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PubMed1978

Natural history of asymptomatic coronary arteriographic lesions in diabetic patients with end-stage renal disease.

Arteriosclerotic heart disease is a major cause of death in insulin-requiring juvenile diabetic patients treated for end-stage renal disease. Eleven consecutive diabetic patients without clinical evidence of coronary artery disease underwent complete cardiac evaluations, including coronary arteriography, as part of transplant recipient work-ups. Seven were women and four were men; their mean age was 32 (21 to 50 years). Angiographically, every patient had multifocal atherosclerotic coronary disease. Four of seven patients tested had positive-stress electrocardiograms. In this group of patients followed for a mean of 19.8 months, eight died. Of these deaths, six were due to coronary heart disease and another due to a stroke. In two patients who became clinically symptomatic, serial angiograms revealed progressive disease of the coronary circulation; in one case, despite normal renal allograft function and serum lipid levels. The mode of end-stage renal disease treatment, serum lipids or blood pressure control could not be linked to mortality. It is concluded that arteriosclerotic heart disease is common in diabetic patients with end-stage renal disease even when angina is absent. The natural history in this high risk population is an important consideration in the selection of patients for end-stage renal disease treatment.

Adult↗

PubMed1979

Amyloid deposition in a renal allograft in a case of amyloidosis secondary to rheumatoid arthritis.

A case of amyloidosis secondary to rheumatoid arthritis is presented in which renal transplantation was performed. Five years after transplantation the patient died following an episode of acute pancreatitis. During the intervening period the rheumatoid arthritis was considered quiescent, but his course was marked by several infectious processes caused by unusual organisms. The allograft function remained normal. Apart from renal amyloid the autopsy showed extensive generalized amyloidosis, most marked in vessel walls and endocrine organs. Amyloid deposits were located exclusively in the vessel walls of the transplanted kidney.

Amyloid↗

PubMed1985

Recurrent thrombotic microangiopathy in a renal allograft. Case report and review of the literature.

Thrombotic microangiopathy in a renal allograft may either reflect a recurrence of the patient's original disease, i.e., thrombotic thrombocytopenic purpura, hemolytic-uremic syndrome, or more commonly may be a manifestation of allograft rejection. This report describes a patient in whom irreversible renal failure developed during thrombotic thrombocytopenic purpura. Two years later while her condition was in clinical remission, she received a 2 DR-matched cadaveric allograft. Nineteen days following transplantation, thrombotic microangiopathy developed in the graft with eventual loss of allograft function despite vigorous plasmapheresis therapy. Multiple factors in addition to possible recurrent disease that may have contributed to this event were identified. The literature on thrombotic microangiopathy and renal transplantation is reviewed.

Adult↗

PubMed1994

A short course of FK506 can induce limited donor-specific graft acceptance.

To examine the hypothesis that a short course of FK506 would induce permanent graft acceptance after lung transplantation, left lung allotransplantation was performed in 14 mongrel dogs. In group 1 (control; n = 3), no immunosuppressive agent was given. In group 2 (n = 7), FK506 (1.2 mg/kg intramuscularly) was given on posttransplantation days 0, 1, and 2. In group 3 (n = 4), FK506 was given at the same dose on posttransplantation days 0, 1, and 2 as well as on days 29 and 30. Allograft function was evaluated by temporarily occluding the right pulmonary artery. A mixed lymphocyte reaction study was performed preoperatively and monthly thereafter. Control lungs were all rejected within 8 days. Group 2 dogs showed improved survival, with a median survival of 49.5 days. One dog in group 2 lived more than 400 days after transplantation. The mixed lymphocyte reaction data suggests that some donor-specific unresponsiveness occurs, which lasts for only a limited time. Supplemental doses of FK506 did not significantly improve survival (median, 74 days). The whole blood level of FK506 was 17.7 +/- 3.98 ng/mL on day 15; however, on day 29 the FK506 level was almost undetectable. We conclude that a 3-day course of 1.2 mg/kg of FK506 can induce donor-specific graft acceptance, but this acceptance is not permanent.

Animals↗

PubMed1992

Treatment of bladder dysfunction in children with end-stage renal disease.

The appropriate management of the urinary bladder in patients requiring a renal transplant is significantly different in children than in adults. The etiology of end-stage renal disease (ESRD) in 13 of 50 children (26%) transplanted since 1985 was obstructive uropathy/dysplasia. Five of these children had small-capacity, poorly compliant bladders. Our current approach is to restore bladder compliance, improve emptying, and transplant into the restored bladder rather than divert. Pretransplant gastrocystoplasty was performed in three children and the donor ureter was implanted into the augmented bladder. One child awaits transplantation following his bladder augmentation. Bladder function is followed postoperatively by voiding cystourethrography (VCUG) and urodynamics. All of the children who have received transplants into augmented bladders are infection-free, voiding per urethra, and have functioning allografts. We recommend: (1) an initial VCUG in all children; (2) complete urodynamics, if appropriate; (3) urological reconstruction to include augmentation prior to transplantation; (4) transplantation into the reconstructed bladder; and (5) comprehensive follow-up including regular urodynamic assessment.

Adolescent↗

PubMed1985

Effect of endocrine pancreas allotransplantation on diabetic nerve dysfunction.

The effect of pancreatic endocrine tissue allotransplantation on the development of peripheral nerve dysfunction in streptozotocin induced diabetic rat recipients across major histocompatibility barrier was evaluated. Motor nerve conduction velocity (MNCV) and evoked muscle potential amplitudes (EMPA) were used to assess nerve function. Of the 49 transplanted diabetic animals, 40 had permanent functional allograft of either intraportal pancreatic whole islets (PWI) or intracerebral pancreatic endocrine cells (PEC). Normal MNCV and EMPA values (47.65 +/- 2.03; 5.22 +/- 0.43) were found among the recipients of intracerebral transplantation of PEC. The MNCV and EMPA were 43.30 +/- 2.59 and 4.49 +/- 0.53 respectively, in recipient rats with successful intraportal whole islet transplant. The nine animals with rejected whole islet allografts yielded MNCV and EMPA values (38.90 +/- 2.73; 3.87 +/- 0.59) comparable to the diabetic control rats.

Animals↗

PubMed1987

Renal transplantation for end-stage polycystic kidney disease.

From 1963 to 1984, 56 renal transplants were performed in 51 patients with end-stage renal failure due to autosomal dominant polycystic kidney disease (ADPKD). There were 49 cadaver and 7 living-related transplants. Overall patient and graft survival was 88 per cent and 66 per cent at one year, 59 per cent and 49 per cent at five years, respectively. There was no significant difference in patient or graft outcome with cadaver versus living-related donor kidneys. One-year graft success with and without pretransplant bilateral nephrectomy (BN) was 78 per cent versus 58 per cent, respectively (n.s.). Patient survival after return to dialysis after graft loss was not compromised by the earlier performance of BN. In patients who did not undergo pretransplant BN, there were no complications from the retained native kidneys after transplantation. In cadaver recipients, the two-year graft success rate with and without preliminary blood transfusions was 54 per cent versus 61 per cent, respectively (n.s.). Cadaver graft survival with and without adjunctive antilymphocyte globulin (ALG), excluding 3 recipients managed with cyclosporine, was 88 per cent versus 50 per cent at one year, and 70 per cent versus 32 per cent at five years, respectively (p less than 0.05). This beneficial effect of ALG was still evident when only transfused cadaver recipients were analyzed and was achieved with no resulting compromise in patient survival. Follow-up computerized tomography (CT) scanning of the transplant kidney in 10 recipients with a long-term (1-9 years) functioning allograft showed no evidence of recurrent ADKPKD.

Adult↗

PubMed1995

Acute cyclosporine A nephrotoxicity in a renal allograft recipient with hypothyroidism.

Cyclosporine A (CsA) is an important immunosuppressant in kidney transplantation. Acute CsA nephrotoxicity secondary to high drug levels is a well-recognized complication in the immediate posttransplant period. Cyclosporine A is metabolized in the body by the hepatic cytochrome P-450 enzyme system. We present a case of a hypothyroid patient who developed toxic blood CsA levels and acute nephrotoxicity with standard doses of CsA. A reduction of CsA levels led to an improvement of allograft function. Correction of the hypothyroid state resulted in the normalization of CsA requirements, but overcorrection led to an increased requirement of CsA. Thyroid dysfunction should be considered as an interacting factor in the metabolism of CsA.

Cyclosporine↗

PubMed1995

Late withdrawal of cyclosporine in stable renal transplant recipients.

The use of cyclosporine (CsA) in renal transplantation has been associated with an improvement in 1-year graft survival, but has not changed the rate of late graft loss. We sought to determine whether the intent to withdraw CsA late after renal transplantation affects renal transplant survival and whether there is a racial difference in the effect of CsA withdrawal. This retrospective study included 384 consecutive patients receiving a renal transplant during the 1984 to 1991 period who were treated with CsA/azathioprine/prednisone and who had a functioning allograft 6 months following transplantation. Of these, 97 were electively withdrawn from CsA at a median of 22 months following transplantation. Factors significantly associated with the decision to withdraw CsA included white race, older age, and lower serum creatinine. Acute rejection within 6 months of stopping CsA occurred in 12 patients (12.4%), including nine of 78 (11.5%) white patients and three of 19 (15.8%) black patients. For the group of 287 patients who were not withdrawn from CsA, the 6-year graft survival rate was 59% (95% confidence interval, 52%, 66%). For the group of patients taken off of CsA, the 6-year graft survival rate was 84% (95% confidence interval, 76%, 92%). Cox proportional hazard survival analysis indicated that the intent to discontinue CsA was associated with better graft survival, with a hazard ratio of 0.37 (95% confidence interval, 0.20, 0.70), independent of other variables that may affect graft survival. A separate analysis controlling for waiting time bias also favored the CsA withdrawal group. There was no detectable racial difference in the effect of CsA withdrawal on graft survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed2006

Differential pulmonary vein gases predict primary graft dysfunction.

BACKGROUND: Donor arterial blood gas measurements correlate poorly with lung allograft function in the recipient. We assessed the utility of reduced pulmonary vein gas (PVG) partial pressure of oxygen (PO2) in predicting the incidence of primary graft dysfunction. METHODS: While the donor was ventilated with 100% oxygen, superior and inferior pulmonary veins were directly aspirated bilaterally and pulmonary venous PO2 measured. A PO2 of less than 300 mm Hg was considered subnormal. These values were assessed for predictive value in terms of primary graft dysfunction in univariate and multivariate analysis. RESULTS: In 112 of the 201 lung and heart-lung transplants performed during the period January 2000 to December 2004, full PVGs were available for analysis. The number of pulmonary veins with sub-normal PVG correlated significantly with the incidence of severe primary graft dysfunction posttransplant in univariate (p = 0.01) and multivariate analysis (hazard ratio 2.35, p = 0.016). When analyzed separately, this correlation remained significant for recipients of single or bilateral transplants alone. No correlation existed between arterial PO2 at donor referral and incidence of primary graft dysfunction. Median duration of ventilation, intensive care unit stay, and 30-day and 90-day mortality were not significantly different for those with any subnormal PVG compared with those with all values in the normal range. CONCLUSIONS: Differential PVGs are a useful tool in the assessment of donor lung function before procurement. It is a helpful indicator of whether preischemic dysfunction is localized or diffuse, and can be used to predict the extent to which ischemia and reperfusion will exacerbate any existing abnormality.

Adult↗

PubMed2005

Impaired circulating dendritic cell reconstitution identifies rejecting recipients after clinical heart transplantation independent of rejection therapy.

OBJECTIVE: Dendritic cell (DC) mediated allo-antigen presentation to host antigen specific T-lymphocytes initiates acute allograft rejection. We investigated peripheral blood DC (PBDC) incidence and DC subset reconstitution in relation to histological diagnosis of acute cellular rejection (AR) and administration of rejection therapy after clinical heart transplantation (post-HTx). METHODS: Venous blood from 20 HTx recipients under standard immunosuppression was collected during serial endomyocardial biopsy (EMB) prior to administration of rejection therapy in a 9-month follow-up post-HTx. Echocardiographic assessment of allograft function during EMB was performed to distinguish clinical necessity for rejection therapy within histologically rejecting patients (R). Myeloid (mDC) and plasmacytoid (pDC) subsets identified by flow-cytometry were analysed for different ISHLT rejection grades. Circulating PBDC incidence and mDC/pDC ratio were compared sequentially between non-rejecting (NR) recipients and R patients treated (3A(+)) or not-treated (3A(-)) with rejection therapy during follow-up. RESULTS: Eleven samples from biopsy-proven AR episodes (AR(+): ISHLT>or=3) were compared to 89 samples from non-rejection episodes (AR(-): ISHLT grade 0, n=52; grade 1, n=29; grade 2, n=8). We observed an inverse correlation of mDCs (P<0.05) but not pDCs with increasing rejection grade. PBDC incidence and mDC/pDC ratio were low in blood samples obtained during AR (P<0.05 and P<0.01, respectively). Both PBDCs and mDC/pDC ratio decreased during each AR episode (P<0.05). Comparison of 3A(+) and 3A(-) rejectors with NR patients after 12 weeks post-HTx revealed lower PBDC incidence (P<0.01) and mDC/pDC ratio (P<0.05) for R patients, independent of rejection therapy. CONCLUSIONS: Defective DC subset reconstitution by dendritic cell profiling identifies patients at risk for AR after 3 months post-HTx. This finding may contribute to further optimization of immunosuppressive treatment strategies after clinical heart transplantation.

Adult↗

PubMed2005

Chlamydia pneumoniae infection after lung transplantation.

BACKGROUND: Chlamydia pneumoniae is established as a common agent of acute respiratory tract infection and has been implicated in the pathogenesis of asthma and chronic obstructive pulmonary disease. Airway disease is a prominent cause of morbidity and mortality after lung transplantation. We investigated the role of C pneumoniae as a pulmonary pathogen after lung transplantation. METHODS: Eighty lung transplant recipients underwent 232 bronchoscopies with bronchoalveolar lavage with or without transbronchial lung biopsy during 1 year for surveillance of rejection and infection, or where clinically indicated. RESULTS: C pneumoniae was detected using nested polymerase chain reaction in 9 of 36 (25%) recipients studied within 30 days of lung transplantation, 3 of whom remained positive on repeat lavage and died from airway disease in the first year post-operatively. By comparison, all 27 recipients with negative lavage survived >1 year. Lavage was positive for C pneumoniae in 18 of 71 (25%) recipients studied >30 days after lung transplantation, 5 of whom had pneumonia and 8 of whom had bronchiolitis obliterans syndrome. Eleven also had acute pulmonary allograft rejection. CONCLUSIONS: Persistent infection with C pneumoniae (whether donor-derived, de novo or re-activated) appears deleterious to pulmonary allograft function and is associated with early mortality, rejection and bronchiolitis obliterans syndrome after lung transplantation. A trial of empiric antibiotic therapy for C pneumoniae may therefore be warranted in the attempt to prevent progressive inflammatory airway disease.

Adult↗

PubMed2005

Atrial fibrillation as a cause of left ventricular dysfunction after cardiac transplantation.

We report 3 cases of late-onset atrial fibrillation several years after cardiac transplantation, each involving left ventricular systolic dysfunction in the absence of cardiac rejection or cardiac allograft vasculopathy. Although the etiology of late-onset atrial fibrillation in cardiac transplant recipients is not clear, its presence in the absence of cardiac rejection or coronary allograft vasculopathy can result in left ventricular systolic dysfunction, and therefore should be considered in the differential diagnosis of cardiac allograft failure. The onset of atrial fibrillation years after a heart transplant is not necessarily an indication of rejection. Aggressive rate control and restoration of normal sinus rhythm may improve allograft function in such cases.

Atrial Fibrillation↗

PubMed2006

Successful combined heart and kidney transplantation in a patient with sickle-cell anemia.

Little is known about the management of dual-organ transplantation for sickle-cell disease (SCD)-related complications. In this case study, we report the successful outcome of combined heart and kidney transplantation in a patient with SCD. The recipient was a 33-year-old man with homozygous SCD, who developed end-stage heart and renal failure requiring combined heart and kidney transplantation. The patient was managed with pre-operative blood transfusion and moderate hypothermic cardiopulmonary bypass, with limited peri-operative complications. During the first 6 months there was one episode of acute heart rejection without concomitant renal rejection. Eighteen months after surgery, the patient is at home without vaso-occlusive crises or septic complications. Heart and renal allograft function is preserved, without coronary artery vasculopathy, but with asymptomatic moderate transplant renal artery stenosis. SCD is managed by periodic transfusion. This case study demonstrates that combined heart and kidney transplantation is feasible in patients with SCD. Careful attention to peri- and post-operative management is required.

Adult↗

PubMed2005

Pregnancy in patients with previous successful renal transplantation.

OBJECTIVE: To evaluate the risk factors affecting pregnancy, perinatal outcomes, and short-term graft condition in women who underwent renal transplantation. METHOD: Between May 1998 and January 2005, the histories of 20 pregnancies in 17 renal transplant recipients were reviewed retrospectively at the Ministry of Health Aegean Obstetrics and Gynecology Teaching Hospital. RESULT: There were significant associations between high serum creatinine level (>1.5 mg/dL) prior to pregnancy and preterm delivery (P=0.04), and between short interval between transplantation and pregnancy (<2 years) and increased rate of cesarean sections (P=0.04). There were no significant changes in serum creatinine levels during pregnancy in these women, and there were no acute rejection and graft loss during pregnancy or in the 6 months following delivery. CONCLUSION: These findings suggest that, although pregnancy does not adversely affect short-term renal allograft function, the rates of obstetric and perinatal complications are increased. Risk factors present before conception are a short interval between renal transplantation and pregnancy and poor renal function.

Adult↗

PubMed2006

Early steroid withdrawal protocol with basiliximab, cyclosporine and mycophenolate mofetil in renal-transplant recipients.

OBJECTIVE: Adverse effects of steroids have led to efforts to minimize their use in recipients of organ transplants. This study evaluated an early steroid withdrawal protocol including basiliximab, cyclosporine (CsA) and mycophenolate mofetil (MMF) in renal-transplant recipients. METHODS: Between January 2001 and April 2005, our early steroid withdrawal protocol was used in 130 patients who underwent renal transplantation. Immunosuppression consisted of CsA (6-8 mg/kg), MMF (2 g/kg) and methylprednisolone (MP); basiliximab was given as induction therapy (steroid withdrawal group). MP was administered in a dose of 500 mg or 250 mg at renal transplantation; thereafter, the dose was rapidly tapered and MP was withdrawn on day 14 post-transplant. RESULTS: The incidence of acute rejection in the steroid withdrawal group was similar to that in the conventional steroid treatment group (without basiliximab) (18% vs. 21%). The severity of rejection episodes was similar in the two groups. Patient and graft survivals were 100% and 97% in the steroid withdrawal group. In 80 of the 130 patients (62%) in the steroid withdrawal group, MP was successfully withdrawn, with good allograft function during follow-up. In the other 50 patients (38%), MP was reinitiated because of acute rejection or other reasons. The success rate of steroid withdrawal 12 months after transplantation in recipients of ABO-compatible grafts was significantly higher than that in recipients of ABO-incompatible grafts (66% vs. 44%). The dose of MMF during the 12 months after renal transplantation was significantly lower in steroid reinitiated group than in the successful withdrawn group (p<0.05). Patients in the successful withdrawn group showed metabolic benefits such as lower cholesterol levels as compared with the steroid reinitiated group. CONCLUSION: Although further follow-up is necessary to confirm our results, our protocol successfully permitted the early withdrawal of steroids in 62% of renal-transplant recipients, with no resumption of steroid treatment during 3 years of follow-up.

ABO Blood-Group System↗

PubMed2005

Recurrence of clinically significant hepatitis A following liver transplantation for fulminant hepatitis A.

BACKGROUND: We report hepatitis A virus (HAV) infection of a liver allograft following transplantation for fulminant liver failure due to HAV infection. This rare condition has been described in only three patients to date. After liver transplantation allograft function was good, but starting 80 days after transplantation, episodes of acute graft dysfunction were observed. OBJECTIVES: To elucidate the reason for acute hepatic dysfunction a large number of differential diagnoses were tested. RESULTS: HAV RNA was undetectable for more than 80 days after transplantation. Detection of genomic HAV RNA by RT-PCR in serum and stool at the time of graft dysfunction led to the diagnosis of recurrent HAV infection. CONCLUSIONS: We suggest that the risk of HAV reinfection after liver transplantation may be far higher than expected as results may be misinterpreted as rejection episodes.

Hepatitis A↗

PubMed2005

Thin basement membrane nephropathy and renal transplantation.

The clinical implications of thin basement membrane nephropathy (TBMN) in renal transplantation must be considered from the perspectives of both the allograft recipient and the donor. Most individuals with TBMN have a benign course, but some develop end-stage renal failure (ESRF) and undergo transplantation. ESRF in patients with TBMN often results from the presence of additional glomerular or interstitial lesions and some of these, such as immunoglobulin (Ig)A disease, may recur in the renal allograft and affect outcome. In addition, individuals with TBMN always must be distinguished from those with glomerular membrane thinning due to Alport syndrome. This is not only to enable appropriate genetic counseling but also to anticipate the possible complication of posttransplant anti-glomerular basement membrane disease. From the perspective of the live renal donor, donation from individuals with TBMN (or carriers of X-linked Alport syndrome with thinned membranes) remains controversial because the risks remain unknown. Any effects of the thinned membranes themselves on allograft function are unclear. Further advances in our understanding of the clinical, pathologic, and molecular features of TBMN should result in improved assessment of potential live donors and help stratify those at risk for renal impairment.

Glomerulonephritis, Membranous↗