Dilemmas in pediatric renal transplantation.

Solid organ transplantation, which began in adults in the 1950s, was extended to the pediatric population in the mid 1960s. Advances in immunosuppression and in surgical and medical skills have led to improving results in all types of organ transplantation. This success has now created many dilemmas especially in pediatric transplantation. In a field where the demands are high and resources limited, the distribution and allocation of resources becomes difficult. Complex decisions must be made with respect to who should be transplanted, when the transplant should occur, and where it should be performed. Of particular concern is the use of powerful immunosuppressive agents that may affect renal function and equally compromise patient's health with the potential for infection and malignancy. The various side effects of immunosuppressive agents may also cause difficulties in management. Decisions whether to retransplant habitual noncompliers are difficult. Diseases such as focal sclerosis and oxalosis, which recur in transplants, may affect decisions in selecting suitable recipients. The skills, experience, and resources of various multidisciplinary teams who manage these patients are often stretched to the utmost in their endeavors to achieve successful outcomes.

Calycoureterostomy: a novel technique for post-renal transplant stricture.

Stenosis and necrosis of the ureter are amongst the severe complications after renal transplantation. Several surgical techniques like simple nephrostomy or native pyeloureterostomy using the native ureter have been applied for repair. We report a case of modification to the conventional pyeloureterostomy where the native ureter was anastomosed to the transplant calyx to restore continuity of the urine collecting system. This technique is recommended as a feasible alternative when secondary reconstruction by native pyeloureterostomy is not possible.

Pregnancy in renal transplant recipients: the Royal Free Hospital experience.

BACKGROUND: For women with end-stage renal failure of child-bearing age, renal transplantation offers a chance to start a family. Pregnancies in renal transplant recipients involve risks for graft and fetus, and need to be carefully managed. AIM: To identify graft, fetal and maternal outcomes in our patients, and compare our results with those of the large national transplant registries. DESIGN: Retrospective case-note review. METHODS: We assessed the outcomes of 48 pregnancies in 24 renal transplant recipients. Obstetric data and renal parameters were examined in 27-30 pregnancies that progressed to delivery. RESULTS: Mean time from transplantation to pregnancy was 6.5 years, with an unfavourable outcome in patients who conceived within 1 year. There was a 41% incidence of fetal growth restriction (FGR), and 33% of infants were small for gestational age. FGR was associated with maternal hypertension, a pre-pregnancy serum creatinine (SCr) >/= 133 micro mol/l (1.5 mg/dl), calcineurin inhibitors and the use of cardioselective beta blockers. Two patients with pre-pregnancy SCr > 200 micro mol/l lost their grafts within 3 years of delivery. A permanent significant decline in graft function occurred in 20%, by 6 months post delivery. DISCUSSION: FGR with SGA infants occurs frequently. Atenolol should be avoided in pregnancy and Metoprolol should not be combined with calcineurin inhibitors. Pregnancy appeared to have a deleterious effect on graft function in patients with SCr > 155 micro mol (1.75 mg/dl). Patients with pre-pregnancy SCr 200 micro mol/l are at greatest risk.

European randomised trial of dual versus triple tacrolimus-based regimens for control of acute rejection in renal allograft recipients.

Two large multicentre studies have shown superiority of tacrolimus-based immunosuppressive regimens compared with standard cyclosporine-based therapy in renal transplantation. In these studies, tacrolimus was used in a triple drug regimen of tacrolimus, corticosteroids, and azathioprine. The present study aimed to determine whether a tacrolimus-based dual regimen achieves a similar efficacy and safety profile compared with conventional triple therapy. In this prospective, open, multicentre trial, 249 patients were randomised to receive either dual therapy (n = 125) of oral tacrolimus (initial daily dose of 0.2 mg/kg) and oral prednisone or additionally, as a triple therapy (n = 124), oral azathioprine. The primary endpoint was the incidence of acute rejection at month 3. In addition, all patients were included into a follow-up evaluation at 1 year after transplantation. Both treatment groups had similar baseline characteristics. At month 3, patient survival was 97.6 % (dual) and 96.7 % (triple); graft survival was 92.7 % (dual) and 91.7 % (triple). The incidence of treated acute rejection confirmed by biopsy was 27.4 % (dual) and 24.8 % (triple); difference 2.6 %, 95 % CI [-9.4 %-12.9 %], P = 0.755. The incidence of corticosteroid-resistant rejection (biopsy-confirmed) was 9.7 % (dual) and 10.7 % (triple). The overall adverse events profile was similar; leukopenia (1.6 % vs 11.6 %, P = 0.002) was more frequent with triple therapy. Between months 4 and 12, six (dual) and eight (triple) patients had a rejection. At month 12, patient survival was 95.6 % (dual) and 93.6 % (triple); graft survival was 91.8 % (dual) and 90.7 % (triple). Tacrolimus proved to be efficacious and safe with both dual and triple low-dose regimens. The addition of azathioprine to a tacrolimus/corticosteroid-based therapy did not result in an increased efficacy.

Long-term outcome of peritoneal dialysis in infants.

Debate continues concerning the treatment of infants with end-stage renal disease. We evaluated progress and outcome of 20 infants with a mean age of 0.34 year (range, 0.02-1 year) in a long-term peritoneal dialysis program at a single center. Mean weight at the start of dialysis was 4.8 kg (range, 1.7-11.4 kg), and the duration of dialysis was 17.3 months (range, 1-59 months). Eleven infants received renal transplants, 4 were switched to hemodialysis and then received transplants, 4 died, and 1 continues to receive peritoneal dialysis. There was significant co-morbidity in 6 infants who died or required hemodialysis. Catheter interventions were frequent, with 12 infants requiring at least one replacement. There were 1.1 episodes of peritonitis per patient-year; 70% of infants had 0 to 1 episode. Mean weight standard deviation score (SDS) was -1.6 at the start, -0.3 at 1 year (P =.0008), and 0.3 at 2 years (P =.0008). Height SDSs were -1.8 at the start, -1.1 at 1 year (P =.046), and -0. 8 at 2 years (P =.06). Head circumference SDSs were -1.9 at the start, -1.3 at 6 months (P =.003), and -0.9 at 1 year (P =.015). Fourteen of 16 survivors are achieving normal developmental milestones or attend mainstream school. Peritoneal dialysis in infancy is a demanding treatment, but outcome for growth, development, and transplantation justifies this intensive approach. When parents are counseled, the importance of non-renal co-morbidity must be emphasized.

Renal transplantation in children under 5 years of age.

Between March 1987 and December 1997, 59 renal transplants [49 cadaveric, 10 live related (LRD)], were performed in 54 children aged 5 years and younger. Six children required a second transplant. The median (range) age of the recipients was 2.9 (1.4-5.0) years; mean weight was 12.6 kg (7.4-23) and donor age 11 (2-50) years. Immunosuppression was cyclosporin or FK506, prednisolone, and azathioprine. Antithymocyte globulin was given as induction therapy for second transplants. Patient survival was 98.3%; 1 patient died from upper gastrointestinal haemorrhage. Graft survival was 67.7% at 1 year, 57.4% at 5 years, and 45.2% at 10 years. No LRD graft was lost during 7 years of follow-up. Thrombosis was the main cause of graft loss (10 cases) followed by vascular rejection (2 cases). There was no significant difference in graft survival between recipients aged less than 2, 2-3, and 3-5 years. The height standard deviation score (+/-SD) improved from -2.1+/-1.3 at transplantation to -1.0+/-1.3 at 1 year, -1.1+/-1.5 at 5 years, and to -0.14+/-1.1 at 10 years.

Calcineurin inhibitors enhance low-density lipoprotein oxidation in transplant patients.

BACKGROUND: Our objective was to assess the pro-oxidant status of neoral and tacrolimus in renal transplant patients and monitor the protection provided by vitamin C and vitamin E in normalizing low density lipoprotein (LDL) oxidation lag time of tacrolimus-treated patients. METHODS: Plasma LDL was isolated by density gradient ultracentrifugation from renal transplant patients receiving neoral, tacrolimus and tacrolimus with vitamin C and vitamin E. Oxidation was initiated by the addition of CuCl2 at 37 degrees C and monitored at 234 nm over 480 minutes and oxidation lag time was computed. Total antioxidant capacity of serum was measured using the enhanced chemiluminescent method. RESULTS: LDL from tacrolimus-treated patients had significantly lower oxidation lag time and serum antioxidant activity in comparison with neoral-treated patients, and this was particularly significant during the first four months after transplantation. Vitamin C and E supplementation in tacrolimus treated patients provided protection against oxidation and normalized their oxidation lag time. CONCLUSION: Calcineurin-inhibiting drugs, CsA and tacrolimus, have pro-oxidant activity and they increase the susceptibility of LDL to oxidation. Neoral formulation is fortified with DL-alpha tocopherol and therefore provides protection against oxidation. The present study clearly demonstrates the benefit of giving vitamin C and E supplements to patients taking tacrolimus and this seems to be particularly important during the early period after transplantation.

Renal transplantation in patients with complete obstruction of the inferior vena cava.

We describe 2 patients with end-stage renal disease who had complete obstruction of the inferior vena cava and were successfully treated with renal transplantation in the usual iliac fossa position. One patient is doing well, with normal renal function more than 20 years after transplantation; the other patient was lost to follow-up after 3 months. Despite some technical difficulties, these patients apparently do well provided that an adequate collateral circulation bypassing the obstruction is confirmed by venography, and the patients receive anticoagulant therapy indefinitely.

Renal transplantation in the management of bilateral Wilms' tumour (BWT) and of Denys-Drash syndrome (DDS).

BACKGROUND: Wilms' tumour (WT) occurs bilaterally in approximately 5-7% of affected children. In some patients, complete surgical removal of the malignant tissue cannot be achieved without bilateral total nephrectomy. In Denys-Drash syndrome (DDS), bilateral nephrectomy is indicated both because of the associated nephropathy usually progressing rapidly to end-stage renal failure and because of the high risk of WT development in any residual renal tissue. METHODS: Case records of patients with a diagnosis of either bilateral WT (BWT) or DDS, who underwent bilateral nephrectomy and subsequent renal transplantation between 1980 and 1996 at the Hospital for Sick Children, London, were reviewed. RESULTS: Allogeneic renal transplantation was performed in two children with BWT and four with DDS, three of whom had developed unilateral WT by the time their kidneys were removed. Renal transplantation was performed 15-49 months after bilateral nephrectomy at a mean age of 45 (26-76) months, with a minimum of 1 year tumour-free survival after completion of chemotherapy in those with WT. One patient died after renal transplantation. Five children had a favourable outcome, with a mean follow-up of 80 (29-121) months post-renal transplantation. CONCLUSION: Advances in dialysis and transplantation programmes for young children offer the potential for a marked improvement in the prognosis for patients with BWT and for those with DDS.

Prolonged action of a chimeric interleukin-2 receptor (CD25) monoclonal antibody used in cadaveric renal transplantation.

A high affinity chimeric CD25 mAb (chRFT5: SDZ CHI 621) blocking interleukin-2 binding to the interleukin-2 receptor alpha-chain was evaluated in a phase I/II study in human renal cadaveric transplantation. The chRFT5 was well tolerated with no immediate adverse effects during 6 spaced infusions (from before transplantation to day 24) in 24 patients escalating from 2.5- to 25-mg dosages. The chRFT5 had a long terminal half-life with a mean of 13.1 days. There was good correlation between the detection of chRFT5 in the serum by radioimmunoassay, the coating and suppression of CD25 on T cells, and antibody activity in patient serum samples. The chRFT5 activity persisted in vivo for up to 120 days. No antibody response to the chRFT5 was detected in any of the patients, even though two patients who required treatment with antithymocyte globulin or OKT3 developed xenogeneic antiglobulin responses while chRFT5 was still present in vivo. There was a 33% incidence of rejection and the first rejection episode always occurred during chRFT5 therapy. Patients who did not reject during therapy did not reject during the first year following transplantation. Equal numbers of patients received dual and triple immunosuppressive therapy together with chRFT5. Posttransplant lymphoproliferative disorder developed in 2 patients, both on triple therapy, at 9 months after transplantation. The disorder did not develop in any patient receiving dual therapy, and no further cases have been observed to a minimum of 2 years' follow-up. No other viral, fungal, or bacterial infectious complications were prevalent in patients treated with chRFT5.

Renal transplantation in young boys with posterior urethral valves: preliminary report.

Seven boys (mean age 38 months) with posterior urethral valves underwent renal transplantation between June 1988 and August 1991. Urodynamic studies were performed before transplantation in 6/7 patients. In 4 the investigation indicated bladders of capacity and compliance which were deemed suitable for transplantation. Two patients had poorly compliant bladders; one of these underwent bladder augmentation before engraftment and the other proceeded to transplantation without bladder surgery. Six patients have functioning renal allografts with a mean follow-up of 1.3 years and a mean plasma creatinine of 51.6 mumol/l. Mean glomerular filtration rate (ml/min/1.73 m2 SA) 6 months after transplantation was 76.8 and at 1 year it was 84.5. In one patient early rejection was followed by transplant nephrectomy. Careful pre-operative evaluation is mandatory for a successful outcome of renal transplantation in young boys with posterior urethral valves.