Abstract

Abstract Background and Aims Endoplasmic reticulum (ER) stress with protein misfolding has been introduced as a key pathogenetic mechanism in patients with lupus nephritis (LN). Pregnancy is thought to exaggerate ER stress in conjunction with autophagy inhibition. This probably explains disease flares during pregnancy; however, this is not fully addressed. The detection of the abnormally misfolded proteins is made using the Congo red stain, which is referred to as congophilia. This study aimed to assess the predictive value of urinary congophilia as a marker of protein misfolding in pregnant and non-pregnant women with lupus nephritis. Method Urine samples from non-pregnant lupus nephritis patients (n = 45) and pregnant women with lupus nephritis (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) criteria. Renal biopsy was done for 26 adults of non-pregnant lupus nephritis patients at time of urine sampling as it was clinically indicated and modified NIH activity index was assessed. Results The median and range values for SLEDAI score were 14(4-34) for non-pregnant LN patients, and 4(0-6) for pregnant women with LN (Table 1). Congo red retention (CRR) was significantly higher for non-pregnant LN patients (24.18%(0.75-126.29%)), in comparison with pregnant LN patients (0.67%(0.31-27.69%), P = 0.001), and healthy controls (0.33%(0.18-2.7%), P≤0.001). There was a significant positive correlation between CRR on one hand, and anti-ds-DNA (r = 0.791, P≤0.001), as well as SLEDAI score (r = 0.623, P≤0.001) on the other hand. However, no significant correlation has been found between CRR with renal histopathological activity index (r = 0.2, P = 0.425). 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 (Fig. 1). Conclusion Urinary congophilia may add a diagnostic value in patients with lupus nephritis and can be a reliable marker of disease activity. CRR is related to disease activity rather than pregnancy.

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