The purpose of this study is to evaluate the safety and efficacy of conversion from a calcineurin inhibitor (tacrolimus or cyclosporine) immunosuppression therapy to Nulojix® (belatacept) immunosuppression therapy in patients with delayed (DGF) or slow graft function (SGF) following kidney transplantation. Patients at risk for SGF or DGF will be consented at the time of kidney transplantation. On post-op Day 5 the patient will be assessed, if they have developed SGF or DGF they will be randomized to convert to Belatacept or continue on their CNI regimen. Up to 20 subjects who do not develop DGF will be followed as control subjects. Seventy randomized subjects will be followed for a total of 14 months with a renal biopsy at Month 12 post transplant. Research Hypotheses: Primary Hypotheses: * Kidneys with slow or delayed graft function are more susceptible to acute and long-term CNI toxicity * Kidneys converted from calcineurin inhibitor based therapy to belatacept will achieve a more rapid recovery from post-ischemic acute tubular necrosis (ATN) and will have improved 1 year calculated GFR. Key Secondary Hypotheses: * Renal Histology: Belatacept converted patients will have a lower chronic allograft damage index (CADI) score and lower interstitial fibrosis and tubular atrophy (IF/TA) score as calculated by Banff criteria at 1 year post- transplant * Biomarker Analysis: Biomarker analysis (clusterin) measured in serial urine collections can 1) directly assess CNI induced kidney injury and 2) improve the prediction of patients that benefit in early belatacept conversion.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
90
Mount Sinai School of Medicine Recanati/Miller Transplantation Institute
New York, New York, United States
RECRUITINGcGFR
Serum creatinine will be checked at each study visit from which GFR will be calculated. 12 month 4 variable MDRD calculated GFR will be compared between the belatacept conversion group and the calcineurin inhibitor group.
Time frame: 12 months
Renal Histology
Chronic Allograft Damage Index (CADI) and Interstitial Fibrosis/Tubular Atrophy (IFTA) renal pathology scores will be assessed by a local pathologist. CADI and IF/TA will be recorded at baseline (reperfusion biopsy) and at the 1 year protocol biopsy. The average progression of CADI and IF/TA will be compared in both groups and the average absolute CADI and IF/TA scores will be compared in both groups at 1 year post transplant.
Time frame: 12 months
Biomarker profile
The results of urine biomarkers (clusterin) will be correlated with the development of the primary and secondary endpoints in both groups. In this manner the investigators will be able to understand which genes/proteins are primarily altered by injury and assess how belatacept affects this process.
Time frame: 12 months
Duration of Delayed (or slow) Graft Function
The average duration of DGF/SGF will be compared in both belatacept and CNI groups
Time frame: 12 months
Incidence of Acute Rejection
Acute rejection by month 12 will be assessed by a local pathologist using the Banff 97 working classification of kidney transplant pathology. All biopsies will be interpreted locally for purposes of the study.
Time frame: 12 months
New Onset Diabetes
Subjects will be evaluated for post-transplant diabetes at visits after week 4.
Time frame: 12 months
Blood Pressure Control
Subjects are to be evaluated at each clinic visit to assess the need for adjustment of antihypertensive medication in order to achieve a BP of \< 130/80 mmHg. Average systolic and diastolic blood pressure in both groups at Month 12, number of antihypertensive medications and change in intensity of hypertension treatment will be observed.
Time frame: 12 months
Dyslipidemia
Cholesterol levels in both groups, number of patients on dyslipidemic therapy at month 12 and change in intensity of dyslipidemia therapy will be observed
Time frame: 12 months
Graft Survival
Graft survival will be observed in both groups and compared at 12 months post-transplant
Time frame: 12 Months
Patient survival
Patient survival will be observed in both groups and compared at 12 months post-transplant
Time frame: 12 months
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