Osmotic stress and mortality in elderly patients with kidney failure: a retrospective study

Authors Grangeon-Chapon C, Dodoi M, Esnault VLM, Favre G Received 5 December 2017 Accepted for publication 18 April 2018 Published 30 January 2019 Volume 2019:14 Pages 225—229 DOI https://doi.org/10.2147/CIA.S158987 Checked for plagiarism Yes Review by Single-blind Peer reviewers approved by Dr Andrew Yee Peer reviewer comments 3 Editor who approved publication: Dr Richard Walker Caroline Grangeon-Chapon,1 Manuella Dodoi,2 Vincent LM Esnault,2,3 Guillaume Favre2,3 1Departments of Nuclear Medicine and Pharmacy, University Côte d’Azur, University Hospital of Nice, Nice, France; 2Department of Nephrology, University Côte d’Azur, University Hospital of Nice, Nice, France; 3Department of Nephrology, University Côte d’Azur, Institute for Research on Cancer and Aging of Nice (IRCAN), “Aging and Diabetes” Team, University Hospital of Nice, Nice, France Purpose: Water balance disorders are associated with a high risk of death in elderly patients. The role of osmotic stress intensity and its direction toward hypo- or hypernatremia is a matter of controversy regarding patients’ survival. The aims of this study were, first, to measure the frequency of cellular hydration disorders in patients over 75 years old hospitalized in nephrology department for reversible acute renal failure, and second, to compare the impact of hyperhydration and hypohydration on the risk of death at 6 months. Patients and methods: We retrospectively studied the data of 279 patients with chronic kidney disease (CKD), aged 75 years or older, with pre-renal azotemia who experienced dysnatremia. We classified them according to natremia levels and compared their outcome in univariate and multivariate analysis. Results: The patients were on average 83.2±5.4 years old. Among them, 128 were normonatremic, 82 were hyponatremic and 69 were hypernatremic. Osmotic stress intensity appreciated by the variation rate of natremia did not differ significantly between hyper- and hyponatremic patients. Patients had CKD stage 3B and 4 with acute kidney injury (AKI) of different severities. We observed that only hypernatremia was linked to death in the first 6 months following hospital discharge. Conclusion: Hypernatremia is a strong predictor of fatal outcome in elderly patients suffering from chronic kidney impairment and referred for pre-renal azotemia. Keywords: acute kidney injury, aging, chronic kidney failure, hypernatremia, osmoregulation Introduction Water balance disorders are commonly found in hospitalized patients, most specifically in the elderly,1,2 and are associated with an increased risk of death.3,4 The kidneys play a major role in the regulation of body water, as illustrated by the higher rate of acute kidney injury (AKI) among patients suffering from hypernatremia.5 However, it is not clear whether dysnatremias are causes or surrogate markers of underlying diseases. Indeed, hyponatremia has been associated with poor outcome in psychiatric inpatients6 and in patients suffering from pulmonary tract infections.7 Hypernatremia has been related to increased mortality following bacterial infectious diseases8 and cerebrovascular injuries.9 Moreover, the role of the direction toward hypo- and hypernatremia and the severity of dysnatremia remains to be clarified. Actually, hypernatremia increases seven times the risk of death,10 whereas hyponatremia doubles this risk,11 as compared to age-matched normonatremic patients. Consequently, one would attribute an overwhelming role to the direction of dysnatremia irrespective of its severity. In contrast, mortality-related dysnatremia follows a U-shaped curve indicating increased mortality risk for extreme dysnatremia. This pattern is established both in intensive care patients12,13 and in a cohort of veterans suffering from chronic kidney disease (CKD).14 Accordingly, the intensity of osmotic stress would be expected to play a major role regardless of its direction toward hypo- or hypernatremia. Taking advantage of the high incidence of dysnatremia observed in CKD patients experiencing pre-renal azotemia, we seek to provide a better insight into this issue. Therefore, we retrospectively compared the outcome of patients with hypo- and hypernatremia of similar severity to the outcome of normonatremic patients. Patients and methods This study was reviewed and approved by the “Sud Méditerranée” Institutional Review Board. This protection committee waived the need for ethical approval and for written informed consent in this retrospective study with no potential for harm to subjects. Nevertheless, an information form on the use of their data for research purposes has been sent to patients. The lack of a negative response from them within a month was considered as their agreement. To ensure patient’s privacy, all details were collected in an anonymized database. We retrospectively studied the data of CKD patients aged 75 years or older who were referred to our nephrology department for pre-renal azotemia over a 5-year time period. One of the parameters studied was osmotic stress. We estimated the intensity of the osmotic stress for hyper- and hyponatremia according to the following formula: In this formula, “extreme” indicates minimal or maximal value during hospital stay, while “discharge” indicates value at hospital discharge. Serum creatinine (SCr) at discharge was used for the staging of CKD15 according to the simplified formula from the Modification of Diet in Renal Disease (MDRD).16 Following the current recommendations,17 the severity of AKI was characterized according to the ratio between the highest SCr level and the discharge SCr level: Disability was assessed according to the dependence from the nursing team and/or to impaired mental status. Finally, the patients were classified according to their natremia levels (<135, 135–145 and >145 mmol/L) and outcomes were compared between groups in univariate and multivariate analysis. Results are presented as mean and SD values. Student’s t-tests or chi-squared tests were used for univariate analysis. We performed a multiple logistic regression in an attempt to identify independent predictors of death within the first 6 months after discharge. The predictors taken into account were age, sex, diabetes, bacterial infection, active neoplasia, length of hospital stay, CKD stage, severity of AKI and disability. The model was developed with a forward selection procedure of characteristics associated with death within the first 6 months after discharge, with cutoffs of P<0.05 for inclusion and P>0.10 for exclusion. Variables with more than two categories were introduced using dummy variables. Model adequacy was estimated by the likelihood ratio goodness-of-fit test. Probability values of <0.05 were accepted as statistically significant. Statistical analysis was performed on SPSS version 11.0 (SPSS Inc., Chicago, IL, USA). Result (...truncated)