Kidney Disease Watch

Specialty Pharmacy Times, February 2011, Volume 2, Issue 1

Naturally High Hemoglobin Not Problematic in Dialysis Patients

Naturally occurring high hemoglobin levels are safe in patients with chronic kidney disease (CKD) on dialysis, according to an epidemiologic study published in the Journal of the American Society of Nephrology in December 2010. The study was part of the large, prospective, international, and observational Dialysis Outcomes and Practice Patterns Study (DOPPS), which enrolled 29,796 patients with kidney disease, 545 of whom had hemoglobin levels >12 g/dL without receiving an erythropoiesis- stimulating agent (ESA). This subgroup was known as the endogenous EPO group. The researchers compared characteristics of this endogenous EPO group with other groups, as well as mortality and quality-oflife scores.

The results showed that the endogenous EPO patients were more likely to be men, have ESRD for a longer duration, and not dialyze via a catheter. Conditions associated with lower oxygen levels in the blood, such as lung disease, cardiovascular disease, and smoking, were also higher in the endogenous EPO group. Quality-of-life scores were not higher among this subset compared with the other patients, and adjusted mortality risk also showed no difference.

Although most guidelines recommend a target hemoglobin maintenance range of 10 to 12 g/dL and caution against a concentration >12 g/dL with use of an ESA, there is a paucity of guidance on how to treat if patients have a concentration >12 g/dL without ESA therapy. Although some guidelines recommend phlebotomizing a dialysis patient who maintains hemoglobin values >12 g/dL without ESA therapy, based on these results, the authors suggest that may not be necessary.

Vitamin D Supplementation Decreases EPO Requirements in Dialysis Patients

Can vitamin D be used effectively for decreasing the doses of recombinant human erythropoietin (EPO) in hemodialysis patients with anemia? Scientists from the University of California, Los Angeles, sought the answer in a study published in the Journal of Nephrology in January/February 2011. The researchers enrolled 81 patients from a southern California facility with end-stage renal disease (ESRD) who received hemodialysis and had documented vitamin D deficiency. The patients were supplemented with ergocalciferol oral capsules for 4 months. Doses of supplementation depended on the severity of deficiency. Simultaneously, monthly doses of EPO were recorded at baseline and after ergocalciferol supplementation. What the researchers found was 46 patients (57%) required significantly less EPO after ergocalciferol compared with baseline (15,450 U/month vs 26,242 U/month; p <0.0001).

Although these results show more than half of the patients were able to decrease their dosage requirements of EPO after vitamin D supplementation, the authors were expecting a higher percentage of patients than was found. They attributed this disparity to the fact that the study was conducted between the months of November and February, when sun exposure is minimal.

High EPO doses are associated with increased mortality, so optimizing benefits of EPO at the lowest possible dose is imperative, according to the authors. The mechanism of how vitamin D supplementation may require less use of EPO is not known, but it may be due to specific vitamin D receptors found on bone marrow EPO cells; vitamin D may stimulate endogenous production of EPO. The study was not randomized, but the authors conclude that the results “should be considered hypothesis generating and should be confirmed with a randomized controlled study,” which will be more conclusive in determining if ergocalciferol can decrease EPO dosage requirements.

Phosphorus Levels May Depend on Source of Protein

The source of protein may affect phosphorus balance in patients with CKD, according to a study published online in the December 2010 issue of the Clinical Journal of the American Society of Nephrology. Patients with CKD, who are often in positive phosphorus balance, excrete excess phosphorus in the urine in response to increases in fibroblast growth factor-23 (FGF23) and parathyroid hormone (PTH).

Researchers from Indiana University School of Medicine in Indianapolis designed a crossover trial in 9 patients with a mean glomerular filtration rate of 32 mL/min and directly compared 7-day vegetarian and meat diets that were equivalent in nutrients. The patients were hospitalized for the last 24 hours of the 7-day diet for frequent urine and blood testing. The researchers found that patients who were on the vegetarian diet had lower serum phosphorus and FGF23 levels, and patients on the meat diet had a significantly higher calcium level during the 24-hour hospitalization period (9.1 vs 8.8 mg/dL; p = 0.0001) and a lower level of PTH.

Study limitations include small sample size and the limited duration of 7 days. Nevertheless, the study shows that although it is generally recommended that patients with CKD limit dietary phosphate intake to 800 mg/day, these patients should also be counseled on the source of this phosphate. Dietary recommendations such as eating more grains and less meat and packaged foods can improve phosphate balance and health outcomes in patients with CKD. SPT