What is new in uremic toxicity?

Uremic syndrome results from a malfunctioning of various organ systems due to the retention of compounds which, under normal conditions, would be excreted into the urine and/or metabolized by the kidneys. If these compounds are biologically active, they are called uremic toxins. One of the more important toxic effects of such compounds is cardio-vascular damage. A convenient classification based on the physico-chemical characteristics affecting the removal of such compounds by dialysis is: (1) small water-soluble compounds; (2) protein-bound compounds; (3) the larger “middle molecules”. Recent developments include the identification of several newly detected compounds linked to toxicity or the identification of as yet unidentified toxic effects of known compounds: the dinucleotide polyphosphates, structural variants of angiotensin II, interleukin-18, p-cresylsulfate and the guanidines. Toxic effects seem to be typically exerted by molecules which are “difficult to remove by dialysis”. Therefore, dialysis strategies have been adapted by applying membranes with larger pore size (high-flux membranes) and/or convection (on-line hemodiafiltration). The results of recent studies suggest that these strategies have better outcomes, thereby clinically corroborating the importance attributed in bench studies to these “difficult to remove” molecules

Kidney transplantation after rescue allocation : the Eurotransplant experience : a retrospective multicenter outcome analysis

Background: At Eurotransplant (ET), kidneys are transferred to 'rescue allocation' (RA), whenever the standard allocation (SA) algorithms Eurotransplant kidney allocation system (ETKAS) and Eurotransplant senior program (ESP) fail. We analyzed the outcome of RA. Methods: Retrospective patient clinical and demographic characteristics association analyses with graft outcomes for 2,421 recipients of a deceased donor renal transplantation (DDRT) after RA versus 25,475 after SA from 71 centers across all ET countries from 2006 to 2018. Results: Numbers of DDRTs after RA increased over the time, especially in Germany. RA played a minor role in ESP vs. ETKAS (2.7% vs. 10.4%). RA recipients and donors were older compared to SA recipients and donors, cold ischemia times were longer, waiting times were shorter, and the incidence of primary non-function was comparable. Among ETKAS-recipients, HLA matching was more favorable in SA (mean 3.7 vs. 2.5). In multivariate modeling, the incidence of death with a functioning graft (DwFG) in ETKAS was reduced in RA compared to SA (subdistribution hazard ratio 0.70, 95% confidence interval [0.60-0.81], p<0.001) whereas other outcomes (mortality, graft loss) were not significantly different. None of the three outcomes were significantly different when comparing RA with SA within the ESP program. Conclusions: Facing increased waiting times and mortality on dialysis due to donor shortage, this study reveals encouragingly positive DDRT outcomes following RA. This supports the extension of RA to more patients and as an alternative tool to enable transplantation in patients in countries with prohibitively long waiting times or at risk of deterioration.Supplemental Visual Abstract; http://links.lww.com/TP/C297