JNEPHROL 2011; 24 ( 06 ) : 749-755

ORIGINAL ARTICLE

DOI:10.5301/JN.2011.6410

Acute kidney injury in patients presenting with hyponatremia Denise Adams 1, Robert de Jonge 2, Tischa van der Cammen 1, Robert Zietse 1, Ewout J. Hoorn 1

Abstract

Departments of Internal Medicine, Erasmus Medical Center, Rotterdam - The Netherlands 2 Clinical Chemistry, Erasmus Medical Center, Rotterdam The Netherlands 1

Introduction

Background: Hyponatremia is the most common electrolyte disorder, but a lack of well-characterized cohorts is hindering a full appreciation of this complex and heterogeneous disorder. Methods: During 4 months, clinical, biochemical, treatment and outcome data were collected for patients presenting with hyponatremia (serum sodium ≤130 mmol/L) to an urban university hospital. Results: Forty-three patients were included (serum sodium 126.6 ± 3.7 mmol/L). The most common causes of hyponatremia were diuretics (n=12), syndrome of inappropriate antidiuretic hormone secretion (n=11) and heart or liver disease (n=5). Renal insufficiency was frequent (n=18, 42%), and usually represented acute kidney injury (AKI; n=14, 78%). In patients with AKI, admission serum creatinine was 271 ± 252 μmol/L (3.4 ± 3.1-fold increase from baseline) and the origin was usually prerenal (12/14, 86%, fractional sodium excretion 0.54% ± 0.38%). Of these, patients with potentially reversible causes (salt loss or sepsis, n=7) had more favorable outcomes than patients with severe underlying disease (heart or liver disease, n=5), despite similar predictions using the RIFLE criteria. Survivors recovered with fluid resuscitation only. No overly rapid correction of hyponatremia was observed. Conclusions: AKI is common in patients presenting with hyponatremia and is usually of prerenal origin. The concurrence of AKI and hyponatremia has previously not been emphasized, but is important pathophysiologically and to plan rational management for both disorders. In this cohort, isotonic fluid replacement corrected both disorders and did not lead to overly rapid correction of hyponatremia. Key words: Diarrhea, Diuretics, Fractional sodium ex-

cretion, Intravenous fluids, Mortality, Prerenal

Hyponatremia is the most common electrolyte disorder in hospitalized patients (1). Severe complications of hyponatremia have long been recognized and include cerebral edema due to acute hyponatremia (2), and osmotic demyelination due to overly rapid correction of chronic hyponatremia (3). Although mild chronic hyponatremia has traditionally been regarded as benign (4), recent studies suggest a need for reappraisal by demonstrating an association with cognitive problems, falls, osteoporosis and fractures (5-7). Furthermore, a large single-center study recently showed that both community- and hospital-acquired hyponatremia were associated with increased mortality even when correcting for comorbidity and medication, and even when hyponatremia was mild (8). Despite these insightful epidemiological data, a full appreciation of the characteristics of patients with hyponatremia is hindered by a lack of well-characterized cohorts. A previous study illustrates the diagnostic shortcomings in patients with hyponatremia strikingly (9). For example, serum glucose, serum osmolality, urine sodium and urine osmolality were measured in less than half of the patients (9). In addition, none of the patients in whom the syndrome of inappropriate antidiuretic hormone secretion (SIADH) was suspected met established diagnostic criteria, usually because insufficient tests were ordered. Therefore, in our prospective, observational study, our aim was to identify new associations in patients presenting with hyponatremia, using complete diagnostic studies. Our results recapitulate some of the existing challenges of hyponatremia, and demonstrate a previously underrecognized association with acute kidney injury (AKI).

© 2011 Società Italiana di Nefrologia - ISSN 1121-8428

749

Adams et al: Acute kidney injury and hyponatremia

Subjects and methods Data collection This study (July-October 2009) was approved by our Medical Ethics Committee (MEC-2009-129). Patients were identified through an electronic alerting system reporting all patients from all specialties with an admission serum sodium ≤130 mmol/L ×4/day. Hyponatremia was defined as a serum sodium ≤130 mmol/L to select clinically significant cases and avoid inclusion of transient causes. The following data were collected: medical history, medication, reason of admission, serum and urine indices, possible symptoms of hyponatremia, therapy and outcomes. In the absence of an alternative explanation, the following symptoms were considered associated with hyponatremia: sensorium changes or a comatose state, seizures and falls. Volume status was recorded, but not used in our analysis, because of the low sensitivity and specificity in hyponatremia (10, 11). Because most patients were admitted on wards, urinary output was not generally available. D.A. collected the data using a standardized data collection sheet; all data were reviewed by E.J.H.

Definitions Hyponatremia The etiology of hyponatremia was analyzed using previously reported definitions (1, 12, 13). Briefly, the following causes of hyponatremia were considered: hyperglycemia (normal measured osmolality with sufficient degree of hyperglycemia to explain hyponatremia), diuretics (urine sodium >40 mmol/L and especially with thiazides or spironolactone), heart failure and liver cirrhosis (only in advanced disease and with urine sodium 40 mmol/L, urine osmolality >100 mOsm/kg, absence of diuretic use and thyroid, adrenal and renal insufficiency), adrenal insufficiency (random cortisol 90 μmol/L for females) in patients with 750

previous normal renal function, or as a rise in serum creatinine of ≥300 μmol/L in patients with chronic kidney disease (“acute on chronic”) (14). Prerenal AKI was defined as fractional excretion of sodium (FENa) 0.1 and a decrease or normalization of serum creatinine after intravenous fluids (15-17). Intrinsic AKI was defined as FENa >1%, characteristic urinalysis and a clear cause for intrinsic AKI. Postrenal AKI was defined as anuria with ultrasound-proven hydronephrosis.

Statistical analysis All data are expressed as means ± standard deviation unless specified otherwise. Comparisons between groups were made using Student’s t-test (continuous variables) or chi-square test (binary variables). A p value