Hyperosmotic stress-induced impairment of erythrocyte deformability correlates with reduced aerobic capacity in end-stage renal disease.

INTRODUCTION

End-stage renal disease (ESRD) causes osmotic imbalance, impairing erythrocyte deformability and microcirculation. Hyperosmotic challenge disrupts calcium homeostasis, which may dysregulate Gardos channels and contribute to erythrocyte dehydration. This study explores the relationship between erythrocyte osmotic deformability and aerobic capacity in ESRD.

METHODS

Eighteen ESRD patients and eighteen age-matched healthy controls underwent a cardiopulmonary exercise test with pre-test blood sampling. Erythrocyte osmotic deformability was assessed via osmotic gradient ektacytometry, while flow cytometry quantified Gardos channel (KCNN4) expression, senescence biomarkers, erythrocyte shape, and intracellular calcium concentration ([Ca2+]i).

RESULTS

The ESRD group had lower VO2peak, erythrocyte count, hemoglobin, and erythrocyte sphericity indices, with lower CD47 and CD147 expression. Osmoscan revealed impaired hyperosmotic deformability, with reduced EImax, Omax, Ohyper, and AUC, all positively correlated with VO2peak in ESRD patients (EImax: r = 0.50, p < 0.05; Omax: r = 0.60, p < 0.01; Ohyper: r = 0.58, p < 0.05; AUC: r = 0.52, p < 0.05). KCNN4, PIEZO1, and [Ca2+]i were elevated in ESRD. t-BHP exposure induced a greater [Ca2+]i increase in ESRD. KCNN4 correlated positively with [Ca2+]i but negatively with Omin, Omax, Ohyper, EImax, MCV, CD47 and CD147. EImax from non-osmotic test showed no correlation with KCNN4. No correlations were found in controls.

CONCLUSION

ESRD patients exhibit heightened susceptibility to hyperosmotic stress, which is positively associated with impaired erythrocyte deformability and reduced aerobic capacity. Within the ESRD cohort, higher Gardos channel expression was associated with lower hyperosmotic deformability indices, and oxidative stress elicited a greater rise in intracellular calcium.