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PubMed1994

Effect of cyclosporin treatment on metabolic and hormonal responses to mixed meal plus oral glucose in dogs with intrasplenic pancreatic islet autograft.

We evaluated the effect of immunosuppressive concentrations of cyclosporin A (CsA), given intramuscularly, on the levels of glucose, insulin, C-peptide, glucagon, pancreatic polypeptide (PP), lactate, alanine and beta-hydroxy-butyrate in a group of pancreatectomized mongrel dogs with intrasplenic islet autografts, given mixed meal and oral glucose, while on or off CsA therapy. In whole blood, HPLC-measured drug levels ranged from 412 to 803 ng/ml. Basal glucose and insulin concentrations did not differ significantly between non-pancreatectomized, control dogs and transplanted animals, whether on or off CsA. After the meal challenge, glucose levels were significantly higher in transplanted animals than in normal dogs, and no additional deleterious effect of CsA was observed. Similar insulin and C-peptide responses were found in animals either on or off CsA treatment. Fasting and post-meal concentrations of glucagon, PP and intermediate metabolites were not affected by the drug. These results suggest that intramuscular CsA, given at doses known to sustain islet allograft function, has no detrimental effect on the hormonal and metabolic responses to mixed meal and oral glucose in dogs with intrasplenic islet autografts.

3-Hydroxybutyric Acid↗

PubMed2004

[Sports after heart transplantation].

Heart transplantation has the potential to change a patient with a life-threatening illness into an active healthy person with a potentially excellent quality of life. Survival with excellent allograft function for 10 years is now common for the majority of patients. However, exercise performance remains impaired when compared to healthy subjects. Reasons include a decrease of maximal heart rate, cardiac output and oxygen uptake, which are present after heart transplantation. The role of these abnormalities may differ as a function of time after surgery. Possible reasons like cardiac denervation, diastolic dysfunction, and endothelial dysfunction are discussed in this article. Furthermore, exercise capacity may be diminished because of peripheral limitations associated with physical deconditioning, abnormal muscle structure and function or pharmacological side effects. Endurance and strength training may greatly improve muscle function and maximal aerobic performance as well as reduce side effects of immunosuppressive therapy. Exercise should be considered a valuable tool in the long-term treatment after heart transplantation.

Exercise Therapy↗

PubMed1998

Long-term follow-up of renal transplant recipients treated with losartan for post-transplant erythrosis.

Post-transplant erythrosis (PTE) develops in 9%-22% of all renal transplant recipients. Defined as a persistently elevated hematocrit (> 0.51), it occurs most commonly during the first 2 years post-transplantation in hypertensive males with excellent allograft function. Several studies have focused on a major role for angiotensin II in PTE pathogenesis, and some case reports have suggested that losartan is an effective treatment for PTE. Nevertheless, its long-term safety and efficiency have not been reported in renal transplant recipients suffering from PTE. We describe four patients successfully treated with losartan for PTE. Hematocrit remained normal for 21, 18, 15, and 15 months, respectively, after the beginning of losartan therapy. Mean erythropoietin concentration was not modified by treatment (17 +/- 3.7 mU/ml vs 17 +/- 3.8 mU/ml) and serum creatinine concentration remained stable. We conclude that losartan is a safe and effective long-term treatment for PTE.

Adult↗

PubMed1999

Permanently reduced plasma ionized magnesium among renal transplant recipients on cyclosporine.

Hypomagnesemia is common after kidney transplantation. Until recently, only the determination of total plasma magnesium was possible, whereas the assessment of ionized magnesium has since become practicable. One hundred and nine renal transplant patients on cyclosporine with allografts functioning stably for more than 6 months and plasma creatinine levels of less than 200 micromol/l entered the study. Total and ionized circulating magnesium were assessed among these 109 patients, as well as among 15 renal transplant patients not on cyclosporine and 21 healthy volunteers. Cyclosporine patients showed significantly lower total and ionized circulating magnesium values than the two control groups. Plasma total and ionized magnesium levels were also significantly lower among cyclosporine patients treated concurrently with insulin or oral hypoglycemic agents than among those who were not. No correlation was noted between time after transplantation and plasma magnesium with respect to patients on cyclosporine. In conclusion, the study demonstrates that a large subset of renal transplant patients treated with cyclosporine have permanent deficiencies of ionized and total magnesium. The tendency towards hypomagnesemia is also more pronounced among patients with diabetes mellitus.

Adolescent↗

PubMed1999

Development of bronchiolitis obliterans syndrome despite blood chimerism in human lung transplant recipients.

Bronchiolitis Obliterans Syndrome (BOS) remains the overwhelming obstacle to the success of lung transplantations (LTx). The presence of donor-specific microchimerism (DSM) and its association with lung allograft function is not well defined. To investigate the relationship between chimerism and BOS, blood was obtained from 21 LTx recipients. Genomic DNA was isolated from patient blood, and PCR-based techniques were used to identify recipient and donor HLA-DR. Fifty percent of the LTx recipients with BOS exhibited DSM at "T1" time post transplant, and 40% at one year follow-up (T2). However, 54% exhibited DSM in the BOS-free group at T1, and 44% at T2. Of the BOS-free, DSM-positive patients at T1, 29% developed BOS by T2. In contrast, 50% of BOS-free DSM-negative patients 50% developed BOS (P > 0.05). Double LTx had a higher prevalence of DSM (73%) and a lower prevalence of BOS (46%) than single LTx (50% and 80% respectively, P > 0.05). One-HLA-DR-antigen-matched LTx recipients show a low prevalence of DSM compared to non-matched (P < 0.05). This study demonstrates that the development of BOS in LTx recipients could also occur in the presence of blood chimerism.

Adult↗

PubMed1998

Long-term results of treatment of chronic hepatitis B, C and D with interferon-alpha in renal allograft recipients.

The aim of this study was to evaluate the efficacy and safety of interferon-alpha (IFN-alpha) therapy of chronic hepatitis B, C and D (HBV, HCV and HDV, respectively) in renal transplant recipients. A group of 42 patients (30 males, 12 females, mean age 38 years) with documented viraemia and chronic active hepatitis (CAH) were studied, of whom 1 had HBV infection alone, 11 had HCV infection alone, 3 had HBV and HDV infection concomitantly, 12 had HBV and HCV infection concomitantly, and 2 had HBV, HCV and HDV infection concomitantly. Patients received 3 MU IFN-alpha three times weekly for 6 months. After IFN-alpha therapy, 18 patients (43%) achieved normal alanine aminotransferase (ALT) activity and a partial response was observed in 12 (29%) patients. Two patients relapsed (one with HCV and one with HBV + HCV infection) immediately after the cessation of IFN-alpha therapy. Repeated liver biopsy was performed in 16 patients after 6-24 months of therapy and revealed progression to cirrhosis in five patients, remission in two and stable disease in nine. None of the patients cleared HCV RNA, four patients cleared HBeAg (two also HDV), and one both HBV and HCV. Five patients died during IFN-alpha therapy (one as a consequence of liver failure), and four died during the 6 months after therapy (two as a consequence of liver failure). During IFN-alpha therapy renal allograft function remained stable in 31 patients and acute rejection episodes occurred in 7, of whom 5 lost their graft and all had experienced rejection episodes before. In 16 patients normalization of ALT continued during long-term follow-up (median 22 months, range 0-84 months). IFN-alpha seemed to be moderately effective in the treatment of chronic HBV or HCV infections, but cannot be recommended for recipients infected with both HBV and HCV.

Adult↗

PubMed1999

Determination of urinary thymidine glycol using affinity chromatography, HPLC and post-column reaction detection: a biomarker of oxidative DNA damage upon kidney transplantation.

Reactive oxygen species are generated during ischaemia-reperfusion of tissue. Oxidation of thymidine by hydroxyl radicals (HO) leads to the formation of 5,6-dihydroxy-5,6-dihydrothymidine (thymidine glycol). Thymidine glycol is excreted in urine and can be used as biomarker of oxidative DNA damage. Time dependent changes in urinary excretion rates of thymidine glycol were determined in six patients after kidney transplantation and in six healthy controls. A new analytical method was developed involving affinity chromatography and subsequent reverse-phase high-performance liquid chromatography (RP-HPLC) with a post-column chemical reaction detector and endpoint fluorescence detection. The detection limit of this fluorimetric assay was 1.6 ng thymidine glycol per ml urine, which corresponds to about half of the physiological excretion level in healthy control persons. After kidney transplantation the urinary excretion rate of thymidine glycol increased gradually reaching a maximum around 48 h. The excretion rate remained elevated until the end of the observation period of 10 days. Severe proteinuria with an excretion rate of up to 7.2 g of total protein per mmol creatinine was also observed immediately after transplantation and declined within the first 24 h of allograft function (0.35+/-0.26 g/mmol creatinine). The protein excretion pattern, based on separation of urinary proteins on sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), as well as excretion of individual biomarker proteins, indicated nonselective glomerular and tubular damage. The increased excretion of thymidine glycol after kidney transplantation may be explained by ischaemia-reperfusion induced oxidative DNA damage of the transplanted kidney.

Adult↗

PubMed2004

The use of a cyclosporin-ketoconazole combination: making renal transplantation affordable in developing countries.

OBJECTIVES: The costs of immunosuppressive drugs in renal transplant recipients remains prohibitively high. Ketoconazole (KZ) has, in limited studies, been shown to significantly reduce the dose of cyclosporin (CyA) after renal transplantation. We report our long-term experience with the use of KZ in a large group of renal transplant recipients. Although this study was not a formal health economic assessment, we undertook a cost-saving analysis of the CyA-KZ combination usage. METHODS: The 170 patients (174 transplants) undergoing renal transplantation between 1991 and 1997 included in the study received CyA (10 mg/kg/day), prednisone (30 mg/day) and azathioprine (100 mg/day) in the immediate perioperative period. At 1 month post-transplantation, KZ (100 mg twice daily) was added and the CyA dose reduced to 25% and the prednisone dose to 50%. The CyA dose was adjusted to maintain trough levels of 150-200 ng/ml. RESULTS: There was an 85% reduction in the dose of CyA. The average costs were 10.61 pounds sterling for CyA alone compared with pound 2.26 (pounds sterling) for the CyA-KZ combination, which represents an average savings of 8.35 pounds sterling (79%) per patient per day. The estimated savings during the study period was 999,930 pounds sterling. The patient and graft survival for patients receiving KZ was similar to patients on the South African Dialysis and Transplant Registry. Graft survival was significantly worse in black patients. CONCLUSION: The use of KZ with CyA in renal transplant recipients with stable allograft function results in a significant reduction in the dose of CyA and a significant cost savings, without compromising patient or graft survival. The regimen may be useful in countries with limited resources.

Adolescent↗

PubMed2003

Staghorn calculus in renal allograft presenting as acute renal failure.

BACKGROUND: Urolithiasis is a rare complication in renal transplant recipients. We report a case of a staghorn calculus occurring in renal allograft, presenting as anuric renal failure with Gram-negative sepsis. METHODS AND RESULTS: A 48-year-old Caucasian female, with end-stage renal disease due to autosomal dominant polycystic kidney disease, underwent cadaveric renal transplantation in 1986. Sixteen years after transplant, she presented with Gram-negative sepsis with Proteus mirabilis and acute anuric renal failure in the allograft. After undergoing an emergency nephrostomy and treatment of sepsis, a staghorn calculus was subsequently removed by percutaneous nephrolithotomy. Based on the stone analysis and history of urinary tract infections with urease splitting bacteria, the calculus was thought to be infection-induced. CONCLUSION: Although a rare complication, urolithiasis in an allograft can be associated with significant morbidity. Immediate recognition is critical to restore renal allograft function and to treat associated serious infection in an immunocompromised patient.

Acute Kidney Injury↗

PubMed2002

Conversion from cyclosporine to tacrolimus in pediatric kidney transplant recipients.

In pediatric kidney transplant recipients, tacrolimus has been proposed either for primary immunosuppression or as a rescue agent for refractory acute rejection, chronic rejection, and cyclosporine toxicity. This paper describes our experience with tacrolimus conversion from cyclosporine-based therapy in six selected cases: four due to refractory acute rejections unresponsive to conventional therapy, one to chronic graft rejection, and one to cyclosporine-related hypertrichosis. A "simple-switch" conversion was used without any overlap, starting with a dose of 0.2 mg/kg per day. The time to conversion varied from 10 to 730 days after the transplant. In the patients with acute rejection, the median time to reversal after tacrolimus conversion was 12 days. The symptoms of the patient with cyclosporine toxicity completely resolved without any loss of allograft function. The patient with chronic rejection maintained stable renal function for more than 1 year after conversion. A new onset of post-transplant diabetes mellitus and dose-related nephrotoxicity were recorded as adverse events. In conclusion, our experience suggests that tacrolimus can play an important role in the salvage treatment of pediatric kidney transplantations with deteriorating graft function due to acute rejection refractory to standard therapy. Tacrolimus conversion also provides excellent results in the presence of cyclosporine toxicity.

Adolescent↗

PubMed2004

Two-hour post-dose cyclosporin A levels in adolescent renal transplant recipients in the late post-transplant period.

Although the success of renal transplantation is closely linked to the immunosuppression provided by cyclosporin A (CsA), the best way to monitor the blood levels of CsA is still not clear. Trough CsA levels (C(0)) are commonly used, but the 2-h post-dose CsA levels (C(2)) are reported to correlate better with area under the curve. The aim of this study was to evaluate the correlation of C(2) levels with allograft function in adolescent renal transplant recipients in the late post-transplant period (6 months after transplantation) compared with C(0 )levels. The data of 17 adolescent renal transplant recipients (12 males, 5 females) were evaluated retrospectively. The mean age at the time of transplantation was 15.212+/-2.918 years and the mean follow-up period was 53.172+/-34.090 months. C(0) levels correlated with oral CsA and diltiazem doses, while C(2) levels exhibited no correlation. When C(2) levels were classified as 0-400, 401-800, and 801-1200 ng/ml, no statistically significant difference was found between these groups with respect to glomerular filtration rate (P=0.830). Although 82% of the patients had C(2 )beneath the therapeutic level (<800 ng/ml), none had an acute rejection episode. In conclusion, optimum C(2) levels could be different from levels in the adult population. Furthermore, the correlation of C(2) levels with CsA dose seems to be weaker than in the adult population. Thus, further studies are needed to determine a more reliable predictor for CsA dose monitoring and target blood CsA levels in adolescent patients.

Adolescent↗

PubMed2004

Pathomechanisms and the diagnosis of arterial hypertension in pediatric renal allograft recipients.

Arterial hypertension is common in pediatric renal allograft recipients. While the causes are multifactorial, including chronic graft rejection, immunosuppressive therapy, and renal vascular disorders, the effect of hypertension on renal allograft function is detrimental. As in adults, if not treated early and aggressively, hypertension may lead to cardiovascular damage and graft failure. Pathophysiological changes in the arteries and kidney af-ter renal transplantation and the impact of receptor regulation have not been studied extensively in children. For identifying children with hypertension following renal transplantation casual blood pressure measurements do not accurately reflect average arterial blood pressure and circadian blood pressure rhythm. Ambulatory 24-h blood pressure monitoring should regularly be applied in trans-plant patients. The purpose of this review is to analyze pathophysiological aspects of risk factors for arterial hypertension and underline the importance of regular blood pressure monitoring and early therapeutic intervention.

Adolescent↗

PubMed2004

Recurrent focal glomerulosclerosis in pediatric renal allografts: the Miami experience.

Recurrence of focal glomerulosclerosis (FSGS) following renal transplantation is a common cause of allograft loss and clinical morbidity. Recent attempts to control proteinuria and morbidity with plasmapheresis (PP) have met with limited success. Our experience with the use of mycophenolate mofetil (MMF) and angiotensin blockade (AB) in the management of refractory FSGS pre transplant suggested its potential benefit in post-transplant recurrence. This report presents our 25-year experience in pediatric renal transplantation of patients with FSGS divided into two treatment eras: Era 1-prior to use of daclizumab (anti-IL-2R) and Era 2-after daclizumab. A total of 179 pediatric patients were transplanted during the 25-year period. FSGS was confirmed in 27 (15%); 16 of 28 allografts (57%) had recurrence of FSGS during the post-transplant period. In Era 1, only 6 of 16 (38%) recurred in the allograft, while 10 of 12 (83%) recurred during Era 2. The odds ratio of recurrence of FSGS in the allograft after induction with anti-IL-2R was 8.3 (95% confidence interval=1.3-52, P =0.02). Only 2 patients in Era 1 received PP, while 10 in Era 2 were entered into an intensive PP protocol followed by maintenance with AB consisting of angiotensin receptor blockers alone, or in combination with angiotensin-converting enzyme inhibitor. Although proteinuria decreased an average of 80+/-16% with PP, the response was variable and severe morbid edema persisted in poor responders. Maximum benefit occurred with the addition of AB and MMF. After a follow-up of 27+/-15 months, proteinuria has shown a sustained decrease of 94+/-8% below baseline. In conclusion, our experience suggests that, with recurrent FSGS, a limited course of PP followed by maintenance therapy with AB and MMF improves symptoms and may preserve allograft function.

Adolescent↗

PubMed2000

Conversion from tacrolimus to neoral for postrenal transplant diabetes.

Diabetes mellitus (DM) is a well-recognized complication of immunosuppressive therapy in the post-transplant (Tx) period. The DM encountered in the setting of tacrolimus therapy has been managed in the past by tacrolimus dose reduction and a rapid corticosteroid taper; frequently insulin therapy is also required to maintain normoglycemia. However, the dose reduction of immunosuppressive agents has often resulted in acute allograft rejection. We are reporting our experience in managing three pediatric renal Tx recipients who developed DM in the post-Tx period while on triple immunosuppressive therapy including tacrolimus and corticosteroids. All of our patients were managed by substitution of tacrolimus with conventional doses of neoral while maintaining their usual corticosteroid dose. All three patients had resolution of hyperglycemia and none experienced acute rejection. Tacrolimus was then successfully reinitiated 4.6 months later; at last follow-up, all of our patients have good allograft function and have maintained a normal blood sugar. In conclusion, we feel that conversion of patients from tacrolimus to neoral should be attempted as a safer alternative to tacrolimus dose reduction, for managing post-Tx DM in tacrolimus treated patients.

Adrenal Cortex Hormones↗

PubMed1999

Etiology and outcome of chronic renal failure in Indian children.

A prospective analysis of all new pediatric cases of chronic renal failure (CRF) was performed at our hospital over a 1-year period. The diagnosis of CRF was based on serum creatinine >2 mg/dl with supportive clinical, laboratory, and radiological findings. There were a total of 48 patients with CRF with a median age of 13 years (range 10 days to 16 years). The causes of CRF included glomerulonephritis (37.5%), obstruction and interstitial (52%), hereditary (6.3%), and undetermined (4.2%). Patients were symptomatic for a mean of 33.2 months (range 10 days to 11 years) at presentation. Eight patients (16.7%) had acute reversible deterioration of renal function at presentation. This was due to accelerated hypertension in 2, infection in 3, volume depletion in 2, and nonsteroidal antiinflammatory drugs in 1 patient. At presentation, 22 (46%) children had mild to moderate renal failure and 26 (54%) had end-stage renal disease. Twenty-one children (43. 7%) had associated illness at presentation. Mean follow-up was 22.9 weeks (range 2-126 weeks). At the end of the study period, 10 (21%) patients were on conservative treatment, 7 (14.6%) on maintenance dialysis, 8 (16.7%) patients had functioning allografts, 4 (8.3%) patients had died, and 19 (39.6%) opted against further therapy. We conclude that CRF in Indian children carries a poor prognosis due to late referral and the limited availability and high cost of renal replacement therapy.

Adolescent↗

PubMed2001

Perioperative management of central diabetes insipidus in kidney transplantation.

Central diabetes insipidus is clinically masked in dialysis patients. We report a 12-year-old girl receiving a living-related donor graft for renal failure from Alport syndrome, in whom a craniopharyngioma had been resected 6 months before transplantation. Pretransplant evaluation had documented central hypothyroidism, growth hormone deficiency, and presumptive hypogonadotropic hypogonadism. The corticotropin-releasing factor test had been normal. Four hours after transplantation, urine output exceeded 1,000 ml/h without diuretic therapy. Serum sodium concentration was 155 mmol/l, serum osmolality 333 mmol/kg, and plasma antidiuretic hormone 4.9 ng/l, while urine osmolality was 233 mmol/kg. Desmopressin acetate was started by continuous intravenous infusion at 1 microgram/day. Serum electrolytes rapidly normalized, urine output stabilized at 2 l/day. The patient was discharged 4 weeks after transplantation with good allograft function, receiving intranasal desmopressin acetate 10 micrograms twice daily. Pre-existing central diabetes insipidus is unmasked after successful kidney transplantation, leading to rapid dehydration and hypernatremia, which can be prevented by prompt institution of desmopressin therapy.

Child↗

PubMed2001

Syndrome X following renal transplantation.

The cardiovascular risk factors that accompany postrenal transplantation include an atherogenic lipid profile, hypertension, new-onset diabetes mellitus, and a chronic prothrombotic state. This picture describes the dysmetabolic syndrome or syndrome X, which can significantly aggravate not only the risk of cardiovascular disease and death in this population, but also the progression of allograft dysfunction. The recognition and aggressive management of the dysmetabolic syndrome in postrenal allograft recipients may have a favorable impact on the incidence of cardiovascular morbidity and mortality in these patients and prolong allograft function.

Humans↗

PubMed1975

Microangiopathic hemolytic anemia in renal allotransplantation. Repart of a successfully treated case and review of the literature.

The development of microangiopathic hemolytic anemia after renal transplantation in a 17 year old white boy is reported, and the literature is reviewed. In this patient microangiopathic hemolytic anemia developed 6 weeks after renal transplantation during a second episode of rejection. Light, fluorescence and electron microscopy demonstrated the renal vascular lesion associated with this syndrome. In contrast to the other four previously reported cases of microangiopathic hemolytic anemia associated with renal allotransplantation, this patient had complete resolution of the microangiopathic hemolytic anemia with heparin therapy and improved allograft function, presumably with diminution of the vascular lesion. He survived a complicated early period after renal transplantation and has shown no recurrence of microangiopathic hemolytic anemia in the 18 months since transplantation. Special red blood cell and fibrinogen studies are discussed.

Adolescent↗