Glomerular capillary wall function in human lupus nephritis.

Eighteen patients with nephrotic-range proteinuria due to lupus nephritis were evaluated with a differential solute clearance technique. Renal plasma flow was similar to that in 17 healthy volunteer controls (506 +/- 75 vs. 503 +/- 32 ml/min, P = NS), while oncotic pressure in pre- and postglomerular plasma was depressed by 9.2 and 17.3 mmHg, respectively. These findings are consistent with elevation of net ultrafiltration pressure and suggest that glomerular hypofiltration (51 +/- 9 vs. 103 +/- 8 ml/min, P less than 0.001) was due to a lowered glomerular ultrafiltration coefficient (Kf). In lupus nephritis the fractional clearance of smaller dextrans (radii less than 50 A) was depressed, while that of larger dextrans (radii greater than 50 A) was elevated. A pore model of solute transport, when applied to the dextran filtration data, revealed a subpopulation of large protein-permeable pores in lupus nephritis not present in controls. Moreover, the fraction of glomerular filtrate permeating these enlarged pores correlated directly with the respective fractional clearances of albumin (r = 0.71) and immunoglobulin G (r = 0.75) in individual patients. Immunosuppression in nine patients was associated with an increase of the filtration rate and filtration fraction. Conversely, fractional protein clearances and the area fraction of the glomerular membrane occupied by large pores decreased. We conclude that human immune glomerular inflammation is manifested by a reduction of Kf and increased glomerular porosity and that these membrane alterations are partially reversible.