IN-HOSPITAL ACUTE KIDNEY INJURY: STUDY OF PREVALENCE, SEX DIFFERECES AND MORTALITY.

Background: Hospital Acute kidney injury (H-AKI) is a complex entity associated with an increased risk of complications and mortality. Its occurrence and outcome are influenced by several patient and organizational-related factors. Due to the biological and genetic differences, sex may greatly influence the kidney function. However, Italian epidemiological data on H-AKI incidence and prognosis are scarce. Moreover, the impact of sex on H-AKI risk and related consequences is still unclear. This retrospective multi-center study aimed to assess H-AKI epidemiology and outcomes in a large cohort of hospitalized patients, with a focus on the association with patients' sex. Method: From adult patients admitted to two large University Hospitals in Italy between 2016 and 2019, we collected clinical data, serum creatinine (sCr), comorbidities, with focus on diabetes mellitus (DM), heart failure (HF), sepsis, kidney transplantation and chronic kidney disease (CKD), primary diagnoses as codified in the hospital discharge form (HDF), and data on discharge, length of hospital stay (LOS), and death. The inclusion criteria were: age >18 years, first hospital admission from January 1, 2016, to December 31, 2019, at least two values of sCr collected during hospitalization. The only exclusion criteria was (CKD) stage 5 reported on HDF. We defined and graded AKI according to the KDIGO criteria, by comparing the peak sCr to the lowest sCr during hospitalization under the assumption that the lowest sCr would represent baseline kidney function. The estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration creatinine-based equation. Results: We analyzed 87,087 patients, with an average age of 69.2±17.7 years of whom 43467 (49.9%) were males and 43620 females (50.1%). Overall, 17946 patients (20.6%) developed H-AKI, with a higher incidence in females (21.4% vs. 19.8%, p=0.000). In respect to the non-AKI population, patients with AKI were significantly older (66.7±18.1 vs 74.8±14.7), with a higher prevalence of females (52.1%) and more comorbid conditions, as diabetes mellitus, heart failure, sepsis and CKD. The logistic regression analysis showed that the risk of AKI was associated to admission sCr (OR 1.55, 95% CI 1.53 -1.58), female gender (OR 1.23, 95% CI 1.18 – 1.27), LOS (OR 1.05, 95% CI 1.05– 1.06) and ICU stay (OR 4.73, 95% CI 4.4– 5.1) in a multivariate model (p<0.0001). AKI patients had worst outcomes considering mortality (17.7% vs 4.3%), LOS (19.2±16 vs 8.9±11.12), ICU admission (8.2% vs 2,4%) and need for protected discharge (30.0% vs 17.7%). At Cox-analysis AKI resulted related to mortality with a hazard ration of 1.23 (IC 1.16-1.30). The distribution of AKI stages was AKI-1 59.5%, AKI-2 25.7% and AKI-3 14%. The higher stages, as expected, presented the worst outcomes and higher sCr values at discharge. Female patients were older than males (69.9±16.5 vs 68.5±18.9 years, p<0.001), had less prevalence of DM (8.7% vs 11.8%) and CKD (6% vs 7,7%), and higher prevalence of HF (9.3% vs 8.6). Females with H-AKI were older and exhibited more heart failure, while males presented more acute myocardial ischemia and sepsis. The male/female ratio varied across AKI severity, with stage 3 AKI more frequent in males. AKI awareness, as evaluated by comparing the incidence of AKI diagnosed according to the sCr changes with AKI diagnoses codified on HDF, showed a higher rate of undetection in females (3.8% vs 4.4%). Moreover, when we stratified our cohort according to the age quartiles, we observed that for each AKI stage in the 1st age quartile H-AKI incidence was higher in males (13.1% vs 10%, p=0.000), in the second quartile there was no difference between male and female patients, while in the last quartiles, AKI incidence was higher in females (25.2 vs 22.6%, p=0.000). This tendency was also confirmed by Kaplan Meier analysis. However, when we separately analyzed the risk of developing AKI in the different quartiles with multivariate logistic regression analysis we found that while in the youngest quartiles the risk of developing AKI was not correlated with sex, in the elderly, female sex was an independent risk factor for developing AKI (3rd quartile OR 1.30, IC 1.21-1.39; 4th quartile OR 1.46 IC 1.38-1.59, adjusted for age, DM, HF, CKD, admission to ICU, sCr, LOS). The analysis of outcomes among AKI patients divided between males and females showed that mortality was the same for the youngest patients, while it was higher in male patients for the 3rd and 4th age quartile. A similar trend was found for ICU admission and LOS. Conclusion: The study of epidemiological data is crucial to plan preventing and monitoring actions with the aim to improve the in-hospital morbidity and mortality, but also the long-term effects as the progression to CKD. Sex emerges as a significant determinant of H-AKI development. However, the relationship between sex and H-AKI is not linear. Indeed, AKI incidence, severity, and outcomes vary between males and females across different age groups, probably reflecting the modifications of health status occurring during a lifetime. Consideration also of gender differences is crucial in studying AKI to ensure accurate and equitable diagnosis and management. The examination of several factor can lead to enhance strategies to identify the patients at higher risk and focus on them to a more rigorous treatment and monitoring.