Salivary potassium measured by genetically encoded potassium ion indicators as a surrogate for plasma potassium levels in hemodialysis patients—a proof-of-concept study

Abstract

Hyperkalemia is a common complication in cardiorenal patients treated with agents interfering with renal potassium (K⁺) excretion. It frequently leads to discontinuation of potentially life-saving medication, which has increased the importance of K⁺-monitoring. Non-invasive means to detect hyperkalemia are currently unavailable, but would be of potential use for therapy guidance. The aim of the present study was to assess the analytical performance of genetically-encoded potassium-ion indicators (GEPIIs) in measuring salivary K⁺ ([K⁺]_Saliva) and to determine whether changes of [K⁺]_Saliva depict those of [K⁺]_Plasma. We conducted this proof-of-concept study: saliva samples from 20 healthy volunteers as well as plasma and saliva from 29 patients on hemodialysis (HD) before and after three consecutive HD treatments were collected. We compared [K⁺]_Saliva as assessed by the gold standard ion-selective electrode (ISE) with GEPII measurements. The Bland-Altmann analysis showed a strong agreement (Bias 0.71; 95% limits of agreement from -2.79 to 4.40) between GEPII and ISE. Before treatment, patients on HD showed significantly higher [K⁺]_Saliva compared to healthy controls (median 37.7 [30.85; 48.46] vs. 23.8 [21.63; 25.23] mmol/L; p < 0.05). [K⁺]_Plasma in HD patients decreased significantly after dialysis. This was paralleled by a significant decrease in [K⁺]_Saliva, and both parameters increased until the subsequent HD session. Despite similar kinetics, we found weak or no correlation between [K⁺]_Plasma and [K⁺]_Saliva. GEPIIs have shown an excellent performance in determining [K⁺]_Saliva. [K⁺]_Plasma and [K⁺]_Saliva exhibited similar kinetics. To determine whether saliva could be a suitable sample type to monitor [K⁺]_Plasma, further testing in future studies are required.