Hemoglobin Targets in Chronic Kidney Disease
Approved by the FDA in 1989, the success of erythropoietin in patients with chronic kidney disease and transfusion-dependent anemia led to trials testing the possible benefits of progressively higher hemoglobin targets. This week’s Annals of Internal Medicine (1) features a systematic review by Palmer et al of 27 trials of erythropoietin and darbepoietin titrated to various hemoglobin targets. The review concludes that hemoglobin targets of >13.0 g/L are associated with increased risk of stroke, hypertension, and vascular site thrombosis and probable increased risk of death, serious cardiovascular events, and end-stage renal disease. The article states that “the rationale for the recommended hemoglobin target of 11.0 to 12.0 g/L in the National Kidney Foundation clinical practice guideline…is unclear.” The authors make no attempt to define a target of their own but do call for trials of fixed doses of the erythropoiesis-stimulating agents (ESA). An accompanying editorial by Weiner and Miskulin refers to the “bursting of the hemoglobin bubble” and mentions “financial incentives promoting greater ESA use.”
Pioglitazone, Vitamin E, or Placebo for Nonalcoholic Steatohepatitis (NASH)
Fatty liver is becoming increasingly common as the American obesity epidemic progresses. During the making of the 2004 documentary Supersize Me, filmmaker Morgan Spurlock developed fatty liver in one month by eating high-fat foods purchased from McDonald’s restaurants. There is no proven therapy for NASH, which can progress to cirrhosis in up to 15% of patients. Insulin resistance and oxidative stress have been implicated as contributors to liver injury in NASH, which is the rationale behind a trial in this week’s New England Journal (2). Sanyal et al randomized 247 nondiabetics with fatty liver at baseline biopsy to the insulin sensitizer pioglitazone (Actos) 30 milligrams daily, the antioxidant vitamin E 800 IU daily, or placebo. The average BMI at baseline was 34 kg/m2. On repeat liver biopsy after 96 weeks of treatment, improvement in histological findings (steatosis, lobular inflammation, hepatocellular ballooning, and fibrosis) was seen in 43% of the vitamin E group (P=0.001) and 34% of the pioglitazone group (P=0.04), compared to 19% of the placebo group. The P value of 0.04 for pioglitazone-versus-placebo was not considered statistically significant; because there were two planned primary comparisons, a higher standard for statistical significance (a “Bonferroni-adjusted” P-value of 0.025) was used. It is likely that both pioglitazone and vitamin E are helpful in the treatment of NASH. The authors caution that their results cannot be generalized to patients with diabetes or cirrhosis.
Barriers to the Use of the Herpes Zoster (Shingles) Vaccine
First of all, let’s straighten out the confusing nomenclature: the disease herpes zoster (commonly known as shingles) is caused by reactivation of the varicella zoster virus that also causes the disease varicella (commonly known as chickenpox). There are 1.2 million cases of herpes zoster in the U.S. per year, and incidence and burden of suffering increase with age. Some degree of post-herpetic neuralgia in the involved dermatome complicates at least half of herpes zoster cases in patients over fifty. The Shingles Prevention Study, the definitive randomized trial, found that the herpes zoster vaccine reduces the incidence of shingles by 51% and postherpetic neuralgia by 67%. In 2008, the CDC’s Advisory Committee on Immunization recommended that all immunocompetent adults aged 60 and over receive a single dose of the live, attenuated herpes zoster vaccine, which has 18 times the varicella zoster virus content of the Oka vaccine given to children aged 1 to 12 to prevent chickenpox. However, only 2% to 7% of eligible Americans have received the herpes zoster vaccine. An article by Hurley et al in this week’s Annals (3) examines the reasons for the low rate of vaccination, which turn out to be primarily financial. The wholesale cost averages $194, making it the most expensive of the vaccines recommended for older adults. It is reimbursed through Medicare Part D (the system Medicare uses to pay pharmacists), not Part B (the system Medicare uses to pay doctors). Purchasing the vaccine entails substantial up-front costs for practices. It needs to be frozen, and patients often need to pick up the vaccine at a pharmacy and “brown-bag” it to the office for administration. The authors correctly maintain that herpes zoster vaccine rates will not improve substantially without changes in the mechanism of reimbursement.
Dr. Tanner is an Associate Editor of Clinical Correlations and Clinical Assistant Professor of Medicine at NYU School of Medicine.