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Cardiovascular Disease Risk in Children With Chronic Kidney Disease: Impact of Apolipoprotein C-II and Apolipoprotein C-III.

ABSTRACT: Cardiovascular disease (CVD) is an evolving process that begins in the early stages of chronic kidney disease (CKD) in children. Several surrogate markers, such as ambulatory blood pressure monitoring (ABPM), left ventricular (LV) mass, and arterial stiffness assessment, allow for the early detection of subclinical CVD in pediatric CKD. Four groups of plasma samples (n = 3/group) from congenital anomalies of the kidney and urinary tract (CAKUT), as well as non-CAKUT patients with or without BP abnormalities, were studied to screen differentially expressed proteins using isobaric tags for relative and absolute protein quantification (iTRAQ)-based proteomics. As a result, 20 differentially expressed proteins associated with hypertension in children with CKD were discovered. Among them, apolipoprotein C-II (apoC-II) was found to have the highest abundance among the CKD patients with hypertension. As such, we hypothesized that apoC-II and apolipoprotein C-III (apoC-III) levels were related to BP abnormalities and CVD in children suffering from mild-to-moderate CKD. We examined their associations with surrogate markers of CV risk in 88 pediatric patients with CKD stages G1-G4. Children with CKD stages G2-G4 had a higher plasma apoC-II level than G1 patients (6.35 vs. 5.05 mg/dl, p < 0.05). We observed that ABPM abnormalities, LV mass, and arterial stiffness parameters were greater in CKD children who had stages G2-G4 than in those who had stage G1 (all p < 0.05). Plasma levels of apoC-II and apoC-III were positively correlated with total cholesterol, triglyceride, and low-density lipoprotein (LDL) (all p < 0.001). In multivariate linear regression analyses, apoC-II was correlated with a high LV mass index and an abnormal ABPM profile, and apoC-III was correlated with 24-h hypertension (r = 0.303, p = 0.003) and asleep hypertension (r = 0.379, p < 0.001). Early evaluations of apoC-II and apoC-III, ABPM, and surrogate markers of CV risk will aid in early preventative interventions to reduce the risk of CV in youths suffering from CKD.

SUBMITTER: Chen WL

PROVIDER: S-EPMC8397580 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Failure of statural growth is one of the major long-term sequelae of chronic kidney disease (CKD) in children. In recent years effective therapeutic strategies have become available that lead to evidence based practice recommendations. To assess the current growth performance of European children and adolescents with CKD, we analyzed a cohort of 594 patients from 12 European countries who were followed prospectively for up to 6 years in the 4C Study. While all patients were on conservative treatment with a mean estimated glomerular filtration rate of 28 ml/min/1.73 m2 at study entry, 130 children commenced dialysis during the observation period. At time of enrolment the mean height standard deviation score (SDS) was -1.57; 36% of patients had a height below the third percentile. The prevalence of growth failure varied between countries from 7 to 44% Whereas patients on conservative treatment showed stable growth, height SDS gradually declined on those on dialysis. Parental height, pubertal status and treatment with recombinant growth hormone (GH) were positively, and the diagnosis of syndromic disease and CKD stage were negatively associated with height SDS during the observation period. Unexpectedly, higher body mass index (BMI) SDS was associated with lower height SDS both at enrolment and during follow up. Renal anemia, metabolic acidosis, and hyperparathyroidism were mostly mild and not predictive of growth rates by multivariable analysis. GH therapy was applied in only 15% of growth retarded patients with large variation between countries. When adjusting for all significant covariates listed above, the country of residence remained a highly significant predictor of overall growth performance. In conclusion, growth failure remains common in European children with CKD, despite improved general management of CKD complications. The widespread underutilization of GH, an approved efficacious therapy for CKD-associated growth failure, deserves further exploration.

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Cardiovascular Disease Risk in Children With Chronic Kidney Disease: Impact of Apolipoprotein C-II and Apolipoprotein C-III.

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