Hong Kong Journal of Nephrology

Volume 6 Number 2, 2004
Abstract

Glomerular Endothelial Dysfunction, Altered Hemorheology and Hemodynamic Maladjustment in Nephrosis with Focal Segmental Glomerulosclerosis

Narisa Futrakul
Department of Physiology, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
fmednft@md2.md.chula.ac.th

Visith Sitprija
Department of Nephrology, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Bangkok, Thailand.

Prasong Siriviriyakul
Department of Physiology, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Bangkok, Thailand.

Prasit Futrakul
Department of Nephrology, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Bangkok, Thailand.

Oxidative stress and a defective immunocirculatory balance induce glomerular endothelial cell (GEC) dysfunction, which is expressed as proteinuria and altered hemorheology, namely blood hypercoagulability, blood hyperviscosity, and local intravascular coagulation in severe nephrosis. In addition, defective release of endothelium-dependent vasodilators in conjunction with enhanced production of vasoconstrictors induces hemodynamic maladjustment by preferential constriction at the efferent arteriole. Such constriction has three significant hemodynamic impacts. Proximal to the efferent arteriolar constriction, it induces an overestimated glomerular filtration rate due to hyperfiltration, and an elevated intraglomerular hydrostatic pressure. Distal to the efferent arteriolar constriction, it exaggeratedly reduces the peritubular capillary flow. Such hemodynamic maladjustment causes over-distension of the glomerular capillary, detaching the podocyte from the basement membrane. Podocyte injury decreases the production of vascular endothelial growth factor, thereby aggravating the GEC injury. Increased GEC injury further aggravates the hemodynamic maladjustment, the podocyte injury, and eventually the GEC injury, in a vicious cycle. Sustained ischemic injury activates the profibrogenic pathway and eventually culminates in tubulointerstitial fibrosis. In accordance with this concept, correction of hemodynamic maladjustment with vasodilators and of altered hemorheology with antiplatelet drugs and anticoagulation will improve renal hemodynamics and function, and prevent the progression of renal disease.

Key words: immunocirculatory disturbance, glomerular endothelial dysfunction, hemodynamic maladjustment, renal perfusion, vasodilators

腎小球內皮細胞(GEC)功能障礙可歸因於氧化壓力與循環免疫失衡,其表現為蛋白尿及血液流變學異常,包括高凝血狀態、高血粘稠度、甚至局部的血管內凝血。此外,內皮性血管擴張物質釋放的不足、及血管收縮物質生成的增加,均會導致出球小動脈的選擇性收縮、及隨之而來的一系列血行動力變化,包括腎小球過濾速率與球內靜水壓的增加、及腎小管周圍微血管血流的下降。這些血行動力失調會導致腎小球微血管的過度膨脹,甚至足細胞自基底膜脫離。足細胞的損傷會減少血管內皮生長因子的生成,進一步加劇 GEC 所承受的傷害;後者又會加重血行動力的失調、足細胞的損傷、及 GEC 本身的損傷,結果是惡性循環的形成。持續的缺血性傷害會增加纖維組織的形成,並造成腎小管間質性纖維化。因此,以血管擴張劑矯治血行動力失調、及抗血小板劑與抗凝血劑矯治血液流變學異常,是改善腎臟血行動力表現及阻止腎病進一步惡化的可行方法。


Back to Previous Page