Table 9a.
Multiple risk factors accelerate CKD progression to ESRD, which have been reported by clinical studies and scientific literature. Our report provides novel data analyses evidences and mechanisms to support the multi-hit model for the development of CKD.
| clinical risk factor for CKD progression | scientific mechanism | PMID |
|---|---|---|
| ethnicity | APOL1 mutant in African | 27312436 |
| Epigenetically heritable changes |
25993323 |
|
| gender | direct effects of sex steroids on kidney | 29355169 |
| sex differences in NO metabolism and oxidative stress | 29355169 | |
| gender-differential impact of comorbidities and lifestyle risk factors |
29355169 |
|
| diabetes | Renal hemodynamic changes | 29486908 |
| ischemia and inflammation | 29486908 | |
| Overactive renin-angiotensin-aldosterone system |
29486908 |
|
| hypertension | Global RAS activation | 29144825 |
| renal inflammation |
29144825 |
|
| obesity | RAAS activation | 31015582 |
| renal compression | 31015582 | |
| Metabolic abnormalities |
31015582 |
|
| gut microbiota | production of uremic toxins | 30464044 |
| promoting translocation of bacterial component | 31243394 | |
| secreting metabolites favoring insulin resistance favoring insulin resistance and endothelial dysfunction |
31243394 |
|
| nephrotoxicity | inducing apoptosis, autophagy and necrosis | 29341864 |
| Oxidant-Induced Renal Injury | 15519281 | |
| mitochondria dysfunction in the proximal tubules |
29939355 |
|
| Hepatitis B and C infections | glomerular immune complex deposition | 28149647 |
| direct viral invasion of the renal parenchyma |
31155101 |
|
| dyslipidemia | Direct lipid-induced cellular injury | 22290079 |
| inflammatory cytokines |
29176657 |
|
| proteinuria | Increased intraglomerular hydraulic pressure | 22137726 |
| damage to glomerular filtration barrier |
22137726 |
|
| mineral bone disorder | VSMC dedifferentiation | 28119179 |
| neointimal atherosclerotic calcification | 28119179 |