Why, when and how should immunosuppressive therapy considered in patients with immunoglobulin A nephropathy?
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.
Department of Internal Medicine, Neurology, Dermatology, Clinic for Endocrinology, Nephrology, Section of Nephrology, University Leipzig, Leipzig, Germany.
F M
FM
Rasche
Department of Internal Medicine I, Division of Nephrology, University Hospital of Ulm, Ulm, Germany. frieder.keller@uni-ulm.de.
F
F
Keller
Department of Head Medicine and Oral Health, Department of Ophthalmology, University Leipzig, Leipzig, Germany.
W G
WG
Rasche
Center for Geriatric Medicine at Bezirksklinikum Regensburg, Department of Psychiatry and Psychotherapy, University Regensburg, Regensburg, Germany.
S
S
Schiekofer
Institute of Clinical Immunology, Medical Faculty, Leipzig, Germany.
A
A
Boldt
Institute of Clinical Immunology, Medical Faculty, Leipzig, Germany.
U
U
Sack
Department of Diagnostic and Interventional Radiology, University Leipzig, Leipzig, Germany.
J
J
Fahnert
D015415:Biomarkers; D019468:Disease Management; D018450:Disease Progression; D005922:Glomerulonephritis, IGA / Q000175:diagnosis / Q000209:etiology / Q000628:therapy*; D006801:Humans; D007165:Immunosuppression Therapy / Q000009:adverse effects / Q000379:methods; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D058990:Molecular Targeted Therapy; D011379:Prognosis; D013997:Time Factors; D016896:Treatment Outcome
D015415:Biomarkers; D007166:Immunosuppressive Agents
IgA nephropathy; corticosteroids; cyclophosphamide; high dose intravenous immunoglobulines; mycophenolic acid