Family History of Kidney Failure, APOL1 Risk Variants, Social Determinants of Health, and Risk of CKD Progression: Findings From the CRIC Study.

RATIONALE &

objectiveKidney disease is often clustered within families, including Black families, which could be due in part to shared adverse social determinants of health (SDoHs) and/or genetic factors. We hypothesize that the association between family history of kidney failure and chronic kidney disease (CKD) progression is largely attenuated when adjusting for adverse SDoHs and apolipoprotein L1 (APOL1) risk allele. STUDY

designLongitudinal observational study. SETTING &

participants5,623 participants from the CRIC (Chronic Renal Insufficiency Cohort) Study. EXPOSURE: Self-reported family history of kidney failure defined as a first-degree relative treated for kidney failure with dialysis or transplant. OUTCOME: CKD progression defined as incident end-stage kidney disease or 50% decrease in estimated glomerular filtration rate versus baseline. ANALYTICAL APPROACH: Logistic regression models were fitted to estimate adjusted odds ratio (aORs) of the outcome of family history of kidney failure according to the main exposures of (1) race/ethnicity combined with APOL1 risk allele status and (2) SDoHs. Next, Cox proportional hazards models were fitted to assess the association of family history of kidney failure with the outcome of CKD progression.

resultsAmong all participants (mean age, 59.6 ± 10.7 years; 44% female; 43% Black), 948 (17%) reported a family history of kidney failure. Compared with White participants, Black participants were more likely to report a family history of kidney failure regardless of APOL1 status (aOR, 2.25; 95% CI, 1.74-2.91 for 0 or 1 risk allele; aOR, 3.46; 95% CI, 2.39-5.02 for 2 risk alleles). Adverse SDoHs such as lower income and lower educational attainment were positively associated with a family history of kidney failure in unadjusted analyses, but not in multivariable models. In a prospective analysis, a family history of kidney failure was significantly associated with an increased risk of CKD progression in crude (HR, 1.33; 95% CI, 1.19-1.49) and multivariable models adjusting for demographic characteristics, APOL1 risk allele status, SDoHs, and clinical factors (HR, 1.16; 95% CI, 1.02-1.33). LIMITATIONS: Possible residual confounding.

conclusionsAmong people with CKD, Black race was significantly associated with a family history of kidney failure, even in those without high-risk APOL1 allele status. After adjusting for SDoHs and APOL1 status, family history of kidney failure remained associated with the risk of CKD progression. These findings highlight the importance of collecting information on family history and the need for further efforts to understand the reasons for familial aggregation of CKD. PLAIN-LANGUAGE SUMMARY: Kidney disease sometimes runs in families. We studied more than 5,600 people with kidney problems to determine whether having a close family member with kidney failure makes someone more likely to experience worse kidney disease. We found that people, especially Black individuals, with family members who had kidney failure were more likely to have worsening kidney problems themselves. This was true even when we considered other health problems like high blood pressure or diabetes. Our study suggests that doctors should ask about family history because it may help identify people who are at higher risk. More research is needed to understand why kidney disease is often clustered within families.