Mechanisms of orthostatic proteinuria: lessons from a transplant donor

Orthostatic proteinuria accounts for 60% of all children and 75% of adolescents with proteinuria. Despite its frequent occurrence, the underlying pathophysiologic mechanisms remain unclear. The following three possibilities have been reviewed: (1) a normal variant; (2) a glomerular abnormality; (3) a hemodynamic abnormality. On the basis of the experience with an individual who had orthostatic proteinuria and who was a donor of a living-related kidney transplant, novel insights and a potentially unifying hypothesis for the pathogenesis of this condition are presented. It is suggested that individuals with orthostatic proteinuria may be predisposed by a subtle glomerular abnormality. However, a precipitating factor, in the form of an exaggerated response to the upright position, appears to be essential to unmask the condition.