Targeted Therapies for Autosomal Dominant Polycystic Kidney Disease

Author(s): Cherie Stayner* , Darby G. Brooke , Michael Bates , Michael R. Eccles .

Journal Name: Current Medicinal Chemistry

Volume 26 , Issue 17 , 2019

  Journal Home
Translate in Chinese

Abstract:

Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common life-threatening genetic disease in humans, affecting approximately 1 in 500 people. ADPKD is characterized by cyst growth in the kidney leading to progressive parenchymal damage and is the underlying pathology in approximately 10% of patients requiring hemodialysis or transplantation for end-stage kidney disease. The two proteins that are mutated in ADPKD, polycystin-1 and polycystin-2, form a complex located on the primary cilium and the plasma membrane to facilitate calcium ion release in the cell. There is currently no Food and Drug Administration (FDA)-approved therapy to cure or slow the progression of the disease. Rodent ADPKD models do not completely mimic the human disease, and therefore preclinical results have not always successfully translated to the clinic. Moreover, the toxicity of many of these potential therapies has led to patient withdrawals from clinical trials.

Results: Here, we review compounds in clinical trial for treating ADPKD, and we examine the feasibility of using a kidney-targeted approach, with potential for broadening the therapeutic window, decreasing treatment-associated toxicity and increasing the efficacy of agents that have demonstrated activity in animal models. We make recommendations for integrating kidney- targeted therapies with current treatment regimes, to achieve a combined approach to treating ADPKD.

Conclusion: Many compounds are currently in clinical trial for ADPKD yet, to date, none are FDA-approved for treating this disease. Patients could benefit from efficacious pharmacotherapy, especially if it can be kidney-targeted, and intensive efforts continue to be focused on this goal.

Keywords: Autosomal dominant polycystic kidney disease, (ADPKD), kidney-specific therapy, kidney disease, targeted therapies, polycystic kidney disease, autosomal disease.

[1]
Fliegauf, M.; Benzing, T.; Omran, H. When cilia go bad: cilia defects and ciliopathies. Nat. Rev. Mol. Cell Biol., 2007, 8(11), 880-893.
[http://dx.doi.org/10.1038/nrm2278] [PMID: 17955020]
[2]
Iglesias, C.G.; Torres, V.E.; Offord, K.P.; Holley, K.E.; Beard, C.M.; Kurland, L.T. Epidemiology of adult polycystic kidney disease, Olmsted County, Minnesota: 1935-1980. Am. J. Kidney Dis., 1983, 2(6), 630-639.
[http://dx.doi.org/10.1016/S0272-6386(83)80044-4] [PMID: 6846334]
[3]
Gabow, P.A. Autosomal dominant polycystic kidney disease. N. Engl. J. Med., 1993, 329(5), 332-342.
[http://dx.doi.org/10.1056/NEJM199307293290508] [PMID: 8321262]
[4]
Parfrey, P.S.; Bear, J.C.; Morgan, J.; Cramer, B.C.; McManamon, P.J.; Gault, M.H.; Churchill, D.N.; Singh, M.; Hewitt, R.; Somlo, S. The diagnosis and prognosis of autosomal dominant polycystic kidney disease. N. Engl. J. Med., 1990, 323(16), 1085-1090.
[http://dx.doi.org/10.1056/NEJM199010183231601] [PMID: 2215575]
[5]
McDonald, S.; Rangan, G. Polycystic kidney disease: Progression of polycystic kidney disease--a lack of progress? Nat. Rev. Nephrol., 2014, 10(9), 489-491.
[http://dx.doi.org/10.1038/nrneph.2014.138] [PMID: 25092149]
[6]
Wuthrich, R.P.; Kistler, A.D.; Rodriguez, D.; Kapoor, S.; Mei, C. Polycystic Kidney Disease., Li, X., Ed.: Brisbane (AU), 2015.
[7]
Rossetti, S.; Consugar, M.B.; Chapman, A.B.; Torres, V.E.; Guay-Woodford, L.M.; Grantham, J.J.; Bennett, W.M.; Meyers, C.M.; Walker, D.L.; Bae, K.; Zhang, Q.J.; Thompson, P.A.; Miller, J.P.; Harris, P.C.; Consortium, C. Comprehensive molecular diagnostics in autosomal dominant polycystic kidney disease. J. Am. Soc. Nephrol., 2007, 18(7), 2143-2160.
[http://dx.doi.org/10.1681/ASN.2006121387] [PMID: 17582161]
[8]
Harris, P.C.; Thomas, S.; MacCarthy, A.B.; Stallings, R.L.; Breuning, M.H.; Jenne, D.E.; Fink, T.M.; Buckle, V.J.; Ratcliffe, P.J.; Ward, C.J. A large duplicated area in the polycystic kidney disease 1 (PKD1) region of chromosome 16 is prone to rearrangement. Genomics, 1994, 23(2), 321-330.
[http://dx.doi.org/10.1006/geno.1994.1507] [PMID: 7835880]
[9]
Polycystic kidney disease: the complete structure of the PKD1 gene and its protein. Cell, 1995, 81(2), 289-298.
[http://dx.doi.org/10.1016/0092-8674(95)90339-9] [PMID: 7736581]
[10]
Mochizuki, T.; Wu, G.; Hayashi, T.; Xenophontos, S.L.; Veldhuisen, B.; Saris, J.J.; Reynolds, D.M.; Cai, Y.; Gabow, P.A.; Pierides, A.; Kimberling, W.J.; Breuning, M.H.; Deltas, C.C.; Peters, D.J.; Somlo, S. PKD2, a gene for polycystic kidney disease that encodes an integral membrane protein. Science, 1996, 272(5266), 1339-1342.
[http://dx.doi.org/10.1126/science.272.5266.1339] [PMID: 8650545]
[11]
Hateboer, N.; Dijk, M.A.; Bogdanova, N.; Coto, E.; Saggar-Malik, A.K.; San Millan, J.L.; Torra, R.; Breuning, M.; Ravine, D. Comparison of phenotypes of polycystic kidney disease types 1 and 2. European PKD1-PKD2 Study Group. Lancet, 1999, 353(9147), 103-107.
[http://dx.doi.org/10.1016/S0140-6736(98)03495-3] [PMID: 10023895]
[12]
Cornec-Le Gall, E.; Audrézet, M.P.; Chen, J.M.; Hourmant, M.; Morin, M.P.; Perrichot, R.; Charasse, C.; Whebe, B.; Renaudineau, E.; Jousset, P.; Guillodo, M.P.; Grall-Jezequel, A.; Saliou, P.; Férec, C.; Le Meur, Y. Type of PKD1 mutation influences renal outcome in ADPKD. J. Am. Soc. Nephrol., 2013, 24(6), 1006-1013.
[http://dx.doi.org/10.1681/ASN.2012070650] [PMID: 23431072]
[13]
Paul, B.M.; Consugar, M.B.; Ryan Lee, M.; Sundsbak, J.L.; Heyer, C.M.; Rossetti, S.; Kubly, V.J.; Hopp, K.; Torres, V.E.; Coto, E.; Clementi, M.; Bogdanova, N.; de Almeida, E.; Bichet, D.G.; Harris, P.C. Evidence of a third ADPKD locus is not supported by re-analysis of designated PKD3 families. Kidney Int., 2014, 85(2), 383-392.
[http://dx.doi.org/10.1038/ki.2013.227] [PMID: 23760289]
[14]
Porath, B.; Gainullin, V.G.; Cornec-Le Gall, E.; Dillinger, E.K.; Heyer, C.M.; Hopp, K.; Edwards, M.E.; Madsen, C.D.; Mauritz, S.R.; Banks, C.J.; Baheti, S.; Reddy, B.; Herrero, J.I.; Banales, J.M.; Hogan, M.C.; Tasic, V.; Watnick, T.J.; Chapman, A.B.; Vigneau, C.; Lavainne, F.; Audrezet, M.P.; Ferec, C.; Le Meur, Y.; Torres, V.E.H.P.o.P.K.D.G. Consortium for Radiologic Imaging Studies of Polycystic Kidney, D.; Harris, P.C., Mutations in GANAB, encoding the glucosidase IIalpha subunit, cause autosomal-dominant polycystic kidney and liver disease. Am. J. Hum. Genet., 2016, 98(6), 1193-1207.
[http://dx.doi.org/10.1016/j.ajhg.2016.05.004] [PMID: 27259053]
[15]
Boletta, A. Emerging evidence of a link between the polycystins and the mTOR pathways. PathoGenetics, 2009, 2(1), 6.
[http://dx.doi.org/10.1186/1755-8417-2-6] [PMID: 19863783]
[16]
Qian, F.; Germino, F.J.; Cai, Y.; Zhang, X.; Somlo, S.; Germino, G.G. PKD1 interacts with PKD2 through a probable coiled-coil domain. Nat. Genet., 1997, 16(2), 179-183.
[http://dx.doi.org/10.1038/ng0697-179] [PMID: 9171830]
[17]
Nauli, S.M.; Zhou, J. Polycystins and mechanosensation in renal and nodal cilia. BioEssays, 2004, 26(8), 844-856.
[http://dx.doi.org/10.1002/bies.20069] [PMID: 15273987]
[18]
Stayner, C.; Zhou, J. Polycystin channels and kidney disease. Trends Pharmacol. Sci., 2001, 22(11), 543-546.
[http://dx.doi.org/10.1016/S0165-6147(00)01832-0] [PMID: 11698076]
[19]
Qian, F.; Boletta, A.; Bhunia, A.K.; Xu, H.; Liu, L.; Ahrabi, A.K.; Watnick, T.J.; Zhou, F.; Germino, G.G. Cleavage of polycystin-1 requires the receptor for egg jelly domain and is disrupted by human autosomal-dominant polycystic kidney disease 1-associated mutations. Proc. Natl. Acad. Sci. USA, 2002, 99(26), 16981-16986.
[http://dx.doi.org/10.1073/pnas.252484899] [PMID: 12482949]
[20]
Yu, S.; Hackmann, K.; Gao, J.; He, X.; Piontek, K.; García-González, M.A.; Menezes, L.F.; Xu, H.; Germino, G.G.; Zuo, J.; Qian, F. Essential role of cleavage of Polycystin-1 at G protein-coupled receptor proteolytic site for kidney tubular structure. Proc. Natl. Acad. Sci. USA, 2007, 104(47), 18688-18693.
[http://dx.doi.org/10.1073/pnas.0708217104] [PMID: 18003909]
[21]
Low, S.H.; Vasanth, S.; Larson, C.H.; Mukherjee, S.; Sharma, N.; Kinter, M.T.; Kane, M.E.; Obara, T.; Weimbs, T. Polycystin-1, STAT6, and P100 function in a pathway that transduces ciliary mechanosensation and is activated in polycystic kidney disease. Dev. Cell, 2006, 10(1), 57-69.
[http://dx.doi.org/10.1016/j.devcel.2005.12.005] [PMID: 16399078]
[22]
Lal, M.; Song, X.; Pluznick, J.L.; Di Giovanni, V.; Merrick, D.M.; Rosenblum, N.D.; Chauvet, V.; Gottardi, C.J.; Pei, Y.; Caplan, M.J. Polycystin-1 C-terminal tail associates with beta-catenin and inhibits canonical Wnt signaling. Hum. Mol. Genet., 2008, 17(20), 3105-3117.
[http://dx.doi.org/10.1093/hmg/ddn208] [PMID: 18632682]
[23]
Braun, D.A.; Hildebrandt, F. Ciliopathies. Cold Spring Harb. Perspect. Biol., 2017, 9(3), a028191.
[http://dx.doi.org/10.1101/cshperspect.a028191] [PMID: 27793968]
[24]
Reiter, J.F.; Leroux, M.R. Genes and molecular pathways underpinning ciliopathies. Nat. Rev. Mol. Cell Biol., 2017, 18(9), 533-547.
[http://dx.doi.org/10.1038/nrm.2017.60] [PMID: 28698599]
[25]
Shillingford, J.M.; Murcia, N.S.; Larson, C.H.; Low, S.H.; Hedgepeth, R.; Brown, N.; Flask, C.A.; Novick, A.C.; Goldfarb, D.A.; Kramer-Zucker, A.; Walz, G.; Piontek, K.B.; Germino, G.G.; Weimbs, T. The mTOR pathway is regulated by polycystin-1, and its inhibition reverses renal cystogenesis in polycystic kidney disease. Proc. Natl. Acad. Sci. USA, 2006, 103(14), 5466-5471.
[http://dx.doi.org/10.1073/pnas.0509694103] [PMID: 16567633]
[26]
Olsan, E.E.; Mukherjee, S.; Wulkersdorfer, B.; Shillingford, J.M.; Giovannone, A.J.; Todorov, G.; Song, X.; Pei, Y.; Weimbs, T. Signal transducer and activator of transcription-6 (STAT6) inhibition suppresses renal cyst growth in polycystic kidney disease. Proc. Natl. Acad. Sci. USA, 2011, 108(44), 18067-18072.
[http://dx.doi.org/10.1073/pnas.1111966108] [PMID: 22025716]
[27]
Bhunia, A.K.; Piontek, K.; Boletta, A.; Liu, L.; Qian, F.; Xu, P.N.; Germino, F.J.; Germino, G.G. PKD1 induces p21(waf1) and regulation of the cell cycle via direct activation of the JAK-STAT signaling pathway in a process requiring PKD2. Cell, 2002, 109(2), 157-168.
[http://dx.doi.org/10.1016/S0092-8674(02)00716-X] [PMID: 12007403]
[28]
Simons, M.; Gloy, J.; Ganner, A.; Bullerkotte, A.; Bashkurov, M.; Krönig, C.; Schermer, B.; Benzing, T.; Cabello, O.A.; Jenny, A.; Mlodzik, M.; Polok, B.; Driever, W.; Obara, T.; Walz, G. Inversin, the gene product mutated in nephronophthisis type II, functions as a molecular switch between Wnt signaling pathways. Nat. Genet., 2005, 37(5), 537-543.
[http://dx.doi.org/10.1038/ng1552] [PMID: 15852005]
[29]
Kim, E.; Arnould, T.; Sellin, L.K.; Benzing, T.; Fan, M.J.; Grüning, W.; Sokol, S.Y.; Drummond, I.; Walz, G. The polycystic kidney disease 1 gene product modulates Wnt signaling. J. Biol. Chem., 1999, 274(8), 4947-4953.
[http://dx.doi.org/10.1074/jbc.274.8.4947] [PMID: 9988738]
[30]
Wallace, D.P. Cyclic AMP-mediated cyst expansion. Biochim. Biophys. Acta, 2011, 1812(10), 1291-1300.
[http://dx.doi.org/10.1016/j.bbadis.2010.11.005] [PMID: 21118718]
[31]
Yamaguchi, T.; Wallace, D.P.; Magenheimer, B.S.; Hempson, S.J.; Grantham, J.J.; Calvet, J.P. Calcium restriction allows cAMP activation of the B-Raf/ERK pathway, switching cells to a cAMP-dependent growth-stimulated phenotype. J. Biol. Chem., 2004, 279(39), 40419-40430.
[http://dx.doi.org/10.1074/jbc.M405079200] [PMID: 15263001]
[32]
Pan, J.; Seeger-Nukpezah, T.; Golemis, E.A. The role of the cilium in normal and abnormal cell cycles: emphasis on renal cystic pathologies. Cell. Mol. Life Sci., 2013, 70(11), 1849-1874.
[http://dx.doi.org/10.1007/s00018-012-1052-z] [PMID: 22782110]
[33]
Ferreira, F.M.; Watanabe, E.H.; Onuchic, L.F. Polycystic. Kidney Dis., 2015.
[34]
Lu, W.; Peissel, B.; Babakhanlou, H.; Pavlova, A.; Geng, L.; Fan, X.; Larson, C.; Brent, G.; Zhou, J. Perinatal lethality with kidney and pancreas defects in mice with a targetted Pkd1 mutation. Nat. Genet., 1997, 17(2), 179-181.
[http://dx.doi.org/10.1038/ng1097-179] [PMID: 9326937]
[35]
Bae, K.; Park, B.; Sun, H.; Wang, J.; Tao, C.; Chapman, A.B.; Torres, V.E.; Grantham, J.J.; Mrug, M.; Bennett, W.M.; Flessner, M.F.; Landsittel, D.P.; Bae, K.T. Segmentation of individual renal cysts from MR images in patients with autosomal dominant polycystic kidney disease. Clin. J. Am. Soc. Nephrol., 2013, 8(7), 1089-1097.
[http://dx.doi.org/10.2215/CJN.10561012] [PMID: 23520042]
[36]
Reeders, S.T. Multilocus polycystic disease. Nat. Genet., 1992, 1(4), 235-237.
[http://dx.doi.org/10.1038/ng0792-235] [PMID: 1338768]
[37]
Wu, G.; D’Agati, V.; Cai, Y.; Markowitz, G.; Park, J.H.; Reynolds, D.M.; Maeda, Y.; Le, T.C.; Hou, H., Jr; Kucherlapati, R.; Edelmann, W.; Somlo, S. Somatic inactivation of Pkd2 results in polycystic kidney disease. Cell, 1998, 93(2), 177-188.
[http://dx.doi.org/10.1016/S0092-8674(00)81570-6] [PMID: 9568711]
[38]
Brasier, J.L.; Henske, E.P. Loss of the polycystic kidney disease (PKD1) region of chromosome 16p13 in renal cyst cells supports a loss-of-function model for cyst pathogenesis. J. Clin. Invest., 1997, 99(2), 194-199.
[http://dx.doi.org/10.1172/JCI119147] [PMID: 9005987]
[39]
Pei, Y.; Watnick, T.; He, N.; Wang, K.; Liang, Y.; Parfrey, P.; Germino, G.; St George-Hyslop, P. Somatic PKD2 mutations in individual kidney and liver cysts support a “two-hit” model of cystogenesis in type 2 autosomal dominant polycystic kidney disease. J. Am. Soc. Nephrol., 1999, 10(7), 1524-1529.
[PMID: 10405208]
[40]
Koptides, M.; Hadjimichael, C.; Koupepidou, P.; Pierides, A.; Constantinou Deltas, C. Germinal and somatic mutations in the PKD2 gene of renal cysts in autosomal dominant polycystic kidney disease. Hum. Mol. Genet., 1999, 8(3), 509-513.
[http://dx.doi.org/10.1093/hmg/8.3.509] [PMID: 9949210]
[41]
Watnick, T.; He, N.; Wang, K.; Liang, Y.; Parfrey, P.; Hefferton, D.; St George-Hyslop, P.; Germino, G.; Pei, Y. Mutations of PKD1 in ADPKD2 cysts suggest a pathogenic effect of trans-heterozygous mutations. Nat. Genet., 2000, 25(2), 143-144.
[http://dx.doi.org/10.1038/75981] [PMID: 10835625]
[42]
Eccles, M.R.; Stayner, C.A. Polycystic kidney disease - where gene dosage counts. F1000Prime Rep., 2014, 6, 24.
[http://dx.doi.org/10.12703/P6-24] [PMID: 24765529]
[43]
Gallagher, A.R.; Germino, G.G.; Somlo, S. Molecular advances in autosomal dominant polycystic kidney disease. Adv. Chronic Kidney Dis., 2010, 17(2), 118-130.
[http://dx.doi.org/10.1053/j.ackd.2010.01.002] [PMID: 20219615]
[44]
Lantinga-van Leeuwen, I.S.; Dauwerse, J.G.; Baelde, H.J.; Leonhard, W.N.; van de Wal, A.; Ward, C.J.; Verbeek, S.; Deruiter, M.C.; Breuning, M.H.; de Heer, E.; Peters, D.J. Lowering of Pkd1 expression is sufficient to cause polycystic kidney disease. Hum. Mol. Genet., 2004, 13(24), 3069-3077.
[http://dx.doi.org/10.1093/hmg/ddh336] [PMID: 15496422]
[45]
Jiang, S.T.; Chiou, Y.Y.; Wang, E.; Lin, H.K.; Lin, Y.T.; Chi, Y.C.; Wang, C.K.; Tang, M.J.; Li, H. Defining a link with autosomal-dominant polycystic kidney disease in mice with congenitally low expression of Pkd1. Am. J. Pathol., 2006, 168(1), 205-220.
[http://dx.doi.org/10.2353/ajpath.2006.050342] [PMID: 16400024]
[46]
Ward, C.J.; Turley, H.; Ong, A.C.; Comley, M.; Biddolph, S.; Chetty, R.; Ratcliffe, P.J.; Gattner, K.; Harris, P.C. Polycystin, the polycystic kidney disease 1 protein, is expressed by epithelial cells in fetal, adult, and polycystic kidney. Proc. Natl. Acad. Sci. USA, 1996, 93(4), 1524-1528.
[http://dx.doi.org/10.1073/pnas.93.4.1524] [PMID: 8643665]
[47]
Thivierge, C.; Kurbegovic, A.; Couillard, M.; Guillaume, R.; Coté, O.; Trudel, M. Overexpression of PKD1 causes polycystic kidney disease. Mol. Cell. Biol., 2006, 26(4), 1538-1548.
[http://dx.doi.org/10.1128/MCB.26.4.1538-1548.2006] [PMID: 16449663]
[48]
Burtey, S.; Riera, M.; Ribe, E.; Pennekamp, P.; Passage, E.; Rance, R.; Dworniczak, B.; Fontés, M. Overexpression of PKD2 in the mouse is associated with renal tubulopathy. Nephrol. Dial. Transplant., 2008, 23(4), 1157-1165.
[http://dx.doi.org/10.1093/ndt/gfm763] [PMID: 18048422]
[49]
McKenna, S.C.; Carpenter, J.L. Polycystic disease of the kidney and liver in the Cairn Terrier. Vet. Pathol., 1980, 17(4), 436-442.
[http://dx.doi.org/10.1177/030098588001700405] [PMID: 7385577]
[50]
McAloose, D.; Casal, M.; Patterson, D.F.; Dambach, D.M. Polycystic kidney and liver disease in two related West Highland White Terrier litters. Vet. Pathol., 1998, 35(1), 77-81.
[http://dx.doi.org/10.1177/030098589803500110] [PMID: 9545140]
[51]
Crowell, W.A.; Hubbell, J.J.; Riley, J.C. Polycystic renal disease in related cats. J. Am. Vet. Med. Assoc., 1979, 175(3), 286-288.
[PMID: 500456]
[52]
Eaton, K.A.; Biller, D.S.; DiBartola, S.P.; Radin, M.J.; Wellman, M.L. Autosomal dominant polycystic kidney disease in Persian and Persian-cross cats. Vet. Pathol., 1997, 34(2), 117-126.
[http://dx.doi.org/10.1177/030098589703400204] [PMID: 9066078]
[53]
Krotec, K.; Meyer, B.S.; Freeman, W.; Hamir, A.N. Congenital cystic disease of the liver, pancreas, and kidney in a nubian goat (Capra hircus). Vet. Pathol., 1996, 33(6), 708-710.
[http://dx.doi.org/10.1177/030098589603300612] [PMID: 8952032]
[54]
Johnstone, A.C.; Davidson, B.I.; Roe, A.R.; Eccles, M.R.; Jolly, R.D. Congenital polycystic kidney disease in lambs. N. Z. Vet. J., 2005, 53(5), 307-314.
[http://dx.doi.org/10.1080/00480169.2005.36565] [PMID: 16220122]
[55]
Stayner, C.; Poole, C.A.; McGlashan, S.R.; Pilanthananond, M.; Brauning, R.; Markie, D.; Lett, B.; Slobbe, L.; Chae, A.; Johnstone, A.C.; Jensen, C.G.; McEwan, J.C.; Dittmer, K.; Parker, K.; Wiles, A.; Blackburne, W.; Leichter, A.; Leask, M.; Pinnapureddy, A.; Jennings, M.; Horsfield, J.A.; Walker, R.J.; Eccles, M.R. An ovine hepatorenal fibrocystic model of a Meckel-like syndrome associated with dysmorphic primary cilia and TMEM67 mutations. Sci. Rep., 2017, 7(1), 1601.
[http://dx.doi.org/10.1038/s41598-017-01519-4] [PMID: 28487520]
[56]
Nagao, S.; Kugita, M.; Yoshihara, D.; Yamaguchi, T. Animal models for human polycystic kidney disease. Exp. Anim., 2012, 61(5), 477-488.
[http://dx.doi.org/10.1538/expanim.61.477] [PMID: 23095811]
[57]
Mangos, S.; Lam, P.Y.; Zhao, A.; Liu, Y.; Mudumana, S.; Vasilyev, A.; Liu, A.; Drummond, I.A. The ADPKD genes pkd1a/b and pkd2 regulate extracellular matrix formation. Dis. Model. Mech., 2010, 3(5-6), 354-365.
[http://dx.doi.org/10.1242/dmm.003194] [PMID: 20335443]
[58]
Paavola, J.; Schliffke, S.; Rossetti, S.; Kuo, I.Y.; Yuan, S.; Sun, Z.; Harris, P.C.; Torres, V.E.; Ehrlich, B.E. Polycystin-2 mutations lead to impaired calcium cycling in the heart and predispose to dilated cardiomyopathy. J. Mol. Cell. Cardiol., 2013, 58, 199-208.
[http://dx.doi.org/10.1016/j.yjmcc.2013.01.015] [PMID: 23376035]
[59]
Lu, W.; Fan, X.; Basora, N.; Babakhanlou, H.; Law, T.; Rifai, N.; Harris, P.C.; Perez-Atayde, A.R.; Rennke, H.G.; Zhou, J. Late onset of renal and hepatic cysts in Pkd1-targeted heterozygotes. Nat. Genet., 1999, 21(2), 160-161.
[http://dx.doi.org/10.1038/5944] [PMID: 9988265]
[60]
Shillingford, J.M.; Piontek, K.B.; Germino, G.G.; Weimbs, T. Rapamycin ameliorates PKD resulting from conditional inactivation of Pkd1. J. Am. Soc. Nephrol., 2010, 21(3), 489-497.
[http://dx.doi.org/10.1681/ASN.2009040421] [PMID: 20075061]
[61]
Pritchard, L.; Sloane-Stanley, J.A.; Sharpe, J.A.; Aspinwall, R.; Lu, W.; Buckle, V.; Strmecki, L.; Walker, D.; Ward, C.J.; Alpers, C.E.; Zhou, J.; Wood, W.G.; Harris, P.C. A human PKD1 transgene generates functional polycystin-1 in mice and is associated with a cystic phenotype. Hum. Mol. Genet., 2000, 9(18), 2617-2627.
[http://dx.doi.org/10.1093/hmg/9.18.2617] [PMID: 11063721]
[62]
Kurbegovic, A.; Côté, O.; Couillard, M.; Ward, C.J.; Harris, P.C.; Trudel, M. Pkd1 transgenic mice: adult model of polycystic kidney disease with extrarenal and renal phenotypes. Hum. Mol. Genet., 2010, 19(7), 1174-1189.
[http://dx.doi.org/10.1093/hmg/ddp588] [PMID: 20053665]
[63]
Happé, H.; Peters, D.J. Translational research in ADPKD: lessons from animal models. Nat. Rev. Nephrol., 2014, 10(10), 587-601.
[http://dx.doi.org/10.1038/nrneph.2014.137] [PMID: 25137562]
[64]
Helal, I. Polycystic Kidney Disease., Li, X., Ed.: Brisbane (AU), 2015.
[65]
Grantham, J.J.; Torres, V.E. The importance of total kidney volume in evaluating progression of polycystic kidney disease. Nat. Rev. Nephrol., 2016, 12(11), 667-677.
[http://dx.doi.org/10.1038/nrneph.2016.135] [PMID: 27694979]
[66]
Grantham, J.J.; Torres, V.E.; Chapman, A.B.; Guay-Woodford, L.M.; Bae, K.T.; King, B.F., Jr; Wetzel, L.H.; Baumgarten, D.A.; Kenney, P.J.; Harris, P.C.; Klahr, S.; Bennett, W.M.; Hirschman, G.N.; Meyers, C.M.; Zhang, X.; Zhu, F.; Miller, J.P.; Investigators, C. Volume progression in polycystic kidney disease. N. Engl. J. Med., 2006, 354(20), 2122-2130.
[http://dx.doi.org/10.1056/NEJMoa054341] [PMID: 16707749]
[67]
Schrier, R.W. Blood pressure in early autosomal dominant polycystic kidney disease. N. Engl. J. Med., 2015, 372(10), 976-977.
[PMID: 25738676]
[68]
Torres, V.E.; Abebe, K.Z.; Chapman, A.B.; Schrier, R.W.; Braun, W.E.; Steinman, T.I.; Winklhofer, F.T.; Brosnahan, G.; Czarnecki, P.G.; Hogan, M.C.; Miskulin, D.C.; Rahbari-Oskoui, F.F.; Grantham, J.J.; Harris, P.C.; Flessner, M.F.; Moore, C.G.; Perrone, R.D. Angiotensin blockade in late autosomal dominant polycystic kidney disease. N. Engl. J. Med., 2014, 371(24), 2267-2276.
[http://dx.doi.org/10.1056/NEJMoa1402686] [PMID: 25399731]
[69]
Huber, T.B.; Walz, G.; Kuehn, E.W. mTOR and rapamycin in the kidney: signaling and therapeutic implications beyond immunosuppression. Kidney Int., 2011, 79(5), 502-511.
[http://dx.doi.org/10.1038/ki.2010.457] [PMID: 21085109]
[70]
Walz, G.; Budde, K.; Mannaa, M.; Nürnberger, J.; Wanner, C.; Sommerer, C.; Kunzendorf, U.; Banas, B.; Hörl, W.H.; Obermüller, N.; Arns, W.; Pavenstädt, H.; Gaedeke, J.; Büchert, M.; May, C.; Gschaidmeier, H.; Kramer, S.; Eckardt, K.U. Everolimus in patients with autosomal dominant polycystic kidney disease. N. Engl. J. Med., 2010, 363(9), 830-840.
[http://dx.doi.org/10.1056/NEJMoa1003491] [PMID: 20581392]
[71]
Grantham, J.J.; Bennett, W.M.; Perrone, R.D. mTOR inhibitors and autosomal dominant polycystic kidney disease. N. Engl. J. Med., 2011, 364(3), 286-287.
[http://dx.doi.org/10.1056/NEJMc1010845] [PMID: 21247328]
[72]
Serra, A.L.; Poster, D.; Kistler, A.D.; Krauer, F.; Raina, S.; Young, J.; Rentsch, K.M.; Spanaus, K.S.; Senn, O.; Kristanto, P.; Scheffel, H.; Weishaupt, D.; Wüthrich, R.P. Sirolimus and kidney growth in autosomal dominant polycystic kidney disease. N. Engl. J. Med., 2010, 363(9), 820-829.
[http://dx.doi.org/10.1056/NEJMoa0907419] [PMID: 20581391]
[73]
Myint, T.M.; Rangan, G.K.; Webster, A.C. Treatments to slow progression of autosomal dominant polycystic kidney disease: systematic review and meta-analysis of randomized trials. Nephrology (Carlton), 2014, 19(4), 217-226.
[http://dx.doi.org/10.1111/nep.12211] [PMID: 24460701]
[74]
Gattone, V.H., II; Wang, X.; Harris, P.C.; Torres, V.E. Inhibition of renal cystic disease development and progression by a vasopressin V2 receptor antagonist. Nat. Med., 2003, 9(10), 1323-1326.
[http://dx.doi.org/10.1038/nm935] [PMID: 14502283]
[75]
Torres, V.E.; Wang, X.; Qian, Q.; Somlo, S.; Harris, P.C.; Gattone, V.H., II Effective treatment of an orthologous model of autosomal dominant polycystic kidney disease. Nat. Med., 2004, 10(4), 363-364.
[http://dx.doi.org/10.1038/nm1004] [PMID: 14991049]
[76]
Wang, X.; Gattone, V., II; Harris, P.C.; Torres, V.E. Effectiveness of vasopressin V2 receptor antagonists OPC-31260 and OPC-41061 on polycystic kidney disease development in the PCK rat. J. Am. Soc. Nephrol., 2005, 16(4), 846-851.
[http://dx.doi.org/10.1681/ASN.2004121090] [PMID: 15728778]
[77]
Irazabal, M.V.; Torres, V.E.; Hogan, M.C.; Glockner, J.; King, B.F.; Ofstie, T.G.; Krasa, H.B.; Ouyang, J.; Czerwiec, F.S. Short-term effects of tolvaptan on renal function and volume in patients with autosomal dominant polycystic kidney disease. Kidney Int., 2011, 80(3), 295-301.
[http://dx.doi.org/10.1038/ki.2011.119] [PMID: 21544064]
[78]
Torres, V.E.; Chapman, A.B.; Devuyst, O.; Gansevoort, R.T.; Grantham, J.J.; Higashihara, E.; Perrone, R.D.; Krasa, H.B.; Ouyang, J.; Czerwiec, F.S.; Investigators, T.T. Tolvaptan in patients with autosomal dominant polycystic kidney disease. N. Engl. J. Med., 2012, 367(25), 2407-2418.
[http://dx.doi.org/10.1056/NEJMoa1205511] [PMID: 23121377]
[79]
Torres, V.E.; Devuyst, O.; Chapman, A.B.; Gansevoort, R.T.; Perrone, R.D.; Ouyang, J.; Blais, J.D.; Czerwiec, F.S.; Sergeyeva, O.; Investigators, R.T. Rationale and design of a clinical trial investigating tolvaptan safety and efficacy in autosomal dominant polycystic kidney disease. Am. J. Nephrol., 2017, 45(3), 257-266.
[http://dx.doi.org/10.1159/000456087] [PMID: 28166521]
[80]
Otsuka, otsuka announces results of Phase 3 data on tolvaptan under development for ADPKD in U.S. Available at https://www.otsuka-us.com/discover/articles-10292017.
[81]
Torres, V.E.; Chapman, A.B.; Devuyst, O.; Gansevoort, R.T. Perrone, Koch, G.; R.D.; Ouyang, J.; McQuade, R.D.; Blais, J.D.; Czerwiec, F.S.; Sergeyeva, O.; Investigators, R.T. Tolvaptan in later-stage autosomal dominant polycystic kidney disease. N. Engl. J. Med., 2017, 377(20), 1930-1942.
[82]
Grantham, J.J. Therapy for polycystic kidney disease? It’s water, stupid! J. Am. Soc. Nephrol., 2008, 19(1), 1-7.
[http://dx.doi.org/10.1681/ASN.2007101100] [PMID: 18032792]
[83]
Nagao, S.; Nishii, K.; Katsuyama, M.; Kurahashi, H.; Marunouchi, T.; Takahashi, H.; Wallace, D.P. Increased water intake decreases progression of polycystic kidney disease in the PCK rat. J. Am. Soc. Nephrol., 2006, 17(8), 2220-2227.
[http://dx.doi.org/10.1681/ASN.2006030251] [PMID: 16807403]
[84]
El-Damanawi, R.; Harris, T.; Sandford, R.N.; Karet Frankl, F.E.; Hiemstra, T.F. Patient survey of current water Intake practices in autosomal dominant polycystic kidney disease: the SIPs survey. Clin. Kidney J., 2017, 10(3), 305-309.
[http://dx.doi.org/10.1093/ckj/sfw153] [PMID: 28616208]
[85]
Chang, M.Y.; Ong, A.C. New treatments for autosomal dominant polycystic kidney disease. Br. J. Clin. Pharmacol., 2013, 76(4), 524-535.
[PMID: 23594398]
[86]
Caroli, A.; Perico, N.; Perna, A.; Antiga, L.; Brambilla, P.; Pisani, A.; Visciano, B.; Imbriaco, M.; Messa, P.; Cerutti, R.; Dugo, M.; Cancian, L.; Buongiorno, E.; De Pascalis, A.; Gaspari, F.; Carrara, F.; Rubis, N.; Prandini, S.; Remuzzi, A.; Remuzzi, G.; Ruggenenti, P. Effect of longacting somatostatin analogue on kidney and cyst growth in autosomal dominant polycystic kidney disease (ALADIN): a randomised, placebo-controlled, multicentre trial. Lancet, 2013, 382(9903), 1485-1495.
[http://dx.doi.org/10.1016/S0140-6736(13)61407-5] [PMID: 23972263]
[87]
Qian, Q.; Wang, H.Y. ALADIN: wish granted in inherited polycystic kidney disease? Lancet, 2013, 382(9903), 1469-1471.
[http://dx.doi.org/10.1016/S0140-6736(13)61541-X] [PMID: 23972262]
[88]
Pisani, A.; Sabbatini, M.; Imbriaco, M.; Riccio, E.; Rubis, N.; Prinster, A.; Perna, A.; Liuzzi, R.; Spinelli, L.; Santangelo, M.; Remuzzi, G.; Ruggenenti, P.; Group, A.S. Longterm effects of octreotide on liver volume in patients with polycystic kidney and liver disease. Clin. Gastroenterol Hepatol, 2016, 14(7), 1022-1030 e1024.
[89]
Meijer, E.; Drenth, J.P.; d’Agnolo, H.; Casteleijn, N.F.; de Fijter, J.W.; Gevers, T.J.; Kappert, P.; Peters, D.J.; Salih, M.; Soonawala, D.; Spithoven, E.M.; Torres, V.E.; Visser, F.W.; Wetzels, J.F.; Zietse, R.; Gansevoort, R.T.; Consortium, D. Rationale and design of the DIPAK 1 study: a randomized controlled clinical trial assessing the efficacy of lanreotide to Halt disease progression in autosomal dominant polycystic kidney disease. Am. J. Kidney Dis., 2014, 63(3), 446-455.
[http://dx.doi.org/10.1053/j.ajkd.2013.10.011] [PMID: 24342522]
[90]
Ecder, T. Statins in the treatment of autosomal dominant polycystic kidney disease. Nephrol. Dial. Transplant., 2016, 31(8), 1194-1196.
[http://dx.doi.org/10.1093/ndt/gfv449] [PMID: 26908774]
[91]
Zafar, I.; Tao, Y.; Falk, S.; McFann, K.; Schrier, R.W.; Edelstein, C.L. Effect of statin and angiotensin-converting enzyme inhibition on structural and hemodynamic alterations in autosomal dominant polycystic kidney disease model. Am. J. Physiol. Renal Physiol., 2007, 293(3), F854-F859.
[http://dx.doi.org/10.1152/ajprenal.00059.2007] [PMID: 17581927]
[92]
Zand, L.; Torres, V.E.; Larson, T.S.; King, B.F.; Sethi, S.; Bergstralh, E.J.; Angioi, A.; Fervenza, F.C. Renal hemodynamic effects of the HMG-CoA reductase inhibitors in autosomal dominant polycystic kidney disease. Nephrol. Dial. Transplant., 2016, 31(8), 1290-1295.
[http://dx.doi.org/10.1093/ndt/gfv394] [PMID: 26614268]
[93]
Fassett, R.G.; Coombes, J.S.; Packham, D.; Fairley, K.F.; Kincaid-Smith, P. Effect of pravastatin on kidney function and urinary protein excretion in autosomal dominant polycystic kidney disease. Scand. J. Urol. Nephrol., 2010, 44(1), 56-61.
[http://dx.doi.org/10.3109/00365590903359908] [PMID: 20034362]
[94]
Cadnapaphornchai, M.A.; George, D.M.; McFann, K.; Wang, W.; Gitomer, B.; Strain, J.D.; Schrier, R.W. Effect of pravastatin on total kidney volume, left ventricular mass index, and microalbuminuria in pediatric autosomal dominant polycystic kidney disease. Clin. J. Am. Soc. Nephrol., 2014, 9(5), 889-896.
[http://dx.doi.org/10.2215/CJN.08350813] [PMID: 24721893]
[95]
Du, J.; Wilson, P.D. Abnormal polarization of EGF receptors and autocrine stimulation of cyst epithelial growth in human ADPKD. Am. J. Physiol., 1995, 269(2 Pt 1), C487-C495.
[http://dx.doi.org/10.1152/ajpcell.1995.269.2.C487] [PMID: 7653531]
[96]
Patil, A.; Sweeney, W.E., Jr; Avner, E.D.; Pan, C. Polycystic Kidney Disease. Li, X., Ed.: Brisbane (AU),, 2015.
[97]
Sweeney, W.E., Jr; von Vigier, R.O.; Frost, P.; Avner, E.D. Src inhibition ameliorates polycystic kidney disease. J. Am. Soc. Nephrol., 2008, 19(7), 1331-1341.
[http://dx.doi.org/10.1681/ASN.2007060665] [PMID: 18385429]
[98]
Tesar, V.; Ciechanowski, K.; Pei, Y.; Barash, I.; Shannon, M.; Li, R.; Williams, J.H.; Levisetti, M.; Arkin, S.; Serra, A. Bosutinib versus placebo for autosomal dominant polycystic kidney disease. J. Am. Soc. Nephrol., 2017, 28(11), 3404-3413.
[http://dx.doi.org/10.1681/ASN.2016111232] [PMID: 28838955]
[99]
Sweeney, W.E.; Frost, P.; Avner, E.D. Tesevatinib ameliorates progression of polycystic kidney disease in rodent models of autosomal recessive polycystic kidney disease. World J. Nephrol., 2017, 6(4), 188-200.
[http://dx.doi.org/10.5527/wjn.v6.i4.188] [PMID: 28729967]
[100]
Yu, A.S.L.; El-Ters, M.; Winklhofer, F.T. In Polycystic Kidney Disease, Li, X., Ed.: Brisbane (AU). 2015.
[101]
Yu, A.S.; El-Ters, M.; Winklhofer, F.T. Polycystic Kidney Disease., Li, X., Ed.: Brisbane (AU),, 2015.
[102]
Stayner, C.; Shields, J.; Slobbe, L.; Shillingford, J.M.; Weimbs, T.; Eccles, M.R. Rapamycin-mediated suppression of renal cyst expansion in del34 Pkd1-/- mutant mouse embryos: an investigation of the feasibility of renal cyst prevention in the foetus. Nephrology (Carlton), 2012, 17(8), 739-747.
[http://dx.doi.org/10.1111/j.1440-1797.2012.01639.x] [PMID: 22725947]
[103]
Wahl, P.R.; Serra, A.L.; Le Hir, M.; Molle, K.D.; Hall, M.N.; Wüthrich, R.P. Inhibition of mTOR with sirolimus slows disease progression in Han:SPRD rats with autosomal dominant polycystic kidney disease (ADPKD). Nephrol. Dial. Transplant., 2006, 21(3), 598-604.
[http://dx.doi.org/10.1093/ndt/gfi181] [PMID: 16221708]
[104]
O’Brien, L.L.; Guo, Q.; Lee, Y.; Tran, T.; Benazet, J.D.; Whitney, P.H.; Valouev, A.; McMahon, A.P. Differential regulation of mouse and human nephron progenitors by the Six family of transcriptional regulators. Development, 2016, 143(4), 595-608.
[http://dx.doi.org/10.1242/dev.127175] [PMID: 26884396]
[105]
Piontek, K.; Menezes, L.F.; Garcia-Gonzalez, M.A.; Huso, D.L.; Germino, G.G. A critical developmental switch defines the kinetics of kidney cyst formation after loss of Pkd1. Nat. Med., 2007, 13(12), 1490-1495.
[http://dx.doi.org/10.1038/nm1675] [PMID: 17965720]
[106]
Canaud, G.; Knebelmann, B.; Harris, P.C.; Vrtovsnik, F.; Correas, J.M.; Pallet, N.; Heyer, C.M.; Letavernier, E.; Bienaimé, F.; Thervet, E.; Martinez, F.; Terzi, F.; Legendre, C. Therapeutic mTOR inhibition in autosomal dominant polycystic kidney disease: What is the appropriate serum level? Am. J. Transplant., 2010, 10(7), 1701-1706.
[http://dx.doi.org/10.1111/j.1600-6143.2010.03152.x] [PMID: 20642692]
[107]
Guler, S.; Cimen, S.; Hurton, S.; Molinari, M. Polycystic Kidney Disease., Li, X., Ed.: Brisbane (AU),, 2015.
[108]
Zhou, P.; Sun, X.; Zhang, Z. Kidney-targeted drug delivery systems. Acta Pharm. Sin. B, 2014, 4(1), 37-42.
[http://dx.doi.org/10.1016/j.apsb.2013.12.005] [PMID: 26579362]
[109]
Deutscher, S.L.; Figueroa, S.D.; Kumar, S.R. Tumor targeting and SPECT imaging properties of an (111)In-labeled galectin-3 binding peptide in prostate carcinoma. Nucl. Med. Biol., 2009, 36(2), 137-146.
[http://dx.doi.org/10.1016/j.nucmedbio.2008.10.015] [PMID: 19217525]
[110]
Wang, S.; Luo, J.; Lantrip, D.A.; Waters, D.J.; Mathias, C.J.; Green, M.A.; Fuchs, P.L.; Low, P.S. Design and synthesis of [111In]DTPA-folate for use as a tumor-targeted radiopharmaceutical. Bioconjug. Chem., 1997, 8(5), 673-679.
[http://dx.doi.org/10.1021/bc9701297] [PMID: 9327130]
[111]
Rangasamy, S.B.; Corbett, G.T.; Roy, A.; Modi, K.K.; Bennett, D.A.; Mufson, E.J.; Ghosh, S.; Pahan, K. Intranasal delivery of NEMO-binding domain peptide prevents memory loss in a mouse model of Alzheimer’s disease. J. Alzheimers Dis., 2015, 47(2), 385-402.
[http://dx.doi.org/10.3233/JAD-150040] [PMID: 26401561]
[112]
Hua, S.; Marks, E.; Schneider, J.J.; Keely, S. Advances in oral nano-delivery systems for colon targeted drug delivery in inflammatory bowel disease: selective targeting to diseased versus healthy tissue. Nanomedicine (Lond.), 2015, 11(5), 1117-1132.
[http://dx.doi.org/10.1016/j.nano.2015.02.018] [PMID: 25784453]
[113]
Suzuki, K.; Susaki, H.; Okuno, S.; Sugiyama, Y. Renal drug targeting using a vector “alkylglycoside”. J. Pharmacol. Exp. Ther., 1999, 288(1), 57-64.
[PMID: 9862753]
[114]
Lin, Y.; Sun, X.; Gong, T.; Zhang, Z.R. Prednisolone succinate-glucosamine conjugate: Synthesis, characterization and in vitro cellular uptake by kidney cell lines. Chin. Chem. Lett., 2012, 23(1), 25-28.
[http://dx.doi.org/10.1016/j.cclet.2011.07.023]
[115]
Liang, Z.; Gong, T.; Sun, X.; Tang, J.Z.; Zhang, Z.R. Chitosan oligomers as drug carriers for renal delivery of zidovudine. Carbohydr. Polym., 2012, 87(3), 2284-2290.
[http://dx.doi.org/10.1016/j.carbpol.2011.10.060]
[116]
Su, M.; He, Q.; Zhang, Z.R.; Hu, B.; Liu, S.W. [Kidney-targeting characteristics of N-acetyl-L-glutamic prednisolone prodrug Yao Xue Xue Bao, 2003, 38(8), 627-630.
[PMID: 14628458]
[117]
Manil, L.; Davin, J.C.; Duchenne, C.; Kubiak, C.; Foidart, J.; Couvreur, P.; Mahieu, P. Uptake of nanoparticles by rat glomerular mesangial cells in vivo and in vitro. Pharm. Res., 1994, 11(8), 1160-1165.
[http://dx.doi.org/10.1023/A:1018993000633] [PMID: 7971718]
[118]
Choi, C.H.; Zuckerman, J.E.; Webster, P.; Davis, M.E. Targeting kidney mesangium by nanoparticles of defined size. Proc. Natl. Acad. Sci. USA, 2011, 108(16), 6656-6661.
[http://dx.doi.org/10.1073/pnas.1103573108] [PMID: 21464325]
[119]
Singh, M.; Ghose, T.; Faulkner, G.; Kralovec, J.; Mezei, M. Targeting of methotrexate-containing liposomes with a monoclonal antibody against human renal cancer. Cancer Res., 1989, 49(14), 3976-3984.
[PMID: 2660984]
[120]
Liang, B.; Shahbaz, M.; Wang, Y.; Gao, H.; Fang, R.; Niu, Z.; Liu, S.; Wang, B.; Sun, Q.; Niu, W.; Liu, E.; Wang, J.; Niu, J. Integrinβ6-targeted immunoliposomes mediate tumor-specific drug delivery and enhance therapeutic efficacy in colon carcinoma. Clin. Cancer Res., 2015, 21(5), 1183-1195.
[http://dx.doi.org/10.1158/1078-0432.CCR-14-1194] [PMID: 25549721]
[121]
Franssen, E.J.; Moolenaar, F.; de Zeeuw, D.; Meijer, D.K. Low molecular weight proteins as carriers for renal drug targeting: naproxen coupled to lysozyme via the spacer L-lactic acid. Pharm. Res., 1993, 10(7), 963-969.
[http://dx.doi.org/10.1023/A:1018946219057] [PMID: 8378258]
[122]
Kok, R.J.; Grijpstra, F.; Walthuis, R.B.; Moolenaar, F.; de Zeeuw, D.; Meijer, D.K. Specific delivery of captopril to the kidney with the prodrug captopril-lysozyme. J. Pharmacol. Exp. Ther., 1999, 288(1), 281-285.
[PMID: 9862782]
[123]
Zhang, Z.; Zheng, Q.; Han, J.; Gao, G.; Liu, J.; Gong, T.; Gu, Z.; Huang, Y.; Sun, X.; He, Q. The targeting of 14-succinate triptolide-lysozyme conjugate to proximal renal tubular epithelial cells. Biomaterials, 2009, 30(7), 1372-1381.
[http://dx.doi.org/10.1016/j.biomaterials.2008.11.035] [PMID: 19100618]
[124]
Dolman, M.E.; Harmsen, S.; Pieters, E.H.; Sparidans, R.W.; Lacombe, M.; Szokol, B.; Orfi, L.; Kéri, G.; Storm, G.; Hennink, W.E.; Kok, R.J. Targeting of a platinum-bound sunitinib analog to renal proximal tubular cells. Int. J. Nanomedicine, 2012, 7, 417-433.
[PMID: 22334775]
[125]
Yuan, Z.X.; Li, J.J.; Zhu, D.; Sun, X.; Gong, T.; Zhang, Z.R. Enhanced accumulation of low-molecular-weight chitosan in kidneys: a study on the influence of N-acetylation of chitosan on the renal targeting. J. Drug Target., 2011, 19(7), 540-551.
[http://dx.doi.org/10.3109/1061186X.2010.521158] [PMID: 21767121]
[126]
Yamamoto, Y.; Tsutsumi, Y.; Yoshioka, Y.; Kamada, H.; Sato-Kamada, K.; Okamoto, T.; Mukai, Y.; Shibata, H.; Nakagawa, S.; Mayumi, T. Poly(vinylpyrrolidone-co-dimethyl maleic acid) as a novel renal targeting carrier. J. Control. Release, 2004, 95(2), 229-237.
[http://dx.doi.org/10.1016/j.jconrel.2003.11.017] [PMID: 14980771]
[127]
Fawell, S.; Seery, J.; Daikh, Y.; Moore, C.; Chen, L.L.; Pepinsky, B.; Barsoum, J. Tat-mediated delivery of heterologous proteins into cells. Proc. Natl. Acad. Sci. USA, 1994, 91(2), 664-668.
[http://dx.doi.org/10.1073/pnas.91.2.664] [PMID: 8290579]
[128]
Morris, M.C.; Depollier, J.; Mery, J.; Heitz, F.; Divita, G. A peptide carrier for the delivery of biologically active proteins into mammalian cells. Nat. Biotechnol., 2001, 19(12), 1173-1176.
[http://dx.doi.org/10.1038/nbt1201-1173] [PMID: 11731788]
[129]
Kang, M.J.; Park, S.H.; Kang, M.H.; Park, M.J.; Choi, Y.W. Folic acid-tethered Pep-1 peptide-conjugated liposomal nanocarrier for enhanced intracellular drug delivery to cancer cells: conformational characterization and in vitro cellular uptake evaluation. Int. J. Nanomedicine, 2013, 8, 1155-1165.
[PMID: 23515421]
[130]
Pan, L.; Liu, J.; He, Q.; Wang, L.; Shi, J. Overcoming multidrug resistance of cancer cells by direct intranuclear drug delivery using TAT-conjugated mesoporous silica nanoparticles. Biomaterials, 2013, 34(11), 2719-2730.
[http://dx.doi.org/10.1016/j.biomaterials.2012.12.040] [PMID: 23337327]
[131]
Patel, A.; Patel, M.; Yang, X.; Mitra, A.K. Recent advances in protein and Peptide drug delivery: a special emphasis on polymeric nanoparticles. Protein Pept. Lett., 2014, 21(11), 1102-1120.
[http://dx.doi.org/10.2174/0929866521666140807114240] [PMID: 25106908]
[132]
Zou, J.; Glinsky, V.V.; Landon, L.A.; Matthews, L.; Deutscher, S.L. Peptides specific to the galectin-3 carbohydrate recognition domain inhibit metastasis-associated cancer cell adhesion. Carcinogenesis, 2005, 26(2), 309-318.
[http://dx.doi.org/10.1093/carcin/bgh329] [PMID: 15528216]
[133]
Geng, Q.; Sun, X.; Gong, T.; Zhang, Z.R. Peptide-drug conjugate linked via a disulfide bond for kidney targeted drug delivery. Bioconjug. Chem., 2012, 23(6), 1200-1210.
[http://dx.doi.org/10.1021/bc300020f] [PMID: 22663297]
[134]
Hogan, M.C.; Masyuk, T.V.; Page, L.; Holmes, D.R., III; Li, X.; Bergstralh, E.J.; Irazabal, M.V.; Kim, B.; King, B.F.; Glockner, J.F.; Larusso, N.F.; Torres, V.E. Somatostatin analog therapy for severe polycystic liver disease: results after 2 years. Nephrol. Dial. Transplant., 2012, 27(9), 3532-3539.
[http://dx.doi.org/10.1093/ndt/gfs152] [PMID: 22773240]
[135]
Fosgerau, K.; Hoffmann, T. Peptide therapeutics: current status and future directions. Drug Discov. Today, 2015, 20(1), 122-128.
[http://dx.doi.org/10.1016/j.drudis.2014.10.003] [PMID: 25450771]
[136]
Möller, G.P.; Müller, S.; Wolfstädter, B.T.; Wolfrum, S.; Schepmann, D.; Wünsch, B.; Carreira, E.M. Oxetanyl amino acids for peptidomimetics. Org. Lett., 2017, 19(10), 2510-2513.
[http://dx.doi.org/10.1021/acs.orglett.7b00745] [PMID: 28459595]
[137]
Zeier, M.; Jones, E.; Ritz, E. Autosomal dominant polycystic kidney disease--the patient on renal replacement therapy. Nephrol. Dial. Transplant., 1996, 11(Suppl. 6), 18-20.
[http://dx.doi.org/10.1093/ndt/11.supp6.18] [PMID: 9044322]
[138]
Belibi, F.; Zafar, I.; Ravichandran, K.; Segvic, A.B.; Jani, A.; Ljubanovic, D.G.; Edelstein, C.L. Hypoxia-inducible factor-1α (HIF-1α) and autophagy in polycystic kidney disease (PKD). Am. J. Physiol. Renal Physiol., 2011, 300(5), F1235-F1243.
[http://dx.doi.org/10.1152/ajprenal.00348.2010] [PMID: 21270095]
[139]
Hunter, F.W.; Wouters, B.G.; Wilson, W.R. Hypoxia-activated prodrugs: paths forward in the era of personalised medicine. Br. J. Cancer, 2016, 114(10), 1071-1077.
[http://dx.doi.org/10.1038/bjc.2016.79] [PMID: 27070712]
[140]
Woo, Y.M.; Bae, J.B.; Oh, Y.H.; Lee, Y.G.; Lee, M.J.; Park, E.Y.; Choi, J.K.; Lee, S.; Shin, Y.; Lyu, J.; Jung, H.Y.; Lee, Y.S.; Hwang, Y.H.; Kim, Y.J.; Park, J.H. Genome-wide methylation profiling of ADPKD identified epigenetically regulated genes associated with renal cyst development. Hum. Genet., 2014, 133(3), 281-297.
[http://dx.doi.org/10.1007/s00439-013-1378-0] [PMID: 24129831]
[141]
Woo, Y.M.; Shin, Y.; Hwang, J.A.; Hwang, Y.H.; Lee, S.; Park, E.Y.; Kong, H.K.; Park, H.C.; Lee, Y.S.; Park, J.H. Epigenetic silencing of the MUPCDH gene as a possible prognostic biomarker for cyst growth in ADPKD. Sci. Rep., 2015, 5, 15238.
[http://dx.doi.org/10.1038/srep15238] [PMID: 26463459]
[142]
Hajarnis, S.; Lakhia, R.; Patel, V. Polycystic Kidney Disease., Li, X., Ed.: Brisbane (AU), 2015.
[143]
Cao, Y.; Semanchik, N.; Lee, S.H.; Somlo, S.; Barbano, P.E.; Coifman, R.; Sun, Z. Chemical modifier screen identifies HDAC inhibitors as suppressors of PKD models. Proc. Natl. Acad. Sci. USA, 2009, 106(51), 21819-21824.
[http://dx.doi.org/10.1073/pnas.0911987106] [PMID: 19966229]
[144]
Xia, S.; Li, X.; Johnson, T.; Seidel, C.; Wallace, D.P.; Li, R. Polycystin-dependent fluid flow sensing targets histone deacetylase 5 to prevent the development of renal cysts. Development, 2010, 137(7), 1075-1084.
[http://dx.doi.org/10.1242/dev.049437] [PMID: 20181743]
[145]
Fan, L.X.; Li, X.; Magenheimer, B.; Calvet, J.P.; Li, X. Inhibition of histone deacetylases targets the transcription regulator Id2 to attenuate cystic epithelial cell proliferation. Kidney Int., 2012, 81(1), 76-85.
[http://dx.doi.org/10.1038/ki.2011.296] [PMID: 21900881]
[146]
Qi, Y.; Wang, D.; Wang, D.; Jin, T.; Yang, L.; Wu, H.; Li, Y.; Zhao, J.; Du, F.; Song, M.; Wang, R. HEDD: the human epigenetic drug database. Database (Oxford), 2016.
[http://dx.doi.org/10.1093/database/baw159]
[147]
Jones, P.A.; Issa, J.P.; Baylin, S. Targeting the cancer epigenome for therapy. Nat. Rev. Genet., 2016, 17(10), 630-641.
[http://dx.doi.org/10.1038/nrg.2016.93] [PMID: 27629931]
[148]
Yheskel, M.; Patel, V. Therapeutic microRNAs in polycystic kidney disease. Curr. Opin. Nephrol. Hypertens., 2017, 26(4), 282-289.
[http://dx.doi.org/10.1097/MNH.0000000000000333] [PMID: 28399020]
[149]
Chapman, A.B.; Stepniakowski, K.; Rahbari-Oskoui, F. Hypertension in autosomal dominant polycystic kidney disease. Adv. Chronic Kidney Dis., 2010, 17(2), 153-163.
[http://dx.doi.org/10.1053/j.ackd.2010.01.001] [PMID: 20219618]
[150]
Schrier, R.W.; Johnson, A.M.; McFann, K.; Chapman, A.B. The role of parental hypertension in the frequency and age of diagnosis of hypertension in offspring with autosomal-dominant polycystic kidney disease. Kidney Int., 2003, 64(5), 1792-1799.
[http://dx.doi.org/10.1046/j.1523-1755.2003.00264.x] [PMID: 14531813]
[151]
Zhang, Y.; Moran, A.E. Trends in the prevalence, awareness, treatment, and control of hypertension among young adults in the United States, 1999 to 2014. Hypertension, 2017, 70(4), 736-742.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.117.09801] [PMID: 28847890]
[152]
Seeman, T.; Dusek, J.; Vondrichová, H.; Kyncl, M.; John, U.; Misselwitz, J.; Janda, J. Ambulatory blood pressure correlates with renal volume and number of renal cysts in children with autosomal dominant polycystic kidney disease. Blood Press. Monit., 2003, 8(3), 107-110.
[http://dx.doi.org/10.1097/00126097-200306000-00003] [PMID: 12900587]
[153]
Wühl, E.; Schaefer, F. Therapeutic strategies to slow chronic kidney disease progression. Pediatr. Nephrol., 2008, 23(5), 705-716.
[http://dx.doi.org/10.1007/s00467-008-0789-y] [PMID: 18335252]
[154]
de Miranda Henriques, M.S.; de Morais Villar, E.J. Polycystic Kidney Disease., Li, X., Ed.: Brisbane (AU), 2015.
[155]
Bae, K.T.; Zhu, F.; Chapman, A.B.; Torres, V.E.; Grantham, J.J.; Guay-Woodford, L.M.; Baumgarten, D.A.; King, B.F., Jr; Wetzel, L.H.; Kenney, P.J.; Brummer, M.E.; Bennett, W.M.; Klahr, S.; Meyers, C.M.; Zhang, X.; Thompson, P.A.; Miller, J.P. Magnetic resonance imaging evaluation of hepatic cysts in early autosomal-dominant polycystic kidney disease: the Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease cohort. Clin. J. Am. Soc. Nephrol., 2006, 1(1), 64-69.
[http://dx.doi.org/10.2215/CJN.00080605] [PMID: 17699192]
[156]
Chandok, N. Polycystic liver disease: a clinical review. Ann. Hepatol., 2012, 11(6), 819-826.
[PMID: 23109444]
[157]
Ruggenenti, P.; Remuzzi, A.; Ondei, P.; Fasolini, G.; Antiga, L.; Ene-Iordache, B.; Remuzzi, G.; Epstein, F.H. Safety and efficacy of long-acting somatostatin treatment in autosomal-dominant polycystic kidney disease. Kidney Int., 2005, 68(1), 206-216.
[http://dx.doi.org/10.1111/j.1523-1755.2005.00395.x] [PMID: 15954910]
[158]
Ong, A.C. Screening for intracranial aneurysms in ADPKD. BMJ, 2009, 339, b3763.
[http://dx.doi.org/10.1136/bmj.b3763] [PMID: 19770180]
[159]
Pirson, Y.; Chauveau, D.; Torres, V. Management of cerebral aneurysms in autosomal dominant polycystic kidney disease. J. Am. Soc. Nephrol., 2002, 13(1), 269-276.
[PMID: 11752048]
[160]
Sung, P.H.; Yang, Y.H.; Chiang, H.J.; Chiang, J.Y.; Chen, C.J.; Liu, C.T.; Yu, C.M.; Yip, H.K. Risk of aortic aneurysm and dissection in patients with autosomal-dominant polycystic kidney disease: a nationwide population-based cohort study. Oncotarget, 2017, 8(34), 57594-57604.
[http://dx.doi.org/10.18632/oncotarget.16338] [PMID: 28915698]
[161]
Aguiari, G.; Catizone, L.; Del Senno, L. Multidrug therapy for polycystic kidney disease: a review and perspective. Am. J. Nephrol., 2013, 37(2), 175-182.
[http://dx.doi.org/10.1159/000346812] [PMID: 23428809]
[162]
Hopp, K.; Hommerding, C.J.; Wang, X.; Ye, H.; Harris, P.C.; Torres, V.E. Tolvaptan plus pasireotide shows enhanced efficacy in a PKD1 model. J. Am. Soc. Nephrol., 2015, 26(1), 39-47.
[http://dx.doi.org/10.1681/ASN.2013121312] [PMID: 24994926]
[163]
Zhu, P.; Sieben, C.J.; Xu, X.; Harris, P.C.; Lin, X. Autophagy activators suppress cystogenesis in an autosomal dominant polycystic kidney disease model. Hum. Mol. Genet., 2017, 26(1), 158-172.
[PMID: 28007903]
[164]
Rysz, J.; Gluba-Brzózka, A.; Franczyk, B.; Banach, M.; Bartnicki, P. Combination drug versus monotherapy for the treatment of autosomal dominant polycystic kidney disease. Expert Opin. Pharmacother., 2016, 17(15), 2049-2056.
[http://dx.doi.org/10.1080/14656566.2016.1232394] [PMID: 27650472]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 26
ISSUE: 17
Year: 2019
Page: [3081 - 3102]
Pages: 22
DOI: 10.2174/0929867325666180508095654
Price: $58

Article Metrics

PDF: 50
HTML: 2