End-Stage Kidney Disease in Areas of Armed Conflicts: Challenges and Solutions.

Violent and protracted conflicts are disastrous to civilian populations and their health care systems. The complex requirements of caring for end-stage kidney disease (ESKD) dialysis patients in such contexts pose unique challenges. Dialysis is procedurally complex and resource-intensive. Delivering ESKD care in man-made conflict settings presents added challenges beyond what is required in natural disasters and resource-limited situations. In this article, we review the medical literature on, and document experience with, managing dialysis ESKD patients in conflict zones. We discuss the impact of war on patient outcomes, dialysis system infrastructure, operational funding, and risks to providers and organizations. This article provides recommendations to health care providers, educators, and policymakers on how to mitigate associated challenges.

Care and outcomes of end-stage kidney disease patients in times of armed conflict: recommendations for action.

BACKGROUND: Conflicts can lead to significant disruption in the care of endstage kidney disease (ESKD) patients. The purpose of this paper is to review the available literature on the care of ESKD patients in times of armed conflict and make recommendations for action. METHOD: A review of all PubMed-published reports between 1965 and 2015 about the care of ESKD patients at the time of conflict. We excluded articles that reported on acute kidney injury and natural disasters. RESULTS: We found a total of 12 reports on dialysis care and/or kidney transplant care from five armed conflicts and resulting refugee crises. These conflicts led to significant shortage of staff and resources and caused several obstacles in providing adequate dialysis to ESKD patients. In one study, the mortality rate of patients on automated peritoneal dialysis was as high as 95%. The kidney transplantation rate decreased in all but one of the reports about kidney transplant care and patients had difficulties securing their immunosuppressive medications. CONCLUSIONS: ESKD patients, especially dialysis patients, comprise a severely vulnerable population during conflicts. Their care can be disrupted and altered leading to a substantial increase in their mortality rate. Efforts to improve their care during conflicts are needed.

A randomized, double-blind, placebo-controlled, dose-ranging study using Genz-644470 and sevelamer carbonate in hyperphosphatemic chronic kidney disease patients on hemodialysis.

BACKGROUND: Genz-644470 is a new, nonabsorbed phosphate binding polymer. In an in vitro competitive phosphate binding assay, Genz-644470 bound significantly more phosphate per gram than sevelamer. As a consequence, this clinical study evaluated the ability of Genz-644470 to lower serum phosphorus in patients on hemodialysis and compared serum phosphorus lowering of Genz-644470 with sevelamer carbonate and placebo. Because three different fixed doses of Genz-644470 and sevelamer carbonate were used, phosphate-lowering dose-responses of each agent were also analyzed. METHODS: A randomized, double-blind, dose-ranging study was conducted. After a 2-week phosphate binder washout, 349 hyperphosphatemic (serum phosphorus >5.5 mg/dL) hemodialysis patients were randomized to one of seven fixed-dose groups: placebo, Genz-644470 2.4 g/day, Genz-644470 4.8 g/day, Genz-644470 7.2 g/day, sevelamer carbonate 2.4 g/day, sevelamer carbonate 4.8 g/day, or sevelamer carbonate 7.2 g/day. Indicated total daily doses were administered in fixed divided doses three times a day with meals for 3 weeks. The change in serum phosphorus during the treatment period and its dose-response patterns were assessed. RESULTS: Dose-dependent reductions in serum phosphorus were observed with both Genz-644470 and sevelamer carbonate. Serum phosphorus-lowering responses to fixed doses of sevelamer carbonate and Genz-644470 were enhanced in a roughly linear fashion with increasing doses over a threefold range after 3 weeks of treatment. Genz-644470 did not show any advantage in phosphorus lowering per gram of binder compared with sevelamer carbonate. Overall toler-ability was similar between active treatment groups. The tolerability of sevelamer carbonate was consistent with prior studies and with the established safety profile of sevelamer. CONCLUSION: Both Genz-644470 and sevelamer carbonate effectively lowered serum phosphate levels in a dose-dependent fashion in patients with chronic kidney disease on hemodialysis. However, Genz-644470 did not provide any advantage over sevelamer carbonate in phosphate lowering in vivo, as had been demonstrated in vitro.

Modified-release calcifediol effectively controls secondary hyperparathyroidism associated with vitamin D insufficiency in chronic kidney disease.

BACKGROUND/AIMS: Vitamin D insufficiency drives secondary hyperparathyroidism (SHPT) and is associated with increased cardiovascular mortality in patients with chronic kidney disease (CKD). SHPT is poorly addressed by current vitamin D repletion options. The present study evaluated a novel investigational vitamin D repletion therapy: a modified-release (MR) formulation of calcifediol designed to raise serum 25-hydroxyvitamin D in a gradual manner to minimize the induction of CYP24 and, thereby, improve the SHPT control. METHODS: This randomized, double-blind, placebo-controlled trial evaluated MR calcifediol in CKD subjects (n = 78) with plasma intact parathyroid hormone (iPTH) >70 pg/ml and serum total 25-hydroxyvitamin D <30 ng/ml. Subjects received daily treatment for six weeks with oral MR calcifediol (30, 60 or 90 µg) or a placebo. RESULTS: More than 90% of subjects treated with MR calcifediol achieved serum 25-hydroxyvitamin D levels ≥30 ng/ml versus 3% of subjects treated with placebo (p < 0.0001). Mean plasma iPTH decreased from baseline (140.3 pg/ml) by 20.9 ± 6.2% (SE), 32.8 ± 5.7 and 39.3 ± 4.3% in the 30, 60 and 90 µg dose groups, respectively, and increased 17.2 ± 7.8% in the pooled placebo group (p < 0.005). No clinically significant safety concerns arose during MR calcifediol treatment. CONCLUSION: Oral MR calcifediol appears safe and highly effective in treating SHPT associated with vitamin D insufficiency in CKD.