AAV and Lupus in Woman with Unusual Kidney Damage Described in Case Report

Different autoimmune pathways — which determine how autoantibodies affect the body — might be involved in cases of lupus nephritis that are positive for ANCAs, leading to unusual kidney symptoms, a case report suggests.

The study “Clinico-pathological considerations in a 48-years-old female with acute kidney injury: is it lupus nephritis, ANCA-associated vasculitis or something else?” was published in the journal BMC Nephrology.

ANCAs, or anti-neutrophilic cytoplasmic autoantibodies, are autoantibodies that normally cause ANCA-associated vasculitis (AAV), an autoimmune disease marked by swollen and inflamed blood vessels (vasculitis). However, ANCAs can be present in healthy people and in people with other inflammatory and autoimmune diseases.

In  systemic lupus erythematosus (SLE), ANCA positivity is quite common, affecting up to 20% of patients. These people tend to have higher disease activity, but the exact role of ANCAs in organ injury is yet to be determined.

Researchers in France detail the case of a 48-year-old Asian woman with rapidly progressing kidney failure who showed symptoms of SLE but was positive for ANCAs.

The woman arrived at the hospital complaining of weakness, muscle and joint pain, poor appetite, and weight loss of 3 kg (around 7 lbs).

Lab exams showed kidney damage, evidenced by high creatinine and proteins and blood in the urine. The woman also had anemia and slightly increased C-reactive protein (a marker of inflammation).

Analysis of the immune system showed several autoantibodies that attack the cell nucleus and DNA, indicating SLE, and ANCAs against three proteins: myeloperoxidase (MPO), proteinase 3 (PR3), and lactoferrin. The woman also had low levels of complement proteins, which is common in autoimmune diseases.

Cases of AAV in which ANCAs attack several proteins at the same time, especially MPO and PR3, are extremely unusual.

The doctors suspected lupus nephritis — kidney damage caused by SLE. A kidney biopsy showed crescentic (rapidly progressing) inflammation of the glomeruli (glomerulonephritis) with no damage to the capillaries.

“These observations show that SLE patients with ANCAs are more likely to present with crescentic lupus nephritis and thus suggest a role for ANCAs in crescent development,” the researchers said.

The woman was started on treatment with steroids and cyclophosphamide, which improved her general condition and kidney function. After three months, her levels of creatinine, proteins in the urine, and autoantibodies had decreased, and the levels of complement proteins had increased.

A second biopsy performed after three months of treatment showed proliferative glomerulonephritis with involvement of the capillaries (small blood vessels) and no areas of dead tissue.

The investigators said that changes from crescentic to proliferative glomerulonephritis in the same patient had never been reported, and suggested that the changes in kidney symptoms might be related to the impact that the immunoregulatory treatment had on the different autoantibodies present in the patient.

Four months after starting treatment, the woman developed toxicity to cyclophosphamide, and this medicine was replaced with mycophenolate mofetil.

“The present case represents a very uncommon overlap presentation of SLE and AAV according to both its immunological and kidney pathological aspects,” the researchers said.

The atypical kidney lesions transitioning from “crescentic to endocapillary proliferative forms … suggests that different auto-immune pathways may be involved at different extent and different timings in the same patient,” the investigators concluded.

They also highlighted “the importance of more systematic kidney biopsy to better understand the pathophysiology of [lupus nephritis], especially in patients with atypical histological and immunological presentations.”