Renal arteriosclerosis is common, underrecognized, and accelerated in patients with lupus nephritis, which has important implications for detection of the early cardiovascular disease (CVD) associated with systemic lupus erythematosus, researchers reported.
In a cohort of 189 patients with incident lupus nephritis whose mean age was 25 years, 41% had renal arteriosclerotic changes, according to Shivani Garg, MD, of the University of Wisconsin in Madison, and colleagues.
And the onset of arteriosclerosis in these patients occurred a full 2 decades earlier than has been seen in published data of healthy kidney donors: The 41% prevalence of individuals ages 30 to 39 was similar to the prevalence of 44% reported for donors ages 50 to 59 (P=0.9), they reported in .
Early CVD confers a nine-fold increased risk of CV events in patients with lupus compared with healthy controls. However, few strategies have been successfully employed to identify the earliest manifestations of CVD in these patients, and few studies have looked at renal changes as potential risk predictors.
The classification system used by the International Society of Nephrology/Renal Pathology for lupus nephritis focuses on glomerular pathology on biopsy, and does not include grading of vascular lesions. In contrast, the that is used for renal transplantation includes quantitative evaluation of all structures of the kidney, including the vasculature.
In other conditions, such as IgA nephropathy and kidney transplantation, the Banff scoring system has shown a correlation between renal arteriosclerosis and coronary atherosclerosis, suggesting that the kidney changes are an early event in a common pathway.
"The presence of renal arteriosclerosis could be used as an early predictor of CVD events that will help clinicians to timely implement CVD preventive strategies and reduce CVD-related morbidity and mortality in lupus nephritis patients," the researchers wrote.
Therefore, to investigate the possibility that systematic assessment of the renal vasculature might be useful in lupus nephritis, Garg and colleagues reviewed the electronic health records and biopsy findings for all patients who underwent renal biopsy at the University of Wisconsin from 1994 to 2017.
As with the Banff system, the renal arteriosclerosis classification ratings were none (no luminal narrowing), mild (less than 25% narrowing), moderate (25% to 50% narrowing), and severe (more than 50% narrowing). A blinded pathologist also over-read with Banff scoring 25% of the more recent biopsy samples which might have been influenced by refinements in grading of transplant biopsies.
The majority of patients were white women whose duration of lupus was less than 2 years. The majority of patients had non-proliferative nephritis, and chronicity was present in 38%. The renal arteriosclerosis was considered mild in 24%, moderate in 6%, and severe in 1%. Arteriolar hyalinosis was observed in 12%.
Among patients older than 30 years in whom arteriosclerosis was present, in 10% it was classified as moderate to severe, but the rate increased to 50% for biopsies over-read using Banff scoring. By ages 60 to 69, one in three patients had moderate to severe changes, which represented a fivefold greater prevalence compared with age-matched controls.
On a multivariate analysis, factors that were predictive of renal arteriosclerosis were:
- Age 30 or older: OR 3.3 (95% CI 1.3-9.1, P=0.02)
- Lupus nephritis chronicity: OR 4 (95% CI 1.5-11.6, P=0.01)
Other factors such as nephritis proliferative class, lupus disease duration, and atherosclerosis disease scores showed no significant association.
In the subgroup of biopsy specimens that were over-read using the Banff grading system, the agreement with the original pathology report was considered poor (κ=0.25). In fact, more than half of the pathology reports missed renal arteriosclerosis altogether, for a negative predictive value of 49%.
"Our study highlights the prevalence of renal arteriosclerosis in lupus nephritis patients along with gaps in current pathology reports, suggesting a need to standardize reporting and grading of renal arteriosclerosis in all lupus nephritis biopsies by using universal Banff arteriosclerosis grading," the investigators stated.
A limitation of the study was its single-center design in an area of the country that is predominantly white, which may not fully reflect the wider U.S. lupus nephritis population.
Disclosures
The authors disclosed no relevant relationships with industry.
Primary Source
Arthritis Care & Research
Garg S, et al "High burden of premature arteriosclerosis on renal biopsies in incident lupus nephritis" Arthritis Care Res 2020; DOI: 10.1002/acr.24138.