Work

Rapid decline in estimated glomerular filtration rate in sickle cell anemia: results of a multicenter pooled analysis

Year: 2020

Type: article

Abstract: Rapid decline in estimated glomerular filtration rate in sickle cell anemia: results of a multicenter pooled analysisChronic kidney disease (CKD), typically defined as kidney damage or decreased kidney function for 3 or more months, is common in sickle cell disease (SCD). 1 Increasing evidence suggests that the glomerulopathy of SCD is progressive.2 CKD is associated with increased mortality in SCD. 3 Based on single center studies, we previously reported on the high prevalence of rapid decline in kidney function, defined as estimated glomerular filtration rate (eGFR) loss >3.0 mL/min/1.73m 2 per year, in SCD.[4][5][6] In the present study, we further examine rapid eGFR decline in sickle cell anemia, using a pooled analysis of patients to better characterize factors associated with such decline and its association with mortality.Patients from four centers, University of North Carolina at Chapel Hill (UNC), Duke University Medical Center (Duke), University of Illinois at Chicago (UIC), and St. Jude Children's Research Hospital/Methodist University Comprehensive Sickle Cell Center (Methodist) were analyzed.4,5,7,8 Patients, at least 18 years old, with sickle cell anemia, were evaluated during routine visits while in "steady state".Baseline visit was defined as the first available serum creatinine measurement during the study period.Only patients with two or more measures of kidney function over the observation period were included.Mortality during the observation period was assessed by medical record review and/or by utilizing the US Social Security Death Index.Approvals were obtained from Institutional Review Boards at each institution.Estimated GFR was calculated using the creatininebased chronic kidney disease epidemiology collaboration (CKD-EPI) equation.9 Rapid decline of kidney function was defined as eGFR loss of >3.0 mL/min/1.73m 2 per year 10 or eGFR loss of >5.0 mL/min/1.73m 2 per year.11 Rapid decline of kidney function, using these thresholds, was ascertained based on the slope in a linear model, with eGFR as the response and time as the covariate, using all available observations from a patient.The slope was defined as the estimate of the regression coefficient for time.CKD progression was defined as a decline in eGFR to <90 mL/min/1.73m 2 and at least 25% decline from baseline, 11 or eGFR decline to <90 mL/min/1.73m 2 and at least 50% decline from baseline or requiring renal replacement therapy.12 Variables of interest were summarized by median and interquartile ranges (IQR) if continuous, or by counts and percentages if categorical.In order to evaluate eGFR change over time, a linear mixed effects model with subject level random effects for intercept and slope for time was fitted, adjusting for baseline age, sex and cohort.Stratified analyses according to hyperfiltration at baseline were conducted.Logistic regression analyses were employed to evaluate variables associated with rapid decline in eGFR.In multivariable analyses, variables associated with rapid decline in eGFR with P-values <0.3 in individual analyses, but without an excess of missing data (<20% missing data), were included in the initial model.Cox regression analyses were employed to evaluate the association of rapid decline in eGFR with mortality, from the period of first eGFR assessment to the last assessment.The analysis included 606 individuals with sickle cell anemia (HbSS, HbSb 0 ), 236 from UNC (followed from 2004 -2013), 203 from Duke (followed from 2002 -2016), 94 from UIC (followed from 2009 -2017) and 73 from Methodist (followed from 2006 -2017).The median observation period was 5.20 years (IQR: 1.56-7.53),with 31,286 patient-years of observation.The median patient age in the pooled analysis was 27 years (IQR: 20-38) and 327 (54.0%) were female (Table 1).Baseline laboratory and clinical data in individual cohorts are shown in the Online Supplementary Table S1.In evaluating the change in eGFR over time in the pooled analysis, only the main cohort effect was retained as the time-cohort interaction was not significant (P=0.19).For all patients, the change in eGFR over time, adjusted for baseline age, sex and main cohort effect, was -2.36 mL/min/1.73m 2 per year (95% Confidence Interval [CI]: -2.68 to -2.04; P<0.0001) (Figure 1A).In patients with hyperfiltration, the time-cohort interaction was significant (P=0.008),so both main cohort and interaction effects were retained.The estimated change in eGFR over time for patients with hyperfiltration, without consideration of the time-cohort interaction, was -2.09 mL/min/1.73m 2 per year (95% CI: -2.50 to -1.69; P<0.0001).In patients without hyperfiltration, the time-cohort interaction was not significant (P=0.97),

Source: Haematologica

DOI: 10.3324/haematol.2020.267419