Marvin Sinsakul

At-home short daily hemodialysis improves the long-term health-related quality of life

Patients with chronic kidney disease treated by in-center conventional hemodialysis (3 times per week) have significant impairments in health-related quality of life measures, which have been associated with increased morbidity and mortality. FREEDOM is an ongoing prospective cohort study measuring the potential benefits of at-home short daily (6 times per week) hemodialysis. In this interim report we examine the long-term effect of short daily hemodialysis on health-related quality of life, as measured by the SF-36 health survey. This was administered at baseline, 4 and 12 months after initiation of short daily hemodialysis to 291 participants (total cohort), of which 154 completed the 12-month follow-up (as-treated cohort). At the time of analysis, the mean age was 53 years, 66% were men, 58% had an AV fistula, 90% transitioned from in-center hemodialysis, and 45% had diabetes mellitus. In the total cohort analysis, both the physical- and mental-component summary scores improved over the 12-month period, as did all 8 individual domains of the SF-36. The as-treated cohort analysis showed similar improvements with the exception of the role-emotional domain. Significantly, in the as-treated cohort, the percentage of patients achieving a physical-component summary score at least equivalent to the general population more than doubled. Hence, at-home short daily hemodialysis is associated with long-term improvements in various physical and mental health-related quality of life measures.

The Safety and Tolerability of Ferric Citrate as a Phosphate Binder in Dialysis Patients

Background: A phase II open-label study was conducted in hemodialysis patients evaluating the short-term safety, tolerability, and iron absorption with ferric citrate when used as a phosphate binder. Methods: Enrollment occurred in two periods. Period 1 recruited patients taking 6–15 pills/day of binder with phosphorus of ≥2.5 mg/dl. Period 2 recruited patients taking ≥12 pills/day of binder with phosphorus of ≥3.5 mg/dl. Participants with ferritin ≥1,000 µg/l or transferrin iron saturation (TSAT) ≥50% at screening were excluded. Subjects discontinued their previous binders and started 4.5 g/day of ferric citrate (period 1) or 6 g/day (period 2) and were titrated for 4 weeks to maintain a phosphorus of 3.5–5.5 mg/dl. Chemistries and complete blood count were obtained weekly and a gastrointestinal questionnaire was administered at drug initiation and final visit. Iron therapy was permitted if the ferritin was <500 µg/l and TSAT <30%. Results: Fifty-five subjects were enrolled. Four serious adverse events were reported; none were related to the study drug. Findings from the gastrointestinal questionnaire included stool discoloration (69%), constipation (15%), and bloating (7%). Mean iron parameters at the beginning of the study were ferritin 554 ± 296 µg/l, iron 68 ± 21 µg/dl, and iron saturation 30 ± 7.8%. At the end of study, mean ferritin was 609 ± 340 µg/l (p = 0.02), iron 75 ± 27 µg/dl (p = 0.04), and TSAT was 35 ± 13% (p = 0.001). Mean phosphorus and calcium levels were unchanged from baseline at the end of study. Conclusion: Ferric citrate was well tolerated by patients after 4 weeks with no significant clinical or biochemical adverse events related to exposure.

Radioactive 131I use in end-stage renal disease: nightmare or nuisance?

Patients with end‐stage renal disease (ESRD) are at risk of prolonged radiation exposure during therapy with radioactive iodine (131I) because it is normally renally excreted. However, 131I is dialyzable and exposure can be monitored with a standard Geiger counter during dialysis. We present two cases of thyroid carcinoma in patients with ESRD who were treated successfully with 131I while continuing chronic hemodialysis (HD). In each case, single HD treatments of 3 and 4 hours performed approximately 20 hours after the administration of 131I resulted in an 80% and 70% reduction in total body radiation levels, respectively. In both cases, Geiger counter measurements after HD following 131I administration revealed levels less than 3 mR/hr, allowing safe discharge from the hospital in a timely manner. All contaminated waste was disposed of by the hospitals Department of Radiation Safety. Postdialysis monitoring revealed no residual radiation contamination of the HD machine or radiation exposure to the dialysis staff. Hemodialyzer reuse was suspended until monitoring demonstrated no appreciable evidence of radioactivity in these spent supplies. HD is a critical aspect in the treatment of patients with ESRD receiving 131I and can safely be administered with close planning between the HD staff and the staff of radiation safety.

The Phosphate Binder Ferric Citrate and Mineral Metabolism and Inflammatory Markers in Maintenance Dialysis Patients: Results From Prespecified Analyses of a Randomized Clinical Trial

BACKGROUND Phosphate binders are the cornerstone of hyperphosphatemia management in dialysis patients. Ferric citrate is an iron-based oral phosphate binder that effectively lowers serum phosphorus levels. STUDY DESIGN 52-week, open-label, phase 3, randomized, controlled trial for safety-profile assessment. SETTING & PARTICIPANTS Maintenance dialysis patients with serum phosphorus levels ≥6.0 mg/dL after washout of prior phosphate binders. INTERVENTION 2:1 randomization to ferric citrate or active control (sevelamer carbonate and/or calcium acetate). OUTCOMES Changes in mineral bone disease, protein-energy wasting/inflammation, and occurrence of adverse events after 1 year. MEASUREMENTS Serum calcium, intact parathyroid hormone, phosphorus, aluminum, white blood cell count, percentage of lymphocytes, serum urea nitrogen, and bicarbonate. RESULTS There were 292 participants randomly assigned to ferric citrate, and 149, to active control. Groups were well matched. For mean changes from baseline, phosphorus levels decreased similarly in the ferric citrate and active control groups (-2.04±1.99 [SD] vs -2.18±2.25 mg/dL, respectively; P=0.9); serum calcium levels increased similarly in the ferric citrate and active control groups (0.22±0.90 vs 0.31±0.95 mg/dL; P=0.2). Hypercalcemia occurred in 4 participants receiving calcium acetate. Parathyroid hormone levels decreased similarly in the ferric citrate and active control groups (-167.1±399.8 vs -152.7±392.1 pg/mL; P=0.8). Serum albumin, bicarbonate, serum urea nitrogen, white blood cell count and percentage of lymphocytes, and aluminum values were similar between ferric citrate and active control. Total and low-density lipoprotein cholesterol levels were lower in participants receiving sevelamer than those receiving ferric citrate and calcium acetate. Fewer participants randomly assigned to ferric citrate had serious adverse events compared with active control. LIMITATIONS Open-label study, few peritoneal dialysis patients. CONCLUSIONS Ferric citrate was associated with similar phosphorus control compared to active control, with similar effects on markers of bone and mineral metabolism in dialysis patients. There was no evidence of protein-energy wasting/inflammation or aluminum toxicity, and fewer participants randomly assigned to ferric citrate had serious adverse events. Ferric citrate is an effective phosphate binder with a safety profile comparable to sevelamer and calcium acetate.

Laparoscopy in the early diagnosis and management of sclerosing encapsulating peritonitis.

Sclerosing encapsulating peritonitis (SEP) is a rare and dreaded complication that can occur in patients undergoing peritoneal dialysis (PD). Although risk factors have been identified, the diagnosis is difficult and is usually made late in the disease after extensive fibrosis of the peritoneal membrane has occurred, at which point therapy is often fruitless. The high mortality rate of SEP is due to complications resulting from recurrent bowel obstruction, malnutrition, and sepsis. We report three patients with signs and symptoms suggestive of SEP all of whom had normal abdominal CT scans. Nevertheless, each patient underwent diagnostic laparoscopy, which confirmed the clinical suspicion of SEP. In each case, the diagnosis was made before extensive peritoneal fibrosis had occurred allowing therapeutic intervention at an early stage. All three patients subsequently became asymptomatic and thrived. This clinical improvement was supported by the lack of progression to overt peritoneal fibrosis on repeat laparoscopy. We conclude that a high index of suspicion in conjunction with a low threshold for diagnostic laparoscopy may be an effective strategy to establish an early diagnosis and treatment regimen for SEP. Additionally, repeat laparoscopy can be used to guide the length of therapy. These interventions may ultimately improve the long‐term morbidity and mortality of SEP.

Ferric citrate spans mineral metabolism and anemia domains in ESRD: a review of efficacy and safety data

Ferric citrate (Zerenex™, Keryx Biopharmaceuticals, Inc.), a phosphate binder drug candidate, recently completed a Phase III program confirming efficacy and demonstrating safety when used to treat hyperphosphatemia in patients with end-stage renal disease. Results of these trials demonstrate that ferric citrate effectively controls serum phosphorus and is well tolerated. Additionally, these studies demonstrate that ferric citrate improves iron parameters and reduces IV iron and erythropoietin stimulating agent utilization while maintaining hemoglobin levels. These unique features may further benefit the management of end-stage renal disease-related anemia.