Relationship of FGF23 to indexed left ventricular mass in children with non-dialysis stages of chronic kidney disease.

BACKGROUND: The aim of this study was to evaluate the association of serum intact fibroblast growth factor 23 (FGF23) concentrations with indexed left ventricular mass in children with non-dialysis stages 3-5 of chronic kidney disease (CKD). METHODS: The study cohort comprised 83 children (51 boys; mean age 12.1 ± 3.2 years) with a mean estimated glomerular filtration rate (eGFR) of 32.3 ± 14.6 ml/min/1.73 m(2) who underwent clinic and ambulatory blood pressure measurement (ABPM), echocardiography and evaluation of biochemical markers of CKD-associated mineral bone disease. RESULTS: The mean left ventricular mass index (LVMI) was 35.9 ± 8.5 g/m(2.7) (± standard deviation), with 30 (36.1 %) children showing left ventricular hypertrophy (LVH), all eccentric, as defined using age-specific criteria. For all subjects, the mean FGF23 concentration was 142.2 ± 204.4 ng/l and the normalised distribution following log transformation was 1.94 ± 0.39. There was significant univariate correlation of LVMI with GFR, body mass index (BMI) z-score and calcium intake, but not with 24-h systolic ABPM z-score, log intact parathyroid hormone or log FGF23. On multivariate analysis following adjustment for confounders, only elemental calcium content (g/kg/day) estimated from prescribed calcium-based phosphate binder dose (ß = 154.9, p < 0.001) and BMI z-score (ß = 2.397, p = 0.003) maintained a significant positive relationship with LVMI (model r (2) = 0.225). CONCLUSIONS: We observed no significant relationship of FGF23 with LVMI. Larger studies in children are needed to clarify the roles of calcium-containing phosphate binders and FGF23 with LV mass and their roles in the evolution of the development of adverse cardiovascular outcomes.

The demographic characteristics of children with chronic kidney disease stages 3-5 in South East England over a 5-year period.

OBJECTIVE: To analyse the demographics of children with moderate to severe chronic kidney disease (CKD) stages 3-5 over a 5-year period for the population of South East England. METHODS: Retrospective study of all children <18 years of age with estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2) managed at Evelina Children's Hospital, London from 2005 to 2009. eGFR was estimated using the Schwartz formula, and stages of CKD were defined using Kidney Disease Outcome Quality Initiative criteria. We excluded all patients with a functioning kidney transplant. RESULTS: There were 293 children (58% male) with a median (IQR) age of 6.7 (2.3, 12.1) years; 288 were aged <16 years and five 16-18 years at first presentation. The mean incidence and prevalence of children <16 years with CKD stage 3-5 during the 5-year study period was 17.5 and 90.0 per million age-related population (pmarp), respectively. There was a marked increase in incidence and prevalence over the 5 years (incidence 8.4 to 25.2 pmarp; prevalence 79.5 to 104.7 pmarp). There was an initial peak in children presenting under 2 years of age (48/141, 34%) due to congenital renal disease, and a second peak in the 12-15.9-year age group (32/141, 23%) due to glomerulonephritides. Forty-five children (15%) were transplanted, and 22 (8%) transitioned to adult care. There were seven deaths giving a death rate of 0.84 per 100 patient-years. CONCLUSIONS: We observed a steady increase in the incidence and prevalence of children with CKD stage 3-5. As a result of improved management, the majority of children with CKD will proceed to kidney transplantation, transition to adult nephrology services, and continue to require lifelong medical care.

Investigating the role of cardiovascular biomarkers in children with pre-dialysis chronic kidney disease: a substitute to echocardiography to detect increased left ventricular mass?

BACKGROUND: Children with chronic kidney disease (CKD) are at increased risk of future cardiovascular (CV) events. Our aim in this prospective single-centre cross-sectional analysis was to assess the relationship of a novel panel of CV biomarkers with left ventricular hypertrophy (LVH). METHODS: A panel of five CV biomarkers (asymmetric dimethyl arginine, high sensitivity C-reactive protein, homocysteine, N-terminal pro-B type natriuretic peptide and uric acid) were measured on the same day as an echocardiogram assessment, in paediatric patients with pre-dialysis stages 3-5 of CKD. RESULTS: Of 73 children aged 5-18 years, LVH, all eccentric, was identified in 38%. Systolic blood pressure (BP), glomerular filtration rate (GFR) and higher intake of calcium-based phosphate binders were significantly worse in children with LVH. In multivariate models analysing each biomarker one at a time with confounders [GFR, systolic BP z-score, anti-hypertensive medication (yes/no) and elemental calcium intake], clinic systolic BP z-score and elemental calcium intake consistently displayed a significant relationship with indexed left ventricular mass (LVMI). None of the evaluated CV biomarkers displayed a significant relationship with LVMI. CONCLUSIONS: In our cohort of children with moderately severe pre-dialysis CKD we have identified no suitable biomarkers to detect LVH. We would therefore recommend that echocardiographic determination of LVMI remains the technique of choice for detection of LVH in children with CKD.

Investigating FGF-23 concentrations and its relationship with declining renal function in paediatric patients with pre-dialysis CKD Stages 3-5.

BACKGROUND: The aims of our study were to investigate (i) the prevalence of elevated fibroblast growth factor-23 (FGF-23), (ii) the relationship between FGF-23 concentrations and level of renal dysfunction and (iii) the main determinants of elevation of FGF-23 concentration in children with pre-dialysis chronic kidney disease (CKD) Stages 3-5. METHODS: In this single-centre prospective observational study, 71 children with pre-dialysis CKD Stages 3-5, aged 11.9 ± 3.1 years, had FGF-23 levels measured. Anthropometry and routine laboratory investigations were measured. RESULTS: Fourteen (19.7%) patients had normal FGF-23 concentrations defined as < 50 ng/L. FGF-23 [median (interquartile range)] concentrations were 78.7 (55.6-137.6) ng/L and following log transformation normalized data with log FGF-23 [mean (SD)] values of 1.96 ± 0.4 ng/L. Log FGF-23 concentrations had a negative reciprocal relationship with estimated glomerular filtration rate (eGFR) (P < 0.0001) and 1,25 vitamin D3 levels (P = 0.01) and a positive relationship with phosphate (P = 0.03) and percent fractional excretion of phosphate (P = 0.01) but not with log-intact parathyroid hormone (PTH) (P = 0.22). Multiple linear regression demonstrated a strong relationship between log FGF-23 and eGFR only. CONCLUSIONS: Elevated FGF-23 concentrations were observed in the majority of a carefully managed cohort of children with non-dialysis CKD with a dominant effect on FGF-23 concentrations with glomerular filtration rate (GFR). These data allow the potential confounding effects of PTH and phosphate elevation with declining GFR to be removed, leaving a clearer picture of the FGF-23-GFR relationship.

Factors affecting success of blood pressure measurements during ambulatory blood pressure monitoring in children with renal disease.

AIM: To analyse blood pressure characteristics during 24-hour ambulatory blood pressure monitoring in children and to assess factors that influence its success over 24 hours and during patient-recorded awake (DAY) and sleep (NIGHT) periods. METHODS: A total of 169 consecutive ambulatory blood pressure monitoring studies were conducted in 154 patients over 30 months. For each ambulatory study, we measured the percentage of successful measurements both at the first attempt (S-initial%) and following any automated repeat attempt if initial attempts had failed (S-final%). These were measured over 24-hour, DAY, and NIGHT periods. RESULTS: We found that blood pressure measurements at NIGHT were more successful than measurements attempted during the DAY (p<0.05). There was no influence of age, gender, height, weight, body mass index and estimated glomerular filtration rate with the proportion of successful measurements during the 24-hour, DAY, and NIGHT periods. On stepwise multiple regression analysis, the indexed mean systolic blood pressure over 24 hours was the only factor having a significant influence on the proportion of successful measurements over the 24-hour and DAY periods, although it only accounted for three-tenths of the variance; it had no influence on the overall success of measurements at NIGHT. CONCLUSION: Ambulatory blood pressure monitoring in children provides reliable data both during the patient's awake and sleep periods with higher success of measurements at NIGHT as opposed to DAY periods.

Blood pressure control and left ventricular mass in children with chronic kidney disease.

BACKGROUND AND OBJECTIVES: Heart disease is a major cause of death in young adults with chronic kidney disease (CKD). Left ventricular hypertrophy (LVH) is common and is associated with hypertension. The aims of this study were to evaluate whether there is a relationship between LVH and BP in children with CKD and whether current targets for BP control are appropriate. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this single-center cross-sectional study, 49 nonhypertensive children, (12.6 ± 3.0 years, mean GFR 26.1 ± 12.9 ml/min per 1.73 m²) underwent echocardiographic evaluation and clinic and 24-hour ambulatory BP monitoring. LVH was defined using age-specific reference intervals for left ventricular mass index (LVMI). Biochemical data and clinic BP for 18 months preceding study entry were also analyzed. RESULTS: The mean LVMI was 37.8 ± 9.1 g/m²·7, with 24 children (49%) exhibiting LVH. Clinic BP values were stable over the 18 months preceding echocardiography. Patients with LVH had consistently higher BP values than those without, although none were overtly hypertensive (> 95th percentile). Multiple linear regression demonstrated a strong relationship between systolic BP and LVMI. Clinic systolic BP showed a stronger relationship than ambulatory measures. Of the confounders evaluated, only elemental calcium intake yielded a consistent, positive relationship with LVMI. CONCLUSIONS: LVMI was associated with systolic BP in the absence of overt hypertension, suggesting that current targets for BP control should be re-evaluated. The association of LVMI with elemental calcium intake questions the appropriateness of calcium-based phosphate binders in this population.

Congenital disorders of glycosylation: a rare cause of nephrotic syndrome.

Congenital disorders of glycosylation (CDG) are inborn errors of metabolism presenting with multi-system organ involvement due to defective glycosylation of glycoproteins. We report here a case of microcephaly, hypotonia, seizure disorder and severe developmental delay since infancy in whom screening for CDG with transferring isoelectric focussing (TIEF) revealed a type I pattern. Following investigation, the specific defect in glycosylation remains to be identified; hence, a diagnosis of CDG Ix (type unknown) was made. At the age of 15-months the patient developed nephrotic syndrome and renal biopsy indicated a histopathological diagnosis of diffuse mesangial sclerosis on histopathology. Since cases of CDG Ix may often develop hypoalbuminaemia secondary to malabsorption or liver disease, this case highlights the need for additional regular monitoring for glomerular proteinuria, and indicates that a diagnosis of nephrotic syndrome should be considered in all types of CDG. Furthermore, we propose that early treatment with anti-proteinuric agents may be necessary to limit proteinuria and slow disease progression.