1. Anemia in CKD The TREAT Trial Reference Pfeiffer MA. A trial of Darbepoetin alpha in type II diabetes and chronic kidney disease. N Engl J Med. 2009;361:2019–2032.

2. Background Anemic patients with type II diabetes and chronic kidney disease (CKD) show greater risk towards cardiovascular disease. The effect of Darbepoetin alpha on the clinical outcome in these cases is to be tested.

3. Aim To investigate whether administration of Darbepoetin alpha decreases the risk of cardiovascular disease in anemic patients suffering from type II diabetes and CKD.

4. Method Study design: The TREAT trial was a randomized, double-blind, placebo- controlled multicentre trial. Study population: The study involved 4038 patients with type II diabetes and chronic kidney disease (estimated glomerular filtration rate [GFR] of 20–60 ml/min per 1.73 m 2 of body surface area, anemia (patients with hemoglobin levels, ≤11.0 g/dl), and with transferrin saturation of 15% or more were considered for the trial. For the trial, the selected patients should have atleast one of the following criterion: uncontrolled hypertension; kidney transplantation or scheduled for a kidney transplant, undergoing treatment with intravenous antibiotics, chemotherapy or radiation therapy; those diagnosed for cancer (except those diagnosed for basal-cell or squamous cell carcinoma of the skin); human immunodeficiency virus infection (HIV infection); having a hematologic disease or having bleeding or pregnancy. Those patients who have grand mal seizure or a cardiovascular event or underwent a cardiovascular surgery or who received an ESA in last 12 weeks before trial were not included in the trial.

5. Treatment regimen: Randomization (1:1) was achieved by determining the baseline level of proteinurea (ratio of total protein to creatinine of ≥1.0 in spot urine sample) and designated history of cardiovascular disease. Drug and placebo were administered in groups simultaneously. The drug concentrations were managed through computer algorithm such that the hemoglobin levels in patients/volunteers were maintained at 13 g/dl. In cases of drastic drop in hemoglobin in patients on placebo, Darbepoetin alpha was administered to maintain the levels. Hemoglobin levels were monitored every 2 weeks, ferritin and transferrin levels were monitored every quarterly and spot urine collections at 24-week intervals. Reported outcomes of trial were assessed at 1, 13 and 25 weeks, and 24 weeks thereafter. Each visit was used to gather information regarding adverse events, hospitalization, concomitant use of other medications and transfusions. End point: Primary end points were assigned as composite outcome of death from any cause or either a cardiovascular event or end-stage renal disease.

6. Results A cardiovascular event or death occurred in 632 patients out of 2012 patients assigned to Darbepoetin alpha and in 602 patients out of 2026 patients assigned to placebo. In 652 patients assigned to Darbepoetin alpha and 618 patients in placebo group renal composite end point has noticed. Fatal and/or non-fatal stroke was observed in 101 patients in the Darbepoetin alpha group and 53 patients in placebo group, whereas red cell transfusion was required to be carried out for 297 in Darbepoetin alpha group and 496 in placebo group. The detailed results can be summarized as table below.

13. Conclusion Darbepoetin alpha in the study has not reduced the risk to the lives of patients having a cardiovascular disease or chronic kidney failure along with moderate anemia not undergoing dialysis. Thus, for people involved in decision-making the potential risks will outweigh the potential benefits of Darbepoetin alpha. Darbepoetin alpha has not reduced the risk to the lives of patients with cardiovascular disease or chronic kidney failure along with moderate anemia not undergoing dialysis.

14. Result After 4 weeks, the LDL cholesterol levels in the atorvastatin group were reduced by 42% as compared to 13% in the placebo group. However, over the follow-up time of 4 years, the reduction in LDL cholesterol levels did not alter the primary end point of cardiovascular death, MI or stroke. The treatment showed no effect on the primary end point except for fatal stroke which significantly increased in the atorvastatin group. The cardiac events were reduced in the atorvastatin group but there was no reduction in the cerebrovascular events or mortality thereby. There was no effect on the sudden cardiac deaths, which are normally reduced by statin therapy.

17. Conclusion In patients with type 2 diabetes on maintenance hemodialysis, routine statin treatment does not reduce the primary end point of death from cardiac causes, myocardial infarction or stroke. The routine statin treatment in patients with type 2 diabetes on maintenance hemodialysis has not reduce the death from cardiac causes, MI or stroke.