Dialysis provides effective and safe treatment of ESRD in children, but patients who are maintained on chronic dialysis are at risk for cardiovascular disease. One major risk factor for cardiovascular disease in adult patients with ESRD is chronic inflammation. The effect of anti-inflammatory therapy with aspirin on serum cytokine concentration was studied in seven children who were receiving hemodialysis (HD) and seven who were receiving continuous cycling peritoneal dialysis (CCPD or PD). A lthough the advent of dialysis provides effective and safe treatment of ESRD in pediatric patients, children who are maintained on long-term dialysis are at risk for significant cardiovascular disease (CVD). Although many CVD risk factors have not been studied in the pediatric dialysis population, studies in adult patients with ESRD demonstrate that cardiovascular calcifications and inflammation (1), abnormal calcium-phosphorus metabolism (2), and malnutrition (3) play a role in CVD development.A burgeoning area of research in the past decade has focused on the role of inflammation in dialysis patients. Inflammation, mediated by proinflammatory cytokines, contributes substantially to morbidity and mortality (4 -8) in adult patients with ESRD. We previously showed that the proinflammatory cytokines IL-1 and TNF-␣ increased significantly after hemodialysis (HD), whereas there was only a mild increase in the antiinflammatory cytokine IL-10, suggesting an imbalance of cytokine production favoring the proinflammatory response. Consistent with the enhanced inflammatory state were the elevated C-reactive protein levels in a majority of the patients whom we studied (9) and that the degree of inflammation correlated with the number of years that patients lived with ESRD (dialysis vintage). A recent study showed that there is increased oxidant stress and early cardiovascular damage in children with various stages of renal insufficiency, although the cohort included only a small number of patients who were receiving dialysis (10). On the basis of our previous studies, we decided to perform a pilot study to assess the anti-inflammatory capacity of daily, low-dosage aspirin on serum cytokine concentrations in children who were receiving maintenance HD or peritoneal dialysis (PD).
Materials and Methods
PatientsAll patients who had been receiving either maintenance HD or continuous cycling PD (CCPD) for at least two consecutive months in the Texas Children's Hospital Renal Dialysis Unit were eligible to enroll in the study. Informed consent was obtained from each patient's parent, and assent was obtained from each patient who was older than 14 yr before study enrollment. The Institutional Review Boards from both Baylor College of Medicine and Louisiana State University Health Sciences Center approved the study protocol before its initiation. Patients were selected to ensure inclusion of a wide spectrum of pediatric ages, with similar mean age and range between the two groups that were receiving HD and PD. Patients were excluded from the ...
Antagonists to the N-methyl-D-aspartate (NMDA) receptor bind to various extraneuronal tissues. We therefore assessed the expression of the main NMDA subunit, NR1, in various tissues. We demonstrate that NR1 appears to be most abundant in the rat kidney and heart. NR1 is present in total rat kidney, cortex, and medulla. Of the NR2 subunits, only the NR2C subunit protein is present in the kidney. The abundance of the NR1 subunit protein increases with kidney development. Both NR1 and NR2C are present in opossum kidney, Madin-Darby canine kidney, and LLC-PK(1) cells. Immunohistochemistry studies show that the NR1 subunit is present in the renal proximal tubule. NR1 is abundant in the atrium and ventricle but is also expressed in the aorta and pulmonary artery. The NR2 subunits are not expressed in the heart. NR1 subunit protein expression is constant throughout heart development. Finally, the NR1 subunit protein is expressed in heart cells (H9c2) grown in culture. These studies reveal the presence of the NMDA receptor in the kidney and the cardiovascular system.
NMDA receptor subunit expression is increased in short-term gentamicin animals, and the receptor likely mediates cell damage via the endothelin-ETBR-nitric oxide pathway. NMDA antagonism ameliorated renal damage after exposure to short-term gentamicin.
Multiple genes are aberrantly expressed in the kidney of rats subjected to chronic neonatal UUO. Elucidation of these genes involved in neonatal UUO may lead to new insight about congenital obstructive nephropathy.
Intrauterine infection with a fetal inflammatory response is a risk factor for neonatal hearing loss while maternal therapies significantly reduced the risk of neonatal hearing loss in very low birthweight infants.
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