Gisela Offner

Oxalate elimination via hemodialysis or peritoneal dialysis in children with chronic renal failure.

Abstract. Oxalate elimination and oxalate dialysance via hemodialysis (HD) or peritoneal dialysis (CAPD) has not been studied in detail in pediatric patients. We studied plasma oxalate, oxalate elimination, and oxalate dialysance in 15 infants and children undergoing CAPD (9 female, 6 male, aged 9 months to 18 years) and in 10 children on HD (4 female, 6 male, aged 7 – 18 years). Two children in each group had primary hyperoxaluria (PH). The mean duration of dialysis prior to examination was 12±11 months in CAPD and 31±23 months in HD patients. Bicarbonate HD was performed 5 h three times a week, CAPD consisted of five daily exchanges in 5 patients and four changes in the remaining 10 children (dwell volume 40 ml/kg body weight, 2.3 g/l glucose). Although oxalate dialysance was significantly higher in HD (mean 115.6 ml/min per 1.73 m2 in HD versus 7.14 ml/min in CAPD), mean oxalate elimination per week was not different between both renal replacement therapies (3,478 μmol/1.73 m2 surface area/week in CAPD versus 3,915 μmol/1.73 m2 per week in HD). Oxalate elimination in patients with PH was between 6,650 and 9,900 μmol/week. Plasma oxalate remained elevated in both procedures [28 – 84 μmol/l in CAPD (92/148 in PH) and 33 – 101 μmol/l in HD (70/93 in PH)]. Oxalate elimination can be increased by a more frequent hemodialysis regimen.

Interleukin-2 receptor antibodyinduced alterations of ciclosporin dose requirements in paediatric transplant recipients

In a retrospective analysis of paediatric renal-transplant recipients receiving basiliximab, we noted significantly increased blood concentrations of cyclosporin, early cyclosporin toxicity, and a lower dose requirement within the first 10 days compared with controls. As the CD25 saturation fades at days 28-50, cyclosporin concentrations decline and 20% higher doses are required to maintain adequate trough concentrations. We suggest that an interleukin-2 receptor-mediated alteration of the cytochrome P450 system causes this systemic drug interaction and propose that the initial ciclosporin dose should be limited to 400 mg/m2 if used in combination with basiliximab.

Paediatric kidney transplantation in small children – a single centre experience

Kidney transplantation (KTx) remains a challenging procedure in small children. This study presents our centre results. From 1983 to 2004, 40 of 442 paediatric KTx were performed in children with a body weight <11 kg. Median body weight was 9.2 kg (range: 7.2–10.9), median age was 2.7 years (range: 0.9–5.9). Preoperative dialysis was performed in 87.5%. In 24 cases (60%) grafts came from cadaveric (CAD) and in 16 cases (40%) from living related donors (LRD). Median donor age of CAD was 8 years (range: 1–40). The overall 1‐, 5‐, 10‐, 15‐year patient survival was 93%, 90%, 90% and 87% respectively. The overall 1‐, 5‐, 10‐, 15‐year graft survival was 90%, 80%, 66% and 56% respectively. There was no significant difference in survival of CAD or LRD grafts. Median follow‐up was 13.7 years. Initial graft function rate was 100% for LRD and 79% for CAD. The relative glomerular filtration rate (GFR) showed no statistical difference between CAD and LRD. Main reasons for graft loss were chronic transplant nephropathy. Paediatric KTx is the treatment of choice even in very small children. Living donor KTx is the preferable donor source in terms of primary graft function and timing to transplantation.

Cyclosporin A in paediatric kidney transplantation.

Cyclosporin A (CyA) is an immunosuppressive agent which has been used in children following kidney transplantation since 1982. The paediatric experience made with CyA in a single centre is reported here. Forty-seven children, ranging in age from 2 to 16 years, were given transplants between September 1982 and May 1986 and received CyA with low-dose prednisolone for immunosuppression. The mean cold ischaemia time of the grafts was 20.9 h. Under routine volume expansion during and 24 h post-transplantation, 40 grafts (85%) functioned immediately. Acute rejection episodes occurred with the highest frequency during the 1st month (0.6 rejection/patient). The actuarial surival rate for patients was 98% after 3 years. Graft survival was 92% after 1 year, 87% after 2 years and 78% after 3 years. The side-effects observed with CyA were hypertrichosis (38%), neurological complications (21%), and infections (17%). One girl of 16 years developed benign mammary fibroadenomas. Hypertension was common (60%), but less so than seen with conventional therapy (83%). Graft function was reduced. The mean creatinine clearance at 6 weeks after transplantation was 60 ml/min per 1.73 m2, after 1 year was 46.4 ml/min per 1.73 m2 and after 2 years it was 42.5 ml/min per 1.73 m2. Twenty-nine children with functioning grafts of at least 1 year could be evaluated for growth performance and normal or even catch-up growth could be demonstrated for the whole group. The individual annual growth rates expressed by standard deviation score (SDS) remained stable or even improved 3 years after kidney transplantation. Longer periods of follow-up are necessary to confirm whether the advantages concerning survival rates and growth rates persist over time and will outweigh the side-effects of CyA treatment.

Aetiology and outcome of acute and chronic renal failure in infants

BACKGROUND The aetiology and outcome of acute (ARF) and chronic renal failure (CRF) in infants were analysed in a retrospective study. METHODS Between January 1997 and April 2004 all children <1 year of age with a serum creatinine >100 mumol/l at Hannover Medical School were followed up for up to 6 years. One hundred and nineteen children with a serum creatinine >100 mumol/l were identified, 70 infants suffering from ARF and 49 from chronic kidney disease (CKD), stages 3-5. RESULTS Renal failure was caused in 49/119 (41%) by congenital and in 70/119 (59%) by acquired diseases. The aetiology of ARF (n = 70) included cardiac (27%), prematurity (27%), septic (10%), hepatic (9%), renal (9%) and other (18%) causes. Twelve infants needed transient dialysis treatment. Renal function recovered in all surviving children. The mortality rate was 37%. Causes of death were unrelated to kidney function. Twenty-one of 49 infants with CKD were dialyzed with a median age of 65 days at the start of dialysis, and 23/49 children received a kidney transplant (RTx). The 5-year patient and graft survival for RTx-children of 95.5% was not different from older children. The 5-year patient survival rate of 26 children with CKD without RTx was 63%. The causes of death were parental refusal of therapy in neonates (n = 4) and life-threatening extra-renal comorbidity (n = 3). CONCLUSION Renal replacement therapy offers good chances of survival in infants without life-threatening comorbidity. Patient survival of infants treated for CKD in the first year of life was comparable to that of older children.

Exercise capacity and blood pressure response in children and adolescents after renal transplantation.

Physical working capacity and cardiovascular response to graded exercise on a bicycle ergometer were investigated in 70 children and adolescents (33F, 37M) after renal transplantation. Results of static and dynamic lung function tests were within the normal range in all patients. Systolic blood pressure, heart rate, pulmonary ventilation and oxygen uptake increased with workload and returned to pre‐exercise levels after 5 m of rest. During exercise, blood pressure values were within the normal range in almost all patients. The increase in heart rate and respiratory frequency was blunted in patients receiving beta blocking agents. Maximum workloads (Wmax) were 2.00 × 0.48 W/kg in females and 2.38 × 0.54 W/ kg in males, which are 78 × 18% and 84 × 18% of the normal values predicted for age. Maximum oxygen consumption (VO2max) was 23.2 × 5.8 ml/min/kg in females and 28.3 × 5.8 ml/min/kg in males. Half of the patients had height below the third percentile. For this reason exercise capacity in relation to height is probably a more relevant parameter than age. Using actual height, Wmax was 102 f 20% and 102 f 29%, and VO2max 74 f 14% and 80 f 18% of predicted values, respectively. We conclude that the adaption of the cardiovascular and respiratory system to graded exercise was influenced by beta blocking agents. Wmax and VO2max were significantly reduced for age in pediatric patients after renal transplantation. Wmax was normal, but VO2max was still reduced if corrected for height.

Cyclosporin A monitoring by 2‐h levels: preliminary target levels in stable pediatric kidney transplant recipients

Abstract: Clinical trials in adults have shown that management of transplanted patients with cyclosporin A (CsA) 2‐h levels (C2) lead to superior outcome compared with monitoring of 12‐h trough levels (C0). In both adults and children, C2 levels enabled a better estimation of the area under the curve concentration than C0 levels. Therefore, it can be suspected that C2 monitoring might also lead to a better outcome in children. Until now C2 target levels for children have not been defined.

Four years' experience with cyclosporin A in pediatric kidney transplantation.

ABSTRACT. From 1982 to 1987 sixty‐three children were treated with cyclosporin A and low dose prednisolone after kidney transplantation. Patient survival rate at 4 years after transplantation was 98.3 %, survival rate of living related grafts 100 % (n = 10), and survival rate of cadaveric grafts 73 % (n = 53). Adequate cyclosporin blood levels were achieved in all children with a dosage regimen related to body surface area. Major concerns during the observation period were the loss of glomerular filtration rate from 51.8 to 40.5 ml/min/1.73 m2, a hypertension rate of 77.8 %, and hyperuricemia. Cyclosporin A‐side effects were mild. Infections occurred in 11.1 %. Growth retardation in prepu‐bertal children improved by 0.74 standard deviations of normal height, and in pubertal children by 0.51. We conclude that cyclosporin A treatment in children enables excellent long term graft survival rates with improved growth rehabilitation, however, the prevention of the cyclosporin associated nephrotoxicity and hypertension remains the major problem.

Long-term follow-up of pediatric transplant recipients: mycophenolic acid trough levels are not a good indicator for long-term graft function

Abstract:  Background:  Mycophenolate mofetil (MMF) has the potential of decreasing acute rejection episodes early following renal transplantation. Pharmocokinetic monitoring of mycophenolic acid (MPA) trough levels is performed by many centers. MMF has also proved successful in improving long‐term graft function in patients with chronic allograft nephropathy (CAN). However, no data for long‐term monitoring of MPA in children have yet been published.

Perioperative management of central diabetes insipidus in kidney transplantation.

Abstract 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. Pre-transplant 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 µg/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 µg 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.