ASSOCIATION BETWEEN HEPARAN-SULFATE PROTEOGLYCAN EXCRETION AND PROTEINURIA AFTER RENAL-TRANSPLANTATION

The aim of the study presented here was to investigate whether, in pat ients showing immediate graft function after renal transplantation, co ld-ischemia and reperfusion lead to damage of the glomerular basement membrane and consequently to a loss of heparan sulfate proteoglycans. Loss of these heparan sulfate proteoglycans is a major cause of protei nuria. Time-dependent changes in urinary excretion rates of heparan su lfate proteoglycans but also of total protein, albumin, low- and high- molecular-weight proteins were analyzed quantitatively and by polyacry lamid-gel-electrophoresis in eight patients. Immediately after renal t ransplantation, severe proteinuria with an excretion rate of up to 251 +/- 108 mg/min was apparent and rapidly declined within 24 h to 4.11 +/- 2.80 mg/min. The gel-electrophoretic pattern showed a nonselective glomerular and tubular proteinuria. The excretion rate of heparan sul fate proteoglycan was increased in this initial reperfusion phase (up to 7 h), most probably because of ischemia- and reperfusion-induced da mage of the glomerular basement membrane. The initial nonselective glo merular proteinuria disappeared within 48 h, changing to a mild select ive glomerular proteinuria, In this second phase (7 to 48 h), lower le vels of heparan sulfate proteoglycan excretion were observed (0.54 +/- 0.54 mu g/min versus 1.66 +/- 1.93 mu g/min, P < 0.05). However, duri ng the repair process of the glomerular basement membrane, heparan sul fate proteoglycan is synthesized de nova, leading to an increasing hep aran sulfate proteoglycan content of the glomerular basement membrane. This second phase is paralleled by the change from a nonselective to a selective glomerular proteinuria, In the third phase, when the hepar an sulfate proteoglycan content of the glomerular basement membrane no rmalizes, glomerular proteinuria was abolished in most of the patients .