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Clinical and Histologic Determinants of Renal Outcome in ANCA-Associated Vasculitis: A Prospective Analysis of 100 Patients with Severe Renal Involvement

Robert A.F. de Lind van Wijngaarden^*, Herbert A. Hauer, Ron Wolterbeek, David R.W. Jayne, Gill Gaskin^||, Niels Rasmussen^¶, Laure-Hélène Noël^**, Franco Ferrario, Rüdiger Waldherr, E. Christiaan Hagen, Jan A. Bruijn^*, Ingeborg M. Bajema^* for the European Vasculitis Study Group (EUVAS)

^* Pathology; Medical Statistics, Leiden University Medical Center; Department of Cardiology, Medical Center Alkmaar; Department of Internal Medicine, Meander Medical Center, Amersfoort, the Netherlands; Renal Unit, Addenbrooke’s Hospital, Cambridge; ^|| Renal Unit, Hammersmith Hospital, London, United Kingdom; ^¶ Department of Otolaryngology, Rigshospitalet, Copenhagen, Denmark; ^** INSERM U507, Hôpital Necker, Paris, France; Renal Immunopathology Center, Ospedale San Carlo Borromeo, Milan, Italy; and Department of Pathology, University of Heidelberg, Heidelberg, Germany

Address correspondence to: Dr. Rob de Lind van Wijngaarden, Leiden University Medical Center, Department of Pathology, Postbus 9600, 2300 RC Leiden, The Netherlands. Phone: +31-71-526-6574; Fax: +31-71-524-81-58; E-mail: r.a.f.de_lind_van_wijngaarden{at}lumc.nl

Received for publication August 22, 2005. Accepted for publication May 17, 2006.

This study aimed to identify clinical and histologic prognostic indicators of renal outcome in patients with ANCA-associated vasculitis and severe renal involvement (serum creatinine >500 µmol/L). One hundred patients who were enrolled in an international, randomized, clinical trial to compare plasma exchange with intravenous methylprednisolone as an additional initial treatment were analyzed prospectively. Diagnostic renal biopsies were performed upon entry into the study. Thirty-nine histologic and nine clinical parameters were determined as candidate predictors of renal outcome. The end points were renal function at the time of diagnosis (GFR₀) and 12 mo after diagnosis (GFR₁₂), dialysis at entry and 12 mo after diagnosis, and death. Multivariate analyses were performed. Predictive of GFR₀ were age (r = –0.40, P = 0.04), arteriosclerosis (r = –0.53, P = 0.01), segmental crescents (r = 0.35, P = 0.07), and eosinophilic infiltrate (r = –0.41, P = 0.04). Prognostic indicators for GFR₁₂ were age (r = –0.32, P = 0.01), normal glomeruli (r = 0.24, P = 0.04), tubular atrophy (r = –0.28, P = 0.02), intraepithelial infiltrate (r = –0.26, P = 0.03), and GFR₀ (r = 0.29, P = 0.01). Fibrous crescents (r = 0.22, P = 0.03) were predictive of dialysis at entry. Normal glomeruli (r = –0.30, P = 0.01) and treatment arm (r = –0.28, P = 0.02) were predictive of dialysis after 12 mo. No parameter predicted death. Both chronic and acute tubulointerstitial lesions predicted GFR₁₂ in severe ANCA-associated glomerulonephritis, whereas plasma exchange was a positive predictor of dialysis independence after 12 mo for the entire patient group. Plasma exchange remained a positive predictor when patients who were dialysis dependent at presentation were analyzed separately (r = –0.36, P = 0.01). Normal glomeruli were a positive predictor of dialysis independence and improved renal function after 12 mo, indicating that the unaffected part of the kidney is vital in determining renal outcome.

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