Histologic versus clinical remission in proliferative lupus nephritis

Abstract

Early clinical and histologic outcomes are discordant in proliferative LN, and neither correlates with long-term renal outcome. The kidney accrues chronic damage rapidly and despite clinical response in LN. Preservation of kidney function may require therapeutic targeting of both chronic damage and inflammation during LN induction treatment.

Lupus nephritis: When and how often to biopsy and what does it mean?

“…The 10 year renal survival rate was 100% for patients with an activity index of 0, it was 80% for those with an activity index of 1 or 2 and 44% for patients with an activity index >2 at s renal biopsy. In 69 patients who underwent a second renal biopsy six months after induction therapy, serum creatinine and a chronicity index >4 at s renal biopsy were independent predictors of renal insufficiency [73]. The predictive value of a chronicity index cut off >4 was confirmed at repeat renal biopsy performed 2 years after a maintenance treatment with azathioprine or mycophenolate mofetil [76].…”

“…Indeed, it has also to be outlined that, despite apparent clinical response to immunosuppressive therapy, repeat biopsies sixeeight months from baseline revealed persisting signs of active nephritis in one third to half of the patients [48,73]. Persistent active lesions in these patients mainly consisted of endocapillary proliferation and subendothelial deposits, only a few patients showed persistence of crescents [73]. Although it is commonly thought that clinical remission may precede histological remission, these data point out the importance of biopsy particularly in patients with partial clinical remission.…”

Update on Lupus Nephritis

“…Persistent histologic evidence of glomerular and interstitial inflammation, glomerular capillary immune complexes, and macrophages in tubular lumens after completing induction therapy were risk factors for future doubling of the serum creatinine concentration (62,63). Increasing chronic damage on the postinduction biopsy also predicted long-term renal outcomes in some studies (57,58). The National Institutes of Health (NIH) activity and chronicity indices (64) were measured in repeat biopsies 12-18 months after starting treatment, while patients were on maintenance immunosuppression (65).…”

“…Repeat biopsies have demonstrated considerable discordance between clinically-and histologicallydefined disease activity. After completing 6-8 months of immunosuppressive therapy, 20%-50% of complete clinical renal responders still had histologic evidence of ongoing active inflammation, and 40%-60% of patients with no histologic evidence of disease activity still had persistent, high-grade proteinuria (57,58). Even after several years of immunosuppressive treatment, histologic activity was found in about 20% of patients who had been in sustained clinical remission.…”

“…Furthermore, although there are no estimates of how many LN patients are left with CKD after treatment, the number is likely to be large. For example, kidney biopsies after induction therapy with high-dose corticosteroids and cyclophosphamide or MMF generally show an increase in chronic damage, even in those patients who achieved a complete clinical remission to induction alone (57). LN flare is also an important risk factor for CKD and CKD progression (76) and flares may occur in 25% of patients (77,78).…”