The Microcirculation, Dialysis Modality and Sequestered Salt

The life expectancy of patients with end-stage kidney disease (ESKD) is poor. Post-dilution online hemodiafiltration (HDF) is associated with a lower mortality than standard hemodialysis (HD), especially when a high convection volume is achieved (high-volume HDF; hvHDF). It is unclear, however, why (hv)HDF improves survival. Neither an increased clearance of middle molecular weight uremic toxins, nor an improved bio-incompatibility can explain the difference. As the effects are already observed within 2.5 years, recovery of a functional disorder is more likely than restoration of structural alterations. The recuperation of vascular dysfunction may be the missing piece of the puzzle. Previous literature showed (1) that the microcirculation (MC) is severely disturbed in dialysis patients, (2) excess sodium can bind to glycosaminoglycans in the interstitium and in the glycocalyx of blood vessels without commensurate water retention (sequestered sodium content \[SSC\]) and (3) that in patients with non-dialysis dependent chronic kidney disease, a disturbed SSC is related to capillary rarefaction and dysfunction. Therefore, the present study aims to assess the influences of both the modality (HD and HDF) and the dialysate sodium concentration (DNa) on the SSC and the MC.

Therefore the following hypotheses will be evaluated: (1, 2) treatment with hvHDF improves the SSC and MC, if compared to HD; (3, 4) disorders of the SSC and the MC are influenced by differences between the dialysate sodium \[DNa\] and plasma sodium \[PNa\] concentrations; (5) SSC and MC are interrelated in this patient group.

• Intradialytic hypotension [Срок оценки: up to 4 hours (=one dialysis treatment); assessed during all dialysis sessions (12 treatments per intervention, measured 4x/hour)]
• Change in intradialytic blood pressure [Срок оценки: up to 4 hours (=one dialysis treatment); assessed during all dialysis sessions (12 treatments per intervention, measured 4x/hour)]
• Peridialytic blood pressure [Срок оценки: up to 24 hours (=one interdialytic day): measured 3x/day every 4 weeks during the last interdialytic day of each treatment period (i.e. 5 times in total)]
• Change in CK-MB [Срок оценки: up to 4 hours (=one dialysis treatment); measured before and immediately after the last dialysis session of each treatment period (i.e. 10 times in total)]
• Change in high sensitivity C-reactive protein (hs-CRP) [Срок оценки: up to 4 hours (=one dialysis treatment); measured before and immediately after the last dialysis session of each treatment period (i.e. 10 times in total)]
• Change in interleukin-6 receptor (IL-6R) [Срок оценки: up to 4 hours (=one dialysis treatment); measured before and immediately after the last dialysis session of each treatment period (i.e. 10 times in total)]
• Change in soluble CD163 (sCD163) [Срок оценки: up to 4 hours (=one dialysis treatment); measured before and immediately after the last dialysis session of each treatment period (i.e. 10 times in total)]
• Change in soluble intercellular adhesion molecule-1 (s-ICAM-1) [Срок оценки: up to 4 hours (=one dialysis treatment); measured before and immediately after the last dialysis session of each treatment period (i.e. 10 times in total)]
• Change in serum glycosaminoglycans [Срок оценки: up to 4 hours (=one dialysis treatment); measured before and immediately after the last dialysis session of each treatment period (i.e. 10 times in total)]
• Change in syndecan-1 [Срок оценки: up to 4 hours (=one dialysis treatment); measured before and immediately after the last dialysis session of each treatment period (i.e. 10 times in total)]
• Change in vascular endothelial growth factor C (VEGF-C) [Срок оценки: up to 4 hours (=one dialysis treatment); measured before and immediately after the last dialysis session of each treatment period (i.e. 10 times in total)]
• Change in extracellular vesicles (EVs) [Срок оценки: up to 4 hours (=one dialysis treatment); measured before and immediately after the last dialysis session of each treatment period (i.e. 10 times in total)]