Case Report: A Novel In-Frame Deletion of GLIS2 Leading to Nephronophthisis and Early Onset Kidney Failure

Variants in the GLIS family zinc finger protein 2 (GLIS2) are a rare cause of nephronophthisis-related ciliopathies (NPHP-RC). A reduction in urinary concentration and a progressive chronic tubulointerstitial nephropathy with corticomedullary cysts are the major characteristic features of NPHP. NPHP demonstrates phenotypic and genetic heterogeneity with at least 25 different recessive genes associated with the disease. We report a female, from a consanguineous family, who presented age 9 years with echogenic kidneys with loss of cortico-medullary differentiation and progressive chronic kidney disease reaching kidney failure by 10 years of age. A novel homozygous in-frame deletion (NM_032,575.3: c.560_574delACCATGTCAACGATT, p.H188_Y192del) in GLIS2 was identified using whole exome sequencing (WES) that segregated from each parent. The five amino acid deletion disrupts the alpha-helix of GLIS2 zinc-finger motif with predicted misfolding of the protein leading to its predicted pathogenicity. This study broadens the variant spectrum of GLIS2 variants leading to NPHP-RC. WES is a suitable molecular tool for children with kidney failure suggestive of NPHP-RC and should be part of routine diagnostics in kidney failure of unknown cause, especially in consanguineous families.

Urinary concentrations of neonicotinoid insecticides were related to renal tubular dysfunction and neuropsychological complaints in Dry-zone of Sri Lanka

Neonicotinoids are systemic insecticides used since the 1990’s , that possess renal tubular toxicity. We conducted a field-based descriptive study in the North Central Dry-zone of Sri Lanka, where chronic kidney disease (CKD) of unknown etiology has been increasing since the 1990’s. To elucidate the relationship between renal tubular dysfunctions and urinary neonicotinoids concentrations, we collected spot urine samples from15 CKD patients, 15 family members, and 62 neighbors in 2015, analyzed two renal tubular biomarkers, Cystatin-C and L-FABP, quantified seven neonicotinoids and a metabolite N-desmethyl-acetamiprid by LC–MS/MS; and we investigated their symptoms using a questionnaire. Cystatin-C and L-FABP had a positive correlation (p < 0.001). N-Desmethyl-acetamiprid was detected in 92.4% of the urine samples, followed by dinotefuran (17.4%), thiamethoxam (17.4%), clothianidin (9.8%), thiacloprid and imidacloprid. Dinotefuran and thiacloprid have never been registered in Sri Lanka. In High Cystatin-C group (> 70 μg/gCre, n = 7), higher urinary concentration of dinotefuran (p = 0.009), and in Zero Cystatin-C group (< LOQ, n = 7), higher N-desmethyl-acetamiprid (p = 0.013), dinotefuran (p = 0.049), and thiacloprid (p = 0.035), and more complaints of chest pains, stomachache, skin eruption and diarrhea (p < 0.05) were found than in Normal Cystatin-C group (n = 78). Urinary neonicotinoids may be one of the potential risk factors for renal tubular dysfunction in this area.

High Iodine Urinary Concentration Is Associated with High TSH Levels but Not with Nutrition Status in Schoolchildren of Northeastern Mexico

According to the Iodine Global Network, Mexico is considered a country with adequate national iodine intake (297 mg/L), but some regions have not been studied. We aimed to evaluate urinary iodine concentration (UIC) and its association with thyroid stimulating hormone (TSH) levels and the nutritional status in 307 children (aged 5 to 11 years) from three elementary schools of Monterrey, northern Mexico. UIC in spot urine samples and capillary TSH levels were measured to assess thyroid function, in addition to weight, height, body mass index (BMI), and waist circumference (WC). We found a median UIC of 442 mg/L and a significant association between UIC and TSH levels by logistic regression when data were adjusted for (1) age and sex; (2) age, sex, and WC; and (3) age, sex, and weight status. UIC values were higher in 7-year-old children compared to 11-year-old children. High prevalences of overweight/obesity (41%) and WC >90 pctl (22%) were observed. This study identified higher UIC levels in children than those previously reported in the country. The UIC showed a positive and significant correlation between TSH levels in the three models evaluated. More studies are needed to assess the causes and possible outcomes of high UIC levels.

Urinary estrogen metabolites and breast cancer risk in Chinese population

Background: In China, the association between estrogen metabolism and breast cancer risk and the differences in metabolic pattern between breast cancer patients and controls are poorly understood. Methods: A total of 84 patients with invasive breast cancer and 47 controls with benign breast diseases were included in this study. Estrogen metabolites from their morning urine were determined by HPLC-MS/MS and evaluated in both groups, and the predictive value of each estrogen metabolite in the malignant group according to their menstrual status was analyzed. Results: Urinary concentration of estrogen metabolites 2-OHE1, 2-OHE2, 4-OHE2, 4-MeOE1, and 16ɑ-OHE1 were lower in postmenopausal patients with breast cancer, compared with benign controls, In logistic regression model, breast cancer risk increased with the decline in the levels of 4-OHE2 and 4-MeOE1. In premenopausal patients,, a difference in the level of 2-OHE2 was observed between both groups, and 2-OHE2 was found to have predictive value for breast cancer. Additionally, urinary 2-OHE2 level in premenopausal HR+ patients was considerably higher compared with HR- patients. Conclusions: We found that lower urinary levels of 4-OHE2 and 4-MeOE1had predictive value for breast cancer, and higher 2-OHE1 were associated with HR+ breast cancer in premenopausal women.

Urinary Metabolomic Profile of Neonates Born to Women with Gestational Diabetes Mellitus

Gestational diabetes mellitus (GDM) is one of the most frequent pregnancy complications with potential adverse outcomes for mothers and newborns. Its effects on the newborn appear during the neonatal period or early childhood. Therefore, an early diagnosis is crucial to prevent the development of chronic diseases later in adult life. In this study, the urinary metabolome of babies born to GDM mothers was characterized. In total, 144 neonatal and maternal (second and third trimesters of pregnancy) urinary samples were analyzed using targeted metabolomics, combining liquid chromatographic mass spectrometry (LC-MS/MS) and flow injection analysis mass spectrometry (FIA-MS/MS) techniques. We provide here the neonatal urinary concentration values of 101 metabolites for 26 newborns born to GDM mothers and 22 newborns born to healthy mothers. The univariate analysis of these metabolites revealed statistical differences in 11 metabolites. Multivariate analyses revealed a differential metabolic profile in newborns of GDM mothers characterized by dysregulation of acylcarnitines, amino acids, and polyamine metabolism. Levels of hexadecenoylcarnitine (C16:1) and spermine were also higher in newborns of GDM mothers. The maternal urinary metabolome revealed significant differences in butyric, isobutyric, and uric acid in the second and third trimesters of pregnancy. These metabolic alterations point to the impact of GDM in the neonatal period.

Serologic and urinary characteristics of laboratory-confirmed genitourinary tuberculosis at a tertiary hospital in the Philippines

Background Genitourinary tuberculosis (GUTB) is known to cause high rates of structural organ damage, however, literature on its biochemical manifestations is limited. Additionally, local studies in the Philippine setting, where cases are rampant, are few and dated. This study aimed to determine the serologic and urinary profile of patients with GUTB admitted at a tertiary hospital within January 2009 to March 2020 and their association with short-term outcomes. Methods This retrospective study included 112 patients with laboratory-confirmed GUTB (i.e., positivity in acid-fast smear, polymerase chain reaction, culture, or histology). Demographic data, clinical characteristics, laboratory and radiologic findings, histopathology reports, treatment, and short-term outcomes were recorded. Results Bladder (54.5%) and kidney (36.4%) were the most affected organs. The male:female ratio was 1:1.15, and the mean age was 35.79 ± 18.29 years. Weakness (14.29%) was the most common chief complaint. A majority presented with anemia (83.04%), while several had leukocytosis (41.96%) and thrombocytosis (26.79%). Hypoalbuminemia (58.10%), impairment of renal function (36.94%), and electrolyte abnormalities such as hyponatremia (50.93%), hypercalcemia (20.19%), and hypokalemia (21.82%) were common. Proteinuria (67.96%) and pyuria (67.96%) were the most frequent abnormal findings, followed by hematuria (51.46%), acidic urine (45.63%) and low specific gravity (31.07%). Age, leukocytosis, and the need for pressors were all significantly associated with mortality (p values of <0.001, 0.010, and <0.001, respectively). Conclusions The young age at presentation with severe clinical and laboratory manifestations may reflect local epidemiology as TB continues to be widespread in the country. Apart from the more commonly cited abnormalities in literature, multiple electrolyte imbalances and urinary concentration defects were also observed in many cases, possibly indicating tubulointerstitial involvement—a complication increasingly mentioned in case reports. As several patient characteristics were found to be associated with the high mortality rates observed in the study, further research is recommended to explore predictive modeling.

Biomonitoring of Bromine-Containing Trihalomethanes in the Pregnant Women: Urinary Levels and Association with Lifestyle Factors

Trihalomethanes containing bromine (Br-THMs) are compounds formed from the reaction of organic and inorganic substances in drinking water with chlorine as a common disinfectant. Epidemiological evidence indicated various outcomes as a result of long-term exposure to these compounds. This study aims to investigate the concentration of urinary Br-THMs in a sample of third-trimester pregnant women and to determine its correlation with lifestyle factors. This cross-sectional study was conducted among 118 pregnant women in Isfahan, Iran. The third-trimester urine Br-THMs including dibromochloromethane (DBCM), bromodichloromethane (BDCM), and broomcorn (TBM) were measured using solid-phase micro-extraction gas chromatography. The distribution of urinary Br-THMs concentration was positively skewed then these variables were subjected to logarithmic transformation. Spearman ranks correlation coefficient, and two independent samples t-test were used to assess the association of urinary Br-THMs concentration with its demographic and lifestyle determinants.The findings showed that the mean (SD) concentrations of DBCM, BDCM, TBM and brominatede THMs were 14.76 (27.17), 10.25 (11.37), 4.96 (3.21) and 30.17 (40.80) ng/L, respectively. In addition, significant inverse correlation was found between the use of water storage tanks and Br-THMs (DBCM, BDCM, TBM and brominatede THMs, P-value = 0.005, 0.019, >0.001 and 0.007 < 0.05, respectively).In this study, among the quantitative and qualitative variables, the use of storage tanks had an inverse correlation with Br-THMs. In addition, the status of urinary concentration of Br-THMs in pregnant women was less than in the other countries in the same area. Improving water quality and using modern methods to eliminate disinfection by-products as well as improving lifestyle patterns are efficient methods to reduce exposure to these contaminants.

Urinary minerals excretion among primary schoolchildren in Dubai—United Arab Emirates

Introduction Urinary excretion of calcium (Ca), magnesium (Mg), phosphorus (P), iodine and fluoride is used to assess their statuses and/or the existence of metabolic abnormalities. In the United Arab Emirates (UAE), the urinary concentration of these minerals among children have not been documented. Materials and methods A cross-sectional study, including 593 subjects (232 boys and 361 girls), was conducted among healthy 6 to 11-year-old Emirati children living in Dubai. Non-fasting morning urine samples and anthropometrical measurements were collected and analyzed. Results were expressed as per mg of creatinine (Cr). Results On average, estimated Cr excretion was 17.88±3.12 mg/kg/d. Mean urinary Ca/Cr, Mg/Cr and P/Cr excretions were 0.08±0.07 mg/mg, 0.09±0.04 mg/mg, and 0.57±0.26 mg/mg respectively. Urinary excretion of Ca, Mg and P were found to decrease as age increased. Urinary excretion and predicted intake of fluoride were lower than 0.05 mg/kg body weight per day. Surprisingly, more than 50% of the children were found to have urinary iodine excretion level above adequate. Conclusion The Emirati schoolchildren had comparable levels of urinary Ca, Mg and P excretion to other countries. The 95% percentile allows the use of the current data as a reference value for the detection of mineral abnormalities. Fluoride excretion implies that Emirati children are at low risk of fluorosis. The level of urinary iodine excretion is slightly higher than recommended and requires close monitoring of the process of salt iodization to avoid the harmful impact of iodine overconsumption.