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February 14, 2020
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eGFR decline among black patients with sickle cell trait, disease

Sickle cell trait and disease were associated with a faster decline in eGFR in black patients, according to a study published in the Journal of the American Society of Nephrology.

“Despite studies describing the association between sickle hemoglobin and CKD, there is limited understanding of the effect of sickle hemoglobin on eGFR decline over time compared with a population with no sickle hemoglobin,” Kabir O. Olaniran, of the division of nephrology at the department of medicine at the Massachusetts General Hospital at Harvard Medical School in Boston, and colleagues wrote.

The study included black patients aged at least 18 years at first available serum creatinine, at least three serum creatinine values, at least 1 year between first and last serum creatinine dates and a hemoglobin electrophoresis. Researchers defined exposure as patients with sickle cell trait (SCT) and sickle cell disease (SCD) confirmed by a hemoglobin electrophoresis test and interpreted by a pathologist. Using data from the Research Patient Data Registry between January 2005 to June 2018, researchers identified 10,210 black patients (1,251 SCT; 230 SCD; 8,729 reference).

Outcomes were the difference between exposure and reference patients in the mean annual change in the eGFR and the risk for incident CKD defined as time to first eGFR less than 60 mL/min per 1.73 m2 in patients with baseline eGFR 65 mL/min per 1.73 m2 or more.

Results showed that compared with reference patients, patients with SCT were older (mean age, 40 vs. 36 years), less likely to be women (78% vs. 88%), had longer follow-up (8.4 vs. 8.1 years), higher prevalence of comorbidities and lower mean eGFR (103 vs. 114 mL/min per 1.73 m2). Compared with reference patients, patients with SCD were younger (mean age, 33 vs. 36 years), less likely to be women (50% vs. 88%), had shorter follow-up (7.3 vs. 8.1 years), lower prevalence of comorbidities and higher mean eGFR (128 vs. 114 mL/min per 1.73 m2).

Researchers performed a comparison of SCD and SCT and found a faster eGFR decline in patients with SCD (0.83 mL/min per 1.73 m2 per year). Across all patients, there were 753 CKD events (115 SCT; 16 SCD; 582 reference) over a mean follow-up of 8 years. Compared with reference patients, risk for incident CKD in SCT increased in both unadjusted (1.74 to 2.47) and adjusted (1.05 to 1.51) analyses.

Factors associated with eGFR decline in patients with SCT and SCD were male sex, diabetes and baseline eGFR 90 mL/min per 1.73 m2 or more. These findings suggest that black patients with SCT lose nearly half an eGFR unit more of kidney function every year than those with a normal hemoglobin phenotype.

“An unexpected and perplexing finding by Olaniran, et al is that, in SCT, a higher rate of eGFR decline was associated with lower levels of hemoglobin S,” Karl A. Nath, of the division of nephrology and hypertension at the department of medicine at the Mayo Clinic, and Gregory M. Vercellotti, of the division of hematology, oncology and transplantation at the University of Minnesota, wrote in an accompanying editorial.

The study highlights a need for knowledge of potential contributions of SCD and SCT to progressive CKD in black patients, they concluded.

“The finding that SCT per se accelerates the decline in eGFR in black patients adds to mounting evidence that SCT may not be a benign condition because SCT predisposes to venous thromboembolic disease, rhabdomyolysis and renal medullary carcinoma,” Nath and Vercellotti wrote. “The study by Olaniran, et al not only underscores the need to re-examine such assumptions and to characterize renal involvement in SCT in depth, but also is relevant to the management of CKD.” by Erin T. Welsh

Disclosures: Olaniran reports no relevant financial disclosures. Please see the full study for other authors’ relevant financial disclosures. The editorial authors report no relevant financial disclosures.