Adenine-induced animal model of chronic kidney disease: current applications and future perspectives

References

• Yan M-T, Chao C-T, Lin S-H. Chronic kidney disease: strategies to retard progression. IJMS. 2021;22(18):1. doi: 10.3390/ijms221810084.
   Google Scholar
• Kalantar-Zadeh K, Jafar TH, Nitsch D, et al. Chronic kidney disease. Lancet. 2021;398(10302):786–22. doi: 10.1016/S0140-6736(21)00519-5.
   PubMed Web of Science ®Google Scholar
• Ruiz-Ortega M, Rayego-Mateos S, Lamas S, et al. Targeting the progression of chronic kidney disease. Nat Rev Nephrol. 2020;16(5):269–288. doi: 10.1038/s41581-019-0248-y.
   PubMed Web of Science ®Google Scholar
• Ku E, Lee BJ, Wei J, et al. Hypertension in CKD: core curriculum 2019. Am J Kidney Dis. 2019;74(1):120–131. doi: 10.1053/j.ajkd.2018.12.044.
   PubMed Web of Science ®Google Scholar
• Webster AC, Nagler EV, Morton RL, et al. Chronic kidney disease. Lancet. 2017;389(10075):1238–1252. doi: 10.1016/S0140-6736(16)32064-5.
   PubMed Web of Science ®Google Scholar
• Panizo S, Martínez-Arias L, Alonso-Montes C, et al. Fibrosis in chronic kidney disease: pathogenesis and consequences. IJMS. 2021;22(1):408. doi: 10.3390/ijms22010408.
   Google Scholar
• Djudjaj S, Boor P. Cellular and molecular mechanisms of kidney fibrosis. Mol Aspects Med. 2019;65:16–36. doi: 10.1016/j.mam.2018.06.002.
   PubMed Web of Science ®Google Scholar
• Becker GJ, Hewitson TD. Animal models of chronic kidney disease: useful but not perfect. Nephrol Dial Transplant. 2013;28(10):2432–2438. doi: 10.1093/ndt/gft071.
   PubMed Web of Science ®Google Scholar
• Noone D, Licht C. Chronic kidney disease: a new look at pathogenetic mechanisms and treatment options. Pediatr Nephrol. 2014;29(5):779–792. doi: 10.1007/s00467-013-2436-5.
   PubMedGoogle Scholar
• Musgrove J, Wolf M. Regulation and effects of FGF23 in chronic kidney disease. Annu Rev Physiol. 2020;82(1):365–390. doi: 10.1146/annurev-physiol-021119-034650.
   PubMedGoogle Scholar
• Kumakura S, Sato E, Sekimoto A, et al. Nicotinamide attenuates the progression of renal failure in a mouse model of adenine-induced chronic kidney disease. Toxins (Basel). 2021;13(1):50. doi: 10.3390/toxins13010050.
   PubMed Web of Science ®Google Scholar
• Bao Y-W, Yuan Y, Chen J-H, et al. Kidney disease models: tools to identify mechanisms and potential therapeutic targets. Zool Res. 2018;39(2):72–86. doi: 10.24272/j.issn.2095-8137.2017.055.
   PubMed Web of Science ®Google Scholar
• Fu Y, Tang C, Cai J, et al. Rodent models of AKI-CKD transition. Am J Physiol Renal Physiol. 2018;315(4):F1098–F1106. doi: 10.1152/ajprenal.00199.2018.
   PubMed Web of Science ®Google Scholar
• Orlando LA, Belasco EJ, Patel UD, et al. The chronic kidney disease model: a general purpose model of disease progression and treatment. BMC Med Inform Decis Mak. 2011;11(1):41. doi: 10.1186/1472-6947-11-41.
   PubMedGoogle Scholar
• Singh S, Grabner A, Yanucil C, et al. Fibroblast growth factor 23 directly targets hepatocytes to promote inflammation in chronic kidney disease. Kidney Int. 2016;90(5):985–996. doi: 10.1016/j.kint.2016.05.019.
   PubMed Web of Science ®Google Scholar
• Vaziri ND, Wong J, Pahl M, et al. Chronic kidney disease alters intestinal microbial flora. Kidney Int. 2013;83(2):308–315. doi: 10.1038/ki.2012.345.
   PubMed Web of Science ®Google Scholar
• Watanabe H, Miyamoto Y, Honda D, et al. p-Cresyl sulfate causes renal tubular cell damage by inducing oxidative stress by activation of NADPH oxidase. Kidney Int. 2013;83(4):582–592. doi: 10.1038/ki.2012.448.
   PubMed Web of Science ®Google Scholar
• Alicic RZ, Rooney MT, Tuttle KR. Diabetic kidney disease. Clin J Am Soc Nephrol. 2017;12(12):2032–2045. doi: 10.2215/CJN.11491116.
   PubMed Web of Science ®Google Scholar
• Wada J, Makino H. Inflammation and the pathogenesis of diabetic nephropathy. Clin Sci (Lond). 2013;124(3):139–152. doi: 10.1042/CS20120198.
   PubMed Web of Science ®Google Scholar
• Reidy K, Kang HM, Hostetter T, et al. Molecular mechanisms of diabetic kidney disease. J Clin Invest. 2014;124(6):2333–2340. doi: 10.1172/JCI72271.
   PubMed Web of Science ®Google Scholar
• Putta S, Lanting L, Sun G, et al. Inhibiting microRNA-192 ameliorates renal fibrosis in diabetic nephropathy. J Am Soc Nephrol. 2012;23(3):458–469. doi: 10.1681/ASN.2011050485.
   PubMed Web of Science ®Google Scholar
• Thomas MC, Brownlee M, Susztak K, et al. Diabetic kidney disease. Nat Rev Dis Primers. 2015;1(1):15018. doi: 10.1038/nrdp.2015.18.
   PubMedGoogle Scholar
• Tuttle KR, Bakris GL, Bilous RW, et al. Diabetic kidney disease: a report from an ADA consensus conference. Am J Kidney Dis. 2014;64(4):510–533. doi: 10.1053/j.ajkd.2014.08.001.
   PubMed Web of Science ®Google Scholar
• Udani S, Lazich I, Bakris GL. Epidemiology of hypertensive kidney disease. Nat Rev Nephrol. 2011;7(1):11–21. doi: 10.1038/nrneph.2010.154.
   PubMed Web of Science ®Google Scholar
• Bertani T, Rocchi G, Sacchi G, et al. Adriamycin-induced glomerulosclerosis in the rat. Am J Kidney Dis. 1986;7(1):12–19. doi: 10.1016/s0272-6386(86)80051-8.
   PubMed Web of Science ®Google Scholar
• Arif E, Solanki AK, Nihalani D. Adriamycin susceptibility among C57BL/6 substrains. Kidney Int. 2016;89(3):721–723. doi: 10.1016/j.kint.2015.10.019.
   PubMed Web of Science ®Google Scholar
• Xiong T, Attar M, Gnirck A-C, et al. Interleukin-9 protects from early podocyte injury and progressive glomerulosclerosis in adriamycin-induced nephropathy. Kidney Int. 2020;98(3):615–629. doi: 10.1016/j.kint.2020.04.036.
   PubMed Web of Science ®Google Scholar
• Breyer MD, Susztak K. The next generation of therapeutics for chronic kidney disease. Nat Rev Drug Discov. 2016;15(8):568–588. doi: 10.1038/nrd.2016.67.
   PubMed Web of Science ®Google Scholar
• Chen D-Q, Hu H-H, Wang Y-N, et al. Natural products for the prevention and treatment of kidney disease. Phytomedicine. 2018;50:50–60. doi: 10.1016/j.phymed.2018.09.182.
   PubMed Web of Science ®Google Scholar
• Jivishov E, Nahar L, Sarker SD. Nephroprotective natural products. In: Annual reports in medicinal chemistry. Elsevier; 2020. p. 251–271. doi: 10.1016/bs.armc.2020.02.003.
   Google Scholar
• Rahman M, Akter S, Dorotea D, et al. Renoprotective potentials of small molecule natural products targeting mitochondrial dysfunction. Front Pharmacol. 2022;13:925993. doi: 10.3389/fphar.2022.925993.
   PubMed Web of Science ®Google Scholar
• Uddin MJ, Kim EH, Hannan M, et al. Pharmacotherapy against oxidative stress in chronic kidney disease: promising small molecule natural products targeting Nrf2-HO-1 signaling. Antioxidants. 2021;10(2):258. doi: 10.3390/antiox10020258.
   Web of Science ®Google Scholar
• Zhou Z, Qiao Y, Zhao Y, et al. Natural products: potential drugs for the treatment of renal fibrosis. Chin Med. 2022;17(1):98. doi: 10.1186/s13020-022-00646-z.
   PubMed Web of Science ®Google Scholar
• Yokozawa T, Zheng PD, Oura H, et al. Animal model of adenine-induced chronic renal failure in rats. Nephron. 1986;44(3):230–234. doi: 10.1159/000183992.
   PubMed Web of Science ®Google Scholar
• Liu X, Deng R, Chen Y, et al. Jian-Pi-Yi-Shen formula improves adenine-induced chronic kidney disease via regulating tryptophan metabolism and aryl hydrocarbon receptor signaling. Front Pharmacol. 2022;13:922707. doi: 10.3389/fphar.2022.922707.
   PubMed Web of Science ®Google Scholar
• Li X, Li W, Zhang Z, et al. SIRT6 overexpression retards renal interstitial fibrosis through targeting HIPK2 in chronic kidney disease. Front Pharmacol. 2022;13:1007168. doi: 10.3389/fphar.2022.1007168.
   PubMed Web of Science ®Google Scholar
• Li L, Li A, Gan L, et al. Roxadustat improves renal osteodystrophy by dual regulation of bone remodeling. Endocrine. 2022;79(1):180–189. doi: 10.1007/s12020-022-03199-1.
   PubMed Web of Science ®Google Scholar
• Diwan V, Mistry A, Gobe G, et al. Adenine-induced chronic kidney and cardiovascular damage in rats. J Pharmacol Toxicol Methods. 2013;68(2):197–207. doi: 10.1016/j.vascn.2013.05.006.
   PubMed Web of Science ®Google Scholar
• Kim K, Anderson EM, Thome T, et al. Skeletal myopathy in CKD: a comparison of adenine-induced nephropathy and 5/6 nephrectomy models in mice. Am J Physiol Renal Physiol. 2021;321(1):F106–F119. doi: 10.1152/ajprenal.00117.2021.
   PubMed Web of Science ®Google Scholar
• Kimura T, Kuragano T, Yamamoto K, et al. Deregulated iron metabolism in bone marrow from adenine-induced mouse model of chronic kidney disease. Int J Hematol. 2019;109(1):59–69. doi: 10.1007/s12185-018-2531-2.
   PubMed Web of Science ®Google Scholar
• Kobuchi S, Ayajiki K. Impairment of endothelial function in adenine-induced renal injury in rats. J. Pharmacol. Sci. 2016;130:s246.
   Web of Science ®Google Scholar
• Mohamed FF, Amadeu de Oliveira F, Kinoshita Y, et al. Dentoalveolar alterations in an adenine-induced chronic kidney disease mouse model. J Bone Miner Res. 2023;38(8):1192–1207. doi: 10.1002/jbmr.4829.
   PubMed Web of Science ®Google Scholar
• Saito H, Miyakoshi N, Kasukawa Y, et al. Analysis of bone in adenine-induced chronic kidney disease model rats. Osteoporos Sarcopenia. 2021;7(4):121–126. doi: 10.1016/j.afos.2021.11.001.
   PubMedGoogle Scholar
• Jia T, Olauson H, Lindberg K, et al. A novel model of adenine-induced tubulointerstitial nephropathy in mice. BMC Nephrol. 2013;14(1):116. doi: 10.1186/1471-2369-14-116.
   PubMedGoogle Scholar
• Mazumder MK, Giri A, Kumar S, et al. A highly reproducible mice model of chronic kidney disease: evidences of behavioural abnormalities and blood-brain barrier disruption. Life Sci. 2016;161:27–36. doi: 10.1016/j.lfs.2016.07.020.
   PubMed Web of Science ®Google Scholar
• Aparicio-Trejo OE, Avila-Rojas SH, Tapia E, et al. Chronic impairment of mitochondrial bioenergetics and β-oxidation promotes experimental AKI-to-CKD transition induced by folic acid. Free Radic Biol Med. 2020;154:18–32. doi: 10.1016/j.freeradbiomed.2020.04.016.
   PubMed Web of Science ®Google Scholar
• Perales-Quintana MM, Saucedo AL, Lucio-Gutiérrez JR, et al. Metabolomic and biochemical characterization of a new model of the transition of acute kidney injury to chronic kidney disease induced by folic acid. Peer J. 2019;7:e7113. doi: 10.7717/peerj.7113.
   PubMed Web of Science ®Google Scholar
• Zhou Y, Luo Z, Liao C, et al. MHC class II in renal tubules plays an essential role in renal fibrosis. Cell Mol Immunol. 2021;18(11):2530–2540. doi: 10.1038/s41423-021-00763-z.
   PubMed Web of Science ®Google Scholar
• Luan J, Fu J, Jiao C, et al. IL-18 deficiency ameliorates the progression from AKI to CKD. Cell Death Dis. 2022;13(11):957. doi: 10.1038/s41419-022-05394-4.
   PubMed Web of Science ®Google Scholar
• Katagiri D, Hamasaki Y, Doi K, et al. Interstitial renal fibrosis due to multiple cisplatin treatments is ameliorated by semicarbazide-sensitive amine oxidase inhibition. Kidney Int. 2016;89(2):374–385. doi: 10.1038/ki.2015.327.
   PubMed Web of Science ®Google Scholar
• Torres R, Velazquez H, Chang JJ, et al. Three-dimensional morphology by multiphoton microscopy with clearing in a model of cisplatin-induced CKD. J Am Soc Nephrol. 2016;27(4):1102–1112. doi: 10.1681/ASN.2015010079.
   PubMed Web of Science ®Google Scholar
• Sharp CN, Doll MA, Megyesi J, et al. Subclinical kidney injury induced by repeated cisplatin administration results in progressive chronic kidney disease. Am J Physiol Renal Physiol. 2018;315(1):F161–F172. doi: 10.1152/ajprenal.00636.2017.
   PubMed Web of Science ®Google Scholar
• Sears SM, Siskind LJ. Potential therapeutic targets for cisplatin-induced kidney injury: lessons from other models of AKI and fibrosis. J Am Soc Nephrol. 2021;32(7):1559–1567. doi: 10.1681/ASN.2020101455.
   PubMed Web of Science ®Google Scholar
• Xu Z, Li W, Han J, et al. Angiotensin II induces kidney inflammatory injury and fibrosis through binding to myeloid differentiation protein-2 (MD2). Sci Rep. 2017;7(1):44911. doi: 10.1038/srep44911.
   PubMedGoogle Scholar
• Yang Q, Hu J, Yang Y, et al. Sirt6 deficiency aggravates angiotensin II-induced cholesterol accumulation and injury in podocytes. Theranostics. 2020;10(16):7465–7479. doi: 10.7150/thno.45003.
   PubMed Web of Science ®Google Scholar
• Su M, Li W, Yuan Y, et al. Epididymal white adipose tissue promotes angiotensin II-induced cardiac fibrosis in an exosome-dependent manner. Transl Res. 2022;248:51–67. doi: 10.1016/j.trsl.2022.05.004.
   PubMed Web of Science ®Google Scholar
• Matsushita Y, Ogawa D, Wada J, et al. Activation of peroxisome proliferator–activated receptor δ inhibits streptozotocin-induced diabetic nephropathy through anti-inflammatory mechanisms in mice. Diabetes. 2011;60(3):960–968. doi: 10.2337/db10-1361.
   PubMed Web of Science ®Google Scholar
• Kostic S, Hauke T, Ghahramani N, et al. Expression pattern of apoptosis-inducing factor in the kidneys of streptozotocin-induced diabetic rats. Acta Histochem. 2020;122(8):151655. doi: 10.1016/j.acthis.2020.151655.
   PubMed Web of Science ®Google Scholar
• Li YJ, Chen X, Kwan TK, et al. Dietary fiber protects against diabetic nephropathy through short-chain fatty acid–mediated activation of G protein–coupled receptors GPR43 and GPR109A. J Am Soc Nephrol. 2020;31(6):1267–1281. doi: 10.1681/ASN.2019101029.
   PubMed Web of Science ®Google Scholar
• Choi SY, Lim SW, Salimi S, et al. Tonicity-responsive enhancer-binding protein mediates hyperglycemia-induced inflammation and vascular and renal injury. J Am Soc Nephrol. 2018;29(2):492–504. doi: 10.1681/ASN.2017070718.
   PubMed Web of Science ®Google Scholar
• Bing P, Maode L, Li F, et al. Expression of renal transforming growth factor-β and its receptors in a rat model of chronic cyclosporine-induced nephropathy. Transplant Proc. 2006;38(7):2176–2179. doi: 10.1016/j.transproceed.2006.07.015.
   PubMed Web of Science ®Google Scholar
• Du H, Le G, Hou L, et al. Nontoxic concentration of ochratoxin a aggravates renal fibrosis induced by adriamycin/cyclosporine a nephropathy via TGF-β1/SMAD2/3. J Agric Food Chem. 2022;70(43):14005–14014. doi: 10.1021/acs.jafc.2c03577.
   PubMedGoogle Scholar
• Chen A, Sheu L-F, Ho Y-S, et al. Experimental focal segmental glomerulosclerosis in mice. Nephron. 1998;78(4):440–452. doi: 10.1159/000044974.
   PubMed Web of Science ®Google Scholar
• Bucciarelli E, Binazzi R, Santori P, et al. Nephrotic syndrome in rats due to adriamycin chlorhydrate. Lav Ist Anat Istol Patol Univ Studi Perugia. 1976;36:53–69.
   PubMedGoogle Scholar
• Cao Q, Lu J, Li Q, et al. CD103+ dendritic cells elicit CD8+ T cell responses to accelerate kidney injury in adriamycin nephropathy. J Am Soc Nephrol. 2016;27(5):1344–1360. doi: 10.1681/ASN.2015030229.
   PubMed Web of Science ®Google Scholar
• Yang B, Xie Y, Guo M, et al. Nephrotoxicity and Chinese herbal medicine. Clin J Am Soc Nephrol. 2018;13(10):1605–1611. doi: 10.2215/CJN.11571017.
   PubMed Web of Science ®Google Scholar
• Furusho T, Sohara E, Mandai S, et al. Renal TNFα activates the WNK phosphorylation Cascade and contributes to salt-sensitive hypertension in chronic kidney disease. Kidney Int. 2020;97(4):713–727. doi: 10.1016/j.kint.2019.11.021.
   PubMed Web of Science ®Google Scholar
• Heidarian E, Jafari-Dehkordi E, Valipour P, et al. Nephroprotective and anti-inflammatory effects of Pistacia atlantica leaf hydroethanolic extract against gentamicin-induced nephrotoxicity in rats. J Diet Suppl. 2017;14(5):489–502. doi: 10.1080/19390211.2016.1267062.
   PubMedGoogle Scholar
• Rizwan F, Yesmine S, Banu SG, et al. Renoprotective effects of stevia (stevia rebaudiana bertoni), amlodipine, valsartan, and losartan in gentamycin-induced nephrotoxicity in the rat model: biochemical, hematological and histological approaches. Toxicol Rep. 2019;6:683–691. doi: 10.1016/j.toxrep.2019.07.003.
   PubMed Web of Science ®Google Scholar
• Ryu SH, Kim JW, Yoon D, et al. Serum and urine toxicometabolomics following gentamicin-induced nephrotoxicity in male Sprague-Dawley rats. J Toxicol Environ Health A. 2018;81(11):408–420. doi: 10.1080/15287394.2018.1451180.
   PubMed Web of Science ®Google Scholar
• S L, X J, Y L, et al. Sodium/calcium overload and Sirt1/Nrf2/OH-1 pathway are critical events in mercuric chloride-induced nephrotoxicity. Chemosphere. 2019;234:579–588. doi: 10.1016/j.chemosphere.2019.06.095.
   PubMed Web of Science ®Google Scholar
• Joshi D, Srivastav SK, Belemkar S, et al. Zingiber officinale and 6-gingerol alleviate liver and kidney dysfunctions and oxidative stress induced by mercuric chloride in male rats: a protective approach. Biomed Pharmacother. 2017;91:645–655. doi: 10.1016/j.biopha.2017.04.108.
   PubMed Web of Science ®Google Scholar
• Tao Y-y, Wang Q-L, Yuan J-L, et al. Effects of vitamin E on mercuric chloride-induced renal interstitial fibrosis in rats and the antioxidative mechanism. Zhong Xi Yi Jie He Xue Bao. 2011;9(2):201–208. doi: 10.3736/jcim20110214.
   PubMedGoogle Scholar
• Nørregaard R, Mutsaers HAM, Frøkiær J, et al. Obstructive nephropathy and molecular pathophysiology of renal interstitial fibrosis. Physiol Rev. 2023;103(4):2827–2872. doi: 10.1152/physrev.00027.2022.
   PubMed Web of Science ®Google Scholar
• Sárközy M, Watzinger S, Kovács ZZA, et al. Neuregulin-1β improves uremic cardiomyopathy and renal dysfunction in rats. JACC Basic Transl Sci. 2023;8(9):1160–1176. doi: 10.1016/j.jacbts.2023.03.003.
   PubMedGoogle Scholar
• Chen Y, Mao C, Gu R, et al. Nidogen-2 is a novel endogenous ligand of LGR4 to inhibit vascular calcification. Circ Res. 2022;131(12):1037–1054. doi: 10.1161/CIRCRESAHA.122.321614.
   PubMed Web of Science ®Google Scholar
• Chou Y-H, Pan S-Y, Shao Y-H, et al. Methylation in pericytes after acute injury promotes chronic kidney disease. J Clin Invest. 2020;130(9):4845–4857. doi: 10.1172/JCI135773.
   PubMed Web of Science ®Google Scholar
• Walker JA, Richards S, Belghasem ME, et al. Temporal and tissue-specific activation of aryl hydrocarbon receptor in discrete mouse models of kidney disease. Kidney Int. 2020;97(3):538–550. doi: 10.1016/j.kint.2019.09.029.
   PubMed Web of Science ®Google Scholar
• Diwan V, Brown L, Gobe GC. Adenine-induced chronic kidney disease in rats. Nephrology (Carlton). 2018;23(1):5–11. doi: 10.1111/nep.13180.
   PubMed Web of Science ®Google Scholar
• Makhloufi C, Nicolas F, McKay N, et al. Female AhR knockout mice develop a minor renal insufficiency in an adenine-diet model of chronic kidney disease. Int J Mol Sci. 2020;21(7):2483. doi: 10.3390/ijms21072483.
   PubMed Web of Science ®Google Scholar
• Melsom T, Norvik JV, Enoksen IT, et al. Sex differences in age-related loss of kidney function. J Am Soc Nephrol. 2022;33(10):1891–1902. doi: 10.1681/ASN.2022030323.
   PubMed Web of Science ®Google Scholar
• Merz CNB, Dember LM, Ingelfinger JR, et al. Sex and the kidneys: current understanding and research opportunities. Nat Rev Nephrol. 2019;15(12):776–783. doi: 10.1038/s41581-019-0208-6.
   PubMed Web of Science ®Google Scholar
• Neugarten J, Golestaneh L. Influence of sex on the progression of chronic kidney disease. Mayo Clin Proc. 2019;94(7):1339–1356. doi: 10.1016/j.mayocp.2018.12.024.
   PubMed Web of Science ®Google Scholar
• Diwan V, Small D, Kauter K, et al. Gender differences in adenine-induced chronic kidney disease and cardiovascular complications in rats. Am J Physiol Renal Physiol. 2014;307(11):F1169–F1178. doi: 10.1152/ajprenal.00676.2013.
   PubMedGoogle Scholar
• Lutwak-Mann C. Adenine derivatives and their biological functions. Biol Rev. 1939;14(4):399–419. doi: 10.1111/j.1469-185X.1939.tb00850.x.
   Google Scholar
• Wu B, Roseland JM, Haytowitz DB, et al. Availability and quality of published data on the purine content of foods, alcoholic beverages, and dietary supplements. J Food Compos Anal. 2019;84:103281. doi: 10.1016/j.jfca.2019.103281.
   Web of Science ®Google Scholar
• Hou C, Xiao G, Amakye WK, et al. Guidelines for purine extraction and determination in foods. Food Frontiers. 2021;2(4):557–573. doi: 10.1002/fft2.100.
   Google Scholar
• Kaneko K, Aoyagi Y, Fukuuchi T, et al. Total purine and purine base content of common foodstuffs for facilitating nutritional therapy for gout and hyperuricemia. Biol Pharm Bull. 2014;37(5):709–721. doi: 10.1248/bpb.b13-00967.
   PubMed Web of Science ®Google Scholar
• Salati LM, Gross CJ, Henderson LM, et al. Absorption and metabolism of adenine, adenosine-5’-monophosphate, adenosine and hypoxanthine by the isolated vascularly perfused rat small intestine. J Nutr. 1984;114(4):753–760. doi: 10.1093/jn/114.4.753.
   PubMed Web of Science ®Google Scholar
• Yokozawa T, Oura H, Okada T. Metabolic effects of dietary purine in rats. J Nutr Sci Vitaminol (Tokyo). 1982;28(5):519–526. doi: 10.3177/jnsv.28.519.
   PubMed Web of Science ®Google Scholar
• Shuvy M, Nyska A, Beeri R, et al. Histopathology and apoptosis in an animal model of reversible renal injury. Exp Toxicol Pathol. 2011;63(4):303–306. doi: 10.1016/j.etp.2010.02.002.
   PubMedGoogle Scholar
• Gorzalka S, Vittori S, Volpini R, et al. Evidence for the functional expression and pharmacological characterization of adenine receptors in native cells and tissues. Mol Pharmacol. 2005;67(3):955–964. doi: 10.1124/mol.104.006601.
   PubMed Web of Science ®Google Scholar
• Coade SB, Pearson JD. Metabolism of adenine nucleotides in human blood. Circ Res. 1989;65(3):531–537. doi: 10.1161/01.RES.65.3.531.
   PubMed Web of Science ®Google Scholar
• Choi HK, Mount DB, Reginato AM. Pathogenesis of gout. Ann Intern Med. 2005;143(7):499. doi: 10.7326/0003-4819-143-7-200510040-00009.
   PubMed Web of Science ®Google Scholar
• Wyngaarden JB, Dunn JT. 8-Hydroxyadenine as the intermediate in the oxidation of adenine to 2,8-dihydroxyadenine by xanthine oxidase. Arch Biochem Biophys. 1957;70(1):150–156. doi: 10.1016/0003-9861(57)90088-7.
   PubMed Web of Science ®Google Scholar
• George J, Struthers AD. Role of urate, xanthine oxidase and the effects of allopurinol in vascular oxidative stress. Vasc Health Risk Manag. 2009;5(1):265–272. doi: 10.2147/VHRM.S4265.
   PubMedGoogle Scholar
• Runolfsdottir HL, Palsson R, Agustsdottir IM, et al. Kidney disease in adenine phosphoribosyltransferase deficiency. Am J Kidney Dis. 2016;67(3):431–438. doi: 10.1053/j.ajkd.2015.10.023.
   PubMed Web of Science ®Google Scholar
• Stockelman MG, Lorenz JN, Smith FN, et al. Chronic renal failure in a mouse model of human adenine phosphoribosyltransferase deficiency. Am J Physiol. 1998;275(1):F154–F163. doi: 10.1152/ajprenal.1998.275.1.F154.
   PubMedGoogle Scholar
• Van Acker KJ, Simmonds HA, Potter C, et al. Complete deficiency of adenine phosphoribosyltransferase. Report of a family. N Engl J Med. 1977;297(3):127–132. doi: 10.1056/NEJM197707212970302.
   PubMed Web of Science ®Google Scholar
• Sharaf El Din UAA, Salem MM, Abdulazim DO. Uric acid in the pathogenesis of metabolic, renal, and cardiovascular diseases: a review. J Adv Res. 2017;8(5):537–548. doi: 10.1016/j.jare.2016.11.004.
   PubMed Web of Science ®Google Scholar
• Katsyuba E, Romani M, Hofer D, et al. NAD + homeostasis in health and disease. Nat Metab. 2020;2(1):9–31. doi: 10.1038/s42255-019-0161-5.
   PubMedGoogle Scholar
• Burnstock G. Purinergic signalling: therapeutic developments. Front Pharmacol. 2017;8:661. doi: 10.3389/fphar.2017.00661.
   PubMed Web of Science ®Google Scholar
• Fukuda T, Majumder K, Zhang H, et al. Adenine has an anti-inflammatory effect through the activation of adenine receptor signaling in mouse macrophage. J Funct Foods. 2017;28:235–239. doi: 10.1016/j.jff.2016.11.013.
   Web of Science ®Google Scholar
• Thimm D, Schiedel AC, Peti-Peterdi J, et al. The nucleobase adenine as a signalling molecule in the kidney. Acta Physiol (Oxf). 2015;213(4):808–818. doi: 10.1111/apha.12452.
   PubMed Web of Science ®Google Scholar
• Bender E, Buist A, Jurzak M, et al. Characterization of an orphan G protein-coupled receptor localized in the dorsal root ganglia reveals adenine as a signaling molecule. Proc Natl Acad Sci USA. 2002;99(13):8573–8578. doi: 10.1073/pnas.122016499.
   PubMed Web of Science ®Google Scholar
• Knospe M, Müller CE, Rosa P, et al. The rat adenine receptor: pharmacological characterization and mutagenesis studies to investigate its putative ligand binding site. Purinergic Signal. 2013;9(3):367–381. doi: 10.1007/s11302-013-9355-6.
   PubMed Web of Science ®Google Scholar
• Peti-Peterdi J, Kishore BK, Pluznick JL. Regulation of vascular and renal function by metabolite receptors. Annu. Rev. Physiol. 2016;78(1):391–414. doi: 10.1146/annurev-physiol-021115-105403.
   PubMedGoogle Scholar
• Thimm D, Knospe M, Abdelrahman A, et al. Characterization of new G protein-coupled adenine receptors in mouse and hamster. Purinergic Signal. 2013;9(3):415–426. doi: 10.1007/s11302-013-9360-9.
   PubMed Web of Science ®Google Scholar
• Kishore BK, Zhang Y, Pop IL, et al. Cellular localization of P0 (adenine) receptor in rat kidney. Faseb J. 2012;26(S1):688.3–688.3. doi:10.1096/fasebj.26.1_supplement.688.3.
   Web of Science ®Google Scholar
• Kamatani N, Carson DA. Dependence of adenine production upon polyamine synthesis in cultured human lymphoblasts. Biochim Biophys Acta. 1981;675(3–4):344–350. doi: 10.1016/0304-4165(81)90024-6.
   PubMedGoogle Scholar
• Caruso V, Zuccarini M, Di Iorio P, et al. Metabolic changes induced by purinergic signaling: role in food intake. Front Pharmacol. 2021;12:655989. doi: 10.3389/fphar.2021.655989.
   PubMed Web of Science ®Google Scholar
• Wright NJ, Lee S-Y. Toward a molecular basis of cellular nucleoside transport in humans. Chem Rev. 2021;121(9):5336–5358. doi: 10.1021/acs.chemrev.0c00644.
   PubMed Web of Science ®Google Scholar
• Inoue K. Molecular basis of nucleobase transport systems in mammals. Biol Pharm Bull. 2017;40(8):1130–1138. doi: 10.1248/bpb.b17-00374.
   PubMed Web of Science ®Google Scholar
• Damaraju VL, Mowles D, Wilson M, et al. Comparative in vitro evaluation of transportability and toxicity of capecitabine and its metabolites in cells derived from normal human kidney and renal cancers. Biochem Cell Biol. 2013;91(6):419–427. doi: 10.1139/bcb-2013-0041.
   PubMedGoogle Scholar
• Hau RK, Wright SH, Cherrington NJ. Addressing the clinical importance of equilibrative nucleoside transporters in drug discovery and development. Clin Pharmacol Ther. 2023;114(4):780–794. doi: 10.1002/cpt.2984.
   PubMed Web of Science ®Google Scholar
• SenGupta DJ, Lum PY, Lai Y, et al. A single glycine mutation in the equilibrative nucleoside transporter gene, hENT1, alters nucleoside transport activity and sensitivity to nitrobenzylthioinosine. Biochemistry. 2002;41(5):1512–1519. doi: 10.1021/bi015833w.
   PubMed Web of Science ®Google Scholar
• Chen C, Xie T, Zhang Y, et al. Erythrocyte ENT1-AMPD3 axis is an essential purinergic hypoxia sensor and energy regulator combating CKD in a mouse model. J Am Soc Nephrol. 2023;34(10):1647–1671. doi: 10.1681/ASN.0000000000000195.
   PubMed Web of Science ®Google Scholar
• Govindarajan R, Leung GPH, Zhou M, et al. Facilitated mitochondrial import of antiviral and anticancer nucleoside drugs by human equilibrative nucleoside transporter-3. Am J Physiol Gastrointest Liver Physiol. 2009;296(4):G910–922. doi: 10.1152/ajpgi.90672.2008.
   PubMed Web of Science ®Google Scholar
• Lu H, Chen C, Klaassen C. Tissue distribution of concentrative and equilibrative nucleoside transporters in male and female rats and mice. Drug Metab Dispos. 2004;32(12):1455–1461. doi: 10.1124/dmd.104.001123.
   PubMed Web of Science ®Google Scholar
• Pastor-Anglada M, Mata-Ventosa A, Pérez-Torras S. Inborn errors of nucleoside transporter (NT)-encoding genes (SLC28 and SLC29. Int J Mol Sci. 2022;23(15):8770. doi: 10.3390/ijms23158770.
   PubMed Web of Science ®Google Scholar
• Cheng X, Klaassen CD. Tissue distribution, ontogeny, and hormonal regulation of xenobiotic transporters in mouse kidneys. Drug Metab Dispos. 2009;37(11):2178–2185. doi: 10.1124/dmd.109.027177.
   PubMed Web of Science ®Google Scholar
• Kishore BK, Zhang Y, Gevorgyan H, et al. Cellular localization of adenine receptors in the rat kidney and their functional significance in the inner medullary collecting duct. Am J Physiol Renal Physiol. 2013;305(9):F1298–F1305. doi: 10.1152/ajprenal.00254.2013.
   PubMed Web of Science ®Google Scholar
• Nicolaier A. Ueber die umwand lung des adenins im thierischen organismus, Z. Klin. Med. 1902;45:359.
   Google Scholar
• Warner WL. Toxicology and pharmacology of adenine in animals and man. Transfusion. 1977;17(4):326–332. doi: 10.1046/j.1537-2995.1977.17477216860.x.
   PubMed Web of Science ®Google Scholar
• Al Za’abi M, Ali B, Yasin J, et al. Development of a new model for the induction of chronic kidney disease via intraperitoneal adenine administration, and the effect of treatment with gum acacia thereon. FASEB J. 2015;29(S1):938–933. doi: 10.1096/fasebj.29.1_supplement.938.3.
   Google Scholar
• Hayeeawaema F, Muangnil P, Jiangsakul J, et al. A novel model of adenine-induced chronic kidney disease-associated gastrointestinal dysfunction in mice: the gut-kidney axis. Saudi J Biol Sci. 2023;30(6):103660. doi: 10.1016/j.sjbs.2023.103660.
   PubMed Web of Science ®Google Scholar
• Manfredi JP, Holmes EW. Purine salvage pathways in myocardium. Annu Rev Physiol. 1985;47(1):691–705. doi: 10.1146/annurev.ph.47.030185.003355.
   PubMedGoogle Scholar
• Herlitz LC, D’Agati VD, Markowitz GS. Crystalline nephropathies. Arch Pathol Lab Med. 2012;136(7):713–720. doi: 10.5858/arpa.2011-0565-RA.
   PubMed Web of Science ®Google Scholar
• Mishima E, Ichijo M, Kawabe T, et al. Germ-free conditions modulate host purine metabolism, exacerbating adenine-induced kidney damage. Toxins (Basel). 2020;12(9):547. doi: 10.3390/toxins12090547.
   PubMed Web of Science ®Google Scholar
• Motohashi H, Tahara Y, Whittaker DS, et al. The circadian clock is disrupted in mice with adenine-induced tubulointerstitial nephropathy. Kidney Int. 2020;97(4):728–740. doi: 10.1016/j.kint.2019.09.032.
   PubMed Web of Science ®Google Scholar
• Ullah MM, Ow CPC, Hilliard Krause LM, et al. Renal oxygenation during the early stages of adenine-induced chronic kidney disease. Am J Physiol Renal Physiol. 2019;317(5):F1189–F1200. doi: 10.1152/ajprenal.00253.2019.
   PubMed Web of Science ®Google Scholar
• Pruijm M, Phan O, Zanchi A. Metformin versus SGLT-2 inhibitors: how low can we go? Kidney Int. 2022;101(5):874–877. doi: 10.1016/j.kint.2022.02.012.
   PubMed Web of Science ®Google Scholar
• Chen D-Q, Chen H, Chen L, et al. The link between phenotype and fatty acid metabolism in advanced chronic kidney disease. Nephrol Dial Transplant. 2017;32(7):1154–1166. doi: 10.1093/ndt/gfw415.
   PubMed Web of Science ®Google Scholar
• Fong D, Ullah MM, Lal JG, et al. Renal cellular hypoxia in adenine-induced chronic kidney disease. Clin Exp Pharmacol Physiol. 2016;43(10):896–905. doi: 10.1111/1440-1681.12621.
   PubMed Web of Science ®Google Scholar
• Klinkhammer BM, Djudjaj S, Kunter U, et al. Cellular and molecular mechanisms of kidney injury in 2,8-dihydroxyadenine nephropathy. J Am Soc Nephrol. 2020;31(4):799–816. doi: 10.1681/ASN.2019080827.
   PubMed Web of Science ®Google Scholar
• Zhang Z-H, Chen H, Vaziri ND, et al. Metabolomic signatures of chronic kidney disease of diverse etiologies in the rats and humans. J Proteome Res. 2016;15(10):3802–3812. doi: 10.1021/acs.jproteome.6b00583.
   PubMed Web of Science ®Google Scholar
• Miao H, Wu X, Wang Y, et al. 1-Hydroxypyrene mediates renal fibrosis through aryl hydrocarbon receptor signalling pathway. Br J Pharmacol. 2022;179(1):103–124. doi: 10.1111/bph.15705.
   PubMed Web of Science ®Google Scholar
• Kobayashi T, Matsumura Y, Ozawa T, et al. Exploration of novel predictive markers in rat plasma of the early stages of chronic renal failure. Anal Bioanal Chem. 2014;406(5):1365–1376. doi: 10.1007/s00216-013-7472-2.
   PubMed Web of Science ®Google Scholar
• Arinze NV, Yin W, Lotfollahzadeh S, et al. Tryptophan metabolites suppress the Wnt pathway and promote adverse limb events in chronic kidney disease. J Clin Invest. 2022;132(1):e142260. doi: 10.1172/JCI142260.
   PubMed Web of Science ®Google Scholar
• Li Q-M, Chena H-R, Zha X-Q, et al. Renoprotective effect of Chinese chive polysaccharides in adenine-induced chronic renal failure. Int J Biol Macromol. 2018;106:988–993. doi: 10.1016/j.ijbiomac.2017.08.101.
   PubMed Web of Science ®Google Scholar
• Zaaba NE, Al-Salam S, Beegam S, et al. Catalpol attenuates oxidative stress and inflammation via mechanisms involving sirtuin-1 activation and NF-κB inhibition in experimentally-induced chronic kidney disease. Nutrients. 2023;15(1):237. doi: 10.3390/nu15010237.
   PubMed Web of Science ®Google Scholar
• Zhao Y-Y, Cheng X-L, Wei F, et al. Serum metabonomics study of adenine-induced chronic renal failure in rats by ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Biomarkers. 2012;17(1):48–55. doi: 10.3109/1354750X.2011.637180.
   PubMed Web of Science ®Google Scholar
• Khan MA, Nag P, Grivei A, et al. Adenine overload induces ferroptosis in human primary proximal tubular epithelial cells. Cell Death Dis. 2022;13(2):104. doi: 10.1038/s41419-022-04527-z.
   PubMed Web of Science ®Google Scholar
• Chevalier RL. The proximal tubule is the primary target of injury and progression of kidney disease: role of the glomerulotubular junction. Am J Physiol Renal Physiol. 2016;311(1):F145–161. doi: 10.1152/ajprenal.00164.2016.
   PubMed Web of Science ®Google Scholar
• Choi J, Choi M-S, Jeon J, et al. In vivo longitudinal 920 nm two-photon intravital kidney imaging of a dynamic 2,8-DHA crystal formation and tubular deterioration in the adenine-induced chronic kidney disease mouse model. Biomed Opt Express. 2023;14(4):1647–1658. doi: 10.1364/BOE.485187.
   PubMed Web of Science ®Google Scholar
• Mulay SR, Shi C, Ma X, et al. Novel insights into crystal-induced kidney injury. Kidney Dis (Basel). 2018;4(2):49–57. doi: 10.1159/000487671.
   PubMed Web of Science ®Google Scholar
• Fang C, Lau WL, Sun J, et al. Chronic kidney disease promotes cerebral microhemorrhage formation. J Neuroinflammation. 2023;20(1):51. doi: 10.1186/s12974-023-02703-2.
   PubMed Web of Science ®Google Scholar
• Nguy L, Shubbar E, Jernås M, et al. Adenine-induced chronic renal failure in rats decreases aortic relaxation rate and alters expression of proteins involved in vascular smooth muscle calcium handling. Acta Physiol (Oxf). 2016;218(4):250–264. doi: 10.1111/apha.12724.
   PubMed Web of Science ®Google Scholar
• Ali BH, Al-Salam S, Za’abi MA, et al. New model for adenine-induced chronic renal failure in mice, and the effect of gum acacia treatment thereon: comparison with rats. J Pharmacol Toxicol Methods. 2013;68(3):384–393. doi: 10.1016/j.vascn.2013.05.001.
   PubMed Web of Science ®Google Scholar
• Rabe M, Schaefer F. Non-transgenic mouse models of kidney disease. Nephron. 2016;133(1):53–61. doi: 10.1159/000445171.
   PubMed Web of Science ®Google Scholar
• Verma R, Niraimathi M, Prasad P, et al. Dihydroxyadenine crystal-induced nephropathy presenting with rapidly progressive renal failure. Kidney Res Clin Pract. 2018;37(3):287–291. doi: 10.23876/j.krcp.2018.37.3.287.
   PubMed Web of Science ®Google Scholar
• Meng X-M, Nikolic-Paterson DJ, Lan HY. Inflammatory processes in renal fibrosis. Nat Rev Nephrol. 2014;10(9):493–503. doi: 10.1038/nrneph.2014.114.
   PubMed Web of Science ®Google Scholar
• de Jong JP, Voerman JS, van der Sluijs-Gelling AJ, et al. A monoclonal antibody (ER-HR3) against murine macrophages. I. Ontogeny, distribution and enzyme histochemical characterization of ER-HR3-positive cells. Cell Tissue Res. 1994;275(3):567–576. doi: 10.1007/BF00318825.
   PubMed Web of Science ®Google Scholar
• Rogers NM, Ferenbach DA, Isenberg JS, et al. Dendritic cells and macrophages in the kidney: a spectrum of good and evil. Nat Rev Nephrol. 2014;10(11):625–643. doi: 10.1038/nrneph.2014.170.
   PubMed Web of Science ®Google Scholar
• Furuichi K, Kaneko S, Wada T. Chemokine/chemokine receptor-mediated inflammation regulates pathologic changes from acute kidney injury to chronic kidney disease. Clin Exp Nephrol. 2009;13(1):9–14. doi: 10.1007/s10157-008-0119-5.
   PubMed Web of Science ®Google Scholar
• Vervaet BA, Verhulst A, D’Haese PC, et al. Nephrocalcinosis: new insights into mechanisms and consequences. Nephrol Dial Transplant. 2009;24(7):2030–2035. doi: 10.1093/ndt/gfp115.
   PubMed Web of Science ®Google Scholar
• Correa-Costa M, Braga TT, Felizardo RJF, et al. Macrophage trafficking as key mediator of adenine-induced kidney injury. Mediators Inflamm. 2014;2014:291024–291012. doi: 10.1155/2014/291024.
   PubMed Web of Science ®Google Scholar
• Aminzadeh MA, Nicholas SB, Norris KC, et al. Role of impaired Nrf2 activation in the pathogenesis of oxidative stress and inflammation in chronic tubulo-interstitial nephropathy. Nephrol Dial Transplant. 2013;28(8):2038–2045. doi: 10.1093/ndt/gft022.
   PubMed Web of Science ®Google Scholar
• Karamouzis I, Sarafidis PA, Karamouzis M, et al. Increase in oxidative stress but not in antioxidant capacity with advancing stages of chronic kidney disease. Am J Nephrol. 2008;28(3):397–404. doi: 10.1159/000112413.
   PubMed Web of Science ®Google Scholar
• Srivastava A, Tomar B, Sharma D, et al. Mitochondrial dysfunction and oxidative stress: role in chronic kidney disease. Life Sci. 2023;319:121432. doi: 10.1016/j.lfs.2023.121432.
   PubMed Web of Science ®Google Scholar
• Ebert T, Neytchev O, Witasp A, et al. Inflammation and oxidative stress in chronic kidney disease and dialysis patients. Antioxid Redox Signal. 2021;35(17):1426–1448. doi: 10.1089/ars.2020.8184.
   PubMed Web of Science ®Google Scholar
• Dounousi E, Papavasiliou E, Makedou A, et al. Oxidative stress is progressively enhanced with advancing stages of CKD. Am J Kidney Dis. 2006;48(5):752–760. doi: 10.1053/j.ajkd.2006.08.015.
   PubMed Web of Science ®Google Scholar
• Chen H, Cao G, Chen D-Q, et al. Metabolomics insights into activated redox signaling and lipid metabolism dysfunction in chronic kidney disease progression. Redox Biol. 2016;10:168–178. doi: 10.1016/j.redox.2016.09.014.
   PubMed Web of Science ®Google Scholar
• Ali BH, Al-Husseni I, Beegam S, et al. Effect of gum Arabic on oxidative stress and inflammation in adenine–induced chronic renal failure in rats. PLoS One. 2013;8(2):e55242. doi: 10.1371/journal.pone.0055242.
   PubMed Web of Science ®Google Scholar
• Ohata K, Kamijo-Ikemori A, Sugaya T, et al. Renoprotective effect of the xanthine oxidoreductase inhibitor topiroxostat under decreased angiotensin II type 1a receptor expression. Eur J Pharmacol. 2017;815:88–97. doi: 10.1016/j.ejphar.2017.09.005.
   PubMed Web of Science ®Google Scholar
• Saleh MA, Awad AM, Ibrahim TM, et al. Small-dose sunitinib modulates p53, bcl-2, STAT3, and ERK1/2 pathways and protects against adenine-induced nephrotoxicity. Pharmaceuticals. 2020;13(11):397. doi: 10.3390/ph13110397.
   Web of Science ®Google Scholar
• Ali BH, Al-Salam S, Al Suleimani Y, et al. Curcumin ameliorates kidney function and oxidative stress in experimental chronic kidney disease. Basic Clin Pharmacol Toxicol. 2018;122(1):65–73. doi: 10.1111/bcpt.12817.
   PubMed Web of Science ®Google Scholar
• Kamijo-Ikemori A, Sugaya T, Hibi C, et al. Renoprotective effect of the xanthine oxidoreductase inhibitor topiroxostat on adenine-induced renal injury. Am J Physiol Renal Physiol. 2016;310(11):F1366–F1376. doi: 10.1152/ajprenal.00517.2015.
   PubMed Web of Science ®Google Scholar
• Saugstad OD. Hypoxanthine as an indicator of hypoxia: its role in health and disease through free radical production. Pediatr Res. 1988;23(2):143–150. doi: 10.1203/00006450-198802000-00001.
   PubMed Web of Science ®Google Scholar
• Wang Y, Cai J, Tang C, et al. Mitophagy in acute kidney injury and kidney repair. Cells. 2020;9(2):338. doi: 10.3390/cells9020338.
   PubMed Web of Science ®Google Scholar
• Cuevas S, Pelegrín P. Pyroptosis and redox balance in kidney diseases. Antioxidants Redox Signal. 2021;35(1):40–60. doi: 10.1089/ars.2020.8243.
   PubMed Web of Science ®Google Scholar
• Carney EF. Ferroptotic stress promotes the AKI to CKD transition. Nat Rev Nephrol. 2021;17(10):633–633. doi: 10.1038/s41581-021-00482-8.
   PubMed Web of Science ®Google Scholar
• Belavgeni A, Meyer C, Stumpf J, et al. Ferroptosis and necroptosis in the kidney. Cell Chem Biol. 2020;27(4):448–462. doi: 10.1016/j.chembiol.2020.03.016.
   PubMed Web of Science ®Google Scholar
• Ni L, Yuan C, Wu X. Targeting ferroptosis in acute kidney injury. Cell Death Dis. 2022;13(2):182. doi: 10.1038/s41419-022-04628-9.
   PubMed Web of Science ®Google Scholar
• Maremonti F, Meyer C, Linkermann A. Mechanisms and models of kidney tubular necrosis and nephron loss. JASN. 2022;33(3):472–486. doi: 10.1681/ASN.2021101293.
   Web of Science ®Google Scholar
• Tang C, Livingston MJ, Liu Z, et al. Autophagy in kidney homeostasis and disease. Nat Rev Nephrol. 2020;16(9):489–508. doi: 10.1038/s41581-020-0309-2.
   PubMed Web of Science ®Google Scholar
• Dixon SJ, Lemberg KM, Lamprecht MR, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell. 2012;149(5):1060–1072. doi: 10.1016/j.cell.2012.03.042.
   PubMed Web of Science ®Google Scholar
• Song X, Pang H, Cui W, et al. Renoprotective effects of enzyme-hydrolyzed polysaccharides from auricularia polytricha on adenine-induced chronic kidney diseases in mice. Biomed Pharmaco. 2021;135:111004. doi: 10.1016/j.biopha.2020.111004.
   PubMed Web of Science ®Google Scholar
• Wu D, Luo N, Wang L, et al. Hydrogen sulfide ameliorates chronic renal failure in rats by inhibiting apoptosis and inflammation through ROS/MAPK and NF-κB signaling pathways. Sci Rep. 2017;7(1):455. doi: 10.1038/s41598-017-00557-2.
   PubMed Web of Science ®Google Scholar
• Awad AM, Saleh MA, Abu-Elsaad NM, et al. Erlotinib can halt adenine induced nephrotoxicity in mice through modulating ERK1/2, STAT3, p53 and apoptotic pathways. Sci Rep. 2020;10(1):11524. doi: 10.1038/s41598-020-68480-7.
   PubMed Web of Science ®Google Scholar
• Tian F, Wang Z, He J, et al. 4-Octyl itaconate protects against renal fibrosis via inhibiting TGF-β/smad pathway, autophagy and reducing generation of reactive oxygen species. Eur J Pharmacol. 2020;873:172989. doi: 10.1016/j.ejphar.2020.172989.
   PubMed Web of Science ®Google Scholar
• Yuan H, Zheng C, Zhu L, et al. Contribution of TFEB-mediated autophagy to tubulointerstitial fibrosis in mice with adenine-induced chronic kidney disease. Biomed Pharmaco. 2021;133:110949. doi: 10.1016/j.biopha.2020.110949.
   PubMed Web of Science ®Google Scholar
• Khamis T, Alsemeh AE, Alanazi A, et al. Breast milk mesenchymal stem cells and/or derived exosomes mitigated adenine-induced nephropathy via modulating renal autophagy and fibrotic signaling pathways and their epigenetic regulations. Pharmaceutics. 2023;15(8):2149. doi: 10.3390/pharmaceutics15082149.
   PubMed Web of Science ®Google Scholar
• Zhao Y-Y, Cheng X-L, Wei F, et al. Application of faecal metabonomics on an experimental model of tubulointerstitial fibrosis by ultra performance liquid chromatography/high-sensitivity mass spectrometry with MSE data collection technique. Biomarkers. 2012;17(8):721–729. doi: 10.3109/1354750X.2012.724450.
   PubMed Web of Science ®Google Scholar
• Zhao Y-Y, Liu J, Cheng X-L, et al. Urinary metabonomics study on biochemical changes in an experimental model of chronic renal failure by adenine based on UPLC Q-TOF/MS. Clin Chim Acta. 2012;413(5–6):642–649. doi: 10.1016/j.cca.2011.12.014.
   PubMed Web of Science ®Google Scholar
• Khattri RB, Thome T, Ryan TE. Tissue-specific 1H-NMR metabolomic profiling in mice with adenine-induced chronic kidney disease. Metabolites. 2021;11(1):45. doi: 10.3390/metabo11010045.
   PubMed Web of Science ®Google Scholar
• Zhao Y-Y, Cheng X-L, Wei F, et al. Intrarenal metabolomic investigation of chronic kidney disease and its TGF-β1 mechanism in induced-adenine rats using UPLC Q-TOF/HSMS/MSE. J. Proteome Res. 2013;12(2):692–703. doi: 10.1021/pr3007792.
   PubMed Web of Science ®Google Scholar
• Chen D-Q, Cao G, Chen H, et al. Identification of serum metabolites associating with chronic kidney disease progression and anti-fibrotic effect of 5-methoxytryptophan. Nat Commun. 2019;10(1):1476. doi: 10.1038/s41467-019-09329-0.
   PubMedGoogle Scholar
• Chen D-Q, Wu X-Q, Chen L, et al. Poricoic acid a as a modulator of TPH-1 expression inhibits renal fibrosis via modulating protein stability of β-catenin and β-catenin-mediated transcription. Therapeutic Adv Chronic Dis. 2020;11:204062232096264. doi: 10.1177/2040622320962648.
   Web of Science ®Google Scholar
• Gewin L, Zent R, Pozzi A. Progression of chronic kidney disease: too much cellular talk causes damage. Kidney Int. 2017;91(3):552–560. doi: 10.1016/j.kint.2016.08.025.
   PubMed Web of Science ®Google Scholar
• Succar L, Pianta TJ, Davidson T, et al. Subclinical chronic kidney disease modifies the diagnosis of experimental acute kidney injury. Kidney Int. 2017;92(3):680–692. doi: 10.1016/j.kint.2017.02.030.
   PubMed Web of Science ®Google Scholar
• Perazella MA. Renal vulnerability to drug toxicity. Clinical J Am Soc Nephrol. 2009;4(7):1275–1283. doi: 10.2215/CJN.02050309.
   PubMed Web of Science ®Google Scholar
• Edeling M, Ragi G, Huang S, et al. Developmental signalling pathways in renal fibrosis: the roles of notch, Wnt and hedgehog. Nat Rev Nephrol. 2016;12(7):426–439. doi: 10.1038/nrneph.2016.54.
   PubMed Web of Science ®Google Scholar
• Wynn T. Cellular and molecular mechanisms of fibrosis. Journal Pathol. 2008;214(2):199–210. doi: 10.1002/path.2277.
   PubMed Web of Science ®Google Scholar
• Duffield JS, Lupher M, Thannickal VJ, et al. Host responses in tissue repair and fibrosis. Annu Rev Pathol. 2013;8:241–276. doi: 10.1146/annurev-pathol-020712-163930.
   Google Scholar
• Yi H, Huang C, Shi Y, et al. Metformin attenuates renal fibrosis in a mouse model of adenine-induced renal injury through inhibiting TGF-β1 signaling pathways. Front Cell Dev Biol. 2021;9:603802. doi: 10.3389/fcell.2021.603802.
   PubMed Web of Science ®Google Scholar
• Thakur R, Sharma A, Lingaraju MC, et al. Ameliorative effect of ursolic acid on renal fibrosis in adenine-induced chronic kidney disease in rats. Biomed Pharmaco. 2018;101:972–980. doi: 10.1016/j.biopha.2018.02.143.
   PubMed Web of Science ®Google Scholar
• Zhang Z-H, Li M-H, Liu D, et al. Rhubarb protect against tubulointerstitial fibrosis by inhibiting TGF-β/smad pathway and improving abnormal metabolome in chronic kidney disease. Front Pharmacol. 2018;9:1029. doi: 10.3389/fphar.2018.01029.
   PubMed Web of Science ®Google Scholar
• Cai H, Su S, Li Y, et al. Protective effects of salvia miltiorrhiza on adenine-induced chronic renal failure by regulating the metabolic profiling and modulating the NADPH oxidase/ROS/ERK and TGF-β/smad signaling pathways. J Ethnopharmacol. 2018;212:153–165. doi: 10.1016/j.jep.2017.09.021.
   PubMed Web of Science ®Google Scholar
• Wang B, Jha JC, Hagiwara S, et al. Transforming growth factor-β1-mediated renal fibrosis is dependent on the regulation of transforming growth factor receptor 1 expression by let-7b. Kidney Int. 2014;85(2):352–361. doi: 10.1038/ki.2013.372.
   PubMed Web of Science ®Google Scholar
• Meng X, Nikolic-Paterson DJ, Lan HY. TGF-β: the master regulator of fibrosis. Nat Rev Nephrol. 2016;12(6):325–338. doi: 10.1038/nrneph.2016.48.
   PubMed Web of Science ®Google Scholar
• Chang Y, Lau WL, Jo H, et al. Pharmacologic blockade of αvβ1 integrin ameliorates renal failure and fibrosis in vivo. JASN. 2017;28(7):1998–2005. doi: 10.1681/ASN.2015050585.
   Web of Science ®Google Scholar
• Wang Y-N, Liu H-J, Ren L-L, et al. Shenkang injection improves chronic kidney disease by inhibiting multiple renin-angiotensin system genes by blocking the Wnt/β-catenin signalling pathway. Front Pharmacol. 2022;13:964370. doi: 10.3389/fphar.2022.964370.
   PubMedGoogle Scholar
• Massini G, Caldiroli L, Molinari P, et al. Nutritional strategies to prevent muscle loss and sarcopenia in chronic kidney disease: what do we currently know? Nutrients. 2023;15(14):3107. doi: 10.3390/nu15143107.
   PubMed Web of Science ®Google Scholar
• Chillon J-M, Massy ZA, Stengel B. Neurological complications in chronic kidney disease patients, nephrol. Nephrol Dial. Transplant. 2016;31(10):1606–1614. doi: 10.1093/ndt/gfv315.
   PubMed Web of Science ®Google Scholar
• Kelly DM, Ademi Z, Doehner W, et al. Chronic kidney disease and cerebrovascular disease. Stroke. 2021;52(7):e328–e346. doi: 10.1161/STROKEAHA.120.029680.
   PubMed Web of Science ®Google Scholar
• Pellicori P, Kalra PR, Clark AL, et al. Chronic kidney disease (CKD) and CKD-ism in heart failure – what a mess!. European J Heart Fail. 2022;24(11):2196–2198. doi: 10.1002/ejhf.2696.
   PubMed Web of Science ®Google Scholar
• Floege J, Drüeke TB. Mineral and bone disorder in chronic kidney disease: pioneering studies. Kidney Int. 2020;98(4):807–811. doi: 10.1016/j.kint.2020.07.002.
   PubMed Web of Science ®Google Scholar
• Abdelrahman AM, Suleimani YA, Za’abi MA, et al. The renoprotective effect of the dipeptidyl peptidase-4 inhibitor sitagliptin on adenine-induced kidney disease in rats. Biomed Pharmacother. 2019;110:667–676. doi: 10.1016/j.biopha.2018.11.117.
   PubMed Web of Science ®Google Scholar
• Ali BH, Al Za’abi M, Adham SA, et al. The effect of sildenafil on rats with adenine—induced chronic kidney disease. Biomed Pharmacother. 2018;108:391–402. doi: 10.1016/j.biopha.2018.09.061.
   PubMed Web of Science ®Google Scholar
• Fang J, Guo Y, Yin W, et al. Neoxanthin alleviates the chronic renal failure-induced aging and fibrosis by regulating inflammatory process. Int Immunopharmacol. 2023;114:109429. doi: 10.1016/j.intimp.2022.109429.
   PubMed Web of Science ®Google Scholar
• Horinouchi Y, Murashima Y, Yamada Y, et al. Pemafibrate inhibited renal dysfunction and fibrosis in a mouse model of adenine-induced chronic kidney disease. Life Sci. 2023;321:121590. doi: 10.1016/j.lfs.2023.121590.
   PubMed Web of Science ®Google Scholar
• Hsu C-N, Hou C-Y, Chang-Chien G-P, et al. Sodium thiosulfate improves hypertension in rats with adenine-induced chronic kidney disease. Antioxidants. 2022;11(1):147. doi: 10.3390/antiox11010147.
   Web of Science ®Google Scholar
• Subhash N, Sriram R, Kurian GA. Sodium thiosulfate protects brain in rat model of adenine induced vascular calcification. Neurochem Int. 2015;90:193–203. doi: 10.1016/j.neuint.2015.09.004.
   PubMed Web of Science ®Google Scholar
• Hsu C-N, Yang H-W, Hou C-Y, et al. Melatonin prevents chronic kidney disease-induced hypertension in young rat treated with adenine: implications of gut microbiota-derived metabolites. Antioxidants. 2021;10(8):1211. doi: 10.3390/antiox10081211.
   Web of Science ®Google Scholar
• Klaerner G, Shao J, Biyani K, et al. Mechanism of action of veverimer: a novel, orally administered, nonabsorbed, counterion-free, hydrochloric acid binder under development for the treatment of metabolic acidosis in chronic kidney disease. J Pharmacol Exp Ther. 2020;375(3):439–450. doi: 10.1124/jpet.120.000190.
   PubMed Web of Science ®Google Scholar
• Matsui I, Hamano T, Inoue K, et al. L-lysine ameliorates vascular calcification in adenine-induced uremic rats. Nephrol Dial Transplant. 2013;28:102–102.
   Web of Science ®Google Scholar
• Shimomura A, Matsui I, Hamano T, et al. Dietary L-lysine prevents arterial calcification in adenine-induced uremic rats. J Am Soc Nephrol. 2014;25(9):1954–1965. doi: 10.1681/ASN.2013090967.
   PubMed Web of Science ®Google Scholar
• Ou Y, Hou W, Li S, et al. Sodium citrate inhibits endoplasmic reticulum stress in rats with adenine-induced chronic renal failure. Am J Nephrol. 2015;42(1):14–21. doi: 10.1159/000437235.
   PubMed Web of Science ®Google Scholar
• Ou Y, Li S, Zhu X, et al. Citrate attenuates adenine-induced chronic renal failure in rats by modulating the Th17/treg cell balance. Inflammation. 2016;39(1):79–86. doi: 10.1007/s10753-015-0225-y.
   PubMed Web of Science ®Google Scholar
• Patel P, Patel S, Chudasama P, et al. Roflumilast alleviates adenine-induced chronic kidney disease by regulating inflammatory biomarkers. Eur J Pharmacol. 2023;949:175731. doi: 10.1016/j.ejphar.2023.175731.
   PubMed Web of Science ®Google Scholar
• Samaha MM, Nour OA, Sewilam HM, et al. Diacerein mitigates adenine-induced chronic kidney disease in rats: focus on TLR4/MYD88/TRAF6/NF-κB pathway. Life Sci. 2023;331:122080. doi: 10.1016/j.lfs.2023.122080.
   PubMed Web of Science ®Google Scholar
• Sato H, Goto M, Nishimura G, et al. Upacicalcet, a positive allosteric modulator of the calcium-sensing receptor, prevents vascular calcification and bone disorder in a rat adenine-induced secondary hyperparathyroidism model. Bone. 2023;167:116613. doi: 10.1016/j.bone.2022.116613.
   PubMed Web of Science ®Google Scholar
• Vaja V, Sun CC, Cappellini MD, et al. A hepcidin inhibitor mobilizes iron for incorporation into red blood cells in an adenine-induced chronic kidney disease model in rats. Blood. 2012;120(21):2082–2082. doi: 10.1182/blood.V120.21.2082.2082.
   Web of Science ®Google Scholar
• Thibodeau J-F, Simard J-C, Holterman CE, et al. PBI-4050 via GPR40 activation improves adenine-induced kidney injury in mice. Clin Sci (Lond). 2019;133(14):1587–1602. doi: 10.1042/CS20190479.
   PubMed Web of Science ®Google Scholar
• Tsuboi Y, Ohtomo S, Ichida Y, et al. EOS789, a novel pan-phosphate transporter inhibitor, is effective for the treatment of chronic kidney disease–mineral bone disorder. Kidney Int. 2020;98(2):343–354. doi: 10.1016/j.kint.2020.02.040.
   PubMed Web of Science ®Google Scholar
• Wu M, Tang R-N, Liu H, et al. Cinacalcet attenuates the renal endothelial-to-mesenchymal transition in rats with adenine-induced renal failure. Am J Physiol Renal Physiol. 2014;306(1):F138–F146. doi: 10.1152/ajprenal.00375.2013.
   PubMed Web of Science ®Google Scholar
• Zeng J, Huang H, Zhang Y, et al. Dapagliflozin alleviates renal fibrosis in a mouse model of adenine-induced renal injury by inhibiting TGF-β1/MAPK mediated mitochondrial damage. Front Pharmacol. 2023;14:1095487. doi: 10.3389/fphar.2023.1095487.
   PubMed Web of Science ®Google Scholar
• Atteia HH, Alamri ES, Sirag N, et al. Soluble guanylate cyclase agonist, isoliquiritigenin attenuates renal damage and aortic calcification in a rat model of chronic kidney failure. Life Sci. 2023;317:121460. doi: 10.1016/j.lfs.2023.121460.
   PubMed Web of Science ®Google Scholar
• Diwan V, Brown L, Gobe GC. The flavonoid rutin improves kidney and heart structure and function in an adenine-induced rat model of chronic kidney disease. J Funct Foods. 2017;33:85–93. doi: 10.1016/j.jff.2017.03.012.
   Web of Science ®Google Scholar
• Li M, Wei Y, Cai M, et al. Perilla peptides delay the progression of kidney disease by improving kidney apoptotic injury and oxidative stress and maintaining intestinal barrier function. Food Biosci. 2021;43:101333. doi: 10.1016/j.fbio.2021.101333.
   Web of Science ®Google Scholar
• Liu X, Gao L, Huang X, et al. Lipidomics reveals the potential mechanism of honokiol against adenine-induced chronic kidney disease. Front Pharmacol. 2022;13:1019629. doi: 10.3389/fphar.2022.1019629.
   PubMedGoogle Scholar
• Long M, Li Q-M, Fang Q, et al. Renoprotective effect of Laminaria japonica polysaccharide in adenine-induced chronic renal failure. Molecules. 2019;24(8):1491. doi: 10.3390/molecules24081491.
   PubMed Web of Science ®Google Scholar
• Sharma A, Thakur R, Lingaraju MC, et al. Betulinic acid attenuates renal fibrosis in rat chronic kidney disease model. Biomed Pharmacother. 2017;89:796–804. doi: 10.1016/j.biopha.2017.01.181.
   PubMed Web of Science ®Google Scholar
• Singh MP, Sharma C, Kang SC. Morin hydrate attenuates adenine-induced renal fibrosis via targeting cathepsin D signaling. Int Immunopharmacol. 2021;90:107234. doi: 10.1016/j.intimp.2020.107234.
   PubMed Web of Science ®Google Scholar
• Zhou W, Chen M, Liu H, et al. Dihydroartemisinin suppresses renal fibrosis in mice by inhibiting DNA-methyltransferase 1 and increasing klotho. Acta Pharmacol Sin. 2022;43(10):2609–2623. doi: 10.1038/s41401-022-00898-3.
   PubMed Web of Science ®Google Scholar
• Ratliff BB, Abdulmahdi W, Pawar R, et al. Oxidant mechanisms in renal injury and disease. Antioxid Redox Signal. 2016;25(3):119–146. doi: 10.1089/ars.2016.6665.
   PubMed Web of Science ®Google Scholar
• Vervloet M, Cozzolino M. Vascular calcification in chronic kidney disease: different bricks in the wall? Kidney Int. 2017;91(4):808–817. doi: 10.1016/j.kint.2016.09.024.
   PubMed Web of Science ®Google Scholar
• Hutcheson JD, Goettsch C. Cardiovascular calcification heterogeneity in chronic kidney disease. Circ Res. 2023;132(8):993–1012. doi: 10.1161/CIRCRESAHA.123.321760.
   PubMed Web of Science ®Google Scholar
• Covic A, Vervloet M, Massy ZA, et al. Bone and mineral disorders in chronic kidney disease: implications for cardiovascular health and ageing in the general population. Lancet Diabetes Endocrinol. 2018;6(4):319–331. doi: 10.1016/S2213-8587(17)30310-8.
   PubMed Web of Science ®Google Scholar
• Reiss AB, Miyawaki N, Moon J, et al. CKD, arterial calcification, atherosclerosis and bone health: inter-relationships and controversies. Atherosclerosis. 2018;278:49–59. doi: 10.1016/j.atherosclerosis.2018.08.046.
   PubMed Web of Science ®Google Scholar
• Chang X, Cui L, Wang X, et al. Quercetin attenuates vascular calcification through suppressed oxidative stress in adenine-induced chronic renal failure rats. Biomed Res Int. 2017;2017:5716204. doi: 10.1155/2017/5716204.
   PubMed Web of Science ®Google Scholar
• Yao Z, Xu Y, Ma W, et al. Magnesium citrate protects against vascular calcification in an adenine-induced chronic renal failure rat model. J Cardiovasc Pharmacol. 2018;72(6):270–276. doi: 10.1097/FJC.0000000000000590.
   PubMed Web of Science ®Google Scholar
• Zhao M-M, Xu M-J, Cai Y, et al. Mitochondrial reactive oxygen species promote p65 nuclear translocation mediating high-phosphate-induced vascular calcification in vitro and in vivo. Kidney Int. 2011;79(10):1071–1079. doi: 10.1038/ki.2011.18.
   PubMed Web of Science ®Google Scholar
• Neven E, Bashir-Dar R, Dams G, et al. Disturbances in bone largely predict aortic calcification in an alternative rat model developed to study both vascular and bone pathology in chronic kidney disease. J Bone Miner Res. 2015;30(12):2313–2324. doi: 10.1002/jbmr.2585.
   PubMed Web of Science ®Google Scholar
• Metzger CE, Swallow EA, Stacy AJ, et al. Strain-specific alterations in the skeletal response to adenine-induced chronic kidney disease are associated with differences in parathyroid hormone levels. Bone. 2021;148:115963. doi: 10.1016/j.bone.2021.115963.
   PubMed Web of Science ®Google Scholar
• Metzger CE, Swallow EA, Stacy AJ, et al. Adenine-induced chronic kidney disease induces a similar skeletal phenotype in male and female C57BL/6 mice with more severe deficits in cortical bone properties of male mice. PLoS One. 2021;16(4):e0250438. doi: 10.1371/journal.pone.0250438.
   PubMed Web of Science ®Google Scholar
• Basson R, Rees P, Wang R, et al. Sexual function in chronic illness. J Sex Med. 2010;7(1 Pt 2):374–388. doi: 10.1111/j.1743-6109.2009.01621.x.
   PubMed Web of Science ®Google Scholar
• Edey MM. Male sexual dysfunction and chronic kidney disease. Front Med (Lausanne). 2017;4:32. doi: 10.3389/fmed.2017.00032.
   PubMed Web of Science ®Google Scholar
• Wang CJ, Cukor D, Johansen KL. Sexual dysfunction among patients with chronic kidney disease. Semin Nephrol. 2021;41(6):534–549. doi: 10.1016/j.semnephrol.2021.10.006.
   PubMed Web of Science ®Google Scholar
• Adachi Y, Sasagawa I, Nakada T. Reproductive insufficiency in the male rat with adenine-induced chronic renal failure. Urol Int. 1993;51(4):228–230. doi: 10.1159/000282550.
   PubMed Web of Science ®Google Scholar
• Adachi Y, Sasagawa I, Tateno T, et al. Influence of adenine-induced chronic renal failure on testicular function in the rat. Andrologia. 1998;30(2):115–118. doi: 10.1111/j.1439-0272.1998.tb01157.x.
   PubMed Web of Science ®Google Scholar