Sickle cell anemia affects glomerular filtration rate, hyperfiltration
SAN DIEGO — Patients with sickle cell anemia experience a faster decline in the glomerular filtration rate and an increased prevalence of hyperfiltration among patients with sickle cell disease, although no association between the two was observed, according to findings presented at the ASH Annual Meeting and Exposition.
Proteinuria and markers of increased hemolysis were the greatest indicators of this accelerated decrease in the glomerular filtration rate.
“Glomerular ischemia, hyperfiltration and hyposthenuria characterize the renal dysfunction found in sickle cell disease, but the natural history of and risk factors contributing to progression of disease remain unclear,” the researchers wrote. “Potential markers of sickle cell disease nephropathy, such as anemia severity, hemolytic rate, blood pressure and albuminuria, have been studied with varied conclusions. We sought to evaluate clinical, laboratory and genetic predictors of sickle cell disease nephropathy progression in a longitudinal sickle cell disease cohort.”
Julia Z. Xu, MD, of the department of medicine at Duke University Medical Center, and colleagues completed a chart review of 280 adults with sickle cell disease who were being followed routinely at the medical center and were participating in an earlier study. All participants were aged 18 years or older at the time of enrollment.
Outpatient data were gathered from the Duke Enterprise Data Unified Content Explorer, a data extraction tool. Descriptive data were obtained during enrollment and at the most recent outpatient follow-up visit.
The researchers performed genotyping of APOL1 variants. Estimated glomerular filtration rate was determined with the extended Modification of Diet in Renal Disease Study and Chronic Kidney Disease Epidemiology Collaboration equations. A glomerular filtration rate below 60 mL/min/1.73 m2 was used to signify kidney disease; a rate above 130 mL/min/1.73 m2 was used to indicate hyperfiltration.
Mean age at the time of enrollment was 33.3 years. The mean glomerular filtration rate at baseline, as measured by the Modification of Diet in Renal Disease Study classification, was 148.6 mL/min/1.73 m2 and 127 mL/min/1.73 m2 as measured by the Chronic Kidney Disease Epidemiology Collaboration. Findings from both equations “correlated well for glomerular filtration rates in the low to normal range, but diverged for glomerular filtration rates over [approximately] 150 mL/min/1.73 m2, with Modification of Diet in Renal Disease Study [classifications] producing a wider range,” the researchers wrote.
The increased rate of hyperfiltration in the cohort led the researchers to conduct additional analyses with the Chronic Kidney Disease Epidemiology Collaboration equation. Baseline glomerular filtration rate correlated with baseline proteinuria (P < .0001), hemoglobinuria (P < .0001), hemoglobin level (P = .03), platelet count (P < .0001), reticulocyte count (P = .03), bilirubin (P < .0001), systolic blood pressure (P = .0003), diastolic blood pressure (P < .0001) and the APOL1 G1 allele (P = .02).
Individuals with at least 5 years of follow up and 3 or more outpatient glomerular filtration rate measurements (n = 183) were then selected to evaluate the pattern of sickle cell disease neuropathy progression. The mean rate of glomerular filtration rate decline was 2.5 ± 5.6 mL/min/1.73 m2 per year, which is greater than the approximate 1.27 mL/min/1.73 m2 annual glomerular filtration rate decline among African Americans in the general population. However, the researchers observed “no statistically significant differences in baseline characteristics for the two cohorts.”
Using these calculations, the researchers characterized sickle cell disease neuropathy as a composite outcome of either rapid decline in the glomerular filtration rate (> 3 mL/min/1.73 m2 per year) or incident chronic kidney disease that occurred in the follow-up period. Seventy-three of the 183 patients examined, or 40%, developed neuropathy based on this classification.
Decreased baseline hemoglobin (P = .008), baseline proteinuria (P = .01), increased reticulocyte count (P = .03) and greater LDH (P = .02) were found to be positive predictors of neuropathy when the researchers conducted multivariable logistic regression modeling with baseline glomerular filtration rate as a covariate.
Baseline hemoglobinuria, white blood cell count, platelet count, bilirubin, blood pressure, BMI and APOL1 variants were not found to be predictive of neuropathy. In addition, patients with hyperfiltration physiology at baseline did not demonstrate an increased rate of neuropathy over a 5-year follow-up period.
These findings demonstrate an accelerated decrease in the glomerular filtration rate and an elevated incidence of hyperfiltration among adults with sickle cell disease, although no correlation between the two was demonstrated, according to the study’s conclusion.
“Additional investigation into the longitudinal trajectory of sickle cell disease nephropathy and potential interventions targeted to slowing the rate of GFR decline may improve outcomes in sickle cell disease,” the researchers wrote. – by Julia Ernst, MS
Xu JZ, et al. Abstract 9. Presented at: ASH Annual Meeting and Exposition; Dec. 3-6, 2016; San Diego.
Disclosures: The researchers report no relevant financial disclosures.