Epidemiology of Pediatric Nephrotic Syndrome: Real-World Data from Brazil

Nephrotic syndrome (NS) is a common proteinuric disorder with defect in the perm-selectivity of the glomerular filtration barrier (GFB). Ultrastructural morphometric evaluation of the GFB in pediatric NS has been attempted in only a few studies. This study was aimed at qualitative and quantitative evaluation of the alterations involving the GFB in pediatric idiopathic NS with an attempt to correlate these alterations with the clinico-laboratory data. For this study, renal biopsies from nine patients with NS and two children with interstitial nephritis were included. Relevant clinical and laboratory data, including degree of 24-h proteinuria and renal function tests, were recorded. Renal biopsies were reviewed for morphologic and electron microscopic diagnosis. Ultrastructural morphometry of the GFB was performed using image analysis software. The age at onset of NS, duration of illness, presence of hypertension, and renal function tests were comparable between the group of patients with minimal change disease (MCD) and those with mesangioproliferative glomerulonephritis (mesPGN)/focal segmental glomerulosclerosis (FSGS). However, the latter group showed higher 24-h proteinuria compared with the group with MCD. Among the detected ultra-structural changes, glomerular basement membrane thickness and foot process width were significantly different between the MCD and the mesPGN/FSGS groups. The slit pore diameter in the glomeruli showed a positive correlation with the degree of proteinuria. We conclude that our study demonstrated remarkable differences in certain parameters and the glomerular ultrastructural alterations in the various categories of NS. These differences might underlie the observed variation in response of these entities to various therapies.

Idiopathic nephrotic syndrome frequently presents with Vitamin D deficiency due to urinary losses of Vitamin D-binding protein. The relationship between Vitamin D status and clinical outcomes remains incompletely understood. To evaluate Vitamin D status in children with idiopathic nephrotic syndrome and assess its association with remission time and relapse patterns. This prospective observational study (October 2022-March 2024) included 60 children aged 1-14 years with idiopathic nephrotic syndrome at a tertiary care center in North India. The study involved 60 patients divided into supplemented (Group I, n = 30) and control (Group II, n = 30) groups. Vitamin D levels were measured at presentation, after 1 month, and at relapse events. Primary outcomes included baseline Vitamin D status, time to remission, and 6-month relapse rates. All participants demonstrated Vitamin D deficiency (51.7%) or insufficiency (48.3%) at presentation. Children with relapses had significantly lower baseline Vitamin D levels compared to those with initial episodes (8.76 ± 2.75 vs. 15.78 ± 2.04 ng/mL, P < 0.001). Despite this association, time to remission was similar between groups with adequate versus inadequate Vitamin D status (11.60±3.2 vs 11.93 ± 3.4 days, p = 0.994). Six-month relapse rates showed no significant correlation with baseline Vitamin D levels (r = -0.18, P = 0.17). Vitamin D deficiency is universal in pediatric nephrotic syndrome, with lower levels observed in relapsing disease. However, Vitamin D status does not appear to significantly influence time to remission or short-term relapse patterns, suggesting its role may be primarily nutritional rather than therapeutic.

Nephrotic syndrome (NS) is a common renal disorder with significant tubulo-interstitial damage due to the combined effects of proteinuria and obstruction of efferent blood flow. Peritubular capillary (PTC) loss has also been correlated with interstitial fibrosis. This study included 30 pediatric cases of idiopathic NS. Clinical details, including biochemical parameters, were recorded and renal biopsy slides were reviewed for histological features. PTCs were highlighted using anti-CD34 antibody and quantified with the help of image analysis software. Postmortem kidney biopsies from seven children were taken as controls for quantification of PTCs and interstitial fibrosis. Wherever possible, as ultrastructural examination of the renal biopsy was performed. Appropriate statistical methods were applied. Patients with minimal change disease (MCD) had lower serum creatinine as compared with those with focal and segmental glomerulosclerosis (FSGS). Similarly, tubular atrophy and interstitial fibrosis were significantly lower in MCD than in FSGS. PTC density was lower in all groups of NS as compared with the controls. Biopsies with FSGS had a lower PTC density compared with both MCD and mesangioproliferative glomerulonephritis. PTC density showed a negative correlation with serum creatinine and degree of proteinuria. PTC loss appears to play an important role in the development of renal biopsy changes in pediatric NS. This aspect of the renal vasculature requires further study in idiopathic NS.

Background Nephrotic syndrome (NS) is the most common kidney disease in children and is characterized by edema, massive proteinuria, hypoalbuminemia, and hyperlipidemia. High relapse rate remains a major problem in the management of this syndrome.&#x0D; Objective To identify risk factors for relapse in pediatric nephrotic syndrome.&#x0D; Methods This study was carried out in the Wahidin Sudirohusodo Teaching Hospital in Makassar, South Sulawesi, Indonesia, from January to August 2017 using complete medical records of children diagnosed with NS. Subjects were divided into 2 groups: 1) relapsed NS or 2) non-relapsed NS. The following potential risk factors for relapse were analyzed using Chi-square test: age, sex, nutritional status, hypertension, serum creatinine level, and infection at the time of established diagnosis of NS.&#x0D; Results A total of 142 children with NS who fulfilled the inclusion criteria aged 1.4 to 17.5 years were included in the study. Subjects were mostly boys (66.2%), with a male: female ratio of 1.95:1. The relapsed NS group had 80 cases (56.3%) and the non-relapsed NS group had 62 cases (43.7%). Statistical analysis revealed that nutritional status was a significant risk factor for relapse in pediatric nephrotic syndrome (P&lt;0.05).&#x0D; Conclusion Nutritional status is an independent risk factor for relapse in pediatric nephrotic syndrome.

PurposeThe nephrotic syndrome (NS) is characterized by the favorable response to glucocorticoid therapy and the development of NS may be associated with dysfunctional immune systems. In order to investigate the serum immunoglobulin E (IgE) levels and cytokines activity in pediatric NS, the total of 32 steroid responsive NS patients and 5 healthy controls were enrolled in this study.Materials and MethodsAll patients were divided into two groups according to the initial serum IgE levels, such as normal and high IgE group, and their clinical characteristics were evaluated. In addition, serum levels of interleukin (IL)-4, IL-5, IL-10 and transforming growth factor (TGF)-β were compared and correlated with serum albumin, proteinuria by means of disease severity, and cytokines.ResultsIn the high IgE group, the higher comorbidity of allergic diseases and relapsing rate, the longer duration of steroid therapy before initial remission, and the higher serum IL-4 and IL-5 levels were found. In all patients, initially higher serum levels of IL-4 and IL-5 declined to normal levels after steroid therapy, whereas the serum IL-10 levels showed no significant difference between nephrotic phase (heavy proteinuria) and remission phase (no proteinuria) of NS. The serum TGF-β levels of the nephrotic phase were significantly lower than those of remission phase or control group, and returned to normal control levels after steroid therapy.ConclusionThis study indicates that initial IgE level is associated with steroid responsiveness and disease severity, and cytokine activities may also be related to the pathogenesis of pediatric steroid responsive NS.

Nephrotic syndrome (NS) is a common pediatric urinary system disease. The aim in this work was to investigate the changes in pediatric NS-related metabolites through serum metabolomics, and explore the new potential metabolites and differential metabolic pathways. Serum samples from 40 pediatric patients with nephrotic syndrome and 40 healthy controls were collected. The targeted and non-targeted metabolomics analyses were performed to determine the metabolic changes in pediatric NS. Based on multivariate statistical analysis and the regression model, the serum potential metabolites were screened and different metabolic pathways were explored. 39 differential metabolites in pediatric NS were obtained based on the metabolomics analysis. 12 differential metabolites (serine, C18: 2 (EFA), C18: 2 (FFA), Isonuatigenin 3- [rhamnosyl- (1- > 2) -glucoside], C18: 4 (EFA), C18: 4 (FFA), caprylic acid, citric acid, methylmalonic acid, caproic acid, canavalioside and uroporphyrin were identified to establish the diagnostic model for pediatric NS. Five metabolic pathways including TCA cycle, amino acid metabolism, bile acid biosynthesis, linoleate metabolism and glyoxylate and dicarboxylate metabolism were the key differential metabolic pathways. These data elucidated the metabolic alterations associated with pediatric NS and suggested a new diagnosis model for monitoring pediatric NS. The current study provides the useful information to bridge the gaps in our understanding of the metabolic alterations associated with pediatric NS and might facilitate the characterization of pediatric NS patients by performing serum metabolomics.

Urinary liver-type fatty acid-binding protein (uL-FABP) has recently been identified as a biomarker for kidney injury. uL-FABP excretion in pediatric relapsing nephrotic syndrome and tubular dysfunction, however, has not been reported previously. We measured uL-FABP level in children with steroid-sensitive nephrotic syndrome (SSNS), in those with tubular dysfunction, and in control subjects. uL-FABP was markedly increased in relapsing SSNS (median, 30.3μg/gCr; range, 12.6-171.0μg/gCr; n= 13), and also in the tubular dysfunction group (median, 164.8μg/gCr; range, 41.6-834.5μg/gCr; n = 7), compared with the control subjects (median, 3.0μg/gCr; range, 1.1-13.9μg/gCr; n = 21). uL-FABP level was significantly correlated with urinary protein excretion in the SSNS group, and in the total group. Additionally, in the SSNS group, elevated uL-FABP in the relapsing stage returned to a level similar to that in the control group on remission of NS. In the tubular dysfunction group, uL-FABP was significantly correlated with urinary β2-microglobulin. Urinary protein amount, and the ability of the proximal tubules to reabsorb low-molecular-weight proteins, should also be considered when evaluating the clinical significance of uL-FABP as a biomarker for kidney injury in children.

To evaluate the safety and efficacy of the hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) as a potential treatment option for the dyslipidemia associated with childhood nephrotic syndrome. Searches of MEDLINE (1966-April 2004), Cochrane Library, International Pharmaceutical Abstracts (1977-April 2004), and an extensive manual review of journals were performed using the key search terms nephrotic syndrome, familial hypercholesterolemia, dyslipidemia, and HMG-CoA reductase inhibitor. Two prospective uncontrolled studies evaluating the safety and efficacy of statin therapy in pediatric nephrotic syndrome were included. While an extensive amount of data is available in adult nephrotic syndrome in which statin therapy decreases total plasma cholesterol 22-39%, low-density lipoprotein cholesterol (LDL-C) 27-47%, and total plasma triglycerides 13-38%, only 2 small uncontrolled studies have been conducted evaluating the utility of these agents in pediatric nephrotic syndrome. These studies indicate that statins are capable of safely reducing total cholesterol up to 42%, LDL-C up to 46%, and triglyceride levels up to 44%. Lowering cholesterol levels during childhood may reduce the risk for atherosclerotic changes and may thus be of benefit in certain patients with nephrotic syndrome. Statins have demonstrated short-term safety and efficacy in the pediatric nephrotic syndrome population. Implementing pharmacologic therapy with statins in children with nephrotic syndrome must be done with care until controlled studies are conducted in this population.

Venous thromboembolism is a condition of great interest to public health, as it is potentially preventable and has a high morbidity and mortality potential. Knowing the real-world data in a country of continental dimensions such as Brazil is essential to help define health policies that enable proper diagnosis and treatment of this disease. The objective of this study was to evaluate the incidence and in-hospital mortality rates of venous thromboembolism in public hospitals under Brazil's public health system. This is a population-based, cross-sectional, retrospective analysis of all hospitalizations for venous thromboembolism in the Brazilian public health system between 2008 and 2022. Using a public database, all hospital admissions for thromboembolic events were selected, defining the incidence, in-hospital mortality, and differences between Brazilian macro-regions. A total of 700,315 admissions for venous thromboembolism were documented in the Brazilian public health system between 2008 and 2022, which represents 3.02 admissions per 10,000 inhabitants per year. The Southeast region accounted for more than half (54.5%) of the hospitalizations. The highest incidence of hospitalizations occurred in the wealthiest regions (Southeast and South), while the lowest incidence was observed in the poorest regions (North and Northeast). On the other hand, a higher proportion of in-hospital mortality was observed in the North and Northeast regions. The highest admission rates were registered in wealthier regions, while a higher proportion of deaths was found in the poorer ones. This may reveal the difficulty in accessing healthcare services in the North and Northeast regions, which is reflected in the potential underdiagnosis of thromboembolic events in these regions.

Abu-Shahin N, Al-Khader A, Qattan D, Akl K. C1q nephropathy among children with nephrotic syndrome: Ten-year experience from a pediatric nephrology unit. Turk J Pediatr 2018; 60: 14-21. C1q nephropathy (C1qN) is a rare glomerulopathy mostly seen in children, and presents with nephrotic syndrome (NS). Diagnosis depends on immunoflourescence or immunohistochemical C1q mesangial deposition, excluding other immune-mediated diseases. We retrospectively investigated C1qN incidence, clinicopathological features, and outcome among pediatric NS in our institution.Clinical data, microscopic slides and corresponding tissue blocks of pediatric renal biopsies were retrieved. According to diagnostic criteria for C1qN, 53 pediatric NS renal biopsies were selected for Anti-C1qA IHC stain microscopic examination. Clinicopathological features and follow up data were recorded. C1qN incidence was 9.4% among pediatric NS biopsies. Mesangial proliferation was the most common histopathological pattern. Steroid dependency with frequent relapses was the most frequent outcome, with a second line immunosuppressant added, yet without impact on progression. Small sample size hinders coherent conclusions; nevertheless, it indicates that C1qN is a rare cause of pediatric NS. C1qN may require second line immunosupressants more often than non-C1q NS.

Introduction: Access to kidney replacement therapy (KRT) in remote areas of Brazil, which spans a territory of 8,510,718 km2, is particularly challenging, posing logistical difficulties for patients. Those living in distant cities often need to travel long distances to reach dialysis facilities, making it difficult to receive timely and effective treatment. Patients who travel more than 60 min to undergo hemodialysis may experience higher mortality and lower quality of life. Objective: The primary aim of this study was to calculate the travel distance between patient city areas and dialysis facility care locations in Brazil. Methods: We conducted a retrospective cohort study using claims data from the Brazilian Public Health System‘s database, focusing on kidney replacement therapy (KRT) by hemodialysis. Our study population comprised all prevalent and incident patients undergoing hemodialysis in Brazil between January 2023 and December 2023. For patients from different city areas, we calculated the Haversine distance between the patient city area and the dialysis facility. We utilized the Brazilian Institute of Geography and Statistics (IBGE) code to retrieve the corresponding latitude and longitude coordinates. Results: We evaluated 154,788 patients who received hemodialysis funded by the Brazilian Public Health System. There were 5570 city areas in Brazil, with 5261 of them having at least one patient undergoing hemodialysis. A total of 449 city areas had dialysis facilities. Fifty-nine percent of the patients underwent dialysis in the same city area. Overall, patients traveled a median (IQR) distance of 35.9 [19.5 – 64.2] kilometers to the facilities, 48% traveled more than 40 km, with a maximum traveling distance of 353 km. Notably, the median distance traveled was shortest in the Southeast (27.6 km) and longest in the North (84.3 km). The proportion of patients that traveled more than 40 kilometers was lower in the Southeast (32%) and higher in the North region (77%). Conclusion: The travel distance to the dialysis facility is an important inequity to KRT access in Brazil. In the South and Southeast, where there is a higher dialysis unit density, patients have higher regional availability of dialysis centers, and lower traveling distances than in the North, Midwest, and Northeast regions.

Patients who travel more than 60 min to undergo hemodialysis may experience higher mortality and lower quality of life. The primary aim of this study was to calculate the travel distance between patient city areas and dialysis facility care locations in Brazil, to highlight barriers and need to optimize access to chronic dialysis. We conducted a retrospective cohort study using claims data from the Brazilian Public Health System's database, focusing on kidney replacement therapy (KRT) by hemodialysis. Our study population comprised all patients undergoing hemodialysis in Brazil between January 2023 and December 2023. For patients from different city areas, we calculated the Haversine distance between the patient city area and the dialysis facility. We evaluated 154,788 patients who received hemodialysis funded by the Brazilian Public Health System. Fifty-nine percent of the patients underwent dialysis in the same city area. Overall, patients traveled a median (IQR) distance of 35.9 [19.5 - 64.2] kilometers to the facilities, 48% traveled more than 40 km, with a maximum traveling distance of 353 km. Notably, the median distance traveled was shortest in the Southeast (27.6 km) and longest in the North (84.3 km). The number of patients that traveled more than 40 km was lower in the Southeast (32%) and higher in the North region (77%). The travel distance to the dialysis facility is an important inequity to KRT access in Brazil. In the South and Southeast, where there is a higher dialysis unit density, patients have greater regional availability of dialysis centers, and shorter traveling distances than in the North, Midwest, and Northeast regions.

Limited Role of Antithrombin Deficiency in Hypercoagulopathy Associated with Nephrotic Syndrome

Whole-exome sequencing of a multicenter cohort identifies genetic changes associated with clinical phenotypes in pediatric nephrotic syndrome

Nephrotic syndrome (NS) is the most common clinical manifestation of glomerular disease in children. Currently, tacrolimus (TAC) is widely used in children with NS. However, pharmacokinetic data in children with nephrotic syndrome is limited. This study was intended to evaluate the population pharmacokinetics (PPK) of TAC in paediatric NS and to optimize dosing regimen. Blood samples from NS children treated with TAC were collected and the blood concentrations of TAC were detected using HPLC-MS/MS. A PPK model was developed using NONMEM software. Pharmacogenetic analysis was carried out in the CYP3A5 gene. The data from 28 children were used for PPK analysis. A one-compartment model and first-order elimination were accorded with the TAC data in paediatric NS. A covariate analysis showed that body weight and CYP3A5 genotype significantly affected TAC pharmacokinetics. Monte Carlo simulation indicated that NS children with CYP3A5*3/*3 receiving 0.10mgkg-1 dose-1 twice daily and NS children with CYP3A5*1 receiving 0.25mgkg-1 dose-1 twice daily TAC could achieve the target concentrations of 5-10ngml-1 . The PPK of TAC was estimated in children with NS and a CYP3A5 genotype-based dosing regimen was set up based on simulations.