SLCO4C1 transporter eliminates uremic toxins and attenuates hypertension and renal inflammation.

@article{Toyohara2009SLCO4C1TE,
  title={SLCO4C1 transporter eliminates uremic toxins and attenuates hypertension and renal inflammation.},
  author={T. Toyohara and T. Suzuki and R. Morimoto and Yasutoshi Akiyama and Tomokazu Souma and H. Shiwaku and Yoichi Takeuchi and E. Mishima and Michiaki Abe and M. Tanemoto and S. Masuda and H. Kawano and K. Maemura and M. Nakayama and Hiroshi Sato and T. Mikkaichi and H. Yamaguchi and S. Fukui and Y. Fukumoto and H. Shimokawa and K. Inui and T. Terasaki and J. Goto and S. Ito and T. Hishinuma and I. Rubera and M. Tauc and Y. Fujii‐Kuriyama and H. Yabuuchi and Y. Moriyama and T. Soga and T. Abe},
  journal={Journal of the American Society of Nephrology : JASN},
  year={2009},
  volume={20 12},
  pages={
          2546-55
        }
}
Hypertension in patients with chronic kidney disease (CKD) strongly associates with cardiovascular events. Among patients with CKD, reducing the accumulation of uremic toxins may protect against the development of hypertension and progression of renal damage, but there are no established therapies to accomplish this. Here, overexpression of human kidney-specific organic anion transporter SLCO4C1 in rat kidney reduced hypertension, cardiomegaly, and inflammation in the setting of renal failure… Expand
Transcriptional regulation of organic anion transporting polypeptide SLCO4C1 as a new therapeutic modality to prevent chronic kidney disease.
Uremic toxins accumulate in patients with chronic kidney diseases (CKDs) and cause further progression of renal damage and cardiovascular diseases. Recently, it was reported that some of the organicExpand
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The expression, localization and/or function of various SLC and ABC transporters as well as DMEs in the kidney and other organs are discussed in the context of CKD and systemic pathophysiology. Expand
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The complex problems associated with uremia warrant a transdisciplinary approach that unites research experts in the area of fundamental biomedical research with their colleagues in clinical nephrology, as well as innovative renal replacement therapies targetting the protein-bound uremic toxins. Expand
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The renal tubular clearance mechanisms for uremic toxins, as well as the intracellular events associated with their accumulation, are described, involving activation of the aryl hydrocarbon receptor, disturbance of mitochondrial functioning, and competition with metabolizing enzymes. Expand
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Functional activity of these transporters plays a key role in drug handling and nephrotoxicity, and may also play a role in remote sensing and signaling, as part of a versatile small molecule communication network operative throughout the body in normal and diseased states, such as AKI and CKD. Expand
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TLDR
In 5/6 nephrectomized rats, treatment with oral adsorbent AST-120 significantly decreased plasma indoxyl sulfate level and conversely increased the expression of slco4c1, following the reduction of plasma level of guanidinosuccinate, suggesting that the removal of indoxol sulfate and blocking its signal pathway may help to restore the SLCO4C1-mediated renal excretion of uremic toxins in CKD. Expand
The Importance of Tubular Function in Chronic Kidney Disease
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Tubular function has an important role for endogenous organic cations, anions and drug excretion in CKD patients, and a deeper understanding of its multiple mechanisms could provide new therapeutic alternatives in this population. Expand
Metabolomic profiling of the autosomal dominant polycystic kidney disease rat model
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The profile of uremic retention solutes of ADPKD by capillary electrophoresis–mass spectrometry (CE-MS) using the Han:SPRD rat model was analyzed and compounds related toADPKD could be useful markers for detecting the early stage of AD PKD. Expand
Uremic Toxins Inhibit Transport by Breast Cancer Resistance Protein and Multidrug Resistance Protein 4 at Clinically Relevant Concentrations
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This study shows that several uremic toxins inhibit active transport by MRP4 and BCRP at clinically relevant concentrations, which are below the maximal plasma concentrations of the tested toxins. Expand
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