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The renal function of 74 children with malignant mesenchymal tumors in complete remission and who have received the same ifosfamide chemotherapy protocol (International Society of Pediatric Oncology Malignant Mesenchymal Tumor Study 84 [SIOP MMT 84]) were studied 1 year after the completion of treatment. Total cumulative doses were 36 or 60 g/m2 of ifosfamide (six or 10 cycles of ifosfamide, vincristine, and dactinomycin [IVA]). None of them had received cisplatin chemotherapy. Ages ranged from 4 months to 17 years; 58 patients were males and 42 females. The most common primary tumor site was the head and neck. Renal function was investigated by measuring plasma and urinary electrolytes, glucosuria, proteinuria, aminoaciduria, urinary pH, osmolarity, creatinine clearance, phosphate tubular reabsorption, beta 2 microglobulinuria, and lysozymuria. Fifty-eight patients (78%) had normal renal tests, whereas 16 patients (22%) had renal abnormalities. Two subsets of patients were identified from this latter group: the first included four patients (5% of the total population) who developed major toxicity resulting in Fanconi's syndrome (TDFS); and the second group included five patients with elevated beta 2 microglobulinuria and low phosphate reabsorption. The remaining seven patients had isolated beta 2 microglobulinuria. Severe toxicity was correlated with the higher cumulative dose of 60 g/m2 of ifosfamide, a younger age (less than 2 1/2 years old), and a predominance of vesicoprostatic tumor involvement. This low percentage (5%) of TDFS must be evaluated with respect to the efficacy of ifosfamide in the treatment of mesenchymal tumors in children.

The efficacy of an inhaled equimolar mixture of nitrous oxide and oxygen (Entonox/MEOPA) to prevent procedural pain during renal percutaneous biopsies in children was assessed.One hundred and seven children who underwent 113 renal biopsies during a 17-month period were included in a prospective uncontrolled pediatric study. Efficacy was evaluated using patients' answers to a questionnaire and nurses' observations.Pain was absent in 86.5% of the cases. Mild adverse events were noted in one-third of the procedures, and were always reversible within a few minutes when the inhalation stopped. Acceptability was good. The use of this gas is easy and safe provided a few precautions are observed.Inhaled equimolar mixture of nitrous oxide and oxygen prevents procedural pain during renal percutaneous biopsies.

Denys-Drash and Frasier syndromes are rare human disorders that associate nephropathy with gonadal and genital abnormalities. In DDS there is a predisposition to Wilms' tumor. Heterozygous point mutations in the Wilms' tumor, type1 gene (WT1), particularly those altering the zinc finger (ZF) encoding exons, have been reported in most DDS patients, while mutations in intron 9 of the same gene cause FS. This paper describes two cases of DDS, one FS and one patient with Wilm's tumor and intersex genitalia, in which mutations were searched by sequencing the exons 8 and 9 of WT1 gene. Patient 1 carried a missense point mutation in exon 8 (ZF2), converting a CGA-Arg codon to a TGA-stop codon. Patient 2 presented a single nucleotide deletion within exon 9 (ZF3) introducing a premature chain termination at codon 398. Patients 3 and 4 had a C--T transition at position +4 of the second alternative splice donor site of exon 9 (this mutation was detected in peripheral blood and in tumor derived DNA of patient 3). However, patient 3 had previously developed a Wilms' tumor. This is the first case of Wilms' tumor development in a phenotypically and genetically confirmed case of FS.

Sixty-five children with steroid-resistant idiopathic nephrosis were treated with cyclosporine, 150 to 200 mg/m2, in combination with prednisone, 30 mg/m2, daily for 1 month and on alternate days for 5 months. Renal biopsy had shown minimal change disease in 45 children and focal segmental glomerular sclerosis in 20. Twenty-seven patients achieved complete remission. At latest examination, 14 to 60 months after initiation of the treatment (mean, 38 months), 17 patients were in complete remission, 8 had had a relapse but had become steroid sensitive, and 2 had a nephrotic syndrome. Four children responded partially to the treatment. At latest examination, 28 to 58 months after initiation of the treatment, 1 was in complete remission, 1 was in partial remission, 1 had a nephrotic syndrome, and 1 had end-stage renal failure. Thirty-four children did not respond to the combined treatment. At latest examination, 12 to 63 months after initiation of the treatment (mean, 38 months), 5 of these patients were in complete remission, 2 were in partial remission, 15 had a persistent nephrotic syndrome (with moderate renal failure in 5), and 12 children had end-stage renal failure. Forty-eight percent of the patients with minimal change disease and 30% of those with focal segmental glomerular sclerosis achieved complete remission (p = 0.27). We conclude that cyclosporine in combination with prednisone can induce a complete remission in some children with steroid-resistant idiopathic nephrosis.

Fourty-two children with idiopathic nephrosis that had not been well controlled by other forms of therapy were treated with ciclosporine. Thirty-three of them were steroid dependent, 2 were partial steroid responders and 7 were steroid resistant. On pretreatment renal biopsy, performed in all patients less than 6 months before starting ciclosporine, minimal change disease (MCD) was diagnosed in 37 children and focal glomerular sclerosis (FGS) in 5. In order to evaluate the morphological changes of the renal parenchyma possibly induced by the drug, posttreatment biopsies were performed in these 42 patients: one in all patients after 4 to 28 months of ciclosporine, 2 in 23 patients after 18 to 42 months of treatment, 3 in 8 patients after 30 to 63 months of treatment and 4 in 2 patients who had been treated respectively for 62 and 63 months. The morphological changes on pre- and posttreatment biopsies were scored according to the severity of tubulointerstitial lesions. Grade I was considered when there were no significant changes of the renal parenchyma or when occasional scattered tubules with thickened basement membranes were present. Grade II was diagnosed when the biopsy showed several small foci of atrophic tubules with thickened basement membranes within stripes of interstitial fibrosis and grade III when confluent or extensive areas of interstitial fibrosis with atrophic and/or collapsed tubules were observed. On pretreatment renal biopsy, only one patient showed tubulointerstitial lesions (grade II). On the latest biopsy obtained, 18 patients showed grade I tubulointerstitial lesions, 15 grade II and 9 grade III. Unspecific arteriolopathy was observed in 10 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

The authors report on a infant who presented with an auto-immune enteropathy characterized by the association of a protracted diarrhea, a neonatal insulin-dependent diabetes, and a dermatitis and who developed a nephrotic syndrome at 4 months of age. A renal biopsy showed a membranous glomerulonephritis (MGN) with IgG linear deposits along the tubular basement membranes (TMB). By indirect immunofluorescence anti-enterocyte antibodies together with anti-TMB antibodies and anti-renal brush border (BB) antibodies were found in the serum of the patient. The patient received various immunosuppressive drugs that failed to improve the disease. In the course of the disease the anti-TBM antibodies disappeared progressively but the BB antibodies persisted. A review of the literature indicates that renal involvement is not uncommon in auto-immune enteropathy and in 5 cases it has been reported as being characterized by a nephrotic syndrome related to the presence of a MGN. In 4 of these cases MGN was associated with the presence of anti-TBM antibodies and in the remaining one with anti-BB antibodies. This case report shows that in human pathology, auto-antibodies to BB proteins may, as well as in experimental models, be responsible for the development of a MGN. It suggests a close relationship (probably a common epitope) between the renal BB proteins and the proteins of the gut epithelium.

From 1976 through 1991, 50 renal transplants (with 7 kidneys from living related donors and 43 cadaver kidneys) were performed in 47 children under five years of age (range 11 to 59 months) at the Enfants-Malades Hospital, Paris, France. Donor age ranged from 3 months to 53 years. Six of the seven kidneys from living related donors are currently functioning after a follow-up of 6 months to 8 years, whereas actuarial survival of cadaver kidneys was 70% at one year and 66% at five years. The main cause of graft loss was vascular thrombosis (40% of lost kidneys). In the most recent years of the study period, graft survival was substantially improved by routine prophylactic anticoagulant therapy with low-molecular weight heparin: one-year graft survival rate was 83% in the 23 children grafted between 1989 and 1991. Posttransplantation growth was closely related to quality of graft function: among the 29 children with sufficiently long follow-up the 19 patients with normal renal function exhibited normal or catch-up growth, whereas the ten patients with chronic renal failure or recent rejection had poor growth. Complications were uncommon with the exception of hypertension. Mortality rate was 12%, i.e., only slightly higher than in older pediatric kidney recipients. Achievement at school was normal in most cases (with a lag in only five patients). Provided effective therapy is given to prevent the main adverse outcome (i.e., vascular thrombosis), renal transplantation does not involve excessive risks even in infants as young as one year of age.

Forty children with steroid-dependent idiopathic nephrotic syndrome and signs of steroid toxicity were randomly assigned to receive either cyclosporin 6 mg/kg body wt. per day for 3 months and at tapering doses over the next 3 months or chlorambucil at a cumulative dose of 8 mg/kg body wt. The two groups of patients did not differ significantly in sex distribution, age of onset of disease, duration of disease, number of relapses and histological findings. Of the 20 patients treated with cyclosporin, 4 relapsed before or on discontinuation of prednisone, 7 relapsed when the initial dose of cyclosporin was tapered, and 8 after withdrawal of cyclosporin. Of the 20 patients treated with chlorambucil, 14 relapsed while 6 were still in remission 27-49 months after completion of the treatment course. Thus the actuarial remission rate at 2 years was 45% after a course of chlorambucil compared with only 5% after a 3-month course of cyclosporin. We believe that children with steroid-dependent idiopathic nephrotic syndrome should be treated with a course of chlorambucil before resorting to cyclosporin.

Clinical and biological features, histologic findings, and outcome were studied in 32 children with systemic lupus erythematosus who underwent at least two renal biopsies during the course of their disease. Results showed that renal biopsy was a useful aid for therapy in that it demonstrated the presence or absence of disease activity, but was unhelpful for predicting the long term outcome. Repeat renal biopsies proved an excellent means for monitoring the course of the nephropathy. This study showed that the various patterns of glomerulonephritis seen in SLE may exhibit changes over time, with either improvement or progression. Regression of lesions was seen mainly after treatment, whereas progression was associated with renal or extrarenal exacerbations of the disease. The absence of clinical improvement may reflect transformation to histologic forms which are unresponsive to therapy.

Cyclosporin A (CyA, Sandimmun) was given to 71 children with idiopathic nephrotic syndrome, 45 of whom were steroid-dependent with signs of steroid toxicity, and 23 who were steroid-resistant. Cyclosporin A was effective in 80% of the steroid-dependent patients, allowing cessation of corticosteroid treatment. However, most of these patients relapsed when CyA was tapered or withdrawn. In these patients, CyA may be required for long periods of time. Conversely, CyA was less effective in steroid-resistant patients; only 7% achieved remission with CyA alone. Cyclosporin A in association with prednisone may be an effective alternative as 8 out of 14 patients entered remission with this treatment combination. Serial renal biopsies were performed in 43 patients to evaluate the potential nephrotoxicity of the treatment. Eighteen patients developed significant tubulointerstitial lesions which were attributable to CyA nephrotoxicity. The risk of developing chronic nephrotoxicity appears to be higher in steroid-resistant patients, and was not related to the duration of treatment. Cyclosporin A nephrotoxicity can develop in patients with normal renal function.

The monoclonal antibody OKT3, administered for 2 to 3 weeks in a dosage of 0.1 mg/kg, in combination with azathioprine and prednisone, proved more effective than conventional antilymphocyte serum for the prevention of renal transplant rejection. Side effects were less marked with OKT3 than with antilymphocyte serum. Infectious complications, especially viral, occurred with the same incidence in both groups. In the long term, following discontinuation of OKT3 or antilymphocyte serum, incidence of rejection episodes and graft survival rates were identical in both groups. OKT3 in a lower dosage of 0.05 mg/kg was less effective, with several patients developing rejection during treatment, and induced more common and earlier anti-OKT3 immunization.

A study was done of 15 children and adolescents, aged 2.5 to 17.5 years, who were treated by continuous ambulatory peritoneal dialysis (CAPD) for 6 to 24 months. Plasma albumin concentration decreased from 34.4 +/- 4.8 g/liter at the onset of therapy to 31.3 +/- 5.3 g/liter after 19 to 24 months. Children less than 6 years old had lower albumin levels (29.4 +/- 1.7 g/liter) than did the older group (36.3 +/- 4.2 g/liter). The lower plasma albumin was related to peritoneal protein loss but not to protein intake. Plasma free amino acid concentrations were not significantly modified. No changes occurred in the oral glucose tolerance test during the course of CAPD. Plasma cholesterol and triglycerides were abnormally high for age, with a correlation seen between cholesterolemia and peritoneal protein loss.

The effects of intravenous Nitrogen Mustard (NM), given with a total cumulative dose of 0.8 mg/kg BW, were studied in 60 children with idiopathic nephrotic syndrome (INS). Thirty patients were frequent relapser with corticosteroid dependence. In this group the actuarial remission rate was 43, 30 and 15% after 1, 2 and 3 years respectively. The relapse rate per year was decreased from 2.76 +/- 1.56 to 0.88 +/- 0.79 after NM. Ten of the 17 patients showing a partial response to steroids went into complete remission after NM but 6 of them relapsed. Of the 13 patients who did not respond to steroids only 3 went into remission for a short time. Vomiting and leukopenia were noted in one third of cases. The data indicate that NM may improve the course of corticosteroid dependent INS, being less effective in partial responders and probably without effect in non responders.

Purified alveolar lymphocytes obtained by bronchial lavage have been studied in 66 subjects: 8 normals, 24 sarcoidosis, 8 tuberculosis, 4 hypersensitivity pneumonitis, 6 collagen diseases and 16 miscellaneous. The following T and B lymphocyte markers have been used: E and EAC Rosettes, Surface membrane immunoglobulins, la antigen and human T lymphocyte antigens. The PHA or ConA responses of some blood and alveolar lymphocyte cultures have also been compared. The results emphasize: -- the tight correlation between the different marker techniques to T and B lymphocytes; -- the larger increases of T lymphocytes in active vs inactive sarcoidosis (p less than 0.001); -- the difference in T lymphocyte number in active vs inactive tuberculosis and in treated vs untreated miliary tuberculosis; -- the absence of alveolar lymphocyte increase in collagen diseases.

Six infants, 4.5 to 19 months old, whose creatinine clearance was less than 6 ml/min/1.73 m2 received, successively, three low-nitrogen diets. Diet A contained 9.3 g of human milk protein; and diet B, 4.2 g of human milk protein plus synthetic essential amino acids. Diet C was the same as B except that five essential amino acids were replaced by alpha-keto and hydroxy analogs. Serum urea decreased as the infants were transferred from diet A to diets B and C, and the serum urea/creatinine ratio decreased from diet A to diet B and from diet B to diet C. Urea appearance was 14.8 +/- 4.5, 9.1 +/- 4.3, and 6.9 +/- 1.7 mmoles/day, with diets A, B, and C, respectively. Weight gain was also lowest with diet C, as was the difference between nitrogen intake and urea nitrogen appearance, an indicator of nitrogen balance. Plasma free amino acids were not modified by diets A and B, but valine, leucine, and the plasma free essential amino acid pool decreased significantly with diet C.

We studied the occurrence of diabetes mellitus in 6 children receiving corticosteroid therapy after renal transplantation. The first hyperglycemic episode occurred in all cases before the fortieth day of treatment but other episodes were observed thereafter. All children were glycosuric, without ketonuria. The diabetes has always been transient, and easily managed with insulin treatment and usual diabetic diet. A glucose tolerance test was performed 3 to 6 months after these episodes; glycemic response to glucose was abnormal in 2 of 6 children; in all cases, the insulin response to the glucose load was inadequate. In 2 children, the fasting blood glucose is still abnormal after a follow-up of 3 years. The other patients have recovered despite sustained corticotherapy. No specific background (genetics, HLA groups) or specific circumstances of treatment were identified. Therefore, we recommend to follow closely glycemia in children after renal transplantation, with a daily glycemic determination especially during the first 3 weeks.

Administration of a circulating thymic factor isolated from normal pig blood prevented the development of the exaggerated production of anti-polyvinyl pyrrolidone (PVP) antibody in young NZB mice. However, treatment was ineffective if initiated after the 4th week of life at a time when endogenous serum thymic factor (TF) normally disappears in these mice. These data suggest that circulating TF is necessary for the survival of short-lived suppressor T cells normally implicated in the regulation of the production of antibodies against PVP, a thymus-independent antigen. In older NZB mice, TF treatment increased paradoxically anti-PVP antibody production, which suggests that "amplifier" T cell activity could also be under TF influence.

The successful transplantation of a human malignant histiocytosis into nude mice allowed the examination of its atypical histiocytic cell proliferation. Histiocytic type cells were identified by positive reactions with acid phosphatase and non-specific esterase and with anti human DR or OKI1 antisera. Presence of OKT9 antigen and negative results obtained with most OKT antisera, rosettes, erythrophagocytosis and lysozyme corroborate the histiocytic immature state of the cells and preclude another type of tumor. All positive tests to prove a mature mononuclear phagocytic origin were attributable to the murine host cell reaction.

Eleven children (7 girls and 4 boys) 2 1/2 to 17 years and 8 months of age were treated with CAPD for periods ranging from 6 to 31 months. All children were treated with commercially available dialysate solutions containing lactate. Peritoneal ultrafiltration capacity (PUFC) decreased progressively in all children without accompanying decrease in peritoneal urea and creatinine clearances. Five children developed membrane failure with negative ultrafiltration. One episode of peritonitis occurred in one of these 5 children and in 4 of them only 1.5% glucose solutions had been used. After an initial period (ranging from 14 to 31 months) of CAPD, 2 children were treated with Intermittent Ambulatory Peritoneal Dialysis (IAPD) and two others with Intermittent Cycling Peritoneal Dialysis (ICPD). In these 4 children, PUFC increased within one month from -3.75 ml/kg/day to + 5 ml/kg/day. By providing a shorter dwell time, IAPD and ICPD may allow a reduction in net inward transport of glucose, the maintenance of osmolar gradient and preservation of ultrafiltration capacity. Furthermore, periods of rest may allow some recovery from the progressive deterioration of the peritoneum resulting from long-term irrigation of the peritoneal cavity. These results indicate that IAPD and CPD may be superior to CAPD to maintain the ultrafiltration capacity of the peritoneum.