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Sickle cell gene linked to increased risk for end-stage renal disease

Patients who carry the sickle cell trait were linked to a twofold increase in developing end-stage renal disease as opposed to noncarriers, according to research published in the Journal of the American Society of Nephrology.

The relationship was independent of known risk factors for end-stage renal disease (ESRD), including APOL1 high-risk genotype status, diabetes, hypertension and age, and could have major public policy implications, the researchers wrote.

“Doctors can use this information to start screening for kidney disease earlier and to aggressively treat any other risk factors [patients] may have, such as diabetes or high [BP],” Rakhi P. Naik, MD, MHS, of the division of hematology at Johns Hopkins University, said in a press release.

Researchers analyzed data from 9,909 self-reporting participants in the REGARDS , incident ESRD occurred in 40 of 739 participants with the sickle cell trait, six of 243 participants with hemoglobin C trait and 234 of 8,927 noncarriers. Further, the incidence rate for ESRD was four per 1,000 person-years for noncarriers of the sickle cell trait; it was 8.5 per 1,000 person-years for carriers. Compared with participants without the sickle cell trait, those with the trait had an HR of 2.03 (95% CI, 1.44-2.84) for ESRD. The incidence rate for ESRD among participants with APOL1 high-risk genotypes was 6.6 per 1,000 person years (HR = 1.77; 95% CI, 1.31-2.38) for participants with vs. those without APOL1 high-risk genotypes. The median follow-up for ESRD was 6.49 years. Naik and colleagues wrote that the hemoglobin C trait did not associate with prevalent chronic kidney disease or ESRD.

Although sickle cell trait screening is routine, checking for APOL1 high-risk genotypes is not, leading researchers to address the significance of their findings, according to Naik and colleagues.

“Because individuals with [sickle cell trait] are identified soon after birth, genetic counseling about ESRD risk could allow for early [chronic kidney disease] screening and risk factor modification such as promoting smoking cessation, weight loss, hypertension/glucose control and avoiding nephrotoxic agents,” they wrote. “Further investigation is needed to assess whether these measures are effective in attenuating [chronic kidney disease] risk in this population. In addition, individuals at high-risk for [sickle cell trait]-related kidney disease may benefit from early intervention.”

Future studies should explore whether the effectiveness of hydroxyurea and angiotensin-converting enzyme inhibition in decreasing albuminuria in patients with sickle cell disease can be mirrored in those with the sickle cell trait, the researchers wrote. – by Janel Miller

Disclosure: The researchers report no relevant financial disclosures.