Acute kidney injury as a key predictor of cardiovascular events in chronic kidney disease patients: the CKD-REIN study

Nans Florens; Estelle Aymes; Victoria Gauthier; Luc Frimat; Maurice Laville; Dimitri Bedo; Thomas Beaudrey; Philippe Amouyel; Nicolas Mansencal; Céline Lange; Sophie Liabeuf; Ziad A Massy; Benedicte Stengel; Natalia Alencar de Pinho; Aghiles Hamroun

doi:10.1093/ckj/sfae337

Acute kidney injury as a key predictor of cardiovascular events in chronic kidney disease patients: the CKD-REIN study

Clin Kidney J. 2024 Dec 11;17(12):sfae337. doi: 10.1093/ckj/sfae337. eCollection 2024 Dec.

Authors

Nans Florens^{1

2

3}, Estelle Aymes^{4

5}, Victoria Gauthier^{4

5}, Luc Frimat⁶, Maurice Laville⁷, Dimitri Bedo^{1

2}, Thomas Beaudrey^{1

2}, Philippe Amouyel^{4

5}, Nicolas Mansencal^{8

9}, Céline Lange^{9

10}, Sophie Liabeuf¹¹, Ziad A Massy^{3

9

12}, Benedicte Stengel⁹, Natalia Alencar de Pinho⁹, Aghiles Hamroun^{4

5}

Affiliations

¹ Nephrology, Dialysis & Transplantation Department, Nouvel Hôpital Civil, Hôpitaux Universitaires de Strasbourg, 1 Place de l'hôpital, Strasbourg, France.
² UMR1109 Molecular Immuno-Rhumatology, FHU TARGET, Translational Medicine Federation of Strasbourg (FMTS), Faculty of Medicine, University of Strasbourg, Strasbourg, France.
³ INI-CRCT (Cardiovascular and Renal Trialists), F-CRIN Network, Vandoeuvre-les-Nancy, France.
⁴ Public Health Department, Epidémiologie - Maison régionale de la recherche clinique, CHU Lille, Lille, France.
⁵ UMR1167 RIDAGE, Institut Pasteur de Lille, INSERM, Univ Lille, Lille, France.
⁶ Nephrology Department, CHRU de Nancy, Vandoeuvre-lès-Nancy; Lorraine University, APEMAC, Vandoeuvre-lès-Nancy, France.
⁷ Université de Lyon, Carmen INSERM, Lyon.
⁸ Cardiology Department, Centre de référence des cardiomyopathies et des troubles du rythme cardiaque héréditaires ou rares, AP-HP, Ambroise Paré Hospital, Université de Versailles-Saint Quentin (UVSQ), Boulogne-Billancourt, France.
⁹ Centre for Research in Epidemiology and Population Health (CESP), Paris-Saclay University, INSERM U1018, Versailles-Saint-Quentin University, Clinical Epidemiology Team, Villejuif, France.
¹⁰ Agence de la Biomédecine, La Plaine Saint-Denis, France.
¹¹ Pharmacoepidemiology Unit, Department of Clinical Pharmacology, Amiens-Picardie University Medical Center, MP3CV Laboratory, Jules Verne University of Picardie, Amiens, France.
¹² AURA Paris - Association pour l'Utilisation du Rein Artificiel en région Parisienne, and Department of Nephrology, Ambroise Paré University Hospital, APHP, Boulogne-Billancourt, Paris, France.

Abstract

Background and hypothesis: Cardiovascular diseases are a leading cause of morbidity and mortality in patients with chronic kidney disease (CKD). Acute kidney injury (AKI) has been increasingly recognized as a potential exacerbating factor for cardiovascular events in these patients. The CKD-REIN study aims to explore the relationship between AKI and the risk of major adverse cardiovascular events (MACE) in a cohort of CKD patients. We hypothesize that AKI is a significant and independent predictor of MACE in patients with CKD, and that the severity of AKI correlates with the risk of subsequent cardiovascular events.

Methods: This prospective cohort study included 3033 adult CKD patients from 40 outpatient nephrology clinics in France. Patients were followed for a median of 5.2 years. AKI episodes were identified and staged based on the KDIGO-AKI criteria. Cardiovascular events, including myocardial infarction, stroke, heart failure hospitalization, and cardiovascular death, were systematically recorded. The association between AKI and MACE was analyzed using a multivariable Cox model, adjusting for confounders such as demographic characteristics, medical history, and baseline kidney function.

Results: During the follow-up, 530 patients experienced at least one episode of AKI. The cumulative incidence of MACE at 1 year post-AKI was 8.1%. Patients with AKI had a significantly increased risk of MACE, with an adjusted hazard ratio (HR) of 5.78 (P < .001). The risk was consistent across different MACE components and was independent of age, sex, CKD stage, or comorbidities. The risk of MACE was higher for more severe AKI stages and for AKI events requiring hospitalization or associated with incomplete renal recovery.

Conclusion: The findings of this study confirm that AKI is a significant independent predictor of MACE in CKD patients, demonstrating a strong severity-response relationship. These results underscore the importance of vigilant cardiovascular monitoring and preventive strategies in CKD patients following AKI episodes. Understanding the mechanisms linking AKI to cardiovascular outcomes is crucial for developing targeted interventions to mitigate these risks.

Keywords: CKD-REIN; acute kidney injury; cardiovascular events; chronic kidney disease; risk factors.