-13

Qiang Ma , Lili Xu , Peng Zhou +3 more | Hereditas

Abstract Background Chronic Kidney Disease (CKD) is a progressive disorder marked by renal impairment and declining kidney function. Aims To investigate the expression of miR-106b-5p in CKD and its regulatory … Abstract Background Chronic Kidney Disease (CKD) is a progressive disorder marked by renal impairment and declining kidney function. Aims To investigate the expression of miR-106b-5p in CKD and its regulatory relationship with the TGF-β/Smad pathway. Methods A total of 150 cases of CKD patients were selected as the observation group, while 100 healthy individuals served as the control group. Lipopolysaccharide (LPS) was utilized to induce damage to HK-2 cells. Real-time fluorescence PCR was used to detect the expression of genes. The CCK − 8 assay was utilized to evaluate cell proliferation, while flow cytometry was applied to measure the cell apoptosis rate. Results miR-106b-5p is notably downregulated in CKD and exhibits a significant positive correlation with the eGFR in affected patients. Additionally, miR-106b-5p demonstrates a strong association with the levels of inflammatory factors in individuals with CKD. Furthermore, the expression of miR-106b-5p is reduced in LPS-induced HK-2 cells. Upregulation of miR-106b-5p can improve the inhibitory effect of LPS on the viability of HK-2 cells, reduce the apoptosis rate of cells, and alleviate the inflammatory response. miR-106b-5p serves as a negative regulatory factor within the TGF-β/Smad signaling pathway by directly targeting the pivotal receptor TGFBR2 and the downstream effectors SMAD2/3 within the TGF-β signaling cascade. Conclusions miR-106b-5p ameliorates CKD progression by suppressing the TGF - β/Smad signaling pathway and could potentially be a therapeutic target for CKD.

102-OR: Long-Term Kidney Outcomes following Metabolic and Bariatric Surgery in Adolescents with Severe Obesity

2025-06-13

John B. Rode , Subin Jang , Petter Bjornstad +7 more | Diabetes

Introduction and Objective: Although metabolic and bariatric surgery (MBS) improves kidney function in adolescents with severe obesity up to 3 years post-surgery, long-term kidney outcomes remain unclear. This study evaluated … Introduction and Objective: Although metabolic and bariatric surgery (MBS) improves kidney function in adolescents with severe obesity up to 3 years post-surgery, long-term kidney outcomes remain unclear. This study evaluated 8-year kidney outcomes in adolescents following MBS. Methods: Data from the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) study, a multicenter cohort of 274 adolescents undergoing MBS, were analyzed. Urine albumin-to-creatinine ratio (ACR) and cystatin C-based estimated glomerular filtration rate (eGFR) were assessed pre- and 8 years post-surgery. Mean differences were compared via Wilcoxon signed-rank and paired t-tests (α=0.05). Results: Participants [mean preoperative age: 16.7±1.6 years; median preoperative BMI: 50.5 (45.2, 58.5) kg/m2] demonstrated significant renal improvements (Figure 1). Participants with baseline eGFR&lt;90 mL/min per 1.73m2 (n=42) improved from 75 ± 12 to 96 ± 23 mL/min per 1.73m2 (p&lt;0.001), while those with albuminuria (ACR≥30 mg/g, n=28) decreased from 117 (75-182) to 15 mg/g (9-24) (p&lt;0.001). Hyperfiltration (eGFR≥135 mL/min per 1.73m2,n=24) was attenuated from 153 ± 18 to 135 ± 25 mL/min/1.73m2 (p=0.005). Conclusion: MBS in youth with severe obesity improves low eGFR and attenuates albuminuria and hyperfiltration over 8 years, highlighting its role in reducing obesity-related kidney disease and CKD risk. Disclosure J.B. Rode: None. S. Jang: None. P. Bjornstad: Consultant; AstraZeneca, Bayer Pharmaceuticals, Inc, Lilly USA LLC, Novo Nordisk. A. Kula: None. T.M. Jenkins: None. S. Sisley: Consultant; Rhythm Pharmaceuticals, Inc. Research Support; Rhythm Pharmaceuticals, Inc, Eli Lilly and Company. A. Courcoulas: Research Support; Allurion, Eli Lilly and Company. M. Michalsky: Other Relationship; Intuitive Surgical, Inc. M. Helmrath: None. J.R. Ryder: Board Member; Calorify. Research Support; Boehringer-Ingelheim, Eli Lilly and Company, Recordati. T. Inge: Consultant; Mediflix, UpToDate, Teleflex, Medtronic, Eli Lilly and Company, BrainStorm Cell Therapeutics, Standard Bariatrics. Funding Funding for Teen-LABS was provided by the National Institutes of Health (NIH) (U01DK072493 / UM1 DK072493 to T.H.I.) (UM1 DK095710 to C.X., T.M.J.) and the National Center for Research Resources and the National Center for Advancing Translational Sciences, NIH (8UL1TR000077). Support also came from the National Center for Research Resources and the National Center for Advancing Translational Sciences, NIH, (UL1TR000114).

1289-P: Cystatin C Predicts Mortality in Patients with Coronary Artery Disease Both among Subjects with and among Those without the Metabolic Syndrome

2025-06-13

THOMAS PLATTNER , Alexander Vonbank , BARBARA LARCHER +7 more | Diabetes

Introduction and Objective: Cystatin C is an established biomarker for renal function and, given the strong impact of chronic kidney disease on life expectancy, might indicate overall mortality. However, evidence … Introduction and Objective: Cystatin C is an established biomarker for renal function and, given the strong impact of chronic kidney disease on life expectancy, might indicate overall mortality. However, evidence for cystatin C as a predictor of mortality in coronary artery disease (CAD) patients is limited and controversial. Methods: We prospectively recorded mortality in 1115 patients with angiographically verified CAD over a mean follow-up of 11.5±5.0 years. Results: At baseline, 514 patients had the metabolic syndrome (MetS) and 601 did not have the MetS. During follow-up, 627 (56.5%) of our patients died. Cystatin C proved to be a strong and independent predictor for mortality in the total study cohort (standardized adjusted HR 1.20 [1.13-1.28], p&lt;0.001). When MetS status was taken into account, cystatin C significantly predicted mortality both in patients with the MetS (HR 1.20 [1.10-1.30], p&lt;0.001) and in non-MetS patients (HR 1.20 [1.10-1.32], p&lt;0.001). Conclusion: We conclude that cystatin C predicts overall mortality in patients with coronary artery disease both among patients with the MetS and in non-MetS individuals. Disclosure T. Plattner: None. A. Vonbank: None. B. Larcher: None. A. Mader: None. L. Schnetzer: None. M. Neyer: None. J. Vogel: None. P. Elsner: None. A. Leiherer: None. A. Muendlein: None. A. Festa: None. H. Drexel: None. C.H. Saely: None.

Understanding and managing the complications of chronic kidney disease: A comprehensive review

2025-06-13

Vankodoth Sireesha , Bhavani Dhomakonda , Mekala Sai Charitha +3 more | International Journal of Science and Research Archive

A progressive illness, chronic kidney disease (CKD) is linked to several systemic consequences that raise morbidity and death. Anemia, fluid retention, renal osteodystrophy, cardiovascular disease (CVD), and sepsis are the … A progressive illness, chronic kidney disease (CKD) is linked to several systemic consequences that raise morbidity and death. Anemia, fluid retention, renal osteodystrophy, cardiovascular disease (CVD), and sepsis are the main consequences of chronic kidney disease (CKD) that are highlighted in this study. Iron dysregulation and decreased erythropoietin production cause anemia, but water and sodium retention cause fluid overload. Unbalances in the metabolism of calcium, phosphate, and vitamin D are the main cause of renal osteodystrophy. Both conventional and CKD-specific risk factors contribute to CVD, the primary cause of death in CKD patients. Because of immunological failure, CKD also makes people more vulnerable to infections and sepsis. To enhance patient outcomes, early detection and focused therapy approaches—such as phosphate binders, erythropoiesis-stimulating medicines, and new drugs like SGLT2 inhibitors and HIF-PHIs—are crucial.

Renal microcirculation and mechanisms in diabetic kidney disease

2025-06-05

Hang Xing , Jun Ma , Yu Wei +5 more | Frontiers in Endocrinology

Diabetic kidney disease (DKD), a severe and long-term complication of diabetes, is a microcirculatory pathology influenced by diabetes-related factors that affects hundreds of millions of people worldwide. DKD is characterized … Diabetic kidney disease (DKD), a severe and long-term complication of diabetes, is a microcirculatory pathology influenced by diabetes-related factors that affects hundreds of millions of people worldwide. DKD is characterized by proteinuria, glomerular injury, and renal fibrosis, ultimately leading to end-stage renal disease. Its pathogenesis is complex and involves multiple cellular and molecular mechanisms. Microcirculatory disorders form the fundamental pathological basis of DKD. These disorders are primarily manifested through changes in the number and structure of renal microvessels, alterations in renal hemodynamics, formation of renal thrombi, glomerular endothelial cell dysfunction, and associated lesions in podocytes and mesangial cells. This article focuses on renal microangiopathy and glomerular endothelial cell (GEC) dysfunction, summarizing the mechanisms associated with microcirculatory lesions in DKD, including nitric oxide (NO), advanced glycation end-products (AGEs), vascular endothelial growth factor (VEGF), the renin-angiotensin-aldosterone system (RAAS), reactive oxygen species (ROS), the NLRP3 inflammasome, protein kinase C (PKC), epidermal growth factor receptor (EGFR), and platelet-derived growth factor (PDGF). Additionally, we briefly introduce the characteristics of DKD animal models in terms of renal microcirculation and discuss the application of relevant technological tools in studying microcirculatory lesions in DKD.

Association of baseline and changes in estimated glucose disposal rate and risk of chronic kidney disease: evidence from a national longitudinal study

2025-06-05

Fan Zhang , Jiao Li , Xueling Li +2 more | Acta Diabetologica

Correlation analysis between hemoglobin and type 2 diabetic nephropathy: a two-center retrospective study

2025-06-05

Xiaoling Liu , Ze Zhang , Lu Lin +6 more | Acta Diabetologica

Variability and misclassification of albuminuria in patients with type 2 diabetes mellitus

2025-06-05

Lukas Buchwinkler , Felix Keller , Stefanie Thöni +2 more | Scientific Reports

Measurement of albuminuria is central in assessment, staging and evaluation of treatment response of diabetic kidney disease. Due to high intra-individual variability of albuminuria, guidelines recommend specific sampling intervals and … Measurement of albuminuria is central in assessment, staging and evaluation of treatment response of diabetic kidney disease. Due to high intra-individual variability of albuminuria, guidelines recommend specific sampling intervals and usually agreement of two out of three samples for correct staging. Nevertheless, different confirmation and staging strategies have been proposed for albuminuria assessment. We report albumin-to-creatine ratio measurements of spot urine samples in a modern European cohort (n = 773) of type 2 diabetes mellitus patients in a primary care setting. Information on albuminuria, its variability and associated baseline characteristics are presented. The amount of "misclassification" of alternative staging strategies compared to the guideline recommended gold standard is reported. Additionally, we applied quantile regression to estimate the conditional quantiles of the second and third measurement, allowing an estimation of likely variability at a given albuminuria level. Overall, the coefficient of variation of albumin-to-creatinine ratio, as a measure of variability, is high with a median of 41%. This variability leads in part to substantial disagreement of alternative staging strategies with the gold standard. In general, higher variability of albuminuria seems to be associated with more severe kidney disease. The high variability of albuminuria necessitates caution and consideration for adequate clinical use. In this study, we provide data regarding the expected variability, correct usage and limitations of albuminuria in a modern primary care diabetes mellitus population.

NF-κB p65 mediated lnc-Traf3ip2 exacerbates renal fibrosis in diabetic kidney disease

2025-06-05

Keqian Wu , Peiling Li , He Zha +7 more | Acta Diabetologica