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      IgA Nephropathy


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          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.

          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.

            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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              Remission of proteinuria improves prognosis in IgA nephropathy.

              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.

                Author and article information

                Clin J Am Soc Nephrol
                Clin J Am Soc Nephrol
                Clinical Journal of the American Society of Nephrology : CJASN
                American Society of Nephrology
                3 April 2017
                03 February 2017
                : 12
                : 4
                : 677-686
                [* ]Department of Medicine, University of Toronto and Division of Nephrology, University Health Network, Toronto, Ontario, Canada;
                []Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California; and
                []Gabor Zellerman Chair in Nephrology Research, University of Toronto, Toronto, Ontario, Canada
                Author notes
                Correspondence: Dr. Heather Reich, Division of Nephrology, University Health Network, 200 Elizabeth Street, Room 8N 849, Toronto, ON M5G 2C4, Canada. Email: heather.reich@ 123456uhn.ca
                PMC5383386 PMC5383386 5383386 07420716
                Copyright © 2017 by the American Society of Nephrology
                Page count
                Figures: 2, Tables: 0, Equations: 0, References: 72, Pages: 10
                Glomerular Diseases: Update for the Clinician
                Custom metadata
                April 03, 2017

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


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