Modeling of progressive glomerular injury in humans with lupus nephritis

Abstract

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 (IIGC) and computed the two-kidney ultrafiltration coefficient (Kf) 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 Kf 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 Kf in all patients and inversely related to IIGC 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 Kf of remnant glomeruli increased to supernormal levels in nonprogressors, the absence of this compensatory phenomenon in progressors permitted GFR and Kf to decline in parallel with the declining number of functional glomeruli.

Effect of Low-Dose Cyclosporine A in the Treatment of Refractory Proteinuria in Childhood-Onset Lupus Nephritis

“…29 The beneficial effect of CSA on proteinuria is important because it has been shown that proteinuria is a predictor of adverse renal function in proliferative lupus nephritis. [30][31][32] In our study, we also observed marked reduction of proteinuria with low-dose CSA in all paediatric patients with proliferative lupus nephritis refractory to previous immunosuppressive therapy, and ACE inhibitors. Moreover, in contrast with the majority of previous reports in which standard dosage of CSA was 5 mg/kg/day, the majority of our patients responded with lower doses (median 3 mg/kg/day, range 2-4).…”

Progression of Chronic Renal Failure

“…Modeling of human lupus nephritis also suggests that hyperfiltration occurs and is indeed beneficial, at least in the short term. 9 Studies of patients who have undergone unilateral nephrectomy have shown no deterioration in renal function. [45][46][47] However, there may be a critical renal mass below which hyperfiltration becomes detrimental.…”

“…1 Once the renal failure is well established, the rate of progression can be estimated, although limitations exist. [2][3][4][5][6][7][8][9] Many features are common to progression of renal failure of various causes, and the final histologic appearance is one of glomerulosclerosis, interstitial fibrosis, and loss of native renal cells. Nevertheless, the causes of chronic renal failure are heterogeneous, and the mechanisms and lo-cations of the initial injury may vary.…”

How to Avoid Delay in SLE Diagnosis and Management

“…Serial studies by the Stanford group demonstrated that heavy proteinuria is a predictor of progressive renal impairment (Buckheit et al, 1997). Therefore, reduction of proteinuria independent of reduction in blood pressure is associated with subsequent beneficial effect on the progression of renal disease (Lewis et al, 1993;Maschio et al, 1996;Petersen et al, 1995;The Gisen Group 1997).…”