A reappraisal of the influence of blood rheology on glomerular filtration and its role in the pathogenesis of diabetic nephropathy

Abstract

The basic assumptions concerning the mechanisms of normal glomerular filtration are discussed. Attention is drawn to blood rheologic changes that follow glomerular filtration and influence postglomerular blood flow adversely. It is proposed that the blood rheologic changes will increase the resistance to flow in the peritubular plexus commensurate with the dimensions of the capillaries and blood viscosity in accordance with the general principles of the Poiseuille formula, even though blood is a non-Newtonian fluid. For this reason, the conditions of flow in the plexus must be a determinant of intraglomerular capillary pressure. When blood rheology is abnormal, as in insulin-dependent diabetic patients, the abnormality will be amplified by glomerular filtration and it is suggested that the consequences will be manifest as problems of blood flow in the peritubular plexus. As the increase in postglomerular intravascular pressure needed to restore the rate of blood flow to normal necessitates dilation of the afferent arteriole and possibly more proximal vessels, such changes will result in an increase in intraglomerular pressure. The increase in pressure that increases filtration is therefore a direct consequence of abnormal blood rheology. This concept provides a basis for understanding the mechanism of diabetic proteinuria and for other proteinurias associated with abnormal blood rheology. A possible role for altered blood rheology in the pathogenesis of both focal and total glomerulosclerosis is discussed, and the potential benefits of agents that improve blood rheology are outlined.