Acute Kidney Injury and Organ Dysfunction: What Is the Role of Uremic Toxins?

Abstract

Acute kidney injury (AKI), defined as an abrupt increase in serum creatinine, a reduced urinary output, or both, is experiencing considerable evolution in terms of our understanding of the pathophysiological mechanisms and its impact on other organs. Oxidative stress and reactive oxygen species (ROS) are main contributors to organ dysfunction in AKI, but they are not alone. The precise mechanisms behind multi-organ dysfunction are not yet fully accounted for. The building up of uremic toxins specific to AKI might be a plausible explanation for these disturbances. However, controversies have arisen around their effects in organs other than the kidney, because animal models usually depict AKI as a kidney-specific injury. Meanwhile, humans present AKI frequently in association with multi-organ failure (MOF). Until now, medium-molecular-weight molecules, such as inflammatory cytokines, have been proven to play a role in endothelial and epithelial injury, leading to increased permeability and capillary leakage, mainly in pulmonary and intestinal tissues.

Screening of Biocompatible MOFs for the Clearance of Indoxyl Sulfate Using GCMC Simulations

“…As shown in Figure 1b, the van der To validate the reliability of the model and force field used in this work, the bulk density of indoxyl sulfate was calculated and compared with the value from ChemSpider. 55 The simulated value at 298 K was 2.05 g/cm 3 , and the reference predicted value was 1.7 ± 0.1 g/cm 3 . According to the experimental study of Kato et al, 15 the uptake of NU-1000 for potassium indoxyl sulfate increases with the concentration of potassium indoxyl sulfate.…”

Physiologically Based Pharmacokinetic Modeling Approaches for Patients With SARS‐CoV‐2 Infection: A Case Study With Imatinib

“… 57 As is the case with chronic kidney disease, AKI may lead to a substantial decrease in renal drug clearance and hepatic CYP2C8 activity, the latter of which is likely due to the accumulation of uremic toxins. 58 , 59 However, clinical data in patients with AKI to support this is currently limited. Renal impairment is unlikely to affect the systemic exposure to imatinib due to very low contribution of renal elimination to the overall drug clearance (Table S1 ).…”

“…There was a downward trend of the estimated glomerular filtration rate in patients with CML over 4 years of treatment with imatinib before stabilizing 57 . As is the case with chronic kidney disease, AKI may lead to a substantial decrease in renal drug clearance and hepatic CYP2C8 activity, the latter of which is likely due to the accumulation of uremic toxins 58,59 . However, clinical data in patients with AKI to support this is currently limited.…”

Gut Microbiota Mediates the Protective Effects of Traditional Chinese Medicine Formula Qiong-Yu-Gao against Cisplatin-Induced Acute Kidney Injury

“…The gut microbiota dysbiosis may induce a predominant proteolytic fermentation and inflate the production of uremic toxins, such as indoxyl sulfate and p -cresyl sulfate ( 12 , 13 ). Uremic toxins are known to accumulate in renal tissue and contribute to pathogenesis and disease progression by inducing fibrosis, inflammation, and apoptosis ( 14 , 15 ). Meanwhile, short-chain fatty acids (SCFAs) are the end products of dietary fiber fermentation ( 16 ).…”