Assessment of total body water in paediatric patients on dialysis

Background Various anthropometric techniques are used to assess total body water in children on dialysis; however, their predictive accuracy and precision has not been validated. Methods We compared total body water measurements obtained by deuterium oxide (D2O) dilution with predictions of total body water from (1) height and weight, (2) skinfold measurements, and (3) bioelectrical impedance analysis, using previously published formulae for healthy children. Measurements were performed in 14 patients on peritoneal and in nine patients on haemodialysis, aged 4-22 years. Results In the total population of dialysed patients, weight was the strongest single predictor of total body water (R2=0.93) followed by the resistance index (RI=height2/impedance; R2=0.85) and height (R2=0.93). A prediction formula based on height and weight predicted total body water with a residual mean square error (RMSE) of 1.97 l (coefficient of variation (CV)=10.0%) and with a systematic overestimation of true total body water by 0.4%. A prediction equation based on skinfold measurements yielded a total body water estimate with an RMSE of 2.15 1 (CV=10.5%) and overpredicted true total body water by an average of 2.2%. Using three published prediction equations incorporating RI, RMSEs of 2.78 1 (CV=14.1%) with a mean under- or overestimation of true total body water by 6.9, 7.1, and 0.8% respectively, were achieved. The prediction of total body water was optimized by linear combinations of RI or the log-transformed sum of four skinfolds (logsum) with weight by the following equations: total body water (1) = 9.97−3.13×logsum +0.59×weight (kg) (1) (R2 = 0.951; RMSE=1.67 1; CV = 8.17%). total body water (1) = 1.99 + 0.144 × RI (Ohm/cm2) + 0.40 × weight (kg) (2) (R2 = 0.949; RMSE = 1.671; CV = 8.53%). The fit of these prediction formulae, which were derived from the total population, did not differ significantly between haemo- and peritoneal dialysis patients or between boys and girls. Conclusions Both skinfold measurements and bioelectrical impedance analysis can be used to improve the height- and weight- based prediction of total body water in children on dialysi

Hypertension in children with chronic kidney disease: pathophysiology and management

Arterial hypertension is very common in children with all stages of chronic kidney disease (CKD). While fluid overload and activation of the renin–angiotensin system have long been recognized as crucial pathophysiological pathways, sympathetic hyperactivation, endothelial dysfunction and chronic hyperparathyroidism have more recently been identified as important factors contributing to CKD-associated hypertension. Moreover, several drugs commonly administered in CKD, such as erythropoietin, glucocorticoids and cyclosporine A, independently raise blood pressure in a dose-dependent fashion. Because of the deleterious consequences of hypertension on the progression of renal disease and cardiovascular outcomes, an active screening approach should be adapted in patients with all stages of CKD. Before one starts antihypertensive treatment, non-pharmacological options should be explored. In hemodialysis patients a low salt diet, low dialysate sodium and stricter dialysis towards dry weight can often achieve adequate blood pressure control. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers are first-line therapy for patients with proteinuria, due to their additional anti-proteinuric properties. Diuretics are a useful alternative for non-proteinuric patients or as an add-on to renin–angiotensin system blockade. Multiple drug therapy is often needed to maintain blood pressure below the 90th percentile target, but adequate blood pressure control is essential for better renal and cardiovascular long-term outcomes

Change in left ventricular geometry during antihypertensive treatment in children with primary hypertension

The pattern of the left ventricle (LV) has important significance in adults with hypertension. The aim of the present study was to analyze changes and determinants of LV geometry after 1 year of antihypertensive treatment in children with primary hypertension (PH) in relation to metabolic abnormalities and anthropometrical parameters. In 86 children (14.1 ± 2.4 years) with newly diagnosed PH, LV geometry and biochemical parameters before and after 12 months of standard antihypertensive therapy were assessed. At baseline, normal LV geometry (NG) was found in 42 (48.9%), concentric remodeling (CR) in 4 (4.6%), concentric hypertrophy (CH) in 8 (9.3%), and eccentric hypertrophy (EH) in 32 (37.2%) patients. The prevalence of NG in patients with severe hypertension was significantly lower than in patients with ambulatory hypertension. There were no differences in dipping status in relation to LV geometry. Patients with CH and EH were more viscerally obese than patients with NG. Patients with CH had higher diastolic blood pressure in comparison with EH patients (p < 0.05). The main predictor of relative wall thickness (RWT) was the triglycerides to high density lipoprotein cholesterol (TG/HDL) ratio (R2 = 0.319, β = 0.246, p = 0.004). Patients received 12 months of antihypertensive treatment, either lifestyle modification only (n = 37) or lifestyle modification plus antihypertensive medications (n = 49) if severe ambulatory hypertension or target organ damage were present. After 12 months of treatment the prevalence of EH (37.2% vs 18.6%, p = 0.003) decreased but prevalence of CH did not change. Patients in whom RWT decreased also decreased waist circumference and TG/HDL; the main predictor of RWT decrease was a decrease of the TG/HDL ratio (β = 0.496, R2 = 0.329, p = 0.002). In adolescents with PH, LV geometry is related to central obesity and insulin resistance. Decrease of abdominal obesity and insulin resistance are the most important predictors of normalization of LV geometry, however CH has lower potential to normalize LV geometry

Therapeutic strategies to slow chronic kidney disease progression

Childhood chronic kidney disease commonly progresses toward end-stage renal failure, largely independent of the underlying disorder, once a critical impairment of renal function has occurred. Hypertension and proteinuria are the most important independent risk factors for renal disease progression. Therefore, current therapeutic strategies to prevent progression aim at controlling blood pressure and reducing urinary protein excretion. Renin-angiotensin-system (RAS) antagonists preserve kidney function not only by lowering blood pressure but also by their antiproteinuric, antifibrotic, and anti-inflammatory properties. Intensified blood pressure control, probably aiming for a target blood pressure below the 75th percentile, may exert additional renoprotective effects. Other factors contributing in a multifactorial manner to renal disease progression include dyslipidemia, anemia, and disorders of mineral metabolism. Measures to preserve renal function should therefore also comprise the maintenance of hemoglobin, serum lipid, and calcium-phosphorus ion product levels in the normal range

Involvement of glomerular renin−angiotensin system (RAS) activation in the development and progression of glomerular injury

Recently, there has been a paradigm shift away from an emphasis on the role of the endocrine (circulating) renin−angiotensin system (RAS) in the regulation of the sodium and extracellular fluid balance, blood pressure, and the pathophysiology of hypertensive organ damage toward a focus on the role of tissue RAS found in many organs, including kidney. A tissue RAS implies that RAS components necessary for the production of angiotensin II (Ang II) reside within the tissue and its production is regulated within the tissue, independent of the circulating RAS. Locally produced Ang II plays a role in many physiological and pathophysiological processes such as hypertension, inflammation, oxidative stress, and tissue fibrosis. Both glomerular and tubular compartments of the kidney have the characteristics of a tissue RAS. The purpose of this article is to review the recent advances in tissue RAS research with a particular focus on the role of the glomerular RAS in the progression of renal disease

Assessment of long-term renal complications in extremely low birth weight children

We assessed the long-term renal complications in a regional cohort of extremely low birth weight (ELBW) children born in 2002–2004. The study group, comprising 78 children born as ELBW infants (88% of the available cohort), was evaluated with measurement of serum cystatin C, urinary albumin excretion, renal ultrasound, and 24-h ambulatory blood pressure measurements. The control group included 38 children born full-term selected from one general practice in the district. Study patients were evaluated at a mean age of 6.7 years, and had a median birthweight of 890 g (25th–75th percentile: 760–950 g) and a median gestational age of 27 weeks (25th–75th percentile: 26–29 weeks). Mean serum cystatin C levels were significantly higher (0.64 vs. 0.59 mg/l; p = 0.01) in the ELBW group. Hypertension was diagnosed in 8/78 ELBW and 2/38 of the control children (p = 0.5). Microalbuminuria (>20 mg/g of creatinine) was detected only in five ELBW children (p = 0.17). The mean renal volume was significantly lower in the ELBW group (absolute kidney volume 81 ml vs. 113 ml; p < 0.001, relative kidney volume 85 vs. 97%; p < 0.001). Abnormally small kidneys (<2/3 of predicted size) were detected in 19 ELBW and four control children (p = 0.08). Multivariate logistic regression revealed that the only independent risk factor for renal complications was weight gained during neonatal hospitalization (odds ratio: 0.67; 95% confidence interval: 0.39–0.94). Serum cystatin C and kidney volume are significantly lower in school-age ELBW children. It is important to include systematic renal evaluation in the follow-up programs of ELBW infants

Therapeutic approach to FSGS in children

Therapy of primary focal segmental glomerulosclerosis (FSGS) in children incorporates conservative management and immunosuppression regimens to control proteinuria and preserve kidney function. In long-term cohort studies in adults and children with primary FSGS, renal survival has been directly associated with degree of proteinuria control. This educational article reviews the current therapeutic approach toward children with primary FSGS

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