Why, when and how should immunosuppressive therapy considered in patients with immunoglobulin A nephropathy?. (8th September 2016)

• Record Type: Journal Article
• Authors: Rasche, F. M.; Keller, F.; Rasche, W. G.; Schiekofer, S.; Boldt, A.; Sack, U.; Fahnert, J.
• Is Part Of: Clinical and experimental immunology. Volume 186:Number 2(2016:Nov.)
• Page Start: 115
• Page End: 133
• Publication Date: 2016-09-08
• Subjects: IgA nephropathy -- cyclophosphamide -- mycophenolic acid -- corticosteroids -- high dose intravenous immunoglobulines; Immunopathology -- Periodicals; 616.079
• DOI: 10.1111/cei.12823
• Languages: English
• ISSNs: 0009-9104

Abstract

Summary: IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Lifelong mesangial deposition of IgA1 complexes subsist inflammation and nephron loss, but the complex pathogenesis in detail remains unclear. In regard to the heterogeneous course, classical immunosuppressive and specific therapeutic regimens adapted to the loss of renal function will here be discussed in addition to the essential common renal supportive therapy. Renal supportive therapy alleviates secondary, surrogate effects or sequelae on renal function and proteinuria of high intraglomerular pressure and subsequent nephrosclerosis by inhibition of the renin angiotensin system (RAASB). In patients with physiological (ΔGFR < 1·5 ml/min/year) or mild (ΔGFR 1·5–5 ml/min/year) decrease of renal function and proteinuric forms (> 1 g/day after RAASB), corticosteroids have shown a reduction of proteinuria and might protect further loss of renal function. In patients with progressive loss of renal function (ΔGFR > 3 ml/min within 3 months) or a rapidly progressive course with or without crescents in renal biopsy, cyclophosphamide with high‐dose corticosteroids as induction therapy and azathioprine maintenance has proved effective in one randomized controlled study of a homogeneous cohort in loss of renal function (ΔGFR). Mycophenolic acid provided further maintenance in non‐randomized trials. Differentiated, precise, larger, randomized, placebo‐controlled studies focused on the loss of renal function in the heterogeneous forms of IgAN are still lacking. Prospectively, fewer toxic agents will be necessary in the treatment of IgAN. Abstract : IgA Nephropathy is the most common primary glomerulonephritis worldwide and usual renal supportive therapy is needed in reducing intraglomerular pressure and immunogenic alterations. The heterogeneous course of this mesangioproliferative glomerulonephritis requires a differentiated therapy in regard to the decrease of renal function in linear regression analysis (ΔGFR). In this review, we will provide a comprehensive view of the pathophysiology, the present and prospective therapies in consideration of the loss of renal function and with particular focus on immunosuppressive treatment.