Interstitial inflammation and interstitial fibrosis and tubular atrophy predict renal survival in lupus nephritis

Abstract

Background

This study examines the effect of interstitial inflammation and interstitial fibrosis and tubular atrophy on renal survival in lupus nephritis.

Methods

Baseline characteristics, initial (n = 301) and repeat biopsies (n = 94) and clinical outcomes for patients with biopsy-proven lupus nephritis from 1998 to 2014 were retrospectively collected from the medical record. Clinical and morphologic variables were evaluated using a Cox proportional hazards model and multiple imputation to address missing data. Renal survival was defined as the time from initial biopsy to end-stage renal disease [estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m²], dialysis or transplant.

Results

A total of 218 patients had follow-up and Class IV had worse renal survival, especially in patients with active and chronic glomerular lesions {relative to non-IV; Class IV-A: hazard ratio [HR] 0.92 [95% confidence interval (CI) 0.41–2.04], Class IV-AC: HR 5.02 [95% CI 2.70–9.36]}. Interstitial inflammation grade [relative to interstitial inflammation <5%; interstitial inflammation 5–25%: HR 2.36 (95% CI 1.13–4.91), interstitial inflammation 25–50%: HR 3.84 (95% CI 1.53–9.62), interstitial inflammation >50%: HR 7.67 (95% CI 3.75–15.67)] and increased interstitial fibrosis and tubular atrophy (IFTA) category [relative to IFTA <5%; IFTA 5–25%: HR 3.93 (95% CI 1.58–9.75), IFTA 25–50%: HR 4.01 (95% CI 1.37–11.70), IFTA >50%: HR 13.99 (95% CI 4.91–39.83)] predicted worse renal survival among all patients and those with Class IV on initial and repeat biopsy (n = 94) in a dose-dependent manner. Interstitial inflammation grade and IFTA category were significant predictors of renal survival in a multivariable model adjusted for age, gender, race, ethnicity and serum creatinine.

Conclusions

Interstitial inflammation and IFTA independently affect renal survival and grading these lesions stratifies risk within the International Society of Nephrology and Renal Pathology Society classification of lupus nephritis.