Ferric citrate controls phosphorus and delivers iron in patients on dialysis.

Patients on dialysis require phosphorus binders to prevent hyperphosphatemia and are iron deficient. We studied ferric citrate as a phosphorus binder and iron source. In this sequential, randomized trial, 441 subjects on dialysis were randomized to ferric citrate or active control in a 52-week active control period followed by a 4-week placebo control period, in which subjects on ferric citrate who completed the active control period were rerandomized to ferric citrate or placebo. The primary analysis compared the mean change in phosphorus between ferric citrate and placebo during the placebo control period. A sequential gatekeeping strategy controlled study-wise type 1 error for serum ferritin, transferrin saturation, and intravenous iron and erythropoietin-stimulating agent usage as prespecified secondary outcomes in the active control period. Ferric citrate controlled phosphorus compared with placebo, with a mean treatment difference of -2.2±0.2 mg/dl (mean±SEM) (P<0.001). Active control period phosphorus was similar between ferric citrate and active control, with comparable safety profiles. Subjects on ferric citrate achieved higher mean iron parameters (ferritin=899±488 ng/ml [mean±SD]; transferrin saturation=39%±17%) versus subjects on active control (ferritin=628±367 ng/ml [mean±SD]; transferrin saturation=30%±12%; P<0.001 for both). Subjects on ferric citrate received less intravenous elemental iron (median=12.95 mg/wk ferric citrate; 26.88 mg/wk active control; P<0.001) and less erythropoietin-stimulating agent (median epoetin-equivalent units per week: 5306 units/wk ferric citrate; 6951 units/wk active control; P=0.04). Hemoglobin levels were statistically higher on ferric citrate. Thus, ferric citrate is an efficacious and safe phosphate binder that increases iron stores and reduces intravenous iron and erythropoietin-stimulating agent use while maintaining hemoglobin.

The management of the failed renal allograft: an enigma with potential consequences.

The number of patients returning to dialysis after their renal allograft fails is increasing in absolute numbers year after year. The management of the failed allograft that is not immediately symptomatic remains controversial. Surgical mortality and morbidity, a rising number of circulating antibodies, reduced erythropoietin, and diuresis are among the arguments to support simply observing the failed allograft. Chronic inflammation, potential for malignancy, infection, and the need for low-dose immunosuppression are concerns that might goad one into performing a preemptive nephrectomy. Based on the current literature and our own clinical experience, we believe allograft nephrectomies should not be routinely performed. They should be reserved for those patients who develop particular symptoms attributable to the allograft or those who require space for retransplantation. Future studies that address this issue in addition to testing various immunosuppression attrition rates may be able to discern a protocol that minimizes drug exposure while leading to reduced nephrectomy rates after returning to dialysis.