Intensive Supportive Care plus Immunosuppression in IgA Nephropathy
Thomas Rauen, 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, STOP-IgAN Investigators, Jürgen Floege, Frank Eitner, Thomas Rauen, Marcus J Moeller, Anneliese Michaelis, Horst Weihprecht, Emek Baatz, Silvia Söllner, Harm Peters, Klemens Budde, Denise Markmann, Saban Elitok, Markus Bieringer, Ralf Schindler, Ulrich Frei, Sima Canaan-Kühl, Christiane Erley, Karsten Schlieps, Uwe Kuhlmann, Frans Zandvoort, Marie-Luise Bodemann, Bernd Hohenstein, Christian Hugo, Catrin Palm, Annegret Fleischer, Karl Hilgers, Kai-Uwe Eckardt, Sabine Jank, Oliver Witzke, Raffaela Kirchmeyer, Oliver Gross, Gerhard Anton Müller, Frauke Weber, Horst Walter Birk, Andreas Feustel, Sönke Jeßen, Rolf A Stahl, Ulf Panzer, Eugen Kinzler, Hermann Haller, Anna Bertram, Elisabeth Bahlmann, Martin Zeier, Claudia Sommerer, Claudia Foellinger, Gunter Wolf, Martin Busch, Christiane Rüster, Thomas Rath, Stephan Ziefle, Susanne Weik, Thomas Benzing, Stefanie Bastek, Tülay Kisner, Peter R Mertens, Hans-Peter Bosselmann, C Piehler, Stefan Westphalen, Stephanie Koepke, Urs Benck, Uwe Göttmann, Birgitta Langhäuser, Joachim Hoyer, Tanja Maier, Birgit Kortus-Goetze, Volker Vielhauer, Michael Fischereder, Florian Vilsmaier, Oliver Sarkar, Sabine Engelhardt, Johannes F E Mann, Marianna Stefanidou, Britta Otte, Hermann Pavenstädt, Britta George, Bernhard Banas, Alexander Böger, Tanja Emmer, Stefan M Weiner, Erich Jochum, Christa Kiefer, Nils Heyne, Ferruh Artunc, Georg Georges, Arndt Petermann, Helmut Reichel, Bernd Krumme, Thomas Mettang, Marlies Hirschberg, Christoph Wanner, Thomas Metzger, Ellen Irmler-Mercier, Thomas Rauen, 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, STOP-IgAN Investigators, Jürgen Floege, Frank Eitner, Thomas Rauen, Marcus J Moeller, Anneliese Michaelis, Horst Weihprecht, Emek Baatz, Silvia Söllner, Harm Peters, Klemens Budde, Denise Markmann, Saban Elitok, Markus Bieringer, Ralf Schindler, Ulrich Frei, Sima Canaan-Kühl, Christiane Erley, Karsten Schlieps, Uwe Kuhlmann, Frans Zandvoort, Marie-Luise Bodemann, Bernd Hohenstein, Christian Hugo, Catrin Palm, Annegret Fleischer, Karl Hilgers, Kai-Uwe Eckardt, Sabine Jank, Oliver Witzke, Raffaela Kirchmeyer, Oliver Gross, Gerhard Anton Müller, Frauke Weber, Horst Walter Birk, Andreas Feustel, Sönke Jeßen, Rolf A Stahl, Ulf Panzer, Eugen Kinzler, Hermann Haller, Anna Bertram, Elisabeth Bahlmann, Martin Zeier, Claudia Sommerer, Claudia Foellinger, Gunter Wolf, Martin Busch, Christiane Rüster, Thomas Rath, Stephan Ziefle, Susanne Weik, Thomas Benzing, Stefanie Bastek, Tülay Kisner, Peter R Mertens, Hans-Peter Bosselmann, C Piehler, Stefan Westphalen, Stephanie Koepke, Urs Benck, Uwe Göttmann, Birgitta Langhäuser, Joachim Hoyer, Tanja Maier, Birgit Kortus-Goetze, Volker Vielhauer, Michael Fischereder, Florian Vilsmaier, Oliver Sarkar, Sabine Engelhardt, Johannes F E Mann, Marianna Stefanidou, Britta Otte, Hermann Pavenstädt, Britta George, Bernhard Banas, Alexander Böger, Tanja Emmer, Stefan M Weiner, Erich Jochum, Christa Kiefer, Nils Heyne, Ferruh Artunc, Georg Georges, Arndt Petermann, Helmut Reichel, Bernd Krumme, Thomas Mettang, Marlies Hirschberg, Christoph Wanner, Thomas Metzger, Ellen Irmler-Mercier
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.).
Source: PubMed