Reduced renal length and volume 20 years after very preterm birth

Intrauterine growth retardation is presumed to be associated with decreased renal size and impaired renal function as a result of stunted kidney development and nephron deficit. To study whether very preterm birth also affects renal size at young adulthood, we sonographically measured bipolar kidney length and volume in 51 very premature individuals (<32 weeks of gestation), either small (SGA) or appropriate (AGA) for gestational age (22 SGA and 29 AGA), and 30 full-term controls 20 years after birth. Relative kidney length and volume were calculated. Both absolute and relative left kidney length and volume were significantly lower in SGA and AGA individuals, notably in women. Renal size did not differ between SGA and AGA individuals. In 70% of controls, the left kidney was larger than the right one compared with 40.9% in SGA [relative risk (RR) 1.7; 95% confidence interval (CI) 1.0−3.0] and 48.3% in AGA (RR 1.5; 95% CI 0.9−2.3) individuals. Renal structural anomalies were present in eight prematurely born participants only. Our data suggest that kidney growth is stunted after preterm birth, especially on the left side, and in the female gender

Very preterm birth is a risk factor for increased systolic blood pressure at a young adult age

Children born very prematurely who show intrauterine growth retardation (IUGR) are suggested to be at risk of developing high blood pressure as adults. Renal function may already be impaired by young adult age. To study whether very preterm birth affects blood pressure in young adults, we measured 24-h ambulatory blood pressure (Spacelabs™ 90207 device) and renin concentration in 50 very premature individuals (<32 weeks of gestation), either small (SGA) or appropriate (AGA) for gestational age (21 SGA, 29 AGA), and 30 full-term controls who all were aged 20 years at time of measurement. The mean (standard deviation) daytime systolic blood pressure in SGA and AGA prematurely born individuals, respectively, was 122.7 (8.7) and 123.1 (8.5) mmHg. These values were, respectively, 3.6 mmHg [95% confidence interval (CI) −0.9 to 8.0] and 4.2 mmHg (95% CI 0.4−8.0) higher than in controls [119.6 (7.6)]. Daytime diastolic blood pressure and nighttime blood pressure did not differ between groups. We conclude that individuals born very preterm have higher daytime systolic blood pressure and higher risk of hypertension at a young adult age

Adjustment for time-invariant and time-varying confounders in ‘unexplained residuals’ models for longitudinal data within a causal framework and associated challenges

‘Unexplained residuals’ models have been used within lifecourse epidemiology to model an exposure measured longitudinally at several time points in relation to a distal outcome. It has been claimed that these models have several advantages, including: the ability to estimate multiple total causal effects in a single model, and additional insight into the effect on the outcome of greater-than-expected increases in the exposure compared to traditional regression methods. We evaluate these properties and prove mathematically how adjustment for confounding variables must be made within this modelling framework. Importantly, we explicitly place unexplained residual models in a causal framework using directed acyclic graphs. This allows for theoretical justification of appropriate confounder adjustment and provides a framework for extending our results to more complex scenarios than those examined in this paper. We also discuss several interpretational issues relating to unexplained residual models within a causal framework. We argue that unexplained residual models offer no additional insights compared to traditional regression methods, and, in fact, are more challenging to implement; moreover, they artificially reduce estimated standard errors. Consequently, we conclude that unexplained residual models, if used, must be implemented with great care

Treatment and long-term outcome in primary nephrogenic diabetes insipidus

Background: Primary nephrogenic diabetes insipidus (NDI) is a rare disorder and little is known about treatment practices and long-term outcome. Methods: Paediatric and adult nephrologists contacted through European professional organizations entered data in an online form. Results: Data were collected on 315 patients (22 countries, male 84%, adults 35%). Mutation testing had been performed in 270 (86%); pathogenic variants were identified in 258 (96%). The median (range) age at diagnosis was 0.6 (0.0–60) years and at last follow-up 14.0 (0.1–70) years. In adults, height was normal with a mean (standard deviation) score of −0.39 (±1.0), yet there was increased prevalence of obesity (body mass index >30 kg/m2; 41% versus 16% European average; P < 0.001). There was also increased prevalence of chronic kidney disease (CKD) Stage ≥2 in children (32%) and adults (48%). Evidence of flow uropathy was present in 38%. A higher proportion of children than adults (85% versus 54%; P < 0.001) received medications to reduce urine output. Patients ≥25 years were less likely to have a university degree than the European average (21% versus 35%; P = 0.003) but full-time employment was similar. Mental health problems, predominantly attention-deficit hyperactivity disorder (16%), were reported in 36% of patients. Conclusion: This large NDI cohort shows an overall favourable outcome with normal adult height and only mild to moderate CKD in most. Yet, while full-time employment was similar to the European average, educational achievement was lower, and more than half had urological and/or mental health problems

Epidemiology of chronic kidney disease in children

In the past 30 years there have been major improvements in the care of children with chronic kidney disease (CKD). However, most of the available epidemiological data stem from end-stage renal disease (ESRD) registries and information on the earlier stages of pediatric CKD is still limited. The median reported incidence of renal replacement therapy (RRT) in children aged 0–19 years across the world in 2008 was 9 per million of the age-related population (4–18 years). The prevalence of RRT in 2008 ranged from 18 to 100 per million of the age-related population. Congenital disorders, including congenital anomalies of the kidney and urinary tract (CAKUT) and hereditary nephropathies, are responsible for about two thirds of all cases of CKD in developed countries, while acquired causes predominate in developing countries. Children with congenital disorders experience a slower progression of CKD than those with glomerulonephritis, resulting in a lower proportion of CAKUT in the ESRD population compared with less advanced stages of CKD. Most children with ESRD start on dialysis and then receive a transplant. While the survival rate of children with ERSD has improved, it remains about 30 times lower than that of healthy peers. Children now mainly die of cardiovascular causes and infection rather than from renal failure