Clinical Characteristics and Renal Prognosis Associated with Interstitial Fibrosis and Tubular Atrophy (IFTA) and Vascular Injury in Lupus Nephritis Biopsies

Abstract Background Interstitial fibrosis and tubular atrophy (IFTA) and vascular injury are frequent histologic features of lupus nephritis renal biopsies, but their clinical correlates and prognostic value are not well understood. This cohort study investigated demographic, clinical and laboratory characteristics, and outcomes, associated with IFTA and vascular injury in lupus nephritis. Methods Reports of all renal biopsies performed at an academic medical center (1990-2017) with WHO/ISN/RPS Class II-V lupus nephritis were reviewed. Demographics, clinical variables and labs at biopsy, treatment, and date of death were collected. Additional data from the U.S. Renal Data System (USRDS) provided dates of ESRD and death after ESRD. Multivariable regression analyses identified demographic and clinical factors associated with each histologic finding. Cumulative incidence functions and multivariable Cox proportional hazard models estimated the risk of progression to ESRD and death. Results Within 202 initial biopsies, IFTA was associated with the patient's SLICC/ACR damage index (without renal domain) and serum creatinine, and vascular injury was associated with serum creatinine in multivariable models. In Cox regression models adjusting for age, sex, race, serum creatinine, calendar year, and biopsy class, moderate/severe IFTA was associated with elevated ESRD (HR SD 5.18, 95% CI 2.53, 10.59) and death (HR 4.19, 95%CI 1.27, 13.81). After adjustment for age, sex and race, moderate/severe vascular injury was associated with ESRD (HR SD 2.13, 95% CI 1.21, 3.75) and but this relationship was not significant after adjustment for serum creatinine and calendar year. Conclusions IFTA is a strong predictor of ESRD and death, even in proliferative nephritis, and a risk factor for poor outcomes independent of class. Vascular injury is a strong predictor of prognosis, but not independent of serum creatinine and class. The prognostic value of these lesions calls for consideration when determining treatment for lupus nephritis.