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.     

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) = 1.98, 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.     

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 21 years of age, respectively. The prevalence of hypertension has increased with age: it was 1.7% for patients with 1 yr–9.9 yr, 1.8% for adolescents with 10 yr–14.9 yr, 4.7% for patients with 15–19.9 yr, and 35% for patients >20 years at the end of the follow-up (P < 0.001). It was estimated by survival analysis that 50% of patients with unilateral and bilateral renal damage would have sustained hypertension at about 30 and 22 years of age, respectively. Hypertension increased with age and was strongly associated with renal damage at entry in an unselected population of primary VUR.     

Height and weight in children with vesicoureteric reflux and renal scarring

Height standard deviation scores (HSDS) and weight-for-height index (WHI) at diagnosis were evaluated in 156 children aged 2 months to 10.8 years (mean 3.7 years) with vesicoureteric reflux (VUR) and normal creatinine clearance, and in 156 age- and sex-matched healthy controls. Forty-three patients had bilateral VUR with scintigraphic signs of renal scarring (B SCAR+), 25 had bilateral VUR without renal scarring (B SCAR–); 40 had unilateral VUR with (U SCAR+) and 48 unilateral VUR without (U SCAR–) renal scarring. B SCAR+ patients had an average HSDS of –0.5±1.4 (SD) which was significantly (P = 0.02) below that of controls (0.05±1 HSDS) and an average WHI of 100.6%±16% which was significantly (P = 0.007) below that of controls (108%±12%); 14% of B SCAR+ patients had a height below –2 HSDS. B SCAR–, U SCAR+, and U SCAR– patients had heights near to O HSDS which was not different from that of controls, as well as WHI between 104% and 107.9%, which was not different from that of controls. HSDS and WHI were significantly (P = 0.00001) correlated in patients but not in controls. B SCAR–, U SCAR+, and U SCAR– patients are similar to healthy controls in weight and in height growth and have, on average, some excess weight as do the latter. In contrast, B SCAR+ subjects have a significant decrease of the relative height and normal WHI. Received May 23, 1995; received in revised form and accepted January 5, 1996     

Catch-up growth in children with vesico-ureteric reflux

A longitudinal retrospective study of height Z score (HZ score) and weight-for-height index (WHI) was performed on 94 pre-pubertal children with vesico-ureteric reflux (VUR) and normal creatinine clearance followed for 1 – 6.8 years (mean 3.1 years). Thirty patients had bilateral VUR with scintigraphic signs of renal scarring (B+), 17 had bilateral VUR without renal scarring (B – ), 27 had unilateral VUR with (U+) and 20 unilateral VUR without (U – ) renal scarring. Thirty-three patients received only antimicrobial medication and 61 underwent successful antireflux operation. The increase in HZ score and WHI during the 1st year of follow-up was significantly (P = 0.001 and 0.00003, respectively) higher than during the 2nd year. At first visit, B+ subjects had an average WHI and HZ score that were significantly (P = 0.02 and 0.04, respectively) lower than the other groups of patients together. At last visit this difference was not significant. In B+ subjects, the WHI and HZ score at last visit were significantly (P = 0.04 for both) higher than at the first visit. B+ patients fully recover their body growth deficit compared with other groups of VUR subjects after medical and/or surgical therapy. Received February 23, 1996; received in revised form and accepted June 24, 1996     

Clinical course of prenatally detected primary vesicoureteral reflux

The purpose of this study was to report the clinical course of medium-long-term follow-up of children with prenatally detected vesicoureteral reflux (VUR). Between 1986 and 2004, 53 (41 males) children with VUR detected by investigation of prenatal hydronephrosis were followed up for a mean time of 66 months (range: 6–200 months). Newborns were investigated by ultrasound, voiding cystourethrogram (VCUG) and DMSA scan. Follow-up clinical visits were performed at 6-month intervals. After 24 months patients were investigated by conventional VCUG or direct isotope cystogram. Survival analysis was performed in order to evaluate the resolution of the reflux. Differences between subgroups (mild vs moderate/severe reflux) were assessed by the two-sided log rank test. Thirty (58%) infants presented bilateral VUR, for a total of 83 renal units. There was a predominance of severe reflux (54%). Renal damage was detected in 33.7% of the units on first renal scan. There was a significant correlation between severe reflux and renal damage scars (RR=3.4, 95% confidence interval [CI], 1.4–8, p=0.002). Forty-seven patients were treated with continuous prophylaxis. One patient developed systolic hypertension. Urinary tract infection occurred in 12 (25%) children conservatively managed. VUR resolution was evaluated in 56 renal units. Spontaneous resolution was observed in 25 units (45%). At 48 months after diagnosis, 75% of the cases of mild reflux (I–III) and 37% of severe reflux (IV–V) had resolved (log-rank, 5.6, p=0.017). There was an improvement of nutritional parameters between admission and the end of follow-up. In conclusion, the clinical course of prenatally detected VUR followed up on a medium-long-term basis is relatively benign. Our study corroborates the results obtained in other series of infants with reflux that emphasized the heterogeneity of this disorder.     

Vesicoureteral reflux in children with suspected and proven urinary tract infection

The aim of this study was to estimate the prevalence of vesicoureteral reflux (VUR) and clinically significant ultrasonography (US) abnormalities in a large group of children with proven and suspected urinary tract infection (UTI). The medical reports on renal US and voiding cystouretrographies (VCUG) of 2,036 children were reviewed. Renal US was performed on all children and VCUG on 1,185 children (58%). Based on the urine culture data, the UTI diagnoses were classified into five reliability classes (proven, likely, unlikely, false and no microbial data). The UTI diagnose was considered proven in 583/2036 (28.6%) and false in 145 (7.1%) cases. The prevalence of VUR was similar among those with proven and false UTI [37.4 vs. 34.8%; relative risk (RR) 1.08, 95% confidence intervals (95% CI) 0.7–1.7, P = 0.75] and decreased with increasing age (P = 0.001). Clinically significant US abnormalities occurred in 87/583 (14.9%) cases with proven UTI and significantly less often (11/145, 7.6%) in the false UTI class (RR 1.96, 95% CI 1.1–3.6, P = 0.02). Our finding supports the claim that VUR is not significantly associated to UTI and that its occurrence among children even without UTI is significantly higher than traditional estimates. This challenges the recommendations of routine VCUG after UTI.     

Vesicoureteric Reflux and Reflux Nephropathy as Seen at a Tertiary Care Adult Nephrology Service in India—An Analysis of 86 Patients

Clinical features and risk factors for renal failure in patients with reflux nephropathy (RN) as seen in an adult nephrology service are likely to be different than those seen in a pediatric service. There are only a few studies on adults with vesicoureteric reflux (VUR) and RN and data on RN as seen in developing countries is still evolving. Retrospective analysis of records of patients diagnosed to have VUR by conventional micturating cystourethrogram over a 13 year period, as seen in the adult nephrology services of this tertiary care hospital in north India was carried out. Results are presented as mean ± 2 SD. Unpaired t-test was used to compare means, chi-square test to define associations, and logistic regression analysis was done to define risk factors. Out of 86 patients diagnosed to have VUR, 69 (80.2%) were males and 22 (25.6%) were children. The mean age at presentation was 24.3 ± 14.5 years and at onset of symptoms was 19.6 ± 14.8 years. Sixty-nine (80.2%) patients had chronic renal failure (CRF) at presentation, including 33 (38.4%) patients who already had end stage renal failure (ESRF) at presentation in whom reflux was diagnosed during routine pretransplant evaluation and these constituted 5.5% of all ESRF patients. The clinical features at presentation were hypertension in 51 (59.3%), recurrent urinary tract infection (UTI) in 31 (36.1%), history of stones in 7 (8.1%), and gross hematuria in 4 (4.7%). Patients with history of recurrent UTI were more likely to be females (p<0.01) and to present without renal failure (p<0.05). Proteinuria >1 g/day was significantly associated (p<0.02) with hypertension at presentation. Patients who presented with renal failure were more likely to be males (p<0.05), not to have history of recurrent UTI (p<0.05), have proteinuria >1 g/day (p < 0.02) and higher grades (grades IV and V) of reflux (p<0.05). On logistic regression analysis, higher age of onset (odds ratio 4.6, p<0.03), proteinuria >1 g/day (odds ratio 3.8, p<0.05), and male gender (odds ratio 3.5, p<0.05) were significant risk factors for presentation for the first time with renal failure. The clinical features and course of VUR and RN as seen in India are different from those reported from elsewhere. The vast majority of patients in India are males and almost two thirds do not have a past history of UTI. Renal failure is present in more than three fourths of patients when a diagnosis of reflux is made and one third of all patients present with ESRD. Patients with a prior history of UTI are more commonly females and are less likely to have renal failure at presentation. Higher age of onset of symptoms, proteinuria >1 g/day and male gender were risk factors for the development of renal failure. It is likely that these asymptomatic patients remain undetected during childhood, presenting late only after having incurred severe renal damage.     

Predictive factors of chronic kidney disease in primary focal segmental glomerulosclerosis

Renal histological features of focal segmental glomerulosclerosis (FSGS) are found in 75% of pediatric patients with steroid-resistant nephrotic syndrome. In order to evaluate the predictive factors of chronic kidney disease (CKD), we retrospectively reviewed the records of 110 children with biopsy-proven FSGS admitted between 1972 and 2004. Renal survival was analyzed by the Kaplan–Meier method and Cox’s regression model. Two multivariate models were developed: (1) from the onset of symptoms to the occurrence of CKD and (2) from the time of renal biopsy to CKD. Mean follow-up time was 10 years [standard deviation ((SD) 5.5], and 24 patients (21.8%) progressed to CKD. At baseline, after adjustment three variables remained as independent predictors of CKD: age >6.5 years (RR=3.3, 95% CI=1.3–7.8), creatinine >1 mg/dl (RR=2.5, 95% CI=0.97–6.5), and non-response to steroids (RR=7.3, 95% CI=2.7–19.7). In a model with continuous variables only age and non-response to steroids were associated with CKD. At the time of renal biopsy, after adjustment two variables remained as independent predictors of CKD: hematuria (RR=3.0, 95% CI=1.2–7.3) and creatinine >0.8 mg/dl (RR=4.3, 95% CI=1.7–10.6). In a model with continuous variables four factors predicted CKD: age, creatinine, hematuria, and percentage of global sclerosis.     

Growth failure,risk of hospitalization and death for children with end-stage renal disease

Growth failure remains a significant problem for children with chronic renal insufficiency and end-stage renal disease (ESRD). We examined whether growth failure is associated with more-frequent hospitalizations or higher mortality in children with kidney disease. We studied data on prevalent United States pediatric patients with ESRD in 1990 who were followed through 1995. Patients were categorized according to the standard deviation score (SDS) of their incremental growth during 1990: severe (<–3 SDS), moderate growth failure (>–3 and <–2 SDS), and normal growth (>–2 SDS). Among 1,112 prevalent pediatric dialysis and transplant patients (<17 years, Tanner I–IV), those with severe and moderate growth failure had higher hospitalization rates {relative risk (RR) 1.14 [95% confidence interval (CI) 1.1, 1.2] and 1.24 [95% CI 1.2, 1.3]} respectively than those with normal growth after adjustment for age, gender, race, cause and duration of ESRD, and treatment modality (dialysis or transplant) in 1990. Kaplan-Meier survival analysis showed 5-year survival of 85% and 90% for patients with severe and moderate growth failure, respectively, compared with 96% for patients with normal growth (P<0.001, log-rank). Cox proportional hazards analysis revealed that those with severe (RR 2.9, 95% CI 1.6, 5.3) and moderate growth failure (RR 2.01, 95% CI 1.1, 3.6) had an increased risk of death compared with youths with normal growth, after adjustment. A higher proportion of deaths in the severe and moderate growth failure groups were attributed to infectious causes (22% and 18.7%, respectively) than in the normal growth group (15.6%). We conclude that growth failure is associated with a more-complicated clinical course and increased risk of death for children with kidney failure. Received: 15 August 2001 / Revised: 14 January 2002 / Accepted: 15 January 2002     

Nutrition and growth in relation to severity of renal disease in children

Practical joint medical/dietetic guidelines are required for children with chronic renal insufficiency (CRI). Nutritional status and growth were compared in 95 children (59 male) >2 years age with CRI, grouped following [⁵¹Cr]-labelled EDTA glomerular filtration rate (GFR, ml/min/1.73 m²) estimations into ’normal’ kidney function [GFR>75 (mean 104 (SD 18.9), n=35], mild (GFR 51–75, n=23), moderate (GFR 25–50, n=19) and severe CRI (GFR<25, n=18). Anthropometry [weight (wt.), height (ht.), and body mass index (BMI)], laboratory investigations and a 3-day dietary record were obtained. All anthropometric indices deteriorated with worsening renal function, from mean SD scores for wt., ht. and BMI in ’normal’ children of 0.32 (SD 1.2), 0.4 (SD 1.0) and 0.1 (SD 1.3), respectively, to values of –1.28 (SD 1.1; P<0.001), –1.52 (SD 1.1; P<0.001) and –0.42 (SD 1.1;NS) in severe CRI. Mean total energy intake decreased from 103% (SD 17) estimated average requirement (EAR) in ’normal’ children to 85% EAR (SD 27; P=0.004) in severe CRI. Mean serum PTH concentrations (normal laboratory range 12–72 ng/l) were higher in moderate [67 ng/l (SD 58), P<0.001] and severe CRI [164 ng/l (SD 164), P<0.001] and mean serum phosphate concentrations were higher in severe CRI (1.54 mmol/l (SD 0.17), P=0.009) compared to ’normal’. Disturbances in nutritional intakes, bone biochemistry and growth occur early in CRI and suggest the need for joint medical/dietetic intervention in children with mild and moderate CRI, in addition to those with more severe CRI. Received: 13 March 2000 / Revised: 11 July 2000 / Accepted: 14 July 2000     

Chronic kidney disease stages 3–5 and cardiovascular disease in the veterans affairs population

Aim  Cardiovascular complications are common in patients with chronic kidney disease in the general population. The study aims to investigate the prevalence and prognosis of CKD stages 3–5 in the veterans affairs (VA) population, which is sicker with more co-morbid conditions. Methods  In this case-controlled study of 6,432 men the associations of risk factors with CKD and its risk of mortality were estimated using, primarily, logistic regression analysis. Results  The 1,045 (16.2%) patients with CKD stages 3–5 were older (72 ± 10 vs. 59 ± 13 years, P < 0.0001) with more hypertension (53.6 vs. 39.6%, P < 0.0001), diabetes (24.9 vs. 19.8%, P < 0.0002), and CVD (35.3 vs. 17.8%, P < 0.0001) at baseline. Age ≥65 years (odds ratio [95% CI]) (4.95 [4.22–5.82]), hypertension (1.56 [1.34–1.79]), diabetes mellitus (1.21 [1.03–1.43]), CVD (1.71 [1.47–2.00]), and White not Hispanic (1.57 [1.32–1.85]) were independently associated with CKD. The prevalence of CVD at baseline increased with decreasing renal function. Old age (1.98 [1.66–2.35]), CKD (1.94 [1.61–2.33], CVD (1.46 [1.23–1.74]) and tobacco use (1.91 [1.05–3.47]) were independently associated with the 750 (11.7%) deaths. Conclusion  Among veterans, traditional cardiovascular risk factors, CVD, and CKD are highly prevalent. CKD is associated with increased risk of baseline CVD and follow-up mortality.     

Fetal renal pelvic dilatation—poor predictor of familial vesicoureteral reflux

The sensitivity and positive predictive value (PPV) of fetal renal pelvic dilatation for detecting vesicoureteral reflux (VUR) can only be determined by performing voiding cystourethrography (VCUG) on all newborns in a study population. We sought to determine this for infants with a family history of reflux. From June 1989 to September 1996, 157 children (80 males) under 2 years with a family history of primary VUR in a first-degree relative had VCUG. VCUG results were compared with the fetal renal pelvic diameter on obstetric sonogram performed after 16 weeks gestation. Of the 157 infants, 33 (11 boys) had primary VUR. In those with a parent as the index case, the prevalence of reflux was 5% in boys and 35% in girls (P=0.03). The largest renal pelvic diameter after 16 weeks was not discriminatory for VUR, but after 30 weeks gestation a 4 mm renal pelvis had a sensitivity of 33% and a PPV of 32%. The sensitivity was higher for grades 4 and 5 (75%) than for grades 1–3 reflux (17%), (P=0.04). In conclusion, fetal renal pelvic diameter has a low sensitivity and poor predictive value for detecting VUR, but this improves a little after 30 weeks gestation.     

Prognostic factors of posterior urethral valves and the role of antenatal detection

The aim of the study was to investigate the significance of different prognostic factors and long-term renal outcome in boys with posterior urethral valves (PUVs) detected either antenatally or during infancy. A total of 46 cases of PUVs, 23 antenatal and 23 postnatal, were followed prospectively from 1983 to 2003. The mean follow-up time was 12.5 years. The impact of vesicoureteral reflux (VUR), urinary tract infections (UTIs), urinary continence, and renal parenchymal damage on patient outcome was evaluated. Long-term renal outcome was defined as favorable if renal function was either normal or moderately impaired (glomerular filtration rate 60 ml/min per 1.73 m²) and poor if the patient had either chronic renal failure or end-stage renal disease. The outcome was poor in 14 (30%) of the 46 boys and was associated with a significantly higher nadir serum creatinine concentration (mean 157 mol/l) during the 1st year of life (P<0.001), with bilateral VUR (P<0.05) and breakthrough UTIs (P<0.05). In our patients, age at achieving urinary continence, and the presence of renal parenchymal damage did not have a statistically significant association with long-term renal outcome. The long-term outcome among boys with antenatally detected PUVs did not differ from that among those cases detected postnatally after developing symptoms (P=0.25).     

Antenatal and postnatal ultrasound in the evaluation of the risk of vesicoureteral reflux

Antenatal hydronephrosis (ANH) is a frequent anomaly detected on fetal ultrasound scans. There is no consensus recommendation for the postnatal follow-up and/or the necessity to perform a voiding cystourethrography (VCUG) to diagnose vesicoureteral reflux (VUR). We conducted a cohort/non-randomized trial of 121 patients with ANH, defined as an anterior posterior diameter (APD) ≥5 mm after the 20th week of gestation, to evaluate the ability of the antenatal and postnatal ultrasonography results to predict VUR. All infants had two successive ultrasounds at 5 days and 1 month, respectively, after birth. A VCUG was performed at 6 weeks in children with a persistent APD ≥5 mm and/or an ureteral dilatation observed on at least one of two postnatal ultrasounds. In total, 88 patients had VCUG and nine had VUR, with five having high-grade reflux (>grade II). The risk of VUR increased significantly with the degree of APD detected on the postnatal ultrasound scan (p = 0.03). The odds ratios were 5.0 [95% confidence interval (CI) 0.5–51.2] for APD = 7–9 mm and 9.1 (95% CI 1.0–80.9) for APD ≥10 mm. The results of this study show that among our patient cohort antenatal ultrasound was not predictive of reflux. There was, however, a relation between the importance of the postnatal renal pelvis diameter and the risk of VUR. A cut-off of 7 mm showed a fair ability of ultrasonography to predict VUR and a cut-off of 10 mm enabled all severe refluxes in the 88 patients who had a VCUG to be diagnosed.     

Serum and urine fibronectin levels in children with vesicoureteral reflux

The study objective was to assess serum and urine fibronectin (FN) levels in children with vesicoureteral reflux (VUR) depending on reflux grade and urine osmolality. The study group (1) consisted of 54 VUR children, median age 4.28 (range 0.6–15) years: subgroup A, 19 children with grade II; subgroup B, 19 with grade III; and subgroup C, 16 with grade IV or V VUR. The control group (2) included 27 healthy children. The immunoenzymatic method enzyme immunoassay (EIA) was used to determine serum soluble and urine FN levels, with an osmometer to measure urinary osmolality. The median urine FN in VUR children was 224.1 (15.4–3537) ng/mg creatinine (Cr), compared with the control group: 137.9 (20.3–670.6) ng/mg Cr (p < 0.05), whereas median serum FN was 395.0 (13.0–779.9) ng/ml and 121.9 (25–345.1) ng/ml (p < 0.05), respectively. A detailed analysis showed that only in subgroup C was the level of urinary FN significantly higher than in the control group (p < 0.01). However, serum concentration was elevated in all VUR children (A–C) compared with controls (p < 0.01). Reduced osmolality, below 800 mOsm/kg H₂O, was observed in subgroup C. Negative correlation between urinary osmolality and urinary FN was found (r = −0.426, p < 0.01). In children with VUR, serum FN increased with reflux grade, whereas its urinary level was elevated only in grade IV and V reflux with impaired urine concentration.     

Effects of intensive blood pressure control on mortality and cardiorenal function in chronic kidney disease patients

BackgroundBlood pressure (BP) variability is highly correlated with cardiovascular and kidney outcomes in patients with chronic kidney disease (CKD). However, appropriate BP targets in patients with CKD remain uncertain.MethodsWe searched PubMed, Embase, and the Cochrane Library for randomized controlled trials (RCTs) of CKD patients who underwent intensive BP management. Kappa score was used to assess inter-rater agreement. A good agreement between the authors was observed to inter-rater reliability of RCTs selection (kappa = 0.77; P = 0.005).ResultsTen relevant studies involving 20 059 patients were included in the meta-analysis. Overall, intensive BP management may reduce the incidence of cardiovascular disease mortality (RR: 0.69, 95% CI: 0.53 to 0.90, P: 0.01), all-cause mortality (RR: 0.77, 95% CI: 0.67 to 0.88, P < 0.01) and composite cardiovascular events (RR: 0.84 95% CI: 0.75 to 0.95, P < 0.01) in patients with CKD. However, reducing BP has no significant effect on the incidence of doubling of serum creatinine level or 50% reduction in GFR (RR: 1.26, 95% CI: 0.66 to 2.40, P = 0.48), composite renal events (RR 1.07, 95% CI: 0.81 to 1.41, P = 0.64) or SAEs (RR: 0.97, 95% CI: 0.90 to 1.05, P = 0.48).ConclusionIn patients with CKD, enhanced BP management is associated with reduced all-cause mortality, cardiovascular mortality, and incidence of composite cardiovascular events.     

Chronic kidney disease in children in Turkey

To determine the incidence, etiology and treatment patterns of chronic kidney disease (CKD) in children a questionnaire was sent to pediatric nephrology centers in Turkey, asking them to report patients under the age of 19 years who had estimated glomerular filtration rates (GFRs) of ≤75 ml/min per 1.73 m² body surface area, diagnosed in 2005. Twenty-nine centers reported 282 patients (123 female/159 male; mean age 8.05 ± 5.25 years). Urological problems such as vesicoureteral reflux (18.5%), obstructive uropathy (10.7%) and neurogenic bladder (15.1%) were the leading causes of CKD. The majority of the patients were in stage V (32.5%), IV (29.8%) or III (25.8%). Growth retardation (49.6%) and secondary hyperparathyroidism (72.4%) were very frequent. The GFR levels correlated positively with hemoglobin/hematocrit and calcium levels and negatively with phosphorus and parathyroid hormone (PTH) levels (P < 0.05). Renal replacement therapies were initiated in 35.8% of the patients, peritoneal dialysis in 23%, hemodialysis in 10.6% and transplantation in 2.2%. This was the first multi-center, epidemiologic study done in children with CKD in Turkey. The most striking result was the predominance of vesicoureteral reflux (VUR) or related urological problems as the underlying causes of CKD. Thus, early diagnosis and treatment of these conditions are of vital importance to decrease the incidence of CKD in children. An erratum to this article can be found at     

Is ACE gene polymorphism a risk factor for renal scarring with low-grade reflux?

The possible relationship between the angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and renal scarring secondary to vesicoureteral reflux (VUR) has recently attracted attention and the DD genotype was postulated to be a risk factor for renal scarring. However, available data represent conflicting results. The aim of this study was to investigate the ACE gene I/D polymorphism and the other known risk factors for renal scarring in children with low- and high-grade VUR. The study included 96 (67 females, 29 males) patients (mean age at diagnosis 3.7±3.3 years) with VUR that were assessed for ACE I/D gene polymorphism. ACE genotypes were determined as II, ID, and DD using the polymerase chain reaction. The control group consisted of 103 healthy children with the same ethnicity to find the distribution of ACE gene I/D polymorphism in the population. The frequency of renal scarring was 80.8% in the high-grade reflux group and 34.3% in the low-grade reflux group. There was no difference between groups with renal scarring and without scarring with respect to gender, family history of VUR, age at diagnosis of VUR, associated urological abnormalities, frequency of urinary tract infection episodes, and the occurrence of bilateral or unilateral VUR. Genotype DD was found to be a significant risk factor for renal scarring in the study group by multivariate regression analysis (odds ratio 3.79, P=0.011). It was not a risk factor in high-grade reflux patients (odds ratio 0.60, P=0.62). However, it was a risk factor in low-grade patients with respect to renal scarring (odds ratio 4.0, P=0.024). Although renal scarring is not common in low-grade reflux patients, there may be scarring in some patients. DD polymorphism of the ACE gene is a significant risk factor in low-grade reflux patients with renal scarring.     

Risk factors for renal scarring in children and adolescents with lower urinary tract dysfunction

Risk factors for renal scarring in children with lower urinary tract dysfunction (LUTD) were evaluated. The medical records of 120 patients were assessed concerning gender, presence of vesicoureteric reflux (VUR), bladder capacity, detrusor overactivity, residual urine, febrile urinary tract infection (UTI), bacteriuria, constipation, detrusor sphincter incoordination (DSI), high detrusor pressure at maximal cystometric capacity (PMCC), low compliance, and thickness and trabeculation of the bladder wall. Renal scarring was diagnosed by ^99mtechnetium-dimercaptosuccinic acid renal scan (DMSA). Renal scarring was detected in 38 patients (31%). VUR, UTI, decreased bladder capacity, urinary residue, and trabeculated and thick bladder wall were associated with scarring at univariate analysis. Multivariate analysis showed VUR (P < 0.0001) as the independent risk factor for renal scarring. Thickness of the bladder wall was a marginal risk factor (P  = 0.07). Although UTI was not a risk factor, it was associated with VUR (P  = 0.03). In our analysis, VUR was the main risk factor; however, renal scarring was probably due to multifactorial causes, as VUR was associated with UTI.