Effect of hemodialysis and transplantation on sodium stores in end-stage renal disease

• Applicants: Dr. Christoph Kopp; Professor Dr. Michael Uder
• Subject Area: Nuclear Medicine, Radiotherapy, Radiobiology ; Nephrology
• Term: from 2015 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 282123235

Salt (NaCl) intake is implicated in causing hypertension and cardiovascular disease, the commonest cause of death worldwide. Our group has previously established that Na+ is stored non-osmotically, bound to glycoproteins such as glycosaminoglycans, in skin and muscle. To visualize these complex processes in man directly, we established Na+ magnetic resonance imaging (23Na-MRI). We found that patients with mineralocorticoid receptor (MR)-dependent primary aldosteronism reduce their Na+ stores after treatment, providing proof-of-principle for the validity of the method. Diminished kidney function, as in chronic kidney disease (CKD) causes salt-sensitive hypertension and hemodialysis (HD) patients are salt-sensitive by virtue of relying on dialysis to remove Na+ from the body. We have recently investigated Na+ stores in HD patients in a cross-sectional study. HD lowered tissue Na+ stores, but effects were highly variable, independent of Na+ or water removal from the body, and were correlated with circulating vascular endothelial growth factor-C (VEGF-C). We hypothesize that accelerated tissue Na+ accumulation occurs in pre-dialysis CKD patients and contributes to hypertension, target-organ damage and increased cardiovascular disease risk. We will now measure Na+ stores in CKD patients and will test the utility of HD and pre-emptive kidney transplantation to reduce Na+ stores. We will also conduct mechanistic studies in blood and tissue samples from our subjects and will test the utility of candidate biomarkers for the detection of tissue Na+ overload.

• DFG Programme: Research Grants