Sickle Cell Trait, Disease Linked With Faster Kidney Function Decline in African American Patients

Sickle-cell trait (SCT) and disease (SCD) among African American patients were associated with a faster kidney function decline, with SCD contributing to a more rapid decline, according to study findings published in the Journal of the American Society of Nephrology.¹

According to the CDC, SCD affects approximately 100,000 Americans and is most common in African-Americans (1 out of every 365 births) and Hispanic-Americans (1 out of every 16,300 births). SCT, characterized by 1 copy of the altered hemoglobin gene compared with SCD’s 2 copies, additionally is found most prominently in African-Americans, affecting up to 8% to 10% of the population.

As study authors note, prior studies have described the association between sickle hemoglobin and chronic kidney disease (CKD), but there is limited understanding of the effect of sickle hemoglobin on the decline in estimated glomerular filtration rate (eGFR) over time compared with a population with no sickle hemoglobin. eGFR, a marker of disease severity and associated comorbid conditions, has been shown to be an accurate predictor of prognosis of renal failure in patients with type 2 diabetes, indicating its potential screening importance among patients with SCD/SCT.

Researchers conducted a multicenter, observational study using registry data collected from January 2005 to June 2018 from adult black patients with SCT (n = 1251) or SCD (n = 230), distinguished as exposures, and reference patients with normal hemoglobin phenotype status (n = 8729).

The study included solely black patients aged ≥ 18 years with at least 1 year of follow-up and 3 eGFR values. Primary outcomes served as 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. Researchers used linear mixed models to evaluate the difference in the mean change in eGFR per year.

Compared with reference patients, those with SCT were older (mean age: 40 vs 36 years), less likely to be female (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). Conversely, patients with SCD were younger (mean age, 33 vs 36 years of age), less likely to be female (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) compared with reference patients.

After performing a comparison of SCD and SCT, researchers found a faster eGFR decline in patients with SCD (0.83 mL/min per 1.73 m2 per year).

In both phenotypes, male sex, diabetes mellitus, and baseline eGFR ≥ 90 ml/min per 1.73 m² were associated with faster eGFR decline. Based on the study findings, research suggests that black patients with SCT lose nearly half an eGFR unit more of kidney function every year than those with a normal hemoglobin phenotype.

Most surprising were data on SCT and eGFR decline, which was highlighted in an accompanying editorial by Karl Nath, MD, division of nephrology and hypertension at the department of medicine at the Mayo Clinic, and Gregory Vercellotti, MD, division of hematology, oncology, and transplantation at the University of Minnesota.²

“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,” said Nath and Vercellotti.

Researchers note that further prospective and mechanistic studies are needed to develop best practices focusing on eGFR decline among black patients with SCD or SCT. “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,” said Nath and Vercellotti.

Reference

1. Olaniran KO, Allegretti AS, Zhao SH, et al. Kidney Function Decline among Black Patients with Sickle Cell Trait and Sickle Cell Disease: An Observational Cohort Study [published online December 6, 2019]. J Am Soc Nephrol. doi: 10.1681/ASN.2019050502.
2. Nath KA, Vercellotti GM. Renal Functional Decline in Sickle Cell Disease and Trait [published online January 24, 2020]. J Am Soc Nephrol. doi: 10.1681/ASN.2019121291.