Apolipoprotein L1 Genotypes and the Association of Urinary Potassium Excretion With Chronic Kidney Disease Progression

Background: Progressive CKD in Black individuals is strongly associated with polymorphisms in the APOL1 gene, but it is unknown whether dietary risk factors for CKD progression vary in high- vs. low-risk APOL1 genotypes. We investigated if APOL1 genotypes modify associations of dietary potassium and sodium with CKD progression and death. Methods: We analyzed 1399 self-identified Black participants enrolled in the Chronic Renal Insufficiency Cohort, from April 2003 to September 2008. Exposures were calibrated 24-hour urine potassium and sodium. The primary outcome was CKD progression defined as time to 50% decline in estimated glomerular filtration rate or kidney failure. The secondary outcome was CKD progression or death. We tested for interaction between urinary potassium and sodium excretion and APOL1 genotypes. Results: Median 24-hour urinary sodium and potassium excretion in Black participants were 150 mmol [IQR 118-188] and 43 mmol [IQR 35-54], respectively. Individuals with high and low-risk APOL1 genotypes were 276 (20%) and 1104 (79%) respectively. After a median follow-up of 5.23 years, CKD progression events = 605, and 7.29 years, CKD progression and death events= 868. There was significant interaction between APOL1 genotypes and urinary potassium excretion with CKD progression and CKD progression or death (p=0.003, p=0.028 respectively). In those with high-risk APOL1 genotypes, higher urinary potassium excretion was associated with lower risk of CKD progression (quartiles 2, 3 & 4 vs. 1: HR 0.83 (0.50,1.39), 0.54 (0.31, 0.93)) & 0.50 (0.27,0.93)). In the low-risk APOL1 genotypes, higher urinary potassium excretion was associated with higher risk of CKD progression (quartiles 2, 3 & 4 vs. 1: HR 1.01 (0.75,1.36), 1.23 (0.91, 1.66) & 1.53 (1.12, 2.09)). We found no interaction between APOL1 genotypes and urinary sodium excretion with CKD outcomes. Conclusions: Higher urinary potassium excretion was associated with lower vs higher risk of CKD in APOL1 high-risk and low-risk genotypes respectively.