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Author Interview: Dr. Guy Rostoker

Modulation of oxidative stress and microinflammatory status by colloids in refractory dialytic hypotension

Guy Rostoker, Mireille Griuncelli, Christelle Loridon, Thomas Bourlet 
Eric Illouz and Abbes Benmaadi
BMC Nephrology 2011, 12:58doi:10.1186/1471-2369-12-58

We have recently shown that systematic colloids infusion during hemodialysis sessions improves hemodynamic parameters in most dialysis hypotension-prone patients unresponsive to usual measures of prevention.We hypothesize that frequent hypotension episodes may induce a noxious inflammatory response mediated by oxidative stress induced by ischemia-reperfusion phenomenon. We found an improvement of oxydative stress by colloids ; hyperoncotic albumin albumin was found to exert more powerful effects. Among colloids, only albumin improves microinflammatory status (serum ceruloplasmin and serum C3). 

C-reactive protein (CRP) and pro-inflammatory cytokines remained unchanged, but their levels were low before any therapeutic intervention.
We explain these low levels by the fact that our patients’ dialysis modality with ultrapure dialysate . Indeed  IL6, IL8 and TNFalpha levels have been shown to be greatly influenced by the type of dialysate : standard dialysate with endotoxin content but not ultrapure dialysate has been shown to be a potent inductor of these mediators. The systematic use of cool dialysate together with the sodium and ultrafiltration profiles and infusion of colloids may have also contributed to this low levels of CRP and pro-inflammatory cytokines.

Our study strongly suggest that dialytic hypotension may contribute to the overproduction of reactive oxygen species seen in end-stage renal failure patients, a multifactorial process mainly related to uremia per-se, the hemoincompatibility of the dialysis system and trace amounts of endotoxin in the dialysate. Oxydative stress may play a pivotal role in cardiovascular morbidity and mortality and in undernutrition/cachexia in dialysis patients. Therefore avoidance of dialytic hypotension by any maneuver may be highly beneficial. In the first part of this study published in the first trimester of this year (J Nephrol 2011; 24 (02): 208-217), we showed using n-of-1 methodology that some patients do respond to both 4% gelatin and 20% albumin; the former being of low cost (cost of 200 ml 20% albumin : 80 Euros as compared to 4 Euros for 4% gelatin), clearly indicating to always trying gelatin as first line colloid therapy.

The need (and interest) of well-designed controlled trials with a sufficient number of patients of hyperoncotic 20% albumin and 4% gelatin in hypotension-prone patients dialysis patients unresponsive to usual preventive measures to confirm these promising preliminary results. 

Intradialytic hypotension may adversely affect the outcome of chronic hemodialysis. Therapeutic albumin has powerful anti-oxidant and anti-inflammatory properties. We have recently shown that systematic colloid infusion during hemodialysis sessions improves hemodynamic parameters in most dialysis hypotension-prone patients unresponsive to usual of preventive measures. We postulated that frequent hypotensive episodes may lead to a noxious inflammatory response mediated by oxidative stress induced by ischemia-reperfusion. The aim of this study was therefore to analyze the effect of 20% albumin and 4% gelatin infusions on oxidative stress and microinflammatory status in hypotension-prone patients unresponsive to usual preventive measures.

Methods

Prospective cross-over study (lasting 20 weeks) of routine infusion of 200 ml of 20% albumin versus 200 ml of 4% gelatin in 10 patients with refractory intradialytic hypotension. We analyzed the effect of 20% albumin and 4% gelatin on microinflammatory status, oxidative stress, serum nitrite and nitrate levels by analysis of variance.

Results

A significant decrease in serum ceruloplasmin and serum C3 was observed during the albumin period (p< 0.05, repeated measure ANOVA). A significant decrease in serum hydrogen peroxide was seen during albumin and gelatin administration (p< 0.01, repeated measure ANOVA) and a very large decrease in serum lipid peroxides was observed during the albumin period only (p< 0.01, Friedman test). Serum lactoferrin, serum proinflammatory cytokines and serum nitrite and nitrate levels remained stable during the different periods of this pilot trial.

Conclusions

We conclude that the improvement in microinflammatory status observed during colloid infusion in hypotension-prone dialysis patients may be related to a decrease in ischemia-reperfusion of noble organs, together with a specific reduction in oxidative stress by albumin. Trial registration: ISRCTN 20957055