Long-Term Risk and Risk Factors for ESKD in Membranoproliferative Glomerulonephritis

Background: Membranoproliferative glomerulonephritis (MPGN) is a distinctive light microscopic injury pattern caused by a wide range of different disease conditions. The classification of MPGN has changed over time, it is now common to divide MPGN caused by immune complexes (IC-MPGN) and MPGN caused by dysregulation of the alternative activation pathway in the complement system, complement C3 nephropathy (C3G). The utility of division by IC-MPGN/C3G versus etiological division for diagnosis, treatment, and prognosis, however, is still uncertain. There is a need for more information about the long-term prognosis of MPGN, including risk factors for progression to end-stage kidney disease (ESKD). We have therefore analyzed the risk of ESKD for patients with MPGN registered in the Norwegian Kidney Biopsy registry (NKBR) in the period 1991-2012. Methods: Cases of biopsy-verified MPGN 1991-2012 including demographic, clinical, laboratory, and histological variables at the time of diagnosis were retrieved from NKBR. Cases of MPGN due to SLE and thrombotic microangiopathy were excluded. The cohort was linked with the Norwegian Kidney Registry for identification of patients with ESKD by May 1, 2014 Results: We identified 158 patients with biopsy-verified MPGN. Male; 85 (54%), age; 47 years (SD 23), systolic BP; 151mmHg (SD 28), diastolic BP; 86 mmHg (SD 16), hypertension; 155 (67%), mean eGFR; 50 ml/min/1.73m2 (SD 35), eGFR<15; 18 (11%), eGFR 15-29; 26 (16%), eGFR 30-59; 49 (31%), s-albumin 28 g/l (SD 7), proteinuria 5.6 g/24h (SD 3.4), nephrotic syndrome; 79 (50%), crescents; 28 (18%), tubulointerstitial fibrosis >50%; 77 (49%) and C1q positive; 111 (70%). During an average observation period of 11 years, 61 (39%) of patients progressed to ESKD. 45 (28%) of the patients died, without ESKD. Cumulative risk for ESKD after 5/10/15/25 y; 25%/37%/43%/48%. A low eGFR was the only significant risk factor of ESKD, 42 vs 55, p=0.03. Conclusion: A cumulative long-term risk for ESKD in patients with MPGN of around 50% corresponds well with previously published studies. The registry data unfortunately does not allow precise classification by IC-MPGN/C3N. C1q positivity is, however, indicative of IC-MPGN and in this study not a significant prognostic factor. Funding: Commercial Support - Novartis