Role of hyperuricemia in diabetic nephropathy

doi:10.16352/j.issn.1001-6325.2025.03.0378

Abstract

Abstract: Hyperuricemia (HUA), characterized by abnormal uric acid (UA) metabolism, leads to the accumulation of urate salts within the kidney. This accumulation not only disrupts glomerular filtration and tubular reabsorption functions but also triggers oxidative stress, inflammation,and up-regulating the renin-angiotensin-aldosterone system (RASS), all of which damage renal cells and tissues. These mechanisms contribute to renal fibrosis and accelerate the progression of diabetic nephropathy (DN)/diabetic kidney disease(DKD). These findings underscore the role of HUA as a risk factor for the advancement of DKD, emphasizing the critical importance of effective UA control in delaying its development.

Key words: hyperuricemia, uric acid metabolism, diabetic kidney disease

CLC Number:

R589

DENG Jie, WEI Jiali. Role of hyperuricemia in diabetic nephropathy[J]. Basic & Clinical Medicine, 2025, 45(3): 378-381.

References

[1] Zhang M, Zhu X, Wu J, et al. Prevalence of hyperuricemia among Chinese adults: findings from two nationally representative cross-sectional surveys in 2015-16 and 2018-19[J]. Front Immunol, 2021, 12: 791983.doi:10.3389/fimmu.2021.791983.
[2] Xu J, Tong L, Mao J. Hyperuricemia and associated factors in children with chronic kidney disease: a cross-sectional study[J]. Children (Basel), 2021, 9.doi:10.3390/children9010006.
[3] Puig JG, Torres RJ, de Miguel E, et al. Uric acid excretion in healthy subjects: a nomogram to assess the mechanisms underlying purine metabolic disorders[J]. Metabolism, 2012,61: 512-518.doi:10.1016/j.metabol.2011.08.005.
[4] Song D, Zhao X, Wang F, et al. A brief review of urate transporter 1 (URAT1) inhibitors for the treatment of hyperuricemia and gout: current therapeutic options and potential applications[J]. Eur J Pharmacol, 2021, 907: 174291.doi:10.1016/j.ejphar.2021.174291.
[5] Johnson RJ. Intestinal hyperuricemia as a driving mechanism for CKD[J]. Am J Kidney Dis, 2022.doi:10.1053/j.ajkd.2022.08.001.
[6] 陶鹏宇,张悦. SIRT1在糖尿病肾病进展中的作用[J]. 基础医学与临床, 2019,39: 439-43.doi:10.16352/j.issn.1001-6325.2019.03.039.
[7] Yaribeygi H, Sathyapalan T, Atkin SL, et al. Molecular mechanisms linking oxidative stress and diabetes mellitus[J]. Oxid Med Cell Longev, 2020, 2020: 8609213.doi:10.1155/2020/8609213.
[8] Qiao S, Liu R, Lv C, et al. Bergenin impedes the generation of extracellular matrix in glomerular mesangial cells and ameliorates diabetic nephropathy in mice by inhibiting oxidative stress via the mTOR/β-TrcP/Nrf2 pathway[J]. Free Radic Biol Med, 2019, 145: 118-135.doi:10.1016/j.freeradbiomed.2019.09.003.
[9] Barutta F, Bellini S, Gruden G, Mechanisms of podocyte injury and implications for diabetic nephropathy[J]. Clin Sci(Lond), 2022, 136: 493-520.doi:10.1042/cs20210625.
[10] Su HY, Yang C, Liang D, et al. Research advances in the mechanisms of hyperuricemia-induced renal injury[J]. Biomed Res Int, 2020,2020: 5817348.doi:10.1155/2020/5817348.
[11] Mehmood A, Zhao L, Ishaq M, et al. Anti-hyperuricemic potential of stevia (Stevia rebaudiana Bertoni) residue extract in hyperuricemic mice[J]. Food Funct, 2020,11:6387-6406.doi:10.1039/c9fo02246e.
[12] Hotta N, Kawamura T, Umemura T. Are the polyol pathway and hyperuricemia partners in the development of non-alcoholic fatty liver disease in diabetes?[J]. J Diabetes Investig, 2020, 11: 786-788.doi:10.1111/jdi.13190.
[13] Gul A, Zager P. Does altered uric acid metabolism contribute to diabetic kidney disease pathophysiology?[J]. Curr Diab Rep, 2018, 18: 18.doi:10.1007/s11892-018-0985-5.
[14] Wang Y, Jin M, Cheng CK, et al. Tubular injury in diabetic kidney disease: molecular mechanisms and potential therapeutic perspectives[J]. Front Endocrinol (Lausanne), 2023,14: 1238927.doi:10.3389/fendo.2023.1238927.
[15] Tuttle KR, Agarwal R, Alpers CE, et al. Molecular mechanisms and therapeutic targets for diabetic kidney disease[J]. Kidney Int, 2022,102: 248-260.doi:10.1016/j.kint.2022.05.012.
[16] Cao Y, Yang Z, Chen Y, et al. An overview of the posttranslational modifications and related molecular mechanisms in diabetic nephropathy[J]. Front Cell Dev Biol, 2021, 9: 630401.doi:10.3389/fcell.2021.630401.
[17] Zhuang J, Zhou X, Liu T, et al. Astaxanthin attenuated hyperuricemia and kidney inflammation by inhibiting uric acid synthesis and the NF-κ B/NLRP3 signaling pathways in potassium oxonate and hypoxanthine-induced hyperuricemia mice[J]. Pharmazie, 2021, 76: 551-558.doi:10.1691/ph.2021.1731.
[18] Ren Q, Tao S, Guo F, et al. Natural flavonol fisetin attenuated hyperuricemic nephropathy via inhibiting IL-6/JAK2/STAT3 and TGF-β/SMAD3 signaling[J]. Phytomedicine, 2021,87: 153552.doi:10.1016/j.phymed.2021.153552.
[19] Kim SM, Lee SH, Kim YG, et al. Hyperuricemia-induced NLRP3 activation of macrophages contributes to the progression of diabetic nephropathy[J]. Am J Physiol Renal Physiol, 2015, 308: F993-F1003.doi:10.1152/ajprenal.00637.2014.
[20] Kosugi T, Nakayama T, Heinig M, et al. Effect of lowering uric acid on renal disease in the type 2 diabetic db/db mice[J]. Am J Physiol Renal Physiol, 2009, 297: F481-F488.doi:10.1152/ajprenal.00092.2009.
[21] Chang J, Yan J, Li X, et al. Update on the mechanisms of tubular cell injury in diabetic kidney disease[J]. Front Med (Lausanne), 2021, 8: 661076.doi:10.3389/fmed.2021.661076.
[22] Bahreini E, Rezaei-Chianeh Y, Nabi-Afjadi M. Molecular mechanisms involved in intrarenal renin-angiotensin and alternative pathways in diabetic nephropathy-a review[J]. Rev Diabet Stud, 2021, 17: 1-10.doi:10.1900/rds.2021.17.1.
[23] Jalal DI, Maahs DM, Hovind P, et al. Uric acid as a mediator of diabetic nephropathy[J]. Semin Nephrol, 2011, 31: 459-465.doi:10.1016/j.semnephrol.2011.08.011.
[24] Wu XQ, Zhang DD, Wang YN, et al. AGE/RAGE in diabetic kidney disease and ageing kidney[J]. Free Radic Biol Med, 2021,171: 260-271.doi:10.1016/j.freeradbiomed.2021.05.025.
[25] Lemiesz M, Tenderenda-Banasiuk E, Sosnowska D, et al. The possible impact of hyperuricemia on serum soluble receptor for advanced glycation end products (sRAGE) levels in teenagers: a case control study[J]. Curr Pharm Des, 2018, 24: 3232-3239.doi:10.2174/1381612824666180813114127.