Pancreas After Kidney Transplantation?
What are the current recommendations for minimum level of renal function in a candidate for pancreas after kidney (PAK) transplantation, pancreas transplant alone, or pancreatic islet transplant? Since the potential PAK recipient is often already on tacrolimus or cyclosporine, is a lower creatinine clearance acceptable in this group?

Robert Harland, MD

In potential candidates for pancreas alone transplantation, a creatinine clearance above 60-70 mL/min is usually required because immunosuppression can cause accelerated deterioration of native renal function in those with a lower creatinine clearance. In 233 pancreas alone transplant recipients at the University of Minnesota, 36 patients (15.4%) subsequently required a kidney transplant. The actuarial probability of this occurrence was 4% at 1 year and 10% at 5 years. This risk was present regardless of whether or not the patient exhibited long-term pancreas function. Although sparse data are available on the contribution of proteinuria, most centers prefer to transplant patients with a 24-hour urine protein excretion below 2 g. Immunosuppression with calcineurin inhibitors will reliably decrease the creatinine clearance by 25%, but it is unknown whether significant proteinuria can cause a greater decline in renal function with these agents. In patients with borderline native renal function, a trial of tacrolimus (TAC) or cyclosporine (CsA) may be indicated to assess renal reserve (TAC or CsA challenge). The decision to offer pancreas alone transplantation is also influenced by the availability of a living kidney donor as well as the severity and progression of diabetic complications.

For islet transplant candidates, a creatinine clearance above 70-80 mL/min and protein excretion below 500 mg are usual requirements. For PAK candidates, a creatinine clearance above 40 mL/min is recommended if the patient is already on a calcineurin inhibitor. If the patient is receiving calcineurin-free immunosuppression after kidney transplant, a creatinine clearance of 55 mL/min or greater is considered safe. Again, it is unclear how to factor the level of proteinuria into the decision analysis, particularly since the use of a calcineurin inhibitor will decrease the actual level of proteinuria. In general, if the serum creatinine is above 2.5 mg/dL in a male and above 2.0 mg/dL in a female, then it may be "too late" to proceed with a PAK transplant and the patient may have to wait to "qualify" for a preemptive simultaneous pancreas-kidney transplant. A baseline kidney transplant biopsy might be useful to document, quantify, and monitor the progression of nephropathy after PAK transplantation. However, there are little data and experience in using the biopsy results to guide the timing and type of pancreas transplant. The presence of chronic allograft nephropathy might be a contraindication to proceeding with a PAK transplant in a patient with otherwise stable renal allograft function.