Influence of albumin supplementation on tacrolimus and cyclosporine therapy early after liver transplantation

Abstract

Liver transplant recipients administered gelatin (GEL) rather than human albumin solution (HAS) can become profoundly hypoalbuminemic in the early postoperative period and often have hepatic dysfunction at this time. The combined effect of these two abnormalities could be an increase in the unbound (active) concentration of lowextraction highly albumin-bound drugs, such as tacrolimus (TAC). This may increase the efficacy and/or toxicity of such drugs. We prospectively compared the clinical outcome of 69 de novo liver transplant recipients randomized primarily to TAC or cyclosporine (CYA) and secondarily to HAS or GEL therapy during the first 14 days after liver transplantation. Antipyrine clearance on the 7th postoperative day was used as a measure of liver metabolic function. Serum albumin levels were significantly lower in both GEL arms than HAS arms during the first 14 days (P < .001). Although antipyrine clearance was similar in all four trial arms, it was intermediate between that found in historic healthy controls and patients with cirrhosis (P < .0001). Serum creatinine concentrations were significantly greater in the TAC plus GEL arm than the other three arms (P < .001). The linearized treated acute rejection rate was significantly greater in the TAC plus HAS arm than the other three arms (relative risk, 2.02; 95% confidence interval, 1.07 to 3.78; P ‫؍‬ .03). These data indicate that excess nephrotoxicity can occur with TAC in liver transplant recipients with impaired hepatic metabolism who are administered GEL. In addition, supplementary albumin may reduce the efficacy of TAC in liver transplant recipients at a time when the risk for rejection is greatest. (Liver Transpl 2002;8:224-232.)

Renal impact of fluid management with colloids: a comparative review

“…Lucas and colleagues, 1978 [19] 52 Hypovolaemia 25% albumin or balanced ERPF, GFR, urine after trauma electrolyte solution output and sodium clearance Boutros and colleagues, 1979 [6] 24 Major abdominal Salt-poor albumin, BUN, serum creatinine, aorta operations 0.45% NaCl or RL serum sodium and sodium excretion Himpe and colleagues, 1991 [22] 105 Pump priming in 2.7% albumin, 3.5% Urine output and serum cardiac surgery urea-linked gelatin or creatinine 3% succinyl-linked gelatin Boldt and colleagues, 1993 [24] 30 Paediatric cardiac 6% HES 200/0.5 or Urine output and surgery 20% albumin serum creatinine Cittanova and colleagues, 1996 [27] 69 Renal transplantation 6% HES 200/0.62 Serum creatinine and from brain-dead donors plus gelatin if HES requirement for 200/0.62 dose limit haemodialysis or exceeded or gelatin only haemodiafiltration Dehne and colleagues, 1997 [11] 25 Hypovolaemia in Standard fluids and ␣ 1 -MG, Tamm-Horsfall surgical ICU parenteral nutrition with protein, NAG, renal or without 10% blood flow and GFR HES 200/0.5 Kumle and colleagues, 1999 [30] 60 Major abdominal surgery 6% HES 70/0.5, 6% ␣ 1 -MG, NAG, CC and HES 200/0.5 or gelatin FSC Dehne and colleagues, 2001 [12] 60 Middle ear surgery 15 mL kg Ϫ1 HES ␣ 1 -MG, Tamm-Horsfall 200/0.5, HES 200/0.62 protein, NAG, urine or HES 450/0.7 or output, renal plasma 60 mL kg Ϫ1 RL flow and GFR Trull and colleagues, 2002 [34] 60 Liver transplantation 20% albumin or gelatin Serum creatinine Boldt and colleagues, 2003 [15] 40 Cardiac surgery 6% HES 130/0.4 or CC, FSC, NAG, ␣ 1 -MG, 4% gelatin GT-and GT-␣ Fenger-Eriksen and colleagues, 2005 [35] 11 Major spine surgery 6% HES 130/0.4 or GFR and ERPF isotonic saline 0.9% Table 1 shows 69 total possible combinations of clinical indication categories, fluid regimens compared and individual renal end-points assessed, with the various HES solutions considered as one colloid type. The 69 combinations were cross-tabulated by computer.…”

“…Both NAG and ␣ 1 -MG were significantly elevated after postoperative volume expansion with gelatin in 30 consecutive major abdominal surgery patients over 65 yr of age with no pre-existing renal insufficiency [66]. Postoperative volume expansion with gelatin increased serum creatinine compared with albumin (P Ͻ 0.001) among tacrolimus-treated patients in a randomized trial of 60 liver transplantation patients [34].…”

“…A total of 92 studies were included in the review: 23 randomized clinical trials [6,11,12,15,17,[19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36]; 17 non-randomized controlled clinical studies [37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53]; 16 non-controlled cohort clinical studies [54][55][56][57][58][59][60][61][62][63][64]…”

Albumin-deficient mouse models for studying metabolism of human albumin and pharmacokinetics of albumin-based drugs

“…37 Longer term studies are needed to determine if Alb -/-mice develop more significant phenotypes at a later age or when exposed to drugs whose toxicity is normally buffered by serum albumin. 38 A major outcome of our FcRn studies here are new insights into the species differences in the pharmacokinetic behavior of serum albumins. In a phenomenon referred to as the concentration-catabolism effect, 6 the efficiency by which FcRn protects its ligands from catabolic elimination is governed by its receptor occupancy.…”

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“…28,29 Also, it has been reported that concomitant drug administration, for example with voriconazole, could affect tacrolimus pharmacokinetics. 30 In the present study, some of the laboratory parameters and associated drugs were not available for all patients in their medical records and subsequently were not included in this analysis; thus, the pharmacokinetics model developed here does take into account only the analytic errors.…”