Kidney Involvement at AAV Diagnosis Predicts Major Renal Relapses, Study Finds

People with ANCA-associated vasculitis (AAV) who have kidney involvement when they are diagnosed are more likely to experience major kidney relapses later, a new study shows.

The study also indicates that induction treatment with cyclophosphamide and/or rituximab can protect against these relapses.

Titled “Renal involvement at baseline can predict major renal relapse in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis,” the study was published in Clinical and Experimental Rheumatology.

In AAV, kidney involvement can greatly affect prognosis. In particular, people who have kidney relapses are more likely to go on to develop kidney failure, a serious condition that necessitates transplant or dialysis. However, little is known about what factors can predict kidney relapses themselves.

In the new study, researchers analyzed clinical data from 96 people with AAV who were seen at Padova University Hospital, in Italy, from 2000 to 2019. This included 73 patients with granulomatosis with polyangiitis (GPA), 21 with microscopic polyangiitis (MPA), and two with renal limited vasculitis (RLV), or vasculitis limited to their kidneys. The group was 98% Caucasian, median age was 54 years, and 53% were female.

All had achieved remission, based on clinician assessment and/or scoring zero on the Birmingham Vasculitis Activity Index version three (BVASv3). With a median follow-up time of 54.5 months (about 4.5 years), 17 individuals experienced at least one major kidney relapse.

Major kidney or renal relapse (also called MR relapse) was defined as the occurrence of at least one item on the BVASv3, which includes blood in the urine and large changes in levels of the kidney biomarker creatinine. The researchers chose to focus only on major relapses (rather than minor ones) because people who experience major relapses are more likely to go to the hospital, so they are less likely to be missed by a retrospective study like this one.

Compared to patients without relapses, those who experienced MR relapses more often had disease involvement of the skin (41.2% vs. 17.7%), nervous system (52.9% vs. 25.3%), and kidneys (94.1% vs. 57%). They were significantly less likely to have disease involvement of the ears, nose, and throat (35.3% vs. 62%).

The researchers constructed statistical models, taking into account these variables and others, to identify clinical features that were predictive of MR relapse.

The strongest predictor of MR relapse was kidney involvement at the time of diagnosis — these individuals were 20.4 times more likely to experience an MR relapse than individuals without kidney involvement at diagnosis. Of note, all but one of the 17 people who experienced an MR relapse had kidney involvement at diagnosis.

“In our cohort, GPA, MPA and RLV patients with renal involvement at the time of diagnosis had higher risk of MR relapse,” the researchers wrote. “However, the absence of renal [kidney] involvement at disease onset does not completely rule out the occurrence of a MR relapse.”

The only other significant predictor of MR relapse was induction treatment with medications other than cyclophosphamide or rituximab, with these patients 4.2 times more likely to experience such a relapse.

This indicates that induction therapies based on cyclophosphamide and/or rituximab “could result in a significantly prolonged remission and lower relapse rate,” the researchers wrote, adding that this finding from real-world data is in agreement with clinical trials testing these medications.

Of note, the researchers assessed only induction therapy and not maintenance therapy in their analyses. This was an acknowledged limitation of the study.