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February 02, 2021
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Risk for atherosclerotic CVD in lupus nephritis ninefold higher with renal arteriosclerosis

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Severe renal arteriosclerosis is associated with a nine times greater risk for atherosclerotic cardiovascular disease in patients with lupus nephritis, according to data published in Arthritis Care & Research.

“Previous studies demonstrated that patients with lupus nephritis who had atherosclerotic cardiovascular disease (ASCVD) were significantly younger than those without lupus nephritis, and ASCVD risk was 42 times higher in patients with lupus nephritis who were aged 30 to 39 years,” Shivani Garg, MD, MS, of the University of Wisconsin, Madison, told Healio Rheumatology. “The risk of ASCVD starts early, at the time of lupus nephritis diagnosis. Often traditional risk factors alone do not explain the accelerated ASCVD risk in such patients.”

“The presence of severe renal arteriosclerosis in lupus nephritis biopsies at the time of diagnosis predicted nine-fold higher subsequent [atherosclerotic cardiovascular disease] risk in lupus nephritis compared to patients who did not have renal arteriosclerosis in diagnostic biopsies,” Shivani Garg, MD, MS, told Healio Rheumatology. Source: Adobe Stock

“Such studies underscore a possible role of immune-mediated and inflammatory risk factors in addition to traditional risk factors as contributors to significantly accelerated ASCVD risk in lupus nephritis patients,” she added. “In our previous study, we found that the burden of renal arteriosclerosis (r-ASCL) in diagnostic lupus nephritis biopsies was significantly higher and occurred earlier in patients with lupus nephritis, starting from 30 to 39 years of age. Therefore, these findings support a mechanistic association between the presence of r-ASCL in lupus nephritis biopsies at the time of LN diagnosis and ASCVD occurrence in LN patients, which led to this study.”

To analyze the associations between a composite of reported and over-read r-ASCL and ASCVD events in lupus nephritis, Garg and colleagues examined data from all patients with the disease who completed a diagnostic biopsy at the University of Wisconsin Hospital and Clinics between 1994 and 2017. Data included demographics, ASCVD risk factors and pathology reports at the time of lupus nephritis diagnosis. In all, 189 patients with incident lupus nephritis were included.

Shivani Garg

The researchers manually validated all incident ASCVD events and over‐read 25% of the biopsies to grade r‐ASCL using Banff criteria. In addition, Garg and colleagues supplemented the over‐read r‐ASCL grade, when available, to determine the composite of reported and over‐read r‐ASCL grade.

According to the researchers, 31% of included participants demonstrated any r‐ASCL, while 7% had moderate‐to-severe r‐ASCL. After incorporating systematically re‐examined r‐ASCL grade, the prevalence of any and moderate‐to-severe r‐ASCL increased to 39% and 12%. In all, Garg and colleagues found 22 incident ASCVD events through 11 years of follow‐up. In addition, using a composite of reported and over‐read r‐ASCL grade, they noted that severe r‐ASCL in diagnostic lupus nephritis biopsies was associated with nine‐fold higher odds of ASCVD.

“Interestingly, we found that after systematically grading renal arteriosclerosis in diagnostic lupus nephritis biopsies, the presence of severe renal arteriosclerosis in lupus nephritis biopsies at the time of diagnosis predicted nine-fold higher subsequent ASCVD risk in lupus nephritis compared to patients who did not have renal arteriosclerosis in diagnostic biopsies,” Garg said. “Further, we found that chronic kidney disease stage 3 or above at the time of lupus nephritis diagnosis predicted subsequent ASCVD risk, while we did not find any association between traditional risk factors at the time of lupus nephritis diagnosis associated with higher ASCVD risk.”

“Our study highlights a possible role of renal arteriosclerosis in diagnostic lupus nephritis biopsies as a predictor of future ASCVD risk,” she added. “The findings of this innovative study will form the basis to further investigate the role of severe renal arteriosclerosis as a predictor of ASCVD events in larger LN cohorts, which will identify high-risk subsets and guide timely prevention in LN patients.”