Serum sodium variability and acute kidney injury: a retrospective observational cohort study on a hospitalized population

Internal and Emergency Medicine https://doi.org/10.1007/s11739-020-02462-5 IM - ORIGINAL Serum sodium variability and acute kidney injury: a retrospective observational cohort study on a hospitalized population Gianmarco Lombardi1 · Pietro Manuel Ferraro2,3 · Alessandro Naticchia2 · Giovanni Gambaro1 Received: 11 March 2020 / Accepted: 24 July 2020 © The Author(s) 2020 Abstract Aim of our study was to analyze the association between serum sodium (Na) variability and acute kidney injury (AKI) development. We performed a retrospective observational cohort study on the inpatient population admitted to Fondazione Policlinico Universitario A. Gemelli IRCCS between January 1, 2010 and December 31, 2014 with inclusion of adult patients with ≥ 2 Na and ≥ 2 serum creatinine measurements. We included only patients with ≥ 2 Na measurements before AKI development. The outcome of interest was AKI. The exposures of interest were hyponatremia, hypernatremia and Na fluctuations before AKI development. Na variability was evaluated using the coefficient of variation (CV). Multivariable Cox proportional hazards and logistic regression models were fitted to obtain hazard ratios (HRs), odds ratios (ORs) and 95% confidence intervals (CIs) for the association between the exposures of interest and AKI. Overall, 56,961 patients met our inclusion criteria. During 1541 person-years of follow-up AKI occurred in 1450 patients. In multivariable hazard models, patients with pre-existent dysnatremia and those who developed dysnatremia had a higher risk of AKI compared with patients with normonatremia. Logistic models suggested a higher risk for AKI in the 3rd (OR 1.41, 95% CI 1.18, 1.70, p < 0.001) and 4th (OR 1.53, 95% CI 1.24, 1.91, p < 0.001) highest quartiles of Na CV with a significant linear trend across quartiles (p trend < 0.001). This association was also independent from Na highest and lowest peak value. Dysnatremia is a common condition and is positive associated with AKI development. Furthermore, high Na variability might be considered an independent early indicator for kidney injury development. Keywords Acute kidney injury · Electrolyte disorders · Hyponatremia · Hypernatremia · Epidemiological study Introduction Electrolyte disturbances are common disorders in the hospitalized population [1]. Serum sodium (Na) imbalance is frequently observed in the hospital setting [2]. Dysnatremia conditions (including hyponatremia [Na < 135 mEq/L] and Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11739-020-02462-5) contains supplementary material, which is available to authorized users. * Pietro Manuel Ferraro 1 U.O.C. Nefrologia, Azienda Ospedaliera Universitaria Integrata di Verona, Verona, Italy 2 U.O.C. Nefrologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Via G. Moscati 31, 00168 Rome, Italy 3 Università Cattolica del Sacro Cuore, Rome, Italy hypernatremia [Na > 145 mEq/L] are reported in approximately 30–40% of all hospital admissions [3]. Medical and scientific interest on these conditions is justified by the significant burden of Na disorders on the patient’s prognosis [4]. Both hyponatremia and hypernatremia have been widely associated with increased morbidity and mortality. Furthermore, as suggested by recently published studies, even small fluctuations in serum Na levels have been associated with a significant increase of in-hospital mortality [5–8]. As the main organ involved in water metabolism and homeostasis, the kidney is generally the main culprit for such disorders. Defective urine dilution with disproportionally high water intake causes hyponatremia. On the other way around, disorders involving urine concentration with inadequately low water intake cause hypernatremia [9, 10]. Therefore, it is not surprising that kidney diseases, especially acute kidney injury (AKI), characterized by an abrupt 13 Vol.:(0123456789) Internal and Emergency Medicine reduction in renal function, are commonly associated with these pathological conditions [11–15]. On the other hand, as sparsely reported in medical literature, an inverse relationship between dysnatremia and AKI emerges, where Na imbalance precedes and predicts kidney damage. A plausible cross-talk on a biological and pathogenetic ground might justify such relationship [16–18], but it still remains poorly investigated [14, 19]. The aim of our study is to analyze the association between dysnatremia, in the whole range of its manifestations (hyponatremia, hypernatremia and mild Na fluctuations in the normonatremic range), and AKI development using a large retrospective cohort of hospitalized patients. Methods Setting and study population We performed a retrospective observational study on the hospitalized population admitted to Fondazione Policlinico Universitario A. Gemelli IRCCS, a tertiary level hospital serving more than 1 million people in Rome, between January 1, 2010 and December 31, 2014. We included only adult patients (aged 18 years or older) with at least two serum Na (with consensual serum glucose) and at least two serum creatinine measurements during hospital stay. For analysis and data calculation we included only patients with at least two Na measurements before AKI development. Patients with end-stage kidney disease (ESKD) were excluded. Study patients were included at the time of their first hospital admission. If a patient was hospitalized multiple times during the study period, we considered only the first one. Data collection All data were extracted from the hospital electronic database. We exported the following demographic, clinical and laboratory data: age, sex, serum Na, glucose, creatinine, primary and secondary ICD-9-CM (International Classification of Disease, 9th Revision, Clinical Modification) diagnosis codes at hospital discharge. Definitions Acute kidney injury (AKI) was defined according to creatinine kinetics criteria [20]. In-hospital AKI was defined as AKI developed after ≥ 48 h from hospital admission. Patients were grouped according to all Na values recorded during hospital stay and preceding AKI development in the following dysnatremic groups: hyponatremia (Na value < 135 mmol/L), hypernatremia (Na 13 value > 145 mmol/L), normonatremia (lowest/highest Na values ≥ 135 mmol/L and ≤ 145 mmol/L). In patients with mixed dysnatremia, only the first Na disorder (what happened first), hypo or hypernatremia, was considered. All Na levels were corrected for the dilutional effect associated with hyperglycemia using a validated method [21]. Na variability (or fluctuations) was evaluated using the coefficient of variation (CV), defined as the ratio between the standard deviation and the mean of all Na values preceding AKI development. Comorbid conditions (cardiovascular diseases, malignancies, gastrointestinal diseases, genitourinary disorders, endocrine/metabolic disorders, infectious and respiratory diseases) were identified usi (...truncated)