Urine Trefoil Factors as Prognostic Biomarkers in Chronic Kidney Disease

Abstract

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.

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

“…Cases with these proteins overexpression had significantly shorter RFS duration. We agree with previous studies reporting urinary TFF3 level is significantly associated with shorter renal survival and rapid progression to ESKD (44). These findings are consistent with our results that HDAC6 and TFF3 are strongly related to amount of proteinuria, which has been proven to be an independent predictor of ESKD and poor renal survival (42,45).…”

“…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).…”

“…In experimental models, urine TFF3 markedly reduced after acute renal toxicity and has been proposed as a marker for kidney toxicity in preclinical stages (15). Additionally, higher urine levels of TFF3 were shown to be associated with incident chronic kidney diseases (CKD) in community-based populations and may be associated with renal progression and the outcomes in patients with CKD (16,17).…”

Urine 5MedC, a Marker of DNA Methylation, in the Progression of Chronic Kidney Disease

“…The eGFR was calculated as described previously [17]. Hypertension was defined as described previously [18, 19]. The mean blood pressure (MBP) was calculated as diastolic blood pressure + (systolic blood pressure − diastolic pressure)/3.…”

“…Of these patients, 199 patients (male 107, female 92) were overlapped with the previous study [19]. In accordance with the established protocol, we excluded any patients with established atherosclerotic complications (congestive heart failure, coronary artery disease, or peripheral vascular disease) [19]. Patients with infection, acute kidney injury, cancer, and Alzheimer's disease at entry were also excluded.…”