Modeling of progressive glomerular injury in humans with lupus nephritis

We studied glomerular function longitudinally for 36-120 mo in 21 patients undergoing treatment for diffuse, proliferative lupus nephritis. We determined glomerular filtration rate (GFR) and glomerular oncotic pressure (Pi(GC)) and computed the two-kidney ultrafiltration coefficient (K-f) at 6- to 12-mo intervals. The relationships and cross talk among the three variables over time were then analyzed by eigenfunction regression and canonical correlations. We also performed a morphometric analysis of serial biopsies and computed single-nephron K-f in patent glomeruli at baseline and after 36-94 mo of follow-up. Patients were divisible into progressors (n = 12) or nonprogressors (n = 9) according to the presence or absence, respectively, of an irrevocable decline in GFR over time. Examination of longitudinal variables revealed GFR to be strongly related to K-f in all patients and inversely related to Pi(GC) in progressors. By serial morphometric analysis we observed a threefold increase in the prevalence of global sclerosis in progressors but unchanged prevalence in nonprogressors. Whereas single-nephron K-f of remnant glomeruli increased to supernormal levels in nonprogressors, the absence of this compensatory phenomenon in progressors permitted GFR and K-f to decline in parallel with the declining number of functional glomeruli.