Renal Arteriosclerosis Strongly Associated Atherosclerotic Cardiovascular Disease Risk in Lupus Nephritis

Objective Lupus nephritis (LN) predicts a 9-fold higher atherosclerosis cardiovascular disease (ASCVD) risk, highlighting the urgent need to target ASCVD prevention. Studies in IgA nephropathy reported that severe renal arteriosclerosis (r-ASCL) in diagnostic biopsies strongly predicted ASCVD risk. We recently found that 50% of LN pathology reports overlooked r-ASCL reporting, which could explain prior negative LN ASCVD risk studies. Therefore, we aimed to examine associations between a composite of reported and over-read r-ASCL and ASCVD events in LN. Methods Data were abstracted from all LN patients who underwent diagnostic biopsy between 1994-2017 including demographics, ASCVD risk factors, and pathology reports at the time of LN diagnosis. We manually validated all incident ASCVD events. We over-read 25% of the biopsies to grade r-ASCL using Banff criteria. We supplemented the over-read r-ASCL grade, when available, to determine the composite of reported and over-read r-ASCL grade. Results Among 189 incident LN patients, 78% were female, 73% white, and the median age was 25. Overall, 31% had any reported r-ASCL, and 7% had moderate-severe r-ASCL. After incorporating systematically re-examined r-ASCL grade, the prevalence of any and moderate-severe r-ASCL increased to 39% and 12%. We found 22 incident ASCVD events over 11 years of follow-up. Using a composite of reported and over-read r-ASCL grade, we found that severe r-ASCL in diagnostic LN biopsies was associated with 9-fold higher odds of ASCVD. Conclusion Severe r-ASCL can predict ASCVD in LN, therefore, larger studies are required to systematically report r-ASCL and examine ASCVD associations.