Factors associated with cardiovascular target organ damage in children after renal transplantation.

BACKGROUND: Cardiovascular disease is the second-most common cause of death in pediatric renal transplant recipients. The aim of this study was to evaluate subclinical cardiovascular target organ damage defined as the presence of arterio- and atherosclerotic lesions and cardiac remodeling and to analyze contributing risk factors in a large cohort of children after renal transplantation (RT). METHODS: A total of 109 children aged 13.1 ± 3.3 years who had undergone RT at one of three German transplant centers were enrolled in this study. Patients had been transplanted a mean of 5.5 (±4.0) years prior to being enrolled in the study. Anthropometric data, laboratory values and office- and 24-h ambulatory blood pressure monitoring (ABPM) were evaluated. Cardiovascular target organ damage was determined through non-invasive measurements of aortic pulse wave velocity (PWV), carotid intima-media thickness (IMT) and left ventricular mass (LVM). RESULTS: Elevated PWV or IMT values were detected in 22 and 58% of patients, respectively. Left ventricular hypertrophy was found in as many as 43% of patients. The prevalence of uncontrolled or untreated hypertension was 41%, of which 16% of cases were only detected by ABPM measurements. In the multivariable analysis, higher diastolic blood pressure, everolimus intake and lower estimated glomerular filtration rate were independently associated with high PWV. Higher systolic blood pressure and body mass index were associated with elevated LVM. CONCLUSIONS: Our results showed an alarming burden of cardiovascular subclinical organ damage in children after RT. Hypertension, obesity, immunosuppressive regimen and renal function emerged as independent risk factors of organ damage. Whereas the latter is not modifiable, the results of our study strongly indicate that the management of children after RT should focus on the control of blood pressure and weight.

Rapid Response to Cyclosporin A and Favorable Renal Outcome in Nongenetic Versus Genetic Steroid-Resistant Nephrotic Syndrome.

BACKGROUND AND OBJECTIVES: Treatment of congenital nephrotic syndrome (CNS) and steroid-resistant nephrotic syndrome (SRNS) is demanding, and renal prognosis is poor. Numerous causative gene mutations have been identified in SRNS that affect the renal podocyte. In the era of high-throughput sequencing techniques, patients with nongenetic SRNS frequently escape the scientific interest. We here present the long-term data of the German CNS/SRNS Follow-Up Study, focusing on the response to cyclosporin A (CsA) in patients with nongenetic versus genetic disease. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Cross-sectional and longitudinal clinical data were collected from 231 patients with CNS/SRNS treated at eight university pediatric nephrology units with a median observation time of 113 months (interquartile range, 50-178). Genotyping was performed systematically in all patients. RESULTS: The overall mutation detection rate was high at 57% (97% in CNS and 41% in SRNS); 85% of all mutations were identified by the analysis of three single genes only (NPHS1, NPHS2, and WT1), accounting for 92% of all mutations in patients with CNS and 79% of all mutations in patients with SRNS. Remission of the disease in nongenetic SRNS was observed in 78% of patients after a median treatment period of 2.5 months; 82% of nongenetic patients responded within 6 months of therapy, and 98% of patients with nongenetic SRNS and CsA-induced complete remission (normalbuminemia and no proteinuria) maintained a normal renal function. Genetic SRNS, on the contrary, is associated with a high rate of ESRD in 66% of patients. Only 3% of patients with genetic SRNS experienced a complete remission and 16% of patients with genetic SRNS experienced a partial remission after CsA therapy. CONCLUSIONS: The efficacy of CsA is high in nonhereditary SRNS, with an excellent prognosis of renal function in the large majority of patients. CsA should be given for a minimum period of 6 months in these patients with nongenetic SRNS. In genetic SRNS, response to CsA was low and restricted to exceptional patients.

Validating a new oscillometric device for aortic pulse wave velocity measurements in children and adolescents.

BACKGROUND: Pulse wave velocity (PWV) is an indicator of aortic stiffness and a predictor of cardiovascular risk. Applanation tonometry (e.g., SphygmoCor) is a well-established method to measure aortic PWV (aPWV). The Vicorder, a new oscillometric device, has not been validated in children and adolescents. METHODS: We performed intra- and interobserver repeatability studies in 14 individuals using the Vicorder. Vicorder and SphygmoCor measurements were compared in 156 healthy children (6-18 years) using two different path length measurements. RESULTS: Intra- and interobserver repeatabilities of the Vicorder were excellent with coefficients of variation of 5.6% and 5.8% and intraclass correlation coefficients (ICCs) of 0.8 and 1.0. aPWV calculated using the distances (suprasternal notch-to-femoral recording point) - (suprasternal notch-to-carotid artery), the path length most commonly used in adults, revealed a mean of 4.8 ± 0.7 m/s for SphygmoCor and 4.9 ± 0.6 m/s for Vicorder. The percentage deviation between both devices was 13.0% and the limit of agreement (LoA) ranged from -1.0 to 1.7 m/s reflecting a good concordance. Using a path length that measured the distance from suprasternal notch to femoral recording point via the umbilicus (Umb), an even better agreement was found (percentage deviation: 11.8%, LoA: -1.0 to 1.6 m/s). CONCLUSIONS: Vicorder aPWV values are similar to those obtained by SphygmoCor applanation tonometry. The best agreement between devices was obtained with the path length that most accurately describes the aortic tree. Excellent intra- and interobserver repeatability and ease of measurements make Vicorder appropriate for large multicentre studies in children and adolescents.