Consequences of intrauterine growth restriction for the kidney

Low birth weight due to intrauterine growth restriction is associated with various diseases in adulthood, such as hypertension, cardiovascular disease, insulin resistance and end-stage renal disease. The purpose of this review is to describe the effects of intrauterine growth restriction on the kidney. Nephrogenesis requires a fine balance of many factors that can be disturbed by intrauterine growth restriction, leading to a low nephron endowment. The compensatory hyperfiltration in the remaining nephrons results in glomerular and systemic hypertension. Hyperfiltration is attributed to several factors, including the renin-angiotensin system (RAS), insulin-like growth factor (IGF-I) and nitric oxide. Data from human and animal studies are presented, and suggest a faltering IGF-I and an inhibited RAS in intrauterine growth restriction. Hyperfiltration makes the kidney more vulnerable during additional kidney disease, and is associated with glomerular damage and kidney failure in the long run. Animal studies have provided a possible therapy with blockage of the RAS at an early stage in order to prevent the compensatory glomerular hyperfiltration, but this is far from being applicable to humans. Research is needed to further unravel the effect of intrauterine growth restriction on the kidney

A Schema Therapy Based Milieu in Secure Residential Youth Care:Effects on Aggression, Group Climate, Repressive Staff Interventions, and Team Functioning

Group care workers of residential youth care settings face the challenge of creating a warm and involved treatment climate against the demands and restrictions of the treatment setting. We tested the effects of SafePath, a milieu-based intervention based on Schema Therapy principles, during the first year of implementation on two secure residential treatment units compared to two control units. Staff’s daily reports on 139 individual patients were coded on use of schema mode language (implementation check), occurrences of aggression (primary outcome) and repressive staff interventions. In addition, repeated questionnaires were filled out by patients (n = 87) on group climate and by staff (n = 50) on team functioning. Compared to the control units, SafePath units showed higher improvements in group climate and repressive interventions. Both SafePath and control units showed decreased aggression over time. Team functioning was consistently better in the SafePath units compared to the care-as-usual units from baseline through 12 months. In conclusion, a Schema Therapy based milieu as implemented with SafePath may contribute to a warm and supportive group climate with less repressive interventions in secure residential youth care

The RECAP Test Rapidly and Reliably Identifies Homologous Recombination-Deficient Ovarian Carcinomas

Recent studies have shown that the efficacy of PARP inhibitors in epithelial ovarian carcinoma (EOC) is related to tumor-specific defects in homologous recombination (HR) and extends beyond BRCA1/2 deficient EOC. A robust method with which to identify HR-deficient (HRD) carcinomas is therefore of utmost clinical importance. In this study, we investigated the proficiency of a functional HR assay based on the detection of RAD51 foci, the REcombination CAPacity (RECAP) test, in identifying HRD tumors in a cohort of prospectively collected epithelial ovarian carcinomas (EOCs). Of the 39 high-grade serous ovarian carcinomas (HGSOC), the RECAP test detected 26% (10/39) to be HRD, whereas ovarian carcinomas of other histologic subtypes (n = 10) were all HR-proficient (HRP). Of the HRD tumors that could be sequenced, 8/9 showed pathogenic BRCA1/2 variants or BRCA1 promoter hypermethylation, indicating that the RECAP test reliably identifies HRD, including but not limited to tumors related to BRCA1/2 deficiency. Furthermore, we found a trend towards better overall survival (OS) of HGSOC patients with RECAP-identified HRD tumors compared to patients with HRP tumors. This study shows that the RECAP test is an attractive alternative to DNA-based HRD tests, and further development of a clinical grade RECAP test is clearly warranted

Interpretation of the Fractional Excretion of Sodium in the Absence of Acute Kidney Injury: A Cross-Sectional Study

Contains fulltext : 177784.pdf (Publisher’s version ) (Open Access)BACKGROUND/AIMS: The fractional excretion of sodium (FeNa) may be helpful in establishing the cause of acute renal failure. This study was performed to determine the influence of the glomerular filtration rate (GFR), sodium intake, and tubular function on FeNa in children without renal failure. METHODS: In this single institute cross-sectional study, 24-h-urine collections from patients (4-18 years of age, GFR >60 mL/min/1.73 m2) were used when considered reliable, and analyzed to determine sodium excretion, creatinine clearance and FeNa. The influence of tubular function was studied in 5 patients with generalized tubular dysfunction. RESULTS: Based on data from 761 patients, a multiple regression formula was designed based on GFR and sodium excretion that predicted over 80% of the variation in FeNa (R2 = 0.824, p < 0.001). Using this formula, the predicted FeNa was significantly lower than the measured FeNa in the children with tubular dysfunction. CONCLUSION: FeNa depends on GFR and sodium intake, and tubular function cannot be assessed without possessing adequate knowledge on all factors. Therefore, no normal range or cut-off value for FeNa to assess tubular function can be given, and doing so is a misapplication of this equation

Risk factors for renal injury in children with a solitary functioning kidney.

Item does not contain fulltextOBJECTIVE: The hyperfiltration hypothesis implies that children with a solitary functioning kidney are at risk to develop hypertension, proteinuria, and chronic kidney disease. We sought to determine the presenting age of renal injury and identify risk factors for children with a solitary functioning kidney. METHODS: We evaluated 407 patients for signs of renal injury, defined as hypertension, proteinuria, an impaired glomerular filtration rate, and/or the use of renoprotective medication. Patients were subdivided on the basis of type of solitary functioning kidney and the presence of ipsilateral congenital anomalies of the kidney and urinary tract (CAKUT). The development of renal injury was analyzed with Kaplan-Meier analysis. Risk factors were identified by using logistic regression models. RESULTS: Renal injury was found in 37% of all children. Development of renal injury increased by presence of ipsilateral CAKUT (odds ratio [OR] 1.66; P = .04) and age (OR 1.09; P < .001). Renal length was inversely associated with the risk to develop renal injury (OR 0.91; P = .04). In all patients, the median time to renal injury was 14.8 years (95% confidence interval 13.7-16.0 years). This was significantly shortened for patients with ipsilateral CAKUT (12.8 years, 95% confidence interval 10.6-15.1 years). CONCLUSIONS: Our study determines independent risk factors for renal injury in children with a solitary functioning kidney. Because many children develop renal injury, we emphasize the need for clinical follow-up in these patients starting at birth.01 februari 201

Unilateral renal agenesis: a systematic review on associated anomalies and renal injury.

Item does not contain fulltextBACKGROUND: Unilateral renal agenesis (URA) is associated with other congenital anomalies of the kidney and urinary tract (CAKUT) and extra-renal anomalies. However, the reported prevalences of these anomalies are highly variable. We estimated the prevalence of associated CAKUT and extra-renal anomalies in patients with URA. Furthermore, we determined the prevalence of renal injury in URA patients. METHODS: We conducted a systematic review of English and non-English articles using PubMed and Embase.com. Included studies reported at least one of the following items: incidence of URA, gender, side of URA, prenatal diagnosis, performance of micturating cystourethrogram, associated CAKUT, urinary tract infection or extra-renal anomalies. Studies that described a mean/median glomerular filtration rate (GFR) and proportions of patients with hypertension, micro-albuminuria or a decreased GFR were also included. RESULTS: Analyses were based on 43 included studies (total number of patients: 2684, 63% male). The general incidence of URA was 1 in approximately 2000. Associated CAKUT were identified in 32% of patients, of which vesicoureteral reflux was most frequently identified (24% of patients). Extra-renal anomalies were found in 31% of patients. Hypertension could be identified in 16% of patients, whereas 21% of patients had micro-albuminuria. Ten per cent of patients had a GFR<60 mL/min/1.73 m2;. CONCLUSIONS: These aggregate results provide insight in the prevalence of associated anomalies and renal injury in patients with URA. Our systematic review implicates that URA is not a harmless malformation by definition. Therefore, we emphasize the need for clinical follow-up in URA patients starting at birth.1 juli 201