Dialysis initiation and clinical outcomes in chronic kidney disease : role of education and biomarkers

Abstract: For patients with chronic kidney disease (CKD) who develop kidney failure, renal replacement therapy (RRT) with kidney transplantation is the best treatment option. But if this is not possible due to lack of organs or medical factors, dialysis initiation with haemodialysis (HD) or peritoneal dialysis (PD) is required. Unplanned start (UPS) of dialysis using in-centre HD with central venous catheter (CVC) as default option is common and associates with increased mortality and lower chance of receiving PD. Educating and providing PD to UPS patients is possible and with clinical outcomes comparable to UPS with HD. As RRT patients have increased cardiovascular disease (CVD) related mortality - due to not only traditional risk factors but also non-traditional risk factors such as inflammation, oxidative stress, endothelial dysfunction and protein energy wasting – there is a need to identify biomarkers reflecting such risk factors. This thesis consists of three studies aimed to improve the knowledge about patient education in conjunction with dialysis initiation and in particular the effect of the unplanned education programme (UPS-EP) on clinical outcomes of UPS patients, and two studies of the predictive role of two putative clinically useful biomarkers (S100A12 and pentosidine) which are components of AGE-RAGE pathway. In Study I we evaluated the feasibility and impact of UPS-EP to allow modality choice in 270 patients. Patients completing UPS-EP were more likely to select PD as their preferred modality. Patient survival in patients choosing and/or receiving PD was similar to HD despite age and comorbidity disadvantages of the PD patients. In Study II, factors influencing three key steps in the UPS patient educational pathway: (1) referral to and receiving UPS-EP, (2) making decision on dialysis modality, (3) receiving preferred dialysis modality after decision making were analyzed. Older age reduced probability of receiving UPS-EP but not the chance of making modality decision. Cultural country factors had strong influence on probability of receiving education and making modality decision. In Study III we compared UPS patients commencing dialysis with PD catheter or CVC, described characteristics of patients switching modality, evaluated patient outcomes such as PD technique failure and investigated predictors of permanent vascular access formation and clinical outcomes of patients undergoing HD during follow up. Older patients and those with congestive heart failure had lower chances receive arteriovenous fistula (AVF). Patients with AVF had better 1-year survival than those remaining on CVC. In Study IV we investigated circulating S100A12 and soluble RAGE (sRAGE) in relation to peripheral or cerebrovascular disease (PCVD), inflammation, nutritional status, and mortality risk in PD patients. Plasma S100A12 and sRAGE were markedly elevated and sRAGE was inversely related to body mass indices while S100A12 associated with increased inflammation, PCVD, and mortality, suggesting that S100A12 may identify PD patients at high risk for vascular disease and increased mortality. In Study V we evaluated factors linked to increased plasma pentosidine and associations with mortality in patients with different stages and treatment of CKD. Plasma pentosidine was markedly elevated and associated with low GFR, oxidative stress and inflammation, and it predicted all-cause and CVD mortality. Despite exposure to glucose containing dialysis fluids in PD patients, their plasma pentosidine concentrations were not higher than in HD patients indicating that other factors than glucose exposure matters.

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