Table 3 Therapeutic strategies for reducing uremic toxins or modulating AhR activation in kidney diseases
From: Uremic toxins mediate kidney diseases: the role of aryl hydrocarbon receptor
Therapies | Techniques | Principles | Functions | References |
|---|---|---|---|---|
Blood Purification | Conventional HD | Diffusion | Removal of water-soluble small molecular-weight uremic toxins | [137] |
HDF | Diffusion and convection | Removal of small and middle molecular-weight uremic toxins | [137] | |
Hemoperfusion | Adsorption | Removal of middle and large molecular-weight and protein-bound uremic toxins | ||
Gastrointestinal dialysis | Carbon adsorbent AST-120 | The intestinal absorption and subsequent fecal excretion of uremic toxin precursors | AST-120 reduced renal and serum uremic toxins and attenuated neointima formation in CKD mice. But it did not attenuate renal injury in CKD mice and slow disease progression in CKD patients. | |
Nutritional therapy | Low protein diet | Reduction of substrate intake for uremic toxin generation | A low protein diet showed lower plasma and urinary uremic toxin levels, preserved kidney function, slowed the progression to ESRD and reduced the rate of all-cause death, but it did not delay the CKD progression in long-term follow-up. | |
Low protein diet supplemented with ketoanalogues | Reduction of substrate intake for uremic toxin generation and compensation for missing essential amino acids | A vegetarian very low protein diet supplemented with ketoanalogues alleviated uremic symptoms and deferred dialysis initiation. | [151] | |
Vegetarian diet | Reduction of animal protein intake and improvement of intestinal microbiota composition and metabolism | Vegetable proteins may induce renal changes comparable to a low protein diet and prevent the proteinuric and vasodilatory effects of meat. Vegetarians or vegans had significantly lower TMAO levels than omnivores. A high-fiber diet induced the production of beneficial metabolites, such as SCFAs. IS and PCS concentrations were negatively correlated with fiber intake and positively correlated with the protein/fiber index in anuric HD patients. | ||
Targeting microbiota | Probiotics | Enhancement of the intestinal epithelial barrier integrity, growth inhibition of pathogenic bacteria, improvement of the host immune system and increased production of the beneficial metabolites SCFAs | Supplementation of Faecalibacterium prausnitzii to 5/6 nephrectomy surgery-induced CKD mice reduced plasma PCS and TMAO levels, and ameliorated renal dysfunction and inflammation. Oral administration of Lactobacillus paracasei X11 reduced serum uric acid and renal inflammation in hyperuricemic mice. Supplementation of CKD patients undergoing HD with well-known Bifidobacteria, Lactobacilli and Streptococci failed to reduce uremic toxins. | |
Prebiotics | Growth stimulation of protective bacteria in the colon and increased production of the beneficial metabolites SCFAs | β-glucan prebiotic intervention decreased plasma IS, PCS and p-cresyl glucuronide levels. β-glucan increased Bifidobacterium and Lactobacillus and then increased the production of SCFAs. | ||
Synbiotics | Combination of probiotics and prebiotics | Synbiotic therapy reduced serum PCS but not IS and altered the intestinal microbiome in nondialysis patients with CKD stage 4 or 5. | [165] | |
AhR agonists and antagonists | 1-aminopyrene | AhR agonist | Treatment with 1-aminopyrene activated AhR. | [91] |
Flavonoids 5',7',3',4',5'-pentahydroxy flavanone, barleriside A and rhoifolin from Semen Plantagini | AhR antagonists | Dietary 5',7',3',4',5'-pentahydroxy flavanone and barleriside A alleviated the decline in renal function and renal fibrosis in 5/6 nephrectomized rats. | [91] | |
Vitamin B12 and FA | AhR antagonists | Treatment with vitamin B12 or FA rescued mice from TCDD- or FICZ-induced anemia and thrombocytopenia. | [169] | |
Flavonoid baicalein from the roots of Scutellaria baicalensis Georgi | AhR agonist | Administration of baicalein significantly decreased serum uric acid and urea nitrogen to attenuate hyperuricemia and renal injury. Baicalin ameliorated aristolochic acid I-induced kidney toxicity through AhR-dependent CYP1A1/2 induction in the liver. | ||
CH223191 | AhR antagonist | CH223191 normalized postischemic angiogenesis in adenine-induced CKD mice to a non-CKD level. CH223191 ameliorated CKD-induced cognitive impairment, astrocyte reactivation and neuronal activity enhancement. CH223191 did not affect cellular senescence under anoxia or reoxygenation. CH223191 prevented the increase in systolic blood pressure and diastolic blood pressure in chronic intermittent hypoxia rats. | ||
Geldanamycin | Indirect AhR antagonist | Geldanamycin inhibited IS-and IAA-upregulated TF expression. | [42] | |
α-NF | AhR antagonist | α-NF attenuated glomerular mesangial cell proliferation, macrophage infiltration, extracellular matrix protein deposition, cyclooxygenase /prostaglandin E2 expression, lipid peroxidation, oxidative stress, NOX activity and N-ɛ-carboxymethyl lysine formation in STZ-induced diabetic mice kidneys. | [122] | |
BAY2416964 | AhR antagonist | BAY2416964 alleviated cisplatin-induced kidney dysfunction and tubular injury by inhibiting cellular senescence. | [133] |