Renal transplantation for patients 60 years of older. A single-institution experience

OBJECTIVE: The authors reviewed renal transplant outcomes in recipients 60 years of age or older. BACKGROUND: Before cyclosporine, patients older than 45 years of age were considered to be at high risk for transplantation. With cyclosporine, the age limits for transplantation have expanded. METHODS: The authors compared patient and graft survival, hospital stay, the incidence of rejection and rehospitalization, and the cause of graft loss for primary kidney recipients 60 years of age or older versus those 18 to 59 years of age. For those patients > or = 60 years transplanted since 1985, the authors analyzed pretransplant extrarenal disease and its impact on post-transplant outcome. In addition, all surviving recipients > or = 60 years completed a medical outcome survey (SF-36). RESULTS: Patient and graft survival for those > or = 60 years of age versus those 18 to 59 years of age were similar 3 years after transplant. Subsequently, mortality increased for the older recipients. Death-censored graft survival was identical in the two groups. There were no differences in the cause of graft loss. Those 60 years of age or older had a longer initial hospitalization, but had fewer rejection episodes and fewer rehospitalizations. Quality of life for recipients 60 years of age or older was similar to the age-matched U.S. population. CONCLUSION: Renal transplantation is successful for recipients 60 years of age or older. Most of them had extrarenal disease at the time of transplantation; however, extrarenal disease was not an important predictor of outcome and should not be used as an exclusion criterion. Post-transplant quality of life is excellent.     

Effects of transplantation on the renin angiotensin system (RAS)

Hypertension in organ transplant recipients is associated with several functional modifications of the renin angiotensin system (RAS), which varies according to the type of transplanted organs (kidney, heart, liver or bone marrow) and the immunosuppressive regimen. Before transplantation, chronic organ failure is associated with direct and indirect stimulation of both systemic and local RASs. After transplantation, cyclosporin per se is the major determinant of hypertension. It induces stimulation of both systemic and local RAS via direct and indirect effects within the kidney and peripheral vessels. In kidney transplant recipients, ischaemia from the native kidneys and from the graft, due to acute or chronic rejection, also contributes to RAS stimulation. In cardiac transplant recipients, several haemodynamic parameters, abnormal cardiorenal neuroendocrine reflex mechanism and other hormonal systems (ANF, AVP, catecholamines) stimulate the RAS.     

Salvage of a renal allograft with renal vein occlusion secondary to extrinsic compression

We report a case of renal vein occlusion in a transplant kidney that occurred secondary to extrinsic compression from a large kidney being placed extraperitoneally in a small iliac fossa. Prompt reexploration in the immediate postoperative period resulted in salvage of the graft. The abdominal wall was reconstructed using prosthetic mesh, which decreased the compartmental pressure within the iliac fossa sufficiently to allow the kidney to perfuse and the renal vein to remain patent. The patient was eventually discharged home with a functioning graft and normal flow in the vessels, as demonstrated by duplex Doppler studies.     

Acute failure of the transplanted kidney--pathophysiology, diagnosis and prevention

Acute failure of the transplanted kidney is a major problem in the early posttransplant phase and is recognized as a major cause of graft loss. Early renal transplant dysfunction is mainly due to ischemic damage (acute tubular necrosis), rejection, infection, and cyclosporin A toxicity. Less common causes include bleeding, ureteral obstruction, urinary leak, venous thrombosis, and stenosis or occlusion of the renal transplant artery. Recent advances in both invasive (renal biopsy) and non-invasive (imaging and biochemical) techniques have improved specificity and sensitivity of the diagnosis of the acute renal failure. Several procedures which aim to prevent the kidney transplant failure have recently been introduced. Although they were shown to reduce the incidence of early allograft failure, their influence on the long-term graft survival remains to be proven.     

Emergency medicine: the Italian experience

BACKGROUND: Studies using tacrolimus and corticosteroids or the combination of cyclosporine, mycophenolate mofetil, and corticosteroids have been shown to reduce the incidence of biopsy-proven acute rejection episodes in cadaveric kidney recipients compared with cyclosporine-based immunosuppression. The current study is a retrospective analysis of our experience with tacrolimus combined with mycophenolate mofetil and steroids as primary immunosuppression for kidney transplant recipients. METHODS: In a retrospective analysis, 72 patients who received primary therapy with tacrolimus, mycophenolate mofetil, and corticosteroids (triple therapy) were compared with a control group of 98 kidney recipients who received tacrolimus and corticosteroids (double therapy). RESULTS: There was a significant reduction in the incidence of biopsy-confirmed acute rejection in the triple therapy group (8.2%) compared with the double therapy group (21%; P=0.003). One-year patient and graft survival did not differ between groups. The incidence of posttransplant diabetes mellitus was 18% and 21% in the triple and double therapy groups, respectively. Leukopenia and gastrointestinal side effects were the most common cause for discontinuation of mycophenolate mofetil. CONCLUSIONS: The combination of tacrolimus with mycophenolate mofetil and corticosteroids is more effective at preventing early acute rejection than tacrolimus and corticosteroids alone. The use of mycophenolate mofetil was associated with a higher incidence of leukopenia and diarrhea, often leading to discontinuation of the drug.     

Unraveling the mysteries of environmental medicine

BACKGROUND: In an outbred pig model of total bowel transplantation, we previously showed that simultaneous donor-specific bone marrow infusion (DSBMI), rather than promoting engraftment, sensitizes recipients and causes rejection; it also aggravates the risk of generalized graft-versus-host disease (GVHD) and infection, and tends to reduce recipient and graft survival. Small and large animal models of bone marrow-induced transplant tolerance suggest that some form of recipient preconditioning (RPC) may facilitate engraftment of co-transplanted bone marrow cells and fully expose their tolerogenic potential. METHODS: In a preclinical model, we prospectively studied the effect of RPC on simultaneous DSBMI and total (i.e., small and large) bowel transplantation. RPC consisted of whole body irradiation with 400 R (day 0); some recipients additionally received horse anti-pig antithymocyte globulin (days -2, -1, and 0). We studied six groups of outbred pigs, all of which underwent at least a total bowel transplant: group 1, nonimmunosuppressed control pigs (n=5); group 2, nonimmunosuppressed DSBMI pigs (n=13); group 3, tacrolimus pigs (n=7); group 4, DSBMI+tacrolimus pigs (n=15); group 5, RPC+nonimmunosuppressed DSBMI pigs (n=11); and group 6, RPC+DSBMI+tacrolimus pigs (n=14). RESULTS: RPC did not prolong overall survival at 7, 14, 21, and 28 days after transplant. Survival rates were 100%, 100%, 86%, and 71% in group 3; 71%, 43%, 29%, and 29% in group 6; 55%, 9%, 0%, and 0% in group 5; and 60%, 0%, 0%, and 0% in Group 1. Moreover, RPC (groups 5 and 6) increased the incidence of death from rejection, GVHD, and infection when compared with group 3. Survival was significantly higher for RPC+DSBMI+tacrolimus pigs (group 6), compared with RPC+nonimmunosuppressed DSBMI pigs (group 5). Survival greater than 28 days was noted only in pigs that received tacrolimus after transplant: 71% in group 3 versus 29% in group 6. With both RPC and DSBMI (groups 5 and 6), rejection, GVHD, and infection were not mutually exclusive events. In groups 5 and 6, at autopsy, the incidence of rejection and GVHD was 17%; rejection and infection, 17%; and GVHD and infection, 45%. A combination of all three immunologic events was noted in 14%. CONCLUSIONS: RPC, combined with DSBMI, and with or without posttransplant immunosuppression, does not prolong survival after total bowel transplantation. Rather, it increases the incidence of death from rejection, GVHD, infection, or a combination of these three immunologic events. According to this preclinical study, RPC and unmodified DSBMI do not improve patient and graft outcome after total bowel transplantation and need to be refined before being applied clinically.     

Radioisotopic evaluation of renal function in cyclosporine-treated pediatric and adult renal transplant recipients and their living donors. A study of 152 donor-recipient pairs

Renal function was studied in 2 groups of renal transplant recipients and their donors by technetium-99m diethylenetriamine pentaacetic acid and a gamma camera. The pediatric group (group A) comprised 40 children and their adult kidney donors. The adult group (group B) consisted of 112 consecutive adult renal transplant recipients and their adult donors. All patients received kidneys from living donors and were given the same immunosuppression protocol (PRED plus CSA). Donor glomerular filtration rate (GFR) was determined before nephrectomy and at a mean period of 30 (range 10-50) months after nephrectomy. The graft GFR was measured at 1, 3, 6, and 12 months and at the most recent follow-up visit. Moreover, the functional reserve of the graft was assessed by infusion of dopamine and an amino acid. The postnephrectomy GFR of donors in groups A and B were 74 +/- 18 and 72 +/- 20 ml/min/1.73 m2, respectively. The GFR of pediatric recipients was significantly lower than that of adult recipients at corresponding time points along the course of follow-up. The mean values of graft GFR were 47.6 +/- 20 and 63.8 +/- 29.6 ml/min/1.73 m2 for pediatric and adult recipients, respectively (P < 0.001). Moreover, the graft functional reserve was significantly lower in pediatric recipients. These data demonstrate that adult kidneys transplanted into pediatric recipients have lower GFR than those transplanted into adults, despite corrections for body surface area. Although the reason for this phenomenon is unknown, the observation may have important implications for management of pediatric recipients.     

The importance of the kidney in primary hypertension: insights from cross-transplantation

Experimental renal cross-transplantation studies with genetically hypertensive and normotensive rats have shown that hypertension travels with the kidney. The underlying mechanisms are currently not well understood. Genetically normotensive recipients of a kidney from spontaneously hypertensive rats show a decreased capacity to excrete sodium when challenged with a high-salt diet. Furthermore, they retain more sodium than recipients of a kidney from genetically normotensive donors immediately after transplantation and removal of the native kidneys. Sodium retention precedes hypertension and may contribute to its development. Most recently, it has been shown that bilateral nephrectomy and transplantation of a genetically normotensive kidney attenuates the development of hypertension in young transplanted spontaneously hypertensive rats. Thus, long-term blood pressure in renal transplanted rats is critically determined by the genetic background of the renal graft. Together, these data indicate that genetically determined renal mechanisms play a major role in primary hypertension.     

Gastric acid secretion and enteric infection in Bangladesh

We present three lung transplant recipients who had sigmoid colonic diverticular perforation within 4 weeks of transplantation, giving an overall incidence of 8.6% (3 of 35) in our population. Our cases are unusual because they all occurred in the early posttransplantation period and because the incidence of perforation is substantially higher than that reported in other transplant populations. The reason for the apparent increased incidence of perforation in our lung transplant recipients is unclear, but it is likely related to the short follow-up period, intense posttransplantation immunosuppression, perioperative hypoperfusion, and increased intraluminal pressure from the use of narcotics and bowel stimulants. We discuss these potential causes and comment on preventive measures being undertaken at our program.     

Ablation of irreversibly rejected renal allograft by embolization with absolute ethanol: a new clinical application

Surgical allograft nephrectomy has been the conventional therapy for removing failed kidney allografts when clinical manifestations of graft intolerance appear. However, removal of a transplanted kidney is an extensive surgical procedure. On the other hand, transcatheter vascular embolization (TVE) has proven useful in ablating organs and could be applied to renal transplant ablation. The aim of this study was to present the results of TVE for the treatment of graft intolerance syndrome (GIS) in failed allograft kidneys. Transcatheter vascular embolization was performed in 14 allograft recipients (33 +/- 13 years of age; 10 men and four women) affected by GIS after irreversible kidney allograft failure. Graft intolerance syndrome was diagnosed by fever (93%), hematuria (50%), graft pain (36%), flu-like symptoms (29%), and increased graft size (29%). Absolute ethanol (0.1 mL/kg body weight) was injected in the allograft artery, and in seven patients a stainless steel coil was left in the renal artery following ethanol injection. All patients showed clinical disappearance of the GIS. No major complication occurred, although a postembolization syndrome of pain, fever, hematuria, numbness, and paresthesia of the affected area appeared in 11 of the 14 patients. After 2 to 56 months of follow-up no late complications occurred, with the exception of a graft abscess formation in one patient after 6 months of embolization. Subsequent transplantectomy was uneventful. In conclusion, TVE is a safe and effective method for kidney graft ablation, and it may become an alternative treatment for GIS following irreversible rejection.     

High-dose rate iridium192 afterloading therapy in combination with external beam irradiation for localized prostate cancer

The number of donors aged 60 years and over has increased. This study examined discard rates and transplant outcomes in organs recovered from older donors. Data were obtained using a standard tool for donors aged 60 years and older during 1993 and 1994 and included demographics, medical history, use of vasopressors, renal/liver function studies, organ disposition, biopsy findings, and recipient organ function. Of 58 kidneys recovered, 24 were transplanted, 26 were used for research, and 8 were discarded. Of 14 livers recovered, 11 were transplanted, 1 was used for research, and 2 were discarded. Sixty-three percent of kidney recipients had immediate function; 79% at 30 days. Nine liver recipients had immediate function; 6 at 30 days, with 1 graft lost. Results show that kidneys and livers can be transplanted from older donors with positive outcomes. Factors such as medical history, use of vasopressors, and organ function studies may help predict organ disposition and function.     

Do cold agglutinins have any impact on the outcome of liver transplantation?

Cold agglutinins, IgM red blood cell autoantibodies, cause cold agglutinin disease with hemolysis and microvascular occlusion. Cold preservation of kidneys during renal transplantation in the presence of cold agglutinins can cause graft malfunction. However, the impact of cold agglutinins on the outcome of liver transplantation is unknown. We measured the pretransplant presence and titer of cold agglutinins in 327 primary liver allograft recipients and analyzed their relationship to outcome after transplant. Thirty-three percent of pretransplant patients had cold agglutinins. Cold agglutinins were more common in patients with viral-related liver diseases (49%) compared with those with nonviral-related liver disease (32%). There was no difference between recipients with and without cold agglutinins in usage of blood products, postoperative day 2 aminotransferase levels, acute rejection at day 7, the development of hepatic artery thrombosis, nonanastomotic biliary strictures, or 4-month allograft survival. In conclusion, cold agglutinins are common in liver transplant patients before surgery, especially those with viral-related liver diseases. However, the presence of cold agglutinins does not impact on outcome after liver transplantation.     

Effect of chemoradiotherapy on the pituitary-thyroid system in children with Hodgkin''s disease

INTRODUCTION: Tacrolimus (FK 506), a potent anti-T cell agent, has been shown to be effective in preventing the rejection of transplanted organs. Published research on tacrolimus has focused on effects associated with therapeutic use. Virtually no literature addresses the acute toxicity or the management of tacrolimus overdose. We report five cases of acute overdose with tacrolimus. CASE REPORTS: A 2-year-old female with no prior medical history ingested 10 mg of tacrolimus. She remained asymptomatic. A 2-year-old female with a history of multiple visceral organ transplants ingested 11 mg of her tacrolimus. She was admitted to the hospital and activated charcoal was administered. Her renal function was monitored and no changes were noted in a 24 h period. She was discharged. A 29-year-old male renal transplant patient took 150 mg of tacrolimus. He recovered with only a minimal creatinine elevation. A 23-year-old heart and lung transplant patient ingested 375 mg of tacrolimus. She had no effects from the overdose. A 34-year-old female experienced an acute/chronic overdose of 7-9 mg and remained asymptomatic. DISCUSSION: Tacrolimus is a neutral macrolide antibiotic that is extracted from the fermentation broth of the soil fungus Streptomyces tsukubaensis. Chronic oral dosing has been associated with numerous side effects. Although these patients ingested significant doses of tacrolimus, they suffered few toxic manifestations associated with tacrolimus. CONCLUSION: Little information is available regarding acute tacrolimus overdosage. In this small series of patients, tacrolimus did not produce acute physiologic incapacitation.     

A unique African HLA haplotype may identify a population at increased risk for kidney graft rejection

We determined HLA-A, -B, and -DR allele frequencies in kidney transplant recipients in relation to graft survival. Most recipients and donors were from African descent. The frequency of HLA-A30 was somewhat increased in recipients who rejected the graft. The frequency of HLA-B42 was significantly (P=0.002) increased in recipients who rejected the graft. Similar results were found for the HLA-DR3 allele; however, this effect was diminished when B42-, DR3+ individuals were analyzed. We further investigated the effect on transplant outcome of a unique African haplotype A30, B42, DR3, and of segments thereof, which have a high frequency in the local population. Log-rank analysis revealed that the negative effect on transplant outcome was least in A30-, B42+ recipients (P=0.417) and most pronounced in A30+, B42+ patients (P=0.006). We postulate that the negative effect on transplant outcome may reside in the A30, B42 segment of chromosome 6 and may be caused by a stronger than average immunoregulatory gene.     

Cardiac allografts from IL-4 knockout recipients: assessment of transplant arteriosclerosis and peripheral tolerance

To study the role of IL-4 in tolerance induction and transplant arteriosclerosis, BALB/c hearts were transplanted into C57BL/6J wild-type or IL-4 knockout (IL-4(-/-)) recipients. A 30-day course of anti-CD4/8 mAb was used to induce long term graft survival. Primary graft survival was 50% (5 of 10) in IL-4(-/-) recipients comparable to 63% (5 of 8) in wild-type recipients. Mice with allografts surviving >80 days were tested for tolerance by challenge with a second donor or third party (CBA) heart. Secondary donor-strain heart grafts survived >30 days, but showed histologic evidence of ongoing alloimmune response. Third party hearts rejected rapidly. Although immunostaining and 32P RT-PCR assays showed no differences in the mononuclear cell infiltration and T cell activation between IL-4(-/-) and wild-type tolerant recipients, some monokines (IL-12, TNF-alpha, and allograft inflammatory factor-1) were up-regulated in grafts from IL-4(-/-) recipients. Computer-assisted analysis of elastin-stained vessels revealed that the severity of vascular thickening (percentage of luminal occlusion, mean +/- SD, n = 329) was similar in grafts from IL-4(-/-) (63.7 +/- 16.9%) and wild-type (69.5 +/- 17.6%) recipients. Thus, IL-4 deficiency did not alter primary or secondary graft survival, infiltration, or vascular thickening. The selective alterations in monokine expression suggests that alternative pathways are activated and may compensate in IL-4(-/-) mice.     

Outcome of plasma exchange therapy in thrombotic microangiopathy after renal transplantation

Thrombotic microangiopathy (TMA) in renal transplant recipients is commonly associated with calcineurin inhibitors (CNIs), though several factors such as vascular rejection, viral infections and other drugs may play a contributory role. We report a series of 29 patients with TMA, all of whom were on CNIs. Though plasma exchange (PEx) is widely used to treat TMA, therapeutic guidelines are not well defined. All our patients were treated with PEx and discontinuation of CNIs. Thrombotic microangiopathy was diagnosed at a median of 7 days post-transplant. The mean decrease in Hgb and platelets during TMA was 66% and 64%, respectively, and peak serum creatinine during TMA was 7.4 +/- 2.9 mg%. Mean duration of PEx therapy was 8.5 (range 5-23) days. Recovery of platelet count to 150K/mcL and Hgb to 8-10 g/dL were used as endpoints for PEx. Twenty-three/29 (80%) patients recovered graft function after PEx. Twenty/23 (87%) patients who recovered were placed back on CNl. Nineteen/20 (95%) patients tolerated reinstitution of CNl without recurrence of TMA. In post-transplant TMA, PEx was associated with a graft salvage rate of 80%, reversal of hematological changes can be used as the endpoint for PEx therapy and CNl can be reintroduced without risk of recurrence in the majority of patients.     

MRI of primitive neuroectodermal tumor of the uterus

PURPOSE: The aim of this study was the assessment of atresia formation after syngeneic fetal small bowel transplantation (SBTx) to clarify its pathogenesis. METHODS: Seventy Lewis rat fetuses (gestational age, 18 to 19 days) were obtained by hysterotomy, and a 30-mm long section of small bowel was excised from each fetus. Each bowel graft was then transplanted into the space between the peritoneum and the rectus abdominis in 70 adult Lewis rats to expose the grafts to ischemic stress. Transplantation was successful in 63 of 70 grafts (90%). Successfully transplanted bowel grafts were harvested for macroscopic and microscopic examination 10 days posttransplantation. RESULTS: Of the successfully transplanted grafts, only two (3%) were atresia free; 127 atretic segments were found in the remaining 61 grafts. Twenty-four grafts (38%) had a single atresia comprised of membranous stenosis (MS) in two, membranous atresia (MA) in 10, and blind ends (BEs) with or without a connecting tissue remnant in 12. Thirty-seven grafts (59%) had multiple atresias, comprised of MS, MA, or both in six, BEs alone in seven, and a combination of BEs with MS or MA in 24. CONCLUSIONS: Our model is the first to succeed in inducing experimentally membranous stenosis and a high incidence (59%) of multiple atresias. These results suggest that bowel ischemia is responsible for multiple bowel atresia formation.     

Experience of 28 deliveries in 21 kidney transplant recipients

BACKGROUND: Risk factors to induce graft dysfunction during pregnancy in kidney transplant recipients were studied. METHODS: A total of 28 deliveries from 21 female kidney transplant recipients were analyzed. RESULTS: All recipients were maintained on either azathioprine-based (n = 17) or cyclosporine-based (n = 11) immunosuppressive regimens. Graft dysfunction (creatinine clearance < 40 ml/min) occurred in 8 cases (8 patients) during pregnancy. No acute rejection, however, could be observed. In a case-controlled study comparing a group with graft dysfunction vs. a group with good graft function, there were significantly differences in the incidence of the cases with pre-existing hypertension (62.5% vs. 10.0%), the age of the grafted kidney (58.1 vs 47.6 year), the maternal anemia (Hb: 10.3 vs. 11.8 g/dl) and the creatinine level (1.4 vs. 1.0 mg/dl) at the first trimester. These findings suggested that poorer graft function had been underlying before pregnancy and that additional loading of the pregnancy reduced further graft function, while the deterioration would be recovered after delivery in all cases except one case. CONCLUSION: Risk factors to induce graft dysfunction during pregnancy are as follows. 1) high age of the grafted kidney (> 50 year), 2) pre-existing hypertension, 3) maternal anemia (Hb: < 11 g/dl) and 4) high creatinine level (> 1.3 mg/dl) at the first trimester.     

Posttransplant hemolytic uremic syndrome in adult retransplanted kidney graft recipients: advantage of FK506 therapy?

BACKGROUND: Posttransplant hemolytic uremic syndrome (pHUS) is a rare but severe disorder that confers a poor prognosis on an allograft due to thrombotic microangiopathy. Immunosuppression with cyclosporine (CsA) is implicated as a significant risk factor for the development of pHUS. In early reports, it was hypothesized that immunosuppression with FK506 (tacrolimus) would avoid the development of pHUS. However, this initially supposed beneficial effect remains controversial, because pHUS associated with tacrolimus therapy has been published in some later case reports. This article aims to further evaluate FK506 with respect to the development and resolution of pHUS. METHODS: We describe the course of seven adult kidney graft recipients with pHUS, treated with FK506 either as initial immunosuppression for retransplantation or after discontinuation of CsA for resolution of pHUS. Work-up for pHUS was initiated when certain clinical features, such as hemolytic anemia, thrombocytopenia, and deterioration of graft function, were found. The diagnosis was confirmed by histologic examination of a renal allograft biopsy specimen (thrombotic microangiopathy). With the onset of pHUS, additional plasma exchange was performed in all patients. RESULTS: Two patients suffered from end-stage renal disease due to primary HUS and had a history of recurrent pHUS in previous renal transplants. In both patients, the attempt to regraft was only made because of the early optimistic reports using FK506. Despite initial FK506 therapy, both recipients developed pHUS again, leading to loss of graft function. Two additional kidney graft recipients with primary renal failure other than HUS also received FK506 as initial immunosuppression. One of them (loss of the first kidney graft due to CsA-induced pHUS) was successfully treated with FK506 for his second renal transplant. The other recipient, a patient in whom de novo pHUS had occurred in the first graft despite initial therapy with FK506, was treated with CsA for his second graft and again developed pHUS. The latter process, however, could be reversed by a switch to steroids and azathioprine. In all three patients regrafted for reasons other than pHUS, development of de novo pHUS was treated by CsA withdrawal and a switch to FK506; this approach was effective in two patients. CONCLUSION: Our results demonstrate that three of seven renal allograft recipients benefited from FK506 therapy for prevention or resolution of pHUS. Treatment or prophylaxis with FK506 can be considered advantageous in some patients with de novo pHUS, but FK506 fails to prevent recurrent pHUS in patients with primary HUS.     

Molecular mechanisms of development of multiple endocrine neoplasia 2 by RET mutations

Although ischemic cholangitis is an important cause of early cholestatic graft failure in hepatic allografts, it rarely leads to biliary tract abnormalities in the late postoperative period. We describe a 54-year-old woman who underwent orthotopic liver transplantation for alcoholic liver cirrhosis in 1988 and presented in April of 1995 with malaise, jaundice, dark urine, clay-colored stools and cholestasis. An endoscopic retrograde cholangiopancreatography demonstrated a rapid progressive sclerosing cholangitis. Liver biopsy findings showed mild portal hepatitis, specimens were non-diagnostic with regard to cholangitis, and no infection was found. Duplex ultrasonography suggested obstruction of hepatic artery blood flow and celiac arteriogram confirmed complete hepatic arterial occlusion. Progressive destruction and irregular stricturing and dilatation of the intra- and extrahepatic biliary tree, complicating ascending infectious cholangitis, progressive cholestatic jaundice and insufficient endoscopic biliary drainage made a hepatic retransplantation in 1995 mandatory. Ischemic cholangitis is an important cause of cholestatic graft failure, but this type of cholangitis is difficult to diagnose because of its misleading biopsy manifestations. We conclude that liver transplant recipients who exhibit nonanastomotic strictures on cholangiography should be evaluated for occlusion of the hepatic artery as a possible cause.