Serum creatinine as marker of kidney function in South Asians: a study of reduced GFR in adults in Pakistan

Migrant populations of South Asian origin have a higher risk for chronic kidney disease than the native whites. Several formulas have been developed to estimate kidney function from serum creatinine concentration. However, none of these has been validated in the South Asian population, which generally has different muscle mass composition than whites. A population-based cross-sectional study was performed on 262 individuals who were aged \u3e or = 40 yr in Karachi, Pakistan. Reduced GFR was defined as creatinine clearance (Ccr) measured in 24-h urine collection of /min per 1.73 m2. Creatinine excretion was compared with age- and gender-matched white individuals by comparison of observed versus expected results on the basis of a formula using t test. The agreement among Cockcroft Gault (CG) Ccr and Modification of Diet in Renal Disease (MDRD) Study GFR equations was assessed by regression analyses, and the degree of accuracy of estimated versus measured GFR was determined. Mean (95% confidence interval) creatinine excretion was 1.7 (1.0 to 2.4) mg/kg per d lower than expected for age- and gender-matched white individuals (P \u3c 0.001). The coefficient of determination for measured Ccr on the logarithmic scale was 66.7 and 55.6% for the CG and MDRD Study equations, respectively. The proportion of estimates within 20, 30, and 50% of measured Ccr values was 47.7 versus 32.8% (P \u3c 0.001), 64.9 versus 49.6% (P \u3c 0.001), and 79.4 versus 72.9 (P = 0.07) for CG versus MDRD Study equations, respectively. Lower mean creatinine excretion in these individuals may explain, in part, suboptimal agreement between estimated versus measured GFR. Inclusion of terms for ethnic and racial groups other than white and black might improve the performance of GFR estimating equations

Screening for acquired cystic kidney disease: A decision analytic perspective

Screening for acquired cystic kidney disease: A decision analytic perspective. Acquired cystic kidney disease (ACKD) increases the risk of renal malignancy, and many authors suggest routine screening of dialysis patients for ACKD and renal tumors. However, they have defined neither the target population, the optimal screening strategy, the magnitude of its benefit, nor its risk. We used decision analysis to evaluate strategies of performing either computed tomography (CT) or ultrasound every three years on all dialysis patients and annually on patients found to have cysts. We compared these strategies to a strategy of seeking cysts and cancer only if these are clinically suspected. The baseline analysis shows that both CT and ultrasound may decrease cancer deaths by half for patients with a life expectancy of 25 years. Screening for ACKD offers these patients as much as a 1.6 year gain in life expectancy. However, for the majority of patients beginning renal replacement therapy, age or comorbid disease substantially limits life expectancy. For such patients, the gain in life expectancy from an ACKD screening program is measured in days. Sensitivity analyses show that the benefit of screening depends on the rate of malignant transformation, which needs better definition. The gain in life expectancy does not appear to be large enough to justify an ACKD screening program for the entire ESRD population. However, for the youngest and healthiest patients, a screening program would be of benefit. The magnitude of this benefit is uncertain, because the analysis was consistently biased in favor of the screening strategies

Aspirin Use and Incident Cardiovascular Disease, Kidney Failure, and Death in Stable Kidney Transplant Recipients: A Post Hoc Analysis of the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial

Cardiovascular disease (CVD) is the leading cause of death in kidney transplant recipients. Whether aspirin may reduce the risk for CVD, death, and kidney failure outcomes is uncertain

C-Reactive protein and risk of ESRD: results from the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT)

Background: To better understand a potential association of elevated C-reactive protein (CRP) level with progression of chronic kidney disease (CKD), we examined the relationship of CRP level with the development of end-stage renal disease (ESRD) in the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT). Study Design Post hoc analysis of a randomized controlled trial. Setting & Participants: 4,038 patients with type 2 diabetes, CKD, and anemia in TREAT. Predictor: Baseline serum CRP concentrations. Outcomes: The primary outcome was development of ESRD; secondary outcomes included doubling of serum creatinine level, a composite of ESRD/serum creatinine doubling, and a composite of death or ESRD. Measurements: We fit unadjusted and adjusted Cox regression models to test the association of baseline CRP level with time to the development of the outcomes of interest. Results: Mean age of participants was 67 years, 43% were men, and 64% were white. Approximately half (48%) the patients had CRP levels > 3.0 mg/L; 668 patients developed ESRD, and 1,270 developed the composite outcome of death or ESRD. Compared with patients with baseline CRP levels ≤ 3.0 mg/L, those with moderately/markedly elevated CRP levels (≥6.9 mg/L; 24% of patients) had a higher adjusted risk for ESRD (HR, 1.32; 95% CI, 1.07-1.63) and the composite outcome of death or ESRD (HR, 1.41; 95% CI, 1.21-1.64). Although nonsignificant, similar trends were noted in competing-risk models. Limitations: Results may not be generalizable to nondiabetic CKD or diabetic CKD in the absence of anemia. Conclusions: Elevated baseline CRP levels are common in type 2 diabetic patients with anemia and CKD and are associated with the future development of ESRD and the composite of death or ESRD

Level of kidney function as a risk factor for atherosclerotic cardiovascular outcomes in the community

AbstractObjectivesThe goal of this study was to determine whether the level of kidney function is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) outcomes in the Atherosclerosis Risk in Communities (ARIC) study, a prospective cohort study of subjects aged 45 to 64 years.BackgroundThe level of kidney function is now recognized as a risk factor for ASCVD outcomes in patients at high risk for ASCVD, but it remains unknown whether the level of kidney function is a risk factor for ASCVD outcomes in the community.MethodsCox proportional-hazards regression was used to evaluate the association of glomerular filtration rate (GFR) with ASCVD after adjustment for the major ASCVD risk factors in 15,350 subjects. We searched for nonlinear relationships between GFR and ASCVD.ResultsDuring a mean follow-up time of 6.2 years, 965 (6.3%) of subjects had ASCVD events. Subjects with GFR of 15 to 59 ml/min/1.73 m2(n = 444, hazard ratio 1.38 [1.02, 1.87]) and 60 to 89 ml/min/1.73 m2(n = 7,665, hazard ratio 1.16 [1.00, 1.34]) had an increased adjusted risk of ASCVD compared with subjects with GFR of 90 to 150 ml/min/1.73 m2. Each 10 ml/min/1.73 m2lower GFR was associated with an adjusted hazard ratio of 1.05 (1.02, 1.09), 1.07 (1.01, 1.12), and 1.06 (0.99, 1.13) for ASCVD, de novo ASCVD, and recurrent ASCVD, respectively. A nonlinear model did not fit the data better than a linear model.ConclusionsThe level of GFR is an independent risk factor for ASCVD and de novo ASCVD in the ARIC study

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

The definition and classification for chronic kidney disease was proposed by the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF-KDOQI) in 2002 and endorsed by the Kidney Disease: Improving Global Outcomes (KDIGO) in 2004. This framework promoted increased attention to chronic kidney disease in clinical practice, research and public health, but has also generated debate. It was the position of KDIGO and KDOQI that the definition and classification should reflect patient prognosis and that an analysis of outcomes would answer key questions underlying the debate. KDIGO initiated a collaborative meta-analysis and sponsored a Controversies Conference in October 2009 to examine the relationship of estimated glomerular filtration rate (GFR) and albuminuria to mortality and kidney outcomes. On the basis of analyses in 45 cohorts that included 1,555,332 participants from general, high-risk, and kidney disease populations, conference attendees agreed to retain the current definition for chronic kidney disease of a GFR <60ml/min per 1.73m2 or a urinary albumin-to-creatinine ratio >30mg/g, and to modify the classification by adding albuminuria stage, subdivision of stage 3, and emphasizing clinical diagnosis. Prognosis could then be assigned based on the clinical diagnosis, stage, and other key factors relevant to specific outcomes. KDIGO has now convened a workgroup to develop a global clinical practice guideline for the definition, classification, and prognosis of chronic kidney disease

Serum Phosphorus and Risk of Cardiovascular Disease, All-Cause Mortality, or Graft Failure in Kidney Transplant Recipients: An Ancillary Study of the FAVORIT Trial Cohort

Mild hyperphosphatemia is a putative risk factor for cardiovascular disease [CVD], loss of kidney function, and mortality. Very limited data are available from sizable multicenter kidney transplant recipient (KTR) cohorts assessing the potential relationships between serum phosphorus levels and the development of CVD outcomes, transplant failure, or all-cause mortality

CKD classification based on estimated GFR over three years and subsequent cardiac and mortality outcomes: a cohort study

<p>Abstract</p> <p>Background</p> <p>It is unknown whether defining chronic kidney disease (CKD) based on one versus two estimated glomerular filtration rate (eGFR) assessments changes the prognostic importance of reduced eGFR in a community-based population.</p> <p>Methods</p> <p>Participants in the Atherosclerosis Risk in Communities Study and the Cardiovascular Health Study were classified into 4 groups based on two eGFR assessments separated by 35.3 ± 2.5 months: sustained eGFR < 60 mL/min per 1.73 m²(1 mL/sec per 1.73 m²); eGFR increase (change from below to above 60); eGFR decline (change from above to below 60); and eGFR persistently ≥60. Outcomes assessed in stratified multivariable Cox models included cardiac events and a composite of cardiac events, stroke, and mortality.</p> <p>Results</p> <p>There were 891 (4.9%) participants with sustained eGFR < 60, 278 (1.5%) with eGFR increase, 972 (5.4%) with eGFR decline, and 15,925 (88.2%) with sustained eGFR > 60. Participants with eGFR sustained < 60 were at highest risk of cardiac and composite events [HR = 1.38 (1.15, 1.65) and 1.58 (1.41, 1.77)], respectively, followed by eGFR decline [HR = 1.20 (1.00, 1.45) and 1.32 (1.17, 1.49)]. Individuals with eGFR increase trended toward increased cardiac risk [HR = 1.25 (0.88, 1.77)] and did not significantly differ from eGFR decline for any outcome. Results were similar when estimating GFR with the CKD-EPI equation.</p> <p>Conclusion</p> <p>Individuals with persistently reduced eGFR are at highest risk of cardiovascular outcomes and mortality, while individuals with an eGFR < 60 mL/min per 1.73 m²at any time are at intermediate risk. Use of even a single measurement of eGFR to classify CKD in a community population appears to have prognostic value.</p

Urine Injury Biomarkers and Risk of Adverse Outcomes in Recipients of Prevalent Kidney Transplants: The Folic Acid for Vascular Outcome Reduction in Transplantation Trial

Recipients of kidney transplants (KTR) are at increased risk for cardiovascular events, graft failure, and death. It is unknown whether urine kidney injury biomarkers are associated with poor outcomes among KTRs. We conducted a post hoc analysis of the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial using a case-cohort study design, selecting participants with adjudicated cardiovascular events, graft failure, or death. Urine neutrophil gelatinase–associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), IL-18, and liver–type fatty acid binding protein (L-FABP) were measured in spot urine samples and standardized to urine creatinine concentration. We adjusted for demographics, cardiovascular risk factors, eGFR, and urine albumin-to-creatinine ratio. Patients had 291 cardiovascular events, 257 graft failure events, and 359 deaths. Each log increase in urine NGAL/creatinine independently associated with a 24% greater risk of cardiovascular events (adjusted hazard ratio [aHR], 1.24; 95% confidence interval [95% CI], 1.06 to 1.45), a 40% greater risk of graft failure (aHR, 1.40; 95% CI, 1.16 to 1.68), and a 44% greater risk of death (aHR, 1.44; 95% CI, 1.26 to 1.65). Urine KIM-1/creatinine and IL-18/creatinine independently associated with greater risk of death (aHR, 1.29; 95% CI, 1.03 to 1.61 and aHR, 1.25; 95% CI, 1.04 to 1.49 per log increase, respectively) but not with risk of cardiovascular events or graft failure. Urine L-FABP did not associate with any study outcomes. In conclusion, among prevalent KTRs, higher urine NGAL, KIM-1, and IL-18 levels independently and differentially associated with greater risk of adverse outcomes