Interactive exploration of adverse events and multimorbidity in CKD

Inga Steinbrenner; Fruzsina Kotsis; Robin Kosch; Heike Meiselbach; Barbara Bärthlein; Helena Stockmann; Jan Lipovsek; Helena U Zacharias; Michael Altenbuchinger; Thomas Dienemann; Monika Wytopil; Helena Bächle; Claudia Sommerer; Stephanie Titze; Anke Weigel; Hansi Weissensteiner; Sebastian Schönherr; Lukas Forer; Nadine S Kurz; Jan Menne; Georg Schlieper; Markus P Schneider; Elke Schäffner; Jan T Kielstein; Thomas Sitter; Jürgen Floege; Christoph Wanner; Florian Kronenberg; Anna Köttgen; Martin Busch; Vera Krane; Matthias Schmid; Kai-Uwe Eckardt; Ulla T Schultheiss

doi:10.1093/ndt/gfae092

Interactive exploration of adverse events and multimorbidity in CKD

Nephrol Dial Transplant. 2024 Apr 25:gfae092. doi: 10.1093/ndt/gfae092. Online ahead of print.

Authors

Inga Steinbrenner¹, Fruzsina Kotsis^{1

2}, Robin Kosch^{3

4}, Heike Meiselbach⁵, Barbara Bärthlein⁵, Helena Stockmann^{6

7}, Jan Lipovsek¹, Helena U Zacharias³, Michael Altenbuchinger⁴, Thomas Dienemann⁸, Monika Wytopil⁹, Helena Bächle¹, Claudia Sommerer¹⁰, Stephanie Titze⁵, Anke Weigel⁵, Hansi Weissensteiner¹¹, Sebastian Schönherr¹¹, Lukas Forer¹¹, Nadine S Kurz⁴, Jan Menne¹², Georg Schlieper^{13

14}, Markus P Schneider⁵, Elke Schäffner¹⁵, Jan T Kielstein¹⁶, Thomas Sitter¹⁷, Jürgen Floege¹⁴, Christoph Wanner¹⁸, Florian Kronenberg¹¹, Anna Köttgen¹, Martin Busch¹⁹, Vera Krane¹⁸, Matthias Schmid²⁰, Kai-Uwe Eckardt^{5

6}, Ulla T Schultheiss^{1

2}

Affiliations

¹ Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center - University of Freiburg, Freiburg, Germany.
² Department of Medicine IV, Nephrology and Primary Care, Faculty of Medicine and Medical Center - University of Freiburg, Freiburg, Germany.
³ Peter L. Reichertz Institute for Medical Informatics of TU Braunschweig and Hannover Medical School, Hannover Medical School, Hannover, Germany.
⁴ Department of Medical Bioinformatics, University Medical Center Göttingen, Göttingen, Germany.
⁵ Department of Nephrology and Hypertension, Friedrich-Alexander-University Erlangen-Nürnberg, Germany.
⁶ Department of Nephrology and Medical Intensive Care, Charité, Berlin, Germany.
⁷ Department of Nephrology, University Medical Center Regensburg, Regensburg, Germany.
⁸ Department of Operative Intensive Care, University Hospital Regensburg, Regensburg, Germany.
⁹ Institute of Clinical and Molecular Virology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
¹⁰ Department of Nephrology, University Hospital Heidelberg, Renal Center, Heidelberg, Germany.
¹¹ Institute of Genetic Epidemiology, Medical University of Innsbruck, Austria.
¹² Department of Nephrology, Rheumatology and Vascular Medicine, KRH Klinikum Siloah, Hannover, Germany.
¹³ Zentrum für Nieren-, Hochdruck- und Stoffwechselerkrankungen, Hannover, Germany.
¹⁴ Division of Nephrology and Clinical Immunology, University Hospital RWTH Aachen, Germany.
¹⁵ Institute of Public Health, Charité - Universitätsmedizin Berlin, Germany.
¹⁶ Medical Clinic V Nephrology, Rheumatology, Blood Purification - Academic Teaching Hospital Braunschweig, Braunschweig, Germany.
¹⁷ Department of Nephrology and Hypertension, Ludwig-Maximilians University, Munich, Germany.
¹⁸ Department of Clinical Research and Epidemiology, German Heart Failure Center, University Hospital Würzburg, Germany.
¹⁹ Department of Internal Medicine III, Nephrology, University Hospital Jena - Friedrich Schiller University Jena, Jena, Germany.
²⁰ Department of Medical Biometry, Informatics, and Epidemiology, University Hospital Bonn, Bonn, Germany.

PMID: 38664006
DOI: 10.1093/ndt/gfae092

Abstract

Background and hypothesis: Persons with chronic kidney disease (CKD) are at increased risk of adverse events, early mortality, and multimorbidity. A detailed overview of adverse event types and rates from a large CKD cohort under regular nephrological care is missing. We generated an interactive tool to enable exploration of adverse events and their combinations in the prospective, observational German CKD (GCKD) study.

Methods: The GCKD study enrolled 5217 participants under regular nephrological care with an estimated glomerular filtration rate of 30-60 or >60 mL/min/1.73m2 and an overt proteinuria. Cardio-, cerebro- and peripheral vascular, kidney, infection, and cancer events, as well as deaths were adjudicated following a standard operation procedure. We summarized these time-to-event data points for exploration in interactive graphs within an R shiny app. Multivariable adjusted Cox models for time to first event were fitted. Cumulative incidence functions, Kaplan-Meier curves and intersection plots were used to display main adverse events and their combinations by sex and CKD etiology.

Results: Over a median of 6.5 years, 10 271 events occurred in total and 680 participants (13.0%) died while 2947 participants (56.5%) experienced any event. The new publicly available interactive platform enables readers to scrutinize adverse events and their combinations as well as mortality trends as a gateway to better understand multimorbidity in CKD: incident rates per 1000 patient-years varied by event type, CKD etiology, and baseline characteristics. Incidence rates for the most frequent events and their recurrence were 113.6 (cardiovascular), 75.0 (kidney), and 66.0 (infection). Participants with diabetic kidney disease and men were more prone to experiencing events.

Conclusion: This comprehensive explorative tool to visualize adverse events (https://gckd.diz.uk-erlangen.de/), their combination, mortality, and multimorbidity among persons with CKD may manifest as a valuable resource for patient care, identification of high-risk groups, health services, and public health policy planning.

Keywords: adverse events; chronic kidney disease; epidemiology; interactive visualization; multimorbidity.