Kidney Function Decline among Black Patients with Sickle Cell Trait and Sickle Cell Disease: An Observational Cohort Study

Abstract

BackgroundSickle cell trait and sickle cell disease are thought to be independent risk factors for CKD, but the trajectory and predictors of kidney function decline in patients with these phenotypes are not well understood.MethodsOur multicenter, observational study used registry data (collected January 2005 through June 2018) and included adult black patients with sickle cell trait or disease (exposures) or normal hemoglobin phenotype (reference) status (ascertained by electrophoresis) and at least 1 year of follow-up and three eGFR values. We used linear mixed models to evaluate the difference in the mean change in eGFR per year.ResultsWe identified 1251 patients with sickle cell trait, 230 with sickle cell disease, and 8729 reference patients, with a median follow-up of 8 years. After adjustment, eGFR declined significantly faster in patients with sickle cell trait or sickle cell disease compared with reference patients; it also declined significantly faster in patients with sickle cell disease than in patients with sickle cell trait. Male sex, diabetes mellitus, and baseline eGFR ≥90 ml/min per 1.73 m2 were associated with faster eGFR decline for both phenotypes. In sickle cell trait, low hemoglobin S and elevated hemoglobin A were associated with faster eGFR decline, but elevated hemoglobins F and A2 were renoprotective.ConclusionsSickle cell trait and disease are associated with faster eGFR decline in black patients, with faster decline in sickle cell disease. Low hemoglobin S was associated with faster eGFR decline in sickle cell trait but may be confounded by concurrent hemoglobinopathies. Prospective and mechanistic studies are needed to develop best practices to attenuate eGFR decline in such patients.

Kidney Transplantation With a Sickle Cell Disease Donor

“…Another recent observational study included 1251 black adult patients with sickle cell trait, 230 with sickle cell disease, and 8729 reference patients, with a median follow-up of 8 years. 5 Sickle cell trait and disease are associated with faster eGFR decline in black patients, with faster decline in sickle cell disease. 5 African American donor ethnicity is one of 10 risk factors in calculating the kidney donor profile index used in assessing organ quality.…”

“…5 Sickle cell trait and disease are associated with faster eGFR decline in black patients, with faster decline in sickle cell disease. 5 African American donor ethnicity is one of 10 risk factors in calculating the kidney donor profile index used in assessing organ quality. A recent study evaluated outcomes of deceased-donor kidney transplants from African American donors stratified by kidney donor profile index.…”

“… 5 Sickle cell trait and disease are associated with faster eGFR decline in black patients, with faster decline in sickle cell disease. 5 …”

Heme Oxygenase 1: A Defensive Mediator in Kidney Diseases

“…Local hypoxia in a restricted area, for example, during a vaso-occlusive crisis, increases their polymerization capacity and instability and induces massive, intravascular hemolysis which can alter renal structure and function [ 121 , 122 ]. Both SCA and its heterozygous state (sickle cell trait, with an attenuated phenotype), are associated with an increased risk of CKD [ 123 ]. In addition to sickle cell susceptibility to hemolysis, HbS is unstable and prone to auto-oxidation and release of its cofactor heme.…”

Mortality and Hospitalizations among Sickle Cell Disease Patients with End-Stage Kidney Disease Initiating Dialysis

“…Furthermore, prior studies have only examined patients in whom ESKD was caused by SCD (SCD-ESKD) [6, 8] instead of ESKD patients with concurrent SCD (SCD with ESKD). This is important because recent studies have shown that severe phenotypes of SCD and SCD patients with more frequent hospitalizations for pain episodes tend to have a faster decline in GFR [17, 18]. This implies that prior studies which examined outcomes in ESKD caused by SCD may have been biased by the most severe SCD phenotypes.…”