After ten years of follow-up, no difference between supportive care plus immunosuppression and supportive care alone in IgA nephropathy

Thomas Rauen; Stephanie Wied; Christina Fitzner; Frank Eitner; Claudia Sommerer; Martin Zeier; Britta Otte; Ulf Panzer; Klemens Budde; 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

doi:10.1016/j.kint.2020.04.046

After ten years of follow-up, no difference between supportive care plus immunosuppression and supportive care alone in IgA nephropathy

Kidney Int. 2020 Oct;98(4):1044-1052. doi: 10.1016/j.kint.2020.04.046. Epub 2020 May 22.

Authors

Thomas Rauen¹, Stephanie Wied², Christina Fitzner², Frank Eitner³, Claudia Sommerer⁴, Martin Zeier⁴, Britta Otte⁵, Ulf Panzer⁶, Klemens Budde⁷, Urs Benck⁸, Peter R Mertens⁹, Uwe Kuhlmann¹⁰, Oliver Witzke¹¹, Oliver Gross¹², Volker Vielhauer¹³, Johannes F E Mann¹⁴, Ralf-Dieter Hilgers², Jürgen Floege¹⁵; STOP-IgAN Investigators

Collaborators

STOP-IgAN Investigators:
Jürgen Floege¹, Frank Eitner¹, Thomas Rauen¹, Marcus J Moeller¹, Horst Weihprecht¹⁶, Klemens Budde¹⁷, Harm Peters¹⁷, Saban Elitok¹⁸, Markus Bieringer¹⁸, Ralf Schindler¹⁹, Ulrich Frei²⁰, Sima Canaan-Kühl²⁰, Christiane Erley¹⁰, Karsten Schlieps¹⁰, Uwe Kuhlmann²¹, Frans Zandvoort²¹, Bernd Hohenstein²², Christian Hugo²², Catrin Palm²², Karl Hilgers¹¹, Oliver Witzke¹¹, Oliver Gross¹², Ulf Panzer²³, Hermann Haller²⁴, Anna Bertram²⁴, Claudia Sommerer²⁵, Martin Zeier²⁵, Gunter Wolf²⁶, Martin Busch²⁶, Thomas Rath²⁷, Stephan Ziefle²⁷, Thomas Benzing²⁸, Franziska Grundmann²⁸, Peter R Mertens⁹, Stefan Westphalen²⁹, Urs Benck⁸, Uwe Göttmann⁸, Volker Vielhauer³⁰, Michael Fischereder³⁰, Oliver Sarkar³¹, Marianna Stefanidou³², Johannes F E Mann³³, Britta Otte⁵, Hermann Pavenstädt⁵, Bernhard Banas³⁴, Alexander Boeger³⁵, Nils Heyne³⁶, Ferruh Artunc³⁶, Helmut Reichel³⁷, Thomas Mettang³⁷, Christoph Wanner³⁸, Thomas Metzger³⁸, Stephanie Wied², Christina Fitzner², Ralf-Dieter Hilgers²

Affiliations

¹ Division of Nephrology and Clinical Immunology, RWTH Aachen University, Aachen, Germany.
² Department of Medical Statistics, RWTH Aachen University, Aachen, Germany.
³ Division of Nephrology and Clinical Immunology, RWTH Aachen University, Aachen, Germany; Bayer AG, Kidney Diseases Research, Wuppertal, Germany.
⁴ Department of Nephrology and Renal Center Heidelberg, University of Heidelberg, Heidelberg, Germany.
⁵ Internal Medicine D, Department of Nephrology, Hypertension and Rheumatology, University Hospital Muenster, Muenster, Germany.
⁶ Division of Nephrology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
⁷ Department of Nephrology, Charité Campus Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany.
⁸ Department of Medicine V, University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany.
⁹ Department of Nephrology and Hypertension, Diabetes and Endocrinology, Otto-von-Guericke University, Magdeburg, Germany.
¹⁰ Medical Clinic III, Central Hospital Bremen, Bremen, Germany.
¹¹ Department of Infectious Diseases, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
¹² Clinic for Nephrology and Rheumatology, University Medical Center Goettingen, Goettingen, Germany.
¹³ Nephrologisches Zentrum, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, LMU München, Munich, Germany.
¹⁴ KfH Kidney Center Munich-Schwabing and Department of Medicine IV, University of Erlangen, Erlangen, Germany.
¹⁵ Division of Nephrology and Clinical Immunology, RWTH Aachen University, Aachen, Germany. Electronic address: [email protected].
¹⁶ Department of Nephrology and Hypertensiology, II. Medical Clinic, Klinikum Augsburg, Augsburg, Germany.
¹⁷ Department of Nephrology, Charité Campus Mitte, Charité-Universitaetsmedizin Berlin, Berlin, Germany.
¹⁸ Department of Cardiology and Nephrology, Klinikum Berlin-Buch, Berlin, Germany.
¹⁹ Clinic for Nephrology and Intensive Care Medicine, Charité-Universitaetsmedizin Berlin, Campus Virchow Clinic, Berlin, Germany.
²⁰ Department of Medicine II, St Joseph-Krankenhaus, Berlin, Germany.
²¹ Department of Internal Medicine III, Division of Nephrology, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany.
²² Department of Nephrology and Hypertension, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany.
²³ University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
²⁴ Department of Nephrology, Hannover Medical School, Hannover, Germany.
²⁵ Department of Nephrology, University of Heidelberg, Heidelberg, Germany.
²⁶ Department of Internal Medicine III, Jena University Hospital, Friedrich Schiller University, Jena, Germany.
²⁷ Medizinische Klinik III, Westpfalz-Klinikum, Kaiserslautern, Germany.
²⁸ Department II of Internal Medicine and Centre for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.
²⁹ Dialysezentrum am Brand, Mainz, Germany.
³⁰ Nephrologisches Zentrum, Medizinische Klinik und Poliklinik IV, Klinikum der Ludwig-Maximilians-Universität, Munich, Germany.
³¹ Technical University Munich, Germany.
³² Department of Nephrology, Hypertension and Rheumatology, Munich General Hospital, Munich, Germany.
³³ KfH Kidney Center Munich-Schwabing and Department of Medicine IV, University of Erlangen, Germany.
³⁴ Department of Nephrology, University Hospital Regensburg, Regensburg, Germany.
³⁵ Department of Internal Medicine IV, University Hospital Tuebingen, Tuebingen, Germany.
³⁶ Nephrologisches Zentrum Villingen-Schwenningen, Villingen-Schwenningen, Germany.
³⁷ Department of Nephrology, Deutsche Klinik für Diagnostik, Wiesbaden, Germany.
³⁸ Department of Medicine, Division of Nephrology, University Hospital of Wuerzburg, Wuerzburg, Germany.

PMID: 32450154
DOI: 10.1016/j.kint.2020.04.046

Abstract

The randomized, controlled STOP-IgAN trial in patients with IgA nephropathy (IgAN) and substantial proteinuria showed no benefit of immunosuppression added on top of supportive care on renal function over three years. As a follow-up we evaluated renal outcomes in patients over a follow-up of up to ten years in terms of serum creatinine, proteinuria, end-stage kidney disease (ESKD), and death. The adapted primary endpoint was the time to first occurrence of a composite of death, ESKD, or a decline of over 40% in the estimated glomerular filtration rate (eGFR) compared to baseline at randomization into STOP-IgAN. Data were analyzed by Cox-regression models. Follow-up data were available for 149 participants, representing 92% of the patients originally randomized. Median follow-up was 7.4 years (inter quartile range 5.7 to 8.3 years). The primary endpoint was reached in 36 of 72 patients randomized to supportive care and 35 of 77 patients randomized to additional immunosuppression (hazard ratio 1.20; 95% confidence interval 0.75 to 1.92). ESKD occurred in 17 of the patients with supportive care and in 20 of the patients with additional immunosuppression. Additionally, the rates of eGFR loss over 40% and annual eGFR loss did not differ between groups. Two patients died with supportive care and three with additional immunosuppression. Thus, within the limitations of a retrospective study, over a follow-up of up to ten years, and using an adapted primary endpoint, we failed to detect differences in key clinical outcomes in IgAN patients randomized to receive added immunosuppression on top of supportive care versus supportive care alone.

Keywords: IgA nephropathy; IgAN; STOP-IgAN; immunosuppression; long term.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Follow-Up Studies
Glomerular Filtration Rate
Glomerulonephritis, IGA* / diagnosis
Glomerulonephritis, IGA* / therapy
Humans
Immunosuppression Therapy
Immunosuppressive Agents / adverse effects
Proteinuria / therapy
Retrospective Studies

Substances

Immunosuppressive Agents