Transforming growth factor β1 is better than α smooth muscle actin for the prediction of renal fibrosis in patients with nephritic lupus

Susianti, Hani; Handono, Kusworini; Gunawan, Atma; Mintaroem, Karyono; Purnomo, Basuki Bambang; Kalim, Handono

doi:10.1016/j.bgm.2014.08.010

Cited by 5 publications

(6 citation statements)

References 15 publications

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“…Fibrosis on biopsy was assessed semi-quantitatively in all three studies. Urine TGF-β positively correlated with fibrosis on biopsy ( r = 0.60, p < 0.001), and was able to diagnose fibrosis >5% with an AUC of 0.90 [ 21 ]. Urine TGF-β was also found to positively correlate with future fibrosis on biopsy in seven patients 1-year post biomarker measurement ( r = 0.86, p = 0.01) [ 20 ].…”

Section: Resultsmentioning

confidence: 99%

Biomarkers for the detection of renal fibrosis and prediction of renal outcomes: a systematic review

et al. 2017

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BackgroundFibrosis is the unifying pathway leading to chronic kidney disease. Identifying biomarkers of fibrosis may help predict disease progression.MethodsWe performed a systematic review to evaluate the reliability of blood and urine biomarkers in identifying fibrosis on biopsy as well as predicting renal outcomes. Using MEDLINE and EMBASE, a two-stage search strategy was implemented. Stage I identified a library of biomarkers correlating with fibrosis on biopsy. Stage II evaluated the association between biomarkers identified in stage I, and renal outcomes. Only biomarkers with moderate positive correlation with fibrosis (r > 0.40) or acceptable area under the curve (AUC >0.65) advanced to stage II.ResultsStage I identified 17 studies and 14 biomarkers. Five biomarkers met criteria to advance to stage II, but only three were independently associated with renal outcomes. Transforming growth factor β (TGF-β) correlated with fibrosis (r = 0.60), and was associated with 1.7–3.9 times the risk of worsening renal function in 426 patients. Monocyte chemoattractant protein-1 (MCP-1) diagnosed fibrosis with AUC of 0.66 and was associated with 2.3–11.0 times the risk of worsening renal function in 596 patients. Matrix metalloproteinase-2 (MMP-2) correlated with fibrosis (r = 0.41), and was associated with 2.5 times the risk of worsening renal function.ConclusionsGiven the heterogeneity of the data due to diverse patient populations along with differing renal outcomes, a meta-analysis could not be conducted. Nonetheless we can conclude from the published data that TGF-β, MCP-1 and MMP-2 may identify patients at risk for renal fibrosis and hence worse renal outcomes.Electronic supplementary materialThe online version of this article (doi:10.1186/s12882-017-0490-0) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Biomarkers for the detection of renal fibrosis and prediction of renal outcomes: a systematic review

et al. 2017

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“…TGF-β, a product of macrophages or proximal tubular cells exposed to proteinuria, stimulates collagen synthesis and tubulointerstitial fibrosis (13,20) . According to Susianti et al, urine TGF-β positively correlated with fibrosis on biopsy and was even able to diagnose fibrosis itself, while Honkanen et al proved that urine TGF-β positively correlated with fibrosis confirmed in future biopsies (17,18) . In their meta-analysis, Mansour et al showed that TGF-β is one of promising biomarkers for the detection of renal fibrosis and prediction of renal outcome (25) .…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, the study focused on identifying biomarkers of renal fibrosis to allow for a non-invasive assessment are worth mentioning. The usefulness of measuring urinary transforming growth factor beta (TGF-β) has been postulated (17)(18)(19)(20) . TGF-β shows a strong ability to stimulate extracellular matrix formation and collagen deposition (13,21) .…”

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confidence: 99%

Urinary procollagen III aminoterminal propeptide/creatinine (PIIINP/Cr) ratio and transforming growth factor beta/creatinine (TGF-β/Cr) ratio in children with idiopathic nephrotic syndrome on corticosteroid and cyclosporine A treatment

Banaszak¹

2021

Pediatr Med Rodz

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Idiopathic nephrotic syndrome is a common nephropathy in children basically treated with corticosteroids and, in some cases, with cyclosporin A. There are concerns that proteinuria itself and cyclosporin A could cause renal fibrosis via activation of transforming growth factor beta (TGF-β), which may stimulate deposition of collagen type III, synthesised as procollagen III amino terminal propeptide (PIIINP). The aim of this study was to assess urinary TGF-β and PIIINP to creatinine (Cr) ratio as markers of renal fibrosis in children with idiopathic nephrotic syndrome put on corticosteroid and cyclosporin A treatment. Materials and methods: The study comprised 20 children with idiopathic nephrotic syndrome in remission on prednisone, aged 6.87 years [interquartile range (IQR): 6.37]; 21 children with idiopathic nephrotic syndrome in remission on cyclosporin A, aged 9.66 years (IQR: 5.0); and 21 healthy subjects, aged 7.16 years (IQR: 9.0). First morning urinary PIIINP/Cr and TGF-β/Cr were obtained and compared with Mann–Whitney U test, with the level of significance at p ≤ 0.05. Results: PIIINP/Cr ratio was significantly elevated in the cyclosporin A group [3.44 (2.5) vs. 1.12 (0.96) μg/mmol], p = 0.000, as well as in the prednisone group when compared to controls [1.33 (1.58) vs. 1.12 (0.96) μg/mmol], p = 0.042. The TGF-β/Cr ratio was significantly higher only in the cyclosporin A group when compared to controls [4.03 (3.25) vs. 2.33 (1.62) μg/mmol], p = 0.004. Conclusions: Increased urinary PIIINP/Cr ratio in children with idiopathic nephrotic syndrome either on steroid or on cyclosporin A therapy may suggest that renal fibrosis is a process generally involved in idiopathic nephrotic syndrome. Elevated urinary TGF-β/Cr and PIIINP/Cr ratios in patients with idiopathic nephrotic syndrome on cyclosporin A may reflect nephrotoxicity of this drug.

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“…Biomarkers with calculated AUC ≤ 0.6 indicate that the test cannot discriminate between patients with and without the disease, while AUCs of 0.60-0.69 = poor, 0.70-0.79 = fair, 0.80-0.89 = good and 0.90-1.00 = excellent discrimination (L.-T. . One of the highest AUCs was calculated for uTGF-β1 (0.90, excellent) which could distinguish between <5% of TIF and ≥5% of TIF in lupus nephritis patients (Susianti et al, 2015). However, it should be noted that this performance was obtained only in lupus nephritis patients; therefore, this biomarker should be studied in a larger patient cohort with CKD of varying aetiologies.…”

Section: Summary Of Tif Biomarkers and Diagnostic Approachesmentioning

confidence: 98%

“…Likewise, a positive correlation ( r = 0.60, P < 0.001) between total uTGF‐β1 and the percentage of TIF (%TIF) was found at the time of biopsy in patients with lupus nephritis (Susianti et al., 2015). The calculated AUC = 0.9 in this study could discriminate patients with low levels of fibrosis (<5% TIF) from those with a higher degree of fibrosis (≥5% TIF).…”

Section: Introductionmentioning

confidence: 96%

Diagnostic and prognostic biomarkers for tubulointerstitial fibrosis

Rende

Guller

Goldys

et al. 2023

The Journal of Physiology

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Renal fibrosis is the final common pathophysiological pathway in chronic kidney disease (CKD) regardless of the underlying cause of kidney injury. Tubulointerstitial fibrosis (TIF) is considered to be the key pathological predictor of CKD progression. Currently, the gold‐standard tool to identify TIF is kidney biopsy, an invasive method that carries risks. Non‐invasive diagnostics rely on an estimation of glomerular filtration rate and albuminuria to assess kidney function, but these fail to diagnose early CKD accurately or to predict progressive decline in kidney function. In this review, we summarize the current and emerging molecular biomarkers that have been studied in various clinical settings and in animal models of kidney disease and that are correlated with the degree of TIF. We examine the potential of these biomarkers to diagnose TIF non‐invasively and to predict disease progression. We also examine the potential of new technologies and non‐invasive diagnostic approaches in assessing TIF. Limitations of current and potential biomarkers are discussed and knowledge gaps identified.

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Transforming growth factor β1 is better than α smooth muscle actin for the prediction of renal fibrosis in patients with nephritic lupus

Cited by 5 publications

References 15 publications

Biomarkers for the detection of renal fibrosis and prediction of renal outcomes: a systematic review

Biomarkers for the detection of renal fibrosis and prediction of renal outcomes: a systematic review

Urinary procollagen III aminoterminal propeptide/creatinine (PIIINP/Cr) ratio and transforming growth factor beta/creatinine (TGF-β/Cr) ratio in children with idiopathic nephrotic syndrome on corticosteroid and cyclosporine A treatment

Diagnostic and prognostic biomarkers for tubulointerstitial fibrosis

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