Risk factors for renal scarring and deterioration of renal function in primary vesico-ureteral reflux children: a long-term follow-up retrospective cohort study.

BACKGROUND AND PURPOSE: The aim was to identify the risk factors for renal scarring and deteriorating renal function in children with primary vesico-ureteral reflux (VUR). MATERIALS AND METHODS: Patients with primary VUR admitted to the National Cheng Kung University Hospital were retrospectively analyzed. The outcomes were renal scarring, assessed by technetium-99 m dimercaptosuccinic acid scanning, and renal function, assessed by estimated glomerular filtration rate. Univariate and multivariate models were applied to identify the corresponding independent predictors. RESULTS: A total of 173 patients with primary VUR were recruited. The median age of VUR diagnosis was 10.0 months (IQR: 4.0-43.0 months). After adjusting for confounding factors, it was found that older age of VUR diagnosis (≥5 years vs. <1 year, adjusted OR = 2.78, 95% CI = 1.00-7.70, p = 0.049), higher grade of VUR (high grade [IV-V] vs. none, adjusted OR = 15.17, 95% CI = 5.33-43.19, p<0.0001; low grade [I-III] vs. none, adjusted OR = 5.72, 95% CI = 2.43-13.45, p<0.0001), and higher number of UTI (≥2 vs. 0, adjusted OR = 3.21, 95% CI = 1.06-9.76, p = 0.039) were risk factors for renal scarring, whereas a younger age of VUR diagnosis (≥5 years vs. <1 year, adjusted HR = 0.16, 95% CI: 0.05-0.51, p = 0.002), renal scarring (yes vs. no, adjusted HR = 3.66, 95% CI: 1.32-10.16, p = 0.013), and APN (yes vs. no, adjusted HR = 3.10, 95% CI: 1.05-9.14, p = 0.041) were risk factors for developing chronic kidney disease stage 2 or higher. CONCLUSIONS: Our findings expand on the current knowledge of risk factors for renal scarring and deteriorating renal function, and this information can be used to modify the management and treatment of VUR

Kaplan-Meier survival curves for the development of renal failure (i.e. chronic kidney disease [CKD] stage 2 or higher) according to the grade and location (i.e. unilateral vs. bilateral) of primary vesico-ureteral reflux (VUR) (log-rank test, P = 0.055).

<p>Kaplan-Meier survival curves for the development of renal failure (i.e. chronic kidney disease [CKD] stage 2 or higher) according to the grade and location (i.e. unilateral vs. bilateral) of primary vesico-ureteral reflux (VUR) (log-rank test, P  = 0.055).</p

Etiology and pediatric chronic kidney disease progression: Taiwan Pediatric Renal Collaborative Study

This study aims to examine the characteristics of Taiwanese children with chronic kidney disease (CKD) and delineate the factors that lead to disease progression in this population. Methods: We reviewed the records of the Taiwan Pediatric Renal Collaborative Study, a multicenter database of Taiwanese children with CKD. Multivariate regression analysis was used to identify the main factors associated with disease progression. Results: A total of 382 children aged 1–18 years were included in the study (median age was 10.6 years; interquartile range: 6.4–13.8). There were 197 males (51.6%) and 185 females. CKD Stage 1 was diagnosed in 159 children (41.6%), Stage 2 in 160 (41.9%), Stage 3 in 51 (13.4%), and Stage 4 in 12 (3.1%). Fifty-six children (14.7%) experienced CKD progression. A multivariate analysis for all patients indicated that the risk for disease progression was increased in children with CKD secondary to a structural abnormality, genetic disease, anemia, elevated diastolic blood pressure, or elevated blood urea nitrogen. Compared with children with Stage 1 CKD, those with Stage 2 and Stage 4 CKD had decreased risk for CKD progression in this short-term cohort follow-up. Conclusion: CKD etiology affects disease progression. Careful monitoring and treatment of anemia and elevated blood pressure in children with CKD may slow disease progression

Mortality Risks among Various Primary Renal Diseases in Children and Adolescents on Chronic Dialysis

There is little information available on the association between primary renal disease (PRD) and long-term mortality in the pediatric dialysis population. The objective of this study was to explore mortality risks in children and adolescents on chronic dialysis, specifically focused on the risk of various PRDs. The study cohort included children and adolescents with end-stage renal disease (ESRD) (aged &lt; 20 years) who had received dialysis for at least 90 days between 2000 and 2014 and were identified from Taiwan&#8217;s National Health Insurance medical claims. A total of 530 children and adolescents were included in the study. The median age of the included patients was 13.6 years and 305 (57.5%) patients were males. One hundred and seven patients died during the follow-up period and the median survival time was 6.0 years. Mortality was highest in the youngest patients. For patients with the following PRDs, mortality was significantly higher than that in patients with primary glomerulonephritis: secondary glomerulonephritis (adjusted hazard ratio (aHR): 2.50; 95% confidence interval (CI): 1.03&#8315;6.08), urologic disorder (aHR: 4.77; 95% CI: 1.69&#8315;13.46), and metabolic diseases (aHR: 5.57; 95% CI: 1.84&#8315;16.85). Several kinds of PRDs appear to have high mortality risks in the pediatric dialysis population. These differences in mortality risk highlight the importance of the focused clinical management of these high-risk subgroups

Functional impact of ABCB1 variants on interactions between P-glycoprotein and methadone.

Methadone is a widely used substitution therapy for opioid addiction. Large inter-individual variability has been observed in methadone maintenance dosages and P-glycoprotein (P-gp) was considered to be one of the major contributors. To investigate the mechanism of P-gp's interaction with methadone, as well as the effect of genetic variants on the interaction, Flp-In™-293 cells stably transfected with various genotypes of human P-gp were established in the present study. The RNA and protein expression levels of human P-gp were confirmed by real-time quantitative RT-PCR and western blot, respectively. Utilizing rhodamine 123 efflux assay and calcein-AM uptake study, methadone was demonstrated to be an inhibitor of wild-type human P-gp via non-competitive kinetic (IC50 = 2.17±0.10 µM), while the variant-type human P-gp, P-gp with 1236T-2677T-3435T genotype and P-gp with 1236T-2677A-3435T genotype, showed less inhibition potency (IC50 = 2.97±0.09 µM and 4.43±1.10 µM, respectively) via uncompetitive kinetics. Methadone also stimulated P-gp ATPase and inhibited verapamil-stimulated P-gp ATPase activity under therapeutic concentrations. These results may provide a possible explanation for higher methadone dosage requirements in patients carrying variant-type of P-gp and revealed the possible drug-drug interactions in patients who receive concomitant drugs which are also P-gp substrates

Secreted Neutrophil Gelatinase-Associated Lipocalin Shows Stronger Ability to Inhibit Cyst Enlargement of ADPKD Cells Compared with Nonsecreted Form

Polycystic kidney disease (PKD) is one of the most common inherited diseases and is characterized by the development of fluid-filled cysts along multiple segments of the nephron. Autosomal dominant polycystic kidney disease (ADPKD) is the most common form of PKD, which is caused by mutations in either PKD1 or PKD2 genes that encode polycystin-1 (PC1) and polycystin-2 (PC2), respectively. As ADPKD progresses, cysts enlarge and disrupt normal kidney architecture, eventually leading to kidney failure. Our previous study showed that overexpression of exogenous kidney-specific neutrophil gelatinase-associated lipocalin (NGAL) reduced cyst progression and prolonged the lifespan of ADPKD mice (Pkd1L3/L3, 2L3 for short). In this study, we attempted to explore the underlying mechanism of reduced cyst progression in the presence of NGAL using immortalized 2L3 cells. The results of MTT and BrdU incorporation assays showed that recombinant mouse NGAL (mNGAL) protein significantly decreased the viability and proliferation of 2L3 cells. Flow cytometry and western blot analyses showed that mNGAL inhibited activation of the ERK and AKT pathways and induced apoptosis and autophagy in 2L3 cells. In addition, a 3D cell culture platform was established to identify cyst progression in 2L3 cells and showed that mNGAL significantly inhibited cyst enlargement in 2L3 cells. Overexpression of secreted mNGAL (pN + LS) and nonsecreted mNGAL (pN &minus; LS) repressed cell proliferation and cyst enlargement in 2L3 cells and had effects on markers involved in proliferation, apoptosis, and autophagy. However, secreted mNGAL had a more pronounced and consistent effect than that of nonsecreted form. These results reveal that secreted mNGAL has stronger ability to inhibit cyst enlargement of ADPKD cells than that of nonsecreted form. These findings could help to identify strategies for the future clinical treatment of ADPKD