Study links kidney artery inflammation to kidney failure in AAV

One in seven people with ANCA-associated vasculitis (AAV) has renal arteritis, or inflammation of the small arteries in the kidney, and this condition appears to be associated with an increased risk of kidney failure, a multicenter study in China showed.

“The presence of renal arteritis may represent a widespread [body-wide arterial inflammation] associated with increased disease activity of AAV,” the researchers wrote. “Renal arteritis was independently associated with an increased risk of [kidney failure] in patients classified as low or moderate risk” of progressing to kidney failure based on a standard measure, but not in those classified as high risk.

The study, “Clinical and pathological characteristics of patients with antineutrophil cytoplasmic antibody-associated vasculitis with renal arteritis,” was published in Kidney International Reports.

AAV is a group of autoimmune diseases in which the body’s immune system produces self-reactive antibodies, called ANCAs, that ultimately lead to inflammation and damage to small blood vessels. The kidneys are commonly affected via glomerulonephritis, or inflammation of the glomeruli, the clusters of tiny blood vessels (capillaries) in the kidneys that filter blood.

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Renal arteritis

In addition to glomerular capillary lesions, small arteries that supply blood to or run through the kidneys can become inflamed, and this is known as renal arteritis. Previous studies have reported arterial involvement in up to 23% of people with AAV-associated glomerulonephritis, but its clinical significance has not been fully characterized, particularly among Chinese patients.

With this in mind, a team of researchers in China described the clinical features of renal arteritis in AAV and assessed its effect on long-term outcomes. A total of 511 AAV patients with confirmed glomerulonephritis who were seen at one of four medical centers were included in the study.

Renal arteritis was present in 73 patients (14.3%). The initial kidney function assessments and the proportion of patients requiring dialysis (a kidney replacement therapy) at diagnosis were similar between the two groups.

However, those with renal arteritis showed more pronounced systemic (body-wide) inflammation, including significantly higher rates of fever, higher C-reactive protein levels (a marker of inflammation), and greater numbers of platelets, the cell fragments that help blood clot.

They were also significantly more likely to have disease involvement beyond the kidneys, such as muscle pain and nerve involvement outside the brain and spinal cord. Accordingly, overall disease activity, measured using the Birmingham Vasculitis Activity Score, was also significantly higher in the renal arteritis group.

Kidney biopsy (where a tiny piece of tissue is collected for analysis under a microscope) showed that nearly all AAV patients with renal arteritis (94.5%) had inflamed interlobular arteries, which supply blood to the glomerular capillaries. Nearby vessels that feed the interlobular arteries, called arcuate arteries, were less frequently inflamed (12.3%).

Other findings in people with AAV-related glomerulonephritis included fibrinoid necrosis, a pattern of cell death in blood vessel walls (82%), infiltration of several types of immune cells (71.2%), and granulomas, or clusters of immune cells (39.7%). Blood clots attached to the arterial wall were noted in 11%, while chronic scarred lesions of kidney arteries were seen in one-fifth (21.9%).

Those with renal arteritis had a significantly higher proportion of normal glomeruli (50% vs. 24.1%) and fewer crescentic lesions, a marker of more severe glomerular injury (40% vs. 58.8%).

This suggests that “in AAV patients without typical manifestations of crescentic glomerulonephritis, attention should be directed toward renal arteritis, particularly in those with severe [kidney] dysfunction that cannot be explained by glomerular capillary damage,” the team wrote.

AAV patients with renal arteritis responded more favorably to initial immunosuppressive AAV treatment in the short term, with 95.2% achieving kidney-related remission (few or no signs or symptoms) at six months, compared with 78.7% of those without renal arteritis.

In line with this finding, fewer of those with renal arteritis experienced treatment failure (4.8% vs. 21.3%) over six months. Despite this, there was no significant difference in kidney survival (no kidney failure) between the two groups over the entire follow-up period (up to 20 years).

However, when patients were stratified using the ANCA kidney risk score (AKRiS), a tool that predicts the likelihood of progression to kidney failure based on blood tests and biopsy results, a different pattern emerged.

Among patients with low or moderate AKRiS scores, those with renal arteritis had significantly worse kidney survival, and renal arteritis was independently associated with a higher risk of kidney failure. No such association was found among patients classified as high risk.

AAV patients with renal arteritis were significantly more likely to die from any cause during follow-up than those without (39.7% vs. 22.3%). But after accounting for other potential influencing factors, including age, kidney function, and disease activity, this difference was no longer statistically significant.

“AAV with renal arteritis is not rare and represents a distinct clinical and [disease-related characteristic] in [the] Chinese population,” the team concluded. “In patients classified as low or moderate risk by the AKRiS, renal arteritis was independently associated with an increased risk of [kidney failure].”