Mycophenolate mofetil in pediatric renal transplantation without induction therapy: results after 12 months of treatment. German Pediatric Renal Transplantation Study Group.

BACKGROUND: Acute rejection episodes (ARE) of kidney transplants are considered as risk factor in the development of chronic rejection. In adult renal transplantation (RTx), ARE have been significantly reduced by mycophenolate mofetil (MMF) in combination with cyclosporin (CyA) and steroids (Pred). Reports of pediatric RTx on a maintenance immunosuppression with MMF are restricted to patients (P) after antibody induction therapy. METHODS: The efficacy and safety of MMF combined with CyA and Pred in pediatric RTx without induction therapy were evaluated in an open-labeled multicenter study. RESULTS: From 10/1996 to 6/1999, 65 pediatric P (MMF group) were followed for at least 6 months, 58 of 65 for 12 months. These P were compared with 54 retrospectively analyzed pediatric P who were transplanted between 1990 and 1996 and had received CyA, Pred, and azathioprine for immunosuppression (historic AZA group). Within the first 6 months after RTx, 18 of 65 (MMF group) and 32 of 54 (historic AZA group) P showed clinical signs of acute rejection (P<0.01). Thereafter only one further P in the MMF group developed a first ARE. Graft loss due to rejection occurred in one MMF- and seven AZA-treated P (P<0.05). The creatinine-clearance 3 and 6 months after RTx was higher in the MMF group. Major adverse events (MMF group) included infections of the urinary and the upper respiratory tract, diarrhea, and leukopenia. Cytomegalovirus-infection occurred in 13 P and 2 P developed cytomegalovirus disease. One P developed PTLD 10 months after RTx and recovered after the reduction of immunosuppression. CONCLUSIONS: The combination of MMF, CyA, and Pred reduced ARE in pediatric RTx without incurring major side effects.

Effect of sodium benzoate in the treatment of atypical nonketotic hyperglycinaemia.

A 6-month-old girl presented with hypotonia and mild psychomotor retardation. Subsequently, an atypical manifestation of a nonketotic hyperglycinaemia was diagnosed, confirmed by significantly reduced activity of the glycine cleavage system in the liver tissue. After the patient developed hypsarrhythmia and had a single cerebral seizure, treatment with both sodium benzoate and dextromethorphan was started. During the following year, the girl was free of seizures with improvement of the EEG activity and showed retarded but continuously progressing psychomotor development. At the age of 20 months she began to walk freely but had generalized muscular hypotonia and moderate mental retardation. Discontinuation of dextromethorphan medication after one year of treatment did not change the clinical and electroencephalographic status. However, after cessation of sodium benzoate therapy, epileptic activity in the EEG and behavioural changes occurred. These changes disappeared promptly after sodium benzoate therapy was reinstituted. Thus, this case of mild atypical nonketotic hyperglycinaemia with only moderate psychomotor retardation and without epilepsy benefited from treatment with sodium benzoate in terms of electroencephalographic and behavioural changes.

Postexercise albuminuria in children with different duration of type-1 diabetes mellitus.

About 30% of diabetic patients develop progressive renal failure. We studied albumin, IgG, and transferrin excretion during exercise in diabetic children without signs of nephropathy to investigate proteinuria under these conditions: 39 patients with insulin-dependent diabetes mellitus and 21 healthy children undertook a bicycle exercise test. Albuminuria measured by nephelometry was calculated as the albumin excretion rate (AER) and albumin-to-creatinine ratio before and after exercise. The diabetic group was divided into three subgroups according to disease duration (DI < 5 years, DII 5-10 years, DIII > 10 years). No significant difference in metabolic control (hemoglobin A1c was detected between the diabetic groups (median hemoglobin A1c: DI 7.2%, DII 7.6%, DIII 8.6%). There was no increase in AER in the healthy children after exercise. Before exercise the diabetic groups had an AER similar to controls. No significant increase in albuminuria after exercise was seen in group DI. Both groups with a disease duration of more than 5 years had a significant increase in albuminuria [median before/after: DII 7.8/16.7 (P < 0.05), DIII 0/57.9 (P < 0.05) micrograms/min per 1.73 m2). Of these patients, 43% also had a measurable urinary excretion of IgG and transferrin, indicating structural glomerular damage. There was no correlation of albuminuria and parameters of metabolic control or renal function. We conclude that in diabetic children an exercise test unveils albuminuria in certain patients, while their AER may be normal at rest.

Urinary excretion of adenosine deaminase binding protein in neonates treated with tobramycin.

The potential tubulotoxicity of tobramycin and cefotaxim were assessed in neonates by measuring the urinary level of adenosine deaminase binding protein (ABP) and urinary alpha 1-microglobulin and beta 2-microglobulin. In a prospective study, 33 neonates who received tobramycin and cefotaxim for suspected neonatal sepsis were compared with 48 untreated newborns during the first 10 days of life. The urinary concentrations of ABP and its excretion rates, corrected for body weight and body surface area, were significantly increased from the 1st day of treatment. Urinary alpha 1-microglobulin and beta 2-microglobulin were not elevated under tobramycin and cefotaxim during the first 2 days of treatment. We conclude that ABP may be a sensitive marker for the detection of proximal renal tubular injury during tobramycin and cefotaxim treatments of neonates. The increase in urinary ABP which occurs before an elevation of urinary alpha 1-microglobulin and beta 2-microglobulin may reflect earlier structural than functional alterations. However, since none of the treated infants had signs of electrolyte disorders or glomerular dysfunction, the clinical relevance of ABP measurement should be reevaluated.

General anaesthesia versus epidural anaesthesia for primary caesarean section--a comparative study.

Forty-seven healthy parturients undergoing elective Caesarean section were randomly allocated to either general anaesthesia (n = 24) or epidural anaesthesia (n = 23) under standardized anaesthetic and surgical conditions. Seven women of the epidural group required additional systemic analgesia or sedation following delivery of the neonate. Nine of 24 newborns obtained 1-min Apgar scores below 7 after general anaesthesia compared to only 3/23 after epidural anaesthesia. The time period to establish normal colour in the babies was 2.2 min after epidural and 4.9 min after general anaesthesia. Three of the 24 general-anaesthesia newborns demonstrated a tendency to hypotonia compared to only one in the epidural group. Twenty-four hours and 7 days after delivery all infants of both groups were completely normal. At the time of delivery maternal PO2 was higher in the general anaesthesia compared to the epidural group, due to higher inspired oxygen concentrations. Comparable results were obtained in umbilical PO2 venous values; lower pH values, however, were observed in the umbilical artery after general anaesthesia. There were no significant differences in the glucose levels between the groups. A significant correlation was established between uterine incision-delivery interval and 1-min neonatal Apgar scores in the general-anaesthesia group, but not in the epidural group. Our investigation did not show either the incision-delivery interval or the start of operation-delivery interval to play a role in neonatal outcome. Epidural anaesthesia is superior to general anaesthesia in Caesarean section under normal conditions with regard to neonatal outcome. Whether this is also true for critical conditions cannot be concluded from this study.

Evaluation of local renal function in newborn infants under tobramycin therapy.

Aminoglycosides (AG) provided for less than 5 days to newborn infants do not produce a marked disturbance of glomerular filtration rate (creatinine clearance) or tubular sodium handling (fractional sodium excretion). However, transient disturbances of proximal tubular cell functions can be noted: the excretion of N-acetylglucosaminidase, a lysosomal enzyme, is elevated, and mature not premature infants show a decreased tubular reabsorption of low-molecular-weight proteins during AG treatment. Preliminary investigations show an increased excretion of villin, a structural protein of proximal tubular cells, and a decreased secretion of Tamm-Horsfall protein by the cells of ascending limb of Henle and early distal tubule.

[Congenital malaria--a rare neonatal infection]. / Konnatale Malaria--eine seltene neonatale Infektion.

Tropical diseases are rare in childhood in European countries, but tourism and an increasing number of immigrants from countries with endemic malaria may lead to a higher incidence. Our report is about a 24 year old german pregnant who was infected with malaria tropica in Togo during the last trimester of pregnancy. Twenty days after delivery by Caesarean section one of the geminies showed symptoms of florid infection: irritability, fever, haemolytic anaemia, hepato-splenomegaly, and thrombocytopenia. Both placenta and peripheral blood smear revealed plasmodium falciparum in the erythrocytes.

[Treatment of renal anemia with recombinant human erythropoietin]. / Behandlung der renalen Anämie mit rekombinantem humanen Erythropoietin.

Anemia is an almost invariable feature of chronic renal failure and is particularly severe in children treated by long-term hemodialysis. Recombinant human erythropoietin (rhEPO) offers entirely new aspects in the treatment of renal anemia. This report presents three patients on maintenance hemodialysis aged 10, 10/10 12, and 18 years who were treated with rhEPO. Two suffered from hemochromatosis secondary to multiple transfusions. 100 U/kg rhEPO were administered three times weekly, and venesection after dialysis was performed when a target hematocrit value of 30% was achieved. Hematocrit, reticulocyte-counts and hemoglobin rose within 3 to 6 weeks after initiation of therapy in all patients. Serumferritin levels declined significantly in the two patients with hemochromatosis. No deterioration of the metabolic status (i.e. increase of blood urea nitrogen, serum-creatinine, -phosphate or -potassium) could be detected. Therapy had to be discontinued in one patient who experienced hypertensive ceisis. This patient, however, had suffered from severe hypertension prior to rhEPO therapy. Blood pressure remained stable in the other patients. We conclude that renal anemia can be effectively treated by rhEPO in children. Increase of blood pressure may necessitate discontinuation of therapy especially in primary hypertensive patients. Extensive studies are necessary to eluciate long-term effects of rhEPO in children.

Cyclosporin A treatment in children with minimal change nephrotic syndrome and focal segmental glomerulosclerosis.

In a pilot study 23 children with nephrotic syndrome were treated with cyclosporin A (Cs) for 6-45 months. 8 children suffered from steroid dependent minimal change nephrotic syndrome (MCNS) and had experienced at least one course with cytotoxic drugs, but had relapsed thereafter. 2 children had diabetes mellitus type I with nephrotic syndrome and 13 children had steroid resistant focal segmental glomerulosclerosis (FSGS). Cs was started with 100 mg/m2/day in two doses and increased stepwise to obtain a Cs whole blood trough level of 200-400 ng/ml. In steroid dependent MCNS treatment with Cs reduced relapse rate significantly, and prednisone therapy could be stopped completely. After discontinuation of Cs, relapses reoccurred as frequently as before. Renal function remained unimpaired despite repeated Cs treatment courses up to 38 months. In cases of nephrotic syndrome with diabetes type I Cs treatment led to complete remission without changing the insulin requirement. However, after discontinuation of Cs relapses reoccurred. In steroid resistant FSGS 6 children benefited from Cs treatment: 4 went into complete remission, 2 into partial remission. The 2 children with complete remission relapsed but remained Cs responsive. The remaining 7 children with FSGS did not respond to Cs but continued the course of their disease, with two patients rapidly progressing to terminal renal failure. Side-effects of Cs treatment were mild. It is concluded that Cs is an effective agent in steroid dependent MCNS and can be used as an alternative drug in specific cases like steroid toxicity or diabetes mellitus. In steroid resistant FSGS a trial with Cs seems to be warranted since some cases do respond favorably. To avoid nephrotoxicity treatment with Cs should always be monitored closely by determination of blood levels and renal function.

Serum creatinine and creatinine clearance in healthy neonates and prematures during the first 10 days of life.

Normal serum creatinine (Scr) and creatinine clearance (Ccr) values during the first 10 days of life were obtained in 63 very premature (28-32 weeks of gestation), premature (33-37 weeks) and term infants (38-42 weeks). Scr fell, and Ccr rose less markedly in the very premature infants. Scr was 80 mumol/l on the 1st day of life both in very premature and premature infants, and 77 mumol/l in full-term neonates. After 10 days, Scr was 73, 53 and 35 mumol/l respectively. There was an exponential correlation between Ccr and gestational age, indicating rapid maturation of glomerular function.

N-acetylglutamate synthetase deficiency, a second patient.

A second patient with N-acetylglutamate synthetase deficiency is described. The first symptoms were noted at 6 days of age. The course was lethal despite vigorous treatment. The diagnosis was established after death.