Background/Purpose: Tubulointerstitial disease (TID), defined as tubulointerstitial inflammation (TII) or interstitial fibrosis/tubular atrophy (IFTA), is associated with progression to end stage renal disease (ESRD) in lupus nephritis. Early detection of TID via non-invasive methods is crucial to identifying those at highest risk for renal failure. A set of urine biomarkers of tubular damage has recently been developed to detect acute kidney injury.¹ This study sought to determine whether these biomarkers of tubular injury collected around the time of clinically indicated biopsies for lupus nephritis were associated with the presence of IFTA/TII.

Methods: Urine samples from 29 adult and pediatric lupus patients with clinically indicated renal biopsies performed between 2010 and 2019 were included. Samples were evaluated for tubular injury markers KIM-1, interleukin-18 (IL-18), clusterin, calbindin, and glutathione S-transferase-π (GST- π) using the Bio-Plex Pro^TM kidney assay. Biomarkers (Table 1) were correlated with presence or absence of IFTA/TII on biopsies performed within 180 days prior to and 21 days after sampling. These biomarkers were normalized to urine creatinine excretion.

Results: Of 29 patients, 18 (62%) had evidence of IFTA on renal biopsy (Table 2). IFTA+ patients had a median age (IQR) of 36 (27, 50) vs. 20 (14, 59) in the IFTA group, p = 0.25. BMI was significantly higher in IFTA+ patients (median (IQR) 30 (24, 36) kg/m² vs. 23 (20, 26) kg/m², p < 0.001), as was blood pressure on day of biopsy. KIM-1 levels were higher when IFTA was present, median (IQR) 0.5 (0, 2) ng/mg vs. 0 (0, 0) ng/mg for IFTA+ and IFTA-, respectively, one sided p-value 0.04. KIM-1 was detectable ( > 0) in 9 (50%) of IFTA+ and in 2 (18%) IFTA-, p = 0.09. No association between KIM-1 and TII was observed. There was no association between the other 4 biomarkers and IFTA or TII (Table 3). KIM-1 levels did not differ by age, sex, race, ethnicity, or lupus nephritis class, and were not associated with serum C3, C4, or dsDNA at time of sample collection. KIM-1, calbindin, GST-π and clusterin were associated with proteinuria.

Conclusion: Though limited by sample size, these pilot results suggest that urinary KIM-1, a kidney injury marker secreted by the proximal tubules, in samples collected around the time of biopsies may serve as a non-invasive biomarker for the presence of IFTA in lupus nephritis.

Reference:

1. Stephen L, et al. Profiling of Human, Canine, and Rat Urine Samples Using Bio-Plex Pro^TM RBM Kidney Toxicity Assays. Available from: http://www.bio-rad.com/webroot/web/pdf/lsr/literature/Bulletin_6400.pdf

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/urine-biomarkers-of-tubulointersitital-damage-in-lupus-nephritis/