scholarly journals The Prescription of Drugs That Inhibit Organic Anion Transporters 1 or 3 Is Associated with the Plasma Accumulation of Uremic Toxins in Kidney Transplant Recipients

Toxins ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 15
Author(s):  
Camille André ◽  
Touria Mernissi ◽  
Gabriel Choukroun ◽  
Youssef Bennis ◽  
Saïd Kamel ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Prescription Drugs ◽  
Organic Anion ◽  
Uremic Toxins ◽  
Renal Elimination ◽  
Organic Anion Transporters ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Anion Transporters ◽  
Liquid Chromatography Tandem Mass

The renal elimination of uremic toxins (UTs) can be potentially altered by drugs that inhibit organic anion transporters 1/3 (OAT1/OAT3). The objective of the present study was to determine whether the prescription of at least one OAT1/OAT3 inhibitor was associated with the plasma accumulation of certain UTs in kidney transplant recipients. We included 403 kidney transplant recipients. For each patient, we recorded all prescription drugs known to inhibit OAT1/OAT3. Plasma levels of four UTs (trimethylamine N-oxide (TMAO), indole acetic acid (IAA), para-cresylsulfate (pCS), and indoxylsulfate (IxS) were assayed using liquid chromatography-tandem mass spectrometry. Plasma UT levels were significantly higher among patients prescribed at least one OAT inhibitor (n = 311) than among patients not prescribed any OAT inhibitors (n = 92). Multivariate analysis revealed that after adjustment for age, estimated glomerular filtration rate (eGFR), plasma level of albumin and time since transplantation, prescription of an OAT1/OAT3 inhibitor was independently associated with the plasma accumulation of pCS (adjusted odds ratio (95% confidence interval): 2.11 (1.26; 3.61]). Our results emphasize the importance of understanding the interactions between drugs and UTs and those involving UT transporters in particular.

scholarly journals Uremic Toxins in Organ Crosstalk

2021 ◽  
Vol 8 ◽  
Author(s):  
Jerome Lowenstein ◽  
Sanjay K. Nigam
Keyword(s):  
Remote Sensing ◽  
Gut Microbiome ◽  
Drug Transporters ◽  
Organic Anion ◽  
Uremic Toxins ◽  
Indoxyl Sulfate ◽  
Drug Metabolizing Enzymes ◽  
Organic Anion Transporters ◽  
Metabolizing Enzymes ◽  
Anion Transporters

Many putative uremic toxins—like indoxyl sulfate, p-cresol sulfate, kynurenic acid, uric acid, and CMPF—are organic anions. Both inter-organ and inter-organismal communication are involved. For example, the gut microbiome is the main source of indole, which, after modification by liver drug metabolizing enzymes (DMEs), becomes indoxyl sulfate. Various organic anion transporters (organic anion transporters, OATs; organic anion-transporting polypeptides, OATPs; multidrug resistance-associated proteins, MRPs, and other ABC transporters like ABCG2)—often termed “drug transporters”—mediate movement of uremic toxins through cells and organs. In the kidney proximal tubule, critical roles for OAT1 and OAT3 in regulating levels of protein-bound uremic toxins have been established using knock-out mice. OATs are important in maintaining residual tubular function in chronic kidney disease (CKD); as CKD progresses, intestinal transporters like ABCG2, which extrude urate and other organic anions into the gut lumen, seem to help restore homeostasis. Uremic toxins like indoxyl sulfate also regulate signaling and metabolism, potentially affecting gene expression in extra-renal tissues as well as the kidney. Focusing on the history and evolving story of indoxyl sulfate, we discuss how uremic toxins appear to be part of an extensive “remote sensing and signaling” network—involving so-called drug transporters and drug metabolizing enzymes which modulate metabolism and signaling. This systems biology view of uremic toxins is leading to a new appreciation of uremia as partly due to disordered remote sensing and signaling mechanisms–resulting from, and causing, aberrant inter-organ (e.g., gut-liver- kidney-CNS) and inter-organismal (e.g., gut microbiome-host) communication.

Involvement of organic anion transporters in the efflux of uremic toxins across the blood-brain barrier

2006 ◽  
Vol 96 (4) ◽  
pp. 1051-1059 ◽  
Author(s):  
Tsuneo Deguchi ◽  
Kouya Isozaki ◽  
Kouno Yousuke ◽  
Tetsuya Terasaki ◽  
Masaki Otagiri
Keyword(s):  
Blood Brain Barrier ◽  
Organic Anion ◽  
Uremic Toxins ◽  
Brain Barrier ◽  
Organic Anion Transporters ◽  
Anion Transporters ◽  
Blood Brain

Long-term follow-up of polyneuropathy in diabetic kidney transplant recipients

Diabetes ◽  
1988 ◽  
Vol 37 (9) ◽  
pp. 1247-1252 ◽  
Author(s):  
J. A. Van der Vliet ◽  
X. Navarro ◽  
W. R. Kennedy ◽  
F. C. Goetz ◽  
J. J. Barbosa ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Diabetic Kidney ◽  
Long Term Follow Up

Factors that Influence the Durability of Transplanted Kidneys in South Africa

2019 ◽  
Vol 21 (2) ◽  
Author(s):  
Hillary Ndemera ◽  
Busisiwe R. Bhengu
Keyword(s):  
South Africa ◽  
Kidney Transplant ◽  
Lifestyle Modification ◽  
P Value ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Kidney Allograft ◽  
Factors Influencing ◽  
Allograft Loss ◽  
Transplanted Kidneys

Kidney transplantation is the cornerstone for renal treatment in patients with end-stage renal failure. Despite improvements in short-term outcomes of renal transplantation, kidney allograft loss remains a huge challenge. The aim of the study was to assess factors influencing the durability of transplanted kidneys among transplant recipients in South Africa. A descriptive cross-sectional study design was used. A random sampling was used to select 171 participants. Data were collected through structured face-to-face interviews developed from in-depth consideration of relevant literature. Data were coded and entered into the SPSS software, version 24. The entered data were analysed using descriptive and inferential statistics. The results revealed that the average durability of transplanted kidneys was 9.07 years among selected kidney transplant recipients in South Africa. Factors associated with the durability of transplanted kidneys included age, the sewerage system and strict immunosuppressive adherence, all with a P-value = .000, followed by the mode of transport (P-value = .001) and support system (P-value = .004). Other variables including demographics, the healthcare system, medication and lifestyle modification engagement were not associated with the durability of transplanted kidneys. Understanding the factors influencing the durability of transplanted kidneys among kidney transplant recipients in South Africa is crucial. The study revealed associated factors and gaps which may be contributory factors to kidney allograft loss. This study provides an opportunity to introduce specific interventions to nephrology professionals to promote prolonged graft durability. It is recommended that a specific intervention model be developed, which targets South African kidney recipients taking into account the significant variables in this study and the socio-economic status of the country.

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