慢性肾病药物研发进展
The Research Status of Drugs for Chronic Kidney Disease
DOI: 10.12677/PI.2022.113030, PDF,   
作者: 王玉婷, 陈建华*：中国药科大学生命科学与技术学院，江苏 南京
关键词: 慢性肾病；药物研发；细胞与基因治疗；Chronic Kidney Disease； Drug Development； Cell and Gene Therapy
摘要: 慢性肾病(Chronic kidney disease, CKD)是由各种原发和(或)继发性肾脏病于急性阶段未经控制后逐渐发展而来的临床综合征，不仅因为终末期肾病对患者带来的严重健康危害，同时高昂的医疗费用也为社会带来了巨大的经济负担，所以CKD已逐渐成为严重的医疗问题和社会性问题。虽然临床上有部分CKD及其并发症(贫血、高磷血、甲旁亢等)的治疗药物，但整体上对CKD进展的控制仍不尽人意。对临床使用的治疗CKD的药物和在临床试验阶段的药物进行系统总结，对新机制药物及其细胞治疗和基因治疗等新靶点、新技术进行梳理，以期为CKD药物的研发及产业化提供支持。
Abstract: Chronic kidney disease (CKD) is a clinical syndrome gradually developed after various primary and (or) secondary kidney diseases are not controlled in the acute stage, not only because of the serious health harm brought by END-stage kidney disease to patients, but also the high medical costs have brought huge economic burden to the society. Therefore, CKD has gradually become a serious medical and social problem. Although there are some therapeutic drugs for CKD and its complications (anemia, hyperphosphatemia, hyperparathyroidism, etc.), the overall control of the progression of CKD is still unsatisfactory. Systematically summarize the drugs used in the clinical treatment of CKD and those in clinical trials, and sort out new mechanism drugs, new targets and new technologies such as cell therapy and gene therapy, in order to provide support for the research and development and industrialization of CKD drugs.
文章引用：王玉婷, 陈建华. 慢性肾病药物研发进展[J]. 药物资讯, 2022, 11(3): 234-240. https://doi.org/10.12677/PI.2022.113030

参考文献

[1] Sarnak, M.J., Levey, A.S., Schoolwerth, A.C., Coresh, J., Culleton, B., Lee Hamm, L., et al. (2003) Kidney Disease as a Risk Factor for Development of Cardiovascular Disease: A Statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Preven-tion. Circulation, 108, 2154-2169. [Google Scholar] [CrossRef] 
[2] Liyanage, T., Nino-miya, T., Jha, V., Neal, B., Patrice, H.M., Okpechi, I., et al. (2015) Worldwide Access to Treatment for End-Stage Kid-ney Disease: A Systematic Review. Lancet, 385, 1975-1982. [Google Scholar] [CrossRef] 
[3] Vanholder, R., De Smet, R., Glorieux, G., Argilés, A., Baurmeister, U., Brunet, P., et al. (2003) Review on Uremic Toxins: Classification, Concentration, and Interindividual Variability. Kidney International, 63, 1934-1943. [Google Scholar] [CrossRef] [PubMed]
[4] Wang, Z., Luo, Y., Yang, S., et al. (2021) Premature Deaths Caused by Smoking in Sichuan, Southwest China, 2015-2030. Scientific Reports, 11, Article No. 171. [Google Scholar] [CrossRef] [PubMed]
[5] Zhang, L., Wang, F., Wang, L., Wang, W., Liu, B., Liu, J., et al. (2012) Prevalence of Chronic Kidney Disease in China: A Cross-Sectional Survey. Lancet, 379, 815-822. [Google Scholar] [CrossRef] 
[6] Hill, N.R., Fatoba, S.T., Oke, J.L., Hirst, J.A., O’Callaghan, C.A., Lasserson, D.S., et al. (2016) Global Prevalence of Chronic Kidney Disease—A Systematic Review and Me-ta-Analysis. PLoS ONE, 11, Article ID: e0158765. [Google Scholar] [CrossRef] [PubMed]
[7] Burgess, E., Muirhead, N., Rene de Cotret, P., Chiu, A., Pichette, V., Tobe, S., et al. (2009) SMART (Supra Maximal Atacand Renal Trial) Investigators. Supramaximal Dose of Candesartan in Proteinuric Renal Disease. Journal of the American Society of Nephrology, 20, 893-900. [Google Scholar] [CrossRef] 
[8] Shabaka, A., Cases-Corona, C. and Fernandez-Juarez, G. (2021) Therapeutic Insights in Chronic Kidney Disease Progression. Frontiers in Medicine, 8, Article ID: 645187. [Google Scholar] [CrossRef] [PubMed]
[9] Fernandez Juarez, G., Luño, J., Barrio, V., et al. (2013) Effect of Dual Blockade of the Renin-Angiotensin System on the Progression of Type 2 Diabetic Nephropathy: A Randomized Trial. American Journal of Kidney Diseases, 61, 211-218. [Google Scholar] [CrossRef] [PubMed]
[10] Cosimato, C., Agoritsas, T. and Mavrakanas, T.A. (2021) Miner-alocorticoid Receptor Antagonists in Patients with Chronic Kidney Disease. Pharmacology & Therapeutics, 219, Article ID: 107701. [Google Scholar] [CrossRef] [PubMed]
[11] Teasdale, E.J., Leydon, G., Fraser, S., et al. (2017) Patients’ Experiences After CKD Diagnosis: A Meta-ethnographic Study and Systematic Review. American Journal of Kidney Diseases, 70, 656-665. [Google Scholar] [CrossRef] [PubMed]
[12] Perkovic, V., Jardine, M.J., Neal, B., et al. (2019) Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. The New England Journal of Medicine, 380, 2295-2306. [Google Scholar] [CrossRef] 
[13] Milder, T.Y., Stocker, S.L., Samocha-Bonet, D., et al. (2019) So-dium-Glucose Cotransporter 2 Inhibitors for Type 2 Diabetes-Cardiovascular and Renal Benefits in Patients with Chronic Kidney Disease. European Journal of Clinical Pharmacology, 75, 1481-1490. [Google Scholar] [CrossRef] [PubMed]
[14] Spithoven, E.M., Kramer, A., Meijer, E., Orskov, B., Wanner, C., Abad, J.M., et al. (2014) Renal Replacement Therapy for Autosomal Dominant Polycystic Kidney Disease (ADPKD) in Europe: Prevalence and Survival—An Analysis of Data from the ERA-EDTA Registry. Nephrology Dialysis Trans-plantation, 29, 15-25. [Google Scholar] [CrossRef] [PubMed]
[15] Wu, T.C., Chang, W.H., Lu, H.Y. and Shih, C.C. (2022) Tolvaptan Re-duces Angiotensin II-Induced Experimental Abdominal Aortic Aneurysm and Dissection. Vascular Pharmacology, 144, Article ID: 106973. [Google Scholar] [CrossRef] [PubMed]
[16] Blair, H.A. (2019) Tolvaptan: A Review in Autosomal Dominant Polycystic Kidney Disease. Drugs, 79, 303-313. [Google Scholar] [CrossRef] [PubMed]
[17] Afkarian, M., Zelnick, L.R., Hall, Y.N., Heagerty, P.J., Tuttle, K., Weiss, N.S., et al. (2016) Clinical Manifestations of Kidney Disease among US Adults with Diabetes, 1988-2014. JAMA, 316, 602-610. [Google Scholar] [CrossRef] [PubMed]
[18] Akihisa, T., Manabe, S., Kataoka, H., et al. (2021) Dose-Dependent Effect of Tolvaptan on Renal Prognosis in Patients with Autosomal Dominant Polycystic Kidney Disease. Kidney360, 2, 1148-1151. [Google Scholar] [CrossRef] 
[19] Kong, X., Zhang, L., Zhang, L., Chen, N., Gu, Y., Yu, X., et al. (2012) Mineral and Bone Disorder in Chinese Dialysis Patients: A Multicenter Study. BMC Nephrology, 13, Article No. 116. [Google Scholar] [CrossRef] [PubMed]
[20] Portillo, M.R. and Rodríguez-Ortiz, M.E. (2017) Secondary Hyperparthyroidism: Pathogenesis, Diagnosis, Preventive and Therapeutic Strategies. Reviews in Endocrine and Meta-bolic Disorders, 18, 79-95. [Google Scholar] [CrossRef] [PubMed]
[21] Himmelfarb, J. and Tuttle, K.R. (2013) New Therapies for Dia-betic Kidney Disease. The New England Journal of Medicine, 369, 2549-2550. [Google Scholar] [CrossRef] 
[22] Garreta, E., Prado, P., Stanifer, M.L., et al. (2022) A Diabetic Milieu Increases ACE2 Expression and Cellular Susceptibility to SARS-CoV-2 Infections in Human Kidney Organoids and Pa-tient Cells. Cell Metab. [Google Scholar] [CrossRef] [PubMed]
[23] Kanda, H. and Yamawaki, K. (2020) Bardoxolone Methyl: Drug Development for Diabetic Kidney Disease. Clin Exp Nephrol, 24, 857-864. [Google Scholar] [CrossRef] [PubMed]
[24] Vincent, K.M., Alrajhi, A., Lazier, J., Bonin, B., Lawrence, S., Weiler, G., et al. (2022) Expanding the Clinical Spectrum of Autosomal-Recessive Renal Tubular Dysgenesis: Two Sib-lings with Neonatal Survival and Review of the Literature. Molecular Genetics & Genomic Medicine, 10, Article No. e1920. [Google Scholar] [CrossRef] [PubMed]
[25] Vaziri, N.D., Liu, S., Farzaneh, S.H., et al. (2015) Dose-Dependent Deleterious and Salutary Actions of the Nrf2 Inducer dh404 in Chronic Kidney Disease. Free Radical Biology and Medi-cine, 86, 374-381. [Google Scholar] [CrossRef] [PubMed]
[26] Chade, A.R., Zhu, X., Lavi, R., Krier, J.D., Pislaru, S., Simari, R.D., et al. (2009) Endothelial Progenitor Cells Restore Renal Function in Chronic Experimental Renovascular Disease. Circulation, 119, 547-557. [Google Scholar] [CrossRef] 
[27] Wang, Z. and Sun, D. (2018) Adipose-Derived Mesenchymal Stem Cells: A New Tool for the Treatment of Renal Fibrosis. Stem Cells and Development, 27, 1406-1411. [Google Scholar] [CrossRef] [PubMed]
[28] Cartón-García, F., Saande, C.J., Meraviglia-Crivelli, D., Aldabe, R. and Pastor, F. (2021) Oligonucleotide-Based Therapies for Renal Diseases. Biomedicines, 9, Article No. 303. [Google Scholar] [CrossRef] [PubMed]