Effects of hemodiafiltration and hemodialysis on hemodynamics, tissue injury and patient discomfort
Authors:   , Rootjes Paul Arjen 
Published: May 2024

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.