Thiazolidinedione Safety and Efficacy in Ambulatory Patients Receiving Hemodialysis

Harold J. Manley, Pharm.D., Nicole M. Allcock, Pharm.D.

Disclosures

Pharmacotherapy. 2003;23(7) 

In This Article

Abstract and Introduction

Study Objectives: To determine whether thiazolidinediones cause significant changes in intravascular volume, anemia, or chronic heart failure; to determine which thiazolidinedione, rosiglitazone or pioglitazone, has a greater propensity to cause these adverse effects; and to evaluate thiazolidinedione efficacy in patients with diabetes mellitus and end-stage renal disease who require hemodialysis.
Design: Retrospective chart review.
Setting: Ambulatory hemodialysis clinic.
Patients: Forty ambulatory patients receiving hemodialysis.
Measurements and Main Results: Of the 40 patients (26 men, 14 women, mean ± SD age 64.8 ± 11.5 yrs), diabetes mellitus was the cause of end-stage renal disease in 37 (92.5%). The men were older than the women (mean ± SD age 67.65 ± 11.43 yrs and 59.58 ± 10.6 yrs, respectively, p=0.03). Additional demographic data collected were start date and cause of end-stage renal disease, comorbid conditions, drug profile, hospitalization dates, and reason for admission. Laboratory values were obtained for hematocrit, iron indexes (transferrin saturation and ferritin), mean corpuscular volume, and hemoglobin A1c (A1C); body weight before and after dialysis, and predialysis systolic and diastolic blood pressures were measured. All monitoring parameters were evaluated for 3 months before and after the start of therapy. Three patients were hospitalized for new or worsening chronic heart failure (two were receiving rosiglitazone therapy, one pioglitazone, p=0.555). Changes in A1C values were reviewed to determine thiazolidinedione efficacy; no statistical difference was observed between thiazolidinedione agents prescribed. Combined thiazolidinedione data yielded nonsignificant effects for all clinical and laboratory findings except A1C (-0.61%, p=0.05) and blood pressure (systolic -5.57 ± 12.09 mm Hg, p=0.01; diastolic -3.24 ± 6.17 mm Hg, p=0.002).
Conclusion: Thiazolidinedione therapy is safe and effective for ambulatory patients receiving hemodialysis. However, as we found that these drugs reduced systolic and diastolic blood pressure, further investigation into this drug effect is warranted.

More than 378,000 people in the United States have end-stage renal disease (ESRD), and this number is projected to nearly double by 2010. Diabetes mellitus is the primary cause of ESRD, accounting for approximately 40% of patients.[1] Although insulin is the principal antidiabetic agent administered in ambulatory patients receiving hemodialysis, approximately 25% of those with diabetes who receive hemodialysis are prescribed oral hypoglycemic agents.[2,3] Administration of these agents is necessary to maintain tight control (hemoglobin A1c [A1C] < 7.5%) of the diabetes and thus decrease mortality.[4]

Thiazolidinediones, a relatively new class of oral hypoglycemic agents, may be administered to treat diabetes in patients receiving hemodialysis, and they are considered safer than other oral hypoglycemic agents. For patients with diminished renal function, other such agents are contraindicated,[5] have been inadequately studied,[6,7] may be ineffective, or may place them at increased risk of hypoglycemic episodes.[8] Thiazolidinediones also reduce insulin resistance,[9,10] which is a risk factor for mortality in patients with ESRD.[11]

Nonetheless, thiazolidinedione therapy involves increased risk for adverse effects, which may be due to thiazolidinedione-induced intravascular volume expansion, leading to anemia, edema, and chronic heart failure.[12,13] These adverse effects may be problematic for patients receiving hemodialysis because they have difficulty with intravascular fluid volume management. Increases in intravascular volume also exacerbate hypertension in patients receiving hemodialysis. Finally, many patients receiving hemodialysis rely on erythropoietin therapy to treat their anemia of chronic kidney disease.[14] Erythropoietin therapy is very expensive, and any concomitant drug therapy that reduces its efficacy would be wasteful.

Patients receiving hemodialysis typically visit a dialysis clinic 3 times/week. Before each session, the patient is weighed to determine the difference between actual body weight and nephrologist-determined desired (dry) weight. Any observed difference is assumed to be excess water, since any acute change in weight since the last hemodialysis session (< 48-72 hrs) would be due to changes in water balance.

Although thiazolidinediones have not been adequately studied in patients receiving hemodialysis, clinical trials have been conducted in relatively healthy patients with diabetes. The frequency of anemia and edema due to thiazolidinediones is small enough in the general population for thiazolidinediones to be considered safe. However, no studies we know of have determined the frequency of thiazolidinedione-associated anemia, exacerbation of hypertension, or chronic heart failure in patients with diabetes receiving hemodialysis.

Therefore, at our ambulatory hemodialysis clinic, we conducted a review of all patients with diabetes who were receiving thiazolidinedione therapy. Our objectives were to determine whether thiazolidinediones cause significant changes in intravascular volume, anemia, or symptoms of chronic heart failure; to determine which thiazolidinedione, rosiglitazone or pioglitazone, has a greater propensity to cause these adverse effects; and to evaluate thiazolidinedione efficacy in patients with diabetes mellitus and ESRD who require hemodialysis.

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