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The Variability of Estimated Glomerular Filtration Rate Decline in Alport Syndrome.

ABSTRACT: A progressive trajectory toward renal failure is common in patients with Alport syndrome. Genotype-phenotype correlations have been well described; however, the natural history of the trajectory toward renal failure is not well described.The objective of this study is to describe the natural history of renal function decline in a cohort of Alport syndrome patients.Retrospective observational cohort study.British Columbia, Canada, chronic renal disease registry 1995-2012.37 biopsy proven Alport syndrome or hematuria with family history of Alport syndrome.Serial estimated glomerular filtration rate (eGFR) Trajectory of renal decline described graphically by fitting a cubic smoothing spline to patient's eGFR measures. Various time points within a trajectory were indexed, randomly sampled, and followed for 2 years to estimate portion of progressors (>5 mL/min/1.73 m2 /y decline), stable state (0-2 mL/min/1.73 m2 /y decline), and regressors (>2 mL/min/1.73 m2 /y incline).In this retrospective observational cohort study, participants were identified through a chronic renal disease registry in British Columbia, Canada, from 1995 to 2012. Inclusion criteria were biopsy proven or hematuria with a family history of Alport syndrome. Individual patients and family group members were studied. Trajectory of renal decline described graphically by fitting a cubic smoothing spline to patient's serial estimated glomerular filtration rate (eGFR) measures. Various time points within a trajectory were indexed, randomly sampled, and followed for 2 years to estimate portion of progressors (>5 mL/min/1.73 m2/y decline), stable state (0-2 mL/min/1.73 m2/y decline), and regressors (>2 mL/min/1.73 m2/y incline).Histological or genetic evidence of Alport syndrome is not available in all patients.Median follow-up time was 48.2 months of 37 patients (78% male), with a median age of 36 (interquartile range [IQR], 18-47) and a median age of renal replacement therapy commencement (n = 23) of 38 (IQR = 20-52). Renal function changes were found to be heterogeneous overall, intra-individual and within families. Portion of progressors in eGFR 45-60 mL/min/1.73 m2 was 73.7% (SD, 10.3), whereas 23.6% (SD, 11.0) remained stable. Within eGFR 30-45 mL/min/1.73 m2, 45.6% (SD, 7.0) were progressors, whereas 53.4% (SD, 7.4) remained stable. A large portion of eGFR 15-30 mL/min/1.73 m2 patients were stable (54.8%; SD, 8.4), whereas 25.7% (SD, 7.1) progressed and 19.5% (SD, 5.6) regressed.The renal decline in Alport syndrome patients is heterogeneous which has implications for designing clinical trials of interventions.

SUBMITTER: Langsford D

PROVIDER: S-EPMC5518963 | biostudies-other | 2016

REPOSITORIES: biostudies-other

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Project description:BackgroundGreater variability in the estimated glomerular filtration rate (eGFR) is associated with higher mortality in patients with chronic kidney disease (CKD). Heart failure (HF) is common in CKD and may increase variability through changes in hemodynamic and volume regulation. We sought to determine if patients with vs without HF have higher kidney function variability in CKD, and to define the association with mortality.Methods and resultsPatients undergoing coronary angiography from 2003 to 2013 with an eGFR of less than 60 mL/min/1.73 m2 were evaluated from the Duke Databank for Cardiovascular Disease. Variability in the eGFR, measured as the coefficient of variation (CV) of residuals from the regression of eGFR vs time, was calculated spanning 3 months to 2 years after catheterization. Mortality was assessed 2 to 7 years after catheterization. Patients were grouped into 3 HF phenotypes: HF with reduced ejection fraction, HF with preserved ejection, and no HF. Regression was used to evaluate associations between HF phenotypes and variability in the eGFR and between variability in the eGFR and mortality rate with stratification by HF phenotype. Among 3767 participants, the median eGFR at baseline was 45 mL/min/1.73 m2 (interquartile range 33-53 mL/min/1.73 m2), and longitudinal measures of eGFR over 21 months had within-patient residual variability (CV) of 14% (9%-20%). In adjusted analyses, variability in the eGFR was greater in those with HF with preserved ejection (n = 695, CV difference 0.98%, 95% confidence interval 0.14%-1.81%) or HF with reduced ejection fraction (n = 800, CV difference 2.51%, 95% confidence interval 1.66%-3.37%) relative to no HF (n = 2272). In 3068 participants eligible for mortality analysis, the presence of HF and greater variability in the eGFR were each associated independently with higher mortality, but there was no evidence of interaction between variability in the eGFR and any HF phenotype (all P for interaction ≥.49).ConclusionsVariability in the eGFR is greater in patients with HF and associated with mortality. Prediction algorithms and classification schemes should consider not only static, but also dynamic eGFR variability in HF and CKD prognostication.

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.

Project description:AimsThe prognostic significance of renal function variability has not been fully elucidated in heart failure (HF). This multicentre, prospective cohort study aimed to evaluate the usefulness of visit-to-visit variability in estimated glomerular filtration rate (eGFR) for predicting patients' outcomes in a real-world HF population.MethodsA total of 564 patients who had survived HF hospitalization were randomly assigned with a 2:1 ratio to derivation and validation cohorts, and they were then followed after discharge. Using the data for 6 months after discharge, each patient's visit-to-visit eGFR variability (EGV) was estimated. In the derivation cohort, Cox regression analyses were performed to assess the association of EGV with a subsequent composite event (death and HF hospitalization). In the validation cohort, the predictive performance was compared among Cox regression models with EGV, those with B-type natriuretic peptide (BNP) and those with eGFR.ResultsIn the derivation cohort (376 patients), median age, left ventricular ejection fraction (LVEF), BNP and eGFR at discharge were 72 years, 53.3%, 134.8 pg/mL and 58.7 mL/min/1.73 m2 , respectively. During a median follow-up of 2.2 years, higher EGV was associated with an increased risk of the composite event (adjusted hazard ratio [per standard deviation increase in log-transformed EGV], 1.5; 95% confidence interval, 1.1-2.0). A similar finding was observed in a stratified analysis by LVEF. In the validation cohort (188 patients), better model fit, discrimination, reclassification and calibration were observed for EGV than for 6-month averaged BNP or eGFR for predicting the composite event when added to HF risk prediction models. Adding EGV to models with BNP or eGFR improved model discrimination and reclassification.ConclusionsEGV predicts HF outcomes regardless of LVEF. Risk prediction models with EGV have good performance in real-world HF patients. The study findings highlight the clinical importance of observing visit-to-visit fluctuations in renal function in this population.

Project description:Background and objectivesMarijuana use has become more widely accepted in the United States and has been legalized in many areas. Although it is biologically plausible that marijuana could affect kidney function, epidemiologic data are lacking.Design, setting, participants, & measurementsWe conducted a cohort study among young adults with preserved eGFR (i.e., eGFR?60 ml/min per 1.73 m2) using data from the Coronary Artery Risk Development in Young Adults (CARDIA) study. At scheduled examinations occurring every 5 years and starting at study year 10 (calendar years, 1995-1996), cystatin C was collected over a 10-year period, and urine albumin-to-creatinine ratio was collected over a 15-year period. We investigated the cross-sectional association between current and cumulative marijuana use (in marijuana-years; one marijuana-year equals 365 days of marijuana use) and eGFR by cystatin C (eGFRcys) at year 10. In longitudinal analyses, we investigated the association between cumulative marijuana use and eGFRcys change and rapid (?3%/year) eGFRcys decline over two 5-year intervals and prevalent albuminuria (urine albumin-to-creatinine ratio ?30 mg/g) over a 15-year period.ResultsPast or current marijuana use was reported by 83% (3131 of 3765) of the cohort, and the mean eGFRcys was 111 ml/min per 1.73 m2 at year 10. Over the following 10 years, 504 had rapid eGFRcys decline, and over the following 15 years, 426 had prevalent albuminuria. Compared with no use, daily current use and ?5 marijuana-years of cumulative use were associated with lower eGFRcys at year 10: -4.5% (95% confidence interval, -8.1 to -0.7%; P=0.02) and -3.0% (95% confidence interval, -5.6 to -0.4%; P=0.03), respectively. Marijuana use was not significantly associated with eGFRcys change, rapid eGFRcys decline, or prevalent albuminuria.ConclusionsAlthough we identified a modest cross-sectional association between higher marijuana exposure and lower eGFRcys among young adults with preserved eGFR, our findings were largely null and did not demonstrate a longitudinal association between marijuana use and eGFRcys change, rapid eGFRcys decline, or prevalent albuminuria.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2017_08_24_CJASNPodcast_17_10.mp3.

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The Variability of Estimated Glomerular Filtration Rate Decline in Alport Syndrome.

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