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PubMed2000

Liver transplantation in a patient with acute liver failure due to sickle cell intrahepatic cholestasis.

BACKGROUND: Sickle cell intrahepatic cholestasis is a potentially catastrophic complication of sickle cell anemia Once acute liver failure develops, transplantation is the only option. We describe a patient with sickle cell intrahepatic cholestasis who underwent liver transplantation. METHODS: Data were obtained from the chart. Serial hemoglobin S levels were monitored, and measures were taken to maintain hemoglobin S <20% to prevent sickle cell crisis. RESULTS: Although the allograft functioned well initially, the patient developed veno-occlusive disease and required repeat transplantation at 5 months after transplant. Histologic examination of the explant revealed occlusion of the terminal hepatic venules due to fibrosis and packed red cells. Repeat transplant was complicated by thrombosis of the intrahepatic portion of the hepatic artery, and sepsis. The patient died of sepsis after a third transplant. CONCLUSION: Liver transplantation for sickle cell disease involving the liver may carry a high risk of graft loss due to vascular problems. Repeat transplantation may not be feasible if disease recurs.

Anemia, Sickle Cell↗

PubMed2000

Laparoscopic live donor nephrectomy: the recipient.

BACKGROUND: Laparoscopic live donor nephrectomy offers advantages to the donor in terms of decreased pain and shorter recuperation. Heretofore no detailed analysis of the recipient of laparoscopically procured kidneys has been performed. The purpose of this study was to determine whether laparoscopic donor nephrectomy had any deleterious effect on the recipient. METHODS: A retrospective review was conducted of all live donor renal transplantations performed from January 1995 through April 1998. The control group received kidneys procured via a standard flank approach (Open). Rejection was diagnosed histologically. Creatinine clearance was calculated using the Cockroft-Gault formula. RESULTS: A total of 110 patients received kidneys from laparoscopic (Lap) and 48 from open donors. One-year recipient (100% vs. 97.0%) and graft (93.5% vs. 91.1%) survival rates were similar for the Open and Lap groups, respectively. A similar incidence of vascular thrombosis (3.4% vs. 2.1%, P=NS) and ureteral complications (9.1% vs. 6.3%, P=NS) were seen in the Lap and Open groups, respectively. The incidence of acute rejection for the first month was 30.1% for the Lap group and 31.9% for the Open group (P=NS). The rate of decline of serum creatinine level in the early posttransplantation period was initially greater in the Open group, but by postoperative day 4 no significant difference existed. No difference was observed in allograft function long-term. The median length of hospital stay was 7.0 days for both groups. CONCLUSIONS: Laparoscopic live donor nephrectomy does not adversely effect recipient outcome. The previously demonstrated benefits to the donor, and the increased willingness of individuals to undergo live kidney donation, coupled with the acceptable outcomes experienced by recipients of laparoscopically procured kidneys justifies the continued development and adoption of this operation.

Acute Disease↗

PubMed2001

Late onset of severe graft-versus-host disease in a pediatric liver transplant recipient.

We report the management of a patient with the late onset of chronic graft-versus-host disease (GVHD) after orthotopic liver transplantation. GVHD is a rare complication of solid organ transplants that usually presents early after transplantation and is fatal in the majority of cases. Our patient differs from the typical patient with GVHD in that the onset of her disease was very late. Although most treatment to date consisted of an increase in immunosuppressive therapy, our patient showed an excellent response to a reduction. This resulted in the abatement of the symptoms of GVHD and the preservation of her allograft function.

Dose-Response Relationship, Drug↗

PubMed2001

Extrapancreatic pseudoaneurysm after pancreas transplantation.

Pseudoaneurysms after pancreatic transplantation are an infrequent event. Repair usually involves removal of the transplant. We describe a patient with a pseudoaneurysm associated with pancreatic transplantation. The pseudoaneurysm originated from the external iliac artery distal to the donor Y-graft anastomosis. Diagnosis was made by duplex ultrasound. Surgical repair was effected through a retroperitoneal incision enabling vascular control. The patient has done well postoperatively, and with 1-year follow-up, continues to have normal renal and pancreatic allograft function.

Aneurysm, False↗

PubMed2001

Angiotensin gene polymorphism as a determinant of posttransplantation renal dysfunction and hypertension.

BACKGROUND: Polymorphism of the genes associated with angiotensin, including angiotensin-converting enzyme (ACE), angiotensinogen (AGT), and the type 1 (AT1) and type 2 (AT2) angiotensin II receptors, has been implicated in the pathophysiology of hypertension, ischemic heart disease, and progression of chronic renal disease. METHODS: We investigated the impact of the ACE, AGT, AT1, and AT2 genotypes on renal allograft function in 148 patients (77 men, 71 women) who underwent transplantation over a 5-year period. Patients were genotyped using polymerase chain reaction sequence-specific primers and polymerase chain reaction followed by restriction fragment length polymorphism analysis. RESULTS: ACE (D) and AGT (A/A) genotypes were associated with poorer chronic renal transplant function and more rapid chronic progression, defined as an increase of serum creatinine level with time. In addition, mean diastolic blood pressure at 3 years was significantly (P<0.02) correlated with C gene dose of AT1 (A-->C, 1166), with levels of 79+/-10 mmHg, 82+/-8.6 mmHg, and 95+/-8.3 mmHg for the A/A, A/C, and C/C genotypes, respectively. An apparent AT2 homozygote disadvantage could be an epiphenomenon because AT2 maps to the X chromosome, and males are homozygous for just one of the AT2 alleles (A/- or G/-). CONCLUSIONS: Pretransplantation testing of the ACE, AGT, and AT1 genotypes may assist clinicians in identifying patients at risk for chronic renal transplant dysfunction and hypertension.

Adult↗

PubMed2001

In situ splitting of the cadaveric liver for two adult recipients.

BACKGROUND: Split-liver transplantation offers a unique opportunity to expand the existing donor pool. However, it has previously been stated that due to inadequate liver volume the advantages of split-liver transplantation would be lost when attempting to split the liver for two adult recipients. In this study, we sought to determine the safety, efficacy, and applicability of split-liver transplantation in select adult liver transplant recipients. METHODS: Liver allografts for eight adult recipients were procured by in situ splitting of four adult cadaveric livers. The donor ages were 17, 19, 22, and 25 years and weights were 72, 77, 78, and 87 kg, respectively. In situ splitting resulted in three right trisegmental grafts, one right lobe graft, one left lobe graft, and three left lateral segmental grafts. The median recipient age was 49 years (range 38-61 years), whereas the median recipient weight was 84 kg (range 78-98 kg) for the right-sided grafts and 52 kg (range 51-53 kg) for recipients of the left-sided grafts. The median graft-to-recipient body weight ratio for right trisegmental, right lobe, left lobe, and left lateral segmental grafts was 1.31%, 1.26%, 1.35%, and 0.70%, respectively. RESULTS: Overall patient and graft survival in this series is 100%. All prothrombin times were normalized within 4 days of transplantation. No evidence of ascites or prolonged hyperbilirubinemia was encountered in any right- or left-sided graft recipient. The incidence of hepatic artery, portal vein, and hepatic vein thrombosis is 0%, 0%, and 0%, respectively. Hepatic arterial anastomotic bleeding and a cut surface bile leak each occurred in one patient. Median United Network for Organ Sharing (UNOS) waiting time was 242 days (range 4-454 days) for the patients to which the donor liver was allocated. In contrast, the median waiting time for the four patients receiving the extra split-liver graft was reduced significantly to 37 days (range 21-101 days) (P<0.02). CONCLUSIONS: This study demonstrates that split-liver transplantation can expand the cadaveric donor liver pool available for select adult liver transplant recipients. When both the donor organ and the transplant recipient are chosen carefully, split-liver transplantation can be safely performed without a delay in allograft function, increase in technical complications, or compromise in graft or patient survival.

Adolescent↗

PubMed2002

Polyomavirus nephropathy in native kidneys of a solitary pancreas transplant recipient.

BACKGROUND: Latent polyomavirus (PV) infection of the urinary tract can be reactivated by immunosuppression. When this occurs in the renal allograft, permanent loss of allograft function can occur. Polyomavirus reactivation could potentially affect the native kidneys of nonrenal transplant recipients and cause renal dysfunction. METHODS: This article describes a case of PV nephropathy in the native kidneys of a solitary-pancreas transplant recipient. This patient had a progressive increase in serum creatinine. Screening urine cytology showed numerous cells with cytopathic changes suggestive of polyomavirus infection. RESULTS: Biopsy of the native kidneys of this patient showed renal tubular cells with intranuclear inclusions characteristic of PV infection, which was confirmed by immunohistochemistry. Electron microscopy showed intranuclear viral particles. Patchy inflammation and fibrosis also were noted. CONCLUSION: Polyomavirus reactivation can occur in the native kidneys of nonrenal solid organ transplant recipients. This should be considered in the differential diagnosis of renal impairment in these patients. The effects of PV reactivation on long-term native kidney function are not known.

Diabetes Mellitus, Type 1↗

PubMed2002

Noninvasive diagnosis of BK virus nephritis by measurement of messenger RNA for BK virus VP1 in urine.

BACKGROUND: Polyoma virus type BK (BKV) nephritis has emerged as an important cause of renal allograft dysfunction and graft failure. Its diagnosis is contingent on the invasive procedure of allograft biopsy. A noninvasive diagnostic test for BKV nephritis could improve clinical outcome. METHODS: We obtained 25 urine specimens from 8 renal allograft recipients with biopsy-confirmed BKV nephritis, 31 samples from 28 recipients in whom BKV nephritis was excluded by allograft biopsy, and 74 specimens from 34 patients with stable allograft function. RNA was isolated from the urinary cells and reverse transcribed to complementary DNA. We designed gene-specific oligonucleotide primers and probes for the measurement of messenger RNA (mRNA) encoding BKV VP1 protein and a constitutively expressed 18S ribosomal RNA (rRNA) by real-time quantitative polymerase chain reaction. We explored the hypothesis that BKV VP1 mRNA levels predict BKV nephritis. RESULTS: The levels of BKV VP1 mRNA but not the levels of 18S rRNA predicted BKV nephritis. Analysis involving the receiver operating characteristic curve demonstrated that BKV nephritis can be predicted with a sensitivity of 93.8% and a specificity of 93.9% with the use of a cutoff value of 6.5 x 10 BKV VP1 mRNA copy number per nanogram of total RNA ( <0.00001). In the receiver operating characteristic curve analysis, the calculated area under the curve was 0.949 (95% confidence interval, 0.912 to 0.987, <0.00001) for BKV VP1 mRNA levels and 0.562 (95% confidence interval, 0.417 to 0.708, >0.2) for 18S rRNA. CONCLUSIONS: Measurement of BKV VP1 mRNA in urinary cells offers a noninvasive and accurate means of diagnosing BKV nephritis.

Adult↗

PubMed2002

Vitamin D as immunomodulatory therapy for kidney transplantation.

Vitamin D (1alpha,25-dihydroxyvitamin D(3) [1alpha,25-(OH)(2)D(3)]) has been studied in the past for its immunosuppressive properties, and, in that context, it may also have potential utility as an immunomodulatory agent for transplantation. A number of studies have demonstrated that 1alpha,25-(OH)(2)D(3) or its analogs regulate immune cell proliferation, differentiation, and responsiveness. A burgeoning number of studies have also explored using 1alpha,25-(OH)(2)D(3) and its analogs directly as therapy in animal models of kidney transplantation with success in prolonging allograft function and preventing acute rejection. Some of these in vivo effects may well be caused by alterations in immune cell function, but it is also possible that exogenous 1alpha,25-(OH)(2)D(3) and its analogs are altering the intragraft milieu as well, specifically through changes in the TGF-beta signaling cascade. Such provocative data and the availability of newer 1alpha,25-(OH)(2)D(3) analogs that may limit side effects (e.g. hypercalcemia) have created interest in examining this secosteroid clinically in kidney transplantation.

Adjuvants, Immunologic↗

PubMed1999

Bacterial and fungal infections after kidney transplantation.

Infectious diseases in renal transplant recipients are a major issue both from the medical and from the economical point of view. The major risk factor is the immunosuppressive therapy. Infections observed during the first weeks after transplantation are not different from those observed in nonimmunosuppressed patients after surgery. Infections with opportunistic pathogens, however, emerge at the beginning of the second month and are mainly determined by the allograft function.

Bacterial Infections↗

PubMed2000

Mechanisms of hypertension after renal transplantation.

Hypertension is extremely prevalent after renal transplantation, affecting up to 70% of all patients. An elevation in blood pressure is associated with an increased cardiovascular risk and may also contribute to chronic allograft failure. Renal transplantation provides interesting insights into the pathogenesis of hypertension. Experimental and human data show that the kidney is an essential organ for blood pressure regulation. In clinical practice a differential diagnosis that is based on excretory allograft function has proved useful.

Animals↗

PubMedDate not supplied

A crossover comparison of the efficacy and safety of lovastatin and gemfibrozil in the treatment of hyperlipidemic organ transplant recipients.

Hypercholesterolemia is associated with accelerated atherosclerosis in transplant recipients. It has been notoriously difficult to treat pharmacologically due to the complex interactions that occur with lipid-lowering drugs and immunosuppressive therapies. The purpose of the current study was to compare the efficacy and safety of a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (lovastatin, 20 mg/d) with a fibric acid derivative (gemfibrozil, 600 mg twice a day). We used a randomized, crossover design in 18 solid organ transplant recipients who followed the National Cholesterol Education Program Adult Treatment Guidelines diet for 8 weeks and had persistent elevations of total cholesterol (>240 mg/dL). Each patient received each therapy for a minimum of 8 weeks (mean 14.2 +/- 2.4, range 8-20 weeks). The participants had stable allograft function and were treated with a standard immunosuppressive regimen containing cyclosporine, prednisone, and azathioprine. Lovastatin therapy reduced the mean total cholesterol by 15.5% (271.9 mg/dL to 229.9 mg/dL; p = 0.02) and the mean low-density lipoprotein (LDL) cholesterol by 22.7% (178.2 mg/dL to 137.8 mg/dL; p = 0.07). There were no significant changes in high-density lipoprotein (HDL) cholesterol or triglycerides. Conversely, when these same patients were treated with gemfibrozil, the mean total cholesterol decreased by 7.9% (271.9 mg/dL to 250.5 mg/dL; p = NS) and the LDL cholesterol decreased by 5.1% (178.2 mg/dL to 169.1 mg/dL; p = NS). In addition, the mean triglyceride concentration decreased significantly by 46.1% (234.0 mg/dL to 126.3 mg/dL; p = 0.002) and the mean HDL cholesterol increased 15.4% (48.8 mg/dL to 56.3 mg/dL; p = 0.09). In all patients, the serum creatinine, hepatocellular enzymes, and creatinine phosphokinase remained stable. Lovastatin was discontinued in three patients for myalgias, one patient with unexplained anemia, and one patient with parasthesias. These results suggest that lovastatin and gemfibrozil are both safe and efficacious in transplant patients. However, neither therapy alone completely corrects abnormalities of high LDL cholesterol and low HDL cholesterol in transplant recipients.

Adult↗

PubMed2002

Graft loss and acute coronary syndromes after renal transplantation in the United States.

The impact of graft loss on acute coronary syndromes (ACS) after renal transplantation has not been studied in a national population. It was hypothesized that ACS might be more frequent after graft loss, as many of the benefits of a functioning allograft on metabolism and volume regulation would be lost. Data from the 2000 United States Renal Data System (USRDS) was used to conduct an historical cohort study of ACS in 14,237 patients who received renal transplants between April 1, 1995, and June 30, 1998, (followed until April 28, 2000) with valid information from CMS Form 2728, excluding patients with hospitalized ACS before renal transplant. Cox nonproportional regression models were used to calculate the time-dependent adjusted hazard ratio (AHR) of graft loss (censored for death) for time-to-first hospitalization for ACS (International Classification of Diseases 9th Modification Diagnosis Codes [ICD9] code 410.x or 411.x) occurring after transplant. The incidence of ACS was 12.1 per 1000 patient-years (PY) in patients after graft loss versus 6.5 per 1000 PY after transplantation (excluding patients with graft loss). As a time-dependent variable, graft loss had an AHR of 2.54 (95% confidence interval, 1.09 to 5.96; P = 0.031 by Cox regression). Other risk factors associated with ACS included diabetes, older recipient, and male recipient. Allograft rejection was NS. Renal transplant recipients share some of the risk factors for ACS with the general population. In addition, graft loss was identified as a unique risk factor for ACS in this population.

Acute Disease↗

PubMed2004

Ex vivo ureteroscopic treatment of calculi in donor kidneys at renal transplantation.

PURPOSE: We evaluated the safety and efficacy of ex vivo ureteroscopy (ExURS) as a means of rendering the donated kidney stone-free at live donor renal transplantation. MATERIALS AND METHODS: A total of 10 suitable kidney donors with small, unilateral nonobstructive calculi underwent live donor nephrectomy (8 open flank, 2 hand assisted transperitoneal). Immediately after cold perfusion, ExURS was performed in an iced saline solution. Access to the collecting system was via the ureteral stump. Calculi were either removed with endoscopic baskets and/or completely fragmented with Holmium laser lithotripsy. RESULTS: Access to the renal collecting system was technically successful in all cases. A total of 10 stones, ranging in largest diameter from 1 to 8 mm (average 5.2) were visualized. Of the kidneys 6 had solitary stones, 2 had 2 stones and 1 had no stone. Of 10 stones 9 were successfully removed and/or fragmented with an average procedure time of 6.5 minutes (range 3 to 28). Indwelling ureteral stents were placed at transplantation in 5 of 10 kidneys. There were no intra-operative or postoperative ureteral complications. At 1 month after transplant serum creatinine ranged from 0.9 to 2.7 mg/dl (average 1.5). At a mean followup of 33.2 months new stones have not formed in any recipients and at mean 36.4-month followup no new calculi have formed in the remaining kidney of any donors. CONCLUSIONS: ExURS is a technically feasible means of rendering a stone bearing kidney stone-free without compromising ureteral integrity or renal allograft function.

Adolescent↗

PubMed2003

One hundred percent patient and kidney allograft survival with simultaneous liver and kidney transplantation in infants with primary hyperoxaluria: a single-center experience.

BACKGROUND: Combined liver-kidney transplantation is the definitive treatment for end-stage renal disease caused by primary hyperoxaluria type I (PH1). The infantile form is characterized by renal failure early in life, advanced systemic oxalosis, and a formidable mortality rate. Although others have reported on overall results of transplantation for PH1 covering a wide age spectrum, none has specifically addressed the high-risk infantile form of the disease. METHODS: Six infants with PH1 underwent simultaneous liver-kidney transplantation at our center between May 1994 and August 1998. Diagnosis was made at 5.2+/-3.3 months of age, they were on dialysis for 11.8+/-2.3 months, and they underwent transplantation at 14.8+/-3.0 months of age when they weighed 10.6+/-1.7 kg. RESULTS: At a mean follow-up of 6.4+/-1.7 years (range, 3.9-8.1 years), we report 100% patient and kidney allograft survival. There were no cases of acute tubular necrosis. Long-term kidney allograft function remained stable in all patients, with serum creatinine values of less than 1.1 mg/dL and a mean creatinine clearance of 99 mL/min/1.73 m2 at follow-up. Those who received combined hemodialysis and peritoneal dialysis pretransplant had lower posttransplant urinary oxalate values than those receiving peritoneal dialysis alone. There was improvement in growth and psychomotor and mental developmental scores after transplantation. CONCLUSIONS: Combined liver-kidney transplantation for the infantile presentation of PH1 is associated with excellent outcome when the approach includes early diagnosis and early combined transplantation, aggressive pretransplant dialysis, and avoidance of posttransplant renal dysfunction.

Body Constitution↗

PubMed2004

Monitoring of NFAT-regulated gene expression in the peripheral blood of allograft recipients: a novel perspective toward individually optimized drug doses of cyclosporine A.

BACKGROUND: With the introduction of cyclosporine A (CsA), long-term allograft function has significantly improved. Problems related to limited therapeutic margins and CsA toxicity remain unsolved. Until now there have been no reliable, practical markers to measure the biologic activity of CsA in vivo. METHODS: Expression of NFAT (nuclear factor of activated T cells)-regulated genes (interleukin 2, interferon-gamma, and granulocyte-macrophage colony-stimulating factor) in phorbol myristate acetate/ionomycin-stimulated peripheral blood from healthy volunteers (n=34) and from stable renal (n=25), cardiac (n=26), and liver (n=14) transplant recipients receiving CsA therapy was measured by quantitative real-time reverse transcriptase-polymerase chain reaction before and 2 hr after drug intake. Gene expression and CsA plasma levels were correlated. RESULTS: Two hours after oral CsA ingestion, the mean suppression of induced interleukin 2, interferon-gamma, and granulocyte-macrophage colony-stimulating factor gene expression was 85%. The individual decline of NFAT-regulated gene expression and the total drug exposure at this time point were closely related. Six hours after oral CsA uptake, gene expression levels reached predose values and subsequently increased further in some patients (rebound effect). CONCLUSION: Quantitative measurement of the inhibition of NFAT-regulated gene expression 2 hr after CsA intake represents a novel approach to assess the biologic effectiveness of CsA therapy and has the potential to enable individualized immunosuppressive regimens.

Adult↗

PubMed2004

Right laparoscopic live donor nephrectomy: a single institution experience.

BACKGROUND: Laparoscopic live donor nephrectomy (LLDN) is increasingly used by transplantation centers worldwide. As in open live donor nephrectomy, the left kidney is preferred for LLDN; however, not all potential donors have anatomy conducive to left nephrectomy. The purpose of our study, therefore, was to report on a large, single-institution experience with right LLDN performed using a hand-assisted, transperitoneal approach. METHODS: We performed a retrospective review of 40 consecutive patients who underwent transperitoneal right hand-assisted LLDN at our institution. Information on donor age, relation to recipient, and indication for right-sided donation was collected. Surgical demographics included operative time, warm ischemia time, and estimated blood loss. Recipients were followed for graft loss and for long-term renal allograft function. RESULTS: The indications for right-sided donor nephrectomy were a difference in split renal function of greater than 10%, multiple left renal vessels, and right renal cysts. The mean surgical time in our series was 115.8 min, with a mean estimated blood loss of 85.7 mL and a warm ischemia time of 116.0 seconds. Surgical and postoperative complications were limited. Mean serum creatinine levels in the recipients were 1.6 mg/dL on day 7, 1.4 mg/dL on day 30, and 1.4 mg/dL at 1 year after transplantation. CONCLUSIONS: Right LLDN using a hand-assisted, transperitoneal technique was performed with minimal morbidity and favorable graft function. We believe that offering hand-assisted LLDN to patients with an indication for right-sided donation can safely and effectively increase the pool of donor organs available to patients with end-stage renal disease.

Adult↗

PubMed2004

Cyclosporine minimization and cost reduction in renal transplant recipients receiving a C2-monitored, cyclosporine-based quadruple immunosuppressive regimen.

BACKGROUND: Targeting 2-hr postdose cyclosporine (C2) levels to 1,000 to 1,700 mg/dL during the first 6 months after renal transplantation is recommended for triple immunosuppressive regimens. This trial determines whether lower C2 levels could be targeted safely in de novo kidney transplant recipients under a quadruple regimen compared with a similar cohort monitored with trough (C0) levels. METHODS: This single-center, sequential, cohort-designed trial included patients who received Thymoglobulin, corticosteroids, an antimetabolite, and cyclosporine monitored by C2 (n=50) or C0 (n=50). Cyclosporine was tapered to maintain the C2 between 1,000 and 1,200 ng/mL months 0 to 3 and between 600 and 1,000 ng/mL thereafter and C0 between 250 and 350 ng/mL months 0 to 3 and between 100 and 250 ng/mL thereafter. RESULTS: Baseline patient and donor characteristics were similar. There were no differences in graft survival (100% C2 vs. 100% C0), acute rejection (4% C2 vs. 6% C0), allograft function, or adverse events at 6 months. C2 levels were lower than the suggested guidelines throughout the study (33% lower at 1 month and 48% lower at 6 months). Lower cyclosporine doses were achieved in the C2 arm compared with the C0 arm by 1 month and were sustained throughout the trial, which translated into an average cyclosporine cost savings of USD $773 in the C2 arm during the 6-month period (P<0.001). CONCLUSION: With a quadruple immunosuppressive regimen and lower C2 targets than recommended for triple therapy, safe and effective cyclosporine minimization was achieved. Lower cyclosporine doses were achieved in C2-monitored patients compared with C0-monitored patients, translating into lower immunosuppressive costs.

Adrenal Cortex Hormones↗