Gender differences in the susceptibility of hospital-acquired acute kidney injury: more questions than answers
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NEPHROLOGY - REVIEW
Gender differences in the susceptibility of hospital‑acquired acute kidney injury: more questions than answers Helmut Schiffl1 Received: 5 April 2020 / Accepted: 25 May 2020 © The Author(s) 2020
Abstract Hospital-acquired acute kidney injury (HA-AKI) is a heterogeneous renal syndrome which occurs in different clinical settings. It is characterized by multiple aetiologies, various pathogeneses and unpredictable outcomes. HA-AKI, once predominantly viewed as a self-limited and reversible short-term condition, is now recognized as a harbinger for chronic kidney disease and a cause of long-term morbidity with an increased risk of cardiovascular, renal and cancer mortality. Recent clinical studies contradict the generally held belief that female sex is a risk factor for HA-AKI. They show, consistent with basic research performed with experimental models of AKI, that only male sex is associated with HA-AKI. The presence of testosterone, more likely than the absence of estrogen, plays a critical role in sex differences in the susceptibility of ischemia/reperfusion kidney injury. The conflicting data in epidemiological studies related to sex as susceptibility variable for human AKI, underscore the need for more rigorous, well designed observational studies taking into account the menopausal status and hormone therapy. Keywords Hospital-acquired acute kidney injury · Sex dimorphism · Testosterone
Introduction Hospital-acquired acute kidney injury (HA-AKI) is a complex clinical syndrome with multiple risk factors and aetiologies, a broad spectrum of clinical presentations and unpredictable short-and long-term outcomes. Currently, treatment of established acute kidney injury (AKI) is mainly supportive in nature. No pharmacological intervention has shown efficacy to improve morbidity and mortality attributable to AKI. Identifying patients at high risk, awareness of preventable AKI, early recognition and management of incipient AKI are key factors to reduce cases of established AKI and to improve the dismal outcome of severe AKI [1]. Observational studies have identified a variety of risk factors including pre-existing susceptibilities of individual patients in combination with the nature and severity of acute kidney insults. Sex differences are of fundamental importance in chronic kidney disease (CKD). Biological sex is increasingly recognized as modulator of the * Helmut Schiffl h‑schiffl@t‑online.de 1
Department of Internal Medicine IV, University Hospital LMU Munich, Ziemssenstr. 1, 80336 Munich, Germany
pathophysiology, disease development, progression and management of CKD. Male patients with proteinuric CKD have a faster progression of CKD to end-stage kidney disease (ESKD) than women with the same grade of proteinuria, indicating that female sex may be reno-protective [2]. Sexual dimorphism has also been examined in HA-AKI. However, observational studies in humans reported conflicting findings [3] such as: (1) women have a greater risk for HA-AKI; (2) no association between sex and HA-AKI w
