Hypomagnesemia as a Risk Factor for the Non-recovery of the Renal Function in Critically Ill Patients With Acute Kidney Injury

Sarah Cascaes Alves; Cristiane Damiani Tomasi; Larissa Constantino; Vinícius Giombelli; Roberta Candal; Maria de Lourdes Bristot; Maria Fernanda Topanotti; Emmanuel A. Burdmann; Felipe Dal-Pizzol; Cassiana Mazon Fraga; Cristiane Ritter


Nephrol Dial Transplant. 2013;28(4):910-916. 

In This Article

Materials and Methods

A prospective cohort study was conducted, which included all the patients admitted into a 20-bed general ICU at a University Hospital (Hospital São José) in Criciúma, Brazil, from March to June, 2011. All procedures were approved by the local Ethics Committee and written informed consent was obtained from all patients or their relatives before inclusion in the study. Patients under 18 years of age, patients with serum creatinine (SCr) values greater than 3.5 mg/dL upon admission into the ICU (to avoid the inclusion of patients with advanced chronic renal disease) and patients with a stay in the ICU of <48 h were excluded from the study.

Demographic, clinical and laboratory data were collected, including age, gender, type of admission and comorbidities. The Acute Physiologic and Chronic Health Evaluation (APACHE) II score was estimated using data collected from the ICU admission (±1 h) and during the first 24 h of ICU stay. The sequential organ failure assessment (SOFA) score was also calculated on the first day of ICU admission. Major comorbidities were assessed revising patient medical charts. Sepsis was diagnosed according to previously published definitions.[5]

Hypomagnesemia was defined as any measure of serum magnesium <0.70 mmol/L[6] during ICU stay. Total serum magnesium levels were determined daily until ICU discharge with a colorimetric method using the VITROS 250 Chemistry Analyzer (Johnson & Johnson Co., USA). Magnesium levels were used to derive four variables: the presence of hypomagnesemia, lower magnesium level, mean magnesium level and severity of hypomagnesemia (≤0.41 mmol/L as severe, 0.41–0.53 mmol/L as moderate and 0.54–0.69 mmol/L as mild).

AKI was diagnosed by the Risk, Injury, Failure, Loss and End-stage kidney disease (RIFLE) criteria.[7] RIFLE is graded in five increasing levels of severity. The first stage, Risk is defined as an abrupt (within 1–7 days) and sustained (>24 h) SCr increase to ≥1.5 times the reference SCr or a urine output <0.5 mL/kg/h for 6 h. The second stage is defined as a SCr increase to two times the reference SCr or a urine output <0.5 mL/kg/h for 12 h. The third stage, Failure is defined as a SCr increase to three times the reference SCr or when reference SCr ≥4 mg/dL as an acute increase >0.5 mg/dL in the reference SCr or as a urine output <0.3 mL/kg/h for 24 h or anuria for 12 h. Loss is defined as complete loss of kidney function for >4 weeks, and end-stage kidney disease as the complete or almost complete failure of the kidneys for >3 months.

The primary study outcomes were the prevalence of AKI and renal function recovery, defined as at least 48 h without AKI in the ICU or at ICU discharge according RIFLE criteria, in patients who developed AKI during ICU stay. Secondary outcome was mortality. Both primary and secondary outcomes were defined until ICU discharge or after a maximum period of up to 28 days in the ICU.

Magnesium supplementation was performed by the ICU staff without interference from the study investigators, following institutional guidelines. This guideline indicates magnesium supplementation in the cases of severe or symptomatic hypomagnesemia, or hypomagnesemia in the setting of hypokalemia.

Clinical data were analyzed using SPSS software (Statistical Package for the Social Sciences, Version 15.0). Standard descriptive statistics were used to describe the study population. Continuous variables were reported as the mean ± SD or the median (25–75% interquartile range), depending on the variable distribution, as determined by analysis with the Kolmogorov–Smirnov test. To identify factors associated with outcomes, a univariate analysis was performed on all collected variables using a χ 2 test for categorical variables, or a Student t-test or Mann–Whitney U-test, as appropriate, for continuous variables. Variables yielding P < 0.15 in the univariate analysis or considered clinically relevant were entered into a binary logistic regression model that included hypomagnesemia, sepsis, age, APACHE II score and the RIFLE score to estimate the independent association of each covariate with the dependent variable. The Hosmer–Lemeshow goodness-of-fit test was used to evaluate the agreement between the observed and expected number of patients who recovered renal function. The area under receiver operating characteristic curve (AUROC) was used to evaluate the ability of magnesium levels to predict the recovery from AKI. The relation between primary and secondary outcomes and hypomagnesemia were analyzed by the Kaplan–Meier curves followed by the log-rank test. A two-tailed test was used to determine statistical significance (P < 0.05).