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PubMed2002

Prospective study of polyomavirus type BK replication and nephropathy in renal-transplant recipients.

BACKGROUND: Nephropathy associated with the polyomavirus type BK (BKV) nephropathy has emerged as a cause of allograft failure linked to immunosuppressive regimens containing tacrolimus or mycophenolate mofetil. The presence of viral inclusions, known as "decoy cells," in urine and the presence of BKV DNA in plasma have been proposed as markers for the replication of BKV and associated nephropathy, but data from prospective studies have been lacking. METHODS: In a prospective, single-center study, we followed 78 renal-transplant recipients who were receiving immunosuppressive therapy that included tacrolimus (37 patients) or mycophenolate mofetil (41 patients). Urine was tested for the presence of decoy cells at routine visits. BKV DNA was measured 3, 6, and 12 months after transplantation and whenever decoy cells were detected. The viral load in plasma was quantified with the use of a real-time polymerase-chain-reaction method. Renal biopsy was performed if allograft function deteriorated. RESULTS: Twenty-three patients had decoy-cell shedding a median of 16 weeks after transplantation (range, 2 to 69), 10 patients had BKV viremia at a median of 23 weeks (range, 4 to 73), and 5 had BKV nephropathy at a median of 28 weeks (range, 8 to 86). Kaplan-Meier estimates of the probability of decoy-cell shedding, viremia, and nephropathy were 30 percent (95 percent confidence interval, 20 to 40 percent), 13 percent (95 percent confidence interval, 5 to 21 percent), and 8 percent (95 percent confidence interval, 1 to 15 percent), respectively. Antirejection treatment, particularly with corticosteroids, was associated with BKV replication and nephropathy. The viral load in plasma was higher in patients with BKV nephropathy than in those without nephropathy (P<0.001 by the Mann-Whitney test). BKV antibodies were detected in 77 percent of the 78 patients before transplantation, including 4 of 5 with BKV nephropathy. CONCLUSIONS: BKV nephropathy in renal-transplant recipients represents a secondary infection associated with rejection and its treatment in most cases and could be monitored by measuring the viral load in plasma.

Adult↗

PubMed2002

Technical and immunologic progress in simultaneous pancreas-kidney transplantation.

BACKGROUND: During the past few years the use of new immunosuppressants and refinements in surgical technique of simultaneous pancreas-kidney (SPK) transplantation have resulted in markedly improved outcomes. This is a retrospective study of 208 SPK transplants performed at Northwestern University, demonstrating the advances made at a single center that are reflective of the field at large. METHODS: An 8.5-year time span was split into 4 distinct eras marking sequential changes in immunosuppression and surgical technique that ensued. SPK transplant outcomes of patient and graft survival and rejection rates were compared. Also examined were end points related to the changing risk profile of the recipients, as well as quality of allograft function and rates of rehospitalizations. RESULTS: Recipients receiving tacrolimus/mycophenolate mofetil-based immunosuppression had patient, kidney, and pancreas survival rates significantly higher than those of earlier cohorts. The elimination of corticosteroids did not reduce survival rates or increase rejection risk. The use of pancreatic exocrine enteric drainage technique over bladder drainage reduced rehospitalizations. CONCLUSIONS: Advances in immunosuppression management combined with technical refinements have made SPK transplantation a safer and more effective treatment option for the diabetic, uremic patient.

Adolescent↗

PubMed2002

Does donor cause of death affect the outcome of lung transplantation?

BACKGROUND: Accumulating evidence suggests that the donor's cause of death may influence posttransplantation allograft function. We conducted a retrospective analysis of our adult lung transplant experience to investigate the influence of donor traumatic brain injury versus nontraumatic brain injury on posttransplantation outcome. METHODS: We retrospectively reviewed donor records and recipient medical charts for 500 consecutive lung transplants performed between July 1988 and December 1999. Recipient follow-up was complete, with a minimum follow-up of 1 year of survival. RESULTS: There were 295 and 205 donors in the traumatic and nontraumatic brain injury groups, respectively. Young male donors predominated in the traumatic brain injury group. Recipients receiving donor lungs from the traumatic and nontraumatic brain injury groups did not differ by age, sex, diagnosis, type of transplant (single-lung versus double-lung) or requirement for pretransplantation mechanical ventilatory assistance. Recipients did not differ in immediate or 24-hour PaO (2)/inspired oxygen ratio, ventilation time, hospital stay, hospital mortality, or overall survival. Recipients of organs from donors who died of traumatic brain injury showed a higher severity and frequency of rejection episodes during the first year after transplantation. Freedoms from bronchiolitis obliterans syndrome at 5 years were 34.5% and 50.8% for recipients of organs from donors who died of traumatic and nontraumatic brain injury, respectively (P =.002). CONCLUSIONS: The cause of donor brain death does not appear to influence early results of lung transplantation. Traumatic brain injury, or some phenomenon associated with it, may predispose a transplanted lung and its recipient toward more severe early rejection episodes and subsequent development of bronchiolitis obliterans syndrome.

Adult↗

PubMed2000

De novo renal artery aneurysm presenting 6 years after transplantation: a complication of recurrent arterial stenosis?

Pseudoaneurysms represent a well-recognized vascular complication of renal transplantation, but true aneurysms involving the donor renal artery have not been described. We report a patient who had a de novo aneurysm of the donor renal artery 6 years after receiving a cadaveric renal transplant from a child. The aneurysm was repaired successfully, and allograft function was preserved. Histologic evidence confirmed that the lesion was a true aneurysm. Given the potential for graft loss associated with complications of unrepaired aneurysms, we believe that the presence of a true aneurysm in a donor renal artery represents an indication for repair.

Adult↗

PubMedDate not supplied

Electron microscopy in the diagnosis of BK-polyoma virus infection in the transplanted kidney.

BK polyomavirus has become an important etiologic agent responsible for significant morbidity in renal transplant recipients. This virus can be detected in transitional cells in the urine (decoy cells) using cytology, but correlation with allograft function status and histologic evidence of renal involvement is poor. Accurate diagnosis of BK polyomavirus infection requires a high index of suspicion and utilization of ancillary diagnostic techniques in many cases. Electron microscopy is very sensitive in depicting the presence of BK virions, but the finding of viral particles is not by itself diagnostic of BK interstitial nephritis. Management of patients with polyoma virus nephropathy is difficult since there is no specific antiviral therapy available at this time.

Animals↗

PubMed1980

Prednisolone clearance in renal transplantation.

Although prednisolone is the most common immunosuppressive agent used in renal transplantation, an accurate formulation of the optimal dose regimen remains to be established. A sensitive and precise radioimmunoassay was developed for this purpose. Fifty microliters of 1:20 dilutions of serum or 1:200 dilutions of urine were incubated at room temperature for two hours with 130 pg of 3H-prednisolone (150muCi/microgram) and a rabbit antiserum against prednisolone (1:1,600 dilution). Serial prednisolone clearances (Cp) for ten renal transplant patients representing variable allograft functions were compared with their corresponding creatine clearances (Cer). The data show that renal metabolism of prednisolone is well correlated with Ccr. Increasing (decreasing) Ccr is accompanied by increasing (decreasing) Cp. The availability of an assay for serum prednisolone, together with a knowledge of the ratio between these two clearances, may prove useful for regulating therapy in renal transplant patients.

Dose-Response Relationship, Drug↗

PubMedDate not supplied

Human immunodeficiency virus infection in patients with solid-organ transplants: report of five cases and review.

Five recipients of solid-organ transplants who were infected with human immunodeficiency virus (HIV) were studied at the University of Minnesota, and our data were compared with data from 83 reported cases of HIV-infected recipients of solid organs from other centers. Sixty-six of the 88 patients were seronegative for HIV before transplantation and received organs or transfusions of blood from individuals who were seropositive for HIV. Seven patients (four recipients of kidney transplants and three recipients of liver transplants) received transplants after routine screening for HIV. Twenty-five (28%) of the 88 patients developed AIDS, and 20 (80%) of these 25 patients died of AIDS-related complications a mean of 37 months after transplantation. Another nine patients (10%) had other HIV-related diseases. The mean time of progression to AIDS was 27.5 months among all patients with AIDS. For patients who were seronegative for HIV at the time of transplantation, the mean time of progression to AIDS was 32 months, whereas patients seropositive before transplantation developed AIDS within 17 months. Shortly after transplantation, eleven (17%) of the patients who were initially seronegative experienced a febrile syndrome attributed to HIV. Ten patients, including eight recipients of kidney transplants and two recipients of liver transplants, maintained normal allograft function despite low-dose immunosuppressive therapy.

Adult↗

PubMed1998

Tuberculosis after renal transplantation: experience of one Turkish centre.

BACKGROUND: In this study, renal transplant recipients with tuberculosis of different organs, were retrospectively analysed with respect to prevalence, outcome and drug toxicity. PATIENTS AND METHODS: In 520 patients, 22 (4.2%) tuberculosis of various organs was diagnosed. The time interval between transplantation and diagnosis of tuberculosis was 44.4 +/- 33.5 (range 3-111) months. In 18 (82%) of the patients, tuberculosis was detected after the first year of transplantation. The most common form was pleuro/pulmonary tuberculosis (54%), and other localizations included jejunum, liver, bone, and urogenital tract. RESULTS: Sixteen of the 22 patients responded favourably to the treatment and maintain excellent allograft function, whereas six patients (27.2%) died. Toxic hepatitis was seen in four (18%) patients, and one case was complicated with acute hepatocellular failure due to isoniazide (INH). However, of the 23 patients at risk of tuberculosis who had had INH prophylaxis for 1 year, neither tuberculosis, nor hepatotoxicity was observed. CONCLUSION: Tuberculosis is a common infection of renal transplant recipients in developing countries. The peak incidence is after the first year of transplantation and mortality is considerable. Hepatoxicity is a considerable risk of treatment, possibly as a result of additive toxic effects of immunosuppressive drugs.

Adult↗

PubMed2001

Effect of closure of the arteriovenous fistula on left ventricular dimensions in renal transplant patients.

BACKGROUND: Left ventricular hypertrophy is common in renal transplant patients. One of the factors that might contribute to this phenomenon is the persisting presence of an arteriovenous (AV) fistula. Several reports have described the presence of high-output cardiac failure, which subsided after closure of the AV fistula. However, the long-term effects of elective closure of the AV fistula on left ventricular dimensions in stable renal transplant patients have never been prospectively studied. SUBJECTS AND METHODS: Twenty patients (15 male, 5 female; mean age 51+/-12 years) with a well-functioning renal transplant were included. Patients with severe heart failure (NYHA III or IV) were excluded. Before and 3-4 months after closure of the AV fistula, an echocardiogram was performed. Fistula flow was assessed by colour duplex-Doppler sonography. RESULTS: Mean fistula flow was 1790+/-648 ml/min. After closure of the fistula, left ventricular end-diastolic diameter (LVEDD) (51.5+/-5.8 vs 49.3+/-5.4 mm, P<0.01) and left ventricular mass index (LVMi) (135.0+/-34.1 vs 119.8+/-23.2) decreased. The change in LVMi after fistula closing was significantly related to the LVMi and LVEDD before operation (r=0.74 and r=0.60, P<0.01), but not to fistula flow. Interventricular septal and posterior-wall diastolic thickness did not change. Heart rate decreased (72+/-10 vs 69+/-9, P:=0.03) Blood pressure and creatinine clearance did not change. CONCLUSION: Closure of the arteriovenous fistula in stable renal transplant patients results in a decrease in LVMi, due to a reduction in LVEDD. The change in LVMi is significantly related to the LVMi and LVEDD before fistula closing. In patients with a well-functioning allograft and persistent LV dilatation, closure of the AV fistula might be considered.

Arteriovenous Fistula↗

PubMed2003

Long-term efficacy of hyperuricaemia treatment in renal transplant patients.

BACKGROUND: Although hyperuricaemia and gout are frequently found in renal transplant recipients, little has been published on the efficacy of urate-lowering therapy (ULT) in this patient population. We therefore examine the effects of allopurinol and benziodarone therapy in a cohort of renal transplant patients. METHODS: We reviewed files from a cohort of 1328 patients that received renal transplantation. The selection criteria included: functioning allograft, hyperuricaemia for >12 months or gout, ULT lasting at least 1 year and at least two control measurements after the onset of ULT. Patients on azathioprine were treated with benziodarone to avoid azathioprine-allopurinol interactions. RESULTS: Two-hundred and seventy-nine patients fulfilled the criteria for review. They were treated with 289 courses of ULT: 100 with allopurinol (mean dose: 376 mg/day/dl/min of creatinine clearance) and 189 with benziodarone (mean dose: 73 mg/day). The mean follow-up was 38 months. Both drugs were effective for the control of hyperuricaemia, but benziodarone caused greater reductions in serum uric acid levels, especially when used at mean doses of >75 mg/day. Severe side effects were uncommon, in both the allopurinol and benziodarone groups. CONCLUSIONS: Both allopurinol and benziodarone were effective for the control of hyperuricaemia in renal transplantation. Benziodarone at doses >75 mg/day was more effective than allopurinol in reducing serum uric acid levels and also reduced the risk of azathioprine-allopurinol interactions.

Adolescent↗

PubMed2004

Analysis of NFAT-regulated gene expression in vivo: a novel perspective for optimal individualized doses of calcineurin inhibitors.

BACKGROUND: With the introduction of cyclosporine A (CsA) long-term allograft function has been significantly improved. Problems regarding limited therapeutic margins and CsA toxicity remain unsolved. Up to now there are no reliable, practical markers to measure the biological activity of CsA in vivo. METHODS: Expression of nuclear factor of activated T lymphocytes (NFAT)-regulated genes in PMA/ionomycin-stimulated peripheral blood from stable renal-transplant (n = 25) recipients under CsA therapy were measured by quantitative real-time RT-PCR before and 2 h after drug intake. The relative expression of three NFAT-regulated genes was scored, averaged and presented as the multi-gene expression score ranging from 0 to 12 points. Gene expression data and CsA plasma levels were correlated. RESULTS: A reliable and precise method to measure functional consequences of calcineurin inhibition in the individual patient was established. The individual decline in NFAT-regulated gene expression and the total drug exposure were in close relation (rho = 0.602). CONCLUSION: Quantitative measurement of NFAT-regulated gene expression in CsA-treated patients represents a potent new approach to assess the biological effectiveness of CsA therapy and has the potential to enable individualized immunosuppressive regimens.

Adult↗

PubMed2005

Secondary effects of immunosuppressive drugs after simultaneous pancreas-kidney transplantation.

BACKGROUND: This report examines the early and late secondary effects of tacrolimus, cyclosporin microemulsion (ME), mycophenolate mofetil (MMF) and rabbit anti-thymocyte globulin (rATG) in simultaneous pancreas-kidney (SPK) recipients. METHODS: Of the 205 patients participating in the Euro-SPK 001 study, 103 were randomized to tacrolimus (0.2 mg/kg) and 102 to cyclosporin-ME (7 mg/kg). All patients received rATG for 4 days [ATG-Fresenius (ATG-F) 4 mg/kg/day or Thymoglobulin (Thymo-S) 1.25 mg/kg/day] plus MMF and short-term corticosteroids. RESULTS: Thymo-S induction therapy was associated with a lower white cell count in the first 3 months than was seen with ATG-F, while ATG-F caused a lower initial nadir in platelet count. Both polyclonal preparations were well tolerated and no clinically relevant differences were observed with respect to side effects such as infections and malignancies. High cyclosporin-ME trough levels were associated with pancreas graft thrombosis, and concentrations >150 ng/ml were associated with poor renal allograft function. Treatment discontinuation was higher with cyclosporin-ME (57.8%) than with tacrolimus-based therapy (36.9%) due to more frequent toxicity, graft loss and lack of efficacy requiring a switch to tacrolimus. The main reason for withdrawal in the tacrolimus group was MMF discontinuation; MMF-related side effects resulted in more frequent dose reductions to <2 g/day and discontinuations in the tacrolimus group, and indirectly indicate a higher dose-corrected exposure to mycophenolic acid, as previously observed in kidney transplant patients. CONCLUSIONS: Short-term induction therapy is effective and well tolerated in patients undergoing SPK transplantation. Tacrolimus was the preferred immunosuppressive agent, resulting in fewer cases of pancreas graft loss and drug discontinuation compared with cyclosporin-ME.

Antilymphocyte Serum↗

PubMed2005

Questionnaire-based evaluation of gastrointestinal disorders in de novo renal-transplant patients receiving either mycophenolate mofetil or enteric-coated mycophenolate sodium.

BACKGROUND: Gastrointestinal (GI) disorders are one of the main adverse events in patients treated by mycophenolic acid (MPA). The aim of our prospective questionnaire-based study was to assess GI side-effects in de novo renal-transplant patients receiving either mycophenolate mofetil (MMF) or enteric-coated mycophenolate sodium (EC-MPS). METHODS: Between January 2002 and April 2003, all patients receiving MPA with a functioning allograft at 1 month post-transplantation were enrolled in this study (n = 130). Ninety-three of them received MMF (group I), and 37 patients received EC-MPS (group II). Each month, every patient completed a questionnaire regarding GI disorders. RESULTS: During the first year post-transplantation, GI disorders occurred in 31 patients from the MMF group (33.3%) and 12 patients from the EC-MPS group (32.4%) (not significant). The incidence of upper GI disorders was also similar in both groups. Diarrhoea was observed in 18 patients (19.3%) from group I, and in five patients from group II (13.5%) (not significant). Its frequency and severity were similar in both groups. Weight loss was observed in three patients receiving MMF. Diarrhoea resolved spontaneously in 10 patients from group I and in all patients from group II. For the other eight patients in group I, the diarrhoea required MMF discontinuation in three patients and dose reduction in five patients. CONCLUSIONS: In conclusion, in this questionnaire-based evaluation, the incidence of GI disorders was similar in patients receiving either MMF or EC-MPS during the first year post-transplantation.

Adult↗

PubMed1997

The alloimmunized patient: monitoring and therapeutics.

The sensitization of renal transplant patients in the form of antihuman leukocyte antigen antibodies often constitutes significant risk to allograft function. Testing for these antibodies is done before, at the time of, and after renal transplantation. Correct interpretation of the results necessitates an understanding of the principles of the tests and of the clinical factors in the patients, especially those receiving another transplant. Treatment remains difficult, although preliminary trials with intravenous gamma globulin have shown promising results in some patients.

Cytotoxicity Tests, Immunologic↗

PubMed2007

Osteomalacia and secondary hyperparathyroidism after kidney transplantation: Relationship to vitamin D deficiency.

Secondary hyperparathyroidism is highly prevalent in patients with end-stage renal disease. After successful kidney transplantation, however, parathyroid glands gradually involute to normal size with subsequent normalization of intact parathyroid hormone (PTH), serum calcium, and phosphorous concentrations. This report describes a 48-year-old diabetic end-stage renal disease patient who underwent a successful cadaveric kidney transplant. Serum calcium and phosphorous concentrations normalized within 6 months. Three years later, he presented with complaints of proximal muscle weakness that was progressively worsening. Physical examination revealed temporal wasting and proximal muscle weakness. Detailed neurologic examination was unremarkable except for decreased vibratory sensation in both feet. Laboratory data showed stable allograft function (serum creatinine, 1.3 mg/dL), hypocalcemia, and hypophosphatemia with markedly elevated alkaline phosphatase level (726 IU/L) and intact PTH level (947 pg/mL). Further laboratory evaluation revealed poor nutritional status and severe deficiency of 25(OH)D (4.0 ng/mL). Past medical history included remote episodes of acute pancreatitis due to prior alcohol abuse. Computed tomography of the abdomen showed calcific atrophic pancreas, and steatorrhea was confirmed on stool studies. Decreased bone mineral density was noted by computed tomography bone density scan. Secondary hyperparathyroidism and osteomalacia had developed due to severe vitamin D deficiency, occurring as a result of previously unrecognized, minimally symptomatic pancreatic exocrine insufficiency. Treatment with vitamin D, calcium, and pancreatic enzyme replacement led to remarkable resolution of clinical symptoms and secondary hyperparathyroidism (intact PTH, 65 pg/mL after therapy) and resulted in significant improvement in bone mineralization. Factors associated with vitamin D deficiency in the chronic kidney disease and post-transplant patient population are reviewed.

Abdominal Cavity↗

PubMed1986

Perforation of the colon in renal homograft recipients. A report of 11 cases and a review of the literature.

Colon perforation in renal transplant recipients is a potentially lethal condition that is amenable to appropriate medical and surgical treatment. The 11 cases seen at the Cleveland Clinic (incidence 1.1% of all renal transplant patients) and previous reports in the literature have been reviewed. The pathogenesis is related to a high incidence of diverticular disease in patients with polycystic kidneys and/or chronic renal failure, the effects of long-term immunosuppression, and the transplant procedure itself. The high mortality of this condition (61% overall) is related to the effects of immunosuppression on the response to sepsis and the surgical procedure used. Mortality has fallen from 88% (1970-1974) to 53% (1975-1979), and there are indications that it is continuing to fall. All four cases operated on here since 1980 have survived, giving a total operative mortality of 2/6, and all have maintained excellent allograft function. A high clinical index of suspicion, prompt exteriorization of the perforated colon, reduction of immunosuppression to minimal levels, and effective antibiotic coverage have all contributed to the declining mortality.

Adolescent↗

PubMed1988

Experience with simultaneous pancreas-kidney transplantation.

With refinements in surgical techniques and increased clinical experience, there has been a resurgence of interest in vascularized pancreas transplantation. From December 1986 to April 1988, 30 whole-organ vascularized pancreas transplants with pancreatico duodenocystostomy were performed simultaneously with renal transplantation. The recipient population consisted of 20 men and ten women, with a mean age of 34.7 years (range of 25-53 years). The mean duration of insulin-dependent diabetes mellitus (IDDM) was 22.6 years (range of 10-37 years). The mean pancreas preservation time was 8.7 hours (range 3-19 years). All patients were immediately insulin-independent. Simultaneous pancreas-kidney engraftment was performed to both iliac fossae via a lower midline incision (n = 28) or through a bilateral lower abdominal incision (n = 2). The mean operating time was 5.9 hours, and packed cell transfusion requirement was 1.3 units. The mean length of hospital stay was 27.4 days. Recipients averaged 2.3 admissions (1-7), with ten patients (34.4%) requiring only one hospital admission. Postoperative immunosuppression consisted of cyclosporine, prednisone, azathioprine, and Minnesota antilymphoblast globulin (MALG). A total of 49 episodes of rejection occurred in 26 patients. Actuarial patient survival rate at two years is 96.3%. The kidney and pancreas survival rates for the same time interval is 94.0% and 84.0%, respectively. Mean serum creatinine at present is 1.75 mg/dl. In conclusion, renal transplantation in concert with pancreas transplantation has a dramatic positive impact on pancreas allograft survival. Combined engraftment does not appear to jeopardize renal allograft functional survival. In view of these results, simultaneous pancreas-kidney transplantation appears to be the treatment of choice for Type I diabetic patients.

Adult↗

PubMed1998

Liver transplantation complicated by misplaced TIPS in the portal vein.

OBJECTIVE: The purpose of this study was to determine the incidence and complications related to transjugular intrahepatic portosystemic shunt (TIPS) stents found in the portal vein at the time of an orthotopic liver transplantation. BACKGROUND: Transjugular intrahepatic portosystemic shunts are frequently used in patients with end-stage liver disease as a bridge to liver transplantation. The incidence of finding the metal stent outside of the liver parenchyma at the time of transplantation is reported as high as 30%. Most cases that have been detailed involve stents misplaced in the vena cava with various outcomes. Almost no data are available regarding stents misplaced into the portal vein. METHODS AND RESULTS: We report our experience with four patients with whom a TIPS stent was found misplaced in the portal vein at the time of liver transplantation, including one patient with a stent extending into the superior mesenteric vein. This patient required extensive venous reconstruction using a retropancreatic "pant" donor-iliac vein graft. The three other patients were transplanted without the need for extensive venous reconstruction. There was no significant difference in operative times for this group of patients, but there was a significant increase in the requirement for blood transfusion. In a follow-up period ranging from 6 months to 2 years, all patients remained alive and had normal portal venous flow and functioning allografts. Most misplaced stents were placed in patients with small cirrhotic livers and by radiologists with minimal experience with the procedure. CONCLUSIONS: Misplaced TIPS in the portal vein before liver transplantation is a more frequent complication than previously reported; however, it does not represent major technical difficulty if a clamp can be placed proximally on the portal vein. In the case of a stent extending below the spleno-mesenteric confluence, interposition grafts such as a donor-iliac vein graft are necessary for venous reconstruction. The experience of the radiologist is critical to prevent this complication.

Adult↗