Circulating endotoxaemia and frequent haemodialysis schedules.

BACKGROUND/AIMS: Endotoxaemia, a driver of systemic inflammation, appears to be driven by dialysis-induced circulatory stress in haemodialysis (HD) patients. More frequent HD regimens are associated with lower ultrafiltration requirements, improved haemodynamic stability and lower systemic inflammation. This study investigated the hypothesis that more frequently dialysed patients, with reduced exposure to dialysis-induced haemodynamic perturbation, would have lower circulating endotoxin (ET) levels. METHODS: A cross-sectional study of 86 established HD patients compared three groups: conventional HD 3× per week (HD3, n = 56), frequent HD 5-6× per week (SDHD, n = 20), and nocturnal HD (NHD, n = 10). Data collection included ultrafiltration volume and rate, serial blood pressures and blood sampling with quantification of ET, troponin T and high-sensitivity CRP (hsCRP). RESULTS: Pre-dialysis serum ET was highest in the conventional HD group (HD3 0.66 ± 0.29 EU/ml vs. NHD 0.08 ± 0.04 EU/ml). Across the study population, severity of endotoxaemia was associated with higher ultrafiltration rates, degree of intradialytic hypotension, troponin T and hsCRP levels. NHD patients had the lowest ultrafiltration requirements, the greatest haemodynamic stability and lower ET levels. CONCLUSION: More frequent HD regimens are associated with lower levels of circulating ET compared with conventional HD. Reduced ET translocation may be related to the greater haemodynamic stability of these treatments, with superior maintenance of splanchnic perfusion.

The impact of hemodialysis on segmental and global longitudinal myocardial strain.

BACKGROUND: Strain analysis derived from the analysis of speckle tracked imaging echocardiography can be used to examine ventricular contractile functions. In this study, we examined the relationship of hemodialysis (HD)-induced circulatory stress with overall ventricular function assessed according to global longitudinal strain (GLS) and segmental distribution of strain. METHODS: This prospective observational study included 104 conventional HD patients at Royal Derby Hospital. Averaged values of segmental and GLS were determined from the echocardiography of these patients before and at peak dialysis. These values were compared with the reference values of healthy individuals, correlated with their demographic characteristics, and the effect on survival was assessed. RESULTS: The global strain value was -11.5% ± 4.42, and the segmental strain values were significantly greater in HD patients than in healthy individuals by 2.7%-9.8% (P < 0.001). The strain values were not significantly different before dialysis and at peak dialysis (P > 0.05), except within the basal lateral segment (P = 0.01). The adjusted hazard ratio for mortality was 4.3 (95% confidence interval, 1.2-14.9; P = 0.021) when > 80% of the segments exhibited more than the mean of segmental strain values. For the 46 patients who died, there were statistically significant negative correlations between survival time and GLS (r = -0.30; P = 0.04). CONCLUSIONS: Global and segmental strain measured using speckle tracked imaging provides information relating to the effects of HD-induced cardiac injury. The segmental strain abnormalities in the watershed area of the left ventricle suggest a higher degree of vulnerability to HD-induced demand ischemia.

Remote ischaemic conditioning-therapeutic opportunities in renal medicine.

Following ischaemic insult, tissue damage is extended after reperfusion, known as an ischaemia reperfusion injury. Ischaemic conditioning-the application of transient, non-lethal, episodes of ischaemia-reduces the effect of a larger ischaemic insult, and limits the reperfusion injury. How this phenomenon might be exploited as a therapeutic treatment is now the subject of a number of clinical trials. From initial trials focusing on the mitigation of cardiac injury, interest has expanded to examine the potential for its use as an adjunctive therapy in different clinical scenarios, including renal medicine. In this Review, we discuss different forms of conditioning, potential molecular mechanisms underpinning its effect, and potential applications in the setting of acute kidney injury, chronic kidney disease and end-stage renal disease.

Tissue advanced glycation end product deposition after kidney transplantation.

BACKGROUND: Tissue advanced glycation end products (AGEs) accumulate in chronic kidney disease (CKD) and are a measure of cumulative metabolic stress. Measurement of tissue AGEs by skin autofluorescence (SAF) correlates well with cardiovascular outcomes in dialysis patients. SAF levels in transplant recipients relative to CKD and dialysis patients have not been previously studied, and the impact of transplantation on SAF levels in dialysis patients is unknown. METHODS: SAF was measured using an AGE reader in 66 patients who had received a kidney transplant. Values were compared to those obtained in 1,707 patients with CKD stage 3 and in 115 patients on dialysis. RESULTS: Mean SAF in transplant recipients [2.81 ± 0.64 arbitrary units (AU)] was significantly lower than in patients on haemodialysis (3.73 ± 0.88 AU) and peritoneal dialysis (3.57 ± 0.75 AU; p < 0.001), but was no different from CKD stage 3 (2.79 ± 0.66 AU; p = 0.42). In the transplant group, SAF correlated most strongly with age (r = 0.316). There was no correlation between SAF and estimated glomerular filtration rate or renal replacement therapy vintage. A small cohort of patients with SAF recorded on dialysis and following transplantation showed a drop in SAF over a mean time of 16 months after transplantation. DISCUSSION: Tissue AGE values in kidney transplant recipients are significantly lower than in patients receiving dialysis and similar to those in patients with CKD stage 3. Our data suggest that transplantation may be associated with a reduction in tissue AGEs, and this might be an important component of the observed reduction in cardiovascular risk in transplant recipients compared to patients on dialysis.