Anemia due to Coadministration of Renin-Angiotensin-System Inhibitors and PPARγ Agonists in Uncomplicated Diabetic Patients

Abstract

Aims: Therapy with either angiotensin converting enzyme inhibitors and angiotensin receptor blockers (ACEI/ARB) or thiazolidinediones (TZD) is associated with dose-dependent decrements in hematocrit and hemoglobin levels. We aimed to investigate the impact of the coadministration of TZD and ACEI/ARB on hematocrit and hemoglobin values in uncomplicated patients with type 2 diabetes mellitus and normal serum creatinine. Methods: Data from patients with type 2 diabetes currently followed, were reviewed and patients treated with ACEI/ARB and/or TZD were identified. For the purpose of this study the following 4 groups of 30 stable non-anemic diabetic patients each matched for age, gender, and BMI were formed. Group ACEI/ARB included patients on ACEI/ARB without TZD, group TZD included patients on TZD and antihypertensive agents other than ACEI/ARB, group ACEI/ARB/TZD consisted of patients on combined therapy with ACEI/ARB and TZD and the control group C included patients never exposed to ACEI/ARB or TZD. Clinical and laboratory data were collected prior to initiation of treatment and after 6 months. Results: Neither hematocrit nor hemoglobin showed any significant change from baseline at the end of the study in group C. In both group ACEI/ARB and group TZD a small, but statistically significant reduction in hematocrit (~?1% point) and hemoglobin levels (~?0.3 g/dl) was seen. A greater statistically and clinically important reduction in hematocrit (~?3% points) and hemoglobin (~?1?g/dl) levels was observed in group ACEI/ARB/TZD. Furthermore, incident anemia at the end reached 7% in group TZD and 23% in group ACEI/ARB/TZD. Conclusions: Coadministration of RAS inhibitors and PPAR-? agonists should be considered in the differential diagnosis of hematocrit lowering and anemia in uncomplicated type 2 diabetic patients with normal serum creatinine. Further studies are required to clarify the mechanism(s), the cardiovascular consequences and the cost utility of anemia workup in such patients.

Anemia complicating type 2 diabetes: Prevalence, risk factors and prognosis

“…39 In the case of glitazone therapy, fluid retention and consequent hemodilution are well recognized, especially in patients treated with renin-angiotensin system inhibitors. 40 The inverse association with diastolic blood pressure is likely to reflect the hemodynamic consequences of anemia. The positive association with PAD has been reported previously 41,42 and may relate to marked oxidative stress, inflammation and atherothrombosis that contribute to dyserythropoiesis and a shortened red cell lifespan in type 2 diabetes.…”

Anemia and Reduced Renal Function are Independent Predictors of Elevated Serum Adiponectin in Elderly Women

“…More than half of the study participants were lacking drug information, so the possible contribution of these drugs to adiponectin levels or other parameters could not be completely excluded. Finally, we did not measure B-type natriuretic peptide (BNP), a reliable marker of heart failure 41) . In addition to anemia and CKD, chronic heart failure is common in the elderly and has been shown to be associated with elevated serum adiponectin 7) .…”

PPARγ and Its Agonists in Chronic Kidney Disease

“…For example, some studies proved that TZDs contributed the fluid retention by altered sodium and water reabsorption in the distal collecting ducts of the kidney [23,110]. Clinical research figured out that uncomplicated diabetic patients' combined use of RAAS inhibitors and PPARc agonists promotes anemia [111]. Besides, people with long-term TZDs drug treatment are also peculiarly prone to the osteoporosis and heart failure [112].…”