The Emergence of Kidney Stone Disease During Childhood-Impact on Adults.

PURPOSE OF REVIEW: The goal of this chapter is to review the recent epidemiologic trends of kidney stone disease and discuss the impact of the increasing incidence of nephrolithiasis among children on adults with respect to extra-renal manifestations, surgical management, and secondary prevention. RECENT FINDINGS: Among pediatric patients, kidney stone disease has been increasing at a rate of approximately 5-10% annually. Kidney stone disease has been associated with increased risks of coronary heart disease, chronic kidney disease, hypertension, and decreased bone mineral density, which is concerning for patients diagnosed at a young age. Improvements in endo-urology have allowed for less invasive surgical treatment of stones in the pediatric population. However, current guidelines often lack recommendations for evaluation, medical, and surgical management of children with kidney stone disease. Nephrolithiasis is a disorder of mineral metabolism, which is beginning during childhood with increasing frequency. Kidney stone disease often exists over the lifetime and is associated with serious conditions that are important for pediatric and adult urologists to recognize and consider in their evaluation and treatment of patients.

The nebulette repeat domain is necessary for proper maintenance of tropomyosin with the cardiac sarcomere.

Nebulette is a cardiac-specific isoform of the giant actin-binding protein nebulin. Nebulette, having a mass of approximately 100 kDa, is only predicted to extend 150 nm from the edge of the Z-lines. Overexpression of the nebulette C-terminal linker and/or SH3 domains in chicken cardiomyocytes results in a loss of endogenous nebulette with a concomitant loss of tropomyosin (TPM) and troponin, as well as a shortening of the thin filaments. These data suggest that nebulette's position in the sarcomere is important for the maintenance of TPM, troponin and thin filament length. To evaluate this hypothesis, N-terminal nested truncations tagged with GFP were expressed in chicken cardiomyocytes and the cells were analyzed for the distribution of myofilament proteins. Minimal effects on the myofilaments were observed with N-terminal deletions of up to 10 modules; however, deletion of 15 modules replicated the phenotype observed with expression of the C-terminal fragments. Expression of internal deletions of nebulette verifies that a site between module 10 and 15 is important for TPM maintenance within the sarcomeric lattice. We have additionally isolated TPM cDNAs from a yeast two hybrid (Y2H) analysis. These data indicate the importance of the nebulette-TPM interactions in the maintenance and stability of the thin filaments.