Study Identifies Early Risk Factors for Kidney Failure in AAV

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by Marta Figueiredo PhD |

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Poor kidney function and worse overall disease severity at diagnosis can predict kidney failure in adults with ANCA-associated vasculitis (AAV), according to a small single-center study in Turkey.

In addition, AAV patients with either hypocomplementemia — low levels of complement proteins in the blood — or a five-factor score (FFS) of at least 2 at diagnosis were significantly less likely to achieve disease remission.

These early findings suggest that kidney function, FFS score, and hypocomplementemia may help identify patients at greater risk of progression to kidney failure so they can promptly start appropriate, more intensive treatment, the researchers noted.

Larger, prospective studies are needed to confirm the predictive value of these factors.

The study, “Predictors of renal and patient outcomes in anti-neutrophil cytoplasmic antibody-associated vasculitis: Our single-center, tertiary care experience,” was published in the journal Archives of Rheumatology.

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AAV is a group of autoimmune diseases caused by abnormal immune attacks against small blood vessels in several organs and tissues, causing inflammation and damage.

One of the leading causes of death in AAV patients is end-stage renal disease (ESRD), or kidney failure, in which patients require lifetime dialysis or a kidney transplant. As such, identifying biomarkers that predict kidney failure and survival in these patients is needed to improve their clinical management.

A team of researchers at the Celal Bayar University’s Faculty of Medicine, in Turkey, set out to identify potential predictors of kidney failure, overall survival, dialysis-free survival, and AAV relapse and remission.

They retrospectively analyzed the demographic, clinical, and laboratory data from 77 adults (49 men and 28 women) diagnosed with AAV at their hospital between January 2006 and November 2019.

Patients’ mean age was 57.3 years (range of 18–71 years), and they were followed for up to 13 years (mean follow-up of 50 months, or about four years). The most common AAV type was granulomatosis with polyangiitis (GPA; 50.6%), followed by renal-limited vasculitis (RLV; 24.7%) and microscopic polyangiitis (MPA; 23.4%).

A total of 59 (77%) patients had kidney involvement: 59% of GPA patients and all of MPA and RLV patients. Of these, 31 (53%) needed dialysis at admission and 21 (35%) developed ESRD during follow-up.

A total of 46 (56%) patients achieved disease remission, and more than a quarter (27%) — all with kidney involvement — experienced disease relapse, with a mean relapse-free survival of 34 months (nearly three years).

Results from predictor analyses showed that dialysis requirement at admission, poorer kidney function at diagnosis, and a 2 or higher FFS score at diagnosis independently predicted progression to kidney failure in these patients.

The FFS is a tool used to assess AAV patients’ prognosis, with higher scores indicating worse general disease and an increased risk of death.

When adjusted for several potential influencing factors, only the initial need for dialysis remained statistically significant, being associated with a nearly six times higher risk of ESRD.

An FFS score of 2 or higher at the time of diagnosis was also the only independent predictor of relapse, providing a nine times higher risk. On the other hand, patients scoring less than 2 had a significantly higher remission rate relative to those with higher scores.

Also, older age was the only significant predictor of mortality.

The complement system is a set of more than 20 blood proteins that form part of the body’s immune defenses and that is thought to play a role in AAV. Hypocomplementemia, namely low levels of the C3 complement protein, may reflect an abnormally high complement activation.

A previous study suggested that hypocomplementemia was associated with the formation of C3 complement protein deposits in the kidneys, severe kidney damage, and overall disease activity.

While none of the analyses identified hypocomplementemia as a predictor of kidney failure or other outcomes, patients with the condition at admission had significantly poorer kidney function, worse disease severity (based on a 2 or greater FFS score), and a lower remission rate, relative to those without it.

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Together, these findings suggest that poorer kidney function and a 2 or higher FFS score at the time of diagnosis “are the major prognostic factors for progression to ESRD in AAV patients,” the researchers wrote.

A higher FFS score was also “a good predictor of long-term renal survival, relapse risk and, therefore, may be useful in deciding the optimal induction treatment and monitoring strategies in AAV,” they added.

The data also suggested, for the first time, an association between hypocomplementemia and lower remission rates, the team noted.

Among the study’s limitations, the researchers noted the small number of patients, which may have prevented the identification of additional independent predictors of AAV outcomes.

“Further large-scale, prospective studies are needed to confirm the predictors of renal and patient outcomes,” the team concluded.