Disfunción endotelial en niños con enfermedad renal crónica / Endothelial dysfunction in children with chronic kidney disease

Antecedentes y objetivo: La enfermedad cardiovascular es la principal causa de muerte en niños con enfermedad renal crónica. La inflamación y la disfunción endotelial se presenta en la mayoría de estos pacientes y son factores asociados a enfermedad cardiovascular. La dilatación mediada por flujo (DMF)<7% es un marcador subrogado validado en la evaluación de la disfunción endotelial. Nuestro objetivo fue identificar los factores de riesgo asociados a disfunción endotelial en niños con enfermedad renal crónica. Materiales y métodos: Se estudió a niños de 2-16 años de edad. Se recopiló su información clínica y variables bioquímicas, incluidos hormona paratiroidea intacta (iPTH), interleucinas 6 y 1β, proteína C reactiva de alta sensibilidad (hsCRP), glutatión reducido, óxido nítrico, malondialdehído y homocisteína. Se consideró DMF alterada<7%. Resultados: Se incluyó a 129 pacientes con edad de 13,1±2,6 años. Tuvieron DMF<7% 69 (52,7%). Los pacientes con DMF<7% tuvieron niveles más altos de triglicéridos y de hsCRP que aquellos con DMF≥7% (145,5 vs. 120,0mg/dl, p=0,042, y 1,24 vs. 0,55U/l, p=0,007, respectivamente), así como una mayor frecuencia de iPTH baja (19,1 vs. 4,9%, p=0,036). Los niveles de hsCRP se correlacionaron significativamente con la DMF (Rho=−0,28, p=0,003). Los pacientes con iPTH baja (OR 4,41, IC 95% 1,13-17,27, p=0,033) y con hsCRP incrementada (OR 2,89, IC 95% 1,16-7,17, p=0,022) tuvieron un riesgo ajustado mayor de DMF<7%. Conclusiones: La hipertrigliceridemia, la inflamación y una iPTH baja se asociaron significativamente a una DMF alterada. Son factores de riesgo de enfermedad cardiovascular frecuentes y tratables. (AU)

Background and objective: Cardiovascular disease is the main cause of death in children with chronic kidney disease. Inflammation and endothelial dysfunction are found in the majority of these patients and are factors associated to cardiovascular disease. Flow mediated dilatation (FMD) is a surrogate marker validated for evaluating endothelial dysfunction. Our objective was to identify risk factors associated to endothelial dysfunction in children with chronic kidney disease. Materials and methods: Children 2-16 years of age were studied. Clinical information and biochemical variables were gathered, including intact parathyroid hormone (iPTH), interleukins 6 and 1β, high sensitivity C reactive protein (hsCRP), reduced glutathione, nitric oxide, malondialdehyde and homocysteine. FMD was measured, and considered altered if<7%. Results: Included were 129 patients aged 13.1±2.6 years. FMD<7% was found in 69 (52.7%). Patients with altered FMD had higher levels of triglycerides and hsCRP than those with normal FMD (145.5 vs. 120.0mg/dL, P=.042, and 1.24 vs. 0.55U/L, P=.007, respectively), as well as higher frequency of low iPTH (19.1 vs. 4.9%, P=.036). Levels of hsCRP correlated significantly with FMD (Rho=−0.28, P=.003). Patients with low iPTH (OR 4.41, 95% CI 1.13-17.27, P=.033) and increased hsCRP (OR 2.89, 95% CI 1.16-7.17, P=.022) had higher adjusted risk of having FMD<7%. Conclusions: Hypertriglyceridemia, inflammation and low iPTH associated significantly with altered FMD. They are frequent, treatable risk factors for cardiovascular disease. (AU)

Endothelial dysfunction in children with chronic kidney disease.

BACKGROUND AND OBJECTIVE: Cardiovascular disease (CVD) is the main cause of death in children with chronic kidney disease (CKD). Inflammation and endothelial dysfunction (ED) are found in the majority of these patients and are factors associated to CVD. Flow mediated dilatation (FMD) is a surrogate marker validated for evaluating ED. Our objective was to identify risk factors associated to ED in children with CKD. MATERIALS AND METHODS: Children 2-16 years of age were studied. Clinical information and biochemical variables were gathered, including intact parathyroid hormone (iPTH), interleukins 6 and 1b, high sensitivity C reactive protein (hsCRP), reduced glutathione, nitric oxide, malondialdehyde and homocysteine. FMD was measured, and considered altered if <7%. RESULTS: Included were 129 patients aged 13.1 ±â€¯2.6 years. FMD < 7% was found in 69 (52.7%). Patients with altered FMD had higher levels of triglycerides and hsCRP than those with normal FMD (145.5 mg/dl vs. 120.0 mg/dl, P = .042, y 1.24 U/L vs. 0.55 U/L, P = .007, respectively), as well as higher frequency of low iPTH (19.1% vs. 4.9%, P = .036). Levels of hsCRP correlated significantly with FMD (Rho = -0.28, P = .003). Patients with low iPTH (OR = 4.41, 95%CI 1.13-17.27, P = .033) and increased hsCRP (OR = 2.89, 95%CI 1.16-7.17, P = .022) had higher adjusted risk of having FMD < 7%. CONCLUSIONS: Hypertriglyceridemia, inflammation and low iPTH associated significantly with altered FMD. They are frequent, treatable risk factors for CVD.

Carotid intima media thickness, oxidative stress, and inflammation in children with chronic kidney disease.

OBJECTIVE: We evaluated the association between inflammation and oxidative stress with carotid intima media thickness (cIMT) and elasticity increment module (E(inc)) in pediatric patients with chronic kidney disease (CKD). METHODS: This analytical, cross-sectional study assessed 134 children aged 6-17 years with CKD. Anthropometric measurements and biochemistry of intact parathyroid hormone (iPTH), high-sensitivity C-reactive protein (CRP), interleukin (IL)-6, IL-1ß, reduced glutathione (GSH), malondialdehyde, nitric oxide, and homocysteine were recorded. Bilateral carotid ultrasound (US) was taken. Patients were compared with controls for cIMT and E(inc) using ≥ 75 percentile (PC). RESULTS: Mean cIMT was 0.528 ± 0.089 mm; E(inc) was 0.174 ± 0.121 kPa × 10(3); cIMT negatively correlated with phosphorus (r -0.19, p =0.028) and the calcium × phosphorus (Ca × P) product (r -0.26, p =0.002), and positively with iPTH (r 0.19,p =0.024). After adjusting for potential confounders, hemodialysis (HD) (ß=0.111, p =<0.001), automated peritoneal dialysis (APD) (ß=0.064, p =0.026), and Ca x P product(ß=-0.002, p =0.015) predicted cIMT (R(2)=0.296). In patients on dialysis, HD (ß=0.068, p =0.010), low-density lipoprotein cholesterol (LDL-C) (ß=0.001, p =0.048), and GSH(ß=-0.0001, p=0.041) independently predicted cIMT (R(2)=0.204); HD, hypoalbuminemia, and high iPTH increased the risk of increased cIMT. In dialysis, E(inc) was inversely associated with GSH, and in predialysis, Ca × P correlated with/predicted E(inc) (ß=0.001, p =0.009). CONCLUSIONS: cIMT and E(inc) strongly associate with several biochemical parameters and GSH but not with other oxidative stress or inflammation markers.

Frequency of low carnitine levels in children on dialysis.

To determine the frequency of low carnitine levels, we measured serum carnitine in pediatric patients on peritoneal dialysis (PD) and hemodialysis (HD). Our prospective cross-sectional study was conducted from September 2004 to March 2005 in a single pediatric center, and included patients under 17 years of age who had been on HD or PD for more than 3 months. Patients with primary carnitine deficiency were excluded. A 4-day food diary was used for carnitine intake quantification. Serum total and free carnitine and acylcarnitine were measured. We compared patients with low and normal carnitine levels using the chi-square test, Mann-Whitney U-test, and Spearman correlation. Of 100 study patients, 70 were on PD, and 61 were male. The median age was 13 years, and the median time on dialysis, 10.5 months. Median serum free carnitine was 32.75 nmol/mL. Carnitine levels were lower than normal in 75 patients and reached the level of deficiency in 29. No difference was found between the dialysis modality types for any fraction of carnitine. No correlation was found between the level of free carnitine and time on dialysis (r = -0.009, p = 0.9) or carnitine intake (r = -0.84, p = 0.4). In conclusion, the frequency ofl ow serum carnitine among pediatric patient on dialysis is high.