SLICC Damage Index is associated with Tubulointerstitial Nephritis on Lupus Nephritis Biopsies

Kristin D’ Silva, Paul Hoover, Gearoid McMahon, Sushrut Waikar, Helmut Rennke, Karen Costenbader

Background/Purpose: The presence of tubulointerstitial nephritis (TIN)on lupus nephritis renal biopsy has been associated with a poorer prognosis.  Clinical factors associated with this biopsy finding have not been clearly defined.    The purpose of this retrospective cohort study was to investigate clinical and laboratory characteristics associated with TIN in patients diagnosed with lupus nephritis.  We predicted low C4, elevated 24-hour urinary protein and elevated dsDNA antibodies would be associated with the presence of TIN.

Methods:   Biopsy reports of all renal biopsies performed at a single academic medical center between 1996 and 2015 showing Class II-VI lupus nephritis were reviewed.  The definition of TIN included interstitial inflammation, tubular atrophy or fibrosis, and was abstracted from the biopsy report.  All biopsies were interpreted by senior pathologists.  Demographics, clinical variables and labs at the time of biopsy were assessed by chart review. Univariable analyses and then multivariable regression models were used to identify potential factors associated with tubulointerstitial nephritis. 

Results:   165 initial lupus nephritis biopsies were identified; 119 had acute (n=5) or chronic interstitial nephritis (n= 97) or both (n=17).  The average patient age was 36 years, 85% were female, and dsDNA antibody was positive in 85%. ISSN lupus nephritis biopsy classes overall were 9% II, 25% III, 40% IV and 24% V, and class was not statistically associated with presence of TIN.  There were no statistically significant differences between groups in duration of SLE at biopsy, prior medications, age or race (Table).  In univariable analyses, presence of TIN was associated with lower hemoglobin [10.5 vs. 11 g/dL, p= 0.02], higher creatinine [1.0 vs. 0.8 mg/dL, p= 0.01], higher 24-hour urinary protein (2.62 vs. 1.4 gm, p= 0.04], and higher SLICC damage index [4 vs. 2, p= 0.0016] compared to no TIN.  Elevated SLICC damage index (DI) was associated with the presence of tubulointerstitial nephritis [OR 1.03 (95% CI 1.01, 1.05)] after controlling for age, race, sex, and 24-hour urinary protein.

Conclusion:   TIN was a common finding on lupus nephritis biopsy and not associated with ISSN Class. Several laboratory findings related to more severe renal impairment were associated with TIN, but in multivariable models only SLICC-DI remained significantly associated. This suggests that increasing SLE-related systemic damage in lupus nephritis patients is associated with increased risk of TIN.  Interestingly, SLE duration was not associated with TIN.   Further work is needed to clarify the relationship between overall SLE damage and TIN in order to identify patients at highest risk for this potentially adverse pathology.