Researchers identify markers of kidney disease common in AAV
Study: High levels of C-reactive protein, lung involvement among predictors
Most people who test positive for ANCAs — the self-reactive antibodies that drive most ANCA-associated vasculitis (AAV) cases — have pauci-immune glomerulonephritis (GN), a type of inflammation of the kidneys’ filtering units, a study found.
A high number of blood-clotting-inducing platelets, high blood levels of the inflammatory marker C-reactive protein (CRP), poorer kidney function, the presence of blood in the urine, and lung involvement were significant predictors of pauci-immune GN.
“Identifying these clinical and laboratory markers may be valuable for improving the diagnostic approach [toward] AAV-related kidney manifestations,” researchers wrote.
The study, “Factors associated with pauci-immune glomerulonephritis in patients undergoing kidney biopsy with positive anti-neutrophil cytoplasmic antibody results,” was published in the Journal of Nephrology by a team of researchers in South Korea.
In AAV, the immune system mistakenly attacks body’s small blood vessels
In AAV, the immune system mistakenly attacks the body’s small blood vessels, causing inflammation. In the kidneys, this can cause glomerulonephritis, a condition that occurs when the filtering units, known as glomeruli, become damaged. Over time, the kidneys may fail to remove waste and excess fluid from the blood.
While pauci-immune GN, a type of glomerulonephritis that doesn’t present with deposits of certain immune proteins, is common in AAV, not all people testing positive for ANCAs have this type of kidney damage.
“Recent studies have described the presence of other kidney diseases,” the researchers wrote. “ANCA positivity is not exclusive to AAV or pauci-immune GN and can be seen in autoimmune diseases, infections, malignancies, and drug exposures. This lack of specificity can complicate diagnostic interpretation.”
In this study, the team compared the features of ANCA-positive people with pauci-immune GN to those with other immune-related kidney diseases.
They analyzed the medical records of 268 people with a mean age of 62.8 years, who tested positive for ANCAs at the time they had a kidney biopsy at a hospital in Seoul, South Korea. A biopsy is a small sample of tissue examined under a microscope. None of the participants had been diagnosed with AAV before their kidney biopsy.
Most participants had pauci-immune glomerulonephritis
Results showed that most participants (72.8%) had pauci-immune GN, while 27.2% had other kidney diseases. The most common of these were IgA nephropathy (20.5%), an inflammation caused by deposits of a protein called immunoglobulin A, and lupus nephritis (16.4%), a kidney complication of the autoimmune disease lupus.
The majority of participants (90.9%) had ANCAs targeting the myeloperoxidase protein, one of the two most common targets of AAV-driving ANCAs.
Nearly two-thirds (65.7%) had hematuria — blood in urine — and this condition was significantly more common in those with pauci-immune GN than those with other kidney diseases (72.3% vs. 47.9%). Proteinuria — excess protein in urine — was significantly less common in the pauci-immune GN group than in the group with other kidney diseases (40.5% vs. 54.8%).
People with pauci-immune GN also had significantly more platelets (335 thousand per microliter vs. 249 thousand per microliter) and higher blood levels of CRP, a marker of inflammation in the body, than those with other kidney diseases (8.38 mg/dL vs. 0.74 mg/dL).
The pauci-immune GN group also exhibited significantly worse kidney function, as reflected by a lower estimated glomerular filtration rate (eGFR), a measure of the kidneys’ ability to filter blood.
Blood in urine, lung involvement strong predictors of pauci-immune GN
Regarding manifestations outside the kidneys, 59% of participants had general symptoms, including fever or weight loss. These symptoms were significantly more common in those with pauci-immune GN (65.1% vs. 42.5%). Lung involvement was also significantly more common in the pauci-immune GN group (55.4% vs. 23.3%), as was nervous system involvement (22.6% vs. 11%).
Statistical models showed that the presence of hematuria and lung involvement were each significantly associated with about a four times higher chance of having pauci-immune GN.
High platelet counts and elevated CRP levels were weaker predictors, being significantly linked to a 1% and a 14% higher chance, respectively.
These findings underscore the critical role of kidney biopsy in distinguishing AAV from other glomerular diseases in ANCA-positive individuals, highlighting the need for a careful assessment of underlying autoimmune conditions and medication history to guide accurate diagnosis and management.
In turn, a higher eGFR, indicating better kidney function, was significantly linked to a 3% lower likelihood of pauci-immune GN, and the presence of proteinuria, in the absence of hematuria, was associated with a 78% lower chance.
“These findings underscore the importance of integrating clinical biomarkers in diagnosing patients with positive ANCA results,” the researchers wrote. “Our study intentionally included ANCA-positive patients with potential [diseases other than AAV] to better understand how such factors may influence both ANCA status and [kidney disease].”
A total of 12 people were diagnosed with lupus nephritis, while two were thought to have kidney inflammation due to exposure to rifampin, an antibiotic that can cause ANCA-positive blood vessel inflammation.
“These findings underscore the critical role of kidney biopsy in distinguishing AAV from other glomerular diseases in ANCA-positive individuals, highlighting the need for a careful assessment of underlying autoimmune conditions and medication history to guide accurate diagnosis and management,” the team concluded.
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