Table 1.
Original studies assessing the relationship between microbiome-derived toxins and acute kidney injury.
| Author | Year | Population | Uremic Toxin/Parameter Assessed | Outcome | Results and Key Observations |
|---|---|---|---|---|---|
| Experimental | |||||
| Jang et al. [5] | 2009 | germ-free mice, afterwards fed bacteria-rich diet | numbers and phenotypes of T cells and NK cells, panel of cytokines | extent of renal injury and functional decline after IRI | microbial stimuli influence the phenotype of renal lymphocytes and ameliorate the extent of renal injury |
| Samanta et al. [6] | 2017 | Wistar rats | microbiota composition | hypoxia induced AKI | hypobaric hypoxia causes both AKI and affects gut microbial population |
| Long et al. [7] | 2017 | C57BL/6 mice | influence of elevated Hcy levels | cisplatin-induced AKI | cisplatin induces more severe tubular injury, tubular cell apoptosis and lower proliferation in hyperHcy mice |
| Li et al. [8] | 2019 | Sprague-Dawley rats | gut-derived endotoxin | increased renal mRNA of TLR4 and proinflammatory mediators (Il-6 and MCP-1) | endotoxin increases intrarenal inflammatory response |
| Yang et al. [9] | 2020 | C57BL/6 mice and germ-free C57BL/6 mice | microbiota composition | severity of IRI | intestinal dysbiosis, inflammation and leaky gut are consequences of AKI but also determine its severity |
| Andrianova et al. [10] | 2020 | Wistar rats | microbiota composition, levels of selected toxins (acylcarnitines) | severity of IRI, creatinine and urea levels | specific bacteria in the gut may ameliorate or aggravate IRI and affect toxin levels |
| Mishima et al. [11] | 2020 | germ-free mice and mice with microbiota | metabolome analysis | extent of kidney damage in adenine-induced AKI | germ-free mice enhanced host purine metabolism and exacerbated kidney damage |
| Human | |||||
| Knoflach et al. [12] | 1994 | retrospective | hippuric acid concentration | acute kidney allograft rejection | hippuric acid concentration was higher in patients with acute allograft rejection and fell after antirejection treatment |
| Carron et al. [13] | 2019 | prospective observational design: 146 kidney transplant recipients | circulating lipopolysaccharide | chronic inflammation and acute rejection episodes | chronic exposure to LPS in the period before transplantation can promote endotoxin tolerance and those patients are less prompt to develop acute rejection after transplantation |
| Wang et al. [14] | 2019 | prospective observational design: 262 patients with hospital-acquired AKI | serum indoxyl sulfate levels | 90-day mortality | serum indoxyl sulfate levels were elevated in patients with AKI and associated with a worse prognosis |
| Veldeman et al. [15] | 2019 | prospective observational design:194 patients with sepsis | serum indoxyl sulfate and p-cresyl sulfate levels | acute kidney injury due to sepsis | serum indoxyl sulfate and p-cresyl sulfate levels were higher in patients with AKI and correlated with AKI course |
Abbreviations: AKI, acute kidney injury; Hcy, homocysteine; Il-6, interleukin-6; IRI, ischemia-reperfusion injury; LPS, lipopolysaccharide MCP-1, monocyte chemoattractant protein-1; mRNA, messenger ribonucleic acid; TL4, toll-like receptor 4.