Improved processing technique for renal biopsies for light microscopy.

Abstract

<h3>Background and objectives</h3> Progressive CKD in Black individuals is strongly associated with polymorphisms in the <i>APOL1</i> gene, but it is unknown whether dietary risk factors for CKD progression vary in high- versus low-risk <i>APOL1</i> genotypes. We investigated if <i>APOL1</i> genotypes modify associations of dietary potassium and sodium with CKD progression and death. <h3>Design, setting, participants, &amp; measurements</h3> 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 excretion. The primary outcome was CKD progression defined as the time to 50% decline in eGFR or kidney failure. The secondary outcome was CKD progression or death. We tested for an interaction between urinary potassium and sodium excretion and <i>APOL1</i> genotypes. <h3>Results</h3> Median 24-hour urinary sodium and potassium excretions in Black participants were 150 mmol (interquartile range, 118–188) and 43 mmol (interquartile range, 35–54), respectively. Individuals with high- and low-risk <i>APOL1</i> genotypes numbered 276 (20%) and 1104 (79%), respectively. After a median follow-up of 5.23 years, CKD progression events equaled 605, and after 7.29 years, CKD progression and death events equaled 868. There was significant interaction between <i>APOL1</i> genotypes and urinary potassium excretion with CKD progression and CKD progression or death (<i>P</i>=0.003 and <i>P</i>=0.03, respectively). In those with high-risk <i>APOL1</i> genotypes, higher urinary potassium excretion was associated with a lower risk of CKD progression (quartiles 2–4 versus 1: hazard ratio, 0.83; 95% confidence interval, 0.50 to 1.39; hazard ratio, 0.54; 95% confidence interval, 0.31 to 0.93; and hazard ratio, 0.50; 95% confidence interval, 0.27 to 0.93, respectively). In the low-risk <i>APOL1</i> genotypes, higher urinary potassium excretion was associated with a higher risk of CKD progression (quartiles 2–4 versus 1: hazard ratio, 1.01; 95% confidence interval, 0.75 to 1.36; hazard ratio, 1.23; 95% confidence interval, 0.91 to 1.66; and hazard ratio, 1.53; 95% confidence interval, 1.12 to 2.09, respectively). We found no interaction between <i>APOL1</i> genotypes and urinary sodium excretion with CKD outcomes. <h3>Conclusions</h3> Higher urinary potassium excretion was associated with lower versus higher risk of CKD progression in <i>APOL1</i> high-risk and low-risk genotypes, respectively.