Do all protein bound renal toxins exert physiological effects on cardiac cells?

Iyngkaran, Pupalan; Tuck, Kellie L.; Ma, Jie; Ho, Pei Yi; Lekawanvijit, Suree; Kompa, A.; Wang, B.; Krum, Henry

doi:10.1016/j.hlc.2009.05.618

Cited by 6 publications

(7 citation statements)

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“…102 More recently, our group examined profibrotic and prohypertrophic effects of IS, cresol, and cresol conjugates in cultured neonatal rat cardiac fibroblasts and myocytes using 3 H-proline and 3 H-leucine incorporation, respectively. 103 Angiotensin II served as positive control. IS had strong dose-dependent profibrotic and prohypertrophic effects, whereas other PBUT, including pCS, p-cresol, m-cresol, m-cresyl sulfate, and phenylacetic acid, had little or no effect (Figures 1 and 2) …”

Section: Evidence Of Adverse CV Effects Of Protein-bound Uremic Toxinsmentioning

confidence: 99%

Cardiorenal Syndrome

Lekawanvijit

Kompa

Wang

et al. 2012

Circulation Research

151

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Cardiorenal syndrome is a condition in which a complex interrelationship between cardiac dysfunction and renal dysfunction exists. Despite advances in treatment of both cardiovascular and kidney disease, cardiorenal syndrome remains a major global health problem. Characteristic of the pathophysiology of cardiorenal syndrome is bidirectional cross-talk; mediators/substances activated by the disease state of 1 organ can play a role in worsening dysfunction of the other by exerting their biologically harmful effects, leading to the progression of the syndrome. Accumulation of uremic toxins is a hallmark of renal excretory dysfunction. Removal of some toxins by conventional dialysis is particularly problematic because of their high protein binding. In this review, we demonstrate that protein-bound uremic toxins may play an important role in progression of cardiovascular disease in the setting of chronic kidney disease. The highly protein-bound uremic toxin indoxyl sulfate has emerged as a potent toxin adversely affecting both the kidney and heart. Direct cardiac effects of this toxin have been recently demonstrated both in vitro and in vivo. Specifically, potent fibrogenic and prohypertrophic effects, as well as oxidative stress-inducing effects, appear to play a central role in both renal and cardiac pathology. Many of these adverse effects can be suppressed by use of a gut adsorbent, AST-120. Potential mechanisms underlying indoxyl sulfate−induced cardiorenal fibrosis are discussed. Future research and clinical implications conclude this review.

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Section: Evidence Of Adverse CV Effects Of Protein-bound Uremic Toxinsmentioning

confidence: 99%

Cardiorenal Syndrome

Lekawanvijit

Kompa

Wang

et al. 2012

Circulation Research

151

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“…IS increases TGF-β1 expression and collagen I in renal cells and cardiac fibroblasts 52 , 53 . PC, as well as PCS, induces fibrosis in kidney tubular cells and cardiomyocytes 54 , 55 , and promotes the redistribution of fat in the body, thereby modifying insulin resistance 56 . However, the role of UT in skeletal muscle fibrosis and fat deposition related to sarcopenia has never been analysed previously.…”

Section: Discussionmentioning

confidence: 99%

Uraemic toxins impair skeletal muscle regeneration by inhibiting myoblast proliferation, reducing myogenic differentiation, and promoting muscular fibrosis

Alcalde-Estévez

Sosa

Asenjo-Bueno

et al. 2021

Sci Rep

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Uraemic toxins increase in serum parallel to a decline in the glomerular filtration rate and the development of sarcopenia in patients with chronic kidney disease (CKD). This study analyses the role of uraemic toxins in sarcopenia at different stages of CKD, evaluating changes in the muscular regeneration process. Cultured C2C12 cells were incubated with a combination of indoxyl sulphate and p-cresol at high doses (100 µg/mL) or low doses (25 µg/mL and 10 µg/mL) resembling late or early CKD stages, respectively. Cell proliferation (analysed by scratch assays and flow cytometry) was inhibited only by high doses of uraemic toxins, which inactivated the cdc2-cyclin B complex, inhibiting mitosis and inducing apoptosis (analysed by annexin V staining). By contrast, low doses of uraemic toxins did not affect proliferation, but reduced myogenic differentiation, primed with 2% horse serum, by inhibiting myogenin expression and promoting fibro-adipogenic differentiation. Finally, to assess the in vivo relevance of these results, studies were performed in gastrocnemii from uraemic rats, which showed higher collagen expression and lower myosin heavy chain expression than those from healthy rats. In conclusion, uraemic toxins impair the skeletal muscular regeneration process, even at low concentrations, suggesting that sarcopenia can progress from the early stages of CKD.

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“…In the setting of CKD there is systemic accumulation of such toxins, many of which can be eliminated by dialysis. However, removal of some toxins, including indoxyl sulphate, phenyl acetic acid, m / p ‐cresol and m / p ‐cresylsulphate, is limited owing to their high protein‐binding capacity 41,42 . Of these non‐dialysable toxins, indoxyl sulphate has been demonstrated to have profibrotic effects to the kidney and, most recently, its profibrotic and prohypertrophic effects on relevant cardiac cells have been demonstrated 42–46 .…”

Section: Pathophysiology Of Crsmentioning

confidence: 99%

“…However, removal of some toxins, including indoxyl sulphate, phenyl acetic acid, m ⁄ p-cresol and m ⁄ p-cresylsulphate, is limited owing to their high protein-binding capacity. 41,42 Of these non-dialysable toxins, indoxyl sulphate has been demonstrated to have profibrotic effects to the kidney and, most recently, its profibrotic and prohypertrophic effects on relevant cardiac cells have been demonstrated. [42][43][44][45][46] In addition, the increased cardiac fibrosis in animals with CKD has been shown to be correlated with indoxyl sulphate serum levels.…”

Section: Other Factorsmentioning

confidence: 99%

“…41,42 Of these non-dialysable toxins, indoxyl sulphate has been demonstrated to have profibrotic effects to the kidney and, most recently, its profibrotic and prohypertrophic effects on relevant cardiac cells have been demonstrated. [42][43][44][45][46] In addition, the increased cardiac fibrosis in animals with CKD has been shown to be correlated with indoxyl sulphate serum levels. 47 Several uraemic toxins, namely asymmetrical dimethyl L-arginine (ADMA), homocysteine, advanced glycation end-products, p-cresyl sulphate, indoxyl sulphate etc., are mostly protein bound and are linked to endothelial dysfunction, atherosclerosis and insulin resistance in end-stage renal disease and advanced CKD.…”

Section: Other Factorsmentioning

confidence: 99%

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Cardiorenal syndrome: Pathophysiology, preclinical models, management and potential role of uraemic toxins

Liu

Lekawanvijit

Kompa

et al. 2012

Clin Exp Pharma Physio

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Cardiorenal syndrome (CRS) describes the primary dysfunction in either the kidney or heart that initiates the combined impairment of both organs. The heart and kidney exert reciprocal control of the respective function to maintain constant blood volume and organ perfusion under continuously changing conditions. The pathophysiology of CRS is not fully understood, but appears to be caused by a complex combination of haemodynamic, neurohormonal, immunological and biochemical feedback pathways. Of these pathways, the contributory role of uraemic toxins that accumulate in CRS has been underexplored. One such toxin, namely indoxyl sulphate, has been found to have direct adverse effects on relevant cardiac cells. Early diagnosis by assessing cardiac and renal injury biomarkers may be critical for timely therapeutic intervention. Such therapies are directed at attenuation of neurohormonal activation, control of elevated blood pressure, correction of anaemia and relief of hypervolaemia. Reduction of non-dialysable uraemic toxins is a further potentially beneficial therapeutic strategy.

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Do all protein bound renal toxins exert physiological effects on cardiac cells?

Cited by 6 publications

References 0 publications

Cardiorenal Syndrome

Cardiorenal Syndrome

Uraemic toxins impair skeletal muscle regeneration by inhibiting myoblast proliferation, reducing myogenic differentiation, and promoting muscular fibrosis

Cardiorenal syndrome: Pathophysiology, preclinical models, management and potential role of uraemic toxins

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