SYSTEMIC AND RENAL HEMODYNAMIC DIFFERENCES BETWEEN FK506 AND CYCLOSPORINE IN LIVER-TRANSPLANT RECIPIENTS

Immunosuppression after transplantation is complicated by hypertension and nephrotoxicity, reflecting widespread vasoconstriction associated with CsA. FK506 is a novel alternative immunosuppressive agent, struc turally unrelated to CsA. These studies compared systemic and renal va scular changes developing in the initial 4 weeks after liver transplan tation in patients treated with FK506 (plus PRED) and CsA (plus PRED a nd AZA). We studied arterial pressure, cardiac index (pulsed doppler u ltrasound), and systemic resistance index (SVRI) before and weekly aft er liver transplant in 32 patients treated with CsA (2 mg/kg initial d ose plus PRED; median dose at week 4, 30 mg/day) and 14 patients treat ed with FK506 (0.15 mg/kg/day initial dose and PRED; mean week 4 dose, 12.5). Renal plasma flow and glomerular filtration rate (GFR) were me asured by clearance of para-amino hippurate and 125-iothalamate. Renin activity, aldosterone, and urinary prostanoids were measured by RIA. Pretransplant pressures and hemodynamics reflected low SVRI and increa sed cardiac index typical of end-stage liver disease. After transplant ation, SVRI and pressures rose in both groups, but after week 2, SVRI was lower in patients treated with FK506. This was associated with les s prevalent clinical hypertension during the subsequent 4 months (4/14 FK506 (28%) vs. 25/32 (78%) CsA, P<0.01). By contrast, renal blood fl ow and GFR fell in both treatment groups similarly, whereas renal vasc ular resistance rose. Urinary 6-keto-PG-F1-alpha was suppressed in all transplant recipients, but to a greater degree in FK506-treated patie nts. This value correlated directly to post-transplant GFR (r = 0.48, P < 0.001). These data indicate that FK506-based immunosuppression dif fers from CsA by inducing less systemic vasoconstriction and hypertens ion. Renal vasoconstrictive effects were at least as great as those se en with CsA, however, and indicate that nephrotoxicity will remain a c ommon feature to both regimens.