Mariana A. Vasconcelos

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 76xa0months (6xa0months to 411xa0months). 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 38xa0months for gradexa0I/II [95% confidence interval (95% CI), 33–43], 98xa0months for gradexa0III (95% CI, 78.5–105), and 156xa0months for gradexa0IV/V (95% CI, 122–189). Twenty patients (3%) developed hypertension. It was estimated that the probability of CKD was 5% at 10xa0years 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 15xa0years.

Risk of hypertension in primary vesicoureteral reflux

The aim of this report was to estimate the risk of hypertension in children with primary vesicoureteral reflux (VUR). Between 1970 and 2004, 735 patients were diagnosed with VUR at a single tertiary renal unit. Of 735 patients, 664 (90%) were systematically followed and had multiple measurements of blood pressure. Hypertension was defined as values persistently above 95th for age, sex, and height in three consecutive visits. Risk of hypertension was analyzed by the Kaplan-Meier method. Of 664 patients followed, 20 (3%) developed hypertension. The estimated probability of hypertension was 2% (95%CI, 0.5%–3%), 6% (95%CI, 2%–10%), 15% (95%CI, 11%–20%) at 10, 15, and 21xa0years of age, respectively. The prevalence of hypertension has increased with age: it was 1.7% for patients with 1xa0yr–9.9xa0yr, 1.8% for adolescents with 10xa0yr–14.9xa0yr, 4.7% for patients with 15–19.9xa0yr, and 35% for patients >20xa0years at the end of the follow-up (Pu2009<u20090.001). It was estimated by survival analysis that 50% of patients with unilateral and bilateral renal damage would have sustained hypertension at about 30 and 22xa0years of age, respectively. Hypertension increased with age and was strongly associated with renal damage at entry in an unselected population of primary VUR.

Gender and vesico-ureteral reflux: a multivariate analysis

The aim of this retrospective cohort study was to describe the characteristics of patients with primary vesico-ureteral reflux (VUR) with special attention to gender-specific differences. Between 1970 and 2004, 735 patients were diagnosed with VUR and were systematically followed in a single tertiary renal unit. The following variables were analyzed: race, age at diagnosis, clinical presentation, weight and height Z-score, unilateral/bilateral reflux, VUR grade, renal damage, severity of renal damage, constipation, and dysfunctional voiding. Comparison of proportion between genders was assessed by the chi-square test with Yates’ correction. The logistic regression model was applied to identify independent variables associated with gender. A survival analysis was performed to evaluate VUR resolution. After adjustment, five variables remained independently associated with male gender at baseline: non-white race [Odds ratio (OR)xa0=xa01.98, 95% confidence interval (95% CI) 1.33–2.95, P=0.001], moderate/severe grade of reflux (OR=2.16, 95% CI 1.45–3.22, P<0.001), severe renal damage (OR=1.60, 95% CI 1.04–2.52, P=0.04), age at diagnosis <24 months (OR=1.79, 95% CI 1.23–2.60, P=0.002), and antenatal clinical presentation (OR=3.56, 95% CI 1.91–6.63, P<0.001). Follow-up data were available for 684 patients (93%). Median follow-up time was 69 months (range 6 months to 411 months). Girls had a greater risk of urinary tract infection (UTI) during follow-up than boys (OR=1.68, 95% CI 1.18–2.38, P=0.003). There was no difference in progression to chronic renal insufficiency (CRI) between boys (3.8%) and girls (2.4%) during this period of follow-up (OR=1.58, 95% CI 0.59–4.15, P=0.44). Gender as an isolated variable is a poor predictor of clinical outcome in an unselected series of primary reflux. Although boys had a more severe pattern at baseline, girls had a greater risk of dysfunctional voiding and recurrent UTI during follow-up.

Effectiveness of dual and triple antiretroviral therapy in the treatment of HIV-infected children

OBJECTIVEnThe use of antiretroviral therapy in HIV-infected children has been a widely discussed issue. The aim of this study was to compare the effectiveness of dual nucleoside analogue reverse transcriptase inhibitor (NRTI) regimens and three-drug regimens [2NRTI+ non-nucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI)] in a cohort of HIV-infected children.nnnMETHODSnThe study was carried out in a referral center for the management of infected children, which is affiliated with the School of Medicine of Universidade Federal de Minas Gerais (UFMG). Those children whose antiretroviral therapy was implemented between January 1998 and December 2000 and who were followed until December 2001 were included in the study. Therapeutic failure or death was regarded as the endpoint in our analysis.nnnRESULTSnA total of 101 patients were assessed, 58 (57.4%) on dual therapy and 43 (42.6%) on triple therapy. No statistically significant difference was observed between the groups in terms of gender, age, CD4+ count and baseline viral load. The average duration of dual therapy was 26.3 months (95%CI 21.3-31.3) and that of triple therapy was 34.3 months (95%CI 29.2-39.5%). There was therapeutic failure in 33 (56.9%) patients on dual therapy and in 11 (25.6%) patients on triple therapy (log rank = 5.03; p = 0.025). The relative risk of therapeutic failure of the dual therapy was 2.2 times higher (95%CI 1.3-3.9). The percentage of initial CD4+ T cells was a predictor of risk for therapeutic failure (p = 0.001). Patients on triple therapy showed a more remarkable reduction in their viral load (p = 0.001).nnnCONCLUSIONnTriple therapy was efficient for a longer time period and showed better virologic response than dual therapy in this cohort of HIV-infected children. Therefore, triple therapy should be the treatment of choice.

Interactions between Cytokines, Congenital Anomalies of Kidney and Urinary Tract and Chronic Kidney Disease

Fetal hydronephrosis is the most common anomaly detected on antenatal ultrasound, affecting 1–5% of pregnancies. Postnatal investigation has the major aim in detecting infants with severe urinary tract obstruction and clinically significant urinary tract anomalies among the heterogeneous universe of patients. Congenital uropathies are frequent causes of pediatric chronic kidney disease (CKD). Imaging techniques clearly contribute to this purpose; however, sometimes, these exams are invasive, very expensive, and not sufficient to precisely define the best approach as well as the prognosis. Recently, biomarkers have become a focus of clinical research as potentially useful diagnostic tools in pediatric urological diseases. In this regard, recent studies suggest a role for cytokines and chemokines in the pathophysiology of CAKUT and for the progression to CKD. Some authors proposed that the evaluation of these inflammatory mediators might help the management of postnatal uropathies and the detection of patients with high risk to developed chronic kidney disease. Therefore, the aim of this paper is to revise general aspects of cytokines and the link between cytokines, CAKUT, and CKD by including experimental and clinical evidence.

Urinary levels of TGF β-1 and of cytokines in patients with prenatally detected nephrouropathies

This study aimed to identify noninvasive biomarkers of clinically significant nephrouropathies in patients with antenatal renal and/or urinary tract alterations. Spot-urine levels of interleukin-6 (IL-6), transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α (TNF-α) were measured in 100 patients with antenatal detected nephrouropathies. Patients were divided in idiopathic hydronephrosis (nu2009=u200947), urinary tract malformations (nu2009=u200935), and dysplastic kidneys (nu2009=u200918). Urinary concentrations of TGF-β1, IL-6, and TNF-α were compared between groups according to clinical and image findings. Receiver-operating characteristic (ROC) curves were analyzed for the overall diagnostic accuracy of TGF-β1, IL-6, and TNF-α levels in discriminating infants with nephrouropathies. No significant differences in urinary TGF- β1, IL-6, and TNF-α levels were found in the comparison between the groups. TGF-β1 levels tended to be higher in patients with renal hypodysplasia compared to idiopathic hydronephrosis (pu2009=u20090.07). Twenty-nine patients had reduced DMSA uptake. In these cases, absolute urinary concentration of TGF-β1 and levels standardized for creatinine were significantly higher than in patients with normal DMSA uptake, while IL6 and TNF-α did not differ between groups. Urinary cytokine measurements were not useful as a screening test for clinically significant nephrouropathies. Conversely, increased concentrations of TGF-β1 pointed out to renal damage as indicated by reduced DMSA uptake.

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

BackgroundThe 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.MethodsIn this cohort study, 822 patients with prenatally detected CAKUT were followed up for a median time of 43xa0months. 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.ResultsChronic kidney disease occurred in 49 of the 822 (6xa0%) 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 [95xa0% confidence interval (CI) 0.89–0.99] and 0.92 (95xa0% CI 0.86–0.95) after a follow-up of 2 and 10xa0years, respectively. Based on survival curves, we estimated that at 10xa0years of age, the probability of survival without CKD stage III was approximately 98 and 58xa0% for the patients assigned to the low-risk and high-risk groups, respectively (pu2009<u20090.001).ConclusionsOur 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.

Efetividade da terapia anti-retroviral dupla e tríplice em crianças infectadas pelo HIV

OBJECTIVE: The use of antiretroviral therapy in HIV-infected children has been a widely discussed issue. The aim of this study was to compare the effectiveness of dual nucleoside analogue reverse transcriptase inhibitor (NRTI) regimens and three-drug regimens [2NRTI+ non-nucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI)] in a cohort of HIV-infected children. METHODS: The study was carried out in a referral center for the management of infected children, which is affiliated with the School of Medicine of Universidade Federal de Minas Gerais (UFMG). Those children whose antiretroviral therapy was implemented between January 1998 and December 2000 and who were followed up until December 2001 were included in the study. Therapeutic failure or death was regarded as the endpoint in our analysis. RESULTS: A total of 101 patients were assessed, 58 (57.4%) on dual therapy and 43 (42.6%) on triple therapy. No statistically significant difference was observed between the groups in terms of gender, age, CD4+ count and baseline viral load. The average duration of dual therapy was 26.3 months (95%CI 21.3-31.3) and that of triple therapy was 34.3 months (95%CI 29.2-39.5%). There was therapeutic failure in 33 (56.9%) patients on dual therapy and in 11 (25.6%) patients on triple therapy (log rank = 5.03; p = 0.025). The relative risk of therapeutic failure of the dual therapy was 2.2 times higher (95%CI = 1.3-3.9). The percentage of initial CD4+ T cells was a predictor of risk for therapeutic failure (p = 0.001). Patients on triple therapy showed a more remarkable reduction in their viral load (p = 0.001). CONCLUSION: Triple therapy was efficient for a longer time period and showed better virologic response than dual therapy in this cohort of HIV-infected children. Therefore, triple therapy should be the treatment of choice.

Effectiveness of dual and triple antiretroviral therapy in the treatment of HlV-infected children

Objective: The use of antiretroviral therapy in HlV-infected children has been a widely discussed issue. The aim of this study was to compare the effectiveness of dual nucleoside analogue reverse transcriptase inhibitor (NRTI) regimens and three-drug regimens [2NRTI+ non-nucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI)] in a cohort of HlV-infected children. Methods: The study was carried out in a referral center for the management of infected children, which is affiliated with the School of Medicine of Universidade Federal de Mnas Gerais (UFMG). Those children whose antiretroviral therapy was implemented between January 1998 and December 2000 and who were followed until December 2001 were included in the study. Therapeutic failure or death was regarded as the endpoint in our analysis. Results: A total of 101 patients were assessed, 58 (57.4%) on dual therapy and 43 (42.6%) on triple therapy. No statistically significant difference was observed between the groups in terms of gender, age, CD4+ count and baseline viral load. The average duration of dual therapy was 26.3 months (95%CI 21.3-31.3) and that of triple therapy was 34.3 months (95%CI 29.2-39.5%). There was therapeutic failure in 33 (56.9%) patients on dual therapy and in 11 (25.6%) patients on triple therapy (log rank = 5.03; p = 0.025). The relative risk of therapeutic failure of the dual therapy was 2.2 times higher (95%CI 1.3-3.9). The percentage of initial CD4+ T cells was a predictor of risk for therapeutic failure (p = 0.001). Patients on triple therapy showed a more remarkable reduction in their viral load (p = 0.001). Conclusion: Triple therapy was efficient for a longer time period and showed better virologic response than dual therapy in this cohort of HlV-infected children. Therefore, triple therapy should be the treatment of choice.

A clinical predictive model of renal injury in children with congenital solitary functioning kidney

BackgroundSolitary functioning kidney (SFK) is an important condition in the spectrum of congenital anomalies of the kidney and urinary tract. The aim of this study was to describe the risk factors for renal injury in a cohort of patients with congenital SFK.MethodsIn this retrospective cohort study, 162 patients with SFK were systematically followed up (median, 8.5xa0years). The primary endpoint was time until the occurrence of a composite event of renal injury, which includes proteinuria, hypertension, and chronic kidney disease (CKD). A predictive model was developed using Cox proportional hazards model and evaluated by c statistics.ResultsAmong 162 children with SFK included in the analysis, 132 (81.5%) presented multicystic dysplastic kidney, 20 (12.3%) renal hypodysplasia, and 10 (6.2%) unilateral renal agenesis. Of 162 patients included in the analysis, 10 (6.2%) presented persistent proteinuria, 11 (6.8%) had hypertension, 9 (5.6%) developed CKD stage ≥u20093, and 18 (11%) developed the composite outcome. After adjustment by the Cox model, three variables remained as independent predictors of the composite event: creatinine (HR, 3.93; Pu2009<u20090.001), recurrent urinary tract infection (UTI) (HR, 5.05; Pu2009=u20090.002), and contralateral renal length at admission (HR, 0.974; Pu2009=u20090.002). The probability of the composite event at 10xa0years of age was estimated as 3%, 11%, and 56% for patients assigned to the low-risk, medium-risk, and high-risk groups, respectively (Pu2009<u20090.001).ConclusionOur findings have shown an overall low risk of renal injury for most of infants with congenital SFK. Nevertheless, our prediction model enabled the identification of a subgroup of patients with an increased risk of renal injury over time.