Advances in diagnosis and treatment of autosomal dominant polycystic kidney disease

doi:10.3877/cma.j.issn.2095-655X.2026.02.009

Abstract

Abstract:

Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited kidney disorder. Its core pathogenesis involves PKD1/PKD2 gene mutations leading to polycystin dysfunction, which subsequently results in cyst formation and kidney injury. Based on the 2025 KDIGO guidelines, renal ultrasound is the preferred screening modality, combined with the Mayo imaging classification (MIC) and predicting renal outcome in polycystic kidney disease (PROPKD) score for precise risk stratification. Magnetic resonance imaging (MRI) is utilized for kidney volume analysis to monitor disease progression, complemented by genetic testing to identify pathogenic variants. Therapeutically, tolvaptan serves as the pivotal agent that can significantly delay cyst growth and kidney failure. This review systematically outlines the background and pathogenesis of ADPKD, with a focus in the latest standards for imaging and genetic diagnosis, as well as cutting-edge advances such as gene and cell therapies, aiming to provide a reference for the precise clinical diagnosis and management of ADPKD.

Key words: Polycystic kidney, autosomal dominant, PKD1/PKD2 gene, Imaging examination, Genetic testing, Drug therapy

Meng Liu, Lu Xu, Xinjian Li, Sha Gong, Tongtong Pan, Shuo Jia. Advances in diagnosis and treatment of autosomal dominant polycystic kidney disease[J]. Chinese Journal of Diagnostics(Electronic Edition), 2026, 14(02): 126-132.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://zhzdxdzzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.2095-655X.2026.02.009

https://zhzdxdzzz.cma-cmc.com.cn/EN/Y2026/V14/I02/126

Figures/Tables 1

References 55

[1]	Chebib FT，Hanna C，Harris PC，et al.Autosomal dominant polycystic kidney disease：a review[J].JAMA，2025，333(19)：1708-1719.DOI：10.1001/jama.2025.0310.
[2]	Suarez M，Titan S，Dahl NK.Autosomal dominant polycystic kidney disease[J].Adv Kidney Dis Health，2024，31(6)：496-503.DOI：10.1053/j.akdh.2024.07.003.
[3]	Torres VE，Ahn C，Barten T，et al.KDIGO 2025 clinical practice guideline for the evaluation，management，and treatment of autosomal dominant polycystic kidney disease (ADPKD)：executive summary[J].Kidney Int，2025，107(2)：234-254.DOI：10.1016/j.kint.2024.07.010.
[4]	Qiu J，Germino GG，Menezes LF.Mechanisms of cyst development in polycystic kidney disease[J].Adv Kidney Dis Health，2023，30(3)：209-219.DOI：10.1053/j.akdh.2023.03.001.
[5]	Sussman CR，Wang X，Chebib FT，et al.Modulation of polycystic kidney disease by G-protein coupled receptors and cyclic AMP signaling[J].Cell Signal，2020(72)：109649.DOI：10.1016/j.cellsig.2020.109649.
[6]	Scholz JK，Kraus A，Lüder D，et al.Loss of Polycystin-1 causes cAMP-dependent switch from tubule to cyst formation[J].iScience，2022，25(6)：104359.DOI：10.1016/j.isci.2022.104359.
[7]	Hansen JN，Kaiser F，Leyendecker P，et al.A cAMP signalosome in primary cilia drives gene expression and kidney cyst formation[J].EMBO Rep，2022，23(8)：e54315.DOI：10.15252/embr.202154315.
[8]	Xu Y，Kuppe C，Perales-Patón J, et al. Adult human kidney organoids originate from CD24(＋) cells and represent an advanced model for adult polycystic kidney disease[J].Nat Genet，2022，54(11)：1690-1701.DOI：10.1038/s41588-022-01202-z.
[9]	Song A，Zhang C，Meng X．Mechanism and application of metformin in kidney diseases：an update[J].Biomed Pharmacother，2021(138)：111454.DOI：10.1016/j.biopha.2021.111454.
[10]	Liu M，Zhang C，Gong X，et al.Kidney organoid models reveal cilium-autophagy metabolic axis as a therapeutic target for PKD both in vitro and in vivo[J].Cell Stem Cell，2024，31(1)：52-70.e8.DOI：10.1016/j.stem.2023.12.003.
[11]	Zhang Y，Daniel EA，Metcalf J，et al.CaMK4 overexpression in polycystic kidney disease promotes mTOR-mediated cell proliferation[J].J Mol Cell Biol，2022，14(7)：mjac050.DOI：10.1093/jmcb/mjac050.
[12]	Remadevi V，Jamadar A，Varghese MM，et al.Pirfenidone treatment attenuates fibrosis in autosomal dominant polycystic kidney disease[J].bioRxiv，2025：2025.08.25.672225.DOI：10.1101/2025.08.25.672225.
[13]	Strubl S，Torres JA，Spindt AK，et al.STAT signaling in polycystic kidney disease[J].Cell Signal，2020(72)：109639.DOI：10.1016/j.cellsig.2020.109639.
[14]	Wu J，Cheng S，Lee G，et al.STING promotes the progression of ADPKD by regulating mitochondrial function，inflammation，fibrosis，and apoptosis[J].Biomolecules，2024，14(10)：1215.DOI：10.3390/biom14101215.
[15]	Zhou JX，Cheng AS，Chen L，et al.CD74 promotes cyst growth and renal fibrosis in autosomal dominant polycystic kidney disease[J].Cells，2024，13(6)：489.DOI：10.3390/cells13060489.
[16]	Lv J, Lan B, Fu L, et al. EZH2 inhibition or genetic ablation suppresses cyst growth in autosomal dominant polycystic kidney disease[J].J Transl Med，2024，22(1)：979.DOI：10.1186/s12967-024-05785-5.
[17]	Lee EJ，Seo E，Kim JW，et al.TAZ/Wnt-β-catenin/c-MYC axis regulates cystogenesis in polycystic kidney disease[J].Proc Natl Acad Sci U S A，2020，117(46)：29001-29012.DOI：10.1073/pnas.2009334117.
[18]	Zhang X，Li LX，Ding H，et al.Ferroptosis promotes cyst growth in autosomal dominant polycystic kidney disease mouse models[J].J Am Soc Nephrol，2021，32(11)：2759-2776.DOI：10.1681/ASN.2021040460.
[19]	Odedra D，Sabongui S，Khalili K，et al.Autosomal dominant polycystic kidney disease：role of imaging in diagnosis and management[J].Radiographics，2023，43(1)：e220126.DOI：10.1148/rg.220126.
[20]	吴双成，郁胜强.2025版KDIGO常染色体显性多囊肾病评估、管理和治疗临床实践指南要点解读[J].诊断学理论与实践，2025，24(3)：255-262.DOI：10.16150/j.1671-2870.2025.03.003.
[21]	Nigro E，Amicone M，D'Arco D，et al. Molecular diagnosis and identification of novel pathogenic variants in a large cohort of Italian patients affected by polycystic kidney diseases[J].Genes (Basel)，2023，14(6)：1236.DOI：10.3390/genes14061236.
[22]	Pei Y，Obaji J，Dupuis A，et al.Unified criteria for ultrasonographic diagnosis of ADPKD[J].J Am Soc Nephrol，2009，20(1)：205-212.DOI：10.1681/asn.2008050507.
[23]	中华医学会遗传学分会遗传病临床实践指南撰写组．多囊肾病的临床实践指南[J].中华医学遗传学杂志，2020，37(3)：277-283.DOI：10.3760/cma.j.issn.1003-9406.2020.03.009.
[24]	Pei Y，Hwang Y H，Conklin J，et al.Imaging-based diagnosis of autosomal dominant polycystic kidney disease[J].J Am Soc Nephrol，2015，26(3)：746-753.DOI：10.1681/asn.2014030297.
[25]	Schönauer R，Baatz S，Nemitz-Kliemchen M，et al.Matching clinical and genetic diagnoses in autosomal dominant polycystic kidney disease reveals novel phenocopies and potential candidate genes[J].Genet Med，2020，22(8)：1374-1383.DOI：10.1038/s41436-020-0816-3.
[26]	Orisio S，Noris M，Rigoldi M，et al.Mutation analysis of PKD1 and PKD2 genes in a large italian cohort reveals novel pathogenic variants including a novel complex rearrangement[J].Nephron，2024，148(5)：273-291.DOI：10.1159/000530657.
[27]	Bleyer AJ，Westemeyer M，Xie J，et al.Genetic etiologies for chronic kidney disease revealed through next-generation renal gene panel[J].Am J Nephrol，2022，53(4)：297-306.DOI：10.1159/000522226.
[28]	Sun Q，Xu P，Mao A，et al.Targeted long-read sequencing enables higher diagnostic yield of ADPKD by accurate PKD1 genetic analysis[J].NPJ Genom Med，2025，10(1)：22.DOI：10.1038/s41525-025-00477-5.
[29]	托伐普坦治疗快速进展型常染色体显性多囊肾病专家组．托伐普坦治疗快速进展型常染色体显性多囊肾病中国专家共识[J].中华肾脏病杂志，2022，38(7)：644-652.DOI：10.3760/cma.j.cn441217-20220110-00093.
[30]	Bais T，Geertsema P，Knol M，et al.Validation of the mayo imaging classification system for predicting kidney outcomes in ADPKD[J].Clin J Am Soc Nephrol，2024，19(5)：591-601.DOI：10.2215/CJN.0000000000000427.
[31]	Bais T，Knol M，Xue L，et al.Predicting kidney outcomes in autosomal dominant polycystic kidney disease：a comprehensive biomarker analysis[J].Clin J Am Soc Nephrol，2025，20(5)：608-618.DOI：10.2215/CJN.0000000680.
[32]	van Luijk F，Gansevoort RT，Blokzijl H，et al.Multidisciplinary management of chronic refractory pain in autosomal dominant polycystic kidney disease[J].Nephrol Dial Transplant，2023，38(3)：618-629.DOI：10.1093/ndt/gfac158.
[33]	Nowak KL，Hopp K．Metabolic reprogramming in autosomal dominant polycystic kidney disease：evidence and therapeutic potential[J].Clin J Am Soc Nephrol，2020，15(4)：577-584.DOI：10.2215/CJN.13291019.
[34]	Capelli I，Lerario S，Aiello V, et al. Diet and physical activity in adult dominant polycystic kidney disease：a review of the literature[J].Nutrients，2023，15(11)：2621.DOI：10.3390/nu15112621.
[35]	Brioni E, Villa G, Manara DF, et al. The educational aspect in promoting a low-sodium diet，physical activity and therapy adherence among patients with autosomal dominant polycystic disease：a literature review[J].G Ital Nefrol，2023，40(5)：2023-vol5.
[36]	Kidney Disease：Improving Global Outcomes(KDIGO) Blood Pressure Work Group.KDIGO 2021 clinical practice guideline for the management of blood pressure in chronic kidney disease[J].Kidney Int，2021，99(3S)：S1-S87.DOI：10.1016/j.kint.2020.11.003.
[37]	Muensterman E，Torres JA，Weimbs T．Real-world outcomes of managing autosomal-dominant polycystic kidney disease using a medical food as part of a nutrition and lifestyle program to improve renal and metabolic health[J].Front Nutr，2025(12)：1624639.DOI：10.3389/fnut.2025.1624639.
[38]	de Chickera S，Alam A．Dialysis and transplant considerations in autosomal dominant polycystic kidney disease[J].Adv Kidney Dis Health，2023，30(5)：461-467.DOI：10.1053/j.akdh.2023.06.005.
[39]	Geertsema P，Bais T，Kuiken V，et al.The long-term effect of tolvaptan treatment on kidney function and volume in patients with ADPKD[J].Nephrol Dial Transplant，2025，40(9)：1764-1774.DOI：10.1093/ndt/gfaf048.
[40]	Betts KA，Nunna S，Kumar R，et al.Tolvaptan and number needed to harm in autosomal dominant polycystic kidney disease[J].Kidney Med，2024，6(4)：100802.DOI：10.1016/j.xkme.2024.100802.
[41]	Stanley IK，Palma AM，Viecelli AK，et al.A secondary analysis of concurrent use of metformin and tolvaptan in ADPKD tolvaptan trials[J].J Nephrol，2024，37(5)：1417-1419.DOI：10.1007/s40620-024-01906-x.
[42]	Ong A，Gansevoort RT.TAMEing ADPKD with metformin：safe and effective？[J].Kidney Int，2021，100(3)：513-515.DOI：10.1016/j.kint.2021.07.021.
[43]	Su L，Yuan H，Zhang H，et al.PF-06409577 inhibits renal cyst progression by concurrently inhibiting the mTOR pathway and CFTR channel activity[J].FEBS Open Bio，2022，12(10)：1761-1770.DOI：10.1002/2211-5463.13459.
[44]	Gulieva RE，Ahmadvand P，Freedman BS.A novel rapalog shows improved safety vs.efficacy in a human organoid model of polycystic kidney disease[J].Stem Cell Reports，2025，20(2)：102395.DOI：10.1016/j.stemcr.2024.102395.
[45]	Bou Antoun MT，Borghol AH，Souvalian L，et al.Sodium-glucose cotransporter 2 inhibitors in autosomal dominant polycystic kidney disease：mechanistic insights and therapeutic promise[J].J Am Soc Nephrol，2026，37(4)：861-880.DOI：10.1681/ASN.0000000943.
[46]	Cebotaru L，Liu Q，Yanda MK，et al.Inhibition of histone deacetylase 6 activity reduces cyst growth in polycystic kidney disease[J].Kidney Int，2016，90(1)：90-99.DOI：10.1016/j.kint.2016.01.026.
[47]	Chen X, Yu C, Hou X, et al. Histone deacetylase 6 inhibition mitigates renal fibrosis by suppressing TGF-β and EGFR signaling pathways in obstructive nephropathy[J].Am J Physiol Renal Physiol，2020，319(6)：F1003-F1014.DOI：10.1152/ajprenal.00261.2020.
[48]	Cao X，Fan Z，Xu L，et al.Benzothiazole derivatives as histone deacetylase inhibitors for the treatment of autosomal dominant polycystic kidney disease[J].Eur J Med Chem，2024(271)：116428.DOI：10.1016/j.ejmech.2024.116428.
[49]	Sun Y，Zou Q，Yu H，et al.Melanin-like nanoparticles slow cyst growth in ADPKD by dual inhibition of oxidative stress and CREB[J].EMBO Mol Med，2025，17(1)：169-192.DOI：10.1038/s44321-024-00167-2.
[50]	Lee E ，Valencia T M ，Varrone F ，et al.Discovery of next-generation anti-miR-17 oligonucleotide RGLS8429 for treatment of autosomal dominant polycystic kidney disease (ADPKD)：TH-PO408 [J].J Am Soc Nephrol，2022，33(11S)：160.DOI：10.1681/ASN.20223311S1160c.
[51]	Bais T，Gansevoort RT，Meijer E．Drugs in clinical development to treat autosomal dominant polycystic kidney disease[J].Drugs，2022，82(10)：1095-1115.DOI：10.1007/s40265-022-01745-9.
[52]	李馨茗，毛志国，梅长林，等．多囊肾病的基因治疗进展 [J].中华肾脏病杂志，2024，40(11)：905-911.DOI：10.3760/cma.j.cn441217-20240320-00328.
[53]	Zhou C，Mei C，Xue C．Preimplantation genetic diagnosis of autosomal dominant polycystic kidney disease applied in China[J].Am J Kidney Dis，2018，72(5)：767.DOI：10.1053/j.ajkd.2018.04.017.
[54]	Liu D，Cheng F，Pan S，et al.Stem cells：a potential treatment option for kidney diseases[J].Stem Cell Res Ther，2020，11(1)：249.DOI：10.1186/s13287-020-01751-2.
[55]	Wang J, Lin Y, Chen X, et al. Mesenchymal stem cells：a new therapeutic tool for chronic kidney disease[J].Front Cell Dev Biol，2022(10)：910592.DOI：10.3389/fcell.2022.910592.

Please choose a citation manager

Content to export