Increased trefoil factor 2 levels in patients with chronic kidney disease

Lebherz-Eichinger, Diana; Tudor, Bianca; Ankersmit, Hendrik Jan; Reiter, Thomas; Haas, Martin; Einwallner, Elisa; Roth‐Walter, Franziska; Krenn, Claus G.

doi:10.1371/journal.pone.0174551

Cited by 8 publications

(11 citation statements)

References 24 publications

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“…The urinary TFF3 excretion was low in a rodent model of AKI, where the renal epithelial cells were observed to have decreased . Urinary TFF3 excretion is also low in the early stages of CKD, and constantly increase during the progression of CKD to end‐stage renal failure . These factors imply that the continuous and certain stimulation of renal epithelial cells is necessary for the increase of TFF3 expression.…”

Section: Discussionmentioning

confidence: 99%

Renal expression of trefoil factor 3 mRNA in association with tubulointerstitial fibrosis in IgA nephropathy

et al. 2018

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AimTrefoil factor 3 (TFF3) is a small peptide that is involved in mucosal protection. TFF3 is widely expressed in multiple tissues including kidney tissue. Previous studies have reported that the levels of urinary TFF3 are significantly increased in patients with chronic kidney disease. The aim of this study is to detect the TFF3 mRNA in kidney and elucidate the relationship between renal TFF3 mRNA and tubulointerstitial fibrosis in IgA nephropathy (IgAN).MethodsWe investigated the renal mRNA expression of TFF3 by real‐time PCR analysis in biopsy specimens from patients with IgAN, other glomerulonephritis (OGN) and minor glomerular abnormalities (MGA). We also determined the renal localization of TFF3 and the levels of urinary TFF3 by immunostaining and ELISA, respectively.ResultsThe renal TFF3 mRNA expression was significantly associated with the urinary TFF3 secretion and the tubulointerstitial fibrosis score in the IgAN group alone. Immunostaining of the renal specimen of IgAN patients revealed that TFF3 is located in the renal tubular epithelial cells. The locations were almost the same as those that showed uromodulin positivity; specifically, the thick ascending limb (TAL) of the loop of Henle and the early portion of the distal tubule. The urinary TFF3 levels were positively correlated with the levels of urinary biomarkers of tubulointerstitial injury in such patients.ConclusionRenal TFF3 mRNA is associated with renal tubulointerstitial fibrosis in IgAN patients. The TFF3 located in the renal tubular epithelial cells may play a role in the progression of tubulointerstitial fibrosis in IgAN patients.

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Section: Discussionmentioning

confidence: 99%

Renal expression of trefoil factor 3 mRNA in association with tubulointerstitial fibrosis in IgA nephropathy

et al. 2018

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“…In the human urinary tract, TFF3 is detected as the most abundant form followed by TFF1 [ 14 ], while urine TFF2 and TFF3 are increased in patients with nephrolithiasis [ 14 ]. A recent study evaluated the urine TFF2 levels in patients with CKD [ 20 ]. Urine TFF2 concentrations were significantly higher in early or middle CKD stages than in later CKD stages and predicted early CKD stages in an ROC analysis, but without significant changes in the fractional excretion of TFF2 among CKD stages [ 20 ], which is also inconsistent with our data on urine TFF2.…”

Section: Discussionmentioning

confidence: 99%

“…A recent study evaluated the urine TFF2 levels in patients with CKD [ 20 ]. Urine TFF2 concentrations were significantly higher in early or middle CKD stages than in later CKD stages and predicted early CKD stages in an ROC analysis, but without significant changes in the fractional excretion of TFF2 among CKD stages [ 20 ], which is also inconsistent with our data on urine TFF2. Further studies will be required to clarify these inconsistencies in data on urine TFF1 and TFF2 levels at different CKD stages.…”

Section: Discussionmentioning

confidence: 99%

“…Higher urine levels of TFF3 were shown to be associated with incident CKD in community-based populations [ 17 ]; however, they were not associated with incident CKD or albuminuria in another prospective cohort of Framingham Heart Study participants [ 18 ]. In recent studies in patients with CKD, increased levels of urine TFF1 [ 19 ] and urine TFF2 [ 20 ] have been reported in early CKD stages, whereas urine TFF3 levels are increased in later CKD stages [ 19 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

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Urine Trefoil Factors as Prognostic Biomarkers in Chronic Kidney Disease

Yamanari

Sugiyama

Tanaka

et al. 2018

BioMed Research International

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Introduction Trefoil factor family (TFF) peptides are increased in serum and urine in patients with chronic kidney disease (CKD). However, whether the levels of TFF predict the progression of CKD remains to be elucidated. Methods We determined the TFF levels using peptide-specific ELISA in spot urine samples and performed a prospective cohort study. The association between the levels of urine TFFs and other urine biomarkers as well as the renal prognosis was analyzed in 216 CKD patients (mean age: 53.7 years, 47.7% female, 56.9% with chronic glomerulonephritis, and mean eGFR: 58.5 ml/min/1.73 m2). Results The urine TFF1 and TFF3 levels significantly increased with the progression of CKD stages, but not the urine TFF2 levels. The TFF1 and TFF3 peptide levels predicted the progression of CKD ≥ stage 3b by ROC analysis (AUC 0.750 and 0.879, resp.); however, TFF3 alone predicted CKD progression in a multivariate logistic regression analysis (odds ratio 3.854, 95% confidence interval 1.316–11.55). The Kaplan-Meier survival curves demonstrated that patients with a higher TFF1 and TFF3 alone, or in combination with macroalbuminuria, had a significantly worse renal prognosis. Conclusion The data suggested that urine TFF peptides are associated with renal progression and the outcomes in patients with CKD.

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“…This confirms that urinary TFF3 excretion constantly increases during CKD progression to ESRD. Also, urinary level of TFF3 was found to be a good predictor of incident CDK (42)(43)(44).…”

Section: Discussionmentioning

confidence: 88%

Baseline HDAC6 and TFF3 proteins overexpression as prognostic markers of lupus nephritis relapse

2020

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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. ABSTRACT Implication for health policy/practice/research/medical education:Lupus nephritis is a leading cause of CKD, so it is crucial to search for markers that could predict tubulointerstitial injury and patients' relapses. HDAC6 and TFF3 are associated with features of renal damage and early relapse of LN. These effects are due to their capacity to up-regulate BCL2 expression promoting survival of autoreactive B cells as well as stimulation of persistent release of inflammatory cytokines by dendritc cells. Therefore, HDAC6 & TFF3 can be used for prognostic stratification of LN patients. Please cite this paper as: Abdelbary EH, Farouk Ahmed N, Abdelmohsen Ghorab A. Baseline HDAC6 and TFF3 proteins overexpression as prognostic markers of lupus nephritis relapse. J Nephropathol. 2020;9(2):e14.

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Increased trefoil factor 2 levels in patients with chronic kidney disease

Cited by 8 publications

References 24 publications

Renal expression of trefoil factor 3 mRNA in association with tubulointerstitial fibrosis in IgA nephropathy

Renal expression of trefoil factor 3 mRNA in association with tubulointerstitial fibrosis in IgA nephropathy

Urine Trefoil Factors as Prognostic Biomarkers in Chronic Kidney Disease

Baseline HDAC6 and TFF3 proteins overexpression as prognostic markers of lupus nephritis relapse

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