Serum human epididymis protein 4 is a predictor for developing nephritis in patients with systemic lupus erythematosus: A prospective cohort study

Ren, Yingpeng; Xie, Jing; Lin, Feng; Luo, Wanwan; Zhang, Zhencheng; Mao, Panying; Zhong, Renqian; Liang, Yan; Yang, Zaixing

doi:10.1016/j.intimp.2018.04.048

Cited by 14 publications

(14 citation statements)

References 23 publications

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“…Our previous studies found a similar result in SLE patients [8, 9]. Furthermore, increased HE4 may be a valuable predictor for lupus nephritis (LN) development in SLE patient without LN [9]. In the present study, we also found that serum HE4 showed a strong, negative correlation with eGFR in T2DM patients, even though adjusting for various confounding factors such as age, urea, uric acid, blood glucose, and blood fat.…”

Section: Discussionsupporting

confidence: 85%

“…Several studies reported increased serum HE4 that is related to the decreased renal function in CKD or AKI patients [10–13]. Our previous studies found a similar result in SLE patients [8, 9]. Furthermore, increased HE4 may be a valuable predictor for lupus nephritis (LN) development in SLE patient without LN [9].…”

Section: Discussionmentioning

confidence: 66%

“…Secondly, there is a positive relationship between serum HE4 and CRP, suggesting that HE4 may also be an inflammatory marker in T2DM. Similarly, the previous studies have found that serum HE4 may be an inflammatory marker in patients with SLE [8, 9] and cystic fibrosis [20]. Therefore, HE4 may play a role in the inflammatory process of DKD, although the detailed mechanisms remained unknown.…”

Section: Discussionmentioning

confidence: 89%

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Serum Human Epididymis Protein 4 is Associated with Renal Function and Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus

Zhang

Zhao

Xie

et al. 2019

BioMed Research International

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Human epididymis protein 4 (HE4) is an available tumor biomarker mainly for detecting ovarian cancer. However, it is unknown whether it can be a novel indicator for diagnosis of diabetic kidney disease (DKD). The aim of this study was to investigate the possibility of serum HE4 as a novel biomarker for DKD in patients with type 2 diabetes mellitus (T2DM). We enrolled 236 patients with T2DM and 82 healthy individuals. Serum HE4 was detected by ARCHITECT i2000 and compared between T2DM patients and healthy controls. The relationships between various variables and HE4 were analyzed by univariate or multivariate linear regression analyses. The receiver operating characteristic (ROC) curve was constructed to assess the diagnostic performance of HE4 for DKD. The association between HE4 and DKD was analyzed by logistic regression analysis. The serum HE4 level was significantly increased in T2DM patients (median, interquartile range (IQR), 69.7, 46.5–153.9, pM) compared with healthy control (median, IQR, 40.3 33.2–46.3, pM) (P < 0.001). Furthermore, it was higher in those with DKD (median, IQR, 211.1, 141.6–367.4, pM) than those without DKD (median, IQR, 55.5, 42.7–79.6, pM) (P < 0.001). The multivariable analysis showed that age, eGFR, HDL, CRP, and urea significantly independently correlated with HE4 level, while other variables did not. The ROC curve showed that the diagnostic performance of serum HE4 for DKD with 82.9 pM as the optimal cutoff value was good (AUC = 0.917, 95% CI: 0.872–0.961, P < 0.001, with a sensitivity and specificity of 92.1% and 76.9%, respectively) in T2DM patients. Multivariable logistic regression analysis showed that increased HE4 level was a significant, independent risk factor for DKD (OR, 95% CI, 57.7, 3.0–1112.9, P < 0.001) after adjusting for factors associated with HE4. Increased serum HE4 level is associated with decreased renal function and increased risks of DKD in patients with DM. It displays a good diagnostic value for DKD.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 66%

Section: Discussionmentioning

confidence: 89%

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Serum Human Epididymis Protein 4 is Associated with Renal Function and Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus

Zhang

Zhao

Xie

et al. 2019

BioMed Research International

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“…[19,20] Proteinuria can indicate potential kidney disorders, suggestive for the presence of LN. [21] With regard to autoimmune antibodies, anti-dsDNA as one of nephrotoxic autoantibodies can directly involve in renal pathology of SLE [22,23] and increased incidence of LN, [24] of which one of the reasons is immune complex with anti-dsDNA can lead to renal inflammation if deposited in kidney, [25] and may result in activation of complement, reactive oxygen species and some cytokines which are also causative factors of LN. [26] Moreover, positive anti-Sm, anti-RNP [27–29] and biomarkers for inflammation such as interleukin [30–32] are also associated with renal involvement.…”

Section: Discussionmentioning

confidence: 99%

Association of GTF2I gene polymorphisms with renal involvement of systemic lupus erythematosus in a Chinese population

Yang¹,

Zhang²,

Xie

et al. 2019

Medicine

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The purposes of the study was to validate the relationship between General transcription factor II-I (GTF2I) genetic variants and kidney involvements of systemic lupus erythematosus (SLE) patients in a Chinese Han population. Samples from 400 SLE patients and 400 age- and sex-matched healthy controls were collected and genotyped by improved multiplex ligation detection reaction technique. The relationship between gene polymorphism of rs117026326, rs73366469, and susceptibility, progression of SLE were analyzed. The present study provided evidence that rs117026326 and rs73366469 were both associated with SLE susceptibility (both C vs T: P < .001). The analysis of dominant, recessive disease model provided us with further validation ( P < .001). Both gene polymorphisms are associated with a triad of disease manifestations among SLE patients. Patients carrying genotype TT of rs117026326 had lower 24-hour urinary total protein (24 hours UTP, g/24 hours), 24-hour urinary protein level (g/L·24 hours), lower frequency of the proteinuria and lupus nephritis (LN). Patients carrying genotype TT at rs73366469 had higher 24-hour urinary protein level, higher frequency of the proteinuria, LN and positive anti-dsDNA than those with other genotypes. This study identified the involvement of GTF2I gene polymorphisms in development of SLE, particularly in renal involvement.

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“…Lupus nephritis (LN) is a common manifestation of systemic lupus erythematosus (SLE) and a major cause of morbidity and mortality in these patients. Increased serum HE4 level was proved to be associated with development of LN in SLE patients in two independent studies [20,21]. However, detailed mechanism leading to development of LN with HE4 contribution remains unclear and needs further research.…”

Section: Kidneymentioning

confidence: 99%

HE4 – not only an ovarian cancer biomarker – a brief review

Maksimiuk

Budzik

Deptała

et al. 2019

Nowotwory. Journal of Oncology

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Human epididymis protein 4 (HE4) was firstly identified in epididymal epithelial cells and described as a protease inhibitor playing a role in spermatogenesis. Regarding numerous studies proving its diverse potential as a prognostic and predictive factor in ovarian cancer, it was incorporated into ROMA algorithm. Nevertheless, recent studies have shown that serum level of HE4 is not exclusive to ovarian cancer. As a result, doctors using ROMA algorithm for stratifying patients with ovarian cancer must be aware of other conditions that may affect serum level of HE4. This review comprises different conditions connected with high level of HE4 that might impact ovarian cancer diagnosing process. Moreover, discovering increased HE4 level in various conditions should open discussion about its applicability in diseases other than ovarian cancer.

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Serum human epididymis protein 4 is a predictor for developing nephritis in patients with systemic lupus erythematosus: A prospective cohort study

Cited by 14 publications

References 23 publications

Serum Human Epididymis Protein 4 is Associated with Renal Function and Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus

Serum Human Epididymis Protein 4 is Associated with Renal Function and Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus

Association of GTF2I gene polymorphisms with renal involvement of systemic lupus erythematosus in a Chinese population

HE4 – not only an ovarian cancer biomarker – a brief review

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