Showing papers in "Advances in nephrology from the Necker Hospital in 1999"

Progress in the pathogenesis of IgA nephropathy.

Abstract: Despite 31 years of clinical and laboratory investigation, the pathogenesis of IgAN remains largely enigmatic. However, it seems clear that IgA1 accumulates in the glomerular mesangia due to a systemic process rather than an abnormality intrinsic in the kidney. Based on recent studies, investigators have proposed a wide range of pathogenetic mechanisms: nonspecific attachment because excessive IgA1 is synthesized in a short or prolonged immune response, increased binding due to an IgA-specific receptor (perhaps with altered characteristics) on mesangial cells, and increased glomerular deposition because an abnormal structure of the antibody (particularly of the glycan moieties in the hinge region) allows it to escape its normal degradative pathways or facilitates binding to a receptor on mesangial cells. Whether one or more of these postulates fully explains IgAN remains to be determined. Until then, treatment of the many affected patients worldwide will continue to lack a disease-specific approach.

Chloride channels in renal disease.

Abstract: Recent studies of hereditary renal tubular disorders have facilitated the identification and roles of chloride channels and cotransporters in the regulation of the most abundant anion, Cl-, in the ECF. Thus, mutations that result in a loss of function of the voltage-gated chloride channel, CLC-5, are associated with Dent's disease, which is characterized by low-molecular weight proteinuria, hypercalciuria, nephrolithiasis, and renal failure. Mutations of another voltage-gated chloride channel, CLC-Kb, are associated with a form of Bartter's syndrome, whereas other forms of Bartter's syndrome are caused by mutations in the bumetanide-sensitive sodium-potassium-chloride cotransporter (NKCC2) and the potassium channel, ROMK. Finally, mutations of the thiazide-sensitive sodium-chloride cotransporter (NCCT) are associated with Gitelman's syndrome. These studies have helped to elucidate some of the renal tubular mechanisms regulating mineral homeostasis and the role of chloride channels.

Mechanisms of endothelial injury in systemic vasculitis.

Abstract: The precise etiology of primary systemic vasculitis remains unknown. However, recent advances in the understanding of the role of and interaction between the vascular endothelium, mediators, and immune effector cells have helped to further elucidate those specific processes that result in endothelial cell damage. In WG and MPA, the evidence favors an autoimmune inflammatory response characterized by specific mediators in which the endothelium is both target and active participant.