Early glomerular dysfunction in human renal allografts

Background. The long-term outcome of renal allografts is characterized by a progressive deterioration of renal function and graft loss. Our aim was to determine early glomerular functional abnormalities, before they become cl inically apparent. Methods. Glomerular hemodynamics and dextran sieving were characterized in 21 well-functioning cadaveric renal allograft recipients [normal glomerular filtration rate (GFR) and albumin excretion rate (AER), who also had a kid ney biopsy with normal or minimal histological changes] and in 15 uninephre ctomized kidney donors. Both groups were one to three years after transplan tation or uninephrectomy. Results. The GFR and renal plasma flow (RPF) were similar in both groups (6 2 +/- 3 vs. 63 +/- 4, and 343 +/- 26 vs. 334 +/- 21 mL/min/1.73 m(2) for GF R and RPF, in cadaveric recipients vs. donors, respectively), the AER was n ormal in both groups, but the mean arterial pressure was higher in renal re cipients (103 +/- 3 vs. 94 +/- 3 mm Hg in uninephrectomy controls, P < 0.05 ). Despite similar levels of overall glomerular function in the two groups, the dextran sieving curve was uniformly elevated in the renal allograft re cipients versus uninephrectomy controls (P < 0.05 for dextrans 38 to 66 Ang strom). Using a log-normal glomerular pore-size distribution model to analy ze potential mechanisms, the elevation in the dextran sieving curve resulte d from a shift in the distribution of glomerular filtering pores to a large r size (mean glomerular pore size 46 +/- 2 vs. 43 +/- 2 Angstrom for uninep hrectomy controls, P < 0.05), resulting in a larger fraction of filtrate vo lume permeating very large pores. By morphometric analysis, the thickness o f the glomerular basement membrane was increased in kidney allograft as com pared to 2-kidney biopsy controls (614 +/- 33 vs. 427 +/- 22 nm, respective ly, P < 0.05). Conclusions. Even in "well functioning" renal allografts there is a glomeru lar dysfunction characterized by increased permeability to macromolecules r esulting from a shift of the glomerular pores to a larger size. These chang es could be mediated by ultrastructural alterations at the glomerular capil lary or by alterations in intraglomerular hemodynamics. Early allograft dys function may contribute to the progressive renal insufficiency of renal all ografts.