Spare the Nephron (STN) Studies
Over the past 15 years, first-year graft survival after transplantation of a renal allograft has dramatically improved.40 Although there has also been an improvement in graft half-life beyond one year after transplantation, the magnitude of this improvement has not been proportionate with the improvement seen in early graft survival.
The improvement in early graft survival is undoubtedly related in part to the dramatic reduction in the incidence of acute rejection that has been achieved over the past 15 years.41
With improved immunosuppression, the reason for graft loss has shifted from early to late graft failure. Death with function and chronic rejection are now the two most common reasons for graft loss. In fact, death with a functioning graft accounts for over 50% and chronic rejection for 40% of renal graft losses 6 months following transplantation.42
The quality of graft function in the first year after transplantation is also an important risk factor for long- term graft outcome. Hariharhan et al. reviewed the national renal transplant registry (UNOS/OPTN) experience for the period from 1988 to 1998 and observed a progressive decline in graft half-life for each incremental increase in serum creatinine at 6 months and one year after transplantation.
At Roche we are committed to finding immunosuppressive regimens that preserve renal function in the first year after transplantation that may lead to improved long-term outcomes. Current therapies expose transplant patients to the full range of specific toxicities associated with individual immunosuppressive agents. Optimizing long-term therapy by finding new ways to limit toxicity is a paramount clinical goal of transplantation medicine.
In the near term, incremental improvement in overall posttransplantation outcomes will require fine-tuning the administration of older immunosuppressive agents.
Roche is exploring combinations of certain non-nephrotoxic drugs, including CellCept, in transplant patients and evaluating their effect on renal function (GFR) and graft survival.
References
40Smak Gregoor PJH, de Sevaux RG, Hene RJ, et al. Effect of cyclosporine on mycophenolic acid trough levels in kidney transplant recipients. Transplantation 1999;68:1603-1606.
41Smak Gregoor PJH, van Gelder T, Hesse CJ, et al. Mycophenolic acid plasma concentrations in kidney allograft recipients with and without cyclosporine: a cross-sectional study. Nephrol Dial Transplant 1999; 14: 706-708.
42Berthoux F, Abramowicz D, Bradley B, et al. European best practice guidelines for renal transplantation (part II). Nephrol Dial Transplantation 2002;17:S71-S74
43Hariharan S, Johnson C, Bresnahan B, et al. Improved graft survival after renal transplantation in the United States, 1988 to 1996. NEJM 200; vol. 342, 9:605-612