Acute tubulointerstitial nephritis in children and chronic kidney disease.

BACKGROUND: Acute tubulointerstitial nephritis (ATIN) is a rare condition in children. The etiology, treatment, and outcome of childhood ATIN remain poorly understood. The long-term prognosis seems to be favorable; however, chronic kidney disease has been reported. This article describes clinical outcomes in a series of children with biopsy-proven ATIN. METHODS: All medical records with biopsy-proven ATIN between January 2006 and 2016 were retrospectively analyzed. The incidence, clinical features, etiology, treatment, and outcome were recorded for each patient. RESULTS: Over 10 years, ATIN was diagnosed in 25 cases (8%) based on 306 renal needle biopsies. The most frequent clinical signs were abdominal pain, asthenia/weight loss, and fever. A median glomerular filtration rate estimated at 30.1mL/min/1.73 m2 (16.5; 45.5). Drug-induced toxicity was the main etiology (eight patients). Other causes were TINU syndrome (tubulointerstitial nephritis and uveitis) (seven patients), infection (two patients), and toxic agents other than medication (one patient). No etiology was found in seven patients (idiopathic cases). Eighteen patients (72%) were treated with steroids. At the end of follow-up, eight patients presented chronic kidney disease, three hypertension, and three tubular dysfunction. Overall, renal function was highest in the idiopathic ATIN group and in children treated without delay. CONCLUSIONS: In a single-center 10-year series of biopsy-confirmed ATIN in children, drugs and TINU syndrome were the main etiologies of ATIN. This study suggests that children with idiopathic ATIN and prompt treatment have a better prognosis. In this series, occurrence of chronic kidney disease justified long-term follow-up.

Rapid differential diagnosis of diabetes insipidus in a 7-month-old infant: The copeptin approach.

INTRODUCTION: Diabetes insipidus is characterized by hypoosmotic polyuria related to deficiency of arginine-vasopressin (AVP) secretion (central diabetes insipidus, CDI) or renal insensitivity to AVP (nephrogenic diabetes insipidus, NDI). The water deprivation test with assessment of AVP activity is currently the gold standard for differential diagnosis in patients presenting polyuria-polydipsia syndrome. Nevertheless, it can be dangerous without proper surveillance and its interpretation may be challenging. Other markers have been suggested. Direct quantification of circulating AVP is not sufficient for diagnosis: vasopressin is unstable, analysis is complex. AVP comes from prohormone preprovasopressin with concomitant release of copeptin (C-terminal moiety) in the equimolar ratio. Copeptin is stable in vitro, with easy and rapid measurement (<4h). Past studies have shown greater sensitivity and specificity of copeptin versus AVP to discriminate etiologies of polyuria in adults, but its value has not been demonstrated in infants yet. OBSERVATION: A 7-month-old infant presented polyuria-polydipsia syndrome with poor weight gain. Laboratory tests pointed out hypernatremia (170mmol/L) and blood hyperosmolarity (330mOsm/L) with inappropriate urinary hypoosmolarity (168mOsm/L). Plasmatic copeptin measurement was found at a very high level, 303pmol/L (1-14pmol/L). DdAVP administration did not improve the polyuria, confirming the final diagnosis of NDI. Hyperhydration with a hypoosmolar diet normalized the hydration status and circulating levels of copeptin within 1 week. CONCLUSION: Copeptin, a stable peptide reflecting AVP secretion, could be a safer and faster biomarker for etiological diagnosis of polyuria-polydipsia syndrome in children. Before regularization of hydration status, a single baseline measurement may be enough to discriminate NDI from other etiologies without the water deprivation test.

Anakinra is safe and effective in controlling hyperimmunoglobulinaemia D syndrome-associated febrile crisis.

Hyper-IgD and periodic fever syndrome (HIDS) is a hereditary autoinflammatory syndrome, characterized by recurrent inflammatory attacks. Treatment of HIDS is difficult. Recently, the IL-1ra analogue anakinra was reported to be successful in aborting the IgD inflammatory attacks in a vaccination model. We report a clinical case of spectacular reduction of febrile attacks in a severe HIDS patient.

C-peptide replacement improves weight gain and renal function in diabetic rats.

AIM: Recent experimental and clinical data suggest that C-peptide replacement during type 1 diabetes exerts beneficial effects on diabetic nephropathy. The aim of this study was to determine if physiological C-peptide administration in replacement dose during 28 days had beneficial effects on metabolic status and renal functions in type-1 diabetic rats. METHODS: Four groups of rats were investigated: a non diabetic group treated with buffer (C group, n=6), three streptozotocin diabetic-induced groups treated with either buffer (D group, n=6), insulin (D-I group, n=6) or rat homologous C-peptide (D-C group, n=6). Weight gain was measured every week. All animals were housed in metabolic cages on day 28 for assessment of metabolic data. Blood and urine samples were collected to allow measurement of plasmatic osmolality, C-peptide concentration, sodium, and glucose losses and proteinuria. Glomerular filtration rate (GFR) was determined by creatinine clearance. RESULTS: All streptozotocin-treated animals were diabetic. Glycaemic control (mg/dl), was markedly improved in D-I (133+/-65) when compared with either D (547+/-49, P<0.05) or D-C (520+/-48, P<0.05) groups. Conversely, weight gain during the study, was improved in D-I and D-C as compared with D animals (135+/-13 and 41+/-18 vs 18+/-21 respectively), despite different glycaemic control. Diabetes-induced glomerular hyperfiltration (ml/min/kg), urinary protein leakage (g/kg/day), and Na urinary losses (mmol/100 g/day) respectively, were significantly (P<0.05) reduced in D-C (3.95+/-0.6; 0.08+/-0.06; 1.5+/-0.9) in comparison with D (4.95+/-0.8; 0.18+/-0.16; 3.7+/-2.1) and D-I (5+/-0.9; 0.19+/-0.11; 2.7+/-0.8) animals. Plasmatic osmolality was significantly increased in D group whereas there were no differences between C group and D-C group. Food and water intakes, urinary volume as well as urinary glucose losses were not significantly different between D-C and D groups. CONCLUSIONS: C-peptide administration in replacement dose to streptozotocin diabetic rats induces weight gain regardless hyperglycaemia or glycosuria. Diabetic animals supplemented with C-peptide exhibit better renal function resulting in reduced urinary sodium waste and protein excretion together with reduction of the diabetes-induced glomerular hyperfiltration.

'Urinacoccus massiliensis' gen. nov. sp. nov., identified in urine sample of a 7-year-old boy hospitalized for dental care under general anaesthesia.

We report here the main characteristics of 'Urinacoccus massiliensis' gen. nov. sp. nov., strain FC2 (CSURP1992). This strain was isolated from the urine of an asymptomatic 7-year-old boy.

Anaerococcus urinomassiliensis sp. nov., isolated from a urine sample of a 17-year-old boy affected by autoimmune hepatitis and membranoproliferative glomerulonephritis.

We report the main characteristics of 'Anaerococcus urinomassiliensis' strain FC4(T) (CSURP2143) that was isolated from a urine sample of a 17-year-old boy affected by autoimmune hepatitis and membranoproliferative glomerulonephritis.

Actinomyces urinae sp. nov., isolated from 13-year-old girl affected by nephritic syndrome.

Here, we report the main characteristics of Actinomyces urinae strain Marseille-P2225(T) (CSURP2225) isolated from a human urine sample.

[Physiological effects of the connecting peptide]. / Les effets physiologiques du peptide connecteur.

Insulin-dependent diabetic (IDDM) patients present significantly altered Na,K-ATPase activity in several organs, including kidney. Particularly in kidney tubule, Na,K-ATPase alteration occurs together with changes in glomerular filtration rate, the first step of IDDM-induced renal failure. The latter is a major cause of morbidity and mortality in IDDM patients. The C-peptide of proinsulin is important for the biosynthesis of insulin but has for a long time been considered to be biologically inert. Recent studies have demonstrated that replacement of C-peptide to normal physiological concentrations in IDDM patients either on a short-term basis (1-3 hours) or on a prolonged administration (1-3 months) was accompanied by improvements in renal glomerular and tubular function. Animal studies have shown that most of the renal tubular effects of C-peptide may in part be explained by its ability to stimulate Na,K-ATPase activity. In conclusion, these combined findings indicate that C-peptide is a biologically active hormone. The possibility that C-peptide therapy in IDDM patients may be beneficial should be considered. The present review focuses on: 1) Making a point about C-peptide-induced tubular effects on the basis of clinical and experimental experiments, and 2) precising the molecular mechanisms involved in C-peptide-induced tubular Na,K-ATPase effects.

Kidney function in cyclosporine-treated paediatric pulmonary transplant recipients.

BACKGROUND: Lung or heart-lung transplantation is a useful therapy in life-threatening pulmonary disorders during childhood. Cyclosporine A is a major immunosuppressive treatment but has a number of adverse effects including nephrotoxicity. There have been no reports on the long-term evolution of renal function in a large series of paediatric pulmonary transplantation recipients. METHODS: We examined 19 patients followed up for at least 3 years after pulmonary transplantation. The mean time of follow-up was 5.36 years. Kidney function was evaluated by calculation of glomerular filtration rate (GFR) according the Schwartz formula. RESULTS: The GFR was normal before transplantation in all patients. The short-term evolution of GFR was marked by a significant drop during the first and until the 6th month. Then, regardless of the level reached at the end of the 6th month, the GFR remained stable in all patients except one until the end of follow-up. At the end of follow-up, 31% had normal GFR, 57% had mild chronic renal failure, and 5% had advanced renal failure. Hypertension was frequent and associated with renal failure. CONCLUSIONS: Paediatric pulmonary recipients showed evidence of long-term cyclosporine A-associated nephrotoxicity. Most of this toxicity occurred during the first 6 months.

The effects ex vivo and in vitro of insulin and C-peptide on Na/K adenosine triphosphatase activity in red blood cell membranes of type 1 diabetic patients.

The decrease in Na/K adenosine triphosphatase (ATPase) activity observed in several tissues of type 1 diabetic patients is thought to play a role in the development of long-term complications. Infusion of insulin may restore this enzyme activity in red blood cells (RBCs), and recent arguments have been developed for a similar role of C-peptide. The aims of this study were to determine whether insulin acts directly on the RBC enzyme and to evaluate the effect of C-peptide on Na/K ATPase activity. Thirty-nine C-peptide-negative type 1 diabetic patients were studied (blood glucose, 11.2 +/- 1.49 mmol/L; hemoglobin A1c [HbA1c], 8.9% +/- 0.1%, mean +/- SEM). Blood samples were obtained in the morning, before breakfast and insulin injection. Intact and living RBCs were resuspended in their own plasma and incubated with or without insulin (50 microU/mL) or C-peptide (6 nmol/L). Ex vivo by microcalorimetry, the heat produced after 1 hour by the enzyme-induced hydrolysis of adenosine triphosphate (ATP), was measured in a thermostated microcalorimeter at 37 degrees C. The results showed that Na/K ATPase activity was significantly increased by insulin (12.4 +/- 0.5 v 15.4 +/- 0.9 mW/L RBCs, P < .05, n = 23) but not by C-peptide (11.9 +/- 0.7 v 12.9 +/- 0.9 mW/L RBCs, NS, P = .26, n = 12). In another experiment, RBC suspensions were incubated at 37 degrees C in a water bath with or without insulin (50 microU/mL) or C-peptide (6 nmol/L) for 10 minutes. RBC membranes were isolated and Na/K ATPase activity was assessed by measuring inorganic phosphate release at saturating concentrations of all substrates. The results showed that insulin and C-peptide significantly increased RBC Na/K ATPase activity (342 +/- 25, P < .005 and 363 +/- 30, P < .005, respectively v255 +/- 22 nmol Pi x mg protein(-1) x h(-1), n = 14). We conclude that insulin and C-peptide act directly on RBC Na/K ATPase, thus restoring this activity in type 1 diabetic patients. The stimulatory effect of C-peptide observed in vitro on RBC Na/K ATPase activity confirms that C-peptide plays a physiological role.

[Pigmentosum retinis and tubulo-interstitial nephronophtisis in Sensenbrenner syndrome: a case report]. / Rétinopathie pigmentaire et néphropathie tubulo-interstitielle lors du syndrome de Sensenbrenner.

PURPOSE: Sensenbrenner syndrome or cranio-ectodermal dysplasia is an extremely rare autosomal recessive condition (12 cases reported in literature). Our observation shows the possibility of both ocular and renal involvement associated with cranio-ectodermal abnormalities. PATIENTS: and method:We report the case of a girl who presented a typical cranio-ectodermal syndrome with dolicocephaly, short thorax, short limbs, short fingers and teeth abnormalities. At five years, she was found to have pigmentosum retinitis with amblyopy and moderate hyperopia. A chronic renal failure with uncontrollable hypertension underwent a cadaveric-donor transplantation at the age of six years. RESULTS: Two years later, the pigmentosum retinitis was stable. The kidney histology revealed a tubulo-interstitial nephronophtisis. The molecular analysis of the NPH 1 locus, which was associated with nephronophtisis, was negative. DISCUSSION: Our observation and two recent publications have in common ocular and renal abnormalities associated with cranio-ectodermal dysplasia. The underlying genetic defect would involve not only morphogenesis but also development and maturation of organs as eye and kidney. Sensenbrenner syndrome would thus be similar to certain disorders affecting the eye, kidney, skeleton and ectodermal structures such as the EEM, Senior-Loken, Mainzer-Saldino, and Jeune syndromes. CONCLUSION: The retinal dystrophy falls within the spectrum of clinical and genetic forms of pigmentosum retinitis. Our observation would confirm possible links between Sensenbrenner syndrome and oculorenal syndromes.

[Postoperative hyponatremia in children: pathophysiology, diagnosis and treatment]. / Les hyponatrémies postopératoires de l'enfant: physiopathologie, diagnostic en traitement.

OBJECTIVES: To review the current data on pathophysiology, causes and management of postoperative hyponatremia in children. DATA SOURCES AND EXTRACTION: The Pubmed database was searched for articles, combined with references analysis of major articles on the field. DATA SYNTHESIS: The incidence of postoperative hyponatremia has been evaluated at 0.34% and its mortality significant. Postoperative hyponatremia is triggered by the diminished renal ability to excrete free water, due to antidiuretic hormone release. Inappropriate secretion of antidiuretic hormone is frequently seen after spine, cardiac and neurosurgery but can occur even after minor surgery. In this context, the infusion of hypotonic fluids represents a strong risk factor for developing hyponatremia. Other causes of hyponatremia are represented by extrarenal fluid losses, cerebral salt wasting syndrome, desalination phenomenon, adrenal insufficiency or some medications. Preventive treatment is essential and based on prohibition of hypotonic fluids infusion and the use of isotonic fluids infusions, maintenance of a normal total blood volume, the observance of the good practice recommendations for fluid infusion in children, and frequent blood and urine sodium concentration determinations in patients at risk for developing hyponatremia. Hyponatremic encephalopathy requires an emergent management, consisting in respiratory care and hypertonic sodium chloride infusion. Chronic hyponatremia is most often asymptomatic and the main neurological risk factor is represented by a too rapid correction of plasma sodium, which may lead to centropontine myelinolysis.

Increased systemic blood pressure and arterial stiffness in young adults born prematurely.

Recent studies have shown that a low birth weight is a risk factor for increased systemic blood pressure (BP) in adulthood. Further, systemic BP and arterial stiffness (AS) are reported to be increased in adolescents born prematurely. The purpose of this study was to characterize systemic BP and AS in young adults born preterm. Systemic BP was measured using an automated oscillometric device. AS was assessed by measuring the right carotid-radial pulse wave velocity (PWV) using a validated non-invasive automated method. Systemic BP, pulse pressure, and PWV [mean (confidence intervals)] were compared between 16 adults (age 21 years) born preterm (age at birth 32 weeks of gestation) with a birth weight (1710 g) appropriate for their gestational age and 15 adults (21 years) born at term (40 weeks of gestation) with a birth weight (3430 g) appropriate for their gestational age. Adults born preterm had a significantly higher systolic BP [122 mmHg (114-144) v. 112 (106-127)], mean BP [89 mmHg (86-98) v. 84 (81-91)], diastolic BP [69 mmHg (66-76) v. 65 (62-78)], pulse pressure [54 mmHg (47-72) v. 47 (42-60)], and PWV [7 m/s (6.3-8.6) v. 6.4 (5.8-8)] than did those born at term. Our findings suggest that young adults with a low birth weight due to preterm birth have increased systemic BP and AS. Accordingly, preterm birth may predispose individuals to cardiovascular diseases in adulthood due to increased AS.

[Amanita proxima poisoning in a child]. / Un cas pédiatrique d'intoxication par Amanita proxima.

Mushroom intoxication due to Amanita proxima poisoning is characterized by moderate gastrointestinal symptoms, followed by severe acute renal failure and sometimes by hepatic cytolysis. This syndrome was described in the 1990s in the southeast of France; we report here the first pediatric case, requiring dialysis but achieving complete recovery. The mother of this 11-year-old boy, who had eaten the same mushrooms but in smaller quantities, had only biological renal and hepatic involvement.