Glomerular filtration rate by differing measures, albuminuria and prediction of cardiovascular disease, mortality and end-stage kidney disease.
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SUBMITTER: Lees JS
PROVIDER: S-EPMC6858876 | biostudies-literature | 2019 Nov
REPOSITORIES: biostudies-literature
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Glomerular filtration rate by differing measures, albuminuria and prediction of cardiovascular disease, mortality and end-stage kidney disease.
Lees Jennifer S JS Welsh Claire E CE Celis-Morales Carlos A CA Mackay Daniel D Lewsey James J Gray Stuart R SR Lyall Donald M DM Cleland John G JG Gill Jason M R JMR Jhund Pardeep S PS Pell Jill J Sattar Naveed N Welsh Paul P Mark Patrick B PB
Nature medicine 20191107 11
Chronic kidney disease is common in the general population and associated with excess cardiovascular disease (CVD), but kidney function does not feature in current CVD risk-prediction models. We tested three formulae for estimated glomerular filtration rate (eGFR) to determine which was the most clinically informative for predicting CVD and mortality. Using data from 440,526 participants from UK Biobank, eGFR was calculated using serum creatinine, cystatin C (eGFRcys) and creatinine-cystatin C. ...[more]
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Project description:We studied here the independent associations of estimated glomerular filtration rate (eGFR) and albuminuria with mortality and end-stage renal disease (ESRD) in individuals with chronic kidney disease (CKD). We performed a collaborative meta-analysis of 13 studies totaling 21,688 patients selected for CKD of diverse etiology. After adjustment for potential confounders and albuminuria, we found that a 15 ml/min per 1.73 m² lower eGFR below a threshold of 45 ml/min per 1.73 m² was significantly associated with mortality and ESRD (pooled hazard ratios (HRs) of 1.47 and 6.24, respectively). There was significant heterogeneity between studies for both HR estimates. After adjustment for risk factors and eGFR, an eightfold higher albumin- or protein-to-creatinine ratio was significantly associated with mortality (pooled HR 1.40) without evidence of significant heterogeneity and with ESRD (pooled HR 3.04), with significant heterogeneity between HR estimates. Lower eGFR and more severe albuminuria independently predict mortality and ESRD among individuals selected for CKD, with the associations stronger for ESRD than for mortality. Thus, these relationships are consistent with CKD stage classifications based on eGFR and suggest that albuminuria provides additional prognostic information among individuals with CKD.
| S-EPMC3917543 | biostudies-literature
Project description:IMPORTANCE:The established chronic kidney disease (CKD) progression end point of end-stage renal disease (ESRD) or a doubling of serum creatinine concentration (corresponding to a change in estimated glomerular filtration rate [GFR] of ?57% or greater) is a late event. OBJECTIVE:To characterize the association of decline in estimated GFR with subsequent progression to ESRD with implications for using lesser declines in estimated GFR as potential alternative end points for CKD progression. Because most people with CKD die before reaching ESRD, mortality risk also was investigated. DATA SOURCES AND STUDY SELECTION:Individual meta-analysis of 1.7 million participants with 12,344 ESRD events and 223,944 deaths from 35 cohorts in the CKD Prognosis Consortium with a repeated measure of serum creatinine concentration over 1 to 3 years and outcome data. DATA EXTRACTION AND SYNTHESIS:Transfer of individual participant data or standardized analysis of outputs for random-effects meta-analysis conducted between July 2012 and September 2013, with baseline estimated GFR values collected from 1975 through 2012. MAIN OUTCOMES AND MEASURES:End-stage renal disease (initiation of dialysis or transplantation) or all-cause mortality risk related to percentage change in estimated GFR over 2 years, adjusted for potential confounders and first estimated GFR. RESULTS:The adjusted hazard ratios (HRs) of ESRD and mortality were higher with larger estimated GFR decline. Among participants with baseline estimated GFR of less than 60 mL/min/1.73 m2, the adjusted HRs for ESRD were 32.1 (95% CI, 22.3-46.3) for changes of ?57% in estimated GFR and 5.4 (95% CI, 4.5-6.4) for changes of ?30%. However, changes of ?30% or greater (6.9% [95% CI, 6.4%-7.4%] of the entire consortium) were more common than changes of ?57% (0.79% [95% CI, 0.52%-1.06%]). This association was strong and consistent across the length of the baseline period (1 to 3 years), baseline estimated GFR, age, diabetes status, or albuminuria. Average adjusted 10-year risk of ESRD (in patients with a baseline estimated GFR of 35 mL/min/1.73 m2) was 99% (95% CI, 95%-100%) for estimated GFR change of ?57%, was 83% (95% CI, 71%-93%) for estimated GFR change of ?40%, and was 64% (95% CI, 52%-77%) for estimated GFR change of ?30% vs 18% (95% CI, 15%-22%) for estimated GFR change of 0%. Corresponding mortality risks were 77% (95% CI, 71%-82%), 60% (95% CI, 56%-63%), and 50% (95% CI, 47%-52%) vs 32% (95% CI, 31%-33%), showing a similar but weaker pattern. CONCLUSIONS AND RELEVANCE:Declines in estimated GFR smaller than a doubling of serum creatinine concentration occurred more commonly and were strongly and consistently associated with the risk of ESRD and mortality, supporting consideration of lesser declines in estimated GFR (such as a 30% reduction over 2 years) as an alternative end point for CKD progression.
| S-EPMC4172342 | biostudies-literature
Project description:BackgroundAccording to studies by the National Kidney Foundation and Food and Drug Administration, 30% and 40% declines in estimated glomerular filtration rate (eGFR) could be used as surrogate endpoints of end-stage renal disease (ESRD). However, the benefits of using these endpoints in diabetic patients remain unclear.MethodsThis cohort study comprised Japanese patients with type 2 diabetes; those with repeated serum creatinine measurements during a baseline period of 2 years (n = 1868) or 3 years (n = 2001) were enrolled. Subsequent risks of ESRD following eGFR declines were assessed.ResultsIn the 2-year baseline analysis, the cumulative prevalence of -20%, -30%, -40%, and -53% changes in eGFR were 23.9%, 11.1%, 6.8%, and 3.7%, respectively. There were 133 cases (7.1%) of subsequent ESRD during a median follow-up period of 6.5 years. In the 3-year baseline analysis, the corresponding proportions were 28.1%, 14.0%, 7.7%, and 3.9%, respectively, with 110 participants (5.5%) reaching ESRD during a median follow-up period of 5.5 years. The adjusted hazard ratios of subsequent ESRD following -53%, -40%, -30%, and -20% changes in eGFR during the 2-year baseline period were 22.9 (11.1-47.3), 12.8 (6.9-23.7), 8.2 (4.3-15.5), and 3.9 (2.2-7.0), respectively when compared with the no changes in eGFR. In the 3-year baseline analysis, the corresponding risks were 29.7 (10.8-81.9), 18.4 (7.6-44.7), 12.8 (5.2-32.2), and 5.4 (2.3-12.8), respectively. In the subgroup analysis, similar trends were observed in patients with macroalbuminuria at baseline.ConclusionsDeclines in eGFR were strongly associated with subsequent risk of ESRD in Japanese type 2 diabetic patients. In addition to 30% and 40% declines, a 20% decline in eGFR over 2 years could be considered as a candidate surrogate endpoint of ESRD in diabetic kidney disease.
| S-EPMC6072050 | biostudies-literature
Project description:Background and objectivesExposure to particulate matter (PM) <2.5 μm in aerodynamic diameter (PM2.5) has been linked to detrimental health effects. This study aimed to describe the relationship between long-term PM2.5 exposure and kidney disease, including eGFR, level of albuminuria, and incident CKD.Design, setting, participants, & measurementsThe study included 10,997 participants from the Atherosclerosis Risk in Communities cohort who were followed from 1996-1998 through 2016. Monthly mean PM2.5 concentrations (μg/m3) were estimated at geocoded participant addresses using geographic information system-based, spatiotemporal generalized additive mixed models-including geospatial covariates such as land use-and then averaged over the 12-month period preceding participant examination. Covariate-adjusted, cross-sectional associations of PM2.5, baseline eGFR, and urinary albumin-creatinine ratio (UACR) were estimated using linear regression. PM2.5 and incident CKD (defined as follow-up eGFR <60 ml/min per 1.73 m2 with ≥25% eGFR decline relative to baseline, CKD-related hospitalization or death based on International Classification of Diseases 9/10 codes, or development of ESKD) associations were estimated using Cox proportional hazards regression. Modeling was stratified by study site, and stratum-specific estimates were combined using random-effects meta-analyses.ResultsBaseline mean participant age was 63 (±6) years and eGFR was 86 (±16) ml/min per 1.73 m2. There was no significant PM2.5-eGFR association at baseline. Each 1-μg/m3 higher annual average PM2.5 was associated with higher UACR after adjusting for demographics, socioeconomic status, and clinical covariates (percentage difference, 6.6%; 95% confidence interval [95% CI], 2.6% to 10.7%). Each 1-μg/m3 higher annual average PM2.5 was associated with a significantly higher risk of incident CKD (hazard ratio, 1.05; 95% CI, 1.01 to 1.10).ConclusionsExposure to higher annual average PM2.5 concentrations was associated with a higher level of albuminuria and higher risk for incident CKD in a community-based cohort.
| S-EPMC7057299 | biostudies-literature
Project description:Background and Objectives The study aimed to evaluate the performance of a predictive model using the kidney failure risk equation (KFRE) for end-stage renal disease (ESRD) in diabetes and to investigate the impact of glomerular filtration rate (GFR) as estimated by different equations on the performance of the KFRE model in diabetes. Design, Setting, Participants, and Measurements A total of 18,928 individuals with diabetes without ESRD history from the UK Biobank, a prospective cohort study initiated in 2006–2010, were included in this study. Modification of diet in renal disease (MDRD), chronic kidney disease epidemiology collaboration (CKD-EPI) or revised Lund–Malmö (r-LM) were used to estimate GFR in the KFRE model. Cox proportional risk regression was used to determine the correlation coefficients between each variable and ESRD risk in each model. Harrell’s C-index and net reclassification improvement (NRI) index were used to evaluate the differentiation of the models. Analysis was repeated in subgroups based on albuminuria and hemoglobin A1C (HbA1c) levels. Results Overall, 132 of the 18,928 patients developed ESRD after a median follow-up of 12 years. The Harrell’s C-index based on GFR estimated by CKD-EPI, MDRD, and r-LM was 0.914 (95% CI = 0.8812–0.9459), 0.908 (95% CI = 0.8727–0.9423), and 0.917 (95% CI = 0.8837–0.9496), respectively. Subgroup analysis revealed that in diabetic patients with macroalbuminuria, the KFRE model based on GFR estimated by r-LM (KFRE-eGFRr-LM) had better differentiation compared to the KFRE model based on GFR estimated by CKD-EPI (KFRE-eGFRCKD-EPI) with a KFRE-eGFRr-LM C-index of 0.846 (95% CI = 0.797–0.894, p = 0.025), while the KFRE model based on GFR estimated by MDRD (KFRE-eGFRMDRD) showed no significant difference compared to the KFRE-eGFRCKD-EPI (KFRE-eGFRMDRD C-index of 0.837, 95% CI = 0.785–0.889, p = 0.765). Subgroup analysis of poor glycemic control (HbA1c >8.5%) demonstrated the same trend. Compared to KFRE-eGFRCKD-EPI (C-index = 0.925, 95% CI = 0.874–0.976), KFRE-eGFRr-LM had a C-index of 0.935 (95% CI = 0.888–0.982, p = 0.071), and KFRE-eGFRMDRD had a C-index of 0.925 (95% CI = 0.874–0.976, p = 0.498). Conclusions In adults with diabetes, the r-LM equation performs better than the CKD-EPI and MDRD equations in the KFRE model for predicting ESRD, especially for those with macroalbuminuria and poor glycemic control (HbA1c >8.5%).
| S-EPMC9205244 | biostudies-literature
Project description:BackgroundSofosbuvir, a prodrug nucleoside inhibitor of hepatitis C virus, has a predominant circulating metabolite that is renally eliminated. Whether sofosbuvir is associated with chronic kidney disease (CKD) progression is not well understood.MethodsWe performed a retrospective analysis of patients with estimated glomerular filtration rate (eGFR) 30-89 mL/min/1.73 m2 treated with sofosbuvir in 76 Phase 2/3 registrational trials. We evaluated eGFR at each study visit. Separately, we performed a retrospective analysis of an administrative claims database (IQVIA PharMetrics Plus™) to compare the risk of incident end-stage renal disease (ESRD) associated with the use of sofosbuvir or non-sofosbuvir regimens among patients with CKD using propensity score methods. Exposure, CKD status and outcomes were determined using diagnosis and medication claim codes. Cox proportional hazards methods were used to estimate ESRD risk.ResultsAmong 4642 trial participants with baseline stage 2 CKD (eGFR 60-89 ml/min/1.73 m2 ) and 682 trial participants with stage 3 CKD (eGFR 30-59 ml/min/1.73 m2 ) mean (SD) eGFR improved from baseline to 4 weeks post-treatment (+0.7 [9.3] and +2.6 [8.8] ml/min/1.73 m2 , respectively; p < 0.001 each). In the second analysis, among 2042 patients with CKD receiving sofosbuvir-based regimens compared to 431 receiving non-sofosbuvir-based regimens, after adjusting for baseline covariates and weighting based on treatment propensity scores, there was no significant difference in risk of ESRD (adjusted HR = 0.85, 95% CI: 0.51-1.42).ConclusionsClinical trial participants with CKD did not experience worsening eGFR during sofosbuvir-based treatment, and sofosbuvir was not associated with an increased risk of ESRD in patients with CKD in a nationally-representative administrative claims database.
| S-EPMC9313579 | biostudies-literature
Project description:BACKGROUND:The usefulness of estimated glomerular filtration rate (eGFR) and albuminuria for prediction of cardiovascular outcomes is controversial. We aimed to assess the addition of creatinine-based eGFR and albuminuria to traditional risk factors for prediction of cardiovascular risk with a meta-analytic approach. METHODS:We meta-analysed individual-level data for 637 315 individuals without a history of cardiovascular disease from 24 cohorts (median follow-up 4·2-19·0 years) included in the Chronic Kidney Disease Prognosis Consortium. We assessed C statistic difference and reclassification improvement for cardiovascular mortality and fatal and non-fatal cases of coronary heart disease, stroke, and heart failure in a 5 year timeframe, contrasting prediction models for traditional risk factors with and without creatinine-based eGFR, albuminuria (either albumin-to-creatinine ratio [ACR] or semi-quantitative dipstick proteinuria), or both. FINDINGS:The addition of eGFR and ACR significantly improved the discrimination of cardiovascular outcomes beyond traditional risk factors in general populations, but the improvement was greater with ACR than with eGFR, and more evident for cardiovascular mortality (C statistic difference 0·0139 [95% CI 0·0105-0·0174] for ACR and 0·0065 [0·0042-0·0088] for eGFR) and heart failure (0·0196 [0·0108-0·0284] and 0·0109 [0·0059-0·0159]) than for coronary disease (0·0048 [0·0029-0·0067] and 0·0036 [0·0019-0·0054]) and stroke (0·0105 [0·0058-0·0151] and 0·0036 [0·0004-0·0069]). Dipstick proteinuria showed smaller improvement than ACR. The discrimination improvement with eGFR or ACR was especially evident in individuals with diabetes or hypertension, but remained significant with ACR for cardiovascular mortality and heart failure in those without either of these disorders. In individuals with chronic kidney disease, the combination of eGFR and ACR for risk discrimination outperformed most single traditional predictors; the C statistic for cardiovascular mortality fell by 0·0227 (0·0158-0·0296) after omission of eGFR and ACR compared with less than 0·007 for any single modifiable traditional predictor. INTERPRETATION:Creatinine-based eGFR and albuminuria should be taken into account for cardiovascular prediction, especially when these measures are already assessed for clinical purpose or if cardiovascular mortality and heart failure are outcomes of interest. ACR could have particularly broad implications for cardiovascular prediction. In populations with chronic kidney disease, the simultaneous assessment of eGFR and ACR could facilitate improved classification of cardiovascular risk, supporting current guidelines for chronic kidney disease. Our results lend some support to also incorporating eGFR and ACR into assessments of cardiovascular risk in the general population. FUNDING:US National Kidney Foundation, National Institute of Diabetes and Digestive and Kidney Diseases.
| S-EPMC4594193 | biostudies-literature
Project description:BackgroundAortic stiffness increases with age and increases pulsatile stress in the microcirculation. Abnormalities in kidney microvascular structure and function may contribute to development or progression of chronic kidney disease in older people.MethodsWe performed a longitudinal analysis of 629 community-dwelling elderly Icelandic adults from the Age, Gene/Environment Susceptibility-Reykjavik Study with two visits over a mean follow-up of 5.3 years. We evaluated the associations of carotid-femoral pulse wave velocity (CFPWV), carotid pulse pressure (CPP) and augmentation index (AI), with the change in estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) assessed as annual change and dichotomized as large changes. Models were adjusted for age, sex, height, heart rate, traditional cardiovascular disease risk factors and baseline kidney measures.ResultsWhen eGFR was analyzed as a continuous variable, higher baseline CFPWV and CPP, but not AI, were significantly associated with a larger annual decline in eGFR in models adjusted for age, sex, height, heart rate and baseline eGFR, but not after additional adjustment for the mean arterial pressure. When eGFR was analyzed as a categorical variable, higher CFPWV was significantly associated with a decrease in eGFR of ?3 mL/min/1.73 m 2 /year [odds ratio (OR) 1.53, 95% confidence interval (CI) 1.11-2.13] and higher AI was associated with 30% eGFR decline during follow-up (OR 1.44 and 95% CI 1.03-2.00) in fully adjusted models. None of the tonometry measures was associated with change in UACR.ConclusionsAbnormalities in vascular health may play a role in large declines in eGFR beyond the traditional cardiovascular disease risks in this older Icelandic cohort.
| S-EPMC5837316 | biostudies-literature
Project description:BACKGROUND:Albuminuria is strongly associated with future risk for cardiovascular and kidney outcomes, and has been proposed to be included in the classification of chronic kidney disease (CKD) along with glomerular filtration rate (GFR). Few data are available on whether albuminuria is associated with concurrent complications of CKD. METHODS:A cross-sectional analysis of 1,665 participants screened for the Modification of Diet in Renal Disease (MDRD) study was performed to examine the association between albuminuria (determined using urine albumin-creatinine ratio (ACR)) and measured GFR (determined using urinary clearance of iothalamate) with anemia, acidosis, hyperphosphatemia, and hypertension. RESULTS:Mean GFR (± SD) was 39 ml/min/1.73 m2 (± 21) and the median (25 - 75th percentile) ACR was 161 (38 - 680) mg/g. In multivariable models adjusted for age, sex, race, kidney disease etiology, and GFR, higher ACR levels were not associated with any complication. For example, comparing ACR > 300 mg/g vs. < 30 mg/g, the prevalence ratio (95% CI) for anemia was 0.98 (0.81 - 1.20), acidosis 1.13 (0.86 - 1.48), hyperphosphatemia 1.69 (0.91 - 3.17), and hypertension 1.04 (0.97 - 1.12). Lower levels of GFR were associated with all complications. For example, GFR levels < 30 ml/min/1.73 m2 vs. GFR levels 60 - 89 ml/min/1.73 m2 were associated with prevalence ratios (95% CI) of anemia 4.35 (3.18 - 5.96), acidosis 5.31 (3.41 - 8.29), hyperphosphatemia 23.8 (7.71 - 73.6), and hypertension 1.21 (1.10 - 1.32). CONCLUSIONS:Albuminuria is not associated with complications after controlling for GFR in patients younger than 70 years of age with non-diabetic CKD and GFR less than 90 ml/min/1.73 m2 and thus would not affect clinical action plans for decisions regarding evaluation and treatment of complications in similar populations.
| S-EPMC4108165 | biostudies-literature
Project description:IntroductionThe Kidney Disease: Improving Global Outcomes (KDIGO) 2012 guidelines recommend classifying patients by glomerular filtration rate (GFR) and albuminuria to predict chronic kidney disease (CKD) prognosis. The aim of this systematic review was to explore the epidemiological burden of CKD stratified by the KDIGO 2012 categories.MethodsMEDLINE® and Embase were searched for observational studies of patients with CKD with results stratified according to the KDIGO 2012 classification. Investigated outcomes were prevalence, incidence, and risk factors and complications of CKD, including mortality.ResultsThe review included ten observational studies with 3033 to 46,949 participants, conducted in the USA, China, France, Italy and Spain. The most frequently reported outcome was the prevalence of CKD (GFR categories G3-5), ranging from 2% to 17%. Most participants were normoalbuminuric, with 0.4-3.2% macroalbuminuric, and most fell within the KDIGO 2012 low-risk or moderate-risk groups, with 0.9-5.6% in the high-risk and 0.3-4.8% in the very high-risk groups. Although scarce, data on the prevalence of comorbidities in CKD according to the KDIGO classification suggest that they increase with albuminuria severity.ConclusionsPatients with CKD frequently have complications, but only a small proportion have severely increased albuminuria or fall within the KDIGO high-risk or very high-risk groups. These groups, however, are associated with the highest burden of disease, as comorbidities are more prevalent with increasing albuminuria severity. New studies framed by the KDIGO 2012 classification are needed to address key gaps in the understanding of CKD burden and outcomes.
| S-EPMC7854398 | biostudies-literature