Spectrum and Prognosis of Noninfectious Renal Mixed Cryoglobulinemic GN

Abstract

Noninfectious mixed cryoglobulinemic GN (MCGN) has been poorly investigated. We analyzed presentation and outcome of 80 patients with biopsy-proven MCGN, which were identified in the retrospective French CryoVas survey. MCGN was related to primary Sjögren's syndrome in 22.5% of patients and to lymphoproliferative disorders in 28.7% of patients, and was defined as essential in 48.8% of patients. At presentation, hematuria, proteinuria ≥1 g/d, hypertension, and renal failure were observed in 97.4%, 84.8%, 85.3%, and 82.3% of cases, respectively. Mean±eGFR was 39.5±20.4 ml/min per 1.73 m(2) Membranoproliferative GN was the predominant histologic pattern, observed in 89.6% of cases. Renal interstitium inflammatory infiltrates were observed in 50% of cases. First-line treatment consisted of steroids alone (27.6%) or in association with rituximab (21.1%), alkylating agents (36.8%) or a combination of cyclophosphamide and rituximab (10.5%). After a mean follow-up of 49.9±45.5 months, 42.7% of patients relapsed with a renal flare in 75% of cases. At last follow-up, mean eGFR was 50.2±26.1 ml/min per 1.73 m(2)with 9% of patients having reached ESRD; 59% and 50% of patients achieved complete clinical and renal remission, respectively. A rituximab+steroids regimen prevented relapses more effectively than steroids alone or a cyclophosphamide+steroids combination did, but was associated with a higher rate of early death when used as first-line therapy. Severe infections and new-onset B-cell lymphoma occurred in 29.1% and 8.9% of cases, respectively; 24% of patients died. In conclusion, noninfectious MCGN has a poor long-term outcome with severe infections as the main cause of death.

Keywords: histopathology,; membranoproliferative GN.

Figure 1.

Glomerular lesions in the course of noninfectious MCV. Light microscopy examination showing typical MPGN with endocapillary proliferation, capillary lumen infiltration by monocytes–macrophages, and Ig-related protein thrombi in the capillary lumen (A, Masson’s trichrome stain, ×400), typical doubles contours (B, Jones’ staining, ×400) and a case of mesangial proliferative GN (C, Masson’s trichrome stain, ×400). Immunofluorescence study showing granular and immune-complex glomerular deposits composed of IgG (D). IgM, and both κ and λ light chains were also detected in a similar pattern (data not shown). Electron microscopy analysis showing capillary thickening and subendothelial granular dense deposits (E; Po, podocyte; Ec, endothelial cell; Rbc, red blood cell; *, dense deposits), and organized microtubular deposits (F).