Chloride-potassium assessment helps diagnose thiazide-associated hyponatraemia

Assessment of apparent strong ion difference (aSID), potassium, and chloride in urine is a useful tool for classifying patients with volume-depleted thiazide-associated hyponatraemia (TAH) requiring fluid substitution relative to those with syndrome of inappropriate antidiuresis (SIAD)-like presentation warranting fluid restriction, according to a recent study.

“[O]ur study suggests new tools and a pragmatic two-step approach in the differential diagnosis of profound TAH, proposing sodium-independent urine indices,” the investigators said.

A post hoc analysis was conducted using prospectively collected data from June 2011 to August 2013 from 98 hospitalized patients with TAH <125 mmol/L enrolled at University Hospital Basel and University Medical Clinic Aarau in Switzerland. Patients were classified based on treatment response in volume-depleted TAD requiring volume substitution or SIAD-like TAH requiring fluid restriction.

The investigators then performed sensitivity analyses with ROC curves for positive predictive value (PPV) and negative predictive value (NPV) of aSID, chloride and potassium score (ChU; chloride‒potassium in urine), and fractional uric acid excretion (FUA) in differential diagnosis of TAH.

An aSID >42 mmol/L achieved a PPV of 79.1 percent in detecting patients with volume-depleted TAH, whereas a value <39 mmol/L excluded it with an NPV of 76.5 percent. Among those with an inconclusive aSID, a ChU <15 mmol/L had a PPV and NPV of 100 percent and 83.3 percent, respectively. On the other hand, FUA <12 percent had a PPV of 85.7 percent and an NPV of 64.3 percent in identifying patients with volume-depleted TAH. [J Clin Endoc Metab 2023;108:2248-2254]

“One could argue that withdrawal of thiazide or thiazide-like diuretic is effective in hyponatraemia treatment, and therefore additional treatments are not required,” the investigators said. “However, sodium levels in general only slightly increase after withdrawing of thiazides and therefore drug withdrawal alone may be insufficient.” [Am J Nephrol 2017;45:420‐430]

Two-step approach

Based on these findings, the investigators recommended a two-step approach for differential diagnosis of TAH: 1) the calculation of blood aSID and 2) the calculation of urine scores ChU and FUA for patients in whom step 1 was inconclusive.

“Despite the lower diagnostic accuracy of the blood score, we chose it as a first step because blood values are available faster than urine samples, and the cutoffs of 39 and 42 mmol/L showed a good reliability in the sensitivity analysis,” they said.

“Evaluation of simplified aSID allows a prompter reaction to profound hyponatraemia in the group of patients showing an aSID <39 or >42 mmol/L,” the investigators added.

This study was limited by its retrospective and exploratory design, and most of the patients had volume-depleted TAH, contradicting literature data which showed a higher rate of SIAD-like TAH. [Am J Nephrol 2017;45:420‐430]

“Further studies should especially validate our cutoff for ChU in the two-step approach, as the number of patients was modest,” the investigators said.