Posterior urethral valve in fetuses: evidence for the role of inflammatory molecules.

BACKGROUND: The aim of this cross-sectional study was to investigate inflammatory biomarkers in urine samples of 24 fetuses with posterior urethral valve (PUV) collected at 22 ± 4 weeks of gestation and to compare the findings with measurements in urine samples of 22 male healthy preterm neonates at 23 ± 4 weeks (control group). METHODS: Inflammatory biomarkers in urine were measured using a cytometric bead array [interleukin (IL)-2, IL-4, IL-6, IL-10, interferon (IFN)-γ, soluable tumor necrosis factor receptor (TNFR) 1, sTNFR2, monocyte chemoattractant protein-1/chemokine ligand 2 (MCP-1/CCL2), eotaxin/CCL11 and interferon gamma-induced protein/10/C-X-C motif chemokine 10 (IP-10/CXCL10)] and ELISA assays [TNF, IL-8/CXCL8 and transforming growth factor-beta (TGF-ß)]. The Mann-Whitney test was used to compare medians. Markers of glomerular (creatinine) and tubular [beta 2 (ß2)-microglobulin, uromodulin, osmolality] functions were correlated with inflammatory biomarkers (Spearman test). RESULTS: An intense inflammatory profile was identified, with significantly increased concentrations of urinary IL-2, IL-4, IL-6, TNF, sTNFRI, sTNFRII, IFN-γ, MCP-1/CCL2, eotaxin/CCL11 and IL-8/CXCL8 in the PUV group compared to the controls. The same was observed for the anti-inflammatory cytokine IL-10 and for the fibrogenic mediator TGF-ß. In the correlation analysis, ß2-microglobulin positively correlated with the presence of MCP-1/CCL2, sTNFRI and eotaxin/CCL11 and negatively correlated with the presence of creatinine. CONCLUSIONS: This study shows that inflammatory molecules are already increased in fetuses with PUV at the mean gestational age of 22 weeks, suggesting a physiopathological role for inflammation just after the embryological formation of the urethral membrane.

A predictive model of chronic kidney disease in patients with congenital anomalies of the kidney and urinary tract.

BACKGROUND: The antenatal detection of congenital anomalies of the kidney and urinary tract (CAKUT) has permitted early management of these conditions. The aim of this study was to identify predictive factors associated with chronic kidney disease (CKD) in CAKUT. We also propose a risk score of CKD. METHODS: In this cohort study, 822 patients with prenatally detected CAKUT were followed up for a median time of 43 months. The primary outcome was CKD stage III or higher. A predictive model was developed using the Cox proportional hazards model and evaluated by using c statistics. RESULTS: Chronic kidney disease occurred in 49 of the 822 (6 %) children with prenatally detected CAKUT. The most accurate model included bilateral hydronephrosis, oligohydramnios, estimated glomerular filtration rate and postnatal diagnosis. The accuracy of the score was 0.95 [95 % confidence interval (CI) 0.89-0.99] and 0.92 (95 % CI 0.86-0.95) after a follow-up of 2 and 10 years, respectively. Based on survival curves, we estimated that at 10 years of age, the probability of survival without CKD stage III was approximately 98 and 58 % for the patients assigned to the low-risk and high-risk groups, respectively (p < 0.001). CONCLUSIONS: Our predictive model of CKD may contribute to an early identification of a subgroup of patients at high risk for renal impairment. It should be pointed out, however, that this model requires external validation in a different cohort.

Diagnostic accuracy of renal pelvic dilatation for detecting surgically managed ureteropelvic junction obstruction.

PURPOSE: In this study we evaluate the diagnostic accuracy of renal pelvic dilatation for detecting infants with prenatal hydronephrosis who will need surgical intervention for ureteropelvic junction obstruction during followup. MATERIALS AND METHODS: Between 1999 and 2010, 371 newborns diagnosed with isolated prenatal hydronephrosis were prospectively followed. The main event of interest was the need for pyeloplasty. Diagnostic odds ratio, sensitivity, specificity and diagnostic accuracy (assessed by AUC) of fetal renal pelvic dilatation and postnatal renal pelvic dilatation were evaluated. RESULTS: A total of 312 patients were included in the analysis and 25 (7.5%) infants underwent pyeloplasty. The diagnostic performance for detecting the need for pyeloplasty was excellent for all ultrasonography measurements. The AUC was 0.96 (95% CI 0.92-0.98) for fetal renal pelvic dilatation, 0.97 (95% CI 0.95-0.98) for postnatal renal pelvic dilatation and 0.95 (95% CI 0.92-0.97) for the Society for Fetal Urology grading system. A cutoff of 18 mm for fetal renal pelvic dilatation and a cutoff of 16 mm for postnatal renal pelvic dilatation had the best diagnostic odds ratio to identify infants who needed pyeloplasty. Considering a diagnosis to be positive only if fetal renal pelvic dilatation was greater than 18 mm and postnatal dilatation was greater than 16 mm, sensitivity was 100% and specificity was 86% (95% CI 80.7-89.9). CONCLUSIONS: Our findings suggest that the combination of fetal and postnatal renal pelvic dilatation is able to increase the diagnostic accuracy for detecting infants who need a more comprehensive postnatal investigation for upper urinary tract obstruction.

Early risk factors for neonatal mortality in CAKUT: analysis of 524 affected newborns.

BACKGROUND: Congenital abnormalities of the kidney and urinary tract (CAKUT) are significant causes of morbidity. The aim of the study was to determine predictive factors of mortality in newborns with CAKUT. METHODS: All 29,653 consecutive newborns hospitalized in a tertiary neonatal unit between 1996 and 2006 were evaluated. The main outcome was neonatal mortality. The variables analyzed as risk factors were maternal age, first pregnancy, low birth weight (LBW), prematurity, oligohydramnios, and CAKUT associated with other malformations (Associated CAKUT). RESULTS: CAKUT was detected in 524 newborns, with an overall prevalence of 17.7 per 1,000 live births. A total of 325 (62%) cases were classified as urinary tract dilatation, 79 (15.1%) as renal cystic disease, and 120 (22.9%) as other subgroups. In the urinary tract dilatation subgroup, independent risk factors for early mortality were Associated CAKUT [odds ratio (OR) 20.7], prematurity (OR 4.5) LBW (OR 3.8), oligohydramnios (OR 3.0), and renal involvement (OR 3.0). In the renal cystic disease subgroup, two variables remained associated with neonatal mortality: LBW (OR 12.3) and Associated CAKUT (OR 21.4). CONCLUSION: The presence of extrarenal anomalies was a strong predictor of poor outcome in a larger series of infants with CAKUT.

Clinical course of 822 children with prenatally detected nephrouropathies.

BACKGROUND AND OBJECTIVES: With the advent of fetal screening ultrasonography, the detection of congenital anomalies of the kidney and urinary tract (CAKUT) in utero has permitted early management of these conditions. This study aims to describe the clinical course of a large cohort of patients with prenatally detected nephrouropathies. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this retrospective cohort study, 822 patients were prenatally diagnosed with CAKUT and systematically followed up at a tertiary Renal Unit for a median time of 43 months. Variables included in the analysis were sex, laterality, fetal ultrasonography (isolated versus associated hydronephrosis), and presence/absence of nephrouropathies. The events of interest were urinary tract infection, surgical interventions, hypertension, CKD, and death. Survival analyses were performed to evaluate time until occurrence of the events of interest. RESULTS: Urinary tract infection occurred in 245 (29.8%) children, with higher risk in females (hazard ratio=1.30, 95% confidence interval=1.02-1.70, P=0.05); 22 patients (2.7%) had hypertension, and 49 (6%) patients developed CKD. The risk of CKD was greater in patients with associated hydronephrosis (hazard ratio=5.20, 95% confidence interval=2.90-9.30, P<0.001). Twelve patients (1.5%) died during follow-up. Death was significantly associated with being born during the first period of the study (hazard ratio=6.00, 95% confidence interval=1.60-22.50, P<0.001), associated hydronephrosis (hazard ratio=9.30, 95% confidence interval=2.90-29.30, P<0.001), and CKD (hazard ratio=170.00, 95% confidence interval=41.00-228.00, P<0.001). CONCLUSIONS: In our series, the clinical course of prenatally detected CAKUT was heterogeneous, and those infants with associated hydronephrosis at baseline were identified as a high-risk subgroup.

Predictive factors for vesicoureteral reflux and prenatally diagnosed renal pelvic dilatation.

PURPOSE: We sought to identify predictive factors for primary vesicoureteral reflux among infants with prenatally detected renal pelvic dilatation. MATERIALS AND METHODS: A total of 250 neonates were diagnosed with isolated renal pelvic dilatation between 1999 and 2008, and followed prospectively. The main event of interest was presence of moderate to severe reflux (grade III to V). Diagnostic odds ratio, sensitivity, specificity, and diagnostic accuracy (assessed by AUC) of fetal and postnatal renal pelvic dilatation were determined. Severity of dilatation was classified by Society for Fetal Urology grade. Binary logistic regression was performed to identify variables significantly associated with vesicoureteral reflux. RESULTS: A total of 23 patients (9.2%) had primary vesicoureteral reflux, of whom 16 had grade III to V disease. Diagnostic accuracy was 0.70 (95% CI 0.63 to 0.75) for fetal and 0.65 (95% CI 0.59 to 0.71) for postnatal renal pelvic dilatation. Combined results of fetal and postnatal renal pelvic dilatation were also assessed. When both tests less than 10 mm were considered negative indicators of moderate to severe vesicoureteral reflux sensitivity increased to 97% and diagnostic odds ratio to 19.1. After adjustment by logistic regression only Society for Fetal Urology grade greater than I and ureteral dilatation were variables independently associated with grade III to V reflux. CONCLUSIONS: Fetal and postnatal renal pelvic dilatation was a poor predictor of vesicoureteral reflux. Nevertheless, diagnostic accuracy regarding clinically significant vesicoureteral reflux improved when fetal and postnatal renal pelvic dilatation less than 10 mm was considered a negative indicator of reflux.

Risk factors for urinary tract infection in children with prenatal renal pelvic dilatation.

PURPOSE: The aim of this study was to identify risk factors for urinary tract infection during followup of children with fetal renal pelvic dilatation. MATERIAL AND METHODS: A total of 192 patients were diagnosed with isolated renal pelvic dilatation between 1999 and 2006 and were prospectively followed. After initial clinical and imaging evaluation ultrasound, clinical examination and laboratory reviews were scheduled at 6-month intervals. The event of interest was incidence of episodes of febrile urinary tract infection. A survival analysis was performed to identify variables significantly associated with the event. Cox model was applied to identify variables that were independently associated with urinary tract infection. RESULTS: A significant uropathy was diagnosed in 78 infants (41%). Median followup was 24 months. During followup urinary tract infection occurred in 27 (14%) of the 192 children. The incidence rate of urinary tract infection decreased from 7.2 episodes per 1,000 person-months in the first year of life to 1.4 after the third year. By survival analysis the cumulative incidence of urinary tract infection for the whole series was estimated at 8% at age 12 months, 13% at 24 months and 21% at 36 months. After adjustment 2 variables were independent predictors of urinary tract infection during followup-female gender (RR 1.4, 95% CI, 1.04 to 1.8, p = 0.02) and presence of uropathy (RR 4.6, 95% CI, 1.8 to 11.3, p = 0.001). CONCLUSIONS: According to our findings, in a cohort of prenatal hydronephrosis girls with vesicoureteral reflux or urinary tract obstruction had a higher risk of urinary tract infection during followup.

Outcome of isolated antenatal hydronephrosis: a prospective cohort study.

The purpose of this study was to report the outcome of infants with antenatal hydronephrosis. Between May 1999 and June 2006, all patients diagnosed with isolated fetal renal pelvic dilatation (RPD) were prospectively followed. The events of interest were: presence of uropathy, need for surgical intervention, RPD resolution, urinary tract infection (UTI), and hypertension. RPD was classified as mild (5-9.9 mm), moderate (10-14.9 mm) or severe (>or=15 mm). A total of 192 patients was included in the analysis; 114 were assigned to the group of non-significant findings (59.4%) and 78 to the group of significant uropathy (40.6%). Of 89 patients with mild dilatation, 16 (18%) presented uropathy. Median follow-up time was 24 months. Twenty-seven patients (15%) required surgical intervention. During follow-up, UTI occurred in 27 (14%) children. Of 89 patients with mild dilatation, seven (7.8%) presented UTI during follow-up. Renal function, blood pressure, and somatic growth were within normal range at last visit. The majority of patients with mild fetal RPD have no significant findings during infancy. Nevertheless, our prospective study has shown that 18% of these patients presented uropathy and 7.8% had UTI during a medium-term follow-up time. Our findings suggested that, in contrast to patients with moderate/severe RPD, infants with mild RPD do not require invasive diagnostic procedures but need strict clinical surveillance for UTI and progression of RPD.

Outcome of apparent ureteropelvic junction obstruction identified by investigation of fetal hydronephrosis.

OBJECTIVES: The purpose of the study was to evaluate the outcome of prenatally detected ureteropelvic junction obstruction (UPJO) managed with a more conservative protocol. METHODS: The records and imaging studies of 77 consecutive neonates with UPJO identified by fetal hydronephrosis were reviewed. A nonoperative approach was attempted in patients with mild/moderate pelvic dilatation, renal units with good function as ascertained by DMSA scan and a non-obstructed pattern on DTPA. Otherwise, the patients were managed surgically by pyeloplasty. Both groups were prospectively followed and the imaging studies were performed before and after the initial approach and at one-year intervals thereafter. RESULTS: Of the 77 infants (85 units), 39 were submitted to surgery (33 pyeloplasty and 7 nephrectomy) and 38 were conservatively managed. During follow-up, 9 (24%) of 38 patients in the non-operative group presented renal function deterioration and 3 presented with urinary infections and were submitted to pyeloplasty. Of the 39 patients surgically managed, 76% presented improvement of hydronephrosis and 90% showed a non-obstructed pattern on diuretic renography. The differential renal uptake, as measured by DMSA scan, remained stable in the three groups analyzed (conservative, initial pyeloplasty, and delayed pyeloplasty). There was a minimal improvement in those units submitted to pyeloplasty with impaired renal function at baseline (< 40%). Mean renal uptake was 28.6% at admission and 33.9% at the end of follow-up. CONCLUSION: There was a wide spectrum of ureteropelvic junction stenosis. Surgical intervention in a subgroup of patients with severe hydronephrosis and impaired function may possibly improve or preserve renal parenchyma. Conversely, conservative management and clinical follow-up are safe and desirable for the subgroup with mild/moderate pelvic dilatation and preserved renal function.

Spontaneous improvement of hypertension in multicystic dysplastic kidney: a case report.

We report a case of transitory hypertension associated with unilateral multicystic dysplastic kidney (MCDK). A newborn girl with MCDK, detected by prenatal ultrasonography, was conservatively treated and has been followed for 18 months at the Pediatric Nephrourology Unit (HC-Belo Horizonte, Brazil). Arterial hypertension was observed at about 4 months of age and was associated with high levels of plasma renin activity and circulating angiotensin, and also with changes in renal Doppler ultrasonography. For these reasons, a nephrectomy was initially proposed. However, a spontaneous improvement of blood pressure levels was noticed at about 10 months of age. Serial Doppler ultrasonography showed involution of the affected renal volume and decreased arterial flow. The anatomical improvement was observed simultaneously with normalization of the peripheral renin and angiotensin values. The literature is reviewed regarding the relationship between hypertension and MCDK.

Prognostic factors in prenatally-detected posterior urethral valves: a multivariate analysis.

To identify prognostic factors associated with chronic renal insufficiency in children with posterior urethral valves (PUV), 22 children with PUV were submitted to a systematic protocol and prospectively followed. Prognostic factors associated with fetal echography and clinical and laboratory findings were studied on admission. Median follow-up was 76 months. The analysis was conducted in two steps: in univariate analysis, variables associated with adverse outcome were identified by the Kaplan-Meier method. The variables that were significantly associated with adverse outcome were then included in a multivariate analysis using the Cox model. Eleven patients (50%) developed chronic renal failure (CRF) during follow-up. After adjustment by the multivariate model, four factors were identified as independent predictors of adverse outcome: oligohydramnios (relative risk [RR] = 10.6, 95% CI = 2.7 - 77, P = 0.02), ventilatory support (RR = 6, 95% CI = 2 - 24, P = 0.01), urea higher than 40 mg/dl (RR = 3.7, 95% CI = 0.92 - 15.0, P = 0.06), and bilateral vesicoureteral reflux (VUR) (RR = 6.1, 95% CI = 1.25 - 30, P = 0.02). On the other hand, the presence of unilateral VUR was a protective factor against the development of CRF or death during follow-up (RR = 0.92, 95% CI = 0.87 - 0.98, P = 0.05).

Curso clínico da válvula de uretra posterior detectada intra-útero: seguimento a longo prazo / Clinical course of posterior urethra detected intra-uterus : long follow-up

Com o objetivo de avaliar o curso clínico da VUP identificada na vida fetal, foram estudadas 15 crianças prospectivamente com o objetivo de avaliar o curso clínico da válvula de uretra posterior (VUP). Pacientes com hidronefrose detectada no pré-natal foram avaliados no período pós-natal, submetidos a um protocolo sistemático e seguidos prospectivamente. Após início daquimioprofilaxia, a avaliaçäo de imagens consistiu de ultrasonografia (US), uretrocistografia miccional (UCM) e cintilografia estática por DMSA. Nos casos confirmados de VUP, as crianças foram submetidas a vesicostomia e seguidas com avaliaçöes clínicas e laboratoriais periódicas. Quinze meninos foram identificados como portadores de VUP entre 1989 e 1998. A média de idade do diagnóstico pré-natal foi de 30 meses. O tempo médio de seguimento foi de 40 meses. Das 15 crianças acompanhadas, 7 (47 porcento) evoluíram com isuficiência renal crônica (IRC) e 6 (40 porcento) faleceram. O óbito esteve associado à perda da funçäo renal (RR = 7, p=0,001). Apesar do diagnóstico precoce, a VUP continua a representar um desafio para a área da nefrologia pediátrica, e os riscos de perda da funçäo renal e de óbito se mantêm elevado