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A Journal on Nephrology and Urology

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Minerva Urologica e Nefrologica 2003 March;55(1):1-11

language: English

The problem of late allograft loss in kidney transplantation

Cardarelli F., Saidman S., Theruvath T., Tolkoff-Rubin N., Cosimi A. B., Pascual M.

Renal and Trans­plan­ta­tion ­Units Mas­sa­chu­setts Gen­er­al Hos­pi­tal Har­vard Med­i­cal ­School, Bos­ton, Mas­sa­chu­setts, USA
Transplantation Center Centre Hospitalier Universitaire Vaudois Lausanne, Switzerland


The 2 prin­ci­pal fac­tors impli­cat­ed in ­late kid­ney allo­graft fail­ure are chron­ic rejec­tion (­also ­called chron­ic allo­graft neph­rop­a­thy) and ­death of the ­patient ­with a func­tion­ing ­graft (main­ly ­from car­di­o­vas­cu­lar caus­es). ­Despite life­long immu­no­sup­pres­sion of the recip­i­ent, immu­no­log­i­cal respons­es ­remain the lead­ing fac­tor in the path­o­gen­e­sis of chron­ic rejec­tion and ­both cel­lu­lar and humo­ral ­immune mech­a­nisms ­have ­been ­shown to ­play impor­tant ­roles.
In ­this ­review, we high­light the rel­e­vance of humo­ral mech­a­nisms of rejec­tion to the path­o­gen­e­sis of ­late allo­graft ­loss. Non immu­no­log­i­cal fac­tors, ­such as ­donor ­organ qual­ity, ­initial ischem­ic inju­ry, cal­ci­neu­rin inhib­i­tor (CNI) tox­ic­ity, hyper­ten­sion, and hyper­lip­i­de­mia, ­also con­trib­ute to pro­gres­sive chron­ic allo­graft inju­ry, but ­will not be ­reviewed in ­detail ­here.
Pos­sible strat­e­gies to sta­bi­lize or ­improve allo­graft func­tion in ­patients ­with ­already estab­lished “chron­ic rejec­tion/chron­ic allo­graft neph­rop­a­thy” (CR/CAN) are the addi­tion of myco­phen­o­late mofe­til (or sirol­i­mus) ­with or with­out a reduc­tion of cyclo­spo­rine dos­age, or con­ver­sion ­from cyclo­spo­rine to tacrol­i­mus. How­ev­er, pros­pec­tive ran­dom­ized clin­i­cal ­trials are need­ed to ­test the effi­ca­cy of ­these strat­e­gies. A ­major cur­rent chal­lenge for trans­plant phy­si­cians is to devel­op reg­i­mens ­that pre­vent CR/CAN, ­since, ­once estab­lished, the pro­cess typ­i­cal­ly pro­gress­es inex­or­ably to ­renal allo­graft ­loss in ­most recip­ients. Evi­dence is now accu­mu­lat­ing ­that new immu­no­sup­pres­sive reg­i­mens ­must con­trol not ­only T ­cell but ­also B ­cell respons­es (i.e. lim­it anti­do­nor anti­body pro­duc­tion) in ­order to pre­vent CR/CAN and ­improve ­long-­term allo­graft sur­vi­val.

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