Modern approaches to conservative therapy of polycystic kidney disease


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Abstract

Polycystic kidney disease (PKD) is a genetically determined pathological process associated with the formation and growth of cysts originating from the epithelial cells of the tubules and/or collecting tubes. PBP is represented by two main types - autosomal dominant (ADPKD) and autosomal recessive PKD (ARPKD), which are different diseases. The main causes of ADPKD are mutations of the PKD1 and PKD2 genes, which encode the formation of polycystin-1 and polycystin-2 proteins. ARPKD-linked mutation in the gene PKHD1, leads to total absence or defective synthesis of receptor protein primary cilia - fibrocystin. There are relationships between the structural and functional defects in the primary cilia and PBP. Mechanisms of cysts formation and growth include a) mutations of polycystines genes located on the cilia; b) increased activity of renal intracellular cAMP; c) vasopressin V2 receptors activation; d) violation of the tubular epithelium polarity (translocation of Na,K-ATPasa from basolateral to apical membrane); e) increased mTOR activity in epithelial cells lining renal cyst. The most promising directions of ADPKD therapy are blockade of vasopressin V2 receptors activation, inhibition of mTOR signaling pathways and reduction of intracellular cAMP level. The review presents clinical studies that assessed the effectiveness of named drugs in ADPKD.

About the authors

T. E Rudenko

Sechenov First Moscow State Medical University (Sechenov University)

Email: atatianaer@yandex.ru
к.м.н., ассистент каф. внутренних, профессиональных болезней и ревматологии медико-профилактического факультета; тел.: +7(499)246-61-76; e-mail: atatianaer@yandex.ru; ORCID: 0000-0002-1296-4494 Moscow, Russia

I. N Bobkova

Sechenov First Moscow State Medical University (Sechenov University)

д.м.н., проф. каф. внутренних, профессиональных болезней и ревматологии медико-профилактического факультета Moscow, Russia

E. V Stavrovskaya

Sechenov First Moscow State Medical University (Sechenov University)

к.м.н., доц. каф. внутренних, профессиональных болезней и ревматологии медико-профилактического факультета Moscow, Russia

References

  1. Нефрология. Национальное руководство. Под ред. Н.А. Мухина. М.: ГЭОТАР-Медиа; 2009. 720 с. [Nefrologiya. Natsional’noe rukovodstvo.
  2. Collins A.J, Foley R.N, Herzog C, Chavers B, Gilbertson D, Ishani A, Johansen K, Kasiske B, Kutner N, Liu J, St. Peter W, Ding S, Guo H, Kats A, Lamb K, Li S, Li S, Roberts T, Skeans M, Snyder J, et al. US Renal Data System 2012 Annual Data Report. Am J Kidney Dis. 2013;61(1 suppl 1):e1-e480. doi: 10.1053/j.ajkd.2012.11.031
  3. Solazzo A, Testa F, Giovanella S, Busutti M, Furci L, Carrera P, et al. The prevalence of autosomal dominant polycystic kidney disease (ADPKD): A meta - analysis of European literature and prevalence evaluation in the Italian province of Modena suggest that ADPKD is a rare and underdiagnosed condition. PLoS ONE. 2018;13(1):e0190430. doi: 10.1371/journal.pone.0190430
  4. Willey C.J, Blais J.D, Hall A.K, Krasa H, Makin A, Czerwiec F. Prevalence of autosomal dominant polycystic kidney disease in the European Union. Nephrol Dial Transplant. 2017;32:1356-63. doi: 10.1093/ndt/gfw240
  5. Ong A.C, Devuyst O, Knebelmann B, Walz G. Autosomal dominant polycystic kidney disease: the changing face of clinical management. Lancet. 2015;385 (9981):1993-2002. doi: 10.1016/S0140-6736(15)60907-2
  6. Porath B, Gainullin V.G, Cornec-Le Gall E, et al. Mutations in GANAB, encoding the glucosidase II alpha subunit, cause autosomal - dominant polycystic kidney and liver disease. Am J Human Genet. 2016;98(6):1193-207. doi: 10.1016/j.ajhg.2016.05.004
  7. Bergmann C, Senderek J, Ellenwindelen F, et al. Clinical consequences of PKHD1 mutations in 164 patients with autosomal - recessive polycystic kidney disease (ARPKD). Kidney Int. 2005;67:829-48.
  8. Chebib F, Torres V. Recent Advances in the Management of Autosomal Dominant Polycystic Kidney. CJASN. 2018;13(11):1765-76. doi: 10.2215/CJN.03960318
  9. Singla V, Reiter J. The primary cilium as the cell's antenna: signaling at a sensory organelle. Science. 2006;313:629-33. doi: 10.1126/science.1124534
  10. 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;70:1849-74. doi: 10.1007/s00018-012-1052-z
  11. Kottgen M, Walz G. Subcellular localization and trafficking of polycystins. Iflugers Arch. 2005;451(1):286-93. doi: 10.1007/s00424-005-1417-3
  12. Nauli S.M, Alenghat F.J, Luo Y, Williams E, Vassilev P, Li X, Elia A.E, Lu W, Brown E.M, Quinn S.J, Ingber D.E, Zhou J. Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells. Nat Genet. 2003;33(2):129-37. doi: 10.1038/ng1076
  13. Nauli S.M, Pala R, Kleene S.J. Calcium channels in primary cilia. Curr Opin Nephrol Hypertens. 2016;25(5):452-8. doi: 10.1097/MNH.0000000000000251
  14. Fliegauf M, Benzing T, Omran H. When cilia go bad: cilia defects and ciliopathies. Nat Rev Mol Cell Biol. 2007;8(11):880-93. doi: 10.1038/nrm2278
  15. Montesano R, Ghzili H, Carrozzino F, Rossier B.C, Feraille E. cAMP-dependent chloride secretion mediates tubule enlargement and cyst formation by cultured mammalian collecting duct cells. Am J Physiol Renal Physiol. 2009;296(2):F446-57. doi: 10.1152/ajprenal.90415.2008
  16. Devuyst O, Torres V.E. Osmoregulation, vasopressin, and cAMP signaling in autosomal dominant polycystic kidney disease. Curr Opin Nephrol Hypertens. 2013;22(4):459-70. doi: 10.1097/MNH.0b013e3283621510
  17. Terryn S, Ho T.A, Beauwens R.C, Devuyst O. Fluid transport and cystogenesis in autosomal dominant polycystic kidney disease. Biochim Biophys Acta. 2011;1812:1314-21. doi: 10.1016/j.bbadis.2011.01.011
  18. Bankir L, Bichet D/G. Polycystic kidney disease: An early urea - selective urine - concentrating defect in ADPKD. Nat Rev Nephrol. 2012;8:437-9. doi: 10.1038/nrneph.2012.139
  19. Torres V, Grantham J.J, Chapman A.B, Mrug M, Bae K.T, King B.F, et al. Potentially modifiable factors affecting the progression of autosomal dominant polycystic kidney disease. Clin J Am Soc Nephrol. 2011;6:640-7. doi: 10.2215/CJN.03250410
  20. Meijer E, Bakker S.J, van der Jagt E.J, et al. Copeptin, a surrogate marker of vasopressin, is associated with disease severity in autosomal dominant polycystic kidney disease. Clin J Am Soc Nephrol. 2011;6:361-8. doi: 10.2215/cjn.04560510
  21. Boertien W.E, Meijer E, Zittema D, et al. Copeptin, a surrogate marker for vasopressin, is associated with kidney function decline in subjects with autosomal dominant polycystic kidney disease. Nephrol Dial Transplant. 2012;27:4131-7. doi: 10.1093/ndt/gfs070
  22. Boertien W.E, Meijer E, Li J, et al. Relationship of copeptin, a surrogate marker for arginine vasopressin, with change in total kidney volume and GFR decline in autosomal dominant polycystic kidney disease: results from the CRISP cohort. Am J Kidney Dis. 2013;61:420-9. doi: 10.1053/j.ajkd.2012.08.038
  23. Wang X, Wu Y, Ward C.J, Harris P.C, Torres V.E. Vasopressin directly regulates cyst growth in polycystic kidney disease. J Am Soc Nephrol. 2008;19:102-8. doi: 10.1681/asn.2007060688
  24. Grantham J.J, Torres V.E. The importance of total kidney volume in evaluating progression of polycystic kidney disease. Nat Rev Nephrol. 2016;12:667-77. doi: 10.1038/nrneph.2016.135
  25. Mc Ewan P, Bennett Wilton H, Ong A.C.M, Orskov B, Sandford R, et al. A model to predict disease progression in patients with autosomal dominant polycystic kidney disease (ADPKD): the ADPKD Outcomes Model. BMC Nephrol. 2018;19:37. doi: 10.1186/s12882-017-0804-2
  26. Rahbari-Oskoui F.F, Landsittel D, Torres V.E. Relationship between renal complications and total kidney volume in autosomal dominant polycystic kidney disease from the Consortium for Radiologic Imaging of Polycystic Kidney Disease Cohort. Presented at: Kidney Week 2013; November 5-10, 2013; Atlanta, GA [abstract]. J Am Soc Nephrol. 2013;24:687A.
  27. Alam A, Dahl N, Lipschutz J, Rossetti S, Smith P, Sapir D, Weinstein J, Mc Farlane P, Bichet D. Total Kidney Volume in Autosomal Dominant Polycystic Kidney Disease: A Biomarker of Disease Progression and Therapeutic Efficacy. Am J Kidney Dis. 2015;66(4):564-76. doi: 10.1053/j.ajkd.2015.01.030
  28. Soroka S, Alam A, Bevilacqua M, Girard L.P, Komenda P, Loertscher R, Mc Farlane P, Pandeya S, Tam P, Bichet D.G. Updated Canadian Expert Consensus on Assessing Risk of Disease Progression and Pharmacological Management of Autosomal Dominant Polycystic Kidney Disease. Can J Kidney Health Dis. 2018;5:1-15. doi: 10.1177/2054358118801589
  29. Ars E, Bernis C, Fraga G, Martínez V, Martins J, Ortiz A, Rodríguez-Pérez J.C, Sans L, Torra R. Spanish guidelines for the management of autosomal dominant polycystic kidney disease. Nephrol Dial Transplant. 2014;29(Suppl 4):iv95-105. doi: 10.1093/ndt/gfu186
  30. Weimbs T, Shillingford J.M, Torres J, Kruger S.L, Bourgeois B.C. Emerging targeted strategies for the treatment of autosomal dominant polycystic kidney disease. Clin Kidney J. 2018 Dec;11(Suppl 1):i27-i38. doi: 10.1093/ckj/sfy089
  31. Bichet D.G. Central vasopressin: dendritic and axonal secretion and renal actions. Clin Kidney J. 2014;7:242-7. doi: 10.1093/ckj/sfu050
  32. Torres V.E, Higashihara E, Devuyst O, Chapman A.B, Gansevoort R.T, Grantham J.J, Perrone R.D, Ouyang J, Blais J.D, Czerwiec F.S. Effect of Tolvaptan in Autosomal Dominant Polycystic Kidney Disease by CKD Stage: Results from the TEMPO 3:4 Trial. Clin J Am Soc Nephrol. 2016;11(5):803-11. doi: 10.2215/CJN.06300615
  33. Gansevoort R.T, van Gastel M.D, Chapman A.B. Copeptin, a surrogate for vasopressin, predicts disease progression and tolvaptan treatment efficacy in ADPKD. Results of the TEMPO 3:4 trial. J Am Soc Nephrol. 2016;27:34A.
  34. Torres V.E, Chapman A.B, Devuyst O, Gansevoort R.T, Perrone R.D, Koch G, Ouyang J, Mc Quade R.D, Blais J.D, Czerwiec F.S, Sergeyeva O. Tolvaptan in Later-Stage Autosomal Dominant Polycystic Kidney Disease.; REPRISE Trial Investigators. N Engl J Med. 2017;377:1930-42. doi: 10.1056/NEJMoa1710030
  35. Torres V.E, Chapman A.B, Devuyst O, Gansevoort R.T, Perrone R.D, Dandurand A, Ouyang J, Czerwiec F.S, Blais J.D. Multicenter, open - label, extension trial to evaluate the long - term efficacy and safety of early versus delayed treatment with tolvaptan in autosomal dominant polycystic kidney disease: the TEMPO 4:4 Trial. Nephrol Dial Transplant. 2018;33(3):477-89. doi: 10.1093/ndt/gfx043
  36. Baur B.P, Meaney C.J. Review of tolvaptan for autosomal dominant polycystic kidney disease. Pharmacotherapy. 2014;34(6):605-16. doi: 10.1002/phar.1421
  37. Blair H.A, Keating G.M. Tolvaptan: A Review in Autosomal Dominant Polycystic Kidney Disease. Drugs. 2015;75(15):1797-806. doi: 10.1007/s40265-015-0475-x
  38. Poch E, Rodas L, Blasco M, Molina A, Quintana L. An update on tolvaptan for autosomal dominant polycystic kidney disease. Drugs Today (Barc). 2018;54(9):519-33. doi: 10.1358/dot.2018.54.9.2776624
  39. Nagao S, Nishii K, Katsuyama M, et al. Increased water intake decreases progression of polycystic kidney disease in the PCK rat. J Am Soc Nephrol. 2006;17:2220-7. doi: 10.1681/asn.2006030251
  40. Hopp K, Wang X, Ye H, Irazabal M.V, Harris P.C, Torres V.E. Effects of hydration in rats and mice with polycystic kidney disease. Am J Physiol Renal Physiol. 2015;308:F261-F266. doi: 10.1152/ajprenal.00345.2014
  41. Barash I, Ponda M.P, Goldfarb D.S, Skolnik E.Y. A pilot clinical study to evaluate changes in urine osmolality and urine cAMP in response to acute and chronic water loading in autosomal dominant polycystic kidney disease. Clin J Am Soc Nephrol. 2010;5:693-97. doi: 10.2215/cjn.04180609
  42. Higashihara E, Nutahara K, Tanbo M, Kurahashi T, Marunouchi T, Takahashi H, Wallace D.P. Does increased water intake prevent disease progression in autosomal dominant polycystic kidney disease? Nephrol Dial Transplant. 2014;29:1710-9. doi: 10.1093/ndt/gfu093
  43. Neijenhuis M.K, Gevers T.J, Nevens F, Hogan M.C, Torres V.E, Kievit W, Drenth J.P. Somatostatin analogues improve health - related quality of life in polycystic liver disease: a pooled analysis of two randomised, placebo - controlled trials. Aliment Pharmacol Ther. 2015;42(5):591-8. doi: 10.1111/apt.13301
  44. 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;26:39-47. doi: 10.1681/ASN.2013121312
  45. Wahl P.R, Serra A.L, Le Hir M, Molle K.D, Hall M.N, Wuthrich 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 Mar;21(3):598-604. doi: 10.1093/ndt/gfl181
  46. Tao Y, Kim J, Schrier R, Edelstein C.L. Rapamycin markedly slows disease progression in rat model of polycystic kidney disease. J Am Soc Nephrol. 2005;16(1):46-51. doi: 10.1681/ ASN.2004080660
  47. Serra A.L, Poster D, Kistler A.D, et al. Sirolimus and kidney growth in autosomal dominant polycystic kidney disease. N Engl J Med. 2010;363(9):820-9. doi: 10.1056/NEJMoa0907419
  48. 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):830-40. doi: 10.1056/nejmoa1003491
  49. Rajani R, Pastor-Soler N.M, Hallows K.R. Role of AMP activated protein kinase in kidney tubular transport, metabolism, and disease. Curr Opin Nephrol Hypertens. 2017;26:375-83. doi: 10.1097/mnh.0000000000000349
  50. Takiar V, Nishio S, Seo-Mayer P, King J.D. Jr, Li H, Zhang L, Karihaloo A, Hallows K.R, Somlo S, Caplan M.J. Activating AMP activated protein kinase (AMPK) slows renal cystogenesis. Proc Natl Acad Sci USA. 2011;108:2462-7. doi: 10.1073/pnas.1011498108
  51. Seliger S, Abebe K, Hallows K, Miskulin D, Perrone R, Watnick T, Bae K. A randomized clinical trial of metformin to treat autosomal dominant polycystic kidney disease. Am J Nephrol. 2018;47:352-60. doi: 10.1159/000488807
  52. Grantham J, Torres V, Chapman A, Guay-Woodford L, Bae K, King B, Wetzel L, Baumgarten D, Kenney P, Harris P, Klahr S, Bennett W, Hirschman G, Meyers C, Zhang X, Zhu F, Miller J. Volume Progression in Polycystic Kidney Disease. N Engl J Med. 2006;354:2122-30. doi: 10.1056/nejmoa054341
  53. 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; HALT-PKD Trial Investigators. Angiotensin blockade in late autosomal dominant polycystic kidney disease. N Engl J Med. 2014;371(24):2267-76. doi: 10.1056/NEJMoa1402686
  54. Schrier R.W, Abebe K.Z, Perrone R.D, Torres V.E, 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, Bae K.T, Moore C.G, Chapman A.B; HALT-PKD Trial Investigators. Blood pressure in early autosomal dominant polycystic kidney disease. N Engl J Med. 2014;371(24):2255-66. doi: 10.1056/NEJMoa1402685
  55. Irazabal M, Abebe K, Bae K, Perrone R, Chapman A, Schrier R, Yu A, Braun W, Steinman T, Harris P, Flessner M, Torres V. Prognostic enrichment design in clinical trials for autosomal dominant polycystic kidney disease: the HALT-PKD clinical trial. Nephrol Dial Transplant. 2017;32(11):1857-65. doi: 10.1093/ndt/gfw294
  56. Schrier R, Mc Fann K, Jonson A, Chapman A, Edelstein C, Brosnahan G, Ecder T, Tison T. Cardiac and Renal Effects of Standard Versus Rigorous Blood Pressure Control in Autosomal-Dominant Polycystic Kidney Disease: Results of a Seven-Year Prospective Randomized Study. J Am Soc Nephrol. 2002;13(7):1733-9. doi: 10.1097/01.asn.0000018407.60002.b9
  57. Klahr S, Breyer J.A, Beck G.J, Dennis V.W, Hartman J.A, Roth D, Steinman T, Wang S.R, Yamamoto M.E. Dietary protein restriction, blood pressure control, and the progression of polycystic kidney disease. Modification of Diet in Renal Disease Study Group. J Am Soc Nephrol. 1995;5(12):2037-47.
  58. Torres V.E, Grantham J.J, Chapman A.B, Mrug M, Bae K.T, King B.F.Jr, Wetzel L.H, Martin D, Lockhart M.E, Bennett W.M, Moxey-Mims M, Abebe K.Z, Lin Y, Bost J.E; Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP). Potentially modifiable factors affecting the progression of autosomal dominant polycystic kidney disease. Clin J Am Soc Nephrol. 2011;6(3):640-7. doi: 10.2215/CJN.03250410
  59. Amro O.W, Paulus J.K, Noubary F, Perrone R.D. Low-Osmolar Diet and Adjusted Water Intake for Vasopressin Reduction in Autosomal Dominant Polycystic Kidney Disease: A Pilot Randomized Controlled Trial. Am J Kidney Dis. 2016 Dec;68(6):882-91. doi: 10.1053/j.ajkd.2016.07.023
  60. Girardat-Rotar L, Puhan M.A, Braun J, Serra A.L. Long - term effect of coffee consumption on autosomal dominant polycystic kidneys disease progression: results from the Suisse ADPKD, a Prospective Longitudinal Cohort Study. J Nephrol. 2018;31(1):87-94. doi: 10.1007/s40620-017-0396-8
  61. Orth S.R, Stockmann A, Conradt C, et alю Smoking as a risk factor for end - stage renal failure in men with primary renal disease. Kidney Int. 1998;54:926-31. doi: 10.1046/j.1523-1755.1998.00067.x
  62. Nowak K.L, You Z, Gitomer B, Brosnahan G, Torres V.E, Chapman A.B, Perrone R.D, Steinman T.I, Abebe K.Z, Rahbari-Oskoui F.F, Yu A.S.L, Harris P.C, Bae K.T, Hogan M, Miskulin D, Chonchol M. Overweight and Obesity Are Predictors of Progression in Early Autosomal Dominant Polycystic Kidney Disease. J Am Soc Nephrol. 2018;29(2):571-8. doi: 10.1681/ASN.2017070819
  63. Cadnapaphornchai M.A, George D.M, Mc Fann 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):889-96. doi: 10.2215/CJN.08350813
  64. Bolignano D, Palmer S.C, Ruospo M, Zoccali C, Craig J.C, Strippoli G.F. Interventions for preventing the progression of autosomal dominant polycystic kidney disease. Cochrane Database Syst Rev. 2015;14(7):CD010294. doi: 10.1002/14651858.CD010294.pub2

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