#3746 RISK OF PROGRESSIVE CHRONIC KIDNEY DISEASE WITH NEPHROSCLEROSIS ON KIDNEY BIOPSY DEFINED USING AGE-BASED VERSUS YOUNG ADULT-BASED THRESHOLDS

Abstract

Abstract Background and Aims The tissue pathology of both aging and chronic kidney disease (CKD) is nephrosclerosis defined by globally sclerotic glomeruli (GSG) and interstitial fibrosis and tubular atrophy (IFTA). We sought to determine if risk of CKD outcomes is better predicted by age-based or young adult-based thresholds for nephrosclerosis. Method Using the Aging Kidney Anatomy study, living kidney donors, kidney tumor patients, and native kidney disease patients had kidney biopsy images analyzed morphometric to quantify %GSG, %IFTA, and IFTA foci density (Figure 1). Using normotensive donors, young (18-29 y) thresholds and age-based (18-29 y, 30-39 y, 40-49 y, 50-59 y, 60-69 y, 70+y) 95th percentile thresholds were defined. Progressive CKD was defined as a 40% decline in serum creatinine based estimated GFR or kidney failure (dialysis or transplantation) from a 4-month post-biopsy baseline (due to the nephrectomy event in tumor patients and due to the common occurrence of acute kidney injury in the native kidney disease patients at the time of biopsy). The age-adjusted risk of progressive CKD in tumor patients and native kidney disease patients was compared between those with nephrosclerosis that was “normal compared to young”, “normal for age but abnormal compared to young”, and “abnormal for age” (Figure 2). Results There were 2583 normotensive living kidney donors, 1363 tumor patients, and 314 native kidney disease patients studied. The 95th percentiles for 18-29y to 70+y age groups among normotensive donors were 1.7% to 16% for %GSG, 0.18% to 6.5% for %IFTA, and 8.2 to 59.3 per cm2 for IFTA foci density. The risk of CKD outcomes did not differ between tumor patients and native kidney disease patients with nephrosclerosis “normal compared to young” versus “abnormal compared to young but normal for age” in both cohorts. Thus, these two categories were combined into “normal for age”. The risk of progressive CKD over a median 5.5 years follow-up for tumor patients was higher with %GSG, %IFTA, and IFTA foci density that was abnormal for age vs normal for age (HRs 2.28, 2.41, and 3.11, respectively, p<.0001 for all). The risk of progressive CKD over a median 7.2 years follow-up for native kidney disease patients was higher with %GSG, %IFTA, and IFTA density that was abnormal for age vs normal for age (HRs 1.87, 2.65, and 3.11, respectively, p<.0001 for all). Conclusion There is a substantial increase in nephrosclerosis from aging alone in healthy adults that is not prognostic for CKD outcomes. Age-based thresholds better identify clinically relevant CKD.