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      IgA Nephropathy.

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          Abstract

          IgA nephropathy (IgAN) is a leading cause of CKD and renal failure. Recent international collaborative efforts have led to important discoveries that have improved our understanding of some of the key steps involved in the immunopathogenesis of IgAN. Furthermore, establishment of multicenter networks has contributed to rigorous design and execution of clinical trials that have provided important insights regarding immunotherapy in IgAN. In this article, we review emerging developments in clinical and translational IgAN research and describe how these novel findings will influence future strategies to improve the outcome of patients with IgAN.

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          Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis.

          Gerald B Appel, Gabriel Contreras, Mary Anne Dooley … (2009)
          Recent studies have suggested that mycophenolate mofetil (MMF) may offer advantages over intravenous cyclophosphamide (IVC) for the treatment of lupus nephritis, but these therapies have not been compared in an international randomized, controlled trial. Here, we report the comparison of MMF and IVC as induction treatment for active lupus nephritis in a multinational, two-phase (induction and maintenance) study. We randomly assigned 370 patients with classes III through V lupus nephritis to open-label MMF (target dosage 3 g/d) or IVC (0.5 to 1.0 g/m(2) in monthly pulses) in a 24-wk induction study. Both groups received prednisone, tapered from a maximum starting dosage of 60 mg/d. The primary end point was a prespecified decrease in urine protein/creatinine ratio and stabilization or improvement in serum creatinine. Secondary end points included complete renal remission, systemic disease activity and damage, and safety. Overall, we did not detect a significantly different response rate between the two groups: 104 (56.2%) of 185 patients responded to MMF compared with 98 (53.0%) of 185 to IVC. Secondary end points were also similar between treatment groups. There were nine deaths in the MMF group and five in the IVC group. We did not detect significant differences between the MMF and IVC groups with regard to rates of adverse events, serious adverse events, or infections. Although most patients in both treatment groups experienced clinical improvement, the study did not meet its primary objective of showing that MMF was superior to IVC as induction treatment for lupus nephritis.
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            The incidence of primary glomerulonephritis worldwide: a systematic review of the literature.

            A. McGrogan, C. F. M. Franssen, C. S. de Vries (2011)
            Little is known about the worldwide variation in incidence of primary glomerulonephritis (GN). The objective of this review was to critically appraise studies of incidence published in 1980-2010 so that an overall view of trends of these diseases can be found. This would provide important information for determining changes in rates and understanding variations between countries. All relevant papers found through searches of Medline, Embase and ScienceDirect were critically appraised and an assessment was made of the reliability of the reported incidence data. This review includes 40 studies of incidence of primary GN from Europe, North and South America, Canada, Australasia and the Middle East. Rates for the individual types of disease were found to be in adults, 0.2/100,000/year for membrano-proliferative GN, 0.2/100,000/year for mesangio-proliferative GN, 0.6/100,000/year for minimal change disease, 0.8/100,000/year for focal segmental glomerulosclerosis, 1.2/100,000/year for membranous nephropathy and 2.5/100,000/year for IgA nephropathy. Rates were lower in children at around 0.1/100,000/year with the exception of minimal change disease where incidence was reported to be 2.0/100,000/year in Caucasian children with higher rates in Arabian children (9.2/100,000/year) and Asian children (6.2-15.6/100,000/year). This study found that incidence rates of primary GN vary between 0.2/100,000/year and 2.5/100,000/year. The incidence of IgA nephropathy is at least 2.5/100,000/year in adults; this disease can exist subclinically and is therefore only detected by chance in some patients. In addition, referral policies for diagnostic biopsy vary between countries. This will affect the incidence rates found.
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              The Oxford classification of IgA nephropathy: rationale, clinicopathological correlations, and classification.

              Daniel C. Cattran, Rosanna Coppo, H. Cook … (2009)
              IgA nephropathy is the most common glomerular disease worldwide, yet there is no international consensus for its pathological or clinical classification. Here a new classification for IgA nephropathy is presented by an international consensus working group. The goal of this new system was to identify specific pathological features that more accurately predict risk of progression of renal disease in IgA nephropathy, thus enabling both clinicians and pathologists to improve individual patient prognostication. In a retrospective analysis, sequential clinical data were obtained on 265 adults and children with IgA nephropathy who were followed for a median of 5 years. Renal biopsies from all patients were scored by pathologists blinded to the clinical data for pathological variables identified as reproducible by an iterative process. Four of these variables: (1) the mesangial hypercellularity score, (2) segmental glomerulosclerosis, (3) endocapillary hypercellularity, and (4) tubular atrophy/interstitial fibrosis were subsequently shown to have independent value in predicting renal outcome. These specific pathological features withstood rigorous statistical analysis even after taking into account all clinical indicators available at the time of biopsy as well as during follow-up. The features have prognostic significance and we recommended they be taken into account for predicting outcome independent of the clinical features both at the time of presentation and during follow-up. The value of crescents was not addressed due to their low prevalence in the enrolled cohort.
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                Author and article information

                Journal
                Journal ID (iso-abbrev): Clin J Am Soc Nephrol
                Title: Clinical journal of the American Society of Nephrology : CJASN
                Publisher: American Society of Nephrology (ASN)
                ISSN (Electronic): 1555-905X
                ISSN (Print): 1555-9041
                Publication date (Electronic): Apr 03 2017
                Volume: 12
                Issue: 4
                Affiliations
                [1 ] Department of Medicine, University of Toronto and Division of Nephrology, University Health Network, Toronto, Ontario, Canada.
                [2 ] Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California; and.
                [3 ] Department of Medicine, University of Toronto and Division of Nephrology, University Health Network, Toronto, Ontario, Canada; heather.reich@uhn.ca.
                [4 ] Gabor Zellerman Chair in Nephrology Research, University of Toronto, Toronto, Ontario, Canada.
                Article
                Publisher Item ID: CJN.07420716
                DOI: 10.2215/CJN.07420716
                PMC ID: 5383386
                PubMed ID: 28159829
                SO-VID: 2cda45a7-b3c9-46c8-b5aa-37e5acf6d781
                History

                Keywords: crescents,humans,immunosuppression,immunotherapy,kidney,pathology,renal insufficiency,review,translational medical research,IGA,IgA nephropathy,chronic,corticosteroids,glomerulonephritis
                Data availability:
                Keywords: crescents, humans, immunosuppression, immunotherapy, kidney, pathology, renal insufficiency, review, translational medical research, IGA, IgA nephropathy, chronic, corticosteroids, glomerulonephritis

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