Renal Arteriosclerosis Common But Under-Reported in Lupus Nephritis

Renal arteriosclerosis is significantly accelerated in patients with lupus nephritis compared with healthy controls, but it is routinely overlooked by pathologists in biopsy reports, according to study results published in Arthritis Care and Research.

Researchers sought to assess the burden of renal arteriosclerosis in kidney biopsy among patients with lupus nephritis and to compare the prevalence rates of renal arteriosclerosis in this patient population with healthy kidney donors by age group. Researchers also aimed to examine whether arteriosclerosis and its associated severity were underreported in pathology reports.

Consecutive patients with lupus nephritis who underwent native renal biopsy between 1994 and 2017 at the University of Wisconsin were included in this study. Investigators abstracted data on patient and disease characteristics from a comprehensive renal biopsy database and patient electronic health records. Diagnoses were validated using the 1997 American College of Rheumatology and 2012 Systemic Lupus Erythematosus (SLE) International Collaborating Clinics criteria.

In total, 189 patients with incident lupus nephritis (median age at biopsy, 25 years; 78% women; 73% white) met the inclusion criteria for the study. At the time of biopsy, 23% of patients were ever smokers, and 34% had more than 1 risk factor for the modified atherosclerotic cardiovascular disease count. In terms of disease characteristics, 41% of patients were classified as proliferative, 38% had lupus nephritis chronicity, and 49% were diagnosed with lupus nephritis within 2 years of SLE diagnosis.

Biopsy reports indicated that 41% of patients with lupus nephritis had renal arterial changes. In total, 31% of patients had renal arteriosclerosis, and 12% had hyaline arteriosclerosis.

Among the study cohort, 40% of patients aged ≥30 years had renal arteriosclerosis, and >10% had moderate to severe arteriosclerosis on biopsy reports. According to investigators, more than 50% of patients aged >30 years had renal arteriosclerosis when biopsies were overread using standard Banff criteria to grade renal arteriosclerosis, the prevalence of which increased with age. Among patients aged 60 to 69 years, the burden of moderate to severe arteriosclerosis was 1 in 3.

Arteriosclerosis onset in patients with lupus nephritis occurred 20 years earlier compared with the published prevalence in healthy kidney donors. The cohort prevalence of 41% renal arteriosclerosis among patients with lupus nephritis aged between 30 and 39 years was comparable to the prevalence among healthy kidney donors aged between 50 and 59 years (41% vs 44%, respectively; P =.9). Patients with lupus nephritis aged between 40 and 49 years had comparable prevalence with healthy controls aged between 60 and 69 years (52% vs 51%; P =.95). Further, the burden of moderately severe arteriosclerosis among patients with lupus nephritis aged between 60 and 69 years was 5-fold higher than that among healthy controls (33% vs 6%).

Results of a univariable analysis found that being ≥30 years of age and lupus nephritis chronicity were predictors of renal arteriosclerosis (odds ratio [OR], 6.9; 95% CI, 3.5-14.0 and OR, 3.0, 95% CI, 1.5-5.7, respectively). Multivariable analysis indicated a 3-fold higher odds of renal arteriosclerosis in patients with lupus nephritis aged >30 years compared with patients with lupus nephritis aged <30 years (OR, 3.3; 95% CI, 1.3-9.1; P =.02); lupus nephritis chronicity predicted 4-fold greater odds of renal arteriosclerosis (OR, 4.0; 95% CI, 1.5-11.6; P =.01). Lupus nephritis proliferative class, modified atherosclerotic cardiovascular disease count, and SLE disease duration were not associated with presence of renal arteriosclerosis.

Using a 25% convenience sample from 43 patients (mean age at lupus nephritis diagnosis, 31 years; 25% black; 72% women), investigators overread renal biopsy slides, with Banff criteria to grade renal arteriosclerosis. Poor agreement was found between overread grades using the Banff criteria and original pathology reports (k=0.25). More than 50% of the original pathology reports missed renal arteriosclerosis, and nearly 40% of reports lacked details on arterial changes. Specificity of these biopsy reports compared with overread reports of arteriosclerosis was 84%.

Study limitations included a lack of generalizability, particularly to nonwhite populations, the use of renal biopsies, which is not a standard procedure in all patients with lupus nephritis, and a potential underreporting of the true burden of renal arteriosclerosis in this patient population.

“Despite the high specificity of renal arteriosclerosis in current biopsy reports, we found significant sensitivity gaps (>50%) in routine pathology reporting on renal arteriosclerosis in [lupus nephritis] biopsies,” the researchers concluded. “[O]ur study underscores a need for universal use of systematic Banff renal arteriosclerosis grading criteria in all [lupus nephritis] biopsies.” 

Reference

Garg S, Bartels CM, Hansen KE, et al. High burden of premature arteriosclerosis on renal biopsies in incident lupus nephritis [published online January 7, 2020]. Arthritis Care Res. doi:10.1002/acr.24138