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Background: Renal scarring is a serious complication in recurrent urinary tract infections (UTIs). Vitamin D deficiency has also been reported to be a risk factor for UTIs although, to date, no association between vitamin D deficiency and renal scarring has yet been identified. In the present study, it was investigated whether vitamin D deficiency may be a risk factor for renal scarring in patients with recurrent UTIs. Methods: The study included patients between the ages of 1 and 18 years who were admitted to the pediatric nephrology department of the center between November 1, 2018 and November 1, 2019 and who were diagnosed with recurrent UTIs. The medical records of the patients were reviewed for the collection of demographic data, vitamin D levels, ultrasonography results and scintigraphic investigations with 99m‐technetium dimercaptosuccinic acid (99mTc‐DMSA). The patients were divided into two groups: those with and without renal scarring, diagnosed via 99mTc‐DMSA. The vitamin D levels and other parameters of the two groups were compared. Results: Vitamin D deficiency (<20 ng/mL) was observed in 73.9% of the patients without renal scarring, and in 94.1% of those with renal scarring (P = 0.015). A logistic regression analysis revealed vitamin D deficiency to be an independent risk factor for renal scarring in patients with recurrent UTIs (OR = 0.796 [0.691–0.917]). Conclusions: Vitamin D deficiency is found to be a risk factor for renal scarring in patients with recurrent UTIs. Vitamin D treatment may contribute to the prevention of renal scarring in patients with recurrent UTI. [ABSTRACT FROM AUTHOR]

Objectives: Functional urinary incontinence is often associated with recurrent urinary tract infection (UTI), vesicoureteral reflux (VUR), and renal scarring. This study aims to evaluate the correlations between urodynamic findings and recurrence of UTI, VUR, and renal scarring in children with functional incontinence. Methods: In this retrospective observational study, data on the presence of VUR, urodynamics and 99Tc‐dimercaptosuccinic acid scintigraphy findings, and episodes of febrile UTI were obtained from patientsʼ records. The patients had at least 3 years of follow‐up. Results: There were significant associations between recurrence of UTI and decreased bladder capacity (hazard ratio: 1.321, P =.028). The receiver operator characteristic curve analysis showed a cutoff value for compliance of 13.25 mL/cmH2O for renal scarring (P =.000). There was a significant association between bladder wall thickening and VUR (odds ratio: 2.311, P =.008). The compliance had a cutoff value of 14.7 mL/cm H2O (P =.023) for severe VUR. The frequency of renal scarring was higher in patients with severe VUR and dysfunctional voiding (P =.001 and P =.041, respectively). The independent risk factors for renal scarring were low compliance, severe VUR, and dysfunctional voiding in children with functional incontinence, but recurrence of febrile UTI was not a risk factor for renal scarring. Decreased bladder capacity was a risk factor for recurrence of febrile UTI. Conclusions: The present study suggests that low compliance, severe VUR, and dysfunctional voiding, but not the recurrence of febrile UTI, are the independent risk factors for renal scarring in children with functional incontinence, and decreased bladder capacity is the risk factor for the recurrence of febrile UTI. [ABSTRACT FROM AUTHOR]

Renal scarring after pyelonephritis is linked to long‐term health risks for hypertension and chronic kidney disease. Androgen exposure increases susceptibility to, and severity of, uropathogenic Escherichia coli (UPEC) pyelonephritis and resultant scarring in both male and female mice, while anti‐androgen therapy is protective against severe urinary tract infection (UTI) in these models. This work employed androgenized female C57BL/6 mice to elucidate the molecular mechanisms of post‐infectious renal fibrosis and to determine how these pathways are altered by the presence of androgens. We found that elevated circulating testosterone levels primed the kidney for fibrosis by increasing local production of TGFβ1 before the initiation of UTI, altering the ratio of transcription factors Smad2 and Smad3 and increasing the presence of mesenchymal stem cell (MSC)‐like cells and Gli1 + activated myofibroblasts, the cells primarily responsible for deposition of scar components. Increased production of TGFβ1 and aberrations in Smad2:Smad3 were maintained throughout the course of infection in the presence of androgen, correlating with renal scarring that was not observed in non‐androgenized female mice. Pharmacologic inhibition of TGFβ1 signaling blunted myofibroblast activation. We conclude that renal fibrosis after pyelonephritis is exacerbated by the presence of androgens and involves activation of the TGFβ1 signaling cascade, leading to increases in cortical populations of MSC‐like cells and the Gli1 + activated myofibroblasts that are responsible for scarring. [ABSTRACT FROM AUTHOR]

Background: Urinary tract infection (UTI) is one of the most common diseases in children, and urinary angiotensinogen (U‐AGT) is a new biomarker gathering attention in many renal diseases. U‐AGT reflects intrarenal renin–angiotensin system (RAS) activity. We conducted a study to measure U‐AGT in children <4 months old with UTI. Methods: All children <4 months old who came to Toshima Hospital with fever between January 2015 and December 2015 were included. Patients were divided into a UTI group and a non‐UTI group, and U‐AGT was measured. Results: Median U‐AGT was higher in patients with UTI compared with patients without UTI: (0.56 ng/dL, range, 0.025–2.753 ng/dL vs 0.13 ng/dL, range, 0.008–1.697 ng/dL, respectively; P < 0.05). Conclusions: U‐AGT is elevated in UTI patients, and RAS activation may contribute to renal injury caused by UTI. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to determine the occurrence of renal cortical scarring and chronic kidney disease (CKD) in children with neurogenic bladder secondary to spina bifida (SB) managed at the Universiti Kebangsaan Malaysia Medical Centre. The secondary objective was to identify the clinical factors associated with these adverse outcomes.Methods: The medical records of 56 children managed from 1997 were available. Socio-demographic and clinical data for SB children managed for a minimum of 2 years (n = 45) were reviewed. This included age at referral, gender, ethnicity, duration of care, type of SB lesion, presence of vesico-ureteric reflux (VUR), symptomatic urinary tract infections, bladder trabeculation, catheterisations and renal function.Results: Forty-nine per cent of SB lesions were open myelomeningocoele, 40% were closed lesions and 11% were occult. Majority (96%) were at lumbar L3 or below. Twenty-nine children (64.5%) were referred before 6 months of age (mean15.8 months; range newborn to 125 months). Thirty-five (77.8%) had neurogenic bladder and 31(69%) had neurogenic bowel. Sixteen developed renal scarring and six, CKD. Late referral (≥6 months of age), small kidneys at referral, dilating VUR and bladder trabeculation were significant independent factors associated with scarring. On multivariate analysis, late referral (odds ratio (OR) 17.4; 95% confidence interval (CI) 1.26-238.7) and dilating VUR (OR 137.0; CI 6.4-2921.1) remained significant.Conclusion: Prevention of renal scarring and CKD remains a challenge in Malaysia even with multidisciplinary proactive care of SB children. Early referrals and more stringent management strategies for dilating VUR are still required. [ABSTRACT FROM AUTHOR]

Background: We tested the hypothesis that patterns of serum creatinine concentrations (S-cr) prior to percutaneous renal biopsy (PRB) predict the utility of PRB in safely making renal diagnoses, revealing treatable disease, and altering therapy in chronic kidney disease patients. Methods: PRB specimens (170 patients) were assigned to 1 of 5 groups: S-cr never greater than 0.11 mM for at least 6 months prior to PRB (Group 1); S-cr greater than 0.11 mM but less than 0.18 mM during the 6 months prior to PRB (Groups 2); S-cr less than 0.18 mM during the 6 months prior to PRB but greater than 0.18 mM prior to these 6 months (Group 3); S-cr greater than 0.18 mM for less than 6 months prior to PRB (Group 4); S-cr greater than 0.18 mM for more than 6 months prior to PRB (Group 5). Results: Histopathology chronicity score (0–9) increased with increasing group number: 2.1 (Group 1); 4.4 (Group 2); 4.5 (Group 3); 5.4 (Group 4); 7.0 (Group 5). Post-PRB bleeding was more common with increasing group number. New therapy was instituted after PRB most frequently in Group 4 (62%) and least frequently in Group 5 (24%). Conclusion: After more prolonged elevations of S-cr, PRB may be less safe and less likely to reveal treatable disease and opportunities for therapy. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to investigate risk factors associated with different extents of renal parenchyma involvement in a paediatric series of primary vesicoureteral reflux (VUR). Methods: A total of 549 patients with VUR were analyzed. The variable of interest was renal scar, assessed by technetium-99m dimercaptosuccinic acid scan, and classified into three subtypes: focal scar, multiple cortical scarring and diffuse scars with a contracted renal unit. The multinomial regression model was applied to identify independent variables associated with each subtype of renal damage. Results: After adjustment, four variables remained independently associated with a contracted renal unit: reflux grades III–V (odds ratio (OR) = 9.7; 95% confidence interval (CI) = 4.1–21.0), age at diagnosis (OR = 3; 95% CI = 1.6–5.1), unilateral reflux (OR = 2.1; 95% CI = 1.2–3.8), and male sex (OR = 2; 95% CI = 1.1–3.8). Two variables were associated with multiple scars: reflux grades III–V (OR = 13.8; 95% CI = 7.4–26.0) and age at diagnosis (OR = 1.9; 95% CI = 1.2–3.0). Two variables were associated with a focal scar: reflux grades III–V (OR = 7.9, 95% CI CI = 3.8–16.4) and male sex as a protective factor (OR = 0.5; 95% CI = 0.25–1.0). Conclusion: Our findings suggest that the development of a contracted renal unit is probably due to congenital malformation, more commonly observed in male infants with high-grade reflux. [ABSTRACT FROM AUTHOR]

Aim: Acute pyelonephritis is a common infectious disease in children and can result in permanent renal damage. Interleukin (IL)-1β is an important inflammatory mediator that appears early during bacterial infection. This prospective study examined urine IL-1β levels in children with acute pyelonephritis documented by 99mTc-dimercaptosuccinic acid (DMSA) scan, and also evaluated whether this cytokine correlated with renal scarring. Methods: A total of 75 children aged 1–121 months with a diagnosis of first-time febrile urinary tract infection (UTI) were studied. The following inflammatory markers were assessed: fever, white blood cell (WBC), neutrophil, C-reactive protein (CRP) and urine IL-1β. Urine samples were collected for IL-1β measurement by enzyme-linked immunosorbent assay before and after antibiotic treatment of the infection. Follow-up DMSA scan was performed at 6–12 months after the acute pyelonephritis to detect renal scarring. Twenty children with other febrile illnesses served as non-renal febrile controls. Results: The 75 children were divided into acute pyelonephritis ( n = 41) and lower UTI ( n = 34) groups according to the findings of DMSA scans. Fever, WBC count, neutrophil count and CRP were significantly higher in the children with acute pyelonephritis than in those with lower UTI (all P < 0.001). The initial urine IL-1β levels of children with acute pyelonephritis were significantly higher when compared with lower UTI and non-renal febrile controls ( P < 0.001). Urine IL-1β in children with acute pyelonephritis was positively correlated with fever, CRP, WBC, neutrophil and leucocyturia. Renal scarring was found in 12 (29.3%) of the 41 children with acute pyelonephritis. The mean age was significantly lower in the children with renal scarring compared with those without ( P < 0.05). Conclusion: These results have shown that urine IL-1β level may serve as a useful marker for the early detection of acute pyelonephritis in febrile children. Young children are at a risk of the development of renal scarring following acute pyelonephritis. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate whether the angiotensin converting enzyme (ACE) and angiotensin II type 1 receptor (A1166C) gene polymorphisms were associated with the renal scar formation secondary to recurrent urinary tract infection in children without uropathy. The polymorphisms were investigated by polymerase chain reaction in 97 children (81 females, 16 males; age, 2.5–13 years) with recurrent urinary tract infection and 100 healthy controls as a single centre study. Children with vesicoureteral reflux, bladder dysfunction and other uropathies were excluded. The dimercaptosuccinic acid (DMSA) scan performed at least 3 months after a proven urinary tract infection and the result of the last DMSA was taken into consideration. Renal scarring was found in 30 patients (30.9%) using DMSA scan. The number of urinary tract infection attacks was significantly higher in patients with renal scarring compared with children without scarring ( P < 0.05). The follow-up period and male/female ratio of patients with or without renal scarring was similar ( P > 0.05). Age at the first urinary tract infection was lower in the group with scarring. The ACE insertion/deletion genotype distribution and D allele frequency were similar between patients and controls ( P > 0.05), and in patients with renal scarring and those without renal scarring. Also, the angiotensin II type 1 receptor gene polymorphism was not associated with renal parenchymal damage ( P > 0.05). The results indicated that the ACE insertion/deletion and angiotensin II type 1 receptor gene polymorphisms were not independent risk factors for renal scar formation in recurrent urinary tract infection of paediatric patients without uropathy. [ABSTRACT FROM AUTHOR]

ObjectiveTo evaluate the efficiency of exogenously administered vitamin A in preventing renal scarring caused by experimental pyelonephritis in rats. Materials and methods Forty Wistar rats were injected with 0.1 mL of solution containing Escherichia coli (1010 /mL) into both renal medullae. Five equal groups were then formed: group 1 was treated only with ciprofloxacin (30 mg/kg per day, twice daily, intraperitoneally) for 5 days, starting 3 days after bacterial inoculation; in group 2, 60 kIU of vitamin A was injected intramuscularly with the bacterial inoculation; in group 3, 60 kIU of vitamin A was injected similarly, but 3 days after bacterial inoculation; in group 4, 60 kIU of vitamin A was given orally with the bacterial inoculation; and group 5 was treated with ciprofloxacin for 5 days and vitamin A intramuscularly from the third day after bacterial inoculation. All the rats were killed 6 weeks after bacterial injection; blood samples were obtained to determine serum vitamin A and β-carotene levels, and both kidneys were examined pathologically for scarring, graded as 0 (none), 1 (mild), 2 (moderate) and 3 (severe). Results Serum vitamin A levels were higher in the rats given vitamin A (group 2–5) than in group 1, being highest in group 4, although only this group had significantly higher levels of vitamin A than group 1 (P<0.05). Histopathologically, the fibrosis was mildest in groups 2 and 4 (two of 16 kidneys grade 1), whereas it was most severe in group 1 (all 16 grade 2–3). Fibrosis was significantly less in groups 2–5 than in group 1 (P<0.05). There was a significant negative correlation between vitamin A levels and the sum of the fibrosis, inflammation and tubular atrophy scores of all rats (r=-0.391, P<0.02). β-carotene levels were unrelated to renal scarring. Conclusion The administration of vitamin A could have a role in preventing renal scar formation from pyelonephritis induced experimentally... [ABSTRACT FROM AUTHOR]

Objective To evaluate the importance of refluxing versus anti-reflux ureteric implantation for the development of renal scarring in patients with a conduit or continent urinary diversion and for the incidence of bacteriuria in the upper urinary tract of patients with a conduit. Patients and methods Renal scintigraphy using 99mTcdimercaptosuccinic acid was performed on 32 of 37 evaluable patients from a prospective, randomized study at a mean of 150 months (range 102-198) after urinary diversion. In five patients with a conduit diversion and unilateral renal scarring, urine was sampled for culture from the proximal end of the conduit and from both renal pelvices by direct percutaneous aspiration. Results Of 35 renal units (18 patients), studied after conduit diversion, scarring was found in 11 (two grade I, six grade H and three grade III) of 17 with refluxing anastomosis and in six (one grade I, four grade II and one grade III) of 18 with anti-reflux anastomosis ( P= 0.06). Of 25 renal units (14 patients) after continent diversion, 16 showed scarring (seven grade I and nine grade II). Bacteriuria was found in four of five upper urinary tracts with a refluxing anastomosis, but in only one of five with an antireflux anastomosis. In these five patients scarring was present in all kidneys with refluxing anastomosis. Conclusion Anti-reflux ureteric anastomosis seems to be important for preventing scarring and bacteriuria in the upper urinary tract of patients with a conduit urinary diversion. Despite the anti-reflux technique of ureteric implantation, most patients with a continent reservoir had renal scarring, though it was generally less severe than in patients with a conduit urinary diversion. [ABSTRACT FROM AUTHOR]