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Idiopathic nephrotic syndrome (INS) in childhood is characterized by massive proteinuria and minimal glomerular changes. Most patients with INS respond to steroid therapy. INS is generally regarded as a sporadic disease with favorable outcome. We investigated a distinct subgroup of nephrosis--the familial form of steroid resistant INS (SRN). These patients always progress to end-stage renal failure within a few years and show absence of recurrence of the disease after renal transplantation. The occurrence of the disorder in siblings and the high incidence of inbreeding in these families made an autosomal recessive mode of inheritance very likely. We performed whole genome linkage analysis in nine multiplex families of European or Northern African origin. Our results allowed us to assign a disease locus (SRN1) to a defined chromosomal region on 1q25-1q31, thus confirming the existence of a distinct entity of autosomal recessive nephrosis. Exclusion of linkage to the entire region in one family proves genetic heterogeneity.

We report a mitochondrial DNA deletion (2.6 kb) in a boy with tubulointerstitial nephritis in whom chronic renal failure and leukodystrophy subsequently developed. Elevated lactate values in plasma and cerebrospinal fluid were suggestive of a defect in the mitochondrial respiratory chain. High amounts of deleted mitochondrial DNA were present in muscle and cerebral white matter. On the basis of this observation, we suggest giving consideration to genetic defects of oxidative phosphorylation in any attempt to determine the origin of unexplained chronic tubulointerstitial nephritis, especially when seemingly unrelated organs are involved.

Previous studies have shown that age at onset of primary haemolytic uraemic syndrome (HUS) is a feature of prognostic significance, the disease being of much better outcome in paediatric patients younger than 3 years than in older children. In an attempt to find an explanation for such a difference, we analysed the clinical and pathological features of 42 children over 3 years of age who presented with HUS between 1955 and 1990 in our department. On the basis of the presence of a prodromal diarrhoea, we divided our patients into two groups: 21 children presented with the diarrhoea-associated (typical or D+) form of HUS, whereas 21 had the non-diarrhoea-associated (atypical or D-) form. Of the 42 children, 20 (47.5%) progressed to end-stage renal failure. However, our study shows that age at onset of HUS is not a prognostic feature per se. The difference in outcome between children and infants is most likely related to the high incidence of the atypical subset of HUS in children over 3 years, a subset that is very uncommon in infants. The ominous features which characterise this form of the disease are: (1) the absence of a diarrhoeal prodrome, (2) normal urine output, (3) marked proteinuria, (4) hypertension, (5) the occurrence of relapses or recurrences and (6) the presence of widespread and severe arteriolar changes on renal biopsy. The poor prognosis of the atypical form of HUS warrants the use of fresh-frozen plasma infusions and/or plasma exchange as early as possible in the course of the disease.

Objectives: Evaluate bacterial infection epidemiology and pathophysiology in children with nephrotic syndrome., Methods: From January 1983 to December 1992, 399 children with the nephrotic syndrome were admitted in 3 University Pediatric wards (Paris Enfants Malades, Lyon Edouard Herriot, Lyon Debrousse). Severe bacterial infection was diagnosed when the patient's condition has justified an intravenous antibiotherapy., Results: Forty-eight bacterial infections were noted in 32 patients (8%); the infection was the first symptom of the disease in 10 patients (31%); one patient died shortly after admission. Severe bacterial infection concerned steroid-resistant nephrotic syndrome in 13 cases (41%), but only 7 out of them received immunosuppressive agents at the time of the infection. Eleven children (34%) experienced recurrent infections (1 to 6 recurrences), several of which under antibioprophylaxy. Half of the infections involved peritonitis and 50% of the identified germs were S. pneumoniae. However, peritonitis was not always related to S. pneumoniae (1 H. influenzae among 9 identified germs)., Conclusions: These data demonstrate the importance of microbiological sampling and justify a first-line antibiotherapy using a third generation cephalosporin. The presentation of severe bacterial infections show that it is less a iatrogenic event than a consequence of immunological disturbances induced by the nephrotic syndrome itself, as suggested by the acquired deficiency of factor I and B. Despite recent advances in antibiotic strategies responsible for a significant reduction in the severity of such infections (1 death among 32 patients), preventive treatments are quite disappointing.

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)

An updated study of the glomerular lesions found in renal grafts in children showed 3 features of interest. 1) In our experience, the incidence of the occurrence of de novo membranous glomerulonephritis (MGN) remains around 9% (48 of 530 grafts). 2) Of the 29 patients we reported in a previous study [Antignac et al. 1988], 18 lost their grafts and 7 received a second graft. Four of these 7 patients recurred de novo MGN on their second graft. Their clinical course is reported in detail. 3) In our population of transplanted children, of the 55 patients who received a second graft, the only recipients who developed a de novo MGN were the 4 patients who had already developed de novo MGN on their first graft. The various factors possibly involved in the pathogenesis of de novo MGN are reviewed. The high incidence of recurrence of de novo MGN indicates that host factors play a major role in the development of this nephropathy.

Several cases of haemolysis after bone marrow or organ transplantation have been reported. An allospecific anti-erythrocyte antibody has been described in each case. We report a similar case after renal transplantation. Berger's disease led to end-stage renal failure in an 18-year-old girl. During haemodialysis carried out for 6 years, the patient had received 9 transfusions of phenotyped, filtered, packed red blood cells. The recipient was grouped as O Rh positive, CcDee, Kell negative, HLA-A24 A11 B35 B-DR1 DR2. The donor was her father, grouped as O Rh negative, ccddee, Kell negative, HLA-A24 A- B35 B- DR2 DR-. Screening for erythrocyte antibodies was negative in the recipient as were screening for lymphocytotoxic antibodies and compatibility testing. However anti-D antibody was present in the donor who had received a transfusion of Rh positive blood several years before renal donation. The recipient was given 2 units of O Rh positive, phenotyped and filtered red blood cell concentrates during transplantation. Immunosuppressive therapy associated azathioprine and prednisone. The onset of graft function was immediate. Haemoglobin fell to 52 g/l on day 14 post transplantation (103 g/l on day 6). Anti-D antibody was identified in the serum. The direct antiglobulin test was positive with anti-IgG, antiglobulin and the eluate contained an antibody exhibiting also anti-D specificity. The anti-D of the patient and the donor had the same Gm allotyping. The outcome was favourable though the antibody was persistent for several months. This case of haemolysis is consistent with the fact that immunocompetent B lymphocytes transferred with the grafted organ are still able to produce clinically significant antibodies.

We report a patient with Pearson syndrome with failure to thrive, exocrine pancreas insufficiency, growth hormone deficiency and severe tubular dysfunction. The patient had no signs of liver involvement. Normal respiratory chain enzyme activity was found in the lymphocytes, but a mitochondrial DNA deletion was demonstrated in lymphocytes and in the kidney. Polymerase chain reaction amplification and sequence analysis revealed the presence of the 4,977 base pair "common" deletion in the mitochondrial genome. Our findings support the view that tubulopathies of unknown origin may be related to mitochondrial respiratory chain deficiency.

Background: Among patients with the idiopathic nephrotic syndrome who have focal and segmental glomerulosclerosis and undergo renal transplantation, 15 to 55 percent have recurrent nephrotic syndrome. The recurrence may be caused by a plasma factor or factors that increase glomerular permeability, because plasma exchange transiently decreases or abolishes proteinuria in some patients. We studied the effect on proteinuria of the removal of protein (mostly immunoglobulins) by adsorption onto protein A from the plasma of patients with recurrent nephrotic syndrome., Methods: Eight patients were treated with one to three cycles of two to seven 1-day sessions of protein adsorption, and the patients' urinary protein excretion was measured repeatedly. Their immunosuppressive regimens were not changed during the treatment. The adsorbed proteins were eluted from the protein A and injected into rats, and the urinary albumin excretion of the rats was measured., Results: The protein-adsorption treatment consistently decreased urinary protein excretion by an average of 82 percent at the end of a cycle (P < 0.001). In one patient proteinuria disappeared, and in another urinary protein excretion remained below 2.5 g per day with repeated cycles of protein adsorption. In all but one patient the effect of adsorption was limited in time, with a return to the preadsorption level of protein excretion within a maximum of two months. The administration to rats of material eluted from the protein A increased urinary albumin excretion 2.9- to 4.6-fold (P < 0.001 and P = 0.005, respectively). Although protein A primarily binds immunoglobulins, the active fraction of the eluted proteins had a molecular weight below 100,000, indicating that immunoglobulin was not directly involved., Conclusions: Adsorption of plasma protein decreases urinary protein excretion in patients with recurrence of the nephrotic syndrome after renal transplantation. Studies of the adsorbed proteins should provide information about the mechanism of this disease.

During the period from January 1973 to December 1970, 774 renal transplantations in 698 children have been performed in our Renal Unit. A total of 540 grafts have been examined both by light and immunofluorescence microscopy at least once. Recurrent glomerulonephritis was diagnosed in 62 grafts, de novo glomerulonephritis in 68 and allograft glomerulopathy (AGP) in 38. AGP was defined as a lesion affecting all glomeruli and characterized by widespread reduplication of the GBM with widening of the subendothelial space and interposition of mesangial matrix and without significant deposits by immunofluorescence. The aim of the current study is to describe the natural history of AGP and to delinate its clinical significance. At time of biopsy, an increase in serum creatinine was present in 30 patients associated with a proteinuria > or = 1 g/day in 21. During the post-transplantation course, proteinuria was present in 29 patients and associated with a nephrotic syndrome in 10 of them. With a mean follow-up of eight years seven months, two patients died, 23 lost their grafts and 13 have a functioning graft. The lesions of AGP recurred in three of the nine children who received a second graft. Thirteen of the 33 patients in whom earlier biopsies were performed showed a different pattern of involvement characterized by a prominent swelling of active endothelial and mesangial cells and a hypercellularity related to the presence of mononuclear cells both in the lumens and in the mesangial areas.(ABSTRACT TRUNCATED AT 250 WORDS)

The anti-OKT3 response was studied in 40 paediatric kidney transplant recipients receiving OTK3 as a prophylactic treatment in association with azathioprine and prednisone. Only 1 patient experienced a reversible acute rejection episode while receiving OKT3. OKT3 induced a rapid disappearance of CD3+ cells, but significant proportions of CD3+ cells reappeared before the end of the treatment in 14 patients. Wide variations in circulating OKT3 levels were observed and in only 50% of patients could stable circulating OKT3 levels be detected until discontinuation of treatment. Anti-OKT3 antibodies detected by the enzyme-linked immunosorbent assay (ELISA) (anti-idiotypic and anti-isotypic antibodies) developed in 91% of patients. Anti-idiotypic antibodies detected by the immunofluorescence inhibition test were found in the sera of 71% of patients, always when high titres of anti-OKT3 antibodies were detected by ELISA. As it has recently been shown that anti-idiotypic antibodies are associated with failure of subsequent OKT3 treatment, we conclude that OKT3 should be restricted to steroid-resistant rejection crises in paediatric patients.

Background: Kawasaki disease is an acute inflammatory condition characterized by various combinations of features but renal involvement is rare. This report is of a case of Kawasaki disease complicated by acute kidney failure., Case Report: A 10 year-old girl was admitted because of acute renal failure with fever. She developed a high fever, and her general condition was poor; she had developed a macular erythematous rash 10 days earlier for which she was given cefadroxil. At admission, she remained febrile and had strawberry tongue, pharyngitis, dry erythematous lips, bilateral conjunctivitis, cervical lymphadenopathy and desquamation of the skin on her hands. She was anemic (hemoglobin = 9.6 g%), leukocytotic (33,100/mm3), but with no burr, fragmented red blood cells or thrombocytopenia. Her plasma C-reactive protein level was 236 mg/l; her blood urea was 9.5 mmol/l, her creatininemia 288 mumol/l and proteinuria was 0.5 g/l without hematuria. Urine cultures did not grow. Her blood transaminase and gammaglutamyltransferase activities were elevated. Ultrasonography of kidneys and coronary arteries was normal. Kidney biopsy performed one day after admission showed no vascular or glomerular changes, but renal tubular necrosis, indicating urinary excretion of pigments. Tests for myoglobinemia, myoglobinuria and blood muscle enzyme activities were all positive. The renal failure disappeared within 10 days but the fever and inflammatory manifestations persisted for 1 1/2-2 months despite two treatments of intravenous gammaglobulins and continuous salicylate administration. The patient developed arthralgias at the end of the first month of disease, but recovered without renal or vascular complications., Conclusions: Several cases of renal involvement have been reported during the course of Kawasaki disease. They have been rarely documented by histological examination so that the vascular origin of changes has not been demonstrated. Myoglobinuria, as seen in muscular crush injury, and in our case possibly due to malignant hyperthermia, may be responsible for the transient acute renal failure.

Proteinuria in children with idiopathic nephrotic syndrome is secondary to a loss of charge selectivity of the glomerular basement membrane. Loss of anionic charges may be secondary to a defect of heparan sulfate proteoglycans, which is also found in the congenital nephrotic syndrome, or to cationic proteins, which neutralize the anionic charges of the membrane. Reports on recurrence of nephrotic syndrome in patients with steroid-resistant idiopathic nephrotic syndrome following renal transplantation suggest that a humoral factor, possibly produced by T lymphocytes, may enhance glomerular permeability. Corticosteroids remain the basic treatment of idiopathic nephrotic syndrome. Most patients respond to steroid therapy and a high proportion of them relapse but continue to respond throughout the subsequent course of the disease. Levamisole may be effective in preventing relapses. Cyclosporine may be useful in steroid-dependent patients with signs of steroid toxicity and after a failure of a course of alkylating agent. Almost 85% of patients respond to cyclosporine, but they relapse after tapering or stopping the drug. In steroid-resistant patients, there is no study showing a clear-cut beneficial effect of alkylating agents, as the remission rate after treatment is close to the rate of spontaneous remission. Cyclosporine in association with prednisone may be effective, but the risk of nephrotoxicity seems to be higher than in steroid-dependent patients.

In paediatric renal transplantation, non-immunological risk factors account for about one-third of graft losses. Recurrence of original disease is observed mainly in primary hyperoxaluria and glomerulopathies such as steroid-resistant nephrotic syndrome and membranoproliferative glomerulonephritis. In both glomerulopathies, 20% of grafts are lost from recurrence. Vascular thrombosis is, in most series, the second cause of graft loss in children, particularly in young recipients or with young donors (under 5 years of age). Non-compliance with treatment is a common non-immunological factor in adolescent recipients, which may trigger a severe rejection process resulting in graft loss. The role of factors related to graft preservation and intra- and post-operative management (ischaemia time, delayed graft function) or to cytomegalovirus infection is less obvious in our series. Prevention of vascular thrombosis and of non-compliance is most important in order to improve the results of paediatric renal transplantation.

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.

Despite the absence of anti-HLA antibodies (Ab) about 10 to 20 percent of renal transplants are lost during the first months from rejection. The role of humoral rejection seems more likely than cellular rejection since they do not respond to standard anti-rejection therapy. We studied 37 patients who rejected their graft despite negative T and B lymphocytes cross-match during the first eight months (m: 59 days, range: 2-240) following kidney transplantation. These patients were compared with 57 patients who experienced a favorable outcome. The sera were tested for the presence of Ab against epidermis of a panel of 5 normal skins and against an epithelial-endothelial hybrid cell line (EA hy 926, Dr C.J.S. Edgell), expressing both endothelial and epithelial antigens. Among the 37 patients who rejected theirs grafts, 8 had anti-keratinocytes Ab, 11 had Ab against epithelial-endothelial hybrid cell line, 9 were positive for both tests. Among the 8 pts who lost their graft before 25 days, 5 were positive for at least our test. Conversely, 7 among the 57 pts with favorable outcome had Ab: 2 against keratinocytes, 5 against hybrid cell line. These data suggest that non anti-HLA Ab may play a role in graft rejection. Furthermore the detection of such Ab prior to transplantation may predict patients at risk of severe rejection. In such cases, plasma exchanges may be proposed if they develop steroid-resistant rejection.

We describe the clinical and pathologic features of a case of pediatric multicentric Kaposi's sarcoma (KS) associated with allograft transplantation in a human immunodeficiency virus (HIV)-negative child. A lethal polyadenopathic and visceral KS occurred in a 5-year-old Caribbean boy who had undergone an allogenic renal transplantation for diffuse mesangial sclerosis with end-stage renal failure 4 months previously. The HIV-1 and HIV-2 serologies were negative. Despite its rarity, KS must be considered as a differential diagnosis in posttransplantation polyadenopathic or multisystemic syndromes in children.

Twenty-nine children with typical Schönlein-Henoch purpura (SHP) were tested at the initial phase of the disease for respiratory function. Of the 29 patients, 28 had a decrease of lung transfer for carbon monoxide (TLCO) as measured by a steady-state method. Lung volumes and blood gas values were normal; slight radiologic signs of interstitial lung involvement were observed in 18 of 26 patients. There was a decrease in TLCO to 56.8% of normal values for height and gender and to 58.5% when normal values were volume-adjusted to functional residual capacity. In 19 of 25 patients, TLCO measurements were performed at 3-month intervals during follow-up. In all cases, normalization of TLCO values was observed only after complete clinical recovery from SHP. All children with persisting symptoms, even limited to microscopic hematuria or slight proteinuria, had low TLCO values. In one patient low TLCO during follow-up preceded a late relapse of SHP in the form of acute nephritic disease with characteristic IgA deposits on renal biopsy. We conclude that low TLCO in SHP is probably related to alteration of the alveolar-capillary membrane by circulating immune complexes. This noninvasive technique may be useful in diagnosis, and during the follow-up of the disease as an early indicator of reactivation.

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.

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.

Idiopathic nephrosis, the most common cause of nephrotic syndrome, is histologically defined by minimal glomerular changes, diffuse mesangial proliferation or focal and segmental glomerulosclerosis. The response to corticosteroids carries greater prognostic weight than the histological features seen on the initial renal biopsy. The severity of the condition lies in the risk of relapses which occurs in more than half of cases when steroid dosage is decreased (steroid dependency), then requiring, in case of steroid toxicity, the use of alkylating agents or, more recently, cyclosporine. In 10% of the cases, nephrosis is steroid resistant and the severity of the disease lies in the risk of developing end stage renal failure which occurs in nearly one half of those cases.

Hyperoxaluria type I (HPI) is a metabolic disorder secondary to liver alanine glyoxylate aminotransferase deficiency. Renal failure occurs due to the excessive production and precipitation of oxalate in the kidney. Combined liver-renal transplantation is the correct treatment for this condition when end-stage renal failure occurs as with renal transplantation alone the risk of recurrence of the same pathology in the transplanted kidney would be high. We report the case of a 4 year-old child with HPI suffering from terminal renal failure in whom a hepato-renal transplantation was performed: six months later, creatinine clearance was 62 ml/min/1.73 m2 and liver function tests were normal.

In infantile cystinosis the amino acid cystine preferentially accumulates in phagocytic cells, polymorphonuclear leucocytes (PMN) and monocytes, rather than in lymphocytes. We previously described functional abnormalities in the oxidative metabolism and locomotion of cystinotic PMN and monocytes. The present study shows an abnormal lymphocyte polyclonal activation as evidenced by a decreased immunoglobulin (Ig) production and generation of Ig-containing cells (ICC) in cultures of peripheral blood mononuclear cells (PBMC) from cystinotic children upon stimulation with pokeweed mitogen and Staphylococcus aureus Cowan I. However, monocyte depletion from cystinotic PBMC fully reconstituted Ig production and ICC generation, indicating: (1) the presence of an increased monocyte-dependent suppression on lymphocyte polyclonal activation, and (2) that the intrinsic ability of cystinotic lymphocytes to respond to polyclonal stimulation was preserved. The increased cystinotic monocyte-dependent suppressive effect was not mediated by prostaglandin E2 (PGE2) since its production by cystinotic PBMC upon polyclonal activation was not different from that of controls. In addition, the sensitivity of cystinotic lymphocytes to the immunosuppressive effect of varying concentrations of exogenous PGE2 was similar to that of controls. Finally, indomethacin and 2-mercaptoethanol, two agents able to scavenge hydroxyl (.OH) radicals, restored Ig production by cystinotic PBMC, suggesting a role for reactive oxygen species in the increased cystinotic monocyte-dependent suppression.

Vascular thrombosis is one of the main causes of early transplant failure in pediatric patients. This paper reports the results of an open trial of the low molecular weight heparin (Enoxaparine) used to prevent renal graft thrombosis in pediatric recipients with risk factors including donor or recipient age under 5 years, multiple arteries supplying the transplant, and positive history for recurrent thrombosis. During 1989, 42 of 67 children given a renal transplant were prophylactically treated with Enoxaparin. Only one transplant was lost to thrombosis among treated patients (1.5%), versus 9 transplants among 73 (12%) children who received their kidney in 1988 without prophylactic Enoxaparin. Risk factors were comparable in both groups of recipients. Enoxaparine therapy was associated with an increased rate of bleeding (12/42) without severe consequences. In conclusion, Enoxaparin is effective in preventing renal graft thrombosis. Availability of this prophylactic therapy makes it possible to use transplants removed from the youngest donors considered as inadequate by some groups.

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.

Background: The B-cell lymphoproliferative syndrome is an infrequent life-threatening complication of marrow or organ transplantation that is the consequence of profound immunosuppression. The results of treatment have been disappointing, although a small number of patients have been cured by chemoradiotherapy or antiviral agents after a reduction in the dosage of immunosuppressive therapy. We report here the results of treating this disorder with anti-B-cell antibodies., Methods: Twenty-six patients in whom aggressive B-cell lymphoproliferative syndrome developed after bone marrow (n = 14) or organ (n = 12) transplantation received 0.2 mg of CD21-specific and of CD24-specific antibodies per kilogram of body weight for 10 consecutive days in an open, prospective, multicenter trial., Results: The treatment was well tolerated. All patients had transient neutropenia, apparently because the CD24 molecule is also expressed on granulocytes. The treatment was ineffective in seven patients with monoclonal B-cell proliferation. In contrast, 16 patients with oligoclonal B-cell proliferation had complete remission. Systemic remission also occurred in two other patients with oligoclonal proliferation who had central nervous system involvement, although they subsequently died because of progression of the central nervous system disease. In one patient who died early, clonality was not determined. Of the 16 patients who had complete remission, 2 with persistent immunodeficiency due to graft (marrow) rejection or acute graft-versus-host disease had a relapse, and the 1 with graft-versus-host disease subsequently died. Eleven patients were alive and disease-free after a median follow-up of 35 months (5 of 14 marrow recipients and 6 of 12 organ recipients). Four other patients in complete remission died of unrelated causes 4 to 12 months after treatment., Conclusions: Intravenous administration of anti-B-cell antibodies may be effective in controlling diffuse, severe, oligoclonal B-cell proliferation not involving the central nervous system.

We report a transient neonatal nephrotic syndrome in two infants born to a mother with idiopathic nephrotic syndromes (INS). The mother, born in Mali in 1966, had a normal first pregnancy, with a normal live child. Six months later a nephrotic syndrome appeared with normal renal function; renal biopsy disclosed slight lesions of focal and segmental glomerulosclerosis. Prednisone and ciclosporin were totally ineffective. In 1986 and 1988 two pregnancies occurred with normal gestation outcome; however, the two births were premature (35 weeks) with hypotrophic infantas (2.160 and 2.080 kg). In both cases urine analysis revealed neonatal heavy proteinuria, with low serum protein and hypoalbuminemia; proteinuria decreased and disappeared within 2 and 3 weeks respectively; simultaneously protidemia and albuminemia were normalized. Thus, a transitory nephrotic syndrome, resolving spontaneously, occurred in two successive offsprings of a patient with INS. These cases are in keeping with the hypothesis that heavy proteinuria in nephrotic syndrome might be linked to a circulating humoral factor and that INS is a disorder linked to T-lymphocyte function with enhanced production of a lymphokine acting on vascular permeability.