mTOR Inhibitors Induce Erythropoietin Resistance in Renal Transplant Recipients.

Aim: To elucidate the role of mTOR inhibitors on iron, hepcidin and erythropoietin-mediated regulation of hemopoiesis in stable renal transplant recipients (RTR). Background: Impaired hemopoiesis is common following renal transplantation managed using mTOR inhibitors. The mechanisms responsible are uncertain but include direct effects on iron, hepcidin or erythropoietin-mediated hemopoiesis. Methods: We conducted a single center prospective case-control study of 26 adult RTR with stable allograft function. RTR received stable mTOR dosing (cases, 11/26 [42%]) or stable tacrolimus dosing (controls, 15/26 [58%]). Baseline demographics, full blood count, renal function, iron studies, hepcidin-25, Interleukin-6 (IL-6) and erythropoietin (EPO) levels were determined. Results: There were no differences in age, gender or allograft function. Mean daily sirolimus dose for cases was 1.72 mg, with mean trough level of 8.46 ng/mL. Mean daily tacrolimus dose for controls was 4.3 mg, with mean trough level of 5.8 ng/mL. There were no differences in mean hemoglobin (143 vs. 147 g/L; p = 0.59), MCV (88 vs. 90 fL; p = 0.35), serum ferritin (150 vs. 85.7 µg/L; p = 0.06), transferrin saturation (26 vs. 23.3%; p = 0.46), IL-6 (11 vs. 7.02 pg/ml; p = 0.14) or hepcidin-25 (3.62 vs. 3.26 nM; p = 0.76) between the groups. EPO levels were significantly higher in the group receiving mTOR therapy (16.8 vs. 8.49 IU/L; p = 0.028). On logistic regression analysis EPO level was the only variable that had a significant impact providing an odds ratio of 0.84 (95%CI 0.66-0.98). The area under the receiver operator characteristic curve (ROC) for the analysis was 0.77 (95%CI 0.54-0.94) with p = 0.04.Conclusion: Higher levels of EPO in the absence of deranged iron biochemistry or hepcidin-25 levels suggest that EPO resistance rather than impaired iron metabolism may contribute to the impaired hemopoiesis previously demonstrated in RTR on mTOR therapy.

Peritoneal Dialysis for Heart Failure.

Heart failure (HF) is a common and important cause of morbidity and mortality in the elderly, imposing a significant burden on healthcare systems. Better management of ischemic heart disease has resulted in increased survival and growth in the number of prevalent heart failure patients, but co-existing renal impairment complicates management and limits traditional therapeutic options. Ultrafiltration (UF) techniques have shown promise in the treatment of diuretic-resistant HF, but the early successes of extracorporeal treatments has not been confirmed by randomized trials. Peritoneal dialysis (PD) may be cheaper and provide more effective UF therapy in selected patients and this review examines the issues surrounding the use of PD for such patients. Whist many nephrologists are enthusiastic about the use of this technique, making a more cogent case for PD in this setting for cardiologists is likely to need a combined strategy of demonstrating improvement in individual cases and further study of potential medicoeconomic benefits.