Fc 057salivary potassium follows plasma potassium dynamics in hemodialysis patients

Abstract Background and Aims Hyperkalemia is common in patients on hemodialysis (HD) and in cardiorenal patients on RAAS inhibitors. Frequently, hyperkalemia is a leading reason to withdraw potentially lifesaving therapy in cardiorenal patients. Out-patient monitoring of plasma K+ levels due to preanalytical problems has proven problematic. The present pilot-study examined salivary K+ levels and kinetics based on plasma K+ measurements in HD patients employing a novel class of genetically-encoded fluorescent potassium-ion indicators, the GEPIIs (Bischof et al. Nat. Commun. 2017). HD patients represent a unique population in whom significant K+ derangements and rapid K+ level changes predictably occur and where these phenomena can be safely investigated. Method K+ assessments were performed in healthy individuals (n=20) and HD patients (n=30). Study-related procedures were approved by the local Institutional Review Board. Healthy individuals were recruited on a voluntary basis and provided only saliva samples. HD patients were recruited from our HD unit. Blood and saliva samples for K+ assessment were collected simultaneously during three consecutive HD sessions (HD1-3) prior to and directly after each session (pre/post HD). Blood was drawn in a standardized procedure directly from the HD access line and plasma K+ was measured immediately using standardized ion-selective electrodes (ISE). Saliva samples were gathered in a standardized procedure using a commercially available collection device (SuperSALTM). Of note, gaining adequate amounts of saliva from chronic HD patients, who frequently suffer from xerostomia, has proven challenging in some cases. The K+ content of saliva samples was measured by ISE and GEPII-technique. For the latter, samples were mixed with purified GEPIIs and were inserted into a fluorescent plate-reader. Probes were illuminated at 430 nm and emission light were collected at 475 nm and 525 nm, respectively. The ratio of the fluorescent intensities (F535/F480) after appropriate calibration is a direct measure of the K+ concentration sensed by GEPIIs. Results K+ determination in saliva samples using the GEPII-technique and ISE showed a strong agreement ((Figure 1A), Bias 0,71; 95% limits of agreement from -2.79 to 4.40). Pre-dialytic [K+]saliva of HD patients compared to healthy individuals, was higher (40,64±1,50 vs. 23,15±0,76 mmol/l, p<0.05). As expected, each HD session (HD1-3) led to a significant reduction in [K+]plasma, which is followed by a similar, significant reduction of [K+]saliva (Figure 1B). Dynamics of plasma and salivary [K+] showed a very similar pattern: strong reduction during a HD session followed by a marked increase in the dialysis-free period until the next session 48-72h later (Figure 1C). Although basal [K+]saliva shows individual variations, [K+]Saliva and [K+]plasma exhibited a tendency of linear association (Figure 1D). Correlation analysis in each HD session (HD1-3 pre/post) revealed however no or weak correlation of pre- and post-dialytic saliva and plasma K+ values (Figure 1E). Conclusion The GEPII-technique is an easy to use, reliable and suitable method for salivary K+ determination in healthy individuals and in HD patients with accuracy and precision comparable to that of ISE. Despite heterogeneous baselines, changes of [K+]saliva represent a sensitive marker of K+ derangements as well as hyper- and normokalemia in HD patients. Although we observed that [K+]saliva dynamically follows [K+]plasma , an exact quantification - most likely due to the low number of cases per HD sessions in this pilot-study – was not possible. Additionally, how closely [K+]saliva tracks [K+]plasma in patients with hypokalemia was not addressed in this study. To confidently answer whether [K+]saliva measurement can potentially be used in the care of patients at increased risk of hyperkalemia, further studies in a larger number of patients need to be conducted.