Nephrolithiasis as a Risk Factor for CKD: The Atherosclerosis Risk in Communities Study

Background and objectives Previous studies demonstrated a higher risk of CKD in persons with a history of kidney stones, but these studies examined mostly white populations and did not evaluate important potential interactions such as race and plasma uric acid. Design, setting, participants, & measurements In 10,678 Atherosclerosis Risk in Communities (ARIC) study participants free of CKD at baseline (ARIC visit 4 in 1996-1998), we assessed the association between a history of nephrolithiasis (a time-varying variable, defined by a combination of self-report and diagnostic codes) and incident CKD (defined by diagnostic codes from linkage to hospitalizations and US Centers for Medicare and Medicaid Services' records). Results At baseline, 856 participants had a history of nephrolithiasis; 322 developed nephrolithiasis during follow-up. Over a mean follow-up of 12 years, there were 1037 incident CKD events. Nephrolithiasis history was associated with a 29% (hazard ratio [HR], 1.29; 95% confidence interval [95% CI], 1.07 to 1.54) higher risk of CKD in demographic-adjusted analyses, but the association was no longer statistically significant after multivariable adjustment (HR, 1.09; 95% CI, 0.90 to 1.32). The multivariable-adjusted association was stronger among participants with plasma uric acid levels <= 6 mg/dl (HR, 1.34; 95% CI, 1.05 to 1.72) compared with those with levels >6 mg/dl (HR, 0.94; 95% CI, 0.70 to 1.28; P-interaction=0.05). There was no interaction of stone disease and race with incident CKD. Conclusions In this community-based cohort, nephrolithiasis was not an independent risk factor for incident CKD overall. However, risk of CKD was unexpectedly elevated in participants with stone disease and lower plasma uric acid levels.