Successful anti-TNFalpha treatment in a child with posttransplant recurrent focal segmental glomerulosclerosis.

Posttransplant recurrence of focal and segmental glomulosclerosis (FSGS) occurs in approximately 30% of patients, and remains after uncontrolled despite increased immunosuppression and plasma exchanges (PE) in approximately 30% of cases. New immunosuppressive drugs might then be warranted. We report the case of a 15-year-old boy with FSGS leading to end-stage renal disease (ESRD) who presented with an early posttransplant recurrence of disease. Reinforced immunosuppression and PE resulted in partial and transient disease control, but proteinuria significantly decreased with anti-TNFalpha treatment (infliximab then etanercep). This is the first case report of successful anti-TNFalpha treatment despite a constant high activity of FSGS, as demonstrated by relapse after discontinuation of anti-TNFalpha agents.

Abnormal fibrin clot architecture in nephrotic patients is related to hypofibrinolysis: influence of plasma biochemical modifications: a possible mechanism for the high thrombotic tendency?

Porosity, viscoelasticity and morphological properties of plasma fibrin from 16 nephrotic patients and 16 healthy volunteers were compared. Nephrotic patients were characterized by formation of tight and rigid plasma fibrin gels which resulted in a slower rate of fibrin lysis studied either under pressure-driven permeation or diffusional transport of fibrinolytic agents. These latter findings indicated that both abnormal fibrin network conformation and abnormal fibrin fiber structure were involved in hypofibrinolysis. Albumin supplementation up to 40 mg/ml partially restored normal fibrin architecture and increased the rate of fibrinolysis in these patients. Multiparametric analysis showed that nephrotic patients were mainly characterized by a low plasma albumin level (R = -0.85), a low albumin to fibrinogen ratio (R = -0.89) and a high resistance to lysis (R = -0.82). High triglycerides level was the only plasma modification related to the slower fibrin lysis rate (R = -0.54). High fibrin rigidity (G') was the only fibrin parameter simultaneously related to the nephrotic state (R = 0.75) and the lysis resistance (R = -0.71). After eliminating the effects of age, albumin and fibrinogen levels, low fibrin porosity (Ks) and low fiber mass-length ratio (mu) were the main features of the nephrotic state. These findings are discussed in relation to both the pathophysiology of thrombotic complications in nephrotic syndrome and their pharmacological prevention.

Insulin-like growth factor-I (IGF-I), insulin-like growth factor binding proteins (IGFBP) and insulin-like growth factor type I receptor in children with various status of chronic renal failure.

Chronic renal failure in childhood causes severe growth retardation. The aim of the study was to identify whether changes in the IGF system could account for the growth retardation observed in children with chronic renal failure. Insulin-like growth factor (IGF-I) serum concentrations, insulin-like growth factor binding proteins (IGFBP) and/or IGF-I binding to erythrocyte type I receptor of IGF were analysed in 69 children (mean age 11.6 +/- 4.3 years) with chronic renal failure and growth retardation (mean height -2.6 +/- 1.8 SD). The study population was separated into three groups, according to their renal status, children on conservative treatment (CRF group: n = 30), on haemodialysis (ESRD group: n = 26) and those transplanted (RT group: n = 13). Nineteen of these children, some from each of the three groups, received recombinant growth hormone therapy (rhGH). Mean basal IGF-I serum concentrations were -0.7 +/- 1.2 SD in the CRF group, + 2.1 +/- 3 SD in the ESRD group and + 1.1 +/- 2 SD in the RT group. Under rhGH therapy, as height velocity improved, mean IGF-I concentrations increased up to + 3.1 +/- 0.6 SD in the CRF group, to + 6.9 +/- 2.8 SD in the ESRD group and to + 3.9 +/- 2 SD in the RT group. Basal IGFBP-3 levels, studied by Western Ligand Blot were low in the CRF group and high in the ESRD and normal in the RT groups, whereas IGFBP-2 and a 30-32 kDa IGFBP were always high in all cases. Western immunoblot analysis showed that this 30-32 kDa IGFBP was mostly composed of IGFBP-1 and IGFBP-6 in all three groups, but IGFBP-6 was particularly abundant in the ESRD group. IGFBP-6 concentrations assessed by RIA were moderately increased in CRF children (392 +/- 177 ng/mL) and very high in children on ESRD (2094 +/- 1525 ng/mL) when compared to normal values (131 +/- 42 ng/mL). Binding studies of IGF type I receptor showed that there was no particular difference in IGF-I binding between renal failure patients and normal children. In poorly growing children, especially in ESRD children and to a lesser extent in RT children, high concentrations of IGF-I and IGFBP-1, 2, 3 and 6, suggest a resistance mainly by a sequestration mechanism. Moreover, in the CRF group, especially in the younger children, low levels of IGF-I and IGFBP-3 are evocative of an associated resistance at the GH receptor level.

Energy balance in children and young adults receiving haemodialysis for chronic renal failure.

This study was designed to determine the contribution of energy expenditure to the energy imbalance seen in uraemic children. Resting energy expenditure (REE) was measured using open-circuit indirect calorimetry in eight uraemic haemodialysed subjects aged 9.3-20.4 years and in 10 healthy children. Linear correlations between REE and both body weight and fat-free mass as measured by anthropometry were found in both controls and uraemic subjects (respectively: r = 0.76 and r = 0.88 for body weight and r = 0.73 and r = 0.90 for fat-free mass). Measured REE in uraemic patients was not different from the value predicted by using actual body weight and fat-free mass in the regression equation of REE on body weight and fat-free mass in controls (paired t test: p = 0.70 and p = 0.19 respectively). These data suggest that the energy imbalance seen in uraemic children is not due to increased energy expenditure and is therefore probably due to decreased food intake.

The nephropathy associated with male pseudohermaphroditism and Wilms' tumor (Drash syndrome): a distinctive glomerular lesion--report of 10 cases.

We report on 10 children, less than 2 years of age, who presented with a genuine type of glomerulopathy: diffuse mesangial sclerosis. In 5, the nephropathy was associated with male pseudohermaphroditism (MPH) and Wilms' tumor (WT); in 3 with MPH and in 2 with WT. The nephropathy was characterized by its very early onset, between the age of 2 weeks and 18 months. Eight patients presented with a nephrotic syndrome with (7 cases) or without (1 case) hypertension. All, but one, who is in advanced RF at 11 years of age, progressed to chronic or end-stage renal failure (ESRF) within a few months to 2 years from the onset. One additional child presented with advanced renal failure at the age of 8 months and the last one, who was hypertensive, developed an anuria related to thrombosis of renal veins at 1 year of age. Drash syndrome is characterized by the association of a "nephron disorder" with MPH and WT. We propose, on the basis of our histological findings, to extend the concept of Drash syndrome to patients who, in addition to the nephropathy, have either WT or MPH and to consider the distinctive glomerular lesions presented by all these patients as their common denominator. The pathogenesis of this glomerulopathy is obscure. Its early onset, its association with a dysembryoplastic tumor and/or with gonadal dysgenesis both suggest an antenatal dysgenetic process.

[Curative treatment of lower urinary tract infections]. / Traitement curatif des infections urinaires basses.

Because it is limited to the bladder, infection of the lower urinary tract does not lead to renal scaring. It may be symptomatic or asymptomatic. When symptomatic it never includes high fever and general symptoms. Only symptomatic infections need treatment using oral antimicrobial monotherapy for 5 to 7 days. It is necessary to search for a predisposing factor--mainly bladder dysfunction and constipation.

[Treatment of urinary tract infections in neurogenic bladder]. / Traitement des infections urinaires sur vessie neurologique.

Urinary tract infections are frequent in children with neurologic bladder. Treatment must be adapted to the type of infection: acute pyelonephritis requires early intravenous treatment: symptomatic infection of the lower urinary tract is to be treated by oral monotherapy; asymptomatic infection needs no treatment.

[Renal complications of non-steroidal anti-inflammatories]. / Complications rénales des anti-inflammatoires non stéroïdiens.

INTRODUCTION: Non-steroidal antiinflammatory drugs (NSAIDs) are known to have adverse effects on kidney function. Situations with stimulated renin-angiotensin system (RAS) like volume depletion or preexisting chronic renal failure predispose to acute renal failure (ARF) via inhibition of prostaglandin synthesis by NSAIDs. To date NSAIDs are frequently used as antipyretic drugs even in situations predisposing to ARF. PATIENTS: Within 20 months seven children presenting with diarrhea and/or vomiting and fever were treated with therapeutic doses (11.5-32 mg/kg per day) of ibuprofen for 1-3 days before developing ARF. Maximum plasma creatinine levels were 180-650 pmol/l. One patient required emergency dialysis for hyperkalemia, uremia, and hyperphosphatemia. After cessation of NSAID treatment and rehydration all patients recovered completely with a normalized creatinine level after 3-9 days. Once the acute phase is controlled long-term outcome is excellent. CONCLUSION: NSAIDs are potentially dangerous in situations with, even moderate, volume depletion.

[The biochemical and hematological assessment of iron metabolism]. / Les outils biochimiques et hématologiques de l'exploration du métabolisme du fer.

Despite the progress in the knowledge of iron metabolism, its precise assessment remains uneasy. Serum ferritin assesses the extent of storage iron. Serum iron and the percentage of transferrin saturation evaluate the tissues' iron supply. But these parameters are indirect measurements and they do not reflect marrow iron supply. Serum transferrin receptors, red cell ferritin and red cell zinc protoporphyrin are good indicators of this iron supply to the erythroid marrow for erythropoiesis. Since the introduction of recombinant human erythropoietin, it has become apparent that an adequate iron supply to the bone marrow is essential for a satisfactory hematopoietic response. In some cases, despite a high baseline ferritin, iron may not be sufficiently released from reserves in the bone marrow, resulting in a functional iron deficiency. The percentage of hypochromic red cells and reticulocyte haemoglobin content tends to reflect direct marrow iron status.

[Alkaptonuria: a rare cause of urine discoloration. Report of a case in a newborn]. / L'alcaptonurie: une cause rare de coloration anormale des urines. A propos d'un cas chez le nourrisson.

UNLABELLED: Alcaptonuria is a rare hereditary disease, characterized by an abnormal blackish coloration of the urine and dark pigmentation of the conjunctive tissue which is due to a deficiency in homogentisate 1,2-dioxygenase (HGO), a phenylalanine catabolizing enzyme. An accumulation of homogentisate (HGA) is then formed, and is responsible for the dark coloration which only occurs after the urine has been exposed to air over a period of time. Signs of this disorder therefore frequently remain unnoticed during childhood, because the urine requires a relatively long exposure to air before it changes color. Diagnosis is generally made at a later date, during adulthood, following complications such as ochronosis, inflammatory arthritis, or urinary calculi. CASE REPORT: In this study, the case has been described of alcaptonuria diagnosed in a five-month old infant. No efficient cure has yet been found, although certain treatments, including high doses of vitamin C, do seem to have a beneficial effect on limiting the complications associated with this disorder. Early diagnosis whenever possible is therefore important. CONCLUSION: This case report is interesting because of the early diagnosis involved. In the event of any abnormal coloration of the urine, diagnosis may be established via the addition of an alkylating agent, and the levels of HGA determined by chromatography.

[Acute urine retention: a rare mode of revelation of cervico-dorsal syringomyelia caused by cyproheptadine]. / Rétention aiguë d'urines: un mode de révélation rare d'une syringomyélie cervicodorsale à l'occasion de la prise de cyproheptadine.

BACKGROUND: Syringomyelia is rare in children aged less than 10 years, and bladder dysfunction is an unlikely first manifestation. This report describes a case of repeated episodes of acute urinary retention in a young girl revealing syringomyelia and Arnold-Chiari malformation. CASE REPORT: A 2.5 year-old girl was admitted because she was suffering from acute urinary retention. Her poor appetite had been treated with cyproheptadine, a histamine type I blocking drug. Clinical investigation revealed no local cause for this bladder dysfunction except moderate spasticity of the legs. Cystography showed no vesicoureteral reflux. Because the episodes of urinary retention recurred each day, magnetic resonance imaging (MRI) was performed; this showed the typical features of syringomyelia extending from C5 to T11 plus Arnold-Chiari malformation. The cyproheptadine was discontinued and the urinary retention disappeared. CONCLUSION: Cyproheptadine may have revealed latent neurogenic bladder in this case, although urodynamic studies, performed 3 months later, detected no bladder dysfunction.

[Transient correction of partial congenital factor V deficiency in nephrotic syndrome]. / Correction transitoire d'un déficit congénital partiel en facteur V au cours d'un syndrome néphrotique.

Plasma concentration of several hemostatic proteins may be modified during the acute phase of nephrotic syndrome. The case of such a syndrome in a patient with congenital factor V deficiency is presented. CASE REPORT--A 5 year-old girl with partial congenital factor V deficiency (level: 30%), was admitted for nephrotic syndrome complicating Henoch-Schönlein purpura. Urine protein excretion was 4 g/24 h. Initial plasma concentrations were: protein: 5.5 g/dl; albumin: 3.3 g/dl; factor II: 85%; factor V: 56%; factors VII + X: 80%. The patient was given methylprednisolone (1 g/1.73 m2) followed by prednisone (2 mg/kg/day). Under this treatment, the plasma concentrations were: protein: 4.5 g/dl; albumin: 2.0 g/dl; factor II: 180%; factor V: 84%; factors VII + X: 120%. Values at the onset of remission were: albumin: 3.4 g/dl; factor V: 49%. CONCLUSION--This observation suggests that hypoalbuminemia may enhance liver synthesis of factor V as known for some other coagulation factors, and transiently correct the hereditary deficiency.

[Digestive manifestations in hemolytic uremic syndrome in children]. / Les manifestations digestives du syndrome hémolytique et urémique de l'enfant.

BACKGROUND: Gastro-intestinal manifestations are relatively frequent during the course of hemolytic uremic syndrome (HUS), some of them requiring special supportive care. This work was aimed at retrospectively studing gastrointestinal manifestations of HUS and determining their place in the prognosis. PATIENTS: Thirty-seven children aged 4 months to 11 years (22 girls and 15 boys) were included in the study. RESULTS: All children but one had gastrointestinal prodromes. During the course of HUS, various manifestations were seen: bloody diarrhea in 32% of patients, ileo-ileal intussusception in 3%, rectal prolapse in 8% and hepatic cytolysis in 38%. Seven patients with bloody diarrhea had a complicated course, lethal in one. Comparison between these seven children and the 30 others revealed some indicators of severe gut involvement: female sex, short duration of gastrointestinal prodromes, hemorrhagic colitis with rectal prolapse, high WBC count, high neutrophils count and less important degree of anemia at admission. Severity of the gastrointestinal lesions was correlated with that of the outcome of the renal disease. CONCLUSION: Gastrointestinal tract is frequently affected in HUS and severe complications can appear, potentially leading to death. Total parenteral nutrition could prevent occurrence of gastrointestinal complications. Severe gastrointestinal lesions are associated with a poor renal outcome.

[Prognosis of prenatal uropathies: should fetal urine tests be continued?]. / Pronostic néphrologique des uropathies à révélation anténatale: faut-il continuer les ponctions d'urine foetale?

Twenty percent of the children with end stage renal failure have severe obstructive uropathies. The assessment of fetal renal function and the degree of renal damage in utero is a critical factor in providing realistic counseling. The prediction of postnatal renal function is made by sonography, fetal urinary biochemistry and fetal serum for beta-2-microglobulin. Ultrasonography is a useful method including assessment of amniotic volume and ultrasonographic evaluation of the renal parenchyma. The analysis of fetal urine for the assessment of renal function leads to conflicting results. Some papers conclude that fetal urine electrolytes are not an accurate predictor of neonatal renal function, others conclude that they provide useful information. The number of studies dealing with the urinary beta-2-microglobulin levels in the assessment of prenatal renal function is too small for allowing definitive conclusions. The predictive value of fetal serum beta-2-microglobulin for neonatal renal function may be interesting but the results are yet preliminary. The studies of fetal urinary biochemistry should be continued within prospective research programs; the data are either too conflicting or too preliminary to use this methodology in commun practise.

[Treatment of urinary infection in children]. / Traitement de l'infection urinaire chez l'enfant.

Urinary tract infection in children includes several and totally different diseases which must be managed according to circumstances. In all cases of acute pyelonephritis the patients must be investigated for abnormalities of urinary tract structures. A strong and prolonged treatment reduces the risk of scars. Lower urinary tract infection without potential deleterious effects on the renal parenchyma requires an oral antimicrobial therapy of not more than 7 days duration. Asymptomatic infection with normal urinary tract structures does not need an antimicrobial treatment. Long-term prophylactic antimicrobial treatment administered in full doses produces bacterial selection. Very low doses are sufficient to reduce the virulence of the pathogen and the risk of infection, without altering the gastrointestinal flora.

[Pharmacokinetics of prednisolone in children. Study of a correlation with tolerability and therapeutic effect in nephrosis]. / Pharmacocinétique de la prednisolone chez l'enfant. Recherche d'une corrélation avec la tolérance et l'effet thérapeutique au cours de la néphrose.

In patients with nephrotic syndrome the response to corticosteroids and the way these drugs are tolerated are extremely variable. The purpose of this study was to investigate possible correlations between the pharmacokinetic values of prednisolone and the main clinical criteria of effectiveness and safety. The study was performed on 18 children under corticosteroid therapy: 16 with nephrotic syndrome and 2 with a systemic disease. Measurements were performed by radiocompetition with transcortine after an oral dose of 1 mg/kg bodyweight. Pharmacokinetic values varied considerably, with peak plasma levels ranging from 1.2 to 6.1 micrograms/ml between 20 and 120 minutes, and T 1/2 values of 77 to 648 minutes. Within this scattering of values, some patients were clearly outside the mean T 1/2 value (3.1 +/- 1 hours) due to a particularly fast or slow metabolisation of the drug. In patients with nephrotic syndrome no correlation was found between pharmacokinetic values and criteria of clinical effectiveness, such as the time and dosage required to obtain remissions and the duration of these remissions. Hypoalbuminaemia had no influence on the metabolism of prednisolone. In contrast, there was a correlation between pharmacokinetic values and side-effects, since patients who presented with side-effects also had a significantly greater area under plasma concentration versus time curves. This pharmacokinetic test may be used when corticosteroids produce unusual or unexplainable therapeutic results or adverse reactions.

[Value of the Hickman catheter in pediatric nephrology]. / Intérêt du cathéter de Hickman en néphrologie pédiatrique.

The Hickman catheter is a single or double lumen catheter made of a silicone polymer; it is introduced surgically into the superior vena cava or the right atrium. The authors have used this catheter in 11 children, aged from 3 to 15 years and weighing from 10 to 40 kg, either for haemodialysis in children without arteriovenous fistula (n = 10), or for plasma exchanges (n = 1). In 5 of the 10 children, an arteriovenous fistula was created while the catheter was being installed. The catheter was left in place for a mean period of 48 days and a maximum period of 5 months. Data from the literature suggests that this instrument can be used for even longer periods. Dialysis was satisfactory in 8 out of 10 cases. No infection or thrombosis of the catheter was observed. The catheter was not perfused between haemodialysis sessions or blood exchanges.

[Renal transplantation in children. Surgical aspects]. / La transplantation rénale chez l'enfant. Aspects chirurgicaux.

The renal transplantation in children has some specificities: urologic anomalies (vesico ureteral reflux, posterior urethral valves) are frequently the cause of the renal failure, and necessitate a thorough surgical preparation before transplantation (nephrectomy, reconstitution of urinary tract). The child must have a sterile, compliant and continent urinary tract on the day of the operation. In small children (< 15 kg), it is often necessary to operate through a transperitoneal incision, especially if the donor is an adult: the anastomoses will then concern the aorta and vena cava. The results are good, even better than in adults, except for very young children (under six years of age). Transplantation with living related donor (LRD) give the best results. Currently, the graft survival is 87% to 90% after three years with LRD, versus 65 to 77% with cadaveric donors.

The effects of childhood trauma upon adult recovery from injury and illness.

Many patients with chronic injury or illness suffer from childhood trauma syndrome. As a result, they do not take proper care of themselves and are at risk of developing long-term disabilities. Physicians who understand the dynamics of CTS can help these patients regain control over their own bodies and health. By building therapeutic relationships with these patients, physicians can restore trust and help them lead happier, healthier lives.