Abstract
Diabetic nephropathy (DN) is a leading cause of end-stage renal disorder (ESRD). It is defined as the increase in urinary albumin excretion (UAE) when no other renal disease is present. DN is categorized into microalbuminuria and macroalbuminuria. Factors like high blood pressure, high blood sugar levels, genetics, oxidative stress, hemodynamic and metabolic changes affect DN. Hyperglycemia causes renal damage through activating protein kinase C (PKC), producing advanced end glycation products (AGEs) and reactive oxygen species (ROS). Growth factors, chemokines, cell adhesion molecules, inflammatory cytokines are found to be elevated in the renal tissues of the diabetic patient. Many different and new diagnostic methods and treatment options are available due to the increase in research efforts and progression in medical science. However, until now, no permanent cure is available. This article aims to explore the mechanism, diagnosis, and therapeutic strategies in current use for increasing the understanding of DN.
Keywords: Diabetic nephropathy, Urinary albumin excretion, microalbuminuria, macroalbuminuria, renal damage.
Graphical Abstract
[http://dx.doi.org/10.1016/S0140-6736(20)32374-6] [PMID: 33189186]
[http://dx.doi.org/10.2337/dc17-1962] [PMID: 29475843]
[http://dx.doi.org/10.1007/s40139-020-00205-x] [PMID: 32655983]
[http://dx.doi.org/10.7717/peerj.11070] [PMID: 33976959]
[http://dx.doi.org/10.1038/s41366-020-00671-8] [PMID: 32943762]
[http://dx.doi.org/10.1007/s00392-018-1316-1] [PMID: 29978353]
[http://dx.doi.org/10.1007/s11892-002-0080-8] [PMID: 12643139]
[http://dx.doi.org/10.1007/s10557-017-6755-9] [PMID: 28956186]
[http://dx.doi.org/10.5772/34541]
[PMID: 24203650]
[http://dx.doi.org/10.1053/j.ackd.2017.12.005] [PMID: 29580581]
[http://dx.doi.org/10.1016/B978-0-12-802761-5.00024-9]
[http://dx.doi.org/10.1155/2020/9416419]
[http://dx.doi.org/10.1016/j.diabet.2020.08.005] [PMID: 32919068]
[http://dx.doi.org/10.1016/j.jdiacomp.2020.107613] [PMID: 32505477]
[http://dx.doi.org/10.14814/phy2.14688] [PMID: 33377622]
[http://dx.doi.org/10.3390/diagnostics9040133] [PMID: 31569548]
[http://dx.doi.org/10.1021/acssensors.8b01072] [PMID: 30350581]
[http://dx.doi.org/10.2169/internalmedicine.9069-17] [PMID: 29269642]
[http://dx.doi.org/10.1093/ndt/gfi074]
[http://dx.doi.org/10.2147/IJNRD.S143186] [PMID: 28860837]
[http://dx.doi.org/10.7717/peerj.7079] [PMID: 31218128]
[http://dx.doi.org/10.1159/000382028] [PMID: 27536666]
[http://dx.doi.org/10.2337/diabetes.52.4.1036] [PMID: 12663477]
[http://dx.doi.org/10.2337/diacare.27.1.195] [PMID: 14693989]
[http://dx.doi.org/10.21037/jlpm.2018.09.07]
[http://dx.doi.org/10.2174/1389203719666180928123449] [PMID: 30264677]
[http://dx.doi.org/10.1016/j.bbadis.2018.08.036] [PMID: 30279139]
[http://dx.doi.org/10.1007/s12272-017-0998-7] [PMID: 29230688]
[http://dx.doi.org/10.1111/j.1440-1797.2006.00673.x] [PMID: 17014557]
[http://dx.doi.org/10.1002/jcp.29605] [PMID: 32017070]
[http://dx.doi.org/10.1039/D1FO03615G] [PMID: 35234233]
[http://dx.doi.org/10.1046/j.1523-1755.2000.07708.x] [PMID: 10997690]
[http://dx.doi.org/10.1016/j.matbio.2018.03.007] [PMID: 29574063]
[http://dx.doi.org/10.1038/sj.ki.5001846] [PMID: 16985515]
[http://dx.doi.org/10.1016/j.freeradbiomed.2022.03.019] [PMID: 35398495]
[http://dx.doi.org/10.1111/j.1440-1797.2005.00448.x] [PMID: 16174288]
[http://dx.doi.org/10.1016/j.redox.2018.02.013] [PMID: 29475133]
[http://dx.doi.org/10.1016/S0074-7696(04)37002-6]
[http://dx.doi.org/10.1089/ars.2006.8.1597] [PMID: 16987014]
[http://dx.doi.org/10.1016/j.jaut.2008.12.003] [PMID: 19200691]
[http://dx.doi.org/10.1159/000334928] [PMID: 22286547]
[http://dx.doi.org/10.1681/ASN.2007091048] [PMID: 18256353]
[http://dx.doi.org/10.2337/diabetes.49.3.466] [PMID: 10868970]
[http://dx.doi.org/10.1159/000098004] [PMID: 17167242]
[http://dx.doi.org/10.1046/j.1523-1755.2001.0590051739.x] [PMID: 11318944]
[http://dx.doi.org/10.1007/BF00400634] [PMID: 7758876]
[http://dx.doi.org/10.1016/j.cytogfr.2017.03.003] [PMID: 28363692]
[http://dx.doi.org/10.1681/ASN.2004110961] [PMID: 15938041]
[http://dx.doi.org/10.2337/diab.44.10.1233] [PMID: 7556963]
[http://dx.doi.org/10.1046/j.1365-2249.2002.01829.x] [PMID: 11985519]
[http://dx.doi.org/10.1002/art.20064] [PMID: 14872485]
[http://dx.doi.org/10.1046/j.1365-2567.2003.01747.x] [PMID: 14632660]
[http://dx.doi.org/10.1016/S1043-4666(03)00150-9] [PMID: 12842762]
[http://dx.doi.org/10.2337/diacare.28.12.2890] [PMID: 16306550]
[http://dx.doi.org/10.1053/meta.2003.50096] [PMID: 12759891]
[http://dx.doi.org/10.1111/j.1365-2249.2007.03389.x] [PMID: 17425653]
[http://dx.doi.org/10.1038/sj.ki.5002242] [PMID: 17396112]
[http://dx.doi.org/10.1038/sj.ki.5002132] [PMID: 17311071]
[http://dx.doi.org/10.1007/s001250051241] [PMID: 10440132]
[http://dx.doi.org/10.1111/j.1523-1755.2005.09918.x] [PMID: 16336586]
[http://dx.doi.org/10.1159/000079121] [PMID: 15205554]
[http://dx.doi.org/10.1152/ajprenal.00026.2002] [PMID: 12388406]
[http://dx.doi.org/10.1016/j.dsx.2020.10.032] [PMID: 33395772]
[http://dx.doi.org/10.1016/S1097-2765(02)00599-3] [PMID: 12191486]
[http://dx.doi.org/10.1038/nrneph.2015.175] [PMID: 26568190]
[http://dx.doi.org/10.1016/j.cell.2016.03.046] [PMID: 27153493]
[http://dx.doi.org/10.3390/ijms222212476] [PMID: 34830358]
[http://dx.doi.org/10.1038/s41423-021-00670-3] [PMID: 33850310]
[http://dx.doi.org/10.2147/DMSO.S199802] [PMID: 31447572]
[http://dx.doi.org/10.1016/j.bbrc.2019.10.194] [PMID: 31703838]
[http://dx.doi.org/10.1038/s41401-019-0297-6] [PMID: 31645661]
[http://dx.doi.org/10.1038/ki.2013.503] [PMID: 24352154]
[http://dx.doi.org/10.1016/j.kint.2016.03.035] [PMID: 27262364]
[http://dx.doi.org/10.1007/s12011-021-02773-4] [PMID: 34241775]
[http://dx.doi.org/10.1038/s41580-022-00456-z] [PMID: 35190722]
[http://dx.doi.org/10.3390/ijms21093289] [PMID: 32384691]
[http://dx.doi.org/10.1146/annurev.nu.07.070187.002543] [PMID: 3300746]
[http://dx.doi.org/10.1002/jat.3393] [PMID: 27682190]
[http://dx.doi.org/10.1007/s00018-017-2639-1] [PMID: 28871310]
[http://dx.doi.org/10.1016/j.redox.2018.03.019] [PMID: 29653411]
[http://dx.doi.org/10.18632/oncotarget.23383] [PMID: 29435125]
[http://dx.doi.org/10.1042/BSR20193006] [PMID: 32186721]
[http://dx.doi.org/10.1152/ajprenal.00409.2015] [PMID: 26764202]
[http://dx.doi.org/10.1016/j.bbrc.2018.09.003] [PMID: 30205956]
[http://dx.doi.org/10.1016/0168-8227(95)01064-K] [PMID: 7587918]
[http://dx.doi.org/10.1016/S0140-6736(98)07019-6] [PMID: 9742976]
[http://dx.doi.org/10.1038/sj.jhh.1001444] [PMID: 12571611]
[http://dx.doi.org/10.1001/archinte.163.13.1555] [PMID: 12860578]
[http://dx.doi.org/10.1016/S0140-6736(98)04311-6] [PMID: 9635947]
[http://dx.doi.org/10.2147/DDDT.S217826] [PMID: 31695333]
[http://dx.doi.org/10.2337/dcS15-3006] [PMID: 27440829]
[http://dx.doi.org/10.37358/RC.19.3.7047]
[http://dx.doi.org/10.1016/j.kisu.2021.11.005] [PMID: 35529090]
[http://dx.doi.org/10.1371/journal.pmed.1003691] [PMID: 34260595]
[http://dx.doi.org/10.3390/nu13030956] [PMID: 33809492]
[http://dx.doi.org/10.1016/j.jacc.2004.07.001] [PMID: 15358046]
[http://dx.doi.org/10.1046/j.1523-1755.2001.00487.x] [PMID: 11135079]
[http://dx.doi.org/10.1016/S0140-6736(03)13636-7] [PMID: 12814710]
[http://dx.doi.org/10.1016/S0002-9394(02)02149-9] [PMID: 12719099]
[http://dx.doi.org/10.2337/diacare.24.3.495] [PMID: 11289474]
[http://dx.doi.org/10.2337/diabetes.52.8.2110] [PMID: 12882930]
[http://dx.doi.org/10.1096/fj.02-1102fje] [PMID: 12958202]
[http://dx.doi.org/10.2337/diabetes.52.2.512] [PMID: 12540629]
[http://dx.doi.org/10.1681/ASN.V11122324] [PMID: 11095655]
[http://dx.doi.org/10.1007/s12325-021-01620-1] [PMID: 33502688]
[http://dx.doi.org/10.1159/000075627] [PMID: 14685005]
[http://dx.doi.org/10.1046/j.1523-1755.2003.00736.x] [PMID: 12472785]
[http://dx.doi.org/10.1084/jem.172.1.391] [PMID: 2358784]
[http://dx.doi.org/10.1016/j.phymed.2013.08.020] [PMID: 24074610]
[http://dx.doi.org/10.1016/j.phymed.2017.10.015] [PMID: 29126698]