Thomas Rauen1, Frank Eitner, Christina Fitzner, Claudia Sommerer, Martin Zeier, Britta Otte, Ulf Panzer, Harm Peters, Urs Benck, Peter R Mertens, Uwe Kuhlmann, Oliver Witzke, Oliver Gross, Volker Vielhauer, Johannes F E Mann, Ralf-Dieter Hilgers, Jürgen Floege. 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.
Abstract
BACKGROUND: The outcomes of immunosuppressive therapy, when added to supportive care, in patients with IgA nephropathy are uncertain. METHODS: We conducted a multicenter, open-label, randomized, controlled trial with a two-group, parallel, group-sequential design. During a 6-month run-in phase, supportive care (in particular, blockade of the renin-angiotensin system) was adjusted on the basis of proteinuria. Patients who had persistent proteinuria with urinary protein excretion of at least 0.75 g per day were randomly assigned to receive supportive care alone (supportive-care group) or supportive care plus immunosuppressive therapy (immunosuppression group) for 3 years. The primary end points in hierarchical order were full clinical remission at the end of the trial (protein-to-creatinine ratio <0.2 [with both protein and creatinine measured in grams] and a decrease in the estimated glomerular filtration rate [eGFR] of <5 ml per minute per 1.73 m(2) of body-surface area from baseline) and a decrease in the eGFR of at least 15 ml per minute per 1.73 m(2) at the end of the trial. The primary end points were analyzed with the use of logistic-regression models. RESULTS: The run-in phase was completed by 309 of 337 patients. The proteinuria level decreased to less than 0.75 g of urinary protein excretion per day in 94 patients. Of the remaining 162 patients who consented to undergo randomization, 80 were assigned to the supportive-care group, and 82 to the immunosuppression group. After 3 years, 4 patients (5%) in the supportive-care group, as compared with 14 (17%) in the immunosuppression group, had a full clinical remission (P=0.01). A total of 22 patients (28%) in the supportive-care group and 21 (26%) in the immunosuppression group had a decrease in the eGFR of at least 15 ml per minute per 1.73 m(2) (P=0.75). There was no significant difference in the annual decline in eGFR between the two groups. More patients in the immunosuppression group than in the supportive-care group had severe infections, impaired glucose tolerance, and weight gain of more than 5 kg in the first year of treatment. One patient in the immunosuppression group died of sepsis. CONCLUSIONS: The addition of immunosuppressive therapy to intensive supportive care in patients with high-risk IgA nephropathy did not significantly improve the outcome, and during the 3-year study phase, more adverse effects were observed among the patients who received immunosuppressive therapy, with no change in the rate of decrease in the eGFR. (Funded by the German Federal Ministry of Education and Research; STOP-IgAN ClinicalTrials.gov number, NCT00554502.).
RCT Entities:
BACKGROUND: The outcomes of immunosuppressive therapy, when added to supportive care, in patients with IgA nephropathy are uncertain. METHODS: We conducted a multicenter, open-label, randomized, controlled trial with a two-group, parallel, group-sequential design. During a 6-month run-in phase, supportive care (in particular, blockade of the renin-angiotensin system) was adjusted on the basis of proteinuria. Patients who had persistent proteinuria with urinary protein excretion of at least 0.75 g per day were randomly assigned to receive supportive care alone (supportive-care group) or supportive care plus immunosuppressive therapy (immunosuppression group) for 3 years. The primary end points in hierarchical order were full clinical remission at the end of the trial (protein-to-creatinine ratio <0.2 [with both protein and creatinine measured in grams] and a decrease in the estimated glomerular filtration rate [eGFR] of <5 ml per minute per 1.73 m(2) of body-surface area from baseline) and a decrease in the eGFR of at least 15 ml per minute per 1.73 m(2) at the end of the trial. The primary end points were analyzed with the use of logistic-regression models. RESULTS: The run-in phase was completed by 309 of 337 patients. The proteinuria level decreased to less than 0.75 g of urinary protein excretion per day in 94 patients. Of the remaining 162 patients who consented to undergo randomization, 80 were assigned to the supportive-care group, and 82 to the immunosuppression group. After 3 years, 4 patients (5%) in the supportive-care group, as compared with 14 (17%) in the immunosuppression group, had a full clinical remission (P=0.01). A total of 22 patients (28%) in the supportive-care group and 21 (26%) in the immunosuppression group had a decrease in the eGFR of at least 15 ml per minute per 1.73 m(2) (P=0.75). There was no significant difference in the annual decline in eGFR between the two groups. More patients in the immunosuppression group than in the supportive-care group had severe infections, impaired glucose tolerance, and weight gain of more than 5 kg in the first year of treatment. One patient in the immunosuppression group died of sepsis. CONCLUSIONS: The addition of immunosuppressive therapy to intensive supportive care in patients with high-risk IgA nephropathy did not significantly improve the outcome, and during the 3-year study phase, more adverse effects were observed among the patients who received immunosuppressive therapy, with no change in the rate of decrease in the eGFR. (Funded by the German Federal Ministry of Education and Research; STOP-IgAN ClinicalTrials.gov number, NCT00554502.).
Authors: Stephen Zewinger; Thomas Rauen; Michael Rudnicki; Giuseppina Federico; Martina Wagner; Sarah Triem; Stefan J Schunk; Ioannis Petrakis; David Schmit; Stefan Wagenpfeil; Gunnar H Heine; Gert Mayer; Jürgen Floege; Danilo Fliser; Hermann-Josef Gröne; Thimoteus Speer Journal: J Am Soc Nephrol Date: 2018-10-02 Impact factor: 10.121