Kidney Allograft Dysfunction Without Reversible Causes

Inclusion Criteria: 1. Serum creatinine increased greater than or equal to 25% over baseline with no acute or reversible cause clinically evident. Although eGFR is arguably better for estimating kidney allograft function than serum creatinine, pragmatics dictate the use of a change in serum creatinine in the initial selection of patients. These criteria are currently used by transplant coordinators for selection of patients for the kidney biopsy as a part of large on-going study at our center. 2. Adequate (greater than or equal to 8 glomeruli) biopsy showing Chronic allograft injury reported as mild/moderate CAN or CNI toxicity based on the previously used Banff 97 classification and no potentially reversible causes of graft dysfunction, e.g. acute rejection or treatable recurrent disease. Patients with histological evidence of mild recurrent disease that does not appear to be severe enough to explain the deterioration in function, e.g. IgA on immunofluorescence, or changes consistent with early diabetic nephropathy, will not be excluded. 3. Receiving CsA (trough level concentration 75-125 ng/mL) or Tacrolimus(trough level concentration 6-12 ng/mL) plus MMF (or AZA) with (or without) prednisone. 4. Able to give informed consent. Exclusion Criteria: 1. Urine total protein excretion \>500 mg/g creatinine. 2. eGFR (estimated by MDRD) \<40 mL/min/1.73 m2 3. Triglycerides \>400 mg/dL or total cholesterol \>300 mg/dL 4. Allergy to macrolide antibiotic or rapamycin 5. Women of child-bearing potential not using effective contraception 6. Treated for acute rejection within the past 2 months 7. \<12 months after transplantation 8. Potentially treatable cause(s) of allograft dysfunction, including acute rejection, dehydration, and congestive heart failure. 9. Recurrent or de novo kidney disease that is histologically severe enough to be causing graft dysfunction 10. Polyoma virus (BK) nephropathy, or serum positive for BK by polymerase chain reaction 11. A second, functioning organ transplant. 12. Receiving sirolimus. 13. Patients with any past or present malignancy (other than non-melanoma skin cancer)