New Classification System Enables Prediction of Kidney Function and Survival in ANCA Glomerulonephritis Patients

A new classification system of types of glomerular lesions in the kidney enables better prediction of renal function and survival in patients with ANCA-associated glomerulonephritis, according to a nationwide study in Japan.

The research, “Histopathological classification of anti-neutrophil cytoplasmic antibody-associated glomerulonephritis in a nationwide Japanese prospective 2-year follow-up cohort study,” appeared in the journal Clinical and Experimental Nephrology.

The European Vasculitis Study Group (EUVAS) recently proposed a new classification for ANCA-associated glomerulonephritis based on types of lesions in the glomeruli, which are the small filtering units in the kidneys.

According to this classification, biopsies of glomeruli are classified in four groups: focal (50% or more normal glomeruli); crescentic (50% or more with cellular crescents, defined by two or more layers of proliferating cells in the kidney’s Bowman’s capsule); sclerotic, and; mixed, which do not meet the criteria for the other classes.

In 2016, the team’s two research groups, part of the Japanese Ministry of Health, Labor and Welfare, conducted a nationwide study of remission induction therapy in 321 patients with newly-diagnosed ANCA-associated vasculitis (UMIN000005136). Then, they started using the two-year follow-up data to assess factors such as disease classification, severity, and prognosis.

Now they analyzed biopsy samples of 67 of these patients with ANCA-associated glomerulonephritis to evaluate the link between the proposed classification and renal survival and function during the follow-up period.

Renal survival was defined as the time to kidney failure requiring dialysis initiation. In turn, renal function was assessed through measurements of the estimated glomerular filtration rate (eGFR) at baseline, six months, and two years.

Results showed that 92.5% of patients had the AAV type microscopic polyangiitis. Thirty were classified into the focal class, 19 into mixed, 10 crescentic, and eight sclerotic.

The focal and mixed classes had higher renal survival rates compared to the other groups. However, the scientists cautioned against taking definitive conclusions, as there were only four patients with kidney failure. Twelve patients were lost to follow-up, five of whom died from causes other than kidney failure.

The immunosuppressive therapy cyclophosphamide was prescribed more often to patients in the focal class, while Rituxan (rituximab, by Genentech and Biogen) was not taken by any patient.

As for renal function, eGFR was highest (best) in the focal group throughout the study, followed by crescentic, mixed, and sclerotic. However, renal function increased with time in all but the focal group. Disease activity assessed with the Birmingham Vasculitis Activity Score 2003 was not significantly different among the four classes.

“Therefore, based on both results, i.e., the renal-survival curve and the comparison of eGFR-values, the Focal class could be the best prognosis,” the scientists wrote.

They then found that the eGFR of the focal group was higher in patients without rapidly progressive glomerulonephritis, a kidney disease characterized by renal failure within a few months.

However, a longer follow-up is needed to better assess therapeutic effects and renal prognosis in this focal class subgroup, the investigators observed. Addressing the influence of specific treatment regimens also is needed, they added.

Overall, the scientists found that the new classification system “was valuable for both the stratification of renal function and the estimation of partial renal survival during 2-year follow-up in ANCA-associated glomerulonephritis.”