Cardiac biomarkers in pediatric CKD-a prospective follow-up study.

BACKGROUND: The N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitive cardiac-specific troponin T (hs-cTnT) are associated with abnormal cardiac structure and function and an increased risk of cardiovascular death in chronic kidney disease (CKD) patients. There is limited knowledge about these cardiac markers in pediatric CKD patients. METHODS: Longitudinal levels of NT-proBNP and hs-cTnT were analyzed in 48 pediatric patients, 22 with CKD (GFR range 8.8-68 mL/min/1.73 m2) and 26 transplanted patients (CKD-T; GFR range 30-99 mL/min/1.73 m2). Follow-up was scheduled after 1 and 3 years. Longitudinal patterns and associations to kidney function, cardiovascular risk markers, and echocardiographic parameters were assessed. RESULTS: High NT-proBNP was present in 27% of CKD and 11% of CKD-T patients. Similarly 32% of CKD and 8% of CKD-T patients had elevated hs-cTnT levels. In longitudinal multivariate analyses, high log NT-proBNP was associated with low GFR (ß = - 0.01, p = 0.01) and elevated left ventricular mass index (LVMI; ß = 0.02, p = 0.05). The strong association to LVMI remained when using GFR-adjusted NT-proBNP in similar analysis. Patients with left ventricular hypertrophy (LVH) also had higher NT-proBNP (235 [146-301] ng/L) than patients without LVH (86 [11-477] ng/L), p = 0.02. High hs-cTnT over-time was also associated with low GFR (ß = - 0.007, p = 0.01) and a low cc-TDI e´/a´, indicating a worse LV diastolic function (ß = - 0.09, p = 0.05). This association did not persist for GFR-adjusted hs-cTnT. CONCLUSIONS: NT-proBNP and hs-cTnT are elevated in pediatric CKD and CKD-T patients. GFR-adjusted NT-proBNP was associated with longitudinal levels of elevated LVMI suggesting this might be a marker for early subclinical myocardial damage. A higher resolution version of the Graphical abstract is available as Supplementary information.

Left ventricular diastolic dysfunction by tissue Doppler echocardiography in pediatric chronic kidney disease.

BACKGROUND: Myocardial dysfunction is common in chronic kidney disease (CKD) and related to poor outcomes. New non-invasive methods to assess cardiac function have been introduced, but comparative studies evaluating their clinical usefulness in pediatric CKD are lacking. We studied left ventricular (LV) function in pediatric CKD and renal transplant patients, comparing conventional pulse-wave Doppler echocardiography (cPWD) with newer tissue Doppler imaging (TDI) and relating the results to known cardiovascular risk factors. METHODS: The study included 34 children/adolescents with CKD stages 2-5, 44 renal transplant patients and 19 patients with a normal renal function. The mean age was 11.4 (range 0.8-18.8) years. RESULTS: Both patient groups had significantly lower LV diastolic function than those with a normal renal function. The most sensitive determinants were TDI E'/A' and cPWD E/TDI E' ratios. In a stepwise linear regression analysis, high blood pressure, young age and the presence of albuminuria all independently predicted LV diastolic function. CONCLUSIONS: Our study confirms the high prevalence of LV diastolic dysfunction in pediatric CKD patients and following renal transplantation, where TDI appears to be more sensitive than cPWD in assessing early myocardial dysfunction. Our results also underline the importance of preventive measures, such as rigorous blood pressure control, in pediatric CKD.

Use of annual ABPM, and repeated carotid scan and echocardiography to monitor cardiovascular health over nine yr in pediatric and young adult renal transplant recipients.

In adult hypertensive patients, increased cIMT and LVH are independent risk factors for cardiovascular events. We have previously observed that in pediatric RTRs with tight control of BP, cIMT did not progress over time. This investigation is an extension of the aforementioned study aimed at re-examining cIMT and also reporting serial echocardiography results. Twenty-two RTRs aged 9.4 ± 3.3 yr at their baseline carotid scan underwent two additional vascular ultrasounds during a follow-up of 9.1 ± 0.9 yr. Carotid scan and echocardiography examinations were carried out simultaneously with ABPM. Antihypertensive therapy was determined according to the recipient's ABPM results, which were performed at yearly intervals. Baseline cIMT was significantly greater in RTRs than in healthy controls. There was no statistical evidence of systematic changes in cIMT over time. At the last examination, 14 of 17 RTRs with treated hypertension had controlled hypertension (prevalence 82%; 95% CI, 56.5-96.2), and the overall prevalence of LVH was 4.5% (95% CI, -0.01 to 23.5). The lack of progression of cIMT over time and the low prevalence of LVH might reflect the effect of long-standing BP control.

Hyperinsulinemia and insulin resistance, early cardiovascular risk factors in children with chronic kidney disease.

BACKGROUND/AIMS: Pediatric chronic kidney disease (CKD) is associated with increased risk of cardiovascular disease. Still, hyperinsulinemia and insulin resistance, common cardiovascular risk factors, are not extensively investigated in children with CKD. We hypothesize that insulin abnormalities are present also in pediatric mild to moderate CKD, and associated with inflammation and malnutrition. METHODS: We enrolled 26 children with CKD, and 34 healthy controls for analyses of blood samples and body composition. Insulin resistance was assessed using the homeostasis model assessment for insulin resistance (HOMA-IR). RESULTS: The patients had higher insulin levels and HOMA-IR compared to the controls (p < 0.01 and p < 0.005), and they correlated inversely with estimated glomerular filtration rate (rho = -0.52, p < 0.01; rho = -0.37, p = 0.08). No association was found with inflammation or malnutrition. CONCLUSION: High insulin levels and HOMA-IR appear to be common in pediatric CKD patients, already in mild to moderate renal failure. We hypothesize that hyperinsulinemia and insulin resistance alone might be important risk factors for cardiovascular disease in children with CKD.