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PubMed1988

[Kaposi's sarcoma following kidney transplantation: remission following reduction of immunosuppression and consequent HIV infection].

Kaposi's sarcoma (KS) in renal allograft recipients is a rare though serious complication of immunosuppressive treatment. Therapeutic procedures such as surgical excision and local irradiation are inappropriate, since the endothelial-originated tumor is often multicentric. However, systemic treatment such as chemotherapy entails further immunosuppression. We observed a patient with renal allograft who developed disseminated KS of legs and trunk while receiving azathioprine, cyclosporin and prednisone after intensive rejection therapy with high dose corticosteroids, antithymocyte globulin and transplant irradiation. At that time the immunological status was similar to that of an AIDS patient, though HIV serology was negative. Azathioprine was withdrawn while cyclosporin and prednisone were continued. KS disappeared shortly after without a decrease in allograft function, and immunological parameters tended to normalize. When KS had disappeared almost completely the patient became infected with HIV. Complete remission was not hampered, nor was there recurrence of KS. The late appearance of HIV-antigenemia with seroconversion in the course of the tumor makes HIV unlikely as a causative factor. The predisposing factors for KS after renal transplantation are discussed: 1. Amplification of immunosuppression due to rejection therapy, 2. Genetic predisposition such as HLA DR5 antigen, 3. Cytomegalovirus infections. For therapy of iatrogenic KS we propose reduction of immunosuppressive therapy before additional chemotherapy is initiated.

Acquired Immunodeficiency Syndrome↗

PubMed1977

Allograft survival in patients receiving anticonvulsant medications.

The use of phenobarbital and diphenylhydantoin in transplant recipients is associated with reduced cadaver allograft survival when compared to transplant recipients not receiving anticonvulsant medication. An attempt was made to overcome the adserve effect on allograft survival by either discontinuing the anticonvulsants (2 patients) or maintaining the dose of prednisone at greater than 1 mg/kg/day (2 patients). Discontinuation of phenobarbital was successful after transplantation, with subsequent stabilization of allograft function. Of the 2 patients receiving greater than 1 mg/kg/day of prednisone, renal function is normal in one patient; however, the second is undergoing chronic rejection. Neither patient appears cushingoid. Anticonvulsant medication should be discontinued prior to transplantation. If the patient has an active seizure disorder, prednisone dosage should be maintained at a higher level.

Adolescent↗

PubMed1977

Microsurgical renal transplantation techniques in small animals.

The laboratory rat has been widely used as a preclinical model of renal transplantation. Surgical anastomosis of the small lumenal structures encountered requires strict adherence to basic principles of microsurgical technique. Nonfatal technical errors may adversely affect renal allograft function and influence experimental results. Experience obtained from a series of more than 600 rat renal transplants is discussed.

Animals↗

PubMed1988

Frozen saphenous vein allografts for constructing vascular access for hemodialysis.

Frozen saphenous vein allografts were used in seven patients to construct vascular access for hemodialysis. In five patients the allografts connected the brachial artery to the axillary vein, and in two, the radial artery to the basilic vein. Five allografts functioned for periods varying from 6 to 20 months, one is still functioning after 3 years, and one graft occluded immediately following surgery. The availability of this biological material, the ease of its preparation, the very low cost, and the satisfactory graft survival, call for further evaluation of this method for complex vascular access problems in patients on chronic hemodialysis.

Adult↗

PubMed1986

The antibody crossmatch in liver transplantation.

Six hundred sixty-seven first, second, and third orthotopic liver allografts in 520 patients were reviewed to determine the effect of recipient panel-reactive antibody (PRA) and donor-recipient antibody crossmatch on 2-year patient and liver allograft survival rates. Neither a high panel-reactive antibody nor a positive crossmatch for donor-specific preformed antibody was associated with decreased patient or liver allograft survival for primary grafts or retransplants. Two patients have been given kidney transplants immediately after a liver allograft from a donor with whom each patient had an initial strongly positive donor-specific antibody crossmatch. The liver apparently removed or neutralized circulating anti-donor antibody, since the renal allografts functioned promptly and did not experience hyperacute rejection.

Actuarial Analysis↗

PubMed1979

Risk of pneumococcal infections in renal transplant patients.

Because of the recent licensing of pneumococcal vaccine, the risk of pneumococcal infections on a renal transplant service was determined. The overall risk of infection was 7% (14 of 197 patients) over a six-year period, or 1% per year. In patients with functioning allografts, this represented a risk of 28 infections per 1,000 patient-years of follow-up. Clinically, the major presentations of pneumococcal infection were pneumonia in the patient who was rejecting his kidney and pneumococcemia of sudden onset that was often fatal. Five of the pneumococci isolated from bacteremic patients were typed; three of the isolates were types that are in the vaccine. The frequency and seriousness of pneumococcal infections in renal transplant patients suggest that pneumococcal vaccine should be given to these patients, probably before transplantation.

Bacterial Vaccines↗

PubMed1985

Cure of cryptococcal infection during continued immunosuppressive therapy.

Cryptococcus neoformans is a significant pathogen in immunosuppressed patients. In renal transplant recipients receiving prednisone, the development of cryptococcosis is associated with a poor prognosis. When such patients develop cryptococcosis they pose a particularly difficult clinical dilemma since withdrawal of prednisone, to facilitate cure of their fungal infection, may predispose to loss of their transplanted kidney. We report our experience with cryptococcal infection in 13 renal transplant patients. In 11 of these patients maintenance immunosuppression was cautiously continued to preserve allograft function. The results of our study suggest that maintenance immunosuppressive therapy may be continued throughout the period of antifungal therapy and does not preclude eradication of the infecting organisms. Our experience indicates that the prognosis for the renal transplant patient who has cryptococcosis can be improved.

Amphotericin B↗

PubMed1985

Primary hyperoxaluria (type I): attempted treatment by combined hepatic and renal transplantation.

A case is reported of a patient with renal failure and developing systemic and renal oxalosis due to pyridoxine-resistant type I primary hyperoxaluria. In spite of vigorous haemodialysis and hydration before and after operation, an allografted cadaveric kidney failed because of oxalate deposits in the transplant. The patient was treated by combined hepatic and renal transplantation. The liver allograft functioned well but the kidney had poor function due to primary acute tubular necrosis aggravated by steroid-associated acute pancreatitis, systemic cytomegalovirus infection and high cyclosporin A levels. The patient died from generalised cytomegalovirus infection. The early course after operation was associated with a reduced rate of oxalate production, which would slow the rate of oxalate deposition in the tissues. The size of the oxalate metabolic pool was also diminished. These observations are compatible with the grafted liver having corrected the metabolic lesion.

Child↗

PubMed1983

Pancreatic transplantation.

This study involved a retrospective analysis of the various factors which may have contributed to the outcome of pancreatic allograft and patient survival in our initial series of 13 segmental pancreatic transplants. Six of these patients received simultaneously renal allografts from the same donor. Pretransplant factors, such as prolonged warm ischemia and hypothermic storage periods greater than 12 hours after harvesting, correlated with an increase in acute post-transplant pancreatic failure. No clear correlation could be established between surgical techniques and final outcome of the pancreatic allograft. Rejection continues to be a major obstacle to achievement of long term pancreatic allograft function, although it was more easily monitored in the combined renal and pancreatic transplant recipients.

Adult↗

PubMed1982

Osteonecrosis of the femoral head and condyle in the post transplantation courses of children and adolescents.

The clinical courses of 29 children and adolescents who received their first renal allografts at the University of Florida from 1973 to 1979 were reviewed for the development of osteonecrosis. A minimum follow-up period of 24 months with adequate allograft function was required for inclusion in the study. The incidence of post transplantation osteonecrosis was 21%. The presence of osteodystrophy prior to transplant was strongly correlated with osteonecrosis. Dialysis against high calcium baths prior to transplantation played a protective role. Extensive reviews of their records failed to clearly identify other predisposing factors. Osteonecrosis of the knee was treated with plaster immobilization and osteonecrosis of the femoral head by resection arthroplasty and angulation osteotomy. Improved functional results were obtained on the Iowa Hip Rating Scales.

Adolescent↗

PubMed1982

Immune response to transplanted pancreas in pigs.

Segmental allografts of the body and tail of the pancreas have been carried out in pigs using an open duct technique. Diabetes was induced by total pancreatectomy. Control animals on no immunosuppression survived an average of 17 days while animals receiving CyA survived 30 days. In the CyA group those with adequate serum levels of CyA survived 46 days while those with low levels survived 18 days. Once the animal became diabetic rejection was not reversible. In this model complement dependent cytotoxicity was more useful than lymphocyte mediated cytotoxicity in predicting rejection. However the rejected pancreas showed intensive mononuclear infiltration. Malabsorption resulting from total pancreatectomy used to induce diabetes may have contributed to the erratic CyA absorption. Prolonged and relatively normal pancreatic allograft function is possible, but adequate CyA levels must be achieved and maintained. Monitoring of serum levels is essential.

Animals↗

PubMed1980

Effect of prednisone dose spacing on plasma lipids.

We have previously reported a low prevalence of hyperlipidemia in renal transplant recipients who were treated with alternate-day corticosteroid. To determine whether alternate-day prednisone per se is associated with lower plasma lipids than is daily prednisone, we studied 14 renal transplant recipients with good allograft function (serum creatinine less than 2.5 mg/dl) who were normolipidemic on alternate-day prednisone. All patients were treated with 6 months of daily prednisone (10.9 +/- 0.4 mg, mean +/- S.E.) and then returned to 6 months of alternate-day prednisone (21.6 +/- 1.0 mg). Mean plasma triglyceride, cholesterol, and cholesterol fractions on either regimen were normal and not different. There were no differences in fasting or 2 hr postprandial glucose and insulin levels. Twelve patients gained weight on daily prednisone, and 11 patients lost weight on reversion to alternate-day prednisone. The changes in ideal body weight in both periods correlated (p less than 0.05) with changes in plasma triglycerides. These data suggest that a daily prednisone regimen per se as compared to an alternate-day regimen does not dispose normolipidemic patients to hyperlipidemia. The factors contributing to the low prevalence of hyperlipidemia in our renal transplant recipients remain obscure.

Adult↗

PubMed1994

Primary disease effects and associations.

1. Although graft survival for most primary disease processes are similar at one year, significant divergence occurs by 5 years. ALP, IGA, and PC had the highest 5-year graft survival rates (72.8%, 71.2%, and 68.5%, respectively) whereas HTN and NS, the lowest (51.8% and 46.0%, respectively). 2. When primary diseases are grouped by pathogenic, pathophysiologic, and clinical similarities, the group of diseases with systemic manifestations had the lowest 5-year graft survival (55%), and the group including cystic and inherited diseases had the highest 5-year graft survival (69%). Black recipients had a predominance of "systemic" primary diseases (57%). 3. Despite having overall lower graft survival than Whites (p < 0.00001), there was no significant difference between Black and White 3-year graft survival for recipients with PC, ALP, IGA, and SLE. 4. PC recipients enjoyed excellent long-term graft survival (69%). Black recipients with PC had a 5-year graft survival rate of 64.6%. Recipients with PC had decreased posttransplant dialysis need, decreased early rejection rate, and better HLA matching than most other recipients. 5. Recipients with SLE as their primary disease had among the highest fraction of grafts lost to rejection (45.4% of all grafts lost) and the highest pretransplant sensitization rate (59.6%). 6. Recipients with HTN as their primary disease had overall lower 5-year graft survival (58% versus 63% in Whites, 44% versus 47% in Blacks), a lower rate of early allograft function (10% versus 12%, p < 0.00001), and more posttransplant dialysis needs (28.8% of patients requiring dialysis vs 23.5%, p < 0.00001) than recipients without HTN. Blacks with HTN had the lowest long-term graft survival (44.4%) of any other single group. 7. IDDM patients who expressed DR3 and/or DR4 alleles had significantly higher graft survival than patients without these DR groups. Whites expressing DR3 and DR4 and DR3 or DR4 alleles had better overall HLA matching (p < 0.001) and graft survival (75.4% and 70.7% versus 58.5% and 65.1%, p < 0.00001) than Blacks with similar DR expression. 8. SPK recipients had better 5-year graft survival than KAT recipients (66.2% versus 54.6%, p < 0.000001). This effect is most likely due to the selection of "better" lower-risk patients for SPK grafts.

Adolescent↗

PubMed1995

HMGCoA reductase inhibitors and omega-3 fatty acids as adjunctive agents in maintenance immunosuppression after solid organ transplantation.

Omega-3 fatty acids have been shown to play a role in preventing development of both acute and chronic rejection. New evidence also suggests that HMGCoA reductase inhibitors may have an immunomodulatory effect and may decrease the incidence of rejection in both animal and human transplant models. Omega-3 fatty acids and HMGCoA reductase inhibitors may be important adjunctive agents in improving short-and long-term allograft function.

Adjuvants, Immunologic↗

PubMed1994

Long-term follow-up after total parathyroidectomy without parathyroid reimplantation in chronic renal failure.

Forty-three patients with secondary or autonomous hyperparathyroidism complicating chronic renal failure (CRF) underwent total parathyroidectomy (PTX) (follow-up 2-18 years, mean 8.7 years). Five were on conservative treatment for CRF, 35 on regular dialysis, and only three had a functioning allograft. At PTX, the most frequent findings were uncontrollable hypercalcaemia, musculo-skeletal pain, radiographic changes in the phalanges, and raised plasma parathyroid hormone (PTH) concentration. Pre-operatively, all patients were loaded with dihydrotachysterol or 1-alpha-OH cholecalciferol. Postoperatively, they were maintained on tapering doses of the same drugs and, briefly, oral calcium supplements. Five glands were identified and removed in two patients, four in 35 patients, three in three patients and only two in one patient. All had changes of hyperplasia and adenoma formation, except for one with a parathyroid carcinoma. Prompt symptomatic and radiographic improvement occurred, with normalization of plasma calcium and alkaline phosphatase. Postoperative PTH levels were available in 33 patients (23 by intact PTH assay): they were persistently high in 10/33 (2/23 intact); normal in seven (6 intact); low in 11 (3 intact), and undetectable in four (3 intact). Thus, PTX was incomplete in the majority of patients. Following transplantation, 3/20 (3/18 intact) patients still had detectable PTH. Only one patient developed symptomatic recurrent parathyroid disease requiring re-operation, and complications were few. Small dosages of vitamin D continue to be required, but not calcium supplementation, and no clinical effects of possible adynamic bone have been noted. At later renal transplantation in 27 patients, an easily treatable, uncomplicated hypocalcaemia was noted in 33%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗

PubMed1994

Should elderly donors be accepted in a live related renal transplant program?

It is a matter of concern that the elderly donor may have increased risks in the peri-operative period due to age-related changes in various organ. Nephrosclerosis, atherosclerosis and low GFR of an elderly kidney may portend a poor graft outcome. A retrospective analysis of our live related renal transplant program (from June 1989 to December 1993) revealed that 27 of the donors were above 60 years of age. 21 of the recipients have been followed up for more than 1 year. These patients were compared with a cohort of 25 patients (donor age < 45 years) with similar HLA match, immunosuppressive protocol, and follow-up period more than 1 year. Graft survival at 1 year was 86% and 88% in the recipients from elderly and younger donors respectively; 1 patient in the control group died of fulminant sepsis. Mean follow-up was 21.6 months in the study group and 22.8 months in the control group. Allograft function was evaluated by serum creatinine and differential GFR by Tc DTPA scan. Serum creatinine (mg%) was 1.3 +/- 0.2 and 1.4 +/- 0.2 in the study group and 1.3 +/- 0.3, 1.2 +/- 0.3 in the control group at 3 and 12 months respectively. Glomerular filtration rate (ml/min) was 36.5 +/- 11.6 and 43.7 +/- 12.4 in the recipients from elderly donors whereas those from the younger donors had GFR (ml/min) of 40.6 +/- 9.6 and 49.6 +/- 14.2 at 3 and 12 months respectively, GFR continued to improve in both groups with follow-up. There was no difference in incidence or severity of ATN In the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Influence of oral felodipine on serum cyclosporine concentrations.

Hypertension and nephrotoxicity are frequent in renal transplant patients treated with cyclosporine. Calcium-channel blockers, because of their vasodilatory effects on the renal afferent arteriole, may be the anti-hypertensive agents of choice in this population. Unfortunately, many calcium channel blockers inhibit the clearance of cyclosporine, resulting in elevated blood levels, and worsening nephrotoxicity. Thirteen hypertensive renal transplant patients, on stable cyclosporine doses and with stable cyclosporine blood levels, had felodipine added to their antihypertensive regimens. The effect on cyclosporine level was measured. Mean trough serum cyclosporine concentration increased slightly, from 122.8 +/- 51.8 ng/ml to 143.1 +/- 81.9 ng/ml with chronic felodipine administration (p = NS). Mean systolic and diastolic pressures both fell significantly, by approximately 10 mmHg (systolic from 161 +/- 14 to 152 +/- 13 mmHg; diastolic from 100 +/- 6 to 90 +/- 7 mmHg). Serum creatinine remained unchanged. Four patients eventually discontinued felodipine. There was no significant change in their mean trough serum cyclosporine concentration when felodipine was discontinued. Thus, felodipine is an effective anti-hypertensive medication in cyclosporine-treated renal transplant recipients, without significant effect on cyclosporine blood levels, or adverse effect on allograft function.

Administration, Oral↗

PubMed1995

Delayed omega-3 fatty acid supplements in renal transplantation. A double-blind, placebo-controlled study.

An earlier reported trial suggests that omega-3 fatty acids in fish oil supplements at 6 g/day with administration commencing at the time of engraftment may reduce acute CsA renal dysfunction. When started at the time of renal transplant, there are improvements in renal hemodynamics and blood pressure, and a decrease in rejection episodes. To examine the effect of later introduction of omega-3 fatty acids, 133 cadaver renal transplant recipients received CsA, prednisone, and AZA for 16 weeks (period 1). If patients were stable without rejection or infection activity, they were randomized to 9 g of eicosapentanoic acid (EPA), 18 g of EPA, 9 g of corn oil, or 18 g of corn oil in 1-g capsules as supplements. Glomerular filtration rate, renal blood flow, number of rejection episodes, blood pressure, and episodes of CsA nephrotoxicity were followed for 26 weeks in a double-blind manner (period 2). Ninety patients were evaluable and completed the protocol. There were 50 corn oil placebo patients, 22 low dose EPA patients, and 18 high dose EPA patients. In period 1, there were 27 rejection episodes in 21 patients without differences among subsequent treatment groups. In period 2, there were 13 rejection episodes in 4 patients. No patient with an EPA level in plasma statistically higher than placebo had a rejection episode. All allografts functioned for the entire 6 months with none lost to rejection. All 5 episodes of acute CsA nephrotoxicity occurred in placebo-treated patients without differences in whole blood CsA among toxic patients, other placebo patients, and EPA-treated recipients. At the end of the study, there were no differences in glomerular filtration rate, renal blood flow, or creatinine clearance among groups. Diastolic blood pressure fell by 9 mmHg during period 2 in high dose fish oil recipients and by 10 mmHg in low dose fish oil recipients (P < 0.05), while it rose by 2 mmHg in placebo patients. No serious adverse effects of EPA supplements were noted, although compliance based on plasma EPA was erratic. Based on our experience and that in the literature, administration of omega-3 fatty acids for purposes of kidney protection would seem to be most useful when started early after surgery. Late administration in our study was associated with minor clinical benefits.

Blood Pressure↗