Effects of hemodiafiltration and hemodialysis on hemodynamics, tissue injury and patient discomfort

Abstract

General Introduction and thesis outline The clinical outcome of dialysis patients may be improved by treatment with high-volume hemodiafiltration (HV-HDF) instead of “standard” high-flux hemodialysis (S-HD). However, the underlying mechanisms are unknown. Repetitive organ and tissue damage due to intradialytic hypotension (IDH) has been postulated as the underlying factor for the association between IDH and mortality. A lower IDH-incidence in HV-HDF may be linked to less IDH-induced tissue injury. Part A: Long-term peridialytic BP changes and mortality in S-HD and HDF Long-term peridialytic BP patterns In chapter II, long-term peridialytic BP patterns from the individual participant data comparing HD with HDF are presented. Mean pre- and postdialytic SBP, DBP and MAP declined significantly in the long-term among chronic HD and HDF patients. The combination of a decreasing SBP and an increasing PP may be the clinical sequelae of a worsening cardiovascular system. This does not support that a superior peridialytic BP control contributes to the prolonged survival by HV-HDF. Long-term peridialytic BP changes and mortality In chapter III, we showed that severe declines in predialytic SBP and postdialytic DBP in the preceding 6 months were independently related to mortality. Therefore, peridialytic BP values should be interpreted in context of their changes and not solely as an absolute value. Part B: Intradialytic hemodynamics and subsequent tissue damage, and symptomatology between S-HD, C-HD, and LV- and HV-HDF Intradialytic hemodynamics and IDH In chapter V, in C-HD and HV-HDF the lowest IDH frequency and the best intradialytic hemodynamic stability was observed, while all parameters were most disrupted in S-HD. The superior survival of HV-HDF may be partly caused by a more beneficial intradialytic BP profile. Assessment of intradialytic tissue damage by extracellular vesicles (EVs) In chapter VI, intradialytic tissue injury was assessed by measuring EVs from circulating blood-cell-elements (bio-incompatibility [BI]-related) and cardiovascular tissues (CV-related). Most EVs increased in both HD and HDF. Regarding platelet derived EVs, HDF appears less biocompatible than HD. Considering CV-related EVs, tissue injury seems less pronounced in HV-HDF as compared to S-HD. The finding that EV-release is IDH-independent needs confirmation. Assessment of microbial DNA and the acute phase response (APR) APR markers and microbial DNA (mDNA) were measured (chapter VII). mDNA could not be demonstrated. After correction for hemoconcentration, APR-markers remained stable or declined. These data do not support that the superior survival of HV-HDF is mediated by improved preservation of gut integrity. Physical intradialytic patient-reported outcome measures In chapter VIII, we showed that PID-PROMs hardly differed between modalities, but varied markedly between patients. Hence, PID-PROMs appear largely patient-dependent. While body temperature (Tb) increased in S-HD, LV- and HV-HDF, thermal perception did not change. Whereas Tb remained unaltered in C-HD, cold perception emerged. Therefore, for bothersome cold sensations, C-HD should be avoided in perceptive individuals. Conclusions 1) Long-term peridialytic BP values decline equally among patients treated with HD and HDF. 2) Severe declines in long-term predialytic SBP and postdialytic DBP compared to moderate changes are independently associated with increased mortality, without differences between HD and HDF. 3) Treatment with HV-HDF or C-HD results in a lower IDH incidence, as compared to S-HD. 4) As the release of cardiovascular related EVs was lower in HV-HDF than in S-HD, treatment with HV-HDF seems associated with less intradialytic damage of the endothelium and the heart. Whether IDH has a role in this respect remains to be elucidated, since reliable continuous BP measurements are absent in the present study. 5) Besides cold sensations, which were observed most frequently during C-HD, adverse PID-PROMs seem largely patient-dependent and not related to the treatment modality.