Nephrotic Child Research Articles

Controversy between biopsy and risk in children with proteinuria: is there a paradigm war?

BackgroundProteinuria is a prevalent symptom of pediatric nephrology, while kidney biopsy remains the gold standard for kidney tissue analysis, and it is currently controversial. We report the rare case that the mutation in the AMN gene was considered to cause chronically isolated proteinuria and also suggest that renal biopsy should be chosen with caution in children with chronic isolated non-nephrotic levels of proteinuria and that genetic testing may be feasible for the early precise diagnosis.Case presentationA 35-month-old boy presented with excessive urine foaming for more than half a month; his proteinuria was considered non-nephrotic range and urine protein electrophoresis was suggestive of mixed proteinuria; other than that, the investigations are non-specific. Given the child’s chronic isolated proteinuria and good renal function, we chose to refine the genetic test rather than a renal biopsy; a compound heterozygous variant was found in the AMN gene of this child which was caused by a point mutation in the father, and a partial chromosomal deletion in the mother.ConclusionsCubilin(encoded by CUBN), amnionless(encoded by AMN), and megalin form a multiligand receptor complex; CUBN or AMN gene variants have been implicated as a hereditary cause of megaloblastic anemia, proteinuria, and neurological impairment. In the past few decades, chronic isolated proteinuria caused by CUBN gene variants is benign, non-progressive, and has normal renal function. However, the child is the first reported case of isolated proteinuria of AMN gene mutation, indicating that the earlier diagnostic genetic sequencing in an otherwise well, not nephrotic proteinuria child may be a convenient, cost-effective, and harmless option, challenging the traditional paradigm.

Non-invasive assessment of volume status of children with edema due to steroid sensitive nephrotic syndrome using urinary indices and inferior venacava ultrasonography

Background: It is clinically difficult to assess the intravascular volume status of children with edema in nephrotic syndrome. This makes decision-making challenging, regarding the use of diuretics or albumin infusion in the management of edema. Ideally, hormonal assay and central venous pressure monitoring are accurate but difficult to do as these methods are invasive and expensive to be applied to every child presenting with edema of nephrotic syndrome. Hence, the need for reliable non-invasive investigations to assess the volume status of children with edema. Aims and Objectives: The aim of the study was to assess the volume status of children with edema due to steroid sensitive nephrotic syndrome using noninvasive methods such as urinary indices (Fractional excretion of sodium (FeNa) and urine Potasium index (K index)) and inferior venacava diameter (IVCD) by ultrasonography and to determine the association between them. Materials and Methods: In this analytical cross-sectional study, 82 subjects fitting the inclusion criteria were included in the study. FeNa, K index and IVCD were determined. The volume status was assessed and association between the three calculated (Fischer exact test). Results: Out of 82 children, 56.1%, 68.3%, and 63.5% based on FeNa, K index, and IVCD respectively were having hypervolemic volume status. There is a statistically significant association between FeNa and K index and between urinary indices and IVCD. Conclusion: The present study supports the overfill hypothesis of edema formation. IVCD like urinary indices is a non-invasive and reliable investigation to determine volume status in nephrotic child with edema.

Intussusception causing bowel obstruction in a nephrotic syndrome child

Abstract Intussusception is defined as an acquired telescoping of proximal bowel into the distal bowel. It is a common cause of bowel obstruction in infancy. Majority are reported between 3 and 9 months, 90% are affected within the first 3 years of life with idiopathic cause. A high index of suspicion must be maintained for bowel obstruction in typical infant age with no demonstrable hernias or previous surgery. Abdominal ultrasound is the gold standard for the diagnosis. We present a rare case in our practice of intussusception in a 4 years old male with nephrotic syndrome at our pediatric surgery department.

Urinary tract infection in nephrotic syndrome in pediatric age group: a hospital based cross-sectional study

Background: Nephrotic syndrome, characterized by the presence of heavy proteinuria, hypoalbuminemia, edema and hyperlipidemia, is a common renal disorder in pediatric population. Aim of this study were to find out the prevalence of Urinary Tract Infection (UTI) in nephrotic syndrome, bacterial etiologies and antibiotic sensitivity pattern.Methods: After matching the criteria, 82 cases, were taken for this prospective, single center, observational study. The diagnosis was confirmed by bacterial culture. This is an institution based cross-sectional descriptive observational study. All newly diagnosed and relapse cases of nephrotic syndrome based on inclusion exclusion criteria was included in this study. Respondent was either of the parents or caregiver of the study subjects. Analysis of all data was done by appropriate statistical software (SPSS-23).Results: Among 82 participants evaluated with nephrotic syndrome 29.3% participants had UTI, majority 66.7% were asymptomatic and 33.3% were symptomatic. Significant microscopic hematuria were found in 20.7% study subjects and significant pyuria were found in 58.54% study subjects. Majority of UTI caused by E.coli 33.3% followed by Klebsiella 25%, Proteus 16.7%, Staphylococcus aureus 12.5%, Citrobacter, Acinetobacter and mixed growth were found in 4.2% each. Mean serum cholesterol of group with UTI was 422.13±34.65 and group without UTI was 307.43±26.13. The variation amongst the two groups were found to be significant (p=0.0001).Conclusions: The children with nephrotic syndrome are frequently predisposed to UTI and in most cases it is asymptomatic, often undiagnosed. Higher serum cholesterol level may predispose the nephrotic child for UTI.

Mother’s Care for Children with Nephritic Syndrome at Home

Background: The mother engages to develop a comprehensive care plan specific to the needs of the child with nephrotic syndrome. The mother seeks to understand the child with respect to health status, abilities, and priorities. Aim: This study aim was to a assess mother’s care for children with nephrotic syndrome at home. Design: Descriptive research design was utilized in this study. Setting: The urologic pediatric outpatient clinic in Pediatric Ain Shams university hospital. Sample: a purposive sample of school age children equal 100 children. Tool: interviewing questionnaire consisted of children and caregivers socio-demographic characteristic, child's past and present medical history, caregivers’ knowledge and practice about nephrotic syndrome. Results: more than one third of the mothers of children with nephrotic syndrome have unsatisfactory knowledge level and the vast majority of them not done correctly care to their children. Also, there were statistically significant differences between mothers’ knowledge and demographic characteristics of the mothers except occupation and their residence. Conclusion: the mothers of nephrotic child had poor caring for their children with no statistically significant differences between mothers’ care and demographic characteristics of the mothers except number of children in the family and their residence; also there was strong positive correlation between mothers' knowledge and their practice. Recommendation: conducting educational classes for the mothers and their children about nephrotic syndrome especially newly diagnosed patients at urology pediatric outpatient clinic.

Relationship between HbA1c and Steroid in Initial Attack of Idiopathic Nephrotic Syndrome in Children

Background: Blood sugar may be raised as a systemic effect of steroid. Haemoglobin A1c (HbA1c) estimation provides an accurate index of mean concentration of blood glucose during preceding two to three months.Objective: The purpose of the present study was to observe the relationship between oral prednisolone and HbA1c levels in children with 1st attack Nephrotic syndrome.Methods: This case-control study was conducted in the Outpatient department of Apollo Hospitals, Dhaka, Bangladesh from January 2012 to July 2013 for a period of nineteenth (19) months. The nephrotic children with first attack who completed 12 weeks steroid therapy were enrolled as study group. Age and sex matched thirty children with other illness without family history of diabetes regarded as control. HbA1c level was estimated in Nephrotic patient just at the end of their 12 weeks of prednisolone therapy.Results: The mean age of study and control group was 4.56±1.54 and 4.90±1.06 years respectively. Male and female ratios were 1.0:0.76 and 1.0:0.88 in case and control group respectively. Age and sex difference between the groups were not significant. The mean HbA1c value was 5.00±0.28 in case and 4.43±0.35 in control group (p<0.0001). The calculated mean blood sugar level was 99.75±9.80 mg/dl and 80.30±12.48 mg/dl in case and control group respectively (p<0.0001).Conclusion: Nephrotic child getting steroid have significantly higher level of HbA1c then their healthy counterpart though the level is not at diabetic level.Journal of National Institute of Neurosciences Bangladesh, 2017;3(1): 7-9

Urinary Tract Infection in Nephrotic Syndrome: A Hospital Based Cross-Sectional Study

Background: Urinary Tract Infection (UTI) is a common infection in nephrotic syndrome and have a propensity for long term renal damage. It may be an important cause of poor steroid response. The objective is to study the frequency and etiological organisms of urinary tract infection in idiopathic nephrotic syndrome children.Methods: This Comparative cross-sectional study was conducted in the Pediatric ward of Chittagong Medical College Hospital, Chittagong from 01.01.2009 to 31.12.2009. 52 nephrotic syndrome children diagnosed by serum albumin, serum cholesterol and 24 hours total urinary protein or protein creatinin index were included. After elaborate clinical evaluation, urine for R/M/E and C/S was done in all patients. Data regarding pyuria, hematuria, etiological organisms were analyzed by statistical method.Results: UTI was found in 30.8% nephrotic children and in majority cases (68.8%) they were asymptomatic. Male female ratio among UTI patients was 1:1. Mean serum cholesterol in nephrotic syndrome with UTI was higher than that of children without UTI (418.94 mg/dl vs 352.03 mg/dl, p value < 0.05).Pyuria had poor association with definite UTI (p value > 0.05). E-coli was the commonest organism isolated in urine culture followed by klebsiella.Conclusion: UTI is one of the most common infections in nephrotic syndrome and may be asymptomatic. It should be screened in every nephrotic child routinely.Chatt Maa Shi Hosp Med Coll J; Vol.15 (2); Jul 2016; Page 41-44

Kimura and #8217;s disease an unusual cause of lymphadenopathy in a nephrotic syndrome child

Kimura’s disease is a rare, benign, chronic inflammatory disorder of unknown etiology which is endemic in Orientals. The disease is characterized by a triad of painless subcutaneous nodule in the head and neck region, blood eosinophilia and elevated serum immunoglobulin E (IgE) levels. Kimura’s disease has various synonyms such as eosinophilic lymphogranuloma, inflammatory angiomatous nodule and atypical pyogenic granuloma. Renal pathology such as nephrotic syndrome has been found to be associated with Kimura’s disease which states a common etiopathogenesis between renal lesion and Kimura’s disease. We present an eleven years old Malay boy with recurrent nephrotic syndrome presented with left post auricular swelling. The diagnosis was based on the characteristic histopathology findings after surgical biopsy as Kimura’s disease.

The separation of unbound prednisolone in plasma by centrifugal ultrafiltration.

To study variable plasma protein binding of prednisolone in children with nephrotic syndrome we have devised a simple rapid method for measuring unbound prednisolone. The plasma was initially ultrafiltered at 37 degrees C fixed angle head at 1500 g for 30 min then the filtrate was analysed by high pressure liquid chromatography. The effects of variable ultrafiltration conditions were studied. The method was used to compare the AUC unbound prednisolone in a nephrotic child (plasma albumin concentration 18 g L-1) with a control (plasma albumin concentration 43 g L-1); their respective AUC unbound prednisolone values were 4.02 mg h L-1 and 1.07 mg h L-1.

Enfermagem e famílias de crianças com síndrome nefrótica: novos elementos e horizontes para o cuidado

A condição crônica tem sido um tema de relevância para a reflexão do processo de viver humano. O artigo apresenta a síntese de uma pesquisa cujo objetivo foi compreender o cuidado às crianças com Síndrome Nefrótica, identificando novos elementos contextuais e horizontes para reconstruir o cuidado de enfermagem, tendo como foco a família. Trata-se de um estudo qualitativo apoiado na hermenêutica, fundamentada em Gadamer e Ricouer, realizado em 2004, com famílias de crianças do Ambulatório de Nefrologia Pediátrica do Hospital Universitário Júlio Müller, em Cuiabá, totalizando 42 pessoas. Na discussão são apresentados: síntese das famílias, na qual elas são mostradas por meio das suas biografias, projetos, personagens e contexto; a trajetória da doença da criança na família e o cuidado da criança com Síndrome Nefrótica, no qual revelam-se os horizontes dos cuidadores, familiares e profissionais de saúde, e o cuidado possível a partir dos arranjos da família e limites da equipe. Conclui-se que o diálogo é a primeira condição para a compreensão e para o cuidado.

A nephrotic child with deep vein thrombosis after a long-haul flight

Sirs, The media has periodically highlighted traveller’s thrombosis, particularly where fatalities have arisen [1]. Several studies recognise the risk factors and incidence of deep vein thrombosis (DVT) after a long-haul flight in the adult population [2, 3]. No cases have been described affecting children. In the case we describe here, a child with the additional risk factors of factor V Leiden deficiency and nephrotic syndrome developed a DVT on return from a transatlantic flight. We report the case of a 13-year-old Caucasian girl diagnosed with biopsy-proven focal segmental glomerulosclerosis (FSGS), who responded to steroids and was in remission and steroid free for 2 years subsequently. Routine urine monitoring was not maintained thereafter and only instituted when clinically indicated. She flew across the Atlantic for a vacation and 2 weeks after her return presented with pain in her left groin. Clinical examination revealed a swollen left calf, which on Doppler ultrasound confirmed a DVT. Urinalysis showed 2+ protein (265 mg/mmol, nephrotic range). Blood biochemistry confirmed a low serum albumin of 19 g/l. There was no evidence of peripheral oedema, but the patient was clearly in relapse of her nephrotic syndrome secondary to FSGS. A history of DVT was noted in the maternal grandfather, secondary to immobilisation. A thrombophilia screen revealed factor V Leiden deficiency. Treatment, on confirmation of the DVT, was low molecular weight heparin, elastic stockings and steroids to treat the nephrotic syndrome, with remission achieved within 2 weeks. Following resolution of her clinical symptoms, she was converted to warfarin. Long-haul flights generate a risk for DVT because of the environment. Combining this with an unrecognised thrombosis risk as well as nephrotic syndrome can only have compounded and significantly increased this risk in our patient. Appreciating that factor V Leiden deficiency is seen in 3% of the population [4], it is perhaps not unreasonable to undertake a thrombophilia screen in all patients that present with nephrotic syndrome. This would aid in immediate management as well as in future relapses and allow for targeted advice. We would consider it good practice to advise all patients with a history of nephrotic syndrome to maintain monitoring of their urine for evidence of relapse prior, during and on return from a long-haul journey. This would also apply to those that have apparently been disease-free for a considerable time and are no longer routinely monitoring their urine. Additionally, the advice would also include the wearing of knee-high stockings, adequate mobility and hydration during a flight [5]. Patients would also be made vigilant of symptoms of a DVT on return. Our patient, now well and off warfarin, will in future inject low molecular weight heparin in the departure lounge before all future flights as well as maintain monitoring for proteinuria.

T-cell transcriptome analysis points up a thymic disorder in idiopathic nephrotic syndrome

Idiopathic nephrotic syndrome is a proteinuric disease secondary to the release of a nonidentified circulating glomerular permeability factor by T cells. Because specificities of T-cell activation in idiopathic nephrotic syndrome remain unknown, we evaluated transcriptional activation of T cells in nephrotic patients during proteinuria. Transcriptomes of CD2+ cells were analyzed by serial analysis of gene expression (SAGE) in a nephrotic child during proteinuria relapse and after remission, away from any immunosuppressive treatment. Expression of specific transcripts overexpressed during proteinuria relapse was compared by reverse transcription-polymerase chain reaction (RT-PCR) in CD2+ cells from 11 nephrotic patients during relapse and remission and 11 non nephrotic patients during infection and after recovery. Differential analysis of CD2+ cell transcriptome identified >200 mRNA tags overexpressed during proteinuria relapse, including many T-cell markers. RT-PCR analysis of expression of specific transcripts indicated that (1) under remission conditions, nephrotic children displayed induction of four transcripts, including IKBKB, and repression of NFKBIA as compared to non nephrotic children after recovery, and (2) proteinuria relapse was associated with induction of L-selectin and T-lymphocyte maturation-associated protein, two markers of T-cell differentiation and recent emigrant/naive T cells. Results indicate that circulating T cells from relapsing nephrotic patients include a significant population of low-mature cells while those from nephrotic patients in remission are characterized by constitutive activation of nuclear factor-kappaB (NF-kappaB), altogether suggesting a thymic dysregulation of apoptosis in nephrotic patients.

The use of cyclosporine in a boy with a prior episode of posterior encephalopathy

We report the case of a 12- year-old Japanese boy who was receiving cyclosporine (Cs A) for steroid-dependent nephrotic syndrome despite a prior episode of Cs A-associated posterior encephalopathy. At the third relapsing of nephrotic syndrome, Cs A was initiated. Eight days after the Cs A therapy, the boy was admitted to the University Hospital of Tsukuba because of generalized convulsion. Magnetic resonance imaging (MRI) showed hyperintense lesions involving the bilateral parieto-occipital region. Cs A was discontinued, and cyclophosphamide was started. The boy had a 6-month drug-free period after the cyclophosphamide treatment and then relapsed three more times in the following 5 months. As the prednisolone dosage could not be decreased to less than 2 mg/kg/48 h, the patient was re-challenged with Cs A 1 1/2 years later. Blood pressure and serum Cs A levels were measured frequently, an anti-hypertensive drug was given, and MRI was done four times to detect hyperintense lesions. He has been receiving Cs A for 9 months, and MRI has revealed no abnormalities. At the latest follow-up, dated 12 April 2004, he was in a remissive state of nephrotic syndrome. This is the first report of giving Cs A to a nephrotic child who had a previous history of Cs A-associated posterior encephalopathy.

Failed peritoneal dialysis in a dehydrated nephrotic child, in acute renal failure: a case report

A case of failed peritoneal dialysis in a 5-year-old male nephrotic who developed acute renal failure following severe P. falciparum malaria infection is presented. Peritoneal dialysis (PD) failure was sequel to undetected severe dehydration which occurred during the diuretic phase of the acute renal failure. Pre-dialysis plasma potassium, bicabonate, urea and creatinine concentrations were 6.0mmol/L, 13mmol/L, 28mmol/L and 900mmol/L respectively, after about 22 hours of PD, the plasma K+, HCO-3 Ur and Cr were 5.7mmol/L, 15mmol/L, 32mmol/L and 1,090mml/L respectively. The peritoneal dialysate Ur concentration (3.5mmol and peritoneal Ur clearance (1.85ml/min/1.73m2) were grossly inadequate. There was also, intradialysis hyperglycaemia (12mmol/L owing to massive absorption of peritoneal dialysate solution which contains high concentration of glucose. Hyperglycaemia was corrected with 0.25 units/kg/dose of soluble insulin intravenously, he had two doses. Owing to similarity of clinical and biochemical features of dehydration and ARF, all efforts must be made to exclude dehydration before embarking on PD in patients with renal failure. Failure to exclude dehydration, led to PD failure in this patient.

Vitamin D metabolites in childhood nephrotic syndrome.

We measured serum levels of total and ionised calcium, phosphate, intact parathyroid hormone, 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)2D] and the vitamin D binding protein (DBP) in 14 children with idiopathic nephrotic syndrome and 10 healthy, age-matched controls. In all nephrotics serum DBP levels were below the normal range. Serum 25(OH)D was below 7 ng/ml in 10 of 14 nephrotic children and in the low normal range in the remaining 4 patients. The average serum 1,25(OH)2D levels were lower in the nephrotic patients than in the controls. However, free 1,25(OH)2D levels were normal in the nephrotic patients. Both serum 25(OH)D and 1,25(OH)2D correlated positively with the concentration of DBP. There was a significant negative correlation between serum DBP levels and the urinary protein excretion and a significant positive correlation between the urinary excretions of DBP and albumin. From this study it can be concluded that the nephrotic child is capable of maintaining appropriate serum concentrations of free calcitriol despite important urinary losses of both substrate and bound calcitriol.

Management of the nephrotic child.

Management of the nephrotic child.

Nephrotic Syndrome Due to Primary Nephropathies

The nephrotic syndrome is characterized by massive proteinuria, hypoproteinemia, and usually hyperlipemia and generalized edema, with or without varying degrees of hematuria, hypertension, and azotemia. Normally, children excrete less than 60 mg of protein in an overnight 12-hour collection of urine, and less than 150 mg in a 24-hour sample. In the nephrotic child, the magnitude of proteinuria exceeds 200 mg in an overnight sample and 1.5 gm in a 24-hour collection. Recognition that the underlying renal histopathology in a nephrotic child has significant implications for response to treatment and for prognosis has led to attempts to predict the type of lesion using various criteria. The associated presence of hematuria, hypertension, or azotemia in individual nephrotic children is remarkedly inconsistent and does not correlate accurately with the underlying histopathology. However, consideration of these plus additional readily obtained data frequently will permit a more reliable prediction of the probable histopathology and potential response to therapy. Such information will include the age of the patient, ancillary physical findings, and selected laboratory studies. From that perspective, the purpose of this review is to discuss the implications of the composite clinical and laboratory findings for diagnosis and management in the child with the nephrotic syndrome. These will include indications for renal biopsy, which is the definitive test in these conditions.

Observations on infection of the urinary tract and childhood nephrosis.

"We would suspect a bacterial pyelonephritis in any nephrotic child who required an unusually large dose of steroids for improvement."

46 Renal Metabolism with Renal Disease in Man

The proximal tubular uptake and utilization of aketoglutarate (αKG) has been linked to corticalblood flow, H+ secretion and anaerobic CO2 production. Oxidation of aKG at the substrate level is the first step in energy-dependent gluconeogenesis by renal cortex. Thus, renal αKG dissimilation and renal glucose production (RGP), might reflect locus and extent of altered cell function in the kidney. To explore this, Na αKG was infused, with parental consent, in 10 children with renal disease (9 acute glomerulonephritis [AGN], I nephrotic) and 12 controls under standard loading, inulin and PAH clearance conditions. Renal extractions of PAH (EPAH) and αKG as well as RGP were determined from frequent concurrent samples of renal vein and aortic blood in 3 patients with AGN, the nephrotic, and 6 controls, with ‘normal’ kidneys but congenital heart defects. The studies were repeated in the 3 AGN patients during healing. Renal uptake and utilization of αKG and RGP were calculated for body size and estimated kidney weight. In vitro RGP by human kidney slices obtained at operation from 2 intact and 2 diseased kidneys also was assayed for comparison. In AGN, significantly reduced renal uptake and utilization of the αKG load with persistently high H+ excretion and decreased reabsorption of Na accompanied the low CIN, EPAH and CPAH (CPAH/EPAH). All patterns approximated controls with healing. RGP usually was impaired, especially in the nephrotic child. RGP with αKG in vivo was similar to in vitro values for ‘normal’ human kidney slices with glycerol, fructose, pyruvate, αKG, succinate or malate as substrates. These results imply increased ‘non-cortical’ renal blood flow and impaired proximal tubule metabolism referrable to αKG in the kidney diseases studied. (APS)

Studies on the pathogenesis of nephrotic edema: With particular emphasis upon changes in renal hemodynamics andthe metabolism of electrolyte and proteins

Summary Some physiologic and biochemical observationson children with the nephrotic syndrome and on rats with an experimental nephrotic syndrome are summarized. Particular reference is made to renal function, including some estimates of renal thermodynamics associated with the secretion of potassium by the edematous nephrotic child. Electrolyte balances illustrate the accumulation and diuresis of nephrotic edema fluid with particular reference to the effect of sodium restriction and sodium loading in nephrotic children. The balance data suggest that edema is asoociated with a decreased intracellular potassium content, as well as an accumulation of Na and Cl extracellularly. Studies of the composition of muscle from a nephrotic child support this thesis. It is suggested that some of the discrepancies in estimating the retention and distribution of Na and Cl by Balance measurements may be explained by correction for the retention of sodium, chloride, and water in skin and skeleton. A technique for such correction is illustrated. The skin appears to be the principal tissue reservor of edema fluid according to such calculations, and some evidence for this is provided by analyses of skin from rats with the experimental nephrotic syndrome. In the edenmatous skins of these animals, sodium and chloride are retained in excess of their anticipated distribution in the extracellular and intracellular fluids. It is suggested that the “excess” sodium and choride might be contained by loose electrostatic apposition to charged polar-end groups in the collagen fibril. Analytical data are given for “excess” Na and Cl of normal human skin, which are consistent with the above concept. Recent studies of cell composition of rats with an experimental nephrotic syndrome indicate a deficit of magnesium and organic phosphate as well as the accumulation of intracellular sodium and decreased concentration of potassium previously described. An attempt has been made to integratethese observations with others taken from the available literature and other studies by our group upon plasma protein metabolism in the nephrotic syndrome, to construc a tentative, hypothetical schema for the pathogenesis of nephrotic edema.