Urinary congophilia as a predictive biomarker of lupus nephritis in pregnant and non-pregnant women with systemic lupus erythematosus

Abstract

Background

Endoplasmic reticulum stress with protein misfolding has been introduced as a key pathogenetic mechanism in lupus nephritis (LN). Pregnancy is thought to exaggerate proteostasis, which leads to the accumulation of potentially pathogenic misfolded proteins in the urine, serum, and placenta particularly in women with preeclampsia. The detection of misfolded proteins is made using Congo red stain, which is referred to as congophilia. This study aimed to assess the predictive value of urinary congophilia as a marker of LN activity in pregnant and non-pregnant LN women.

Methods

Urine samples from non-pregnant LN women (n = 45), pregnant LN women (n = 12), as well as pregnant healthy controls (n = 38) were collected. Urinary congophilia was assessed by Congo Red Dot Blot assay. The disease activity was defined according to SLE Disease Activity Index (SLEDAI) score, and SLE Disease Activity Index-Renal Domain (SLEDAI-R) score. Renal biopsy was done for 33 non-pregnant LN women as it was clinically indicated, and modified NIH activity index (AI) was assessed according to the classification of LN by the International Society of Nephrology/Renal Pathology Society (ISN/RPS).

Results

Congo red retention (CRR) values were significantly higher for pregnant active LN patients, in comparison with pregnant inactive LN patients (p = .014), as well as pregnant healthy controls (p = .009). Additionally, CRR values were significantly higher for non-pregnant active LN patients, in comparison with non-pregnant inactive LN patients (p = .016), as well as pregnant healthy controls (p ≤ .001). There were significant positive correlations between CRR on one hand, and anti-ds-DNA (r = 0.791, p ≤ .001), serum creatinine (r = 0.620, p ≤ .001), SLEDAI score (r = 0.623, p ≤ .001), as well as SLEDAI-R score (r = 0.473, p = .005) on the other hand. A highly significant negative correlation was detected between CRR, and serum albumin (r = −0.454, p = .001). CRR at a cut point ≥21.85 had 83% sensitivity, and 58% specificity to capture high LN activity status (NIH-AI >10) versus lower LN activity status.

Conclusion

Urinary congophilia may add a diagnostic value in patients with LN and can be a reliable marker of disease activity. CRR is related to disease activity rather than pregnancy.