Reconsidering Garth Robinson: fluid flow and the glomerular filtration barrier.

PURPOSE OF REVIEW: The goal of this review is to present recent models of the filtration barrier that may suggest mechanism-based treatments for proteinuric renal disease. The vast majority of renal failure occurs in diseases of glomerular proteinuria. The physiology of the filtration barrier remains incompletely understood, preventing invention of mechanism-based therapies. Research is currently dominated by molecular biology approaches to the kidney instead of engineering-based filtration and transport models.

RECENT FINDINGS: Reexamination of two older paradigms (basement membrane and slit diaphragm) and critical analysis of newer models may provide mechanistic insight to guide further research. We expand on our theory of podocyte-basement membrane mechanical interactions and speculate on mechanisms of action of the leading treatment for proteinuria, angiotensin blockade.

SUMMARY: Treatment of proteinuria remains largely empiric and based on inhibition of the renin-angiotensin-aldosterone system, with additional benefit from statins and vitamin D. Improved definition of transport phenomena in the capillary wall may suggest rational design of new interventions.