HDCN Article Review/Hyperlink

Hogan SL, Nachman PH, Wilkman AS, Jennette CH, Falk RJ, and teh Glomerular Disease Collab. Network

Prognostic markers in patients with antineutrophil cytoplasmic antibody-associated polyangiitis and glomerulonephritis

J Am Soc Nephrol (Jan) 7:23-32 1996

The clinical course of 107 patients with necrotizing crescenteric glomerulonephritis (NCGN) alone or with evidence of microscopic polyarteritis (MPA) was reported in detail. Patients with clear cut Wegener's, i.e. with granulomatous inflammation or those with nodular or cavitary lung lesions, were excluded. All biopsies revealed pauci-immune necrotizing GN; 68 were P-ANCA positive (100% of these myeloperoxidase specific); 39 were C-ANCA positive (87% proteinase-3 specific). Of 17 patients dialyzed at the onset of illness, 9 recovered renal function; four of these eventually required reinstitution of dialysis. Twenty five patients received steroids alone, 72 patients received IV or PO Cytoxan, and 10 patients were not treated. Forty two patients reached ESRD requiring dialysis or transplantation, 12 patients died; the mean follow-up was 2.5 years for the entire patient group. This small sample size limited the number of prognostic variables studied to 8.

Pulmonary hemorrhage was found to be the strongest predictor of death (RR 8.64); patients with C-ANCA also had a higher mortality (RR 2.36). There was no increased risk of death for patients with NCGN alone, compared with those who also had MPA. Black and white patients had the same mortality rate. Patients treated with Cytoxan, as opposed to steroids alone, had lower mortality (RR 0.18).

Renal survival was 78% at 12 months, 66% at 24 months and 44% at 48 months. The higher the serum creatinine at presentation, the higher the risk of developing ESRD. Blacks had a higher risk of ESRD (RR 4.6). Renal arterial sclerosis pathologically predicted loss of renal function (RR 1.67); none of the other 9 pathological variables measured were predictive of loss of renal function in the multivariate analysis, when the other clinical and demographic factors were accounted for.

Comment: This report from the Glomerular Disease Collaborative Network, which comprises some 150 physicians in the North Carolina area, is a classic work and should be required reading for any physician interested in glomerulonephritis. It brings into sharp focus for the first time the course of this relatively common clinical entity, necrotizing crescenteric glomorulonephritis, which is defined clinically, pathologically and serologically. The fact that many patients had a poor long term renal prognosis is worrisome; it is accounted for by the severity of the renal inflammation on presentation. All patients should be treated with Cytoxan in addition to corticosteroids. (Stephen Pastan, M.D., Emory University)