A Study on the Effect of Hemoglobin Level and the Vascular Reactivity Using th Generic Erythropoeitin Alpha (Renogen) on Incident Peritoneal Dialysis Patients

This is an investigator-initiated study partially subsidized by the Unilab- Biomedis- Biomedis by providing the drug Renogen® 4,000 units/vial, H2 Receptor Blocker and Ferrous Sulfate. The supporting company will also pay the monthly laboratory and ultrasound of the brachial artery of the patients. All patients for inclusion will sign an informed consent. The study will be conducted for 3 months. Patients will be required to follow-up at least twice a month for 3 months to give the 2 week supply of erythropoietin alpha (Renogen), administration of subcutaneous drug, give the laboratory request , for physical examination and to return the pre filled syringe to monitor their compliance. The patients will be given free Renogen, H2 Blockers and ferrous sulfate, free monthly CBC test and ultrasound of the brachial artery on baseline and after the 3rd month of the administration of the drug. No monetary compensation will be given to the patient.

The following data will be collected: patient age, sex, primary renal disease, and weight. The following laboratory data will be collected at baseline: complete blood count, reticulocyte count, blood urea nitrogen, serum creatinine, lipid profile, albumin, calcium, phosphorus, ALT, serum ferritin, TIBC, reticulocyte count, CRP and albumin and ultrasound of the brachial artery to assess the flow mediated dilatation. The following laboratory test will be repeated on the 1st and 3rd month. CBC will be repeated monthly. Reticulocyte count, TIBC and serum ferritin will be repeated after 1 month of using Renogen. Serum ferritin needs to be >200 and TSAT ng/ml prior to entry into the study. The patient will have a folder for medical record keeping. Only the investigators can access the patients' medical record and all subsequent recording of data will be anonymized. The investigators may generate or derive in the course of performing the Study (''Confidential Information''), to use such confidential information only for the purpose of the study, and not to transfer or disclose confidential information to any third party other than study personnel involved in the performance of the study with ''need to know''.

Vascular Assessment

Endothelium-dependent flow-mediated vasodilatation and endothelium-independent vasodilatation (NMD) of the brachial artery will be assessed non-invasively, using high-resolution ultrasound based on the International Brachial Artery Reactivity Task Force. Measurements will be performed using a single observer using an ATL 5000 ultrasound system (Advanced Technology Laboratories Inc., Bothell, WA, USA) with a 12-MHz prob. All vasoactive medications will be withheld for 24h before the procedure. The subjects will remain at rest in the supine position for at least 15min before the examination starts. Subject's arm will be comfortably immobilized in the extended position to allow consistent recording of the brachial artery 2-4cm above the antecubital fossa. Three adjacent measurements of end-diastolic brachial artery diameter will be performed from single two-dimensional frames. All ultrasound images will be recorded on an S-VHS videotape for subsequent blinded analysis. A pneumatic tourniquet will be inflated to 300mmHg with obliteration of the radial pulse. After 5min, the cuff will be deflated. Flow measurements will be performed 60s after deflation. After a further 15min, measurements will be repeated, and after 3 minutes of administration of sublingual glyceryl trinitrate (400mcg). Nitroglycerine will be given to determine the maximum obtainable vasodilator response, and to serve as a measure of endothelium-independent vasodilation reflecting vascular smooth muscle function. NTG should not be administered to individuals with clinically significant bradycardia or hypotension. The maximum FMD diameters will be calculated as the average of the three consecutive maximum diameter measurements after hyperemia and nitroglycerin, respectively. The FMD will then calculated as the percent change in diameter compared with baseline resting diameters.

Patients will be censored at death, modality change (PD to HD or to kidney transplantation), or at the end of the follow-up period. Patients who will not complete the three months study period and the reasons for their withdrawal will be described.