Abstract
Introduction: Lupus nephritis (LN) is a substantial manifestation of systemic lupus erythematosus (SLE). HDAC6 is overexpressed in various kidney diseases, and its inhibition slows kidney injury progression. Urinary TFF3 increases in chronic kidney diseases (CKDs) and may be associated with patient’s outcome. Objectives: This study aimed to examine the relationship between renal HDAC6 and TFF3 proteins expression and with clinicopathologic characteristics and outcome of LN. Patients and Methods: HDAC6 and TFF3 proteins’ expression was immunohistochemically detected in 56 cases of LN. They were correlated to patients’ age, gender, urinary 24 hours protein and serum creatinine levels at baseline and during follow up. Additionally, they were correlated to LN classes, activity index (AI) and chronicity index (CI) and relapse free survival (RFS). Results: HDAC6 overexpression was significantly associated with serum creatinine and 24 hours proteinuria levels at baseline (P = 0.041 and P =0.026 respectively) and during follow up (P < 0.001). It was associated with AI and CI of class III and IV LN (P = 0.047 and 0.003 respectively). TFF3 overexpression was associated with higher serum creatinine and more proteinuria at baseline (P = 0.015 and 0.001 respectively) and during follow up (P < 0.001). It was significantly associated with higher CI (P = 0.001). Both markers were associated with shorter RFS (P < 0.001). Conclusion: HDAC6 and TFF3 proteins are associated with clinicopathologic features of renal damage in LN. They are reliable predictors of patients’ RFS, which makes them good candidates for risk stratification of patients and targeted therapy.
Highlights
Lupus nephritis (LN) is a substantial manifestation of systemic lupus erythematosus (SLE)
We found that Trefoil factor 3 (TFF3) protein overexpression was associated with high serum creatinine and 24-hour urinary protein levels as well as class IV and V LN, known to have more tubulointerstitial injury than other classes
To analyze the ability of HADC6 and TFF3 proteins overexpression in baseline renal biopsy to predict renal relapse of LN, we examined the relationship between the proteins overexpression and serum creatinine and 24 hours urinary protein quantity as laboratory evidence of renal relapse
Summary
Lupus nephritis (LN) is a substantial manifestation of systemic lupus erythematosus (SLE). Patients and Methods: HDAC6 and TFF3 proteins’ expression was immunohistochemically detected in 56 cases of LN They were correlated to patients’ age, gender, urinary 24 hours protein and serum creatinine levels at baseline and during follow up. They were correlated to LN classes, activity index (AI) and chronicity index (CI) and relapse free survival (RFS). Results: HDAC6 overexpression was significantly associated with serum creatinine and 24 hours proteinuria levels at baseline (P = 0.041 and P =0.026 respectively) and during follow up (P < 0.001). These classes and indices have the potential to predict renal prognosis [2]
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