The Bergamo Kidney Transplant Program.
Since the beginning of transplant activities in 1989, the Kidney Transplant Center at the Ospedali Riuniti Bergamo has based its clinical program on the most recent achievements of transplant medicine, in order to optimize the outcome of kidney grafts and improve the quality of life of kidney transplant recipients. Although the transplantation community attempts to keep up with increasing demand for transplantable organs, the supply continues to fall far short of the need. This observation prompted us to focus on the expansion of the available pool of deceased donor organs. In 1997, we established a dual kidney transplant program for donors older than 60 years based on a pretransplant histology protocol with a scoring system ranging from low-dose RATG and delayed CsA administration has been successfully adopted in this population of kidney transplant recipients in our routine clinic practice. In kidney transplantation, chronic deterioration of renal function and death with a functioning graft, mainly due to side effects of the medications, represents a major limitation for long-term success of many transplant programs. We recently documented that per-protocol biopsy more than one year after kidney transplantation is a safe procedure to guide change of conventional immunosuppressive regimens and to lower the risk of major drug-related side effects. In particular, substantial reduction of the CsA dose, leading to extremely low CsA trough level, has no major detrimental effect on renal function and histology during 3 years follow-up, while patients remain free of rejection episodes with concomitant steroid and azathioprine therapy. Novel induction therapies with Campath-1H or Simulect and low-RATG have also helped to minimize maintenance immunosuppression in most patients largely avoiding the use of corticosteroids, Monitoring a patient's exposure to immunosuppressive agents is a critical issue in a minimum of 0 (no renal lesions) to a maximum of 12 (marked changes in renal parenchyma). The assumptions of the proposed algorithm to guide acceptance of single suboptimal or dual marginal kidneys for transplantation were validated in a prospective pilot study involving centers in Europe and North America. Whether the encouraging short-term data translate into improved graft survival is currently a matter of investigation in a prospective, multicenter, matched-cohort trial. As kidneys from marginal donors have an increased risk of delayed graft function, we also studied strategies to manage and prevent this complication. A dual immunosuppressive regimen of basiliximab and transplantation. By pharmacokinetics studies, we documented that a fixed dose regimen of MMF--adopted in the majority of transplant units worldwide--might no longer be the best approach for the management of transplant patients, and MPA pharmacokinetic monitoring is advised. Similarly, we reported pharmacokinetic interaction of concomitant immunosuppression on blood levels of the new immunosuppressant sirolimus. We have a special multiorgan transplant program at our center for patients affected by rare diseases, such as the recurrent hemolytic uremic syndrome (HUS). Based on genotyping for complement factor H-1, membrane co-factor protein or factor I gene mutations, we are exploring the possibility of combining liver and renal transplant or performing renal transplant alone in patients with recurrent HUS who have end-stage renal disease. The achievements of our clinical center are the result of the continuous support by an intense clinical and basic research program. This has allowed us to create a unique model to address the major challenges of transplant medicine.
Perico
Norberto
N
Department of Medicine and Transplantation, Ospedali Riuniti - Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
Cravedi
Paolo
P
Ruggenenti
Piero
P
Gotti
Eliana
E
Rota
Giovanni
G
Locatelli
Giuseppe
G
Gambara
Vincenzo
V
Perna
Annalisa
A
Rota
Stefano
S
Remuzzi
Giuseppe
G
D002102:Cadaver; D006085:Graft Survival; D016027:Heart Transplantation / Q000401:mortality / Q000706:statistics & numerical data; D006801:Humans; D007558:Italy; D016030:Kidney Transplantation / Q000401:mortality / Q000706:statistics & numerical data*; D016031:Liver Transplantation / Q000401:mortality / Q000706:statistics & numerical data; D019520:Living Donors / Q000706:statistics & numerical data; D018579:Patient Selection; D016019:Survival Analysis; D013997:Time Factors; D014019:Tissue Donors / Q000706:statistics & numerical data / Q000600:supply & distribution