Glomerular proteinuria in renal transplant patients: mechanisms and treatment.

Proteinuria in chronic kidney transplant failure (CKTF) is due to an alteration of glomerular permselectivity and two major determinants can be characterized experimentally: (1) size selectivity, that is, the ability of the glomerular filter to progressively hinder the passage of macromolecules with increasing molecular radius and (2) charge selectivity, the ability to restrict filtration of negatively charged molecules more effectively than that of equally sized uncharged or cationic compounds. The fractional clearance values of neutral polydisperse dextran molecules create a sieving profile to describe size selectivity, and anionic dextransulfate is used to evaluate charge selectivity. We characterized permselectivity in renal transplants recipients with various degrees of proteinuria. Proteinuria < 1 g/day is caused by an isolated defect of glomerular charge selectivity, whereas nephrotic range proteinuria (characterized histologically by transplant glomerulopathy) is due to an additional impairment of glomerular size selectivity. This sequence is similar to the one observed in patients with chronic native kidney disease (such as diabetic nephropathy). It therefore can be speculated that therapeutic interventions which have been shown to reduce proteinuria in patients with chronic native kidney disease will also beneficially affect permselectivity in CKTF.