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RATIONALE & OBJECTIVE: The KDIGO (Kidney Disease: Improving Global Outcomes) guideline on CKD presented an international classification system that ranks patients' risk for CKD progression. Few data on children informed guideline development STUDY DESIGN: Observational cohort study SETTINGS AND PARTICIPANTS: Children aged 1-18 years enrolled in the North American Chronic Kidney Disease in Children (CKiD) cohort study and the European Effect of Strict Blood Pressure Control and ACE Inhibition on the Progression of CRF in Pediatric Patients (ESCAPE) trial. PREDICTOR: Level of estimated glomerular filtration rate (eGFR) and proteinuria (urine protein-creatinine ratio (mg/mg)) at study entry OUTCOME: A composite event of renal replacement therapy, 50% reduction of estimated GFR (eGFR), or eGFR 2.0 at study entry. Six ordered stages with varying combinations of eGFR categories (60-89, 45-59, 30-44 and 15-29 ml/min/1.73m(2)) and UPCR categories (2.0) described the risk continuum. Median times to event ranged from >10 years for eGFR 45-90 and UPCR 2. Children with glomerular disease were estimated to have a 43% shorter time to event than children with nonglomerular disease. Cross-validation demonstrated risk patterns that were consistent across the ten subsample validation models. LIMITATIONS: Observational study, utilized cross validation rather than external validation CONCLUSION: CKD staged by level of eGFR and proteinuria characterizes the timeline of progression and can guide management strategies in children.

El trasplante renal es el tratamiento optimo de la insuficiencia renal terminal en la edad pediatrica. En Francia, por ejemplo, entre 100 y 120 ninos menores de 18 anos reciben un trasplante renal cada ano. La duracion de la espera para los ninos es inferior a la de los adultos, debido a un cierto grado de prioridad de acceso al trasplante. La preparacion del injerto conlleva la actualizacion de las vacunaciones (en especial contra la hepatitis B y la varicela), la correccion de las posibles malformaciones de las vias urinarias, la busqueda de una trombofilia, la determinacion de los antigenos de histocompatibilidad y la busqueda de anticuerpos dirigidos contra estos antigenos. Los resultados del trasplante han mejorado gracias a los nuevos inmunosupresores, con una reduccion de los episodios de rechazo agudo, que es el factor determinante de la supervivencia a largo plazo de los injertos. Los resultados son mejores tras el trasplante de un rinon de donante vivo (en la mayoria de los casos, de uno de los progenitores) en comparacion con un rinon de donante en estado de muerte encefalica, con una supervivencia de los injertos a los 10 anos del 77 y 65%, respectivamente. Aparte de las complicaciones inmunologicas del rechazo, las otras complicaciones son las infecciones, en especial virales por citomegalovirus o virus de Epstein-Barr, los problemas urologicos, el riesgo de trombosis precoz y la recidiva de la enfermedad causal, como el sindrome nefrotico corticorresistente, la hiperoxaluria primaria o el sindrome hemolitico uremico atipico. El crecimiento longitudinal despues del trasplante sigue siendo una preocupacion fundamental. Dicho crecimiento se ve ralentizado en caso de disfuncion del injerto y por la corticoterapia. Los nuevos tratamientos inmunosupresores permiten reducir las dosis e incluso evitar o suspender los corticoides. Por ultimo, la observacion del tratamiento inmunosupresor es un factor esencial de la supervivencia de los injertos a largo plazo y los peores resultados se observan durante la adolescencia.

El sindrome de Fanconi es secundario a un defecto mas o menos generalizado de la reabsorcion en los tubulos renales proximales, con una perdida excesiva de aminoacidos, glucosa, fosforo, bicarbonato y otros electrolitos. Los ninos afectados presentan retraso de crecimiento, raquitismo, poliuria y deshidratacion. La causa mas frecuente es la cistinosis. Esta, de transmision autosomica recesiva, es una enfermedad lisosomica caracterizada por la acumulacion de cistina en todos los tejidos y organos. El gen causal, CTNS, codifica la cistinosina, un transportador lisosomico de cistina. La anomalia observada en el 60-70% de los ninos con sindrome de Fanconi originarios de Europa del Norte, es una gran delecion de 57 kb. Se han descrito alrededor de 80 mutaciones del gen CTNS. En la forma infantil de la enfermedad, al comienzo prevalece un sindrome de Fanconi, que se manifiesta entre los 3-6 meses. Sin tratamiento, la lesion renal avanza hacia la insuficiencia renal terminal despues de los 6 anos de edad. Los depositos corneales de cistina causan fotofobia. Las otras manifestaciones son mas tardias: insuficiencia tiroidea, diabetes mellitus, miopatia y encefalopatia. El diagnostico se basa en la determinacion biologica de la concentracion de cistina intraleucocitica, que esta elevada. El tratamiento consiste en una compensacion de las perdidas urinarias de agua y electrolitos, en la administracion de indometacina y en un tratamiento de fondo con cisteamina, que permite la deplecion de cistina de las celulas. Las otras enfermedades responsables de un sindrome de Fanconi en el nino son geneticas en su mayoria, en especial la intolerancia a la fructosa, la galactosemia, la tirosinosis, la enfermedad de Wilson, las glucogenosis, la enfermedad de Dent, el sindrome de Lowe y las citopatias mitocondriales.

El sindrome nefrotico, definido por una proteinuria y una hipoalbuminemia inferior a 30 g/l, siempre es secundario a una afeccion glomerular. Cualquiera que sea su causa, el sindrome nefrotico se puede complicar con infecciones bacterianas, hipovolemia con colapso e insuficiencia renal, trombosis venosas o arteriales y malnutricion. El sindrome nefrotico idiopatico o nefrosis es la causa de mas del 90% de los sindromes nefroticos entre los 3-10 anos. La nefrosis es corticosensible en un 85% de los casos. El riesgo principal es el de las recaidas que se pueden producir a medida que disminuye la corticoterapia (corticodependencia) o cuando finaliza. Los tratamientos alternativos se reservan para los casos en los que la corticoterapia discontinua, prescrita para mantener la remision, provoca efectos secundarios importantes, como la detencion de la curva de crecimiento estatural. Entre estos tratamientos estan el levamisol, los agentes alquilantes, la ciclosporina y el micofenolato mofetilo (MMF). En alrededor del 50% de los casos la nefrosis corticorresistente evoluciona hacia la insuficiencia renal terminal. Aparte de la nefrosis, el sindrome nefrotico puede ser secundario a una glomerulonefritis primitiva (glomerulonefritis extramembranosa, enfermedad de Berger) o secundaria (purpura reumatoidea, lupus eritematoso diseminado) o a otras causas (amilosis, sindrome hemolitico y uremico, sindrome de Alport). Antes de la edad de 1 ano, es muy comun que el sindrome nefrotico sea de origen genetico y su evolucion, desfavorable, hacia una insuficiencia renal terminal. Ademas de los tratamientos especificos, cuando estos son aplicables, el tratamiento sintomatico tambien es importante para evitar las complicaciones del sindrome nefrotico.

Resumen El sindrome hemolitico y uremico (SHU) se caracteriza por la asociacion de anemia hemolitica con esquistocitos, trombocitopenia y afectacion renal secundaria a lesiones de microangiopatia trombotica. La forma tipica es la mas frecuente en el nino. Esta se presenta tras un episodio de diarrea por Escherichia coli enteropatogena. Pueden estar implicados otros germenes como Shigella dysenteriae o Streptococcus pneumoniae. La insuficiencia renal es reversible en la mayoria de casos, pero se observan secuelas renales a largo plazo en alrededor de una tercera parte de los pacientes cuando la duracion de la anuria inicial sobrepasa 1 semana. El tratamiento de esta forma es puramente sintomatico (transfusion de concentrado de hematies, tratamiento de la insuficiencia renal aguda). Las formas atipicas son menos frecuentes, pero a menudo de peor pronostico. El SHU atipico puede asociarse a mutaciones del gen del factor H, a un deficit de proteasa del factor von Willebrand, a un deficit congenito del metabolismo de la vitamina B12 y a determinados farmacos, o ser en apariencia primario. Las formas familiares son corrientes. La recidiva despues de trasplante renal resulta excepcional en las formas postinfecciosas, pero frecuente en las atipicas.

Resume La nephrose ou syndrome nephrotique idiopathique est la nephropathie glomerulaire la plus frequente chez l'enfant. Les rechutes sont frequentes, mais l'evolution a long terme est faisable. En cas de corticoresistance, le pronostic est different car l'evolution vers l'insuffisance renale terminale est observee dans la moitie des cas. Le syndrome nephrotique est confirme par la decouverte d'une proteinurie associee a une hypoallumenie.

Resume La decouverte d'une HTA chez l'enfant implique la recherche poussee d'une cause et une prise en charge a long terme pour en prevenir les complications L'hypertension arterielle essentielle debute dans l'enfance et des valeurs plus elevees de pression arterielle a ce moment-la permettent de prevoir la survenue a l'âge adulte d'une hypertension arterielle.

Resumen El trasplante renal es el tratamiento de referencia de la insuficiencia renal terminal en el nino. La preparacion para el trasplante es una etapa importante, incluye un estudio exhaustivo, con especial enfasis en la actualizacion de las vacunas, la eventual correccion de las anomalias del tracto urinario, la determinacion del grupo HLA (human leukocyte antigen) y la busqueda de anticuerpos linfocitotoxicos. El rinon trasplantado puede proceder de un donante en estado de muerte encefalica o de un donante vivo emparentado (la mayoria de las veces uno de los dos padres). Los resultados en terminos de supervivencia actuarial de los injertos son mejores con los rinones procedentes de donantes vivos emparentados. Las causas de fracaso son, esencialmente, el rechazo, ya sea agudo, precoz e irreversible o, mas frecuentemente, cronico al cabo de varios anos. Una de las principales causas de rechazo cronico que aparece despues de unos cuantos anos es el seguimiento incorrecto del tratamiento inmunosupresor. A lo largo de los ultimos anos, se han realizado importantes progresos en el tratamiento inmunosupresor que permiten reducir la incidencia del rechazo agudo y, de este modo, prolongar la supervivencia de los trasplantes. Entre estos tratamientos, se pueden citar los anticuerpos monoclonales humanizados dirigidos contra el receptor de la interleucina 2, el tacrolimus, el micofenolato de mofetilo y la rapamicina. Dichos tratamientos tienen efectos secundarios que es importante conocer. Tambien pueden presentarse otras complicaciones tras el trasplante: trombosis vascular, sobre todo en los ninos menores de 5 anos, complicacion urologica, hipertension arterial, complicacion infecciosa, en particular las infecciones por citomegalovirus o por el virus de Epstein-Barr (EBV) o recidiva de la enfermedad causal. El crecimiento estatural de los ninos despues del trasplante depende de la funcion renal y de la dosis de corticoides. Se observa un crecimiento de recuperacion cuando la funcion renal es normal o casi normal y cuando se ha podido reducir el nivel de la corticoterapia. La corticoterapia discontinua a partir del primer ano de tratamiento mejora el crecimiento.

An 18-month-old girl presented with macrocytic megaloblastic anaemia followed by haemolytic uraemic syndrome. Metabolic investigations led to the identification of an inborn error of cobalamin metabolism consisting of defective methylcobalamin biosynthesis, probably cobalamin G, since methionine synthase activity was decreased under standard reducing conditions. Despite treatment, pulmonary hypertension progressively developed and responded to oxygen therapy. Renal involvement evolved to terminal failure and haemodialysis, while pulmonary hypertension was controlled by oxygen therapy. Such clinical manifestations have never been reported in association with a defect of methylcobalamin and thus of methionine biosynthesis. A congenital abnormality of cobalamin metabolism was suspected then confirmed in the presence of typical haematological features associated with unusual clinical manifestations such as progressive renal failure and pulmonary hypertension.

Resume L'endotheline 1 (ET-1) possede une puissante action vasoconstrictrice, en particulier au niveau renal. Cette etude decrit la mise au point d'un dosage de l'ET-1 a partir de reactifs commerciaux sur un volume de plasma reduit (0,6 ml) et evalue chez l'enfant l'influence de l'insuffisance renale sur les concentrations plasmatiques de l'ET-1. L'ET-1 est prealablement extraite sur minicolonnes Sep Pack C18 activees par du methanol, equilibrees par de l'eau distillee, eluees par un melange acide trifluoroacetique, acetonitrile, eau (v/v/v). Les rendements d'extraction sont de 90,5 ± 8,9%. Le dosage radio-immunologique utilise un standard ET-1 Novabiochem et un immunserum anti-ET-1 Peninsula. Les coefficients de variation intra- et interessais sont respectivement de 10,7 et 15,8%. Chez les enfants insuffisants renaux non dialyses, les concentrations plasmatiques d'ET-1 (9,8 ± 3,2 pg/ml; moyenne ± DS; n =48) sont plus elevees ( P n = 29) et inversement correlees ( P n = 41; P

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.

Childhood-onset systemic lupus erythematosus (SLE) is often severe and has a serious long-term morbidity. Pediatric guidelines about its management do not exist. The French study group of childhood-onset SLE proposes recommendations about the investigation which are needed at diagnosis and during follow-up of SLE, in order to adjust the treatment according to the severity of the disease and to avoid unnecessary investigations.

Schönlein-Henoch purpura is a clinical syndrome characterized by the association of skin, joint and gastrointestinal symptoms consisting respectively in purpura, arthralgia and abdominal pain. The incidence of renal symptoms ranges from 33 to 50%. The long term prognosis is related to the renal disease which is characterized by a glomerular involvement, with hematuria and sometimes proteinuria. In more severe cases, a nephrotic syndrome is present with a decrease in renal function. A renal biopsy is performed when proteinuria is in excess of 1 g/day. It shows a mesangial proliferation and in more severe cases extracapillary proliferation while mesangial IgA deposits are seen by immunofluorescence. Severe forms require a treatment with corticosteroids, started with methylprednisolone pulses. Treatment should be started early in the course of the disease before glomerular crescents become fibrous.

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.

Cardiac hypertrophy and arterial dysfunction have been described in end-stage renal disease (ESDR) in adults. The incremental elastic modulus (Einc), is a marker of vascular wall material stiffness and an independant predictor of cardiovascular mortality in adults with ESRD on hemodialysis. The relationship between arterial changes and the heart is unknown in the children with ESRD in the same conditions. Using a high-resolution vascular ultrasound and a computerized system of measurement (Iotec), we assessed noninvasively 10 ESRD patients (mean +/- SD, age, 11.5 +/- 4 years; blood pressure [BP], 120 +/- 10/63 +/- 4 mmHg) and 10 age-, sex-, and BP-matched controls (mean +/- SD, age, 11 +/- 4 years; BP, 114 +/- 8/58 +/- 8 mmHg). The systolic and diastolic diameter of the common carotid artery (CCA), the thickness of the wall (intima-media thickness, IMT), the cross sectional compliance (CSC), the cross sectional distensibility (CSD) and the (Einc) were determined. CSC and CSD were evaluated at the same level of pressure. The CCA pressure waveform was obtained by applanation tonometry to assess the reflected wave by the augmentation index (AI). Further the left ventricular mass index was assessed. The flow mediated dilation (FMD) (endothelium-dependent function) and the vasodilation induced by glyceryl-trinitrate (GTNMD) (GTN, an endothelium-independent dilator) were evaluated at the brachial artery site. Compared to control subjects, ESRD patients have mechanical artery dysfunction with lower CSC and CSD (0.11 +/- 0.04 vs 0.18 +/- 0.05 mm2.mmHg-1; p0.01; 0.43 +/- 0.10 vs 0.82 +/- 0.20 mmHg-1.10(-2); p0.001) and higher Einc (2.60 +/- 1.00 vs 1.40 +/- 0.30 mmHg.10(3); p0.001). Furthermore an earlier return of the reflected pulse wave (AI -0.24 +/- 0.08 vs -0.58 +/- 0.06; p0.005) is correlated to LV mass index (r = 0.55, P0.01) that is significantly increased (134 +/- 63 vs 69 +/- 25 g/m2; p0.005). These patients have an impaired FMD (4 +/- 2 vs 7 +/- 1%; p = 0.02) with a normal GTNMD. This study shows that early arterial dysfunction can occur in children with ESRD.

Objectif Analyser en microscopie confocale in vivo et en OCT de segment anterieur la cornee de patients atteints de cystinose. Materiels et Methodes Dans cette etude, les dossiers de 4 enfants âges de 7 a 16 ans ayant beneficie d’un examen ophtalmologique complet, d’une analyse de la cornee en microscopie confocale in vivo (Heidelberg Retina Tomograph-Rostock Cornea Module, HRT-RCM) ainsi qu’en OCT de segment anterieur (OCT-Visante®) ont ete retrospectivement analyses. Discussion Tous les patients presentaient des depots hyper-reflectifs correspondant a des cristaux de cystine au niveau de la cornee. En microscopie confocale in vivo, ces cristaux apparaissaient sous la forme de fins depots lineaires hyper-reflectifs d’une longueur variable de quelques microns jusqu’a 100 microns. Ces cristaux ont ete retrouves au niveau de l’epithelium, de la couche de Bowman, du stroma anterieur, du stroma moyen et du stroma posterieur. L’endothelium apparaissait indemne de ces depots. La densite maximale de ces cristaux a ete observee au niveau du stroma anterieur. Les images d’OCT de segment anterieur permettaient egalement de visualiser ces depots au niveau de la cornee et confirmaient leur localisation preferentielle au niveau du stroma anterieur. Cette derniere technique montrait egalement un gradient de depots au sein de la cornee, les cristaux etant plus nombreux au limbe par rapport a la cornee centrale. Conclusion La microscopie confocale in vivo et l’OCT de segment anterieur permettent une analyse a la fois qualitative et quantitative des depots de cristaux de cystine au sein de la cornee. Ces deux techniques d’imagerie peuvent etre utiles lors du suivi de patients atteints de cystinose et notamment pour l’evaluation de nouvelles therapeutiques.

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.

Steroid-resistant nephrotic syndrome with either minimal changes or focal and segmental glomerular sclerosis on initial biopsy is a severe condition as more than 50% of patients with the disease progress to end-stage renal failure within 10 years. We recently identified a distinct form of idiopathic nephrotic syndrome with an autosomal recessive mode of inheritance and were able to map the gene on the long arm of chromosome 1. The absence of recurrence of the disease after renal transplantation suggest a primary defect in a glomerular basement membrane protein. Several reports suggest that cyclosporine is effective in a proportion of patients with steroid-resistant idiopathic nephrotic syndrome, particularly when used in combination with corticosteroids. There are also data suggesting that high doses of cyclosporine may be necessary in patients with severe hypercholesterolemia. However, cyclosporine treatment should be carefully monitored in view of the high risk of nephrotoxicity, as shown by the results of repeat renal biopsies. The beneficial role of cyclosporine in recurrent steroid-resistant nephrotic syndrome is still debated. Preliminary observations suggest that the early use of intravenous cyclosporine may be effective in these patients.

Mitochondrial cytopathies are metabolic diseases, expressing mutations in nuclear DNA, punctiform mutations or depletions in mitochondrial DNA. These genetic lesions alter mitochondrial oxidative phosphorylation, with a reduction in energy produced for cell activity. Renal disease may be the first sign of mitochondrial cytopathy, or it may appear together with neurological and neuromuscular signs. Fanconi's syndrome, a benign sign of renal tubulopathy, is particularly frequent in newborns with mitochondrial cytopathy, whereas tubulointerstitial nephropathy, which affects infants and adults, is more serious because it develops into terminal uremia. Findings of hyperlactatemia and reduced enzymatic activity on the respiratory chain in tissue biopsies are of diagnostic significance in mitochondrial cytopathy. A breakthrough is being made in our understanding of genetic alterations in mitochondrial DNA, and with future therapy, the kidney, a target organ, may be safeguarded.

Background There is increasing evidence from clinical trials on which to base a rational approach to the care of lupus nephritis (LN). Objectives To develop recommendations for the management of LN. Methods Questions were compiled using a modified Delphi technique. A systematic PubMed search was performed, and evidence-based and expert-opinion approach was followed to prepare recommendations. Results No clinical, serologic or laboratory tests can accurately predict renal biopsy findings in SLE; any sign of renal involvement, especially proteinuria >0.5 g/24-hr, should be an indication for biopsy. Assessment should include glomerular changes, activity and chronicity indices, tubulointerstitial lesions, and vascular lesions. Because of more favourable efficacy/toxicity ratio, for most patients with ISN/RPS2003 Class IIIA or A/C and Class IVA or A/C (±V) LN, mycophenolate mofetil (MMF) or low-dose intravenous cyclophosphamide (CY) in combination with glucocorticoids is recommended. Induction regimens should be combined initially with three daily pulses of IV methylprednisolone, followed by oral prednisolone 0.5 mg/kg/day. In patients with adverse clinical or histological features, CY can also be prescribed monthly at higher doses (0.75-1g/m2) for 6 months or orally for 3 months. For pure class V disease with nephrotic-range proteinuria, MMF in combination with oral prednisolone may be used initially. In patients responding to initial therapy (≥50% reduction in proteinuria and stable/improved GFR) within 6-12 months, maintenance immunosuppression is recommended with MMF or azathioprine for at least 3 years. For MMF or CY failures, we recommend switching to the other or rituximab. Pregnancy should be planned in stable patients with inactive lupus and serum creatinine

Evaluation of fetal renal function by analysis of fetal urine sampled in utero may improve perinatal care after a prenatal diagnosis of bilateral obstructive uropathy. We provide reference intervals for 10 fetal urinary compounds and examine their variation with gestational age. Forty-one fetuses with bilateral obstructive uropathy (urine sampled between 20 and 38 weeks of gestational age) had normal, healthy values for serum creatinine (or = 50 mumol/L) at ages 1-2 years. These cases were thus assumed to represent a reasonable approximation to healthy values. Sodium and beta 2-microglobulin concentrations significantly decreased with gestational age; calcium, ammonia, and creatinine significantly increased; glucose, phosphorus, chloride, urea, and total protein concentrations did not vary. Our results provide reference values for prenatal evaluation of fetal renal function and suggest that glomerular filtration of macromolecules and tubular reabsorption of glucose and phosphorus are mature by 20 weeks of gestation, whereas tubular reabsorption of sodium and beta 2-microglobulin increases progressively during the second half of gestation.

Juvenile chronic arthritis (JCA) was diagnosed in 2 young girls. In one of them, antinuclear antibodies (ANA) were strongly positive during the course of erosive polyarthritis. After 5 years followup, severe renal insufficiency occurred. Antineutrophil cytoplasmic antibodies (ANCA) were positive with a perinuclear pattern on indirect immunofluorescence (IIF) and antimyeloperoxidase (MPO) specificity. Renal biopsy showed severe crescentic glomerulonephritis without significant deposits on IIF. Treatment consisted of prednisone and monthly intravenous cyclophosphamide pulse. Renal failure worsened and hemodialysis was necessary. A 2nd patient was referred for polyarthritis with positive rheumatoid factors without positive ANA. The presence of microscopic hematuria led to the discovery of crescentic glomerulonephritis with positive ANCA of anti-MPO specificity. At latest examination, after prednisone for 10 months and azathioprine for 6 months, the patient had moderate proteinuria with normal renal function. These observations emphasize that in juvenile onset chronic polyarthritis, renal microscopic angiitis with ANCA of anti-MPO specificity may occur.

We recently described a case of anaphylaxis occurring at the time of retreatment with OKT3 of a renal allograft recipient in whom, for the first time, high anti-OKT3 IgE levels were documented. This led us to examine a large series of sera from 181 OKT3-treated patients to better define the frequency of IgE sensitization, its fine specificity (anti-isotypic and/or anti-idiotypic) and its relation to the appearance of IgG anti-OKT3 antibodies (Abs). Six patients out of the 181 assayed have developed anti-OKT3 IgE Abs as detected by ELISA. The earliest time of appearance of IgE anti-OKT3 Abs was 10 days after starting OKT3 (range, 10-25). The IgE response peaked by day 18 (range, 11-35) and had usually disappeared at 3 months after treatment. A more careful dissection of the fine specificity of the IgE response revealed that three of the four patients tested had developed an exclusive anti-idiotypic response. In the last patient, an anti-isotypic component was present since anti-OKT3 IgE Abs also reacted with control IgG2a, IgG2b, and IgG3 monoclonal antibodies. Importantly, anti-OKT3 IgE Abs were only detected in heavily sensitized patients also showing high titers of IgG specific Abs by ELISA (or = 1/1000) as well as "blocking" anti-OKT3 antibodies, as assessed by immunofluorescence. We conclude that (1) exposure to OKT3 may lead to specific IgE sensitization that, however, only appears in about 38% of the patients; (2) IgE Abs mostly appear in patients also showing high levels of conventional IgG anti-OKT3 Abs including the presence of "blocking" anti-idiotypic Abs, and (3) IgE Abs may be directed to both idiotypic and isotypic determinants of the monoclonal antibody.

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)

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.

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.