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BACKGROUND: Levamisole is less expensive and has a better toxicity profile compared to other steroid sparing agents used in nephrotic syndrome. It has a plasma half-life of 2.0 to 5.6 hours, but is conventionally administered on alternate days. We aimed to assess whether daily levamisole is safe and more effective than standard alternate-day therapy in maintaining remission in children with frequently relapsing or steroid-dependent nephrotic syndrome (FR/SDNS). METHODS: An open-label randomized controlled trial was conducted in children with FR/SDNS. Group A received daily while Group B received alternate-day levamisole (2-3 mg/kg/dose) for 12 months. Prednisolone was tapered off by 3 months. Patients were monitored for relapses, further steroid requirement, and adverse effects. RESULTS: A total of 190 children with FR/SDNS (94 in Group A and 96 in Group B) were analyzed. Sustained remission for 12 months was observed in 36% of Group A and 27% of Group B patients (p = 0.18). Numbers completing 12 months in the study were 67% in Group A and 56% in Group B (p = 0.13). Time to first relapse, persistent FR/SDNS, and withdrawal due to poor compliance were statistically similar in both groups, while relapse rate and cumulative steroid dosage were significantly lower in Group A compared to Group B (p = 0.03 and p = 0.02, respectively). The incidence of adverse effects was comparable in both groups, with reversible leucopenia and hepatic transaminitis being the commonest. CONCLUSIONS: Daily levamisole therapy was not superior to alternate-day therapy in maintaining sustained remission over 12 months. Nevertheless, relapse rate and cumulative steroid dosage were significantly lower without increased adverse effects.
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BACKGROUND: Levamisole is a commonly used steroid-sparing agent (SSA), but the reported incidence of antineutrophil cytoplasmic antibody (ANCA) positivity has been concerning. METHODS: Observational cross-sectional study wherein children aged 2 to 18 years with frequently relapsing/steroid dependent nephrotic syndrome (FRNS/SDNS) on levamisole for ≥ 12 months were tested for ANCA. RESULTS: A total of 210 children (33% female), median age of 7.3 (IQR: 5.6-9.6) years, and a median duration of levamisole exposure of 21 (IQR: 15-30) months were tested. ANCA was positive in 18% (n = 37): 89% (n = 33) perinuclear ANCA (pANCA), 3% (n = 1) cytoplasmic ANCA (cANCA), and 8% (n = 3) both. Of ANCA-positive children, none had reduced eGFR or abnormal urinalysis. The majority of these children were asymptomatic (81%, n = 30). Rash was more common among ANCA-positive children [6/37 (16%) vs. 3/173 (2%), p = 0.0001]. On multivariate analysis, higher age (OR = 1.02, [95th CI: 1.01 to 1.03], p = 0.007) and longer duration of levamisole exposure (OR = 1.05, [95th CI: 1.02 to 1.08], p = 0.0007) were associated with ANCA positivity. Levamisole was stopped in ANCA-positive children with the resolution of any clinical manifestations if present. Repeat ANCA testing was performed in 54% (20/37), and all were ANCA negative by 18 months. CONCLUSIONS: Children with FRNS/SDNS on longer duration of levamisole were associated with increasing prevalence of ANCA positivity, but most of these children were clinically asymptomatic. Prospective studies are required to determine the chronology of ANCA positivity and its clinical implication.
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Anticuerpos Anticitoplasma de Neutrófilos , Levamisol , Síndrome Nefrótico , Humanos , Levamisol/efectos adversos , Niño , Femenino , Masculino , Estudios Transversales , Anticuerpos Anticitoplasma de Neutrófilos/sangre , Anticuerpos Anticitoplasma de Neutrófilos/inmunología , Síndrome Nefrótico/tratamiento farmacológico , Síndrome Nefrótico/inmunología , Síndrome Nefrótico/sangre , Preescolar , Adolescente , Estudios de CohortesRESUMEN
Introduction: Congenital anomalies of the kidney and urinary tract (CAKUT) are the predominant cause of chronic kidney disease (CKD) and the need for kidney replacement therapy (KRT) in children. Although more than 60 genes are known to cause CAKUT if mutated, genetic etiology is detected, on average, in only 16% of unselected CAKUT cases, making genetic testing unproductive. Methods: Whole exome sequencing (WES) was performed in 100 patients with CAKUT diagnosed in the first 1000 days of life with CKD stages 1 to 5D/T. Variants in 58 established CAKUT-associated genes were extracted, classified according to the American College of Medical Genetics and Genomics guidelines, and their translational value was assessed. Results: In 25% of these mostly sporadic patients with CAKUT, a rare likely pathogenic or pathogenic variant was identified in 1 or 2 of 15 CAKUT-associated genes, including GATA3, HNF1B, LIFR, PAX2, SALL1, and TBC1D1. Of the 27 variants detected, 52% were loss-of-function and 18.5% de novo variants. The diagnostic yield was significantly higher in patients requiring KRT before 3 years of age (43%, odds ratio 2.95) and in patients with extrarenal features (41%, odds ratio 3.5) compared with patients lacking these criteria. Considering that all affected genes were previously associated with extrarenal complications, including treatable conditions, such as diabetes, hyperuricemia, hypomagnesemia, and hypoparathyroidism, the genetic diagnosis allowed preventive measures and/or early treatment in 25% of patients. Conclusion: WES offers significant advantages for the diagnosis and management of patients with CAKUT diagnosed before 3 years of age, especially in patients who require KRT or have extrarenal anomalies.
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With variable atomic ratios, Ce-Al bimetallic oxides were fabricated using the sol-gel combustion method and utilized for efficient fluoride removal. The synthesized bimetallic oxides were extensively studied using advanced characterization techniques, including TGA, XRD, FTIR, BET surface area analysis, EDX-assisted FESEM, XPS and impedance analysis. These techniques facilitate the interpretation of the chemical and physical properties of the synthesized material. The Ce-Al (1:1) bimetallic oxide was selected as an adsorbent for the defluoridation. The Ce-Al (1:1) oxide demonstrates a moderately high surface area of 108.67 m2/g. The sorption behaviour of fluoride on Ce-Al (1:1) was thoroughly investigated using batch and column modes. The maximum fluoride removal efficiency (99.4%) was achieved at a temperature of 45 °C and pH of 7.0 using an adsorbent dose of 0.18 g/L for 35 min. Pseudo-second-order kinetic model appropriately describes the sorption process. Freundlich's adsorption isotherm was more pertinent in representing fluoride adsorption behaviour. The maximum fluoride adsorption capacity is 146.73 mg/g at 45 °C. Thermodynamics study indicates fluoride adsorption on Ce-Al (1:1) bimetallic oxide is spontaneous and feasible. The adsorption mechanism was interpreted through XPS spectra, indicating that the physisorption process is mainly responsible for fluoride adsorption. An in-depth investigation of the adsorption dynamics was carried out using mass transfer models and found that the external diffusion process limits the overall adsorption rate. An electrochemical investigation was performed to understand the effect of fluoride adsorption on the electrochemical behaviour of bimetallic oxide. The fixed-bed column adsorption study suggested that the lower flow rate and increased bed height favourably impacted the overall defluoridation process, and column adsorption results were suitably interpreted through both the Adam-Bohart model and Yoon-Nelson dynamics model. The sustainable aspect of the defluoridation process was elucidated in terms of carbon footprint measurement using life cycle assessment analysis. The carbon footprint of the entire treatment process was calculated as 0.094 tons/year.
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Contaminantes Químicos del Agua , Purificación del Agua , Óxidos/química , Agua , Fluoruros/análisis , Adsorción , Purificación del Agua/métodos , Concentración de Iones de Hidrógeno , Contaminantes Químicos del Agua/análisis , CinéticaRESUMEN
OHVIRA syndrome (or Herlyn-Werner-Wunderlich syndrome) is a rare condition, consisting classically of obstructed hemi-vagina with ipsilateral renal agenesis. It may be associated with complex uterine malformations and more rarely with lower urinary tract anomalies. The contralateral kidney usually has normal function. A genetic etiology of this syndrome has not yet been confirmed. We report a patient who was diagnosed to have unilateral renal agenesis in early childhood, and then presented after menarche with features of OHVIRA syndrome. The contralateral kidney was relatively small and echogenic, and serum creatinine and uric acid were raised. A likely causal variant of the UMOD gene was detected on whole exome sequencing. Genetic studies in more patients with OHVIRA syndrome may elucidate further, whether the association with UMOD gene is causal in nature.
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Anomalías Múltiples , Enfermedades Renales , Anomalías Urogenitales , Femenino , Preescolar , Humanos , Riñón/anomalías , Vagina/anomalías , Anomalías Múltiples/diagnóstico , Enfermedades Renales/diagnóstico , UromodulinaRESUMEN
The purpose of this literature review was to identify interventions designed to improve healthcare team communication in the United States. We conducted a review of peer-reviewed, English-language articles describing interventions aimed at improving healthcare team communication. We analyzed articles that met pre-specified inclusion and exclusion criteria and characterized who is testing communication interventions, the rationale for testing, and ways of measuring effectiveness. We descriptively categorized the strength and types of study findings. Thirty articles were retained in our analysis. Most assessments were conducted by academic medical centers, the Veterans Health Administration, and teaching hospitals. Interventions sought to improve teamwork, patient safety, clinical outcomes, costs of care, and enhance provider job satisfaction and well-being. Intervention strategies included didactic lectures, simulation, Crew Resource Management, quality improvement, or a combination of these approaches. The vast majority employed a pre-post survey design and measured outcomes using participant feedback. Many assessments failed to utilize a social science theory or communication-specific measures. Interventions with the best training content were conducted at academic medical centers, used a pre-post design, and utilized statistical analysis to analyze results. While interventions for improving healthcare team communication are diverse and have uneven effectiveness, early markers of success merit continued development and assessment.
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Comunicación , Mejoramiento de la Calidad , Humanos , Estados Unidos , Grupo de Atención al PacienteRESUMEN
Idiopathic nephrotic syndrome is the most frequent pediatric glomerular disease, affecting from 1.15 to 16.9 per 100,000 children per year globally. It is characterized by massive proteinuria, hypoalbuminemia, and/or concomitant edema. Approximately 85-90% of patients attain complete remission of proteinuria within 4-6 weeks of treatment with glucocorticoids, and therefore, have steroid-sensitive nephrotic syndrome (SSNS). Among those patients who are steroid sensitive, 70-80% will have at least one relapse during follow-up, and up to 50% of these patients will experience frequent relapses or become dependent on glucocorticoids to maintain remission. The dose and duration of steroid treatment to prolong time between relapses remains a subject of much debate, and patients continue to experience a high prevalence of steroid-related morbidity. Various steroid-sparing immunosuppressive drugs have been used in clinical practice; however, there is marked practice variation in the selection of these drugs and timing of their introduction during the course of the disease. Therefore, international evidence-based clinical practice recommendations (CPRs) are needed to guide clinical practice and reduce practice variation. The International Pediatric Nephrology Association (IPNA) convened a team of experts including pediatric nephrologists, an adult nephrologist, and a patient representative to develop comprehensive CPRs on the diagnosis and management of SSNS in children. After performing a systematic literature review on 12 clinically relevant PICO (Patient or Population covered, Intervention, Comparator, Outcome) questions, recommendations were formulated and formally graded at several virtual consensus meetings. New definitions for treatment outcomes to help guide change of therapy and recommendations for important research questions are given.
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Nefrología , Síndrome Nefrótico , Niño , Humanos , Síndrome Nefrótico/diagnóstico , Síndrome Nefrótico/tratamiento farmacológico , Síndrome Nefrótico/epidemiología , Glucocorticoides/uso terapéutico , Inmunosupresores/efectos adversos , Proteinuria/tratamiento farmacológico , Esteroides/efectos adversos , RecurrenciaRESUMEN
Hypovitaminosis D has been reported to be common in chronic kidney disease (CKD) as well as in proteinuric disorders. We reviewed available evidence to assess clinically relevant effects of low vitamin D status and native vitamin D (NVD) therapy, in pediatric renal diseases. Online medical databases were searched for articles related to vitamin D status, associations of hypovitaminosis D and effects of NVD therapy in kidney disease. Hypovitaminosis D was associated with worse skeletal, cardiovascular, inflammatory, and renal survival outcomes in CKD. Low serum 25 hydroxy-vitamin D (25[OH]D) levels correlated positively with glomerular filtration rate and negatively with serum parathyroid (PTH) levels. However, to date, evidence of benefit of NVD supplementation is restricted mainly to improvements in serum PTH, and biochemical 25[OH]D targets form the basis of clinical practice recommendations for NVD therapy. In nephrotic syndrome (NS) relapse, studies indicate loss of 25[OH]D along with vitamin D binding protein in urine, and serum total 25[OH]D levels are low. Preliminary evidence indicates that free 25[OH]D may be a better guide to the biologically active fraction. NVD therapy in NS does not show consistent results in improving skeletal outcomes and hypercalciuria has been reported when total 25[OH]D levels were considered as indication for therapy. NVD formulations should be regularised, and therapy monitored adequately to avoid adverse effects.
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Insuficiencia Renal Crónica , Raquitismo , Deficiencia de Vitamina D , Humanos , Niño , Relevancia Clínica , Vitamina D/uso terapéutico , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/tratamiento farmacológico , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/tratamiento farmacológico , Riñón , Vitaminas , Hormona ParatiroideaRESUMEN
Road traffic vehicular noise is one of the main sources of environmental pollution in urban areas of India. Also, steadily increasing urbanization, industrialization, infrastructures around city condition causes health risks among the urban populations. In this study, we have explored noise descriptors (L10, L90, Ldn, LNI, TNI, NC), contour plotting and find the suitability of artificial neural networks (ANN) for the prediction of traffic noise all around the Dhanbad township in 15 monitoring stations. In order to develop the prediction model, measuring noise levels of five different hours, speed of vehicles, and traffic volume in every monitoring point have been studied and analyzed. Traffic volume, percent of heavy vehicles, speed, traffic flow, road gradient, pavement, road side carriageway distance factors were taken as input parameter, whereas LAeq as output parameter for formation of neural network architecture. As traffic flow is heterogenous which mainly contains 59%, two wheelers and different vehicle specifications with varying speeds also affect driving and honking behavior which constantly changing noise characteristics. From radial noise diagrams shown that average noise levels of all the stations beyond permissible limit and the highest noise levels were found at the speed of 50-55 km/h in both peak and non-peak hours. Noise descriptors clearly indicate high annoyance level in the study area. Artificial neural network with 7-7-5 formation has been developed and found as optimum due to its sum of square and overall relative error 0.858 and .029 in training and 0.458 and 0.862 in testing phase respectively. Comparative analysis between observed and predicted noise level shows very less deviation up to ± 0.6 dB(A) and the R2 linear values are more than 0.9 in all five noise hours indicating the accuracy of model. Also, it can be concluded that ANN approach is much superior in prediction of traffic noise level to any other statistical method.
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Ruido del Transporte , Ciudades , Contaminación Ambiental , India , Redes Neurales de la ComputaciónRESUMEN
BACKGROUND: Inherited tubulopathies are a heterogeneous group of genetic disorders making whole-exome sequencing (WES) the preferred diagnostic methodology. METHODS: This was a multicenter descriptive study wherein children (< 18 years) with clinically suspected tubular disorders were recruited for molecular testing through WES. Multiplex ligation-dependent probe amplification (MLPA) and Sanger sequencing were done when required. Variants were classified as per American College of Medical Genetics 2015 guidelines and pathogenic (P)/likely pathogenic (LP) variants were considered causative. RESULTS: There were 77 index cases (male =73%). Median age at diagnosis was 48 months (IQR 18.5 to 108 months). At recruitment, the number of children in each clinical group was as follows: distal renal tubular acidosis (dRTA) = 25; Bartter syndrome = 18; isolated hypophosphatemic rickets (HP) = 6; proximal tubular dysfunction (pTD) = 12; nephrogenic diabetes insipidus (NDI) = 6; kidney stone/nephrocalcinosis (NC) = 6; others = 4. We detected 55 (24 novel) P/LP variants, providing genetic diagnoses in 54 children (70%). The diagnostic yield of WES was highest for NDI (100%), followed by HP (83%; all X-linked HP), Bartter syndrome (78%), pTD (75%), dRTA (64%), and NC (33%). Molecular testing had a definite impact on clinical management in 24 (31%) children. This included revising clinical diagnosis among 14 children (26% of those with a confirmed genetic diagnosis and 18% of the overall cohort), detection of previously unrecognized co-morbidities among 8 children (sensorineural deafness n = 5, hemolytic anemia n = 2, and dental changes n = 1) and facilitating specific medical treatment for 7 children (primary hyperoxaluria n = 1, cystinosis n = 4, tyrosinemia n = 2). CONCLUSION: WES is a powerful tool in the diagnosis and management of children with inherited tubulopathies in the Indian population. A higher resolution version of the Graphical abstract is available as Supplementary information.
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Acidosis Tubular Renal , Síndrome de Bartter , Diabetes Insípida Nefrogénica , Nefrocalcinosis , Acidosis Tubular Renal/diagnóstico , Acidosis Tubular Renal/genética , Síndrome de Bartter/diagnóstico , Síndrome de Bartter/genética , Niño , Femenino , Humanos , India/epidemiología , Masculino , Secuenciación del ExomaRESUMEN
BACKGROUND: Nearly 50% of the world population and 60% of children aged 0 to 14 years live in low- or lower-middle-income countries. Paediatric nephrology (PN) in these countries is not a priority for allocation of limited health resources. This article explores advancements made and persisting limitations in providing optimal PN services to children in such under-resourced areas (URA). METHODS: Medline, PubMed and Google Scholar online databases were searched for articles pertaining to PN disease epidemiology, outcome, availability of services and infrastructure in URA. The ISN and IPNA offices were contacted for data, and two online questionnaire surveys of IPNA membership performed. Regional IPNA members were contacted for further detailed information. RESULTS: There is a scarcity of published data from URA; where available, prevalence of PN diseases, managements and outcomes are often reported to be different from high income regions. Deficiencies in human resources, fluoroscopy, nuclear imaging, immunofluorescence, electron microscopy and genetic studies were identified. Several drugs and maintenance kidney replacement therapy are inaccessible to the majority of patients. Despite these issues, regional efforts with support from international bodies have led to significant advances in PN services and infrastructure in many URA. CONCLUSIONS: Equitable distribution and affordability of PN services remain major challenges in URA. The drive towards acquisition of regional data, advocacy to local government and non-government agencies and partnership with international support bodies needs to be continued. The aim is to optimise and achieve global parity in PN training, investigations and treatments, initially focusing on preventable and reversible conditions.
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Nefrología , Niño , Costos y Análisis de Costo , Humanos , Renta , Terapia de Reemplazo Renal , Recursos HumanosRESUMEN
JUSTIFICATION: Steroid sensitive nephrotic syndrome (SSNS) is one of the most common chronic kidney diseases in children. These guidelines update the existing Indian Society of Pediatric Nephrology recommendations on its management. OBJECTIVE: To frame revised guidelines on diagnosis, evaluation, management and supportive care of patients with the illness. PROCESS: The guidelines combine evidence-based recommendations and expert opinion. Formulation of key questions was followed by review of literature and evaluation of evidence by experts in two face-to-face meetings. RECOMMENDATIONS: The initial statements provide advice for evaluation at onset and follow up and indications for kidney biopsy. Subsequent statements provide recommendations for management of the first episode of illness and of disease relapses. Recommendations on the use of immunosuppressive strategies in patients with frequent relapses and steroid dependence are accompanied by suggestions for step-wise approach and plan of monitoring. Guidance is also provided regarding the management of common complications including edema, hypovolemia and serious infections. Advice on immunization and transition of care is given. The revised guideline is intended to improve the management and outcomes of patients with SSNS, and provide directions for future research.
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Nefrología , Síndrome Nefrótico , Niño , Humanos , Inmunosupresores , Síndrome Nefrótico/diagnóstico , Síndrome Nefrótico/tratamiento farmacológico , RecurrenciaRESUMEN
BACKGROUND: There is scarcity of data on impact of rituximab on anthropometrical parameters (weight, height and body mass index i.e. BMI SD score (SDS)) among children with steroid-dependent nephrotic syndromes (SDNS). METHODS: Multicentre retrospective review. RESULTS: 102 children with SDNS (male: 63%; n=64), median age 7 (IQR: 4.3-9.6) years, received a total of 217 rituximab infusions (total 110 cycles). At median follow-up of 2.1 (IQR: 1.3-2.8) years, 58 (57%) children were off steroids and a significant fall in steroid threshold for relapse was noted (median 0.6; IQR 0.4-0.9 to median 0.3; IQR 0.12 - 0.5 mg/kg/alternate day, p=0.005). Anthropometric parameters (BMI SDS: 0.92±1.8 to 0.25±1.47, p=0.003; weight SDS: 0.20±1.6 to -0.11±1.3, p=0.01; and height SDS: -0.93±1.88 to -0.45±1.54, p=0.04) as well as obesity (38% to 20%, p=0.003) and short stature (11% to 3%, p=0.02) improved. Results remained significant even when analysis was restricted to children ≤12 years (n=88), (BMI SDS: 0.97±1.98 to 0.25±1.5, p=0.001; weight SDS: 0.33±1.6 to 0.02±1.2, p=0.01; and height SDS: -0.67±1.84 to -0.186±1.42, p=0.001). CONCLUSIONS: Use of rituximab resulted in significant steroid sparing effect with an improvement in both growth and obesity parameters.
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Trastornos del Crecimiento/inducido químicamente , Factores Inmunológicos/farmacología , Síndrome Nefrótico/tratamiento farmacológico , Rituximab/farmacología , Esteroides/efectos adversos , Antropometría , Estatura/efectos de los fármacos , Índice de Masa Corporal , Peso Corporal/efectos de los fármacos , Niño , Preescolar , Femenino , Estudios de Seguimiento , Trastornos del Crecimiento/epidemiología , Humanos , Factores Inmunológicos/administración & dosificación , Infusiones Intravenosas , Masculino , Síndrome Nefrótico/fisiopatología , Obesidad/inducido químicamente , Obesidad/epidemiología , Estudios Retrospectivos , Rituximab/administración & dosificación , Esteroides/uso terapéuticoRESUMEN
INTRODUCTION: Detrusor dysfunction is known to persist in several patients of Posterior Urethral Valve (PUV) after successful fulguration leading to progressive deterioration of renal function. Persistent bladder outlet obstruction (BOO) in the form of bladder neck hypertrophy, residual valves or strictures may contribute to progressive detrusor dysfunction. These are assessed radiologically or cystoscopically and are managed variedly by anticholinergics, alpha-adrenergic blockers or even bladder neck incision. Unfortunately, currently we do not have any objective measures to evaluate the degree of BOO in children or follow treatment outcome of any such measures. OBJECTIVE: To assess the feasibility of pressure flow studies in children and proposition of an age independent index to quantify outflow parameters. STUDY DESIGN: We retrospectively studied the urodynamic data of the follow up cases of PUV who had been referred to us for urodynamic evaluation. Free flow uroflowmetries and filling and voiding cystometrogram were performed as per recommended protocol. Parameters like Adjusted Bladder Capacity (ABC = Voided volume + post void residue; expressed as percentage of expected bladder capacity {EBC}), overactivity, compliance, Qmax and P det at Qmax were taken into consideration. Indices like Bladder Outlet Obstruction Index (BOOI) and Bladder Contractility Index (BCI) were calculated. Multivariate analysis was run to assess correlation of ABC with other parameters. Receiver Operating Characteristics (ROC) curve analysis was performed to assess predictive values of BOOI for ABC. RESULTS: We did not find the ABC to change with age as has been classically described. Qmax and BCI were found to correlate with age. Values obtained for P det at Qmax and BOOI were not dependent on age and were in similar range as observed in adults. On multivariate analysis, small bladder was found to positively correlate with presence of overactivity, high BOOI and low BCI. ROC curve analysis showed a BOOI >29 could predict ABC to be <100% EBC with moderate sensitivity and specificity. DISCUSSION: Pressure flow studies are the only objective means of quantifying outlet resistance, hitherto they have been considered to be unrepresentative in children. Documentation and correction of high outflow pressures may arrest the cycle of detrusor hypertrophy and dysfunction. CONCLUSION: Quality pressure flow studies are feasible in children. Values of P det at Qmax and BOOI in children are age independent and similar to those observed in adults. BOOI can be potentially used in children to assess degree of BOO.
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Obstrucción del Cuello de la Vejiga Urinaria , Urodinámica , Adulto , Niño , Humanos , Curva ROC , Estudios Retrospectivos , Obstrucción del Cuello de la Vejiga Urinaria/diagnóstico por imagen , Obstrucción del Cuello de la Vejiga Urinaria/etiologíaRESUMEN
INTRODUCTION: Body stores of vitamin D are measured as "total" serum 25-hydroxy vitamin D (25(OH)D). Its largest component is protein bound and lost in urine in nephrotic syndrome (NS). Our study investigates whether "free" 25(OH)D levels are a better guide to bone health and need for vitamin D supplementation in patients with steroid-sensitive NS (SSNS). METHODS: A cross-sectional study was performed in children with SSNS and healthy controls. Blood was tested for albumin, creatinine, calcium, phosphate, ALP, total and free (by direct ELISA) 25(OH)D, iPTH, and urine for protein-creatinine ratio. RESULTS: Seventy-nine NS patients (48 in relapse, 31 in remission) and 60 healthy controls were included. The levels of total 25(OH)D were significantly different (lowest in NS relapse and highest in controls) (p < 0.001). Corrected calcium and phosphate levels were normal, and there were no differences in free 25(OH)D, ALP, or iPTH levels between groups. Only total and not free 25(OH)D correlated significantly and negatively with urinary protein creatinine ratios (rs = - 0.42 vs. 0.04). Free 25(OH)D values of 3.75 and 2.85 pg/ml corresponded to total 25(OH)D levels of 20 and 12 ng/ml, respectively, in healthy controls. CONCLUSION: These results confirm that total 25(OH)D levels are low in NS and related to degree of proteinuria. However levels of free 25(OH)D, ALP, and iPTH did not change in relapse or remission in comparison with healthy controls. Our results suggest that in proteinuric renal diseases, free 25(OH)D rather than total 25(OH)D levels should be used to diagnose vitamin D deficiency and guide therapy.
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Colecalciferol/sangre , Ergocalciferoles/sangre , Síndrome Nefrótico/complicaciones , Proteinuria/diagnóstico , Deficiencia de Vitamina D/epidemiología , Estudios de Casos y Controles , Niño , Preescolar , Colecalciferol/administración & dosificación , Colecalciferol/deficiencia , Estudios Transversales , Suplementos Dietéticos , Ergocalciferoles/administración & dosificación , Ergocalciferoles/deficiencia , Femenino , Glucocorticoides/farmacología , Glucocorticoides/uso terapéutico , Humanos , Masculino , Síndrome Nefrótico/sangre , Síndrome Nefrótico/diagnóstico , Síndrome Nefrótico/tratamiento farmacológico , Proteinuria/sangre , Factores de Riesgo , Albúmina Sérica Humana/análisis , Índice de Severidad de la Enfermedad , Deficiencia de Vitamina D/diagnóstico , Deficiencia de Vitamina D/etiología , Deficiencia de Vitamina D/prevención & controlRESUMEN
BACKGROUND: There is a paucity of information on epidemiology, diagnosis, and treatment outcomes of congenital nephrotic syndrome (CNS) in developing countries. METHODS: Retrospective (2012-2017) review of case records undertaken across 12 Indian pediatric nephrology centers. RESULTS: Sixty-five children (58% male, median birth weight 2.4 kg [interquartile range (IQR) 2.1-2.86]) were identified with CNS. Nearly half (45%) were preterm with previous history of fetal loss/sibling death in 22% and history of consanguinity in a third. No infective etiology was confirmed. Genetic reports available for 15 (23%) children identified causal mutations in 10 (8 in NPHS1 [1 novel variant], 1 in WT 1 [novel variant], and 1 in PLCE-1 gene). In addition, 1 child was clinically diagnosed as Galloway Mowat syndrome. Next-generation sequencing showed 80% yield and Sanger sequencing 20%. Albumin infusion and angiotensin-converting enzyme inhibitors were used initially in around two-third of cohort, while only 12% of children received indomethacin. Totally, 22 (34%) children were lost to follow-up after initial visit, and among the rest median follow-up was 69 days (IQR 20-180) with 18 (42%) deaths. Eight children showed partial response (including 2 with NPHS1 compound mutation), 1 complete response, and all of them were alive at last follow-up in contrast to 53% mortality among nonresponders, p = 0.004. CONCLUSION: This largest reported series on CNS from India revealed suboptimal management with poor outcome as well as low number of CNS being subjected to genetic evaluation.