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Uremic Toxins in Organ Crosstalk
Jerome Lowenstein1, Sanjay K Nigam2
1Department of Nephrology, New York University School of Medicine, New York, NY, United States.
Frontiers in Medicine
|May 3, 2021
Summary
Uremic toxins, like indoxyl sulfate, are organic anions involved in gut-kidney communication. These toxins, regulated by drug transporters and metabolizing enzymes, highlight disordered signaling in chronic kidney disease (CKD).
Area of Science:
- Uremic toxin research
- Systems biology of kidney disease
- Gut-microbiome-host interactions
Background:
- Many uremic toxins are organic anions, including indoxyl sulfate, p-cresol sulfate, and uric acid.
- The gut microbiome is a primary source of indole, a precursor to indoxyl sulfate after liver metabolism.
- Inter-organ and inter-organismal communication are crucial in uremia.
Approach:
- Investigated the roles of organic anion transporters (OATs, OATPs, MRPs, ABCG2) in uremic toxin transport.
- Utilized knockout mouse models to establish the function of OAT1 and OAT3 in the kidney proximal tubule.
- Examined the impact of uremic toxins on signaling and metabolism in both renal and extra-renal tissues.
Key Points:
- Organic anion transporters (e.g., OAT1, OAT3, ABCG2) are critical for regulating uremic toxin levels.
- Intestinal transporters like ABCG2 play a role in restoring homeostasis during chronic kidney disease (CKD) progression.
- Indoxyl sulfate and other uremic toxins influence gene expression and signaling pathways.
Conclusions:
- Uremic toxins are integral to a remote sensing and signaling network involving drug transporters and metabolizing enzymes.
- CKD can be viewed as a condition with disordered inter-organ and inter-organismal communication.
- A systems biology approach reveals uremia results from aberrant sensing and signaling mechanisms.
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