<p>Excretion of sodium and water through the skin as sweat represents a regulatory mechanism of electrolyte- and fluid balance. Since patients with chronic kidney disease (CKD) exhibit increased skin sodium content, we investigated the feasibility of sweat testing as a novel experimental tool to provide a more complete assessment of fluid- and sodium status. In this cross-sectional feasibility study, we applied pilocarpine iontophoresis to induce sweat testing in 58 patients across various stages of CKD including kidney transplant recipients and a healthy control cohort (n = 6) to investigate possible effects of CKD and transplantation status on sweat weight and sodium concentration. Due to non-linear relationships, we modeled our data using polynomial regression. Decline of kidney function showed a significant association with lower sweat weight: adj R² = 0.2278, F(2, 61) = 10.29, p = 0.0001. Sweat sodium concentrations were increased in moderate CKD, however, this effect was lost in end-stage kidney disease with and without requirement of hemodialysis: adj R² = 0.3701, F(4, 59) = 10.26, p = 2.261e-06. Diagnostic sweat analysis represents an innovative, non-invasive option for a more thorough investigation of sodium- and fluid homeostasis in CKD. Lower sweat weight and higher sweat sodium concentrations represent a unique feature of CKD patients with potential therapeutic implications.</p><p>Trial registration: This study is registered at ClinTrials.gov with the study number NCT06354842.</p>