Læknablaðið - 15.09.2000, Blaðsíða 20

FRÆÐIGREINAR / LÍFFÆRAFLUTNINGAR
halda steraskammti í lágmarki, fitusnauðu fæði og
kólesteróllækkandi lyfjameðferð (74). Statín eru
kjörlyf sökum virkni þeirra og lítilla aukaverkana.
Nýrnabilun: Cýklósporín og takrólímus geta leitt
til langvinnrar nýmabilunar hjá líffæraþegum
(75,76). Eldri rannsóknir á hjartaþegum sýndu að allt
að 10% fengu lokastigsnýrnabilun eftir átta ára
cýklósporínmeðferð (77). Nýlegri rannsóknir benda
til mun lægri áhættu samfara lægri skömmtum
cýklósporíns eða innan við 3% (78). Mikilvægt er að
forðast önnur lyf sem geta haft skaðleg áhrif á nýru.
Beinsjúkdómar: Beinþynning er algengt vanda-
mál meðal líffæraþega. Sterar valda minnkun
beinmassa og cýklósporín og takrólímus hafa einnig
áhrif í þá veru (77). Mikilvægt er að fylgjast með
beinþéttni. Meðferð er svipuð og hjá öðrum sjúk-
lingum með beinþynningu, það er kalsíum og D
vítamín, bisfosfonöt, ásamt estrógen uppbótar-
meðferð hjá konum eftir tíðahvörf. Beindrep, oftast í
lærleggshaus, sést hjá allt að 15% líffæraþega og
krefst yfirleitt ísetningar gerviliðs. Það er talið
tengjast sterameðferð.
Niðurlag
Skammtíma lifun ígræddra líffæra er nú mjög góð en
hægfara tap græðlinga af völdum langvinnrar höfn-
unar er mikið vandamál. Framfarir á sviði ónæmis-
bælandi meðferðar hafa ekki haft nein teljandi áhrif á
það ferli. Nauðsynlegt er að finna sértækari ónæmis-
bælandi lyf sem fyrirbyggja höfnun hins ígrædda
líffæris en hafa ekki í för með sér alvarlega fylgikvilla
eins og sýkingar og krabbamein. Endanlegt markmið
er að þróa aðferðir til að framkalla þol (tolerance)
gegn ígræddum líffærum. Takist það verður ónæmis-
bælandi meðferð væntanlega óþörf og þá munu þær
alvarlegu aukaverkanir sem henni fylgja verða úr
sögunni.
Heimildir
1. Murray J, Merrill J, Harrison J, Wilston R, Dammin G.
Prolonged survival of human kidney homografts by
immunosuppressive drug therapy. N Engl J Med 1963; 268:
1315-23.
2. Borel J. Comparative study of in vitro and in vivo drug effects
on cell-mediated cytotoxicity. Immunology 1976; 31: 631-41.
3. European Multicenter Trial Group. Cyclosporine in cadaveric
renal transplantation: one year follow up of a multicenter trial.
Lancet 1983; II: 986-9.
4. Penn I. The effect of immunosuppression on preexisting
cancers. Transplantation 1993; 55:742-7.
5. Watanabe F, Mullon C, Hewitt W, Arkadopoulos N, Kahaku
E, Eguchi S, et al. Clinical experience with a bioartificial liver
in the treatment of severe liver failure. A phase I clinical trial.
Ann Surg 1997; 225:484-91.
6. Scherr K, Jensen L, Koshal A. Mechanical circulatory support
as a bridge to cardiac transplantation: toward the 21st century.
Am J Crit Care 1999; 8: 324-37.
7. Krensky A, Weiss A, Crabtree G, Davis M, Parham P. T-
lymphocyte-antigen interactions in transplant rejection. N
Engl J Med 1990; 322: 510-7.
8. Germain R. MHC-dependent antigen processing and peptide
presentation: providing ligands for T lymphocyte activation.
Cell 1994; 76: 287-99.
9. Sayegh M, Turka L. The role of T cell costimulatory activation
in transplant rejection. N Engl J Med 1998; 338:1813-21.
10. Miceli M, Parnes J. The roles of CD4 and CD8 in T cell
activation. Semin Immunol 1991; 3:133-41.
11. Smith K. Interleukin-2: inception, impact and implication.
Science 1988; 240:1169-76.
12. Williams G, Hume D, Hudson RJ, Morris P, Kano K, Milgrom
F. "Hyperacute" renal-homograft rejection in man. N Engl J
Med 1968; 279: 611-8.
13. Rush D, Nickerson P, Gough J, McKenna R, Grimm P, Cheang
M, et al. Beneficial effects of treatment of early subclinical
rejection: a randomized study. J Am Soc Nephrol 1998; 9:
2129-34.
14. Tullius SG, Tilney NL. Both alloantigen-dependent and -
independent factors influence chronic allograft rejection.
Transplantation 1995; 59: 313-8.
15. Carpenter CB. Long-term failure of renal transplants: adding
insult to injury. Kidney Int 1995; 48/Suppl. 50: S40-S44.
16. Kahan BD. Cyclosporine. N Engl J Med 1989; 321: 1725-38.
17. O'Keefe S, Tamura J, Kincaid R, Tocci M, O'Neill E. FK-506-
and CsA-sensitive activation of the interleukin-2 promoter by
calcineurin. Nature 1992; 357: 692-4.
18. Fruman D, Klee C, Bierer B, Burakoff S. Calcineurin
phosphatase activity in T lymphocytes is inhibited by FK 506
and cyclosporin A. Proc Natl Acad Sci USA 1992; 89:3686-90.
19. Kovarik J, Mueller E, van Bree J, Fluckiger S, Lange H,
Schmidt B, et al. Cyclosporine pharmacokinetics and
variability from a microemulsion formulation: multicenter
investigation in kidney transplant patients. Transplantation
1994; 58: 658-63.
20. Sawada S, Suzuki G, Kawase Y, Takafu F. Novel
immunosuppressive agent, FK506: in vitro effects on the
cloned T cell activation. J Immunol 1987; 139:1797-803.
21. Pirsch J, Miller J, Deierhoi M, Vincenti F, Filo R. A
comparison of tacrolimus (FK506) and cyclosporine for
immunosuppression after cadaveric renal transplantation.
Transplantation 1997; 63: 977-83.
22. Mayer A, Dimetrewski J, Squifflet J, Besse T, Grabensee B,
Klein B, et al. Multicenter randomized trial comparing
tacrolimus (FK506) and cyclosporine in the prevention of
renal allograft rejection. Transplantation 1997; 64: 436-43.
23. Textor S, Weisner R, Wilson D, Porayko M, Romero J, Burnett
J Jr, et al. Systemic and renal hemodynamic differences
between FK506 and cyclosporine in liver transplant recipients.
Transplantation 1993; 55:1332-9.
24. European FK506 Multicenter Liver Study Group.
Randomized trial comparing tacrolimus (FK506) and
cyclosporine in prevention of liver allograft rejection. Lancet
1994; 344: 423-8.
25. The US Multicenter FK506 Liver Study Group. A comparison
of tacrolimus (FK506) and cyclosporine for
immunosuppression in liver transplantation. N Engl J Med
1994; 331:1110-5.
26. Elion G. Biochemistry and pharmacology of purine analogues.
Fed Proc 1967; 26: 898-904.
27. Suthanthiran M, Strom TB. Renal Transplantation. N Engl J
Med 1994; 331: 365-76.
28. Sievers T, Rossi S, Ghobrial R. Mycophenolate mofetil.
Pharmacotherapy 1997; 17:1178-97.
29. Sollinger H, for the US Renal Transplant Mycophenolate
Mofetil Study Group. Mycophenolate mofetil for the
prevention of acute rejection in primary cadaveric renal
allograft recipients. Transplantation 1995; 60: 225-32.
30. The Tricontinental Mycophenolate Study Group. A blinded,
long-term, randomized multicentre study of mycophenolate
mofetil in cadaveric renal transplantation: results at three
years. Transplantation 1998; 65:1450-4.
31. Scheinman R, Cogswell P, Lofquist A, Baldwin AJ. Role of
transcriptional activation of IkBa in mediation of
immunosuppression by corticosteroids. Science 1995; 270:283-
6.
32. Auphan N, Di Donato J, Rosette C, Helmberg A, Karin M.
Immunosuppression by glucocorticoids: inhibition of NF-kB
activation through induction of IkBa. Science 1995; 270: 286-
90.
33. Morris R. Rapamycins: antifungal, antitumor,
antiproliferative, and immunosuppressive macrolides.
Transplant Rev 1992; 6: 39-87.
34. Chung J, Kuo C, Crabtree G, Blenis J. Rapamycin-FKBP
specifically blocks growth-dependent activation of and
signaling by the 70 kd S6 protein kinases. Cell 1992; 69:1227-
36.
35. Brunn G, Hudson C, Sekulik A, Williams J, Hosoi H,
Houghton PJ, et al. Phosphorylation of the translational
repressor PHAS-1 by the mammalian target of rapamycin.
Science 1997; 277: 99-101.
564 Læknablaðið 2000/86