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Congenital nephrotic syndrome (CNS) is one of the important causes of end-stage kidney disease in children. Studies on the genotype, phenotype, and clinical outcome in infants with CNS caused by genetic mutations are scarce. We analyzed the genetic background, clinical manifestations, treatment response, and prognosis of pediatric patients with CNS in Taiwan. Fifteen infants with CNS were enrolled, and 11 patients of median age 21 (interquartile range 3∼44) days caused by genetic mutations from 10 unrelated families were included in the study. Of the eleven patients, 9 had extra-renal manifestations including microcephaly, facial dysmorphism, and skeletal anomalies. More than two-thirds of the patients had disease onset before 1 month of age. Diffuse meningeal sclerosis was the most common histological characteristic. Whole exome sequencing followed by direct Sanger sequence revealed mutations in OSGEP (R247Q), WT1 (R366H and R467Q), LAMB2 (Q1209∗ and c. 5432–5451 19 bp deletion), NUP93 (D302V), and LAGE3 (c.188+1G > A). Three of the variants were novel. Corticosteroids and/or immunosuppressants were administered in 2 patients, but both were refractory to treatment. During the mean 3.5 years of follow-up, all but two died of uremia and sepsis. The two survivors reached end-stage kidney disease and required peritoneal dialysis, and one of them underwent uneventful renal transplantation. The majority of patients with CNS in Taiwan were caused by OSGEP followed by WT1 mutation. R247Q is the hotspot mutation of OSGEP in Taiwan. CNS patients in Taiwan suffer from significant morbidity and mortality. [ABSTRACT FROM AUTHOR]

The incidence of ischemic stroke (IS) is higher in nephrotic syndrome (NS) patients compared to general population. However, there is limited information on the specific characteristics to stroke patients with NS. In this study, we aimed to examine the clinical manifestations of acute IS in a large group of NS patients, comparing to those without NS. We conducted a retrospective cohort study to compare the clinical presentations of acute IS in patients with and without NS. This study was a multi-institutional study and used data from Chang Gung Research Database of Taiwan from 1 January 2001, to 31 December 2017. A total of 233 IS patients with NS and 1358 IS patients without NS were enrolled. The median age of participants was 68 (range: 59-79) years. The risk of dependent functional status (modified Rankin Scale score≤3) after IS was higher in NS patients compared to those without NS (Odd ratio (OR) 4.02, 95% confidence interval (CI) 2.39 to 6.76, p < 0.001), particularly in stroke subtypes as small-artery occlusion (OR 8.02, 95% CI 3.94 to 16.32, p < 0.001), and stroke of undetermined etiology (OR 2.47, CI 1.06 to 5.76, p = 037). The risks of mortality or stroke recurrence within 30 days were similar between the two groups for all stroke subtypes. In conclusion, NS was associated with a higher risk of functional dependence following IS. Intensive treatment and rehabilitation should be considered for IS patients with NS. [ABSTRACT FROM AUTHOR]

Background: While an increased incidence of intracerebral hemorrhage (ICH) has been reported in patients with nephrotic syndrome (NS), comprehensive understanding of the characteristics of ICH in this population remains elusive. This study explored the clinical features of ICH in a larger cohort of NS patients., Methods: To compare the clinical characteristics of ICH in patients with and without NS, we conducted a multi-institutional retrospective cohort study using the data from Chang Gung Research Database of Taiwan from January 1, 2001, to December 31, 2017., Results: This study enrolled a total of 120 ICH patients with NS, and 271 ICH patients without NS. Patients with NS had a longer average length of stay in the acute medicine ward (17.7 ± 15.9 days vs 14.4 ±13.3 days, P = 0.047) and higher incidence of urinary tract infection (20.0% vs 10.0%, P = 0.006), gastrointestinal bleeding (16.7% vs 4.8%, P < 0.001), and pulmonary edema (4.2% vs 0%, P = 0.003) compared to those without ICH. Furthermore, the risk of 30-day dependent outcome (modified Rankin Scale score≧3) was significantly higher in ICH patients with NS compared to those without NS (Odds ratio 3.43, 95% confidence interval 1.49 to 7.91, P = 0.004). However, the 30-day mortality rate was similar between the NS patients and the control group., Conclusions: NS is associated with a significantly increased risk of functional dependence following ICH, highlighting the critical need for tailored intensive treatment and rehabilitation specifically for this patient population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: To date, there is insufficient knowledge about the association of air pollution and childhood nephrotic syndrome in the real world. This study aimed to evaluate the effects of the three common gaseous air pollutants, including sulfur dioxide, total hydrocarbon, and methane, on the risk of idiopathic nephrotic syndrome (INS) in children. Methods: We collected data from the Taiwan National Health Insurance Research Database and Taiwan Air Quality-Monitoring Database. Children younger than 18 years old, identified from January 1, 2000, were followed up until the first diagnosis of INS was established or until December 31, 2012. We measured the incidence rates and hazard ratios for INS stratified based on the quartiles (Q1–Q4) of air pollutant concentration. Multivariate Cox proportional hazards models were also applied by adjusting age, sex, monthly income, and urbanization. Results: Compared with participants exposed to Q1 concentrations, the adjusted hazard ratios (aHRs) for INS increased progressively along the four quartiles of sulfur dioxide, total hydrocarbon, and methane, from 1 (Q1) to 1.78 (Q4), 1 (Q1) to 3.49 (Q4), 1 (Q1) to 7.83 (Q4), respectively. Conclusions: Our study revealed that children with exposure to higher concentrations of sulfur dioxide, total hydrocarbon, and methane was associated with an increased risk of INS. [ABSTRACT FROM AUTHOR]

Background: The incidence of cerebral stroke, including ischemic infarction and intracranial hemorrhage (ICH), increases in patients with nephrotic syndrome (NS). However, the clinical characteristics of patients with NS and stroke remain elusive. We aimed to investigate the clinical presentation and prognosis among patients with NS and ischemic stroke (IS) or ICH.Methods: We conducted a population-based retrospective cohort study of patients with NS and acute stroke using the Chang Gung Research Database of Taiwan from January 1, 2001, to December 31, 2017. The participants were recruited from the 7 branches of Chang Gung Memorial Hospital.Results: A total of 233 patients with IS and 57 patients with ICH were enrolled. The median age was 60 (52-70) years. The prevalence rates of hyperlipidemia, hyperuricemia, and smoking were higher in IS than in ICH. IS demonstrated lower white blood cell count (7.80 vs. 8.92 × 109/L) and high-sensitivity C-reactive protein level (33.42 vs. 144.10 nmol/L) and higher cholesterol (5.74 vs. 4.84 mmol/L), triglyceride (1.60 vs. 1.28 mmol/L), and albumin (24 vs. 18 g/L) levels compared with ICH. The dependent functional status and 30-day mortality were higher in ICH than in IS. The risk factors for 30-day mortality for patients with NS and stroke were coronary artery disease (CAD), ICH, and total anterior circulation syndrome. The multivariate Cox regression analysis revealed that CAD was positively associated with 30-day mortality in patients with IS (hazard ratio 24.58, 95 % CI 1.48 to 408.90). In patients with ICH, CAD and subarachnoid hemorrhage were positively associated with 30-day mortality (hazard ratio 5.49, 95 % CI 1.54 to 19.56; hazard ratio 6.32, 95 % CI 1.57 to 25.53, respectively).Conclusions: ICH demonstrated a higher risk of dependence and 30-day mortality compared with IS in patients with NS. Intensive monitoring and treatment should be applied particularly in patients with NS and ICH. [ABSTRACT FROM AUTHOR]

The incidence of ischemic stroke (IS) is higher in nephrotic syndrome (NS) patients compared to general population. However, there is limited information on the specific characteristics to stroke patients with NS. In this study, we aimed to examine the clinical manifestations of acute IS in a large group of NS patients, comparing to those without NS. We conducted a retrospective cohort study to compare the clinical presentations of acute IS in patients with and without NS. This study was a multi-institutional study and used data from Chang Gung Research Database of Taiwan from 1 January 2001, to 31 December 2017. A total of 233 IS patients with NS and 1358 IS patients without NS were enrolled. The median age of participants was 68 (range: 59-79) years. The risk of dependent functional status (modified Rankin Scale score≧3) after IS was higher in NS patients compared to those without NS (Odd ratio (OR) 4.02, 95% confidence interval (CI) 2.39 to 6.76, p  < 0.001), particularly in stroke subtypes as small-artery occlusion (OR 8.02, 95% CI 3.94 to 16.32, p  < 0.001), and stroke of undetermined etiology (OR 2.47, CI 1.06 to 5.76, p  = 037). The risks of mortality or stroke recurrence within 30 days were similar between the two groups for all stroke subtypes. In conclusion, NS was associated with a higher risk of functional dependence following IS. Intensive treatment and rehabilitation should be considered for IS patients with NS.

Background: Clinical and immunological studies have consistently shown a relationship between atopic diathesis and idiopathic nephrotic syndrome (INS). However, no large population cohort study has yet to demonstrate the nature of the relationship between these disorders. Methods: Claims data from a random selection of children representing half of the insured population in Taiwan were examined. During the period from 1998 to 2007, we identified 192,295 children aged <18 years with newly diagnosed atopic dermatitis (AD) and 769,169 frequency-matched controls. Incidence of INS and hazard ratios (HRs) were calculated. Results: The AD cohort had a 2-fold higher overall incidence of INS than the non-AD cohort [7.20 vs. 3.60 per 100,000 person-years, respectively; 95 % confidence interval (CI) 1.50-2.66]. The HR for INS increased with age and was higher among females. The HR for INS was also higher in AD children with more medical visits per year, ranging from 0.94 for those having ≤3 visits to 38.6 for those having >6 visits (trend test P < 0.0001). In particular, the risk of INS clearly increased during the initial 5 years after AD onset. Conclusions: Children with AD have a greater incidence and risk of developing INS and this risk increases with AD severity. [ABSTRACT FROM AUTHOR]

ABSTRACT: Aim: The present study was conducted to investigate the trends of childhood nephrotic syndrome (NS) admissions and factors associated with childhood NS admissions with major infections in Taiwan. Methods: A retrospective analysis was performed using Taiwan National Health Research Insurance Database (NHIRD) to explore the associated factors and health care burden for childhood NS admissions with major infections in 1997 to 2007. Results: Of 133 927 children, a total of 176 children had NS, which incurred 508 hospital admissions. Nineteen percent of admissions were associated with major infections. Pneumonia was the most common infection (49%), followed by urinary tract infection (UTI), bacteraemia/sepsis, peritonitis and cellulitis. Pneumonia was the most common infection among children age younger than 10 years, whereas UTI was more common among children aged greater than 10 years. NS admission with infections had longer periods of hospital length of stay and higher hospital total costs compared to those without infections. Regression analysis reveals that younger age, regional hospitals, admission hospital located in middle and south areas and admission made in spring were associated with increased risk for developing major infections. Conclusions: While 19% of childhood NS admissions were associated with major infections, young age, admissions made in spring, located in middle and south Taiwan and in regional hospitals were the major associated factors for infection. Age plays an important role in risk and types of infection. [ABSTRACT FROM AUTHOR]

Abstract: Background: Membranous glomerulonephritis (MGN) is one of the most common causes of nephrotic syndrome in adults. NPHS1 encoding nephrin is a transmembrane protein of the immunoglobulin family. We clarified the relationship between NPHS1 gene polymorphisms and the susceptibility or progression of MGN. Methods: We recruited a cohort of 132 biopsy-diagnosed MGN patients and 257 healthy subjects. Genotyping of three SNPs (rs401824, rs437168 and rs3814995) at chromosome positions 41034749 (5′UTR), 41026259(exon17) and 41034052 (exon 3) was performed using a Taqman SNP genotyping assay. Results: There was a significant difference in genotype frequency distribution of rs437168 polymorphism between MGN patients and controls. The results also showed that the frequency of the G allele was significantly higher in the patient group. Among the polymorphisms rs437168, rs401824 and rs3814995, no significant haplotype was shown in MGN patients. A stratified analysis revealed that a high disease progression in the AA genotype of rs401824 and GG genotype of rs437168 patients were associated with a low rate of remission. Conclusions: The presence of the different genotypes of NPHS1 was associated with susceptibility of MGN and the remission of proteinuria during disease progression after the therapy. [Copyright &y& Elsevier]

Ethnicity and age play important roles in the epidemiology of idiopathic nephrotic syndrome (INS) in children. The purposes of this study were to compare the clinical features, renal histopathology, steroid response, and long-term prognosis in Chinese children between different age groups. This is a retrospective cohort study of children aged between 2 and 18 years old with INS. Patients were divided into two groups according to age. Group I consisted of children between 2 and 8 years old (n = 49). Group II consisted of the remaining patients (n = 50). The clinical biochemical parameters, response to steroid treatment, renal histology, and long-term outcomes were analyzed. The biochemical parameters at the onset were similar in the two groups. Group II had a significantly higher frequency of microscopic hematuria (P = 0.011). Of the 67 children biopsied, minimal change disease was the most common histopathology for both groups. There was a higher frequency with focal and segmental glomerulosclerosis in group II (24% vs. 6.1%), but the difference between the two groups was not significant. During follow-up, the frequency of hypertension was significantly higher in group II (P = 0.006). Two cases in group I developed chronic kidney disease (CKD) vs. eight cases in group II. The frequency of progression to CKD is significantly higher (P = 0.042) in Group II. In conclusion, children beyond 8 years of age with INS have a higher incidence of microscopic hematuria, higher risk of hypertension and progression to CKD in long-term follow-up. [ABSTRACT FROM AUTHOR]

Background: Nephrotic syndrome (NS) is characterized by various etiologies that damage the glomerulus. Central serous chorioretinopathy (CSCR) is a retinal disease characterized by neurosensory detachment of the retina. Several case reports have described the relationship between both. Therefore, we try to analyze the epidemiological associations between NS and CSCR using the National Health Insurance Research Database in Taiwan., Methods: Data spanning 14 years were extracted from the National Health Insurance Research Database and sub-grouped. The variables were analyzed using Pearson's chi-squared test and Fisher's exact test. The risk factors for disease development with or without comorbidities were examined using an adjusted hazard ratio (aHR). Kaplan-Meier analysis was performed to evaluate the cumulative incidence of CSCR with or without NS., Results: A total of 14 794 patients with NS and 14 794 matched controls without NS were enrolled in this cohort study. The incidence rate of CSCR was higher in the study cohort than in the control cohort (aHR = 3.349, p < 0.001). The overall incidence of CSCR was 44.51 per 100 000 person-years in the study cohort and 33.39 per 100 000 person-years in the control cohort. In both groups, CSCR occurred more frequently in males than in females. Patients aged 40-49, 50-59, and ≥60 years in the study cohort had a significantly higher risk of developing CSCR than those in the control cohort (aHR = 3.445, 5.421, and 4.957, all p < 0.001). NS patient with a 4-week history of steroid usage has a higher risk of developing CSCR (aHR = 2.010, p < 0.001)., Conclusion: Our data showed that patients with NS have an increased risk of developing subsequent CSCR. Physician should routinely refer their NS patients to ophthalmologist for ophthalmic evaluation. This is the first nationwide epidemiological study reporting the association between these two diseases. Further studies are needed to clarify this relationship., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2021, the Chinese Medical Association.)

Background: To determine if the nephrotic syndrome (NS) is an independent risk factor of ischemic stroke., Methods: This is a retrospective nationwide cohort study through an analysis of the National Health Insurance Research Database in Taiwan. To evaluate the risk of stroke, the corresponding controls were selected at a 4:1 ratio in the number of subjects, and they were matched with the study group in age, gender, Charlson comorbidity index (CCI), and index date., Results: From a total of 16,245 surveyed subjects, ischemic stroke occurred in 1235 (7.6%) and hemorrhagic stroke in 129 (.74%) of them. The incidence of ischemic stroke was significantly higher in patients with NS (n = 3496) compared to control patients without NS (n = 13,984) (9.92 versus 7.10, per 1000 person-year, P < .001). In the multivariate analysis, the overall adjusted hazard ratio (aHR) of stroke in NS patients was 1.37 (95% CI, 1.21-1.54, P < .001). The risk factors of ischemic stroke were NS (aHR, 1.38 [95% confidence interval {CI}, 1.21-1.57]; P < .001), age greater than 45 years (aHR, 7.98 [95% CI, 6.47-9.48]; P < .001), male gender (aHR, 1.23 [95% CI, 1.10-1.38]; P < .001), CCI greater than or equal to 1 (aHR ≥ 1.25 in different CCI score groups, all at P ≤ .003), ischemic heart disease (aHR, 1.95 [95% CI, 1.67-2.29]; P < .001), heart failure (HR, 1.77 [95% CI, 1.30-2.42]; P < .001). Risk factors of hemorrhagic stroke were those aged greater than 45 years, or with systemic lupus erythematosus, but not NS., Conclusions: We provided the first evidence that patients with NS had an increased risk of ischemic stroke., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Galloway-Mowat syndrome (GAMOS) is a rare autosomal recessive disease characterized by the combination of glomerulopathy with early-onset nephrotic syndrome and microcephaly with central nervous system anomalies. Given its clinical heterogeneity, GAMOS is believed to be a genetically heterogenous group of disorders. Recently, it has been reported that mutations in KEOPS-encoding genes, including the OSGEP gene, were responsible for GAMOS.Results: Overall, 6 patients from 5 different Taiwanese families were included in our study; the patients had an identical OSGEP gene mutation (c.740G > A transition) and all exhibited a uniform clinical phenotype with early-onset nephrotic syndrome, craniofacial and skeletal dysmorphism, primary microcephaly with pachygyria, and death before 2 years of age. We reviewed their clinical manifestations, the prenatal and postnatal presentations and ultrasound findings, results of imaging studies, associated anomalies, and outcome on follow-up. All individuals were found to have an "aged face" comprising peculiar facial dysmorphisms. Arachnodactyly or camptodactyly were noted in all patients. Neurological findings consisted of microcephaly, hypotonia, developmental delay, and seizures. Brain imaging studies all showed pachygyria and hypomyelination. All patients developed early-onset nephrotic syndrome. The proteinuria was steroid-resistant and eventually resulted in renal function impairment. Prenatal ultrasound findings included microcephaly, intrauterine growth restriction, and oligohydramnios. Fetal MRI in 2 patients confirmed the gyral and myelin abnormalities.Conclusions: Our study suggests that a careful review of the facial features can provide useful clues for an early and accurate diagnosis. Prenatal ultrasound findings, fetal MRI, genetic counseling, and mutation analysis may be useful for an early prenatal diagnosis. [ABSTRACT FROM AUTHOR]

Background: Galloway-Mowat syndrome (GAMOS) is a rare autosomal recessive disease characterized by the combination of glomerulopathy with early-onset nephrotic syndrome and microcephaly with central nervous system anomalies. Given its clinical heterogeneity, GAMOS is believed to be a genetically heterogenous group of disorders. Recently, it has been reported that mutations in KEOPS-encoding genes, including the OSGEP gene, were responsible for GAMOS., Results: Overall, 6 patients from 5 different Taiwanese families were included in our study; the patients had an identical OSGEP gene mutation (c.740G > A transition) and all exhibited a uniform clinical phenotype with early-onset nephrotic syndrome, craniofacial and skeletal dysmorphism, primary microcephaly with pachygyria, and death before 2 years of age. We reviewed their clinical manifestations, the prenatal and postnatal presentations and ultrasound findings, results of imaging studies, associated anomalies, and outcome on follow-up. All individuals were found to have an "aged face" comprising peculiar facial dysmorphisms. Arachnodactyly or camptodactyly were noted in all patients. Neurological findings consisted of microcephaly, hypotonia, developmental delay, and seizures. Brain imaging studies all showed pachygyria and hypomyelination. All patients developed early-onset nephrotic syndrome. The proteinuria was steroid-resistant and eventually resulted in renal function impairment. Prenatal ultrasound findings included microcephaly, intrauterine growth restriction, and oligohydramnios. Fetal MRI in 2 patients confirmed the gyral and myelin abnormalities., Conclusions: Our study suggests that a careful review of the facial features can provide useful clues for an early and accurate diagnosis. Prenatal ultrasound findings, fetal MRI, genetic counseling, and mutation analysis may be useful for an early prenatal diagnosis.

Background : Air pollution has been associated with autoimmune diseases. Nephrotic syndrome is a clinical manifestation of immune-mediated glomerulopathy. However, the association between nephrotic syndrome and air pollution constituents remains unknown. We conducted this nationwide retrospective study to investigate the association between PM 2.5 and nephrotic syndrome. Methods : We used the Longitudinal Health Insurance Database (LHID) and the Taiwan Air Quality-Monitoring Database (TAQMD). We combined and stratified the LHID and the TAQMD data by residential areas of insurants linked to nearby air quality-monitoring stations. Air pollutant concentrations were grouped into four levels based on quartile. Univariable and multivariable Cox proportional hazard regression models were applied. Findings : Relative to Q1-level SO₂, subjects exposed to the Q4 level were associated with a 2.00-fold higher risk of nephrotic syndrome (adjusted HR = 2.00, 95% CI = 1.66⁻2.41). In NOx, relative to Q1 NOx concentrations, the adjusted HRs of nephrotic syndrome risk were 1.53 (95% CI = 1.23⁻1.91), 1.30 (95% CI = 1.03⁻1.65), and 2.08 (95% CI = 1.69⁻2.56) for Q2, Q3, and Q4 levels, respectively. The results revealed an increasing trend for nephrotic syndrome risk correlating with increasing levels of NO, NO₂, and PM 2.5 concentrations. Interpretation : High concentrations of PM 2.5 , NO, NO₂, and SO₂ are associated with increased risk of nephrotic syndrome.

Objectives: Previous research has shown that patients with nephrotic syndrome (NS) have a higher risk of cognitive impairment, dementia or neurodegenerative disorder. The present study aimed to examine a relationship, if any exists between NS and Parkinson's disease (PD), a neurodegenerative disorder and secondary parkinsonism (sPS)., Methods: A nationwide retrospective observational study conducted using data from the 2000-2010 Taiwan National Health Insurance Research Database. This study included 3663 patients with NS and 14 652 randomly selected, age-matched and sex-matched patients without NS. A Cox multivariable proportional hazards model was used to evaluate the risk of PD and sPS (PDsPS) in the NS cohort., Results: This study identified a positive association between NS and the risk of PDsPS in both men and women and in all age groups (adjusted HR 1.51; 95% CI 1.37 to 1.66). Compared with patients without NS and comorbidities, those with NS with two or more comorbidities exhibited an 8.23-fold higher risk of PDsPS (95% CI 6.22 to 10.9) and patients with NS and one comorbidity exhibited a 2.93-fold higher risk of PDsPS (95% CI 2.37 to 3.63)., Conclusions: Patients with NS have an increased risk of PDsPS. This increased risk may be related to brain vascular damage or blood-brain barrier impairment. Further research is necessary to explore the underlying relationship between NS and PDsPS., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)