Combination of Lactulose and Sodium Polystyrene Sulfonate Improves Potassium Reduction in Hyperkalemia: Study
A recent study published in the Indian Journal of Nephrology in April 2026 reveals that combining lactulose and sodium polystyrene sulfonate achieves a significant absolute reduction of 1.75 mmol/L in serum potassium concentrations between the second and seventh days of treatment, offering a potent pragmatic strategy for managing subacute hyperkalemia in hospitalized patients.
Hyperkalemia is a life-threatening risk for hospitalized patients, yet sodium polystyrene sulfonate (SPS) remains standard treatment despite a lack of robust evidence for acute cases. To address the clinical uncertainty regarding laxative-driven potassium loss via big potassium (BK) channels, Mohidin Esaadi and colleagues from Stellenbosch University evaluated the comparative efficacy of lactulose, SPS, and combined therapy in a real-world setting.
Therefore, the retrospective post-hoc analysis evaluated 134 adults at Tygerberg Hospital over one year, comparing potassium responses at 24 hours and 2–7 days while excluding patients on kidney replacement therapy. Using analysis of variance and multilinear regression, researchers assessed the primary endpoint of absolute potassium reduction in patients with baseline levels below 5.5 mmol/L.
Key Clinical Findings of the Study Include:
Initial Latency: The investigation discovered that within the first 24 hours, there were no statistically significant differences in potassium reduction between the groups, with the combination group showing a median decrease of -1.3 mmol/L
Subacute Efficacy: By the second to seventh day of therapy, the research demonstrated that the combination group achieved a superior absolute potassium reduction of -1.75 mmol/L, whereas the lactulose-only group saw a more modest decline of -0.9 mmol/L.
Predictive Factors: Multivariable analysis from the trial identified that the baseline potassium level was the most significant independent predictor of success, where every 1 mmol/L increase at the start resulted in a 0.87 mmol/L greater reduction over the follow-up period.
Comorbidity Correlation: The study noted that while all patients in the combination group suffered from kidney dysfunction, sensitivity analyses confirmed that the observed potassium drops remained robust even after adjusting for the severity of chronic kidney disease.
Resource Pragmatism: The analysis observed that in low-resource settings where newer, expensive potassium binders are unavailable, the combination of these older agents provides a pragmatic option for subacute management.
The results suggest that among hospitalized patients suffering from hyperkalaemia, utilizing both lactulose and SPS is associated with a more pronounced reduction in serum potassium by day seven, though the study clarifies that the high baseline potassium concentration of 7.2 mmol/L in the combination group was the primary driver of this trend.
These findings suggest that clinicians might find value in pairing osmotic laxatives with traditional resins to optimize gastrointestinal potassium clearance, particularly when managing subacute cases in resource-limited environments.
While the retrospective nature and lack of specific dosing information represent notable constraints, the findings emphasize the importance of future prospective randomized controlled trials to definitively establish the safest and most effective dosing strategies for this combined therapeutic approach.
Reference
Esaadi M, Davids MR, Chothia MY. Potassium Reduction Associated with Lactulose and Sodium Polystyrene Sulfonate Use in Hospitalized Patients with Hyperkalemia: A Real-World Observational Study. Indian Journal of Nephrology. 2026;.
