Testosterone Replacement Therapy in Advanced Chronic Kidney Disease

All subjects will undergo baseline testing that will consist of functional capacity tests, blood tests and muscle biopsies (described in detail below). Subjects will then receive testosterone gel which will be applied daily to the skin of the abdomen or thighs every morning at the same time for 16 weeks. Two days after the hormone treatment is started, the blood testosterone (TT) level will be measured 6 hours after administration. Our goal will be the attainment of serum total TT levels in the mid- to upper normal young adult range. If the serum TT is not at goal, the dose of gel will be increased or decreased repeat testing will be performed within one week. All subjects will be tested for serum TT levels every 4 weeks to assure that the serum total TT remains at goal level. Measurements will be repeated at 8 and 16 weeks.

Inclusion Criteria: Inclusion criteria: CKD subjects; males with calculated GFR (MRDR equation) between 15 and 40 ml/min/1.73m2 and stable or slowly progressive renal failure (decline in function of \<1ml/min/month) including those patients requiring hemodialysis and serum testosterone levels of \<300 ng/ml and capable of safely performing required exercise testing and serum testosterone levels of \<300ng/ml and capable of safely performing required exercise testing. Exclusion Criteria: Exclusion criteria: applicable to both CKD and control subjects. Any unstable chronic medical condition, previous kidney transplant. Uncontrolled diabetes mellitus, active vasculitis, active autoimmune disease, malignancy(\<5 yrs), obesity (BMI \> 35), alcoholism or other recreational drug use, active heart disease, angina, uncontrolled arrhythmias or myocardial infarct within past 3 months, peripheral vascular disease with claudication, active lung, liver or GI disease, sleep apnea, medically unstable subjects and subjects who received anabolic, catabolic or cytotoxic medications during the prior 3 months. History of prostate CA, PSA \>4g/ml, or advanced BPH (AUA symptom score \> 21) and abnormal prostate on digital rectal examination. Bone or joint abnormalities that would preclude exercise testing.