Indoxyl sulfate and <i>p</i>-cresol sulfate activated transforming growth factor-β pathway and increased Snail expression in vitro.

<p>A: Results of western blotting show that mouse proximal renal tubular cells (PKSV) cells had significantly increased protein expression of Sma- and Mad-related protein (Smad)2/Smad2-P, Smad3/Smad3-P, and Smad4, when treated with indoxyl sulfate (IS) and <i>p</i>-cresol sulfate (PCS). B: Western blotting and immunostaining for Snail show that PKSV cells had significantly increased nuclolear expression of Snail, when treated with IS and PCS. In the immunostaining study of Snail, PKSV cells were treated with 5 mg/dL IS or PCS for 3 days. C: The transforming growth factor-β1 (TGF-β1) concentrations in the culture medium were measured by ELISA method. PKSV cells treated with IS (5 and 50 mg/L) and PCS (1, 5 and 50 mg/L) had significantly higher TGF-β1 concentration in culture medium than control cells. (600×) (*: <i>P</i><0.05; **: <i>P</i><0.01; ***: <i>P</i><0.001, <i>vs.</i> control).</p

Indoxyl sulfate and <i>p</i>-cresol sulfate increased tumor growth factor-β1 and Snail protein expression in vivo.

<p>Western blot results show that mice treated with indoxyl sulfate and <i>p</i>-cresol sulfate had significantly increased intrarenal <u>transforming</u> growth factor-β1 and Snail protein expression. (*: <i>P</i><0.05; **: <i>P</i><0.01; ***: <i>P</i><0.001, <i>vs.</i> control).</p

Indoxyl sulfate and <i>p</i>-cresol sulfate induced epithelial-to-mesenchymal-like transition in mouse proximal renal tubular cells.

<p>A: Real-time polymerase chain recation results show that mouse proximal renal tubular (PKSV) cells treated with indoxyl sulfate (IS) and <i>p</i>-cresol sulfate (PCS) had significantly increased fibronectin and decreased E-cadherin expression. PKSV cells treated with IS and PCS at concentrations of 5 and 50 mg/L had significantly increased α-smooth muscle actin (SMA) expression. B: Results of immunohistological staining show that PKSV cells treated with IS and PCS at a concentration of 5 mg/L for 3 days had significant staining for fibronectin and α-SMA. The staining for E-cadherin was significantly decreased in PKSV cells treated with IS or PCS. (400×) (*: <i>P</i><0.05; **: <i>P</i><0.01; ***: <i>P</i><0.001, <i>vs.</i> control).</p

Potential mechanisms for the vitreous cycle of kidney injury induced by indoxyl sulfate and <i>p</i>-cresol sulfate.

<p>IS, indoxyl sulfate; PCS, <i>p</i>-cresol sulfate; RAAS, renin-angiotension-aldosterone system; TGF-β, transforming growth factor-β; EMT, epithelial-to-mesenchymal transition.</p

Indoxyl sulfate and <i>p</i>-cresol sulfate activated the renin–angiotensin–aldosterone system in vitro.

<p>A: Real-time polymerase chain reaction analysis shows that mouse proximal renal tubular cells (PKSV) cells had significantly increased renin, angiotensinogen, and angiotensin 1 (AT1) receptor mRNA expression, and decreased AT2 receptor mRNA expression. B: Western blotting shows that PKSV cells treated with indoxyl sulfate (IS) and <i>p</i>-cresol sulfate (PCS) at concentrations of 5 and 50 mg/L had significantly increased AT1 receptor protein expression. IS and PCS at concentrations of 1, 5, and 50 mg/L significantly decreased AT2 receptor protein expression <i>in vitro</i>. C: The angiotensin II concentrations in the culture medium were measured by EIA method. The angiotensin II concentration of control PKSV cells was lower than detection limit. Treatment with IS (5 and 50 mg/L) and PCS (1, 5 and 50 mg/L) significantly increased angiotensin II production. (*: <i>P</i><0.05; **: <i>P</i><0.01; ***: <i>P</i><0.001, <i>vs.</i> control).</p

Renin–angiotensin–aldosterone system inhibition with losartan significantly inhibited transforming growth factor-β1/Smads pathway and decreased Snail expression in vitro.

<p>A: ELISA analysis showed that losartan (1, 10, and 100 uM) significantly decreased the transforming growth factor-β1 concentration in the culture medium of PKSV cells treated with indoxyl sulfate (IS) (50 mg/L) and <i>p</i>-cresol sulfate (PCS) (50 mg/L). In addition, the Westren blotting results showed that significantly decreased the expression of Smad2-P, Smad3-P and Snail in PKSV cells treated wioth IS and PCS. (*: <i>P</i><0.05; **: <i>P</i><0.01; ***: <i>P</i><0.001).</p

Indoxyl sulfate and <i>p</i>-cresol sulfate activated renin–angiotensin–aldosterone system in vivo.

<p>A: Real-time polymerase chain reaction analysis show that mice treated with indoxyl sulfate (IS) and <i>p</i>-cresol sulfate (PCS) had significantly increased intra-renal renin, angiotensinogen, and angiotensin 1 (AT1) receptor mRNA expression, and decreased AT2 receptor mRNA expression. B: Western blotting shows that mice treated with IS and PCS had significantly increased intrarenal AT1 receptor and decreased AT2 receptor protein expression. (*: <i>P</i><0.05; **: <i>P</i><0.01; ***: <i>P</i><0.001, <i>vs.</i> control).</p

Indoxyl sulfate and <i>p</i>-cresol sulfate induced epithelial-to-mesenchymal-like transition in vivo.

<p>A: Real-time polymearse chain reaction results show that mice treated with indoxyl sulfate (IS) and <i>p</i>-cresol sulfate (PCS) had significantly increased fibronectin and α- smooth muscle actin (SMA) expression in kidney. E-cadherin expression was significantly decreased in mice treated with IS and PCS. B: Results of immunohistological staining show that the staining for fibronectin and α-SMA was significantly increased in mice treated with IS and PCS. The staining for E-cadherin was significantly decreased in mice treated with IS and PCS. (400×) (*: <i>P</i><0.05; **: <i>P</i><0.01; ***: <i>P</i><0.001, <i>vs.</i> control).</p

Renin–angiotensin–aldosterone system inhibition with losartan significantly decreased transforming growth factor-β1 and Snail expression and kidney injury in vivo.

<p>A: Western bloting shows that losartan significantly decreased renal transforming growth factor-β1 and Snail expression in mice treated with indoxyl sulfate (IS) and <i>p</i>-cresol sulfate (PCS). B: Western blotting results revealed that losartan significantly increaesd E-cadherin, and decreased fibronectin and α- smooth muscle actin protein expression in mice treated with IS or PCS. C: Masson trichrome staining results revealed that kidneys of mice treated with IS and PCS had significantly increased intersitial and glomerular fibrosis than control mice. Renin–angiotensin–aldosterone system inhibition with losartan significantly decreased kidney fibrosis in mice treated with IS and PCS. D: The nephrosclerosis scores of control and experimental mice were plotted. Nephrosclerosis scores were significantly higher in the IS- and PCS-injected mice than in the control mice. The nephrosclerosis scores were significantly lower in the losartan treatment groups (IS+L and PCS+L) than in the IS and PCS groups. (400×) (*: <i>P</i><0.05, <i>vs.</i> control; #: <i>P</i><0.05, IS+L <i>vs</i>. IS; §: <i>P</i><0.05, PCS+L <i>vs.</i> PCS) (L: losartan).</p

Data_Sheet_1_The Incidence of Contrast-Induced Nephropathy and the Need of Dialysis in Patients Receiving Angiography: A Systematic Review and Meta-Analysis.docx

ObjectivesThe risk of dialysis following contrast exposure is unclear. We aimed to examine the overall risk of contrast induced nephropathy and the need of dialysis based on a systematic review with random-effects meta-analysis.MethodsWe searched the electronic database including PubMed, Medline, Embase, and Cochrane Library from inception to 31 October, 2020 with predetermined search term to identify relevant studies. Observational studies investigating the association between contrast induced nephropathy after angiography and the need of dialysis were included, and summary risks were estimated. Two independent reviewers extracted the data, followed with random effects model to calculate the overall pooled incidence of contrast induced nephropathy and the need of dialysis after angiography. Subgroup-analysis and meta-regression were performed to assess heterogeneity of incidence across studies.ResultsOf 2,243 identified articles, 259 met our inclusion criteria were included in the meta-analysis after screening. Pooled effect estimates had the following summary incidence proportion for contrast induced nephropathy after angiography: 9.06% (95% CI: 8.53–9.58%; derived from 120 studies) and 0.52% (95% CI: 0.37–0.70%; derived from 110 studies) for the need of dialysis, respectively. The stratified summary incidence proportion of contrast induced nephropathy after contrast administration via intra-arterial route was 9.60% (95% CI: 9.0–10.2%; derived from 106 studies) and was 0.6% (95% CI: 0.40–0.80%; derived from 100 studies) for the need of dialysis, respectively. Our meta-regressions found that the amount of contrast medium exposure was associated with contrast-induced nephropathy.ConclusionThe potential risk of dialysis needs to be communicated to patients undergoing procedures requiring contrast, especially via intra-arterial exposure.Systematic Review Registration[https://reurl.cc/8Wrlry], identifier [CRD42020170702].</p