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PubMed1983

Vitamin A and its transport proteins in patients with chronic renal failure receiving maintenance haemodialysis and after renal transplantation.

Serum vitamin A, retinol binding protein, prealbumin and transferrin have been studied in chronic renal failure patients receiving maintenance haemodialysis and after renal transplantation. Vitamin A and retinol binding protein were uniformly raised in haemodialysis patients and this was unrelated to the period on dialysis. There was a molar excess of retinol binding protein to both vitamin A and prealbumin as compared with normal individuals. Renal transplantation significantly reduces serum vitamin A and retinol binding protein concentrations but has no effect on prealbumin concentrations. The reduction in vitamin A and retinol binding protein is variable in individual patients and cannot be predicted either by the allograft function or time since transplantation. Several years after transplantation, with normal serum creatinine, both serum vitamin A and retinol binding protein levels may still be greatly increased. Despite the very high vitamin A and retinol binding protein concentrations, the close correlation between the two seen in normal individuals is well maintained. The continuing high vitamin A and retinol binding protein levels in patients with satisfactorily functioning transplants is unexplained.

Creatinine↗

PubMed2004

Aldosterone resistance in kidney transplantation is in part induced by a down-regulation of mineralocorticoid receptor expression.

BACKGROUND: After renal transplantation immunosuppressive drugs-like cyclosporin A (CsA) and FK506 induce either hypoaldosteronism or pseudo-hypoaldosteronism presenting with hyperkalemia and metabolic acidosis. We investigated the relationship between renal allograft function under CsA therapy and plasma aldosterone concentration, potassium- and water homeostasis and mineralocorticoid receptor (MR) expression level in peripheral leukocytes. METHODS: We studied 21 renal transplant patients under CsA therapy and 12 healthy controls. Transplant recipients were studied before and under fludrocortisone treatment. Using quantitative reverse-phase polymerase chain reaction (RT-PCR) specific for the MR, we analyzed the level of expression of MR in peripheral leukocytes. RESULTS: In acidotic transplant recipients (HCO(3) 18.5 +/- 1.2 mM) renal function was only slightly impaired with 2.0 +/- 0.2 mg creatinine/dL when compared with 1.8 +/- 0.3 mg/dL (ns) in non-acidotic patients (HCO(3) 23.0 +/- 2.8 mM). Mean plasma aldosterone levels in renal transplant recipients did not differ from control levels (150 +/- 33 pg/mL vs. 148 +/- 33 pg/mL, ns). In contrast, the expression level of MR in peripheral leukocytes of renal transplant recipients treated with CsA was significantly decreased when compared with healthy controls without renal disease (120 +/- 78 vs. 423 +/- 73 RNA molecules/0.5 microg total RNA, p < 0.01). The level of expression of MR in renal transplant recipients did not differ between acidotic patients and non-acidotic patients (ns). The application of fludrocortisone reversed hyperkalemia and metabolic acidosis without significant effect on MR expression. CONCLUSIONS: The present data demonstrate that hyperkalemia and metabolic acidosis following CsA treatment in kidney transplantation might be associated with a down-regulation of MR expression on peripheral leukocytes. Electrolyte imbalance is reversible on application of fludrocortisone. This observation supports fludrocortisone treatment in transplant patients with severe electrolyte disturbances.

Acidosis↗

PubMed2003

Chronic renal vein thrombosis in a renal allograft.

Acute renal vein thrombosis in a renal allograft is uncommon and usually occurs in the post-transplant period. Chronic renal vein thrombosis can occur insidiously many years after transplant without significant deterioration in renal allograft function or symptoms.

Adult↗

PubMed2001

Coronary artery disease in uremia: Etiology, diagnosis, and therapy.

Cardiovascular disease is a major challenge to nephrologists, whether we deal with patients with pre-end-stage renal failure, on dialysis or after successful renal transplantation. It is the most common cause for death in patients with a functional allograft, and prevents many dialysis patients from being engrafted. Coronary artery disease is a diagnostic and therapeutic challenge, as it differs in some respects from that seen in non-uremic cohorts, and lacks much of the evidence-base on which therapeutic intervention rests. This review examines the experimental and clinical literature on cardiovascular disease in uremia, focusing on coronary artery disease. We focus on the incidence, presenting syndromes, screening tools, and interventions in the context of acute and chronic coronary syndromes. Recent evidence comparing coronary angioplasty, coronary artery stenting, and bypass surgery in subjects with renal failure is also reviewed. Coronary artery disease is more prevalent in uremia, more difficult to diagnose and less rewarding to treat compared to non-uremic subjects. Many more randomized trials are needed. In the absence of information from such trials, we advocate aggressive control of conventional and novel cardiovascular risk factors, and early intervention for symptomatic coronary disease.

Arteriosclerosis↗

PubMed2001

Outcome of living unrelated (commercial) renal transplantation.

BACKGROUND: Due to inadequate cadaveric and living related organ supply, many end-stage renal disease patients go to Third World countries for commercial transplantation, although the high risk of complications is well established and ethical arguments debate this practice. METHODS: The midterm outcome of 115 patients who had been commercially transplanted in various countries and admitted to our center for post-transplant care and follow-up between 1992 and 1999 was retrospectively analyzed. Data considering the transplantation practice and post-transplant course were collected from the patient files. Outcome of these patients was compared with those with a living related transplant performed at our center. RESULTS: The patients (91 male and 24 female; mean age of 42 +/- 12 years) were transplanted in India (N = 106), Iraq (N = 7), and Iran (N = 2). The mean follow-up period was 64.5 +/- 23.9 months. Post-transplant course was complicated by numerous surgical and/or medical complications, and many of the latter were unconventional infections caused by malaria, invasive fungal infections, and pneumonia due to various opportunistic pathogens. Overall, 52 patients still have functioning allografts, while 22 lost their grafts, 20 died, and 21 were lost to follow-up. Graft survival rates at two, five, and seven years were 84, 66, and 53%, respectively, for the study group, while it was 86, 78, and 73% for living related transplantations performed at our center (P = 0.036). Patient survival rates for the same periods were 90, 80, and 74% for the study group and 90, 85, and 80% for the living related transplantations (P = 0.53). CONCLUSIONS: Besides the ongoing ethical debate, commercial transplantation carries a high risk of unconventional complications, and despite that the patient survival rate is comparable, graft survival is worse than conventional living related transplantations at the midterm.

Adult↗

PubMed2000

Clinical risk factors associated with nonmelanoma skin cancer in renal transplant recipients.

A single-center, cross-sectional, longitudinal study was conducted to determine the prevalence, annual incidence, and clinical risk factors for skin cancer in a white renal transplant population. One hundred eighty-two white patients (95% of population) with functioning allografts, a mean age at transplantation of 38.9 +/- 15. 6 (SD) years, and a mean follow-up of 8.5 +/- 6.3 years were interviewed and examined between May 1997 and June 1999. All case notes were carefully reviewed. Since transplantation, 16.5% of the patients had developed nonmelanoma skin cancer; 15.4%, actinic keratoses (AK); 53%, viral warts; and 1.6%, lentigo maligna melanoma (n = 3). Thirty-nine percent of the tumors were detected as a consequence of this study, and 20% of these occurred on covered body sites. The squamous cell (SCC)-basal cell carcinoma (BCC) ratio was 3.8:1. Eighty-two percent of the patients were examined a second time 12 months after the initial assessment. Using these data to identify new lesions, the annual incidence was calculated at 6.5%, increasing to 10.5% at more than 10 years posttransplantation. Duration of immunosuppression, older age at transplantation, presence of AK, male sex, and outdoor occupation were significantly associated with both SCC and BCC; SCC alone was associated with a history of having smoked tobacco. Early identification of those at greatest risk using a clinical risk profile may allow the development of more structured preventative and surveillance strategies than currently exist.

Adult↗

PubMed2001

Ranitidine-induced acute interstitial nephritis in a cadaveric renal allograft.

Ranitidine frequently is used for preventing peptic ulceration after renal transplantation. This drug occasionally has been associated with acute interstitial nephritis in native kidneys. There are no similar reports with renal transplantation. We report a case of ranitidine-induced acute interstitial nephritis in a recipient of a cadaveric renal allograft presenting with acute allograft dysfunction within 48 hours of exposure to the drug. The biopsy specimen showed pathognomonic features, including eosinophilic infiltration of the interstitial compartment. Allograft function improved rapidly and returned to baseline after stopping the drug.

Acute Disease↗

PubMed2001

Osteoprotegerin levels before and after renal transplantation.

Osteoprotegerin (OPG) is a newly identified glycoprotein that belongs to the tumor necrosis factor receptor superfamily and regulates bone mass by inhibiting osteoclastic bone resorption. The regulatory mechanism of OPG is still unclear after successful renal transplantation (RTX), however, resulting in resolution of uremia. The present study was designed to clarify the potential role of OPG in uremia and after RTX under immunosuppressive therapy. We evaluated circulating OPG levels by measuring them before and after RTX (postoperative days 2, 14, and 28). Our protocol of immunosuppressive drugs was dual therapy using cyclosporine and steroids. Serum OPG was quantitated using enzyme-linked immunosorbent assay. After successful RTX, serum OPG levels decreased significantly on day 14 and day 28 compared with the baseline level (P < 0.05). Creatinine clearance dramatically increased until day 14 and decreased thereafter. Serum OPG declines for the first 2 weeks after RTX owing to functioning allograft and decreases again for the next 2 weeks because of steroids and possible immunosuppressive agents.

Adult↗

PubMed2002

Retransplantation in a patient with type 2 Jeune's syndrome.

Jeune's syndrome is a rare inherited cause of kidney failure associated with skeletal dysplasia in children. We report the case of a 20-year-old girl who had Jeune's syndrome type 2 and underwent a second kidney transplant after failure of the first allograft. The patient had 16 years of good allograft function with the first transplant and successfully received a second cadaveric graft.

Adult↗

PubMed2002

Pretransplant serum C-reactive protein and the risk of chronic allograft nephropathy in renal transplant recipients: a pilot case-control study.

Multiple factors contribute to the development of chronic allograft nephropathy (CAN) in renal transplant recipients, and atherogenesis is considered to be an important pathologic process contributing to the development of this disease. There is growing acknowledgment of the role of inflammation in the pathogenesis of atherosclerosis, and markers of inflammation, such as C-reactive protein (CRP), have been shown to predict atherosclerotic vascular disease in the general and end-stage renal disease populations. In this pilot study, we hypothesized that elevations in pretransplant concentrations of CRP predict an increased incidence of CAN after renal transplantation. This case-control study compared pretransplant CRP levels in patients with allograft dysfunction and biopsy-proven CAN (n = 15) with a control group of transplant recipients with normal allograft function (n = 43). The median concentration of serum CRP was significantly higher in the CAN versus the control patients (13.1 +/- 3.9 mg/L versus 3.5 +/- 2.5 mg/L; P = 0.01). This difference was sustained when restricting to patients who did not experience acute rejection. When dividing the patients into tertiles based on CRP concentration, the adjusted risk of CAN increased more than threefold with each increment in CRP by tertile (adjusted odds ratio, 3.16; P = 0.03). The findings of our pilot study show an association between pretransplant elevations of CRP and CAN in end-stage renal disease patients who go on to receive a renal transplant. Cohort studies in larger groups of transplant patients are needed to confirm a causal pathway between pretransplant inflammation, atherogenesis, and CAN.

C-Reactive Protein↗

PubMed2000

Rehabilitating patients with hepatopulmonary syndrome using living-related orthotopic liver transplant: a case report.

The objective of this study was to rehabilitate a patient with hepatopulmonary syndrome (HPS) who underwent living-related orthotopic liver transplantation (LT). HPS is rare; it presents severe complication in patients with liver disease. A 17-year-old woman with HPS developed portal hypertension after undergoing Kasai's surgery for congenital biliary atresia and underwent a living-related orthotopic LT. After LT, her allograft functioned well, but she continued to have hypoxemia and orthodeoxia. She was referred for rehabilitation for disuse atrophy, contracture of hip and shoulder joints, left common peroneal nerve palsy, and rehabilitation for respiratory dysfunction. By day 106 after LT, her orthodeoxia and disuse atrophy had improved because of daily exercise training and active joint range of motion exercises. Patients with HPS have orthodeoxia and poor responsiveness to oxygen therapy, and correction of hypoxemia after LT may be delayed. Therefore, rehabilitation approaches for patients with HPS should be based on the pathophysiology and characteristics of HPS.

Adolescent↗

PubMed2000

Experience with the use of sirolimus in liver transplantation--use in patients for whom calcineurin inhibitors are contraindicated.

Sirolimus (SRL) provides effective immunosuppression for kidney transplantation and may be useful in patients with delayed allograft function after kidney transplantation. We review our experience with SRL in liver transplant recipients for whom calcineurin inhibitors are undesirable. Fourteen patients with renal insufficiency or acute mental status impairment were administered SRL after liver transplantation (5- to 10-mg load, 1 to 4 mg/d). Immunosuppression also consisted of mycophenolate mofetil and corticosteroids. On resolution of neurological or renal dysfunction (return to baseline mental status or serum creatinine level), tacrolimus (TAC) therapy was initiated. Twelve patients received primary transplants, 1 patient received a combined liver-kidney transplant, and 1 patient received a third transplant. Follow-up was 2 to 7 months. Calcineurin inhibitors were initially withheld in 9 patients, and therapy was aborted because of toxicity in the remaining 5 patients. Mean times to the initiation of SRL and TAC therapy were 5.4 +/- 4.6 and 26.8 +/- 24.4 days, respectively. Serum trough levels of SRL did not correlate with dose or other patient variables. Two patients died after prolonged pretransplantation hospital courses in the intensive care unit. Six patients experienced acute rejection, but only 1 patient required antilymphocyte therapy. Serum creatinine levels at the start of SRL therapy were 2.2 +/- 1.1 and 1.2 +/- 0.6 mg/dL at 3 months. All 3 patients with neurological indications for SRL had a return to their baseline mental status. All patients had improved liver function chemistry test results and prothrombin times. No patients developed leukopenia or thrombocytopenia. SRL is safe after liver transplantation in patients with acute neurological or renal impairment. SRL is an attractive alternative when calcineurin inhibitors are undesirable, but serum trough levels of SRL should be monitored. A prospective randomized study of an SRL-based calcineurin inhibitor-avoiding regimen compared with standard therapy in patients with renal insufficiency will further evaluate the role for SRL in liver transplantation.

Adult↗

PubMed2000

Spontaneous clearance of hepatitis C virus infection post-liver transplantation is associated with rapidly changing quasispecies: a single case report.

Hepatitis C virus (HCV) clearance post-liver transplantation is uncommon. This is a case report of a patient who, after liver transplantation, developed cholestatic hepatitis characterized by severe graft dysfunction, in conjunction with high viral load. This was, however, followed by viral clearance and normalization of allograft function. The clinical features of this case and the quasispecies patterns during the illness and the clearance periods are described. In addition, management implications in terms of immunosuppressive therapy are discussed.

Amino Acid Sequence↗

PubMed2003

Primary hyperoxaluria: simultaneous combined liver and kidney transplantation from a living related donor.

Primary hyperoxaluria type 1 (PH1) is a rare inherited metabolic disorder in which deficiency of the liver enzyme AGT leads to renal failure and systemic oxalosis. Timely, combined cadaveric liver-kidney transplantation (LKT) is recommended for end-stage renal failure (ESRF) caused by PH1; however, the shortage of cadaveric organs has generated enthusiasm for living-related transplantation in years. Recently, successful sequential LKT from the same living donor has been reported in a child with PH1. We present a sister-to-brother simultaneous LKT in a pediatric patient who suffered from PH1 with ESRF. Twelve months after transplantation, his daily urine oxalate excretion was decreased from 160 mg to 19.5 mg with normal liver and renal allograft functions. In addition to the well-known advantages of living organ transplantation, simultaneous LKT may facilitate early postoperative hemodynamic stability and may induce immunotolerance and allow for low-dose immunosuppression.

Adult↗

PubMed2000

Skin cancer in liver transplant recipients.

Skin cancer is the most common malignancy arising in the posttransplantation setting. Multiple factors contribute to the high risk for cutaneous carcinoma in immunosuppressed organ-transplant recipients. We review the phenomenon of skin cancer in solid-organ transplant recipients and further delineate the problem in the context of liver transplantation. Skin cancer is a significant medical and surgical problem for organ-transplant recipients. With prolonged allograft function and patient survival, the majority of solid-organ transplant recipients will eventually develop skin cancer. Although squamous cell carcinoma is the most common cutaneous malignancy in this population, basal cell carcinoma, melanoma, and Kaposi's sarcoma, as well as uncommon skin malignancies, may occur. Highly susceptible patients may develop hundreds of squamous cell carcinomas, which may be life threatening. Management strategies focus on regular full-skin and nodal examination, aggressive treatment of established malignancies, and prophylactic measures to reduce the risk for additional photodamage and malignant transformation. Skin cancer is a substantial cause of morbidity and even mortality among solid-organ transplant recipients. As a byproduct of immunosuppression, liver transplant recipients experience a high incidence of skin cancer and should be educated and managed accordingly.

Animals↗

PubMed2005

Repair of partial lesions with nerve grafting methods in the rat tibial nerve.

A partial nerve lesion and associated neuroma can be either left alone or repaired with a graft. A by-pass graft around the undisturbed lesion with end-to-side attachments might be a good alternative. This study in rats examines these strategies using walking-track analysis, muscle weights, and histology. After a tibial nerve partial lesion (3 mm) and a 21-day delay, the reexposed lesion was either not repaired, repaired with an interposed allograft, or a by-pass allograft. Functional results showed that all three groups had a steady improvement over the 8-week period, but without significant group differences. Gastrocnemius muscle ratios reflected intermediate atrophy. Axons regenerating through the lesion were more advanced than those which regenerated through the grafts and a neuroma was absent. The partial lesion can regenerate to an intermediate level without any intervention, including a by-pass graft, although the delayed repair strategy may have counteracted any potential benefits.

Animals↗

PubMed1976

Anti-B lymphocytotoxins in renal-allograft rejection.

To determine the possible role of the B lymphocyte alloantigen system in renal-transplant rejection, we examined serum specimens from 81 allograft recipients for cytotoxic activity against a panel of normal B lymphocytes. Specimens from 22 of 25 recipients undergoing allograft rejection demonstrated strong B-lymphocyte cytotoxicity whereas only 13 of 56 recipients with normal allograft function showed similar B lymphocyte cytotoxocitiy (P less than 0.0001). In the serum samples of recipients with graft rejection who were followed sequentially, B-lymphocyte cytotoxicity preceded or was concurrent with the onset of functional impairment. The results show that anti-B-lymphocyte antibodies are associated with rejection, but it is quite possible that they are the products of rejection rather than the cause.

Antibodies↗

PubMed1989

Cyclosporine-induced hyperuricemia and gout.

To evaluate the frequency and the pathogenesis of hyperuricemia and gout during cyclosporine therapy, we studied renal-transplant recipients who were treated with either cyclosporine and prednisone (n = 129) or azathioprine and prednisone (n = 168). Among the patients with stable allograft function and serum creatinine concentrations below 265 mumol per liter, hyperuricemia was more common in the cyclosporine group than in the azathioprine group (84 percent vs. 30 percent; P = 0.0001). Gout developed in nine patients (7 percent) in the cyclosporine group, but no episodes occurred in the azathioprine group. Serum urate levels became elevated in 90 percent of the patients in the cyclosporine group who were treated with diuretics, as compared with 60 percent of those not treated with diuretics (P = 0.001); in the azathioprine group, the corresponding values were 47 percent and 15 percent (P = 0.0001). Serum urate levels did not correlate with trough blood cyclosporine levels in a selected subgroup (n = 40) of patients from the cyclosporine group, who were studied from 4 to 96 weeks after transplantation. Detailed studies of urate metabolism in six cyclosporine-treated patients revealed normal turnover rates for urate and decreases in creatinine and urate clearance, as compared with seven control subjects. We conclude that hyperuricemia is a common complication of cyclosporine therapy and is caused by decreased renal urate clearance. Gouty arthritis is the cause of considerable morbidity among renal-transplant recipients who receive cyclosporine.

Adult↗