Successful treatment of neonatal atypical hemolytic uremic syndrome with C5 monoclonal antibody.

Hemolytic uremic syndrome (HUS) is rare in neonates. We report the case of atypical HUS (aHUS) revealed by neonatal seizures. This 18-day-old baby presented with repeated clonus of the left arm and eye deviation. Four days earlier, she had suffered from gastroenteritis (non-bloody diarrhea and vomiting without fever). Her work-up revealed hemolytic anemia (120 g/L), thrombocytopenia (78 g/L), and impaired renal function (serum creatinine=102 µmol/L) compatible with the diagnosis of HUS. Levels of C3 and C4 in the serum were normal. Shiga-toxin in the stools as well as the IgM and IgG against Escherichia coli O157 were negative. ADAMTS 13 deficiency, inborn error of the cobalamin pathway, deficiency in the H and I protein, and factor H antibodies were excluded and we concluded in aHUS. Genetic screening of the alternative complement pathway was normal. Cerebral magnetic resonance imaging performed after 24 h and 1 week showed restricted diffusion areas with periventricular white matter ischemic-hemorrhagic lesions. Extensive infectious work-up was negative. Upon admission the baby received antiepileptic drugs and 2 days later C5 monoclonal antibody (eculizumab) and two transfusions of packed erythrocytes because the hemoglobin value had dropped to 55 g/L. The platelet value was minimal at 30 g/L. Renal function normalized in 48 h without dialysis and neurological examination was normal in 1 week. She was discharged from the hospital at day 10 with eculizumab perfusions (300 mg) planned every 3 weeks. After 24 months, she was relapse-free and seizure-free, with a normal neurological examination.

[Transition in kidney transplantation]. / Transition en transplantation rénale.

Transition from pediatric to adult care in renal transplantation has emerged as a critical step in the life of a young kidney recipient. During this phase, young patients are faced with the physiological and psychological changes associated with adolescence that can lead to non-compliance and potentially graft loss. To date, there is not a unique accepted model of transition, however it has been proved that the presence of a multidisciplinary team including specialists in adolescent management and in the transition from pediatric to adult transplant care is beneficial during this at-risk phase. The goal of this team is to ensure a progressive transition of the patients according to a precise plan and time line.

Widespread intracranial calcifications in the follow-up of a patient with cartilage-hair hypoplasia--anauxetic dysplasia spectrum disorder: a coincidental finding?

BACKGROUND/PURPOSE: Intracranial calcifications have been identified in many neurological disorders. To our knowledge, however, such findings have not been described in cartilage-hair hypoplasia - anauxetic dysplasia spectrum disorders (CHH-AD), a group of conditions characterized by a wide spectrum of clinical manifestations. METHODS/RESULTS: We report a 22-year old female patient, diagnosed with this disorder during her first year of life, and in whom bilateral intracranial calcifications (frontal lobes, basal ganglia, cerebellar dentate nuclei) were discovered by brain MRI at the age of 17 years. CONCLUSION: The etiology of this finding remains unclear. Some causes of such deposits can be of a reversible nature, thus prompting early recognition although their consequences on clinical outcome remain mostly unknown.

[Premature kidneys and oligonephronia: long term repercussion]. / Immaturité rénale et oligonéphronie du prématuré: conséquences à long terme.

The premature has a reduced number of nephrons. This condition, added to an immature renal function at birth, increases the vulnerability to hemodynamic changes, drug toxicity, and nephrocalcinosis. The oligonephronia worsens the risk to present in adulthood, hypertension and renal insufficiency. Nephrocalcinosis appears in the postnatal period, secondary to renal calcifications. This condition increases the risk of further renal endowment. The nephrocalcinosis is closely related to rickets in the premature. Indeed, an excess of vitamin D and calcium, increases the risk of nephrocalcinosis. The early recognition of markers, such as microalbuminuria, hypertension and hypercalciuria, allow targeting prevention measures.

Combined serum creatinine and cystatin C Schwartz formula predicts kidney function better than the combined CKD-EPI formula in children.

BACKGROUND: The combined serum creatinine (SCreat) and cystatin C (CysC) CKD-EPI formula constitutes a new advance for glomerular filtration rate (GFR) estimation in adults. Using inulin clearances (iGFRs), the revised SCreat and the combined Schwartz formulas, this study aims to evaluate the applicability of the combined CKD-EPI formula in children. METHOD: 201 iGFRs for 201 children were analyzed and divided by chronic kidney disease (CKD) stages (iGFRs ≥90 ml/min/1.73 m(2), 90 > iGFRs > 60, and iGFRs ≤59), and by age groups (<10, 10-15, and >15 years). Medians with 95% confidence intervals of bias, precision, and accuracies within 30% of the iGFRs, for all three formulas, were compared using the Wilcoxon signed-rank test. RESULTS: For the entire cohort and for all CKD and age groups, medians of bias for the CKD-EPI formula were significantly higher (p < 0.001) and precision was significantly lower than the solely SCreat and the combined SCreat and CysC Schwartz formulas. We also found that using the CKD-EPI formula, bias decreased and accuracy increased while the child age group increased, with a better formula performance above 15 years of age. However, the CKD-EPI formula accuracy is 58% compared to 93 and 92% for the SCreat and combined Schwartz formulas in this adolescent group. CONCLUSIONS: The performance of the combined CKD-EPI formula improves in adolescence compared with younger ages. Nevertheless, the CKD-EPI formula performs more poorly than the SCreat and the combined Schwartz formula in pediatric population.

Glomerular and tubular function following orthotopic liver transplantation in children treated with tacrolimus.

The aim of this study was to analyze the impact of TAC on medium term (three-yr follow-up) renal function in pediatric liver transplant (OLT) recipients. Glomerular and tubular indices were retrospectively analyzed in 24 consecutive OLT pediatric recipients on TAC. CrCl increased significantly each month post-OLT (p = 0.003), with a trend toward significance between pre-OLT and 36 months (p = 0.17). There was no correlation between CrCl and TAC troughs (p = 0.783). Sixteen percent of patients had CrCl <60 mL/min/1.73 m(2) pre-OLT vs. none at 36 months post-OLT. TRP values were normal throughout the study. UPr/Cr decreased insignificantly over time and correlated significantly with TAC trough levels (p = 0.031). UCa/Cr values normalized by the third-month post-OLT, decreasing significantly over the time (p = 0.000) but did not correlate with TAC troughs. At three months post-OLT, 65.2% of patients needed antihypertensive therapy, and no patients needed more than one antihypertensive treatment after one yr. Despite nephrotoxic side effects in the early postoperative phase, this study shows that 65.5% patients had a normal renal function by three yr post-OLT. Tubular indices correlated with TAC trough levels.

Do NK cells contribute to the pathophysiology of transplant-associated thrombotic microangiopathy?

Transplant-associated thrombotic microangiopathy (TA-TMA) is a life-threatening complication caused by the aggregation of platelets exposed to the thrombogenic subendothelial matrix of injured endothelial cells. Here, we present a case of a patient transplanted for idiopathic aplastic anemia with a T-cell depleted hematopoietic stem cell graft from an HLA-C mismatched unrelated donor. At day 7 posttransplant, she suffered from acute renal failure with hematuria. The presence of numerous schistocytes, an increased level of lactate dehydrogenase and a renal biopsy with multiple vascular injuries confirmed the diagnosis of severe TA-TMA. At day 14, she developed graft versus host disease and died 7 months posttransplantation of multiorgan failure. At day 15, we observed a sizable population of natural killer (NK) cells in the peripheral blood, the number of which reached 0.8 G/L at 4 months posttransplant. Most NK cells lacked inhibitory killer immunoglobulin-like receptors (KIR) specific for the KIR-ligands expressed in the patient. NK cells were also abundantly present in pericardial and pleural fluids and had invaded the kidney, where they colocalized with the renal vasculopathy. Because there are several mechanisms through which NK cells and platelets can activate each other reciprocally, it is conceivable that NK cells contribute to TA-TMA and its progression.

Longitudinal analyses of renal lesions due to acute pyelonephritis in children and their impact on renal growth.

PURPOSE: Acute pyelonephritis is a common condition in children, and can lead to renal scarring. The aim of this study was to analyze the progression of renal scarring with time and its impact on renal growth. MATERIALS AND METHODS: A total of 50 children who had renal scarring on dimercapto-succinic acid scan 6 months after acute pyelonephritis underwent a repeat scan 3 years later. Lesion changes were evaluated by 3 blinded observers, and were classified as no change, partial resolution or complete disappearance. Renal size at time of acute pyelonephritis and after 3 years was obtained by ultrasound, and renal growth was assessed comparing z-score for age between the 2 measures. Robust linear regression was used to identify determinants of renal growth. RESULTS: At 6 months after acute pyelonephritis 88 scars were observed in 100 renal units. No change was observed in 27%, partial resolution in 63% and complete disappearance in 9% of lesions. Overall, 72% of lesions improved. Increased number of scars was associated with high grade vesicoureteral reflux (p = 0.02). Multivariate analysis showed that the number of scars was the most important parameter leading to decreased renal growth (CI -1.05 to -0.35, p <0.001), and with 3 or more scars this finding was highly significant on univariate analysis (-1.59, CI -2.10 to -1.09, p <0.0001). CONCLUSIONS: Even 6 months after acute pyelonephritis 72% of dimercapto-succinic acid defects improved, demonstrating that some of the lesions may be not definitive. The number of scars was significantly associated with loss of renal growth at 3 years.

Postnatal management of isolated mild pelvic dilatation detected in antenatal period.

AIM: Mild antenatal renal pelvic dilatation (ARPD) revealed by prenatal ultrasound (US) raises the question whether or not screening for vesicoureteral reflux (VUR) is mandatory. The aim of our study was to suggest guidelines for postnatal management of infants with mild ARPD defined as an antero-posterior (AP) dilatation >5 and <10 mm. METHOD: Therefore we assessed the value of postnatal US at day 30 to predict VUR, the incidence of VUR at day 30 and the rate of spontaneous resolution at 1 year. Two hundred (200) infants with ARPD were included and had renal US and voiding cystourethrography (VCUG) at day 30. If VUR was present, VCUG was repeated 1 year later. RESULTS: Incidence of VUR was 10% (20/200) at day 30 after birth and only 3% (6/200) 1 year later. VUR at day 30 was twice as frequent in children with postnatal dilatation (11%) than in nondilated kidneys (6%). CONCLUSIONS: Considering the low incidence of VUR at 1 year, screening for VUR in mild ARDP seems not to be justified. However follow-up by US to detect increase in dilatation and clinical monitoring for signs of urinary infection is required.

[Enuresis and voiding disorders in childhood]. / Enurésies et troubles mictionnels diurnes chez l'enfant.

Nocturnal enuresis is a common problem seen by the primary care physician. It is mandatory to distinguish between children having monosymptomatic nocturnal enuresis with normal daytime voiding habits and patients having polysymptomatic bed wetting (associated with urgency, frequency, or other signs of unstable bladder). Investigations and treatment of polysymptomatic enuresis are different than treatment of monosymptomatic nocturnal enuresis. A thorough and thoughtful history of voiding pattern is important to separate urge syndrome from organic causes of enuresis. Management of patients who have urge syndrome include general advices like regular voiding routine, physiotherapy, anticholinergic medication and prevention or treatment of urinary tract infections. If the nocturnal enuresis persists after the control of the voiding dysfunctions, treatment of nocturnal enuresis must be undertaken.

[Hematuria and proteinuria in childhood]. / Hématurie et protéinurie chez l'enfant: attitude pratique.

Hematuria and proteinuria are often the first signs of potentially severe kidney diseases. Investigations of a child with proteinuria +/- hematuria should start at the primary care physician office, and will permit to rapidly identify the most serious kidney diseases, such as the glomerulonephritis, but also to avoid excessive and costly investigations in patients with a benign condition such as orthostatic proteinuria. Isolated microscopic hematuria is also relatively frequently found during routine pediatric office visit. Secondary to a glomerulonephritis, it is often associated with proteinuria. Urologic causes should be excluded in case of isolated microscopic or macroscopic hematuria.

[Antenatally detected hydronephrosis: practical approach for the pediatrician]. / Dilatation pyélocalicielle chez le nouveau-né: attitude pratique pour le pédiatre.

Approximately 1% of the fetuses present some dilatation of their urinary tract in utero. More than 50% of these antenatally detected hydronephrosis will disappear spontaneously after birth. The other 50% comprises ureteropelvic junction obstruction, vesico-ureteral reflux and primary megaureters. Postnatal radiological evaluation (renal ultrasonography and VCUG) is performed in every infant with a significantly dilated renal pelvis (> 8 mm between 20 and 30 weeks or > 10 mm after 30 weeks in utero). Renal nuclear scan should be done in every child with significant/worsening post-natal hydronephrosis. Antibioprophylaxis will be started from birth to prevent urinary tract infection. Medical or surgical approach will be chosen in the light of the uroradiological exam results and the clinical progress.

Studies of urinary cystine precipitation in vitro: ontogeny of cystine nephrolithiasis and identification of meso-2,3-dimercaptosuccinic acid as a potential therapy for cystinuria.

Children with fully recessive (Type I/I) cystinuria have a high risk of stone formation in the first decade of life. To assess the tendency for cystine to precipitate in individual urine samples, we developed an in vitro assay in which radiolabelled cystine (4mM) was dissolved in urine at 37 degrees C after alkalization to pH 10. Samples were then brought to pH 5, cooled, and centrifuged. The % decrease in supernatant cpm was used as a measure of cystine precipitation (CP). CP varied widely among normal children (74%+/-34) whereas variability of repeated determinations on a single adult individual was modest (64%+/-3.3). The assay was used to compare various potential therapies for cystinuria. Precipitation of exogenous cystine from normal urine was strongly inhibited by addition of D-penicillamine (CP: 8%+/-3) or dimercaptosuccinic acid (DMSA) (CP: 5%+/-1), at urinary concentrations attained by standard oral doses of each drug. Mercaptopropionylglycine (MPG) was moderately effective (CP: 43%+/-9), whereas captopril was a weak inhibitor (CP: 63%+/-12). Precipitation of endogenous cystine (2191 micromol/L) from a cystinuric patient showed that DMSA and D-penicillamine were again highly effective compared to the other agents. In addition DMSA and penicillamine added to the same patient's urine reduced the free cystine by 50% (as measured by automated amino acid analyzer) whereas MPG and captopril had no effect. In conclusion, DMSA is comparable to D-penicillamine as an in vitro inhibitor.

[Surgery for root arthrosis: retrospective study and search for an algorithm]. / Chirurgie de la rhizarthrose: étude rétrospective et recherche d'un algorithme.

Several treatments, conservative or surgical, have been proposed for painful arthritis of the base of the thumb with various outcomes. Swanson trapezium implant, arthrodesis of the trapezio-metacarpal (T.M.) joint and suspension arthroplasty are three of the most used techniques for treatment of this condition. Two hundred patients operated on using one of the three techniques were reviewed for a retrospective study to assess the advantages and disadvantages of each method of treatment and their indications. Patient satisfaction rate is high whatever the technique used. Complete pain relief was obtained more often with the Swanson implant (Alnot 0) but differences between the three methods decrease when patients with pain only for particular strains (Alnot 1) are included. Swanson implants (patient satisfaction Alnot 0 and 1: 85.5%) provide excellent subjective and objective results for patients with light activity of daily living causing little stress to the implant. Complication rate with reoperation is equal to other techniques. Surgical treatment is well come through and recovery is fast and not painful. Suspensioplasty (patient satisfaction Alnot 0 and 1: 78.2%) have a low complication and reoperation rate when the technique is well applied. Patient satisfaction rate is high but duration of recovery is long (strength, nimbleness). T.M. arthrodesis is the only type of surgery providing a good strength identical to the opposite side at the price of a limited decrease of range of motion. In conclusion, we propose the following algorithm: for patients over years of age: Swanson trapezium implant; for young and active patients presenting a radiological stage less than Dell III and an intact Scaphotrapezial joint: T.M. arthrodesis; for other patients: suspensioplasty using the A.P.L.

Reversible encephalopathy associated with tacrolimus in pediatric renal transplants.

Neurological complications post transplant have been described with the use of calcineurin inhibitors. Although tacrolimus may be a better immunosuppressant than cyclosporine, its neurological side effects may be worse. Two children, living-related kidney transplant recipients, were treated with antibody induction, mycophenolate mofetil, prednisone, and tacrolimus. Soon after transplant, they each developed an encephalopathy, which when visualized by magnetic resonance imaging showed that it affected both white and grey matter of the brain. Although the encephalopathy was associated with the use of tacrolimus, there was a complete neurological recovery without cessation of the drug.

Rapid loss of renal parenchyma after acute obstruction.

Urinary tract obstruction (UTO) is a frequent cause of renal failure in the pediatric population. We report a patient with type I/I cystinuria, followed prospectively from birth with yearly ultrasonography, who developed acute UTO due to a cystine stone at 10 years of age. In animal models of UTO, acute obstruction produces rapid loss of renal parenchyma secondary to apoptosis of tubular cells. Since we had prospectively obtained serial ultrasonographic measurements of renal growth, we were able to document sudden decrease in kidney size and function following UTO, suggesting that programmed cell death may similarly have caused the rapid irreversible loss of renal parenchyma in our patient. Despite surgical relief of the obstruction, kidney size decreased for at least 3-4 months. We speculate that anti-apoptotic drugs might be considered as a therapeutic strategy to protect ongoing renal parenchyma loss in UTO.