Donor-derived Cell-free DNA: Advancing a Novel Assay to New Heights in Renal Transplantation.

Despite advances in transplant immunosuppression, long-term renal allograft outcomes remain suboptimal because of the occurrence of rejection, recurrent disease, and interstitial fibrosis with tubular atrophy. This is largely due to limitations in our understanding of allogeneic processes coupled with inadequate surveillance strategies. The concept of donor-derived cell-free DNA as a signal of allograft stress has therefore rapidly been adopted as a noninvasive monitoring tool. Refining it for effective clinical use, however, remains an ongoing effort. Furthermore, its potential to unravel new insights in alloimmunity through novel molecular techniques is yet to be realized. This review herein summarizes current knowledge and active endeavors to optimize cell-free DNA-based diagnostic techniques for clinical use in kidney transplantation. In addition, the integration of DNA methylation and microRNA may unveil new epigenetic signatures of allograft health and is also explored in this report. Directing research initiatives toward these aspirations will not only improve diagnostic precision but may foster new paradigms in transplant immunobiology.

When end-stage kidney disease complicates abdominal surgery.

Patients receiving peritoneal dialysis (PD) encounter an increased risk for infection, bleeding, and PD fluid leakage after abdominal surgery. These complications may affect the future use of PD. Appropriate patient preparation may mitigate complications. Certain complications or procedures allow patients to remain on PD while others require transition to hemodialysis. We review the etiology and management of infection, bleeding, and PD fluid leakage associated with abdominal surgery as well as the relationship of specific abdominal procedures to continuing PD.

Safety and dose-finding study of activated protein C (drotrecogin alfa activated) as an anticoagulant in end-stage renal disease patients treated with hemodialysis.

BACKGROUND/AIMS: End-stage renal disease (ESRD) patients treated with hemodialysis (HD) experience a high risk of death. ESRD patients with elevated levels of pro-inflammatory cytokines are at increased risk of death from cardiovascular events and infection. HD is often facilitated by the use of an anticoagulant. We hypothesized that the use of an anticoagulant that also possessed anti-inflammatory qualities without significant immunosuppressive effects may reduce the risk of death. In this pilot study, we sought to determine the optimal dose of activated protein C (APC) to achieve adequate regional anticoagulation for HD and determine if the drug can be safely used in ESRD patients treated with HD. METHODS: Twelve stable HD patients were enrolled into this safety and dose-finding study. Varying doses of APC were administered in place of usual heparin at varying doses to determine the range of APC that can be used for extracorporeal circuit anticoagulation. Partial thromboplastin time was assessed at fixed intervals during the HD treatment. RESULTS: The average age of study patients was 49 ± 12 years. 75% of patients were African-American and 66.7% were male. The optimal dose of APC to induce adequate anticoagulation was 24-30 µg/kg/h. No patients experienced any serious adverse events. One patient had their infusion stopped early due to refractory intradialytic hypertension. CONCLUSIONS: For ESRD patients undergoing HD, an initial starting dose of 24-30 µg/kg/h achieves a target partial thromboplastin time that should be adequate for circuit anticoagulation. This dose appears safe and was well tolerated.