High-risk apolipoprotein L1 genotype correlates with kidney failure risk
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Regardless of proteinuria, the presence of a high-risk apolipoprotein L1 genotype in patients with chronic kidney disease correlates with an increased risk of kidney failure, according to data published in Kidney Medicine.
“Some variants in the apolipoprotein 1 (APOL1) gene are a major risk factor for developing kidney failure and are typically only found in Black individuals. However, it is unclear whether the increased risk from these ‘high-risk alleles’ is due entirely to the development of proteinuria (protein in the urine),” Anthony Nguyen, PhD, from the University of Southern California Viterbi School of Engineering, and colleagues wrote. They added, “Understanding this mechanism is critical clinically because it could inform whether providers should regularly test patients for APOL1 high-risk alleles.”
In a retrospective observational study, researchers examined data of the
African American Study of Kidney Disease and Hypertension cohort (AASK) and Chronic Renal Insufficiency Cohort (CRIC). The AASK cohort consists of patients who self-identify as Black and have CKD due to hypertension. The CRIC cohort consists of patients of various races with moderate to severe CKD.
With self-identified race and the presence of high-risk APOL1 genotype serving as exposures, researchers considered the time to kidney failure the primary outcome. Kidney failure was defined as dialysis or transplantation.
Using Cox proportional hazard models, researchers explored how proteinuria mediated the correlation between APOL1 and kidney failure. Researchers also created models of proteinuria at baseline and as a time-varying covariate.
Overall, researchers identified an association between a high-risk APOL1 genotype and a higher risk of kidney failure. This also applied to patients with minimal proteinuria. However, the correlation was not significant in patients with high proteinuria.
Among patients who never developed proteinuria, a high-risk APOL1 genotype correlated with higher risk of kidney failure when modeling proteinuria as a time-varying covariate.
Analyses revealed Black patients without a high-risk APOL1 genotype did not experience an increased risk of kidney failure, compared with patients who were not Black.
“In summary, we find that APOL1 is significantly associated with the long-term risk of developing kidney failure, even for patients without underlying proteinuria in populations with CKD. Although proteinuria may be one mechanism by which APOL1 leads to kidney failure, our findings suggest the importance of confirming whether APOL1-mediated kidney damage could stem from alternate mechanisms,” Nguyen and colleagues wrote. “Providers should consider the value using APOL1 high-risk alleles as a risk-stratifying characteristic.”
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