ANCA-Associated Glomerulonephritis: Diagnosis and Therapy Proceedings of the Henry Shavelle Lectureship.

Background: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) frequently affects the kidney. Glomerulonephritis (GN) in AAV, ANCA-GN, not only dictates therapeutic decisions but is also of relevance for overall survival influencing the risk of cardiovascular disease and serious infections.

Summary: A diagnosis of ANCA-GN includes laboratory investigations including urinalysis and a thorough assessment of potential organ involvement. A kidney biopsy can be performed to ascertain the diagnosis but has an additional prognostic relevance and tools have been established to predict long-term kidney survival. Experimental biomarkers indicating kidney inflammation include urinary soluble CD163 and the presence of urinary T cells. Therapeutic options are refined and some of these therapies, such as the added value of performing plasma exchange, are the matter of controversial discussions. Safe reduction of cumulative exposure to glucocorticoids and eventually the use of avacopan to substantially reduce glucocorticoid exposure has been implemented in most centers. In the remission of maintenance, the optimal duration of therapy is still unclear, but extended use of rituximab as maintenance agent has shown long-term remission rates, thus limiting the damage accrued by relapsing disease and thus also reducing the risk of end-stage kidney disease (ESKD). Avacopan has been the first agent with a glomerular filtration rate-sparing effect, likely due to more rapid control of kidney inflammation. Those reaching ESKD should be evaluated for kidney transplantation and the risk of remaining on dialysis must be balanced against the risk of recurrence of disease following transplantation.

Key messages: The advent of a magnitude of landmark studies in ANCA-GN has refined diagnostic approaches, implemented tools to predict kidney outcome, and eventually led to the approval of newer therapies with avacopan, the latest addition to the armamentarium. Once ESKD is present, patients should be considered for kidney transplantation as remaining on dialysis portends poor overall prognosis.