Renal Transplantation in Recipients With Nephropathic Cystinosis

Cystinosis is an autosomal recessive disorder due to impaired cystine transport across the lysosomal membrane, resulting in abnormal cystine accumulation throughout the body. Fanconi syndrome manifests in the first year of life, and end-stage renal failure occurs at \~10 years of age, requiring dialysis or kidney transplantation. Oral cysteamine therapy delays but does not always prevent the need for a renal allograft in cystinosis, which accounts for \~3% of all pediatric transplants in the United States. With improvements in immunosuppression, short-term graft and patient survival is quite good for cystinosis patients, although not as good as for patients with ESRD due to structural defects. Long-term graft survival can be affected by the non-renal complications of cystinosis, which persist after renal transplantation. The aim of this study is to establish standards for the transplantation of kidneys into patients with nephropathic cystinosis using steroid-sparing immunosuppression. Our goals are to: 1. Analyze the long and short term outcome of cystinosis patients following living and cadaveric kidney transplantation using steroid-free immunosuppression; 2. Determine a consistent clinical approach to recipients with cystinosis in the immediate post-operative period, specifically regarding fluid and electrolyte management, retention of native kidneys, and timing of the re-initiation of cystinosis therapy after transplantation; 3. Assess the immunologic impact of cystinosis by monitoring immune responses using a number of in vitro assays. In this study, patients will receive a living donor or cadaveric kidney transplant with steroid free immunosuppression. Graft function, histology and graft and patient survival will be measured. Progression of cystinosis in other organ systems will be monitored. Additional studies on the graft will include transcriptional analysis of inflammatory and immunologic mediators. Serum will be assayed for inflammatory mediators and peripheral white blood cells assayed for immune function. This study will represent the first comprehensive, prospective analysis of kidney transplantation in patients with cystinosis.