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Background: Preemptive kidney transplantation (prior to the institution of dialysis) avoids the morbidity and mortality of dialysis; however, detailed studies of high-risk patients are lacking. The aim of the current study was to compare recent outcomes of preemptive (P) versus nonpreemptive (NP) living donor kidney transplantation with an emphasis on high-risk recipients., Methods: We retrospectively analyzed 438 sequential solitary living donor kidney transplants at our institution between January 2000 and December 2002. In all, 44% were preemptive. NP recipients were dialyzed for 21+/-36 months (range 1-312 months)., Results: Overall, three-year patient survival was similar in the NP and P groups. When stratified by diabetes and age >65 years, P and NP recipients again showed similar survival. Death-censored three-year graft survival was better in the P group (97% vs. 90%, P=0.01), but was not significant by multivariate analysis. Delayed graft function was more frequent in NP vs. P (10% vs. 4%; P=0.01), but other early complications were similar including: acute rejection, 16% vs. 11% (P=0.11); primary nonfunction, 3% vs. 2% (P=0.38); and wound complications, 19% vs. 17% (P=0.54). Glomerular filtration rate at three years was similar in the two groups (53+/-23 preemptive vs. 52+/-20 ml/min nonpreemptive; P=0.37)., Conclusion: With prompt referral and workup, preemptive kidney transplantation can be performed successfully in a large percentage of renal allograft recipients. Preemptive transplantation avoids unnecessary dialysis and should be emphasized as initial therapy for many patients with end-stage renal disease.

Background: The current success of cardiac transplantation is in part attributable to the development of effective immunosuppressive agents such as cyclosporine. However, concern remains regarding the potential for cyclosporine-induced nephrotoxicity. Animal studies and early reports of renal protective effects of pentoxifylline in bone marrow transplant recipients prompted a randomized trial in cardiac transplant recipients., Methods: Twenty-nine patients were randomized to receive pentoxifylline 400 mg p.o. t.i.d. or matching placebo for 1 year after cardiac transplantation. Renal function was assessed preoperatively and at 1, 6, and 12 months postoperatively. Glomerular filtration rate and renal plasma flow were measured with iothalamate and para-aminohippurate, respectively. Serum creatinine was also measured. Ambulatory blood pressure monitoring after withdrawal of antihypertensives for 3 days was performed 12 months postoperatively., Results: Twenty-seven patients completed the study. Glomerular filtration rate rose between 1 and 6 months after transplantation, presumably due to the reduction in goal cyclosporine level in that period, and then fell modestly between 6 and 12 months, presumably due to ongoing nephrotoxic effects of cyclosporine. No difference in glomerular filtration rate or creatinine was seen between pentoxifylline and placebo groups at any interval. Renal plasma flow increased modestly between baseline and 6 months in the pentoxifylline group, but not in the placebo group, and then fell between 6 and 12 months. Serum creatinine increased between baseline and 6 months in both groups, apparently due to increased body weight. Results of 18-hr ambulatory blood pressure monitoring obtained 1 year after transplantation was not different between groups., Conclusions: Renal function declines only modestly in the first year after cardiac transplantation. Pentoxifylline did not attenuate this process and had no effect on blood pressure. The modest decline in renal function may be related to current immunosuppressive strategies.

Transplant immunosuppression using either cyclosporine (CsA) or tacrolimus (FK506) leads to renal vasoconstriction and nephrotoxicity. Despite producing similar effects within the kidney and blood vessels, clinical hypertension occurs less frequently with tacrolimus during the first year after transplantation, compared with CsA. To examine the role of steroid dose in early posttransplant hypertension, we measured blood pressure and kidney function in liver transplant recipients treated with tacrolimus and either high-dose (TAC-HI-P, n = 19) or low-dose (TAC-LO-P,n = 20) prednisone, compared with CsA-treated recipients (n = 29) receiving prednisone doses similar to the TAC-HI-P group. At 1 month, hypertension occurred more often with CsA (72%) than with TAC-HI-P (42%, P < 0.05) or TAC-LO-P (30%, P < 0.05). By 4 months after transplantation, hypertension developed in nearly twice as many TAC-HI-P (63%) as TAC-LO-P patients (32%, P < 0.05), with no difference between TAC-HI-P and CsA (86%, NS). Daily prednisone dose at 1 month closely paralleled cumulative steroid dose in the first month in the TAC-HI-P and TAC-LO-P groups. Fourteen of 19 TAC-HI-P patients (74%) required bolus steroids for treatment of rejection within the first month, compared with 3/20 (15%) TAC-LO-P and 10/29 (34%) CsA recipients. Glomerular filtration rate fell from pretransplant levels at 1 month and 4 months to the same degree in CsA, TAC-HI-P, and TAC-LO-P patients. These results demonstrate a central role for steroid dose in the rate of onset of hypertension early after liver transplantation using tacrolimus immunosuppression. Both daily dose and cumulative dosage, including bolus treatment for rejection, may impact on the development of hypertension. Since prevalence rates rise to levels comparable to CsA by 24 months regardless of steroid dose, hypertension after liver transplant may be mediated by different mechanisms at different stages of the posttransplant course.

Immunosuppression after transplantation is complicated by hypertension and nephrotoxicity, reflecting widespread vasoconstriction associated with CsA. FK506 is a novel alternative immunosuppressive agent, structurally unrelated to CsA. These studies compared systemic and renal vascular changes developing in the initial 4 weeks after liver transplantation in patients treated with FK506 (plus PRED) and CsA (plus PRED and AZA). We studied arterial pressure, cardiac index (pulsed doppler ultrasound), and systemic resistance index (SVRI) before and weekly after liver transplant in 32 patients treated with CsA (2 mg/kg initial dose plus PRED; median dose at week 4, 30 mg/day) and 14 patients treated 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 measured 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 increased cardiac index typical of end-stage liver disease. After transplantation, SVRI and pressures rose in both groups, but after week 2, SVRI was lower in patients treated with FK506. This was associated with less prevalent clinical hypertension during the subsequent 4 months (4/14 FK506 (28%) vs. 25/32 (78%) CsA, P < 0.01). By contrast, renal blood flow and GFR fell in both treatment groups similarly, whereas renal vascular resistance rose. Urinary 6-keto-PG-F1-alpha was suppressed in all transplant recipients, but to a greater degree in FK506-treated patients. This value correlated directly to post-transplant GFR (r = 0.48, P < 0.001). These data indicate that FK506-based immunosuppression differs from CsA by inducing less systemic vasoconstriction and hypertension. Renal vasoconstrictive effects were at least as great as those seen with CsA, however, and indicate that nephrotoxicity will remain a common feature to both regimens.

Patients with hepatic cirrhosis develop widespread abnormalities in kidney function and vasoactive hormones. These change rapidly after liver transplantation during immunosuppression with cyclosporine. The role of changing eicosanoid excretion and endothelin levels in regulating renal function after transplantation in humans remains uncertain. We studied 32 patients with regard to renal hemodynamics, glomerular filtration, urinary prostacyclin (6-keto-PG-F1-alpha), thromboxane (TBX2), and endothelin before and during the first four weeks after orthotopic liver transplantation. Arterial pressure rose from 106 +/- 2/61 +/- 2 to 146 +/- 4/81 +/- 2 mmHg, (P less than .001), while renal blood flow fell (686 +/- 38 to 453 +/- 24 ml/min/1.73 m2, P less than .05), as did GFR. Pretransplant excretion of 6-keto and TBX2 was above that of normal subjects and fell progressively after transplant, as did plasma renin activity and aldosterone. The 6-keto levels fell below normal after two weeks. The ratio of TBX2/6-keto remained elevated compared with normal subjects throughout the month after transplant (1.54 +/- 0.38 vs. 0.54 +/- 0.07, P less than .01). Endothelin levels rose during the first week (7.4 +/- 1.4 vs. 12.4 +/- 2.7 pg/ml, P less than .05), but fell back to baseline thereafter. These results indicate that high levels of urinary eicosanoids in patients with liver disease fall rapidly after liver transplantation during CsA immunosuppression. Unlike results in many experimental models, these data suggest that renal vasoconstriction in humans may be associated primarily with suppression in renal prostacyclin excretion rather than stimulation of thromboxane.

Endothelin (ET) is a 21-amino-acid peptide of endothelial origin, is a potent systemic and renal vasoconstrictor associated with sodium retention and modulation of the renin-angiotensin-aldosterone system. The present study was designed to determine if plasma ET is elevated in humans with cirrhosis (n = 12), a state characterized by sodium retention and increased plasma renin activity (PRA) and plasma aldosterone (PA), and to determine the effect of orthotopic liver transplantation (OLT) upon plasma ET, PRA, and PA at 1, 3, and 7 days after transplantation. Plasma ET before OLT was 1.62 +/- 0.23 pg/ml, which was not different as compared with normal controls. Plasma ET significantly increased to 4.18 +/- 0.66, 3.87 +/- 0.58, and 4.07 +/- 0.61 pg/ml, respectively following OLT. PRA remained elevated throughout the postoperative course, in contrast to PA that decreased following OLT. Mean arterial pressure increased significantly from 82 +/- 4 pre-OLT to 98 +/- 4 and 103 +/- 2 mmHG on days 3 and 7 respectively.