Small kidney associated with primary vesicoureteral reflux in children. A pathological overhaul

In this series two quite distinct pathological entities accounted for the small, often deformed, kidney found over a severe primary ureterovesical reflux. One of them is due to dysplastic abnormal metanephric differentiation, and the other is a segmental tubular atrophy with glomerular metamorphosis. In our material there is no evidence to support an inflammatory pathogenesis in these conditions. An abnormal excess vascularization is explained by an arteriovenous fistula present in both. Proper identification of the pathology underlying such cases will assist further studies on the natural history of these two diverse malformations.     

Urinary calcium excretion in children with vesicoureteral reflux.

BACKGROUND: Renal malformations including vesico-ureteral reflux (VUR) are associated with urolithiasis. However, studies on urinary calcium excretion in children with VUR have not been reported. This study was conducted to find out whether children with VUR have a higher prevalence of hypercalciuria and whether their family members are affected by hypercalciuria and/or urolithiasis. METHODS: We studied the prevalence of hypercalciuria and urolithiasis in 46 children (12 males and 34 females) with VUR and in their parents. RESULTS: Three out of 46 children had renal colic and nine out of 46 exhibited calyceal microlithiasis in the renal sonography. According to Stapleton's criteria, we found that 27 out of 46 children (58.6%) had hypercalciuria. These children were significantly shorter than children with normal calciuria and showed lower values of maximal urinary osmolality. We found no differences in urinary calcium excretion values related to the VUR grading, or to the presence or absence of renal scars, or to whether VUR was still unresolved or already resolved at the time of study. Seventeen out of 27 children with hypercalciuria (63%) had one or both parents affected by hypercalciuria, and there was a history of urolithiasis in six first-degree relatives and in four second-degree relatives (37%). Besides, 10 out of 19 children without hypercalciuria (52.6%) had one or both parents affected by hypercalciuria and there was a history of urolithiasis in three first-degree relatives and in three second-degree relatives (31.6%). Among the 27 children whose parents had hypercalciuria, four had both parents affected, 19 had only the mother affected and in four patients only the father was affected. CONCLUSION: Our results showed that the prevalence of hypercalciuria was greater in paediatric patients with VUR than in the general population. Urolithiasis in patients with VUR had a metabolic origin. Hypercalciuria was inherited as an autosomal dominant trait although with a higher probability to be inherited from the mother.     

Urinary Tamm-Horsfall protein excretion in patients with primary vesicoureteral reflux

The excretion of urinary Tamm-Horsefall protein (THP) was determined by enzyme-linked immunosorbent assay and glomerular filtration rate (GFR) was calculated with technetium-99m diethylenetriamine pentacetic acid (99mTc-DTPA) renal scintigraphy in 26 consecutive patients with primary vesicoureteral reflux (VUR) before and after antireflux surgery. Wide variations of urinary THP excretion and GFR were seen in all grades of VUR. On the basis of the relationship between urinary THP excretion and GFR before the surgery, patients were divided into three groups. The first group (group A, n = 8) had normal urinary THP values and normal values of GFR. The second group (group B, n = 11) had high THP excretion and moderately decreased GFR, the third group (group C, n = 7) had normal urinary THP excretion and severely decreased GFR. In group A, urinary THP values remained normal and GFR improved in all patients after surgery. In group B, GFR improved when urinary THP dropped immediately, but GFR did not improve when urinary THP remained high after surgery. In group C, GFR did not improve and urinary THP continued to be low or tended to drop again after the surgery. The results suggested that serial measurements of urinary THP excretion and GFR by 99mTc-DTPA renal scintigraphy before and after antireflux surgery are useful for the evaluation of renal function in patients with primary VUR.     

Urinary calcium and uric acid excretion in children with vesicoureteral reflux

Urolithiasis is relatively common in children, and identifiable predisposing factors for stone formation, including metabolic and structural derangements, can be established in most cases. Vesicoureteral reflux (VUR) is a common cause of kidney stone formation. The pathophysiological mechanism of urolithiasis in reflux is related to urinary tract infection and urinary stasis, both of which promote urinary crystal formation, but metabolic causes, such as crystallurias (mostly hypercalciuria), may also be involved in this process. However, few studies on urinary calcium and uric acid excretion in children with VUR have been conducted. We have studied the frequency of hypercalciuria and hyperuricosuria in children with VUR and compared the results with those from a control group. The VUR group comprised 108 children with VUR (19 boys, 89 girls; age range 3 months to 12 years), and the control group comprised 110 healthy children without any history of reflux or urinary tract infection (30 boys, 80 girls; age range 2 months to 12 years). Fasting urine was analyzed for the calcium/creatinine (Ca/Cr) and uric acid/creatinine (UA/Cr) ratios. Hypercalciuria was more frequently diagnosed in the VUR patients than in the control group (21.3 vs. 3.6%; P = 0.0001). Significant differences between the two groups were also found for the mean Ca/Cr and UA/Cr ratios (P = 0.0001 and P = 0.0001, respectively). No differences were found in the urinary Ca/Cr or UA/Cr ratios related to VUR grading or unilateral/bilateral VUR in the patient group, with the exception of those for hypercalciuria and mild VUR (P = 0.03). The association of urinary stones and microlithiasis in the VUR group was 29.6%. Our results demonstrate that the frequency of hypercalciuria and hyperuricosuria was higher in pediatric patients with VUR than in healthy children. Knowing this relationship, preventive and therapeutic interventions for stone formation in VUR could be greatly expanded.     

Cystitis follicularis in children with primary vesicoureteral reflux

In an attempt to determine whether cystitis follicularis affects the spontaneous resolution of primary vesicoureteral reflux we reviewed the records of 65 children with reflux and cystitis follicularis. A group of children with primary vesicoureteral reflux but without cystitis follicularis was included as controls. The data did not reveal a statistically significant difference in either the rate of spontaneous resolution of reflux or the need for surgical correction between these 2 groups of children.     

Urinary biomarkers of latent inflammation and fibrosis in children with vesicoureteral reflux

International Urology and Nephrology - To investigate the urinary levels of TGF-β1, VEGF, and MCP-1 as potential biomarkers of latent inflammation and fibrosis in the kidney before and...     

Probiotics prophylaxis in children with persistent primary vesicoureteral reflux

Probiotics, beneficial living microorganisms, have been proven to be effective in preventing gastrointestinal infections, but their effect in preventing urinary tract infection (UTI) is inconclusive. A prospective randomized controlled study was done to compare the preventive effect of probiotics with conventional antibiotics in children with persistent primary vesicoureteral reflux (VUR). One hundred twenty children who had had persistent primary VUR after antibiotic prophylaxis for 1 year were randomly allocated into a probiotics (Lactobacillus acidophilus 10⁸ CFU/g 1 g b.i.d., n = 60) or an antibiotics (trimethoprim/sulfamethoxazole 2/10 mg/kg h.s., n = 60) prophylaxis group during the second year of follow-up. The incidence of recurrent UTI was 18.3% (11/60) in the probiotics group, which was not different from 21.6%(13/60) in the antibiotic group (P = 0.926). The causative organisms of recurrent UTI were not significantly different between the two groups (P = 0.938). Even after stratification by VUR grade, age, gender, phimosis, voiding dysfunction and renal scar, the incidence of recurrent UTI did not differ significantly between the two groups (P > 0.05). The development of new renal scar was not significantly different between the two groups (P > 0.05). In conclusion, probiotics prophylaxis was as effective as antibiotic prophylaxis in children with persistent primary VUR.     

Management of primary vesicoureteral reflux in children

The management of primary vesicoureteral reflux (VUR) in child suffered major changes by focusing on the medical treatment in order to prevent the urinary tract infections and the occurrence of postinfectious renal scars. Continuous antibiotic prophylaxis and the follow-up by serial cystography of the spontaneous resolution of the reflux are considered nowadays the best choice in most of the cases. Surgery is recommended only in selected cases. Sub-ureteral injection of bulking agents to correct the reflux holds promise as an alternative to open surgery, but presents the challenge of identifying the ideal bulking agent.     

Remission of primary vesicoureteral reflux in children with medical management

We studied the spontaneous resolution rate in children with primary vesicoureteral reflux (VUR) and the interference of some specific factors. We reviewed the records of 110 children (14 days - 16 years) admitted in the 4th Pediatric Clinic Ia?i with primary VUR, between 1994 - 2003, which had exclusive medical management and minimum one follow-up cystogram. We used Kaplan-Meier curves to analyze the resolution rate of VUR during the follow-up in relation with initial grade, age at diagnosis, gender, recurrent urinary tract infections (UTIs) and the presence of renal scarring. The remission rate for all the cases was 70%, with differences based on the reflux grade: 100% for grade I and 45% for grade IV. The cases diagnosed during infancy recovered faster than those diagnosed after this period. The presence of renal scarring and breakthrough UTIs increased the remission time. In conclusion the majority of patients with VUR resolved during medical management, the remission rate being influenced by the reflux grade, presence of renal scarring and breakthrough UTIs.     

Clinical analysis of primary vesicoureteral reflux in children

The retrospective analysis of 64 patients between 1 month and 14 years old with 87 primary vesicoureteral units with reflux was reviewed. They were followed-up for a period of 3 to 60 months. Thirty one patients were managed conservatively by chemotherapy (group A) and 28 patients were treated surgically. As the anti-reflux operation the Politano-Leadbetter procedure was used in 27 patients and the modified Politano-Leadbetter procedure in 1 patient (group B). Five patients were not treated (group C). In 13 of the 30 renal units of group A, the vesico-ureteral reflux disappeared spontaneously and in group B the post-operative cystourethrography revealed cure of reflux in all the renal units. In 2 of the 21 renal units of group A excretory urography (IVP) revealed improvement and in 3 deterioration. Post-operative IVP revealed improvement in 13 of 39 renal units of group B and in 2 deterioration. In 3 of the 22 renal units of group A the renogram revealed improvement and in 3 deterioration. The post-operative renogram revealed improvement in 8 of the 28 renal units of group B and deterioration in renal units. Analysis was also made according to the vesicoureteral reflux grade.     

Clinical course of 735 children and adolescents with primary vesicoureteral reflux

The purpose of this retrospective cohort study was to report the clinical course of children with primary vesicoureteral reflux (VUR). Between 1970 and 2004, 735 patients were diagnosed with VUR and were systematically followed in a single tertiary renal unit. Patients were followed up for a mean time of 76 months (6 months to 411 months). The events of interest were reflux resolution, renal damage, urinary tract infection (UTI), chronic kidney disease (CKD), and hypertension. Survival analysis was performed in order to evaluate reflux resolution and CKD. Renal damage was detected at admission in 319 patients (43.4%). Continuous low-dose antibiotic prophylaxis was administered to 624 patients (91.2%); 499 (73%) patients subsequently had no UTI or fewer than three episodes. The median time of persistence of reflux according to Kaplan–Meier analysis was 38 months for grade I/II [95% confidence interval (95% CI), 33–43], 98 months for grade III (95% CI, 78.5–105), and 156 months for grade IV/V (95% CI, 122–189). Twenty patients (3%) developed hypertension. It was estimated that the probability of CKD was 5% at 10 years after diagnosis of VUR; for children diagnosed after 1990 the probability of CKD was only 2%. Renal function impairment occurred in patients with severe bilateral reflux or in patients with contralateral renal hypoplasia. There has been an improvement of prognosis for patients diagnosed in the past 15 years.     

Validity of urine neutrophile gelatinase-associated lipocalin in children with primary vesicoureteral reflux

International Urology and Nephrology - Vesicoureteral reflux (VUR) is the most common congenital urinary tract abnormality in children. The objective of this study was to evaluate the diagnostic...     

Urinary kidney injury molecules in children with febrile seizures

Objective: Hypoxia occurs following convulsions, and hypoxia is one of the most common causes of acute renal damage. The aim of this study was to investigate urinary levels of kidney injury molecules, including neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-β-D-glucosaminidase (NAG), and liver-type fatty acid-binding protein (L-FABP) in children with febrile seizures (FS) for the first time.

Methods: The study included 28 children with FS and 34 age and gender matched healthy children. Serum biochemistry and blood gases were measured in the serum samples. Estimated glomerular filtration rate (eGFR) was calculated. NGAL, NAG, L-FABP, and creatinine (Cr) were measured in the urine samples. The ratios of kidney injury markers to urinary Cr were used for comparisons.

Results: There were no significant differences in eGFR and serum chemistry values between the FS and the control group (p?>?0.05). Hypoxia was detected in 67.9% of the FS patients. The FS group had significantly higher urinary kidney injury molecules to Cr ratios compared to the controls, including NGAL/Cr (17.9?±?9.8; 6.7?±?4.0, respectively; p?p?p?Conclusion: Increased urinary NGAL/Cr, NAG/Cr, and L-FABP/Cr values, in patients with FS compared to healthy controls, suggest a possible subclinical renal damage in these patients.     

High incidence of a generally small kidney and primary vesicoureteral reflux

PURPOSE: We distinguished the scintigraphy pattern of congenital reflux nephropathy from that of acquired scarring in children with primary vesicoureteral reflux. MATERIALS AND METHODS: We retrospectively evaluated the frequency and pattern of renal scintigraphy abnormalities in 41 patients with prenatally detected primary vesicoureteral reflux and in 322 with a mean age plus or minus standard deviation of 3.6 + or - 1 years in whom primary reflux was detected after urinary tract infection. Dimercapto-succinic acid scintigraphy was performed 4 to 6 and 1 to 4 months after reflux was diagnosed and/or the infection was cured in patients with urinary tract infection and prenatal detection, respectively. RESULTS: We identified 3 patterns of renal damage, including overall decreased uptake of renal radionuclide that was 20% to 40% of relative uptake, focal defects in uptake and shrunken kidney with relative uptake less than 20%. Scintigraphy revealed renal damage in 12 prenatally detected cases of vesicoureteral reflux, including overall decreased uptake in 58% and shrunken kidney in 42%, and in 111 cases of reflux detected at urinary tract infection, including overall decreased uptake in 50%, uptake focal defects in 37% and shrunken kidney in 13%. In the urinary tract infection group overall decreased uptake was present in 25 of 90 boys and in 40 of 232 girls (p = 0.05). Of these children 15% of the girls had uptake focal defects and 17% had overall decreased uptake. Overall decreased uptake and uptake focal defects were significantly more common in kidney-ureter units with reflux grade 4 or greater than in those with grade 3 or less (p = 0. 00001 and 0.027, respectively). CONCLUSIONS: When assuming that overall decreased radionuclide uptake indicates congenital reflux nephropathy and uptake focal defects indicate postnatal acquired scarring, congenital reflux nephropathy appears to be an important cause of renal damage in children with primary vesicoureteral reflux even beyond the neonatal age and even in girls. This finding is of interest because postnatally acquired scarring may but congenital reflux nephropathy may not be prevented.     

Renal tissue oxygenation in children with chronic kidney disease due to vesicoureteral reflux

Background

Vesicoureteral reflux (VUR) is a frequent cause of chronic kidney disease (CKD) in children. Using blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI), we measured cortical and medullary oxygenation in children with CKD due to VUR and compared the results to those obtained on healthy controls.

Method

The study population comprised 37 children (19 with CKD due to VUR and 18 healthy age-matched controls). BOLD-MRI was performed before and after furosemide treatment. MR images were analyzed with the region-of-interest (ROI) technique to assess the mean R2* values (=1/T2*) of the cortex and medulla of each kidney and with the concentric object (CO) technique that divides renal parenchyma in 12 equal layers.

Results

R2* values were significantly lower (corresponding to higher oxygenation) in the cortex and medulla of kidneys of children with CKD due to VUR than in those of the healthy controls (cortex 16.4?±?1.4 vs. 17.2?±?1.6 s^?1 , respectively; medulla 28.4?±?3.2 vs. 30.3?±?1.9 s^?1 , respectively; P?<?0.05), and furosemide-induced changes in medullary R2* were smaller in the former than in the latter (?5.7?±?3.0 vs. ?6.9?±?3.4 s^?1, respectively; P?<?0.05). Similar results were found with the CO technique. In children with a history of unilateral reflux (n?=?9), the non-affected contralateral kidneys presented similar R2* values as the diseased kidneys, but their response to furosemide was significantly larger (?7.4?±?3.2 vs. ?5.7?±?3.0, respectively; P?=?0.05).

Conclusions

Chronic kidney disease due to VUR is not associated with kidney tissue hypoxia in children. The significantly larger furosemide-induced decrease in medullary R2* levels in the healthy group and unaffected contralateral kidneys of the VUR group points towards more intense renal sodium transport in these kidneys.