Intensive Supportive Care plus Immunosuppression in IgA Nephropathy.

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Abstract

The outcomes of immunosuppressive therapy, when added to supportive care, in patients with IgA nephropathy are uncertain.

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Most cited references 22

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Decline in estimated glomerular filtration rate and subsequent risk of end-stage renal disease and mortality.

Josef Coresh, Tanvir Turin, Kunihiro Matsushita … (2014)

The established chronic kidney disease (CKD) progression end point of end-stage renal disease (ESRD) or a doubling of serum creatinine concentration (corresponding to a change in estimated glomerular filtration rate [GFR] of −57% or greater) is a late event. To characterize the association of decline in estimated GFR with subsequent progression to ESRD with implications for using lesser declines in estimated GFR as potential alternative end points for CKD progression. Because most people with CKD die before reaching ESRD, mortality risk also was investigated. Individual meta-analysis of 1.7 million participants with 12,344 ESRD events and 223,944 deaths from 35 cohorts in the CKD Prognosis Consortium with a repeated measure of serum creatinine concentration over 1 to 3 years and outcome data. Transfer of individual participant data or standardized analysis of outputs for random-effects meta-analysis conducted between July 2012 and September 2013, with baseline estimated GFR values collected from 1975 through 2012. End-stage renal disease (initiation of dialysis or transplantation) or all-cause mortality risk related to percentage change in estimated GFR over 2 years, adjusted for potential confounders and first estimated GFR. The adjusted hazard ratios (HRs) of ESRD and mortality were higher with larger estimated GFR decline. Among participants with baseline estimated GFR of less than 60 mL/min/1.73 m2, the adjusted HRs for ESRD were 32.1 (95% CI, 22.3-46.3) for changes of −57% in estimated GFR and 5.4 (95% CI, 4.5-6.4) for changes of −30%. However, changes of −30% or greater (6.9% [95% CI, 6.4%-7.4%] of the entire consortium) were more common than changes of −57% (0.79% [95% CI, 0.52%-1.06%]). This association was strong and consistent across the length of the baseline period (1 to 3 years), baseline estimated GFR, age, diabetes status, or albuminuria. Average adjusted 10-year risk of ESRD (in patients with a baseline estimated GFR of 35 mL/min/1.73 m2) was 99% (95% CI, 95%-100%) for estimated GFR change of −57%, was 83% (95% CI, 71%-93%) for estimated GFR change of −40%, and was 64% (95% CI, 52%-77%) for estimated GFR change of −30% vs 18% (95% CI, 15%-22%) for estimated GFR change of 0%. Corresponding mortality risks were 77% (95% CI, 71%-82%), 60% (95% CI, 56%-63%), and 50% (95% CI, 47%-52%) vs 32% (95% CI, 31%-33%), showing a similar but weaker pattern. Declines in estimated GFR smaller than a doubling of serum creatinine concentration occurred more commonly and were strongly and consistently associated with the risk of ESRD and mortality, supporting consideration of lesser declines in estimated GFR (such as a 30% reduction over 2 years) as an alternative end point for CKD progression.

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Remission of proteinuria improves prognosis in IgA nephropathy.

Heather N. Reich, Stéphan Troyanov, James W. Scholey … (2007)

Proteinuria has been shown to be an adverse prognostic factor in IgA nephropathy. The benefit of achieving a partial remission of proteinuria, however, has not been well described. We studied 542 patients with biopsy-proven primary IgA nephropathy in the Toronto Glomerulonephritis Registry and found that glomerular filtration rate (GFR) declined at -0.38 +/- 0.61 ml/min per 1.73 m2/mo overall, with 30% of subjects reaching end-stage renal disease. Multivariate analysis revealed that proteinuria during follow-up was the most important predictor of the rate of GFR decline. Among the 171 patients with 3 g/d (n = 121) lost renal function 25-fold faster than those with or =3 g/d who achieved a partial remission (<1 g/d) had a similar course to patients who had < or =1 g/d throughout, and fared far better than patients who never achieved remission. These results underscore the relationship between proteinuria and prognosis in IgA nephropathy and establish the importance of remission.

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Randomized controlled clinical trial of corticosteroids plus ACE-inhibitors with long-term follow-up in proteinuric IgA nephropathy.

Francesco Paolo Schena, D. Torres-Lagares, Carlo Manno … (2009)

Immunoglobulin A nephropathy (IgAN) is the most common cause of chronic renal failure among primary glomerulonephritis patients. The best treatment for IgAN remains poorly defined. We planned a long-term, prospective, open-label, multicentre, centrally randomized controlled trial to assess whether the combination of prednisone and ramipril was more effective than ramipril alone in patients with proteinuric IgAN. Ninety-seven biopsy-proven IgAN patients with moderate histologic lesions, 24-h proteinuria > or =1.0 g and estimated glomerular filtration rate (eGFR) > or = 50 ml/min/ 1.73 m(2) were randomly allocated to receive a 6-month course of oral prednisone plus ramipril (combination therapy group) or ramipril alone (monotherapy group) for the total duration of follow-up. The primary outcome was the progression of renal disease defined as the combination of doubling of baseline serum creatinine or end-stage kidney disease (ESKD). The secondary outcomes were the rate of renal function decline defined as the eGFR slope over time, and the reduction of 24-h proteinuria. After a follow-up of up to 96 months, 13/49 (26.5%) patients in the monotherapy group reached the primary outcome compared with 2/48 (4.2%) in the combination therapy group. The Kaplan-Meier analysis showed a significantly higher probability of not reaching the combined outcome in the combination therapy group than in the monotherapy group (85.2% versus 52.1%; log-rank test P = 0.003). In the multivariate analysis, baseline serum creatinine and 24-h proteinuria were independent predictors of the risk of primary outcome; treatment with prednisone plus ramipril significantly reduced the risk of renal disease progression (hazard ratio 0.13; 95% confidence interval 0.03-0.61; P = 0.01). The mean rate of eGFR decline was higher in the monotherapy group than in the combination therapy group (-6.17 +/- 13.3 versus -0.56 +/- 7.62 ml/min/ 1.73 m(2)/year; P = 0.013). Moreover, the combined treatment reduced 24-h proteinuria more than ramipril alone during the first 2 years. Our results suggest that the combination of corticosteroids and ramipril may provide additional benefits compared with ramipril alone in preventing the progression of renal disease in proteinuric IgAN patients in the long-term follow-up.

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Journal

Journal ID (iso-abbrev): N. Engl. J. Med.

Title: The New England journal of medicine

ISSN (Electronic): 1533-4406

ISSN (Print): 0028-4793

Publication date (Electronic): Dec 3 2015

Volume: 373

Issue: 23

Affiliations

[1 ] From the Division of Nephrology and Clinical Immunology (T.R., F.E., J.F.) and Department of Medical Statistics (C.F., R.-D.H.), RWTH Aachen University, Aachen, Bayer Pharma, Kidney Diseases Research, Wuppertal (F.E.), Department of Nephrology, University of Heidelberg, Heidelberg (C.S., M.Z.), Internal Medicine D, Department of Nephrology, Hypertension and Rheumatology, University Hospital Muenster, Muenster (B.O.), University Medical Center Hamburg-Eppendorf, Hamburg (U.P.), Department of Nephrology and Dieter Scheffner Center for Medical Education, Charité Campus Mitte, Charité-Universitätsmedizin Berlin, Berlin (H.P.), Department of Medicine V, University Medical Center Mannheim, University of Heidelberg, Mannheim (U.B.), Department of Nephrology and Hypertension, Diabetes and Endocrinology, Otto-von-Guericke University, Magdeburg (P.R.M.), Medical Clinic III, Central Hospital Bremen, Bremen (U.K.), Department of Nephrology, University Hospital Essen, University of Duisburg-Essen, Essen (O.W.), Clinic for Nephrology and Rheumatology, University Medical Center Goettingen, Goettingen (O.G.), and Nephrologisches Zentrum, Medizinische Klinik und Poliklinik IV, Klinikum der Ludwig-Maximilians-Universität (V.V.), and Department of Nephrology, Hypertension and Rheumatology, Munich General Hospital (J.F.E.M.), Munich - all in Germany.

Article

DOI: 10.1056/NEJMoa1415463

PubMed ID: 26630142

SO-VID: 3a040bfd-a602-4d0f-814d-3d50cb20bfd4

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Intensive Supportive Care plus Immunosuppression in IgA Nephropathy.

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Most cited references 22

Decline in estimated glomerular filtration rate and subsequent risk of end-stage renal disease and mortality.

Remission of proteinuria improves prognosis in IgA nephropathy.

Randomized controlled clinical trial of corticosteroids plus ACE-inhibitors with long-term follow-up in proteinuric IgA nephropathy.

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