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  • Review Article
  • Published:

New treatment paradigms for ADPKD: moving towards precision medicine

Nature Reviews Nephrology volume 13, pages 750–768 (2017)Cite this article

Subjects

Key Points

  • Clinicians are now able to identify which patients with autosomal dominant polycystic kidney disease (ADPKD) are at highest risk of progression and most likely to benefit from early therapy

  • MRI measurement of total kidney volume (TKV) is a valuable method to predict future rate of increase in TKV, rate of decline in kidney function and risk of end-stage renal disease (ESRD)

  • The availability of genetic testing will continue to increase and can provide a diagnosis in unusual or atypical cases or in young (<30 years of age) patients being assessed for kidney donation

  • ADPKD is typically the result of germline PKD1 or PKD2 mutations, with somatic mutations, genetic mosaicism and modifier mutations occasionally contributing to the ADPKD phenotype

  • Disruption of polycystin trafficking and signalling, environmental exposures and the compounding 'snowball' effects of regional ischaemia, inflammation and tubular obstruction further contribute to disease progression

  • Novel strategies intended to limit cyst burden have provided encouraging results, whereas treatment of hypertension and proteinuria remain the mainstays of medical management of ADPKD

  • Assessment and treatment of ADPKD-related complications, including cyst haemorrhage, cyst infection, nephrolithiasis and chronic pain, require special consideration and attention

Abstract

The natural history of autosomal dominant polycystic kidney disease (ADPKD) is characterized by a variable rate of cyst development and increase in total kidney volume (TKV), variable kidney function decline and age of onset of end-stage renal disease (ESRD), and variable presentation of renal and extrarenal manifestations. Precision medicine is proposed to improve patient outcomes by tailoring therapy to the specific genetic background, pathophysiology, disease burden, prognosis and status of each individual. This approach to the management of patients with ADPKD is nearing clinical implementation owing to advances in genetics, imaging, biomarker development and therapeutics. In this Review, we discuss pharmacological and non-pharmacological interventions for the treatment of hypertension and proteinuria, and for slowing the rate of cyst growth in patients with ADPKD before the development of ESRD. We provide recommendations for the management of renal complications, including cyst infection, nephrolithiasis, haematuria and chronic pain. The early treatment of patients with ADPKD who are largely asymptomatic is associated with a therapeutic burden but slows cyst growth and delays subsequent loss of kidney function, which ultimately delays the need for renal replacement therapy and has a positive effect on the quality of life of patients.

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Figure 1: Pathogenic mechanisms and pathways in ADPKD.
Figure 2: Sources of data to characterize the ADPKD clinical phenotype.
Figure 3: Theoretical relationship between total kidney volume (TKV) and kidney function.
Figure 4: The theoretical contribution of genetic and environmental factors to polycystin protein dosage explains the rate of cyst progression in patients with autosomal dominant polycystic kidney disease (ADPKD).

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References

  1. Gabow, P. A. Autosomal dominant polycystic kidney disease. N. Engl. J. Med. 329, 332–342 (1993).

    Article  CAS  PubMed  Google Scholar 

  2. Reule, S. et al. ESRD from autosomal dominant polycystic kidney disease in the United States, 2001–2010. Am. J. Kidney Dis. 64, 592–599 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  3. Spithoven, E. M. et al. Renal replacement therapy for autosomal dominant polycystic kidney disease (ADPKD) in Europe: prevalence and survival — an analysis of data from the ERA-EDTA Registry. Nephrol. Dial. Transplant. 29, iv15–iv25 (2014).

    Article  PubMed  Google Scholar 

  4. Fernando, M. R., Dent, H., McDonald, S. P. & Rangan, G. K. Incidence and survival of end-stage kidney disease due to polycystic kidney disease in Australia and New Zealand. Popul. Health Metr. 15, 7 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  5. Chapman, A. B. et al. Renal structure in early autosomal-dominant polycystic kidney disease (ADPKD): The Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP) cohort. Kidney Int. 64, 1035–1045 (2003).

    Article  PubMed  Google Scholar 

  6. Schrier, R. W. et al. Blood pressure in early autosomal dominant polycystic kidney disease. N. Engl. J. Med. 371, 2255–2266 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Torres, V. E. et al. Tolvaptan in patients with autosomal dominant polycystic kidney disease. N. Engl. J. Med. 367, 2407–2418 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Torres, V. E. et al. 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. http://dx.doi.org/10.1093/ndt/gfx043 (2017).

  9. Committee on A Framework for Developing a New Taxonomy of Disease. Toward Precision Medicine: Building a Knowledge Network for Biomedical Research and a New Taxonomy of Disease. (The National Academies Press, 2011).

  10. Harris, P. C. & Torres, V. E. Genetic mechanisms and signaling pathways in autosomal dominant polycystic kidney disease. J. Clin. Invest. 124, 2315–2324 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Cornec- Le Gall, E., Audrezet, M. P., Le Meur, Y., Chen, J. M. & Ferec, C. Genetics and pathogenesis of autosomal dominant polycystic kidney disease: 20 years on. Hum. Mutat. 35, 1393–1406 (2014).

    Article  CAS  Google Scholar 

  12. Besse, W. et al. Isolated polycystic liver disease genes define effectors of polycystin-1 function. J. Clin. Invest. 127, 1772–1785 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  13. Lantinga-van Leeuwen, I. S. et al. Lowering of Pkd1 expression is sufficient to cause polycystic kidney disease. Hum. Mol. Genet. 13, 3069–3077 (2004).

    Article  CAS  PubMed  Google Scholar 

  14. Rowe, I. et al. Defective glucose metabolism in polycystic kidney disease identifies a new therapeutic strategy. Nat. Med. 19, 488–493 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. 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. 19, 102–108 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Takakura, A. et al. Renal injury is a third hit promoting rapid development of adult polycystic kidney disease. Hum. Mol. Genet. 18, 2523–2531 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Leonhard, W. N. et al. Scattered deletion of PKD1 in kidneys causes a cystic snowball effect and recapitulates polycystic kidney disease. J. Am. Soc. Nephrol. 26, 1322–1333 (2015).

    Article  CAS  PubMed  Google Scholar 

  18. Houle, D., Govindaraju, D. R. & Omholt, S. Phenomics: the next challenge. Nat. Rev. Genet. 11, 855–866 (2010).

    Article  CAS  PubMed  Google Scholar 

  19. Lanktree, M. B., Hassell, R. G., Lahiry, P. & Hegele, R. A. Phenomics: expanding the role of clinical evaluation in genomic studies. J. Investig. Med. 58, 700–706 (2010).

    Article  CAS  PubMed  Google Scholar 

  20. Grantham, J. J. et al. Determinants of renal volume in autosomal-dominant polycystic kidney disease. Kidney Int. 73, 108–116 (2008).

    Article  CAS  PubMed  Google Scholar 

  21. Irazabal, M. V. et al. Imaging classification of autosomal dominant polycystic kidney disease: a simple model for selecting patients for clinical trials. J. Am. Soc. Nephrol. 26, 160–172 (2015).

    Article  CAS  PubMed  Google Scholar 

  22. Gansevoort, R. T. et al. Recommendations for the use of tolvaptan in autosomal dominant polycystic kidney disease: a position statement on behalf of the ERA-EDTA Working Groups on Inherited Kidney Disorders and European Renal Best Practice. Nephrol. Dial. Transplant. 31, 337–348 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  23. Grantham, J. J. Rationale for early treatment of polycystic kidney disease. Pediatr. Nephrol. 30, 1053–1062 (2015).

    Article  PubMed  Google Scholar 

  24. Cornec-Le Gall, E. et al. The PROPKD score: a new algorithm to predict renal survival in autosomal dominant polycystic kidney disease. J. Am. Soc. Nephrol. 27, 942–951 (2016).

    Article  CAS  PubMed  Google Scholar 

  25. Schrier, R. W. et al. Predictors of autosomal dominant polycystic kidney disease progression. J. Am. Soc. Nephrol. 25, 2399–2418 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Hwang, Y. H. et al. Refining genotype-phenotype correlation in autosomal dominant polycystic kidney disease. J. Am. Soc. Nephrol. 27, 1861–1868 (2016).

    Article  CAS  PubMed  Google Scholar 

  27. Heyer, C. M. et al. Predicted mutation strength of nontruncating PKD1 mutations aids genotype-phenotype correlations in autosomal dominant polycystic kidney disease. J. Am. Soc. Nephrol. 27, 2872–2884 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Cornec-Le Gall, E. et al. Type of PKD1 mutation influences renal outcome in ADPKD. J. Am. Soc. Nephrol. 24, 1006–1013 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Iliuta, I. A. et al. Polycystic kidney disease without an apparent family history. J. Am. Soc. Nephrol. 28, 2768–2776 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Barua, M. et al. Family history of renal disease severity predicts the mutated gene in ADPKD. J. Am. Soc. Nephrol. 20, 1833–1838 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Porath, B. et al. Mutations in GANAB, encoding the glucosidase IIα subunit, cause autosomal-dominant polycystic kidney and liver disease. Am. J. Hum. Genet. 98, 1193–1207 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Braun, D. A. & Hildebrandt, F. Ciliopathies. Cold Spring Harb. Perspect. Biol. 9, a028191 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Song, X., Haghighi, A., Iliuta, I. A. & Pei, Y. Molecular diagnosis of autosomal dominant polycystic kidney disease. Expert Rev. Mol. Diagn. 13, 1–11 (2017).

    Google Scholar 

  34. Kinoshita, M. et al. Technical evaluation: identification of pathogenic mutations in PKD1 and PKD2 in patients with autosomal dominant polycystic kidney disease by next-generation sequencing and use of a comprehensive new classification system. PLoS ONE 11, e0166288 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Mallawaarachchi, A. C. et al. Whole-genome sequencing overcomes pseudogene homology to diagnose autosomal dominant polycystic kidney disease. Eur. J. Hum. Genet. 24, 1584–1590 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Bergmann, C. et al. Mutations in multiple PKD genes may explain early and severe polycystic kidney disease. J. Am. Soc. Nephrol. 22, 2047–2056 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Cnossen, W. R. et al. LRP5 variants may contribute to ADPKD. Eur. J. Hum. Genet. 24, 237–242 (2016).

    Article  CAS  PubMed  Google Scholar 

  38. Rossetti, S. et al. Incompletely penetrant PKD1 alleles suggest a role for gene dosage in cyst initiation in polycystic kidney disease. Kidney Int. 75, 848–855 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Losekoot, M. et al. Neonatal onset autosomal dominant polycystic kidney disease (ADPKD) in a patient homozygous for a PKD2 missense mutation due to uniparental disomy. J. Med. Genet. 49, 37–40 (2012).

    Article  CAS  PubMed  Google Scholar 

  40. Ward, C. J. et al. The gene mutated in autosomal recessive polycystic kidney disease encodes a large, receptor-like protein. Nat. Genet. 30, 259–269 (2002).

    Article  PubMed  Google Scholar 

  41. Soroka, S. et al. Assessing risk of disease progression and pharmacological management of autosomal dominant polycystic kidney disease: a canadian expert consensus. Can. J. Kidney Health Dis. 4, 2054358117695784 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  42. Pei, Y. et al. Unified criteria for ultrasonographic diagnosis of ADPKD. J. Am. Soc. Nephrol. 20, 205–212 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Tangri, N. et al. Total kidney volume as a biomarker of disease progression in autosomal dominant polycystic kidney disease. Can. J. Kidney Health Dis. 4, 2054358117693355 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  44. Turco, D., Busutti, M., Mignani, R., Magistroni, R. & Corsi, C. Comparison of total kidney volume quantification methods in autosomal dominant polycystic disease for a comprehensive disease assessment. Am. J. Nephrol. 45, 373–379 (2017).

    Article  PubMed  Google Scholar 

  45. Grantham, J. J. & Torres, V. E. The importance of total kidney volume in evaluating progression of polycystic kidney disease. Nat. Rev. Nephrol. 12, 667–677 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Grantham, J. J., Chapman, A. B. & Torres, V. E. Volume progression in autosomal dominant polycystic kidney disease: the major factor determining clinical outcomes. Clin. J. Am. Soc. Nephrol. 1, 148–157 (2006).

    Article  PubMed  Google Scholar 

  47. Grantham, J. J. et al. Volume progression in polycystic kidney disease. N. Engl. J. Med. 354, 2122–2130 (2006).

    Article  CAS  PubMed  Google Scholar 

  48. Cadnapaphornchai, M. A. et al. 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. 9, 889–896 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  49. Serra, A. L. et al. Sirolimus and kidney growth in autosomal dominant polycystic kidney disease. N. Engl. J. Med. 363, 820–829 (2010).

    Article  CAS  PubMed  Google Scholar 

  50. Walz, G. et al. Everolimus in patients with autosomal dominant polycystic kidney disease. N. Engl. J. Med. 363, 830–840 (2010).

    Article  CAS  PubMed  Google Scholar 

  51. Torres, V. E. et al. Angiotensin blockade in late autosomal dominant polycystic kidney disease. N. Engl. J. Med. 371, 2267–2276 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Caroli, A. et al. Effect of longacting somatostatin analogue on kidney and cyst growth in autosomal dominant polycystic kidney disease (ALADIN): a randomised, placebo-controlled, multicentre trial. Lancet 382, 1485–1495 (2013).

    Article  CAS  PubMed  Google Scholar 

  53. Stallone, G. et al. Rapamycin for treatment of type I autosomal dominant polycystic kidney disease (RAPYD-study): a randomized, controlled study. Nephrol. Dial. Transplant. 27, 3560–3567 (2012).

    Article  CAS  PubMed  Google Scholar 

  54. Hogan, M. C. et al. Randomized clinical trial of long-acting somatostatin for autosomal dominant polycystic kidney and liver disease. J. Am. Soc. Nephrol. 21, 1052–1061 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Braun, W. E., Schold, J. D., Stephany, B. R., Spirko, R. A. & Herts, B. R. Low-dose rapamycin (sirolimus) effects in autosomal dominant polycystic kidney disease: an open-label randomized controlled pilot study. Clin. J. Am. Soc. Nephrol. 9, 881–888 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  56. Perico, N. et al. Sirolimus therapy to halt the progression of ADPKD. J. Am. Soc. Nephrol. 21, 1031–1040 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Ruggenenti, P. et al. Safety and efficacy of long-acting somatostatin treatment in autosomal-dominant polycystic kidney disease. Kidney Int. 68, 206–216 (2005).

    Article  CAS  PubMed  Google Scholar 

  58. Kim, Y. et al. Automated segmentation of kidneys from MR images in patients with autosomal dominant polycystic kidney disease. Clin. J. Am. Soc. Nephrol. 11, 576–584 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Spithoven, E. M. et al. Estimation of total kidney volume in autosomal dominant polycystic kidney disease. Am. J. Kidney Dis. 66, 792–801 (2015).

    Article  PubMed  Google Scholar 

  60. Perrone, R. D. et al. Total kidney volume is a prognostic biomarker of renal function decline and progression to end-stage renal disease in patients with autosomal dominant polycystic kidney disease. Kidney Int.Rep. 2, 442–450 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  61. Casteleijn, N. F. et al. Urine and plasma osmolality in patients with autosomal dominant polycystic kidney disease: reliable indicators of vasopressin activity and disease prognosis? Am. J. Nephrol. 41, 248–256 (2015).

    Article  CAS  PubMed  Google Scholar 

  62. Torres, V. E., Bankir, L. & Grantham, J. J. A case for water in the treatment of polycystic kidney disease. Clin. J. Am. Soc. Nephrol. 4, 1140–1150 (2009).

    Article  CAS  PubMed  Google Scholar 

  63. Zittema, D. et al. Kidney function and plasma copeptin levels in healthy kidney donors and autosomal dominant polycystic kidney disease patients. Clin. J. Am. Soc. Nephrol. 9, 1553–1562 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Boertien, W. E. 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. 61, 420–429 (2013).

    Article  CAS  PubMed  Google Scholar 

  65. Boertien, W. E. 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. 27, 4131–4137 (2012).

    Article  CAS  PubMed  Google Scholar 

  66. Corradi, V. et al. Copeptin levels and kidney function in ADPKD: case-control study. Clin. Nephrol. 86, 147–153 (2016).

    Article  CAS  PubMed  Google Scholar 

  67. Meijer, E. et al. Copeptin, a surrogate marker of vasopressin, is associated with disease severity in autosomal dominant polycystic kidney disease. Clin. J. Am. Soc. Nephrol. 6, 361–368 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Nakajima, A., Lu, Y., Kawano, H., Horie, S. & Muto, S. Association of arginine vasopressin surrogate marker urinary copeptin with severity of autosomal dominant polycystic kidney disease (ADPKD). Clin. Exp. Nephrol. 19, 1199–1205 (2015).

    Article  CAS  PubMed  Google Scholar 

  69. Pejchinovski, M. et al. Urine peptidome analysis predicts risk of end-stage renal disease and reveals proteolytic pathways involved in autosomal dominant polycystic kidney disease progression. Nephrol. Dial. Transplant. 32, 487–497 (2017).

    CAS  PubMed  Google Scholar 

  70. Salih, M. et al. Proteomics of urinary vesicles links plakins and complement to polycystic kidney disease. J. Am. Soc. Nephrol. 27, 3079–3092 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Street, J. M., Koritzinsky, E. H., Glispie, D. M. & Yuen, P. S. T. Urine exosome isolation and characterization. Methods Mol. Biol. 1641, 413–423 (2017).

    Article  CAS  PubMed  Google Scholar 

  72. Hogan, M. C. et al. Identification of biomarkers for PKD1 using urinary exosomes. J. Am. Soc. Nephrol. 26, 1661–1670 (2015).

    Article  CAS  PubMed  Google Scholar 

  73. Kistler, A. D. et al. Urinary proteomic biomarkers for diagnosis and risk stratification of autosomal dominant polycystic kidney disease: a multicentric study. PLoS ONE 8, e53016 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Chapman, A. B., Stepniakowski, K. & Rahbari-Oskoui, F. Hypertension in autosomal dominant polycystic kidney disease. Adv. Chron. Kidney Dis. 17, 153–163 (2010).

    Article  Google Scholar 

  75. Chapman, A. B. & Gabow, P. A. Hypertension in autosomal dominant polycystic kidney disease. Kidney Int. Suppl. 61, S71–S73 (1997).

    CAS  PubMed  Google Scholar 

  76. Johnson, A. M. & Gabow, P. A. Identification of patients with autosomal dominant polycystic kidney disease at highest risk for end-stage renal disease. J. Am. Soc. Nephrol. 8, 1560–1567 (1997).

    CAS  PubMed  Google Scholar 

  77. Yu, A. S. et al. Trajectory of the GFR in autosomal dominant polycystic kidney disease. J. Am. Soc. Nephrol. 27, abstr., FR-OR006 (2016).

    Article  Google Scholar 

  78. Schrier, R. W. Hypertension and autosomal dominant polycystic kidney disease. Am. J. Kidney Dis. 57, 811–813 (2011).

    Article  PubMed  Google Scholar 

  79. Ecder, T. Cardiovascular complications in autosomal dominant polycystic kidney disease. Curr. Hypertens. Rev. 9, 2–11 (2013).

    Article  PubMed  Google Scholar 

  80. Chapman, A. B. et al. Left ventricular hypertrophy in autosomal dominant polycystic kidney disease. J. Am. Soc. Nephrol. 8, 1292–1297 (1997).

    CAS  PubMed  Google Scholar 

  81. Chapman, A. B., Johnson, A., Gabow, P. A. & Schrier, R. W. The renin-angiotensin-aldosterone system and autosomal dominant polycystic kidney disease. N. Engl. J. Med. 323, 1091–1096 (1990).

    Article  CAS  PubMed  Google Scholar 

  82. Kip, S. N. et al. [Ca2+]i reduction increases cellular proliferation and apoptosis in vascular smooth muscle cells: relevance to the ADPKD phenotype. Circ. Res. 96, 873–880 (2005).

    Article  CAS  PubMed  Google Scholar 

  83. Rahbari-Oskoui, F., Williams, O. & Chapman, A. Mechanisms and management of hypertension in autosomal dominant polycystic kidney disease. Nephrol. Dial. Transplant. 29, 2194–2201 (2014).

    Article  CAS  PubMed  Google Scholar 

  84. Hessheimer, A. J., Vidal, O., Valentini, M. & Garcia-Valdecasas, J. C. Pheochromocytoma as a rare cause of arterial hypertension in a patient with autosomal dominant polycystic kidney disease: a diagnostic and therapeutic dilemma. Int. J. Surg. Case Rep. 14, 85–88 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  85. Hoorn, E. J. et al. A case of primary aldosteronism revealed after renal transplantation. Nat. Rev. Nephrol. 7, 55–60 (2011).

    Article  PubMed  Google Scholar 

  86. Schrier, R. W. ACE inhibitors, left ventricular mass and renal cyst growth in ADPKD. Pharmacol Res. 114, 166–168 (2016).

    Article  CAS  PubMed  Google Scholar 

  87. Nutahara, K. et al. Calcium channel blocker versus angiotensin II receptor blocker in autosomal dominant polycystic kidney disease. Nephron Clin. Pract. 99, c18–c23 (2005).

    Article  CAS  PubMed  Google Scholar 

  88. Zeltner, R., Poliak, R., Stiasny, B., Schmieder, R. E. & Schulze, B. D. Renal and cardiac effects of antihypertensive treatment with ramipril versus metoprolol in autosomal dominant polycystic kidney disease. Nephrol. Dial. Transplant. 23, 573–579 (2008).

    Article  CAS  PubMed  Google Scholar 

  89. van Dijk, M. A., Breuning, M. H., Duiser, R., van Es, L. A. & Westendorp, R. G. No effect of enalapril on progression in autosomal dominant polycystic kidney disease. Nephrol. Dial. Transplant. 18, 2314–2320 (2003).

    Article  CAS  PubMed  Google Scholar 

  90. Ecder, T. et al. Diuretics versus angiotensin-converting enzyme inhibitors in autosomal dominant polycystic kidney disease. Am. J. Nephrol. 21, 98–103 (2001).

    Article  CAS  PubMed  Google Scholar 

  91. Kidney Disease: Improving Global Outcomes (KDIGO) Chronic Kidney Disease Work Group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int. Suppl. 3, 1–150 (2013).

  92. Klahr, S. et al. Dietary protein restriction, blood pressure control, and the progression of polycystic kidney disease. J. Am. Soc. Nephrol. 5, 2037–2047 (1995).

    CAS  PubMed  Google Scholar 

  93. Appel, L. J. et al. Intensive blood-pressure control in hypertensive chronic kidney disease. N. Engl. J. Med. 363, 918–929 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Ku, E. et al. Association between strict blood pressure control during chronic kidney disease and lower mortality after onset of end-stage renal disease. Kidney Int. 87, 1055–1060 (2015).

    Article  PubMed  Google Scholar 

  95. Group, S. R. et al. A randomized trial of intensive versus standard blood-pressure control. N. Engl. J. Med. 373, 2103–2116 (2015).

    Article  CAS  Google Scholar 

  96. Ruzicka, M., Burns, K. D. & Hiremath, S. Precision medicine for hypertension management in chronic kidney disease: relevance of SPRINT for therapeutic targets in nondiabetic renal disease. Can. J. Cardiol. 33, 611–618 (2017).

    Article  PubMed  Google Scholar 

  97. Gansevoort, R. T. et al. Albuminuria and tolvaptan in autosomal-dominant polycystic kidney disease: results of the TEMPO 3:4 Trial. Nephrol. Dial.Transplant. 31, 1887–1894 (2016).

    Article  CAS  PubMed  Google Scholar 

  98. Akinbodewa, A. A., Adejumo, O. A., Ogunsemoyin, A. O., Osasan, S. A. & Adefolalu, O. A. Co-existing autosomal dominant polycystic kidney disease and nephrotic syndrome in a Nigerian patient with lupus nephritis. Ann. Afr. Med. 15, 83–86 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Yenigun, E. C. et al. Coexistence of autosomal dominant polycystic kidney disease and amyloidosis in a patient with nephrotic-range proteinuria. Iran. J. Kidney Dis. 8, 243–245 (2014).

    PubMed  Google Scholar 

  100. Torres, V. E. et al. Potentially modifiable factors affecting the progression of autosomal dominant polycystic kidney disease. Clin. J. Am. Soc. Nephrol. 6, 640–647 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Torres, V. E. et al. Analysis of baseline parameters in the HALT polycystic kidney disease trials. Kidney Int. 81, 577–585 (2012).

    Article  CAS  PubMed  Google Scholar 

  102. Torres, V. E. et al. Effect of tolvaptan in autosomal dominant polycystic kidney disease by CKD stage: results from the TEMPO 3:4 Trial. Clin. J. Am. Soc. Nephrol. 11, 803–811 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Devuyst, O. et al. Urine osmolality, response to tolvaptan, and outcome in autosomal dominant polycystic kidney disease: results from the TEMPO 3:4 Trial. J. Am. Soc. Nephrol. 28, 1592–1602 (2017).

    Article  CAS  PubMed  Google Scholar 

  104. Casteleijn, N. F. et al. Tolvaptan and kidney pain in patients with autosomal dominant polycystic kidney disease: secondary analysis from a randomized controlled trial. Am. J. Kidney Dis. 69, 210–219 (2017).

    Article  CAS  PubMed  Google Scholar 

  105. Torres, V. E. et al. Rationale and design of a clinical trial investigating tolvaptan safety and efficacy in autosomal dominant polycystic kidney disease. Am. J. Nephrol. 45, 257–266 (2017).

    Article  CAS  PubMed  Google Scholar 

  106. Zand, L. et al. Renal hemodynamic effects of the HMG-CoA reductase inhibitors in autosomal dominant polycystic kidney disease. Nephrol. Dial. Transplant. 31, 1290–1295 (2016).

    Article  CAS  PubMed  Google Scholar 

  107. Namli, S. et al. Improvement of endothelial dysfunction with simvastatin in patients with autosomal dominant polycystic kidney disease. Ren Fail 29, 55–59 (2007).

    Article  CAS  PubMed  Google Scholar 

  108. van Dijk, M. A., Kamper, A. M., van Veen, S., Souverijn, J. H. & Blauw, G. J. Effect of simvastatin on renal function in autosomal dominant polycystic kidney disease. Nephrol. Dial. Transplant. 16, 2152–2157 (2001).

    Article  CAS  PubMed  Google Scholar 

  109. 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. 44, 56–61 (2010).

    Article  CAS  PubMed  Google Scholar 

  110. Brosnahan, G. et al. Effect of statin therapy on the progression of autosomal dominant polycystic kidney disease. A secondary analysis of the HALT PKD trials. Curr. Hypertens. Rev. http://dx.doi.org/10.2174/1573402113666170427142815 (2017).

  111. 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 19, 217–226 (2014).

    Article  PubMed  Google Scholar 

  112. van Keimpema, L. et al. Lanreotide reduces the volume of polycystic liver: a randomized, double-blind, placebo-controlled trial. Gastroenterology 137, 1661–1668.e2 (2009).

    Article  CAS  PubMed  Google Scholar 

  113. Hogan, M. C. et al. Somatostatin analog therapy for severe polycystic liver disease: results after 2 years. Nephrol. Dial. Transplant. 27, 3532–3539 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Meijer, E. et al. 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. 63, 446–455 (2014).

    Article  CAS  PubMed  Google Scholar 

  115. Lantinga, M. A. et al. Hepatic cyst infection during use of the somatostatin analog lanreotide in autosomal dominant polycystic kidney disease: an interim analysis of the randomized open-label multicenter DIPAK-1 study. Drug Saf. 40, 153–167 (2017).

    Article  CAS  PubMed  Google Scholar 

  116. Novalic, Z. et al. Dose-dependent effects of sirolimus on mTOR signaling and polycystic kidney disease. J. Am. Soc. Nephrol. 23, 842–853 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Hajarnis, S. et al. microRNA-17 family promotes polycystic kidney disease progression through modulation of mitochondrial metabolism. Nat. Commun. 8, 14395 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Yheskel, M. & Patel, V. Therapeutic microRNAs in polycystic kidney disease. Curr. Opin. Nephrol. Hypertens. 26, 282–289 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Knight, T. et al. Medical resource utilization and costs associated with autosomal dominant polycystic kidney disease in the USA: a retrospective matched cohort analysis of private insurer data. Clinicoecon. Outcomes Res. 7, 123–132 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  120. Neuville, M., Hustinx, R., Jacques, J., Krzesinski, J. M. & Jouret, F. Diagnostic algorithm in the management of acute febrile abdomen in patients with autosomal dominant polycystic kidney disease. PLoS ONE 11, e0161277 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Hogan, M. C. & Norby, S. M. Evaluation and management of pain in autosomal dominant polycystic kidney disease. Adv. Chron. Kidney Dis. 17, e1–e16 (2010).

    Article  Google Scholar 

  122. Chapman, A. B. et al. Autosomal-dominant polycystic kidney disease (ADPKD): executive summary from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int. 88, 17–27 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  123. Suwabe, T. et al. Clinical features of cyst infection and hemorrhage in ADPKD: new diagnostic criteria. Clin. Exp. Nephrol. 16, 892–902 (2012).

    Article  CAS  PubMed  Google Scholar 

  124. Chapman, A. B., Gabow, P. A. & Schrier, R. W. Reversible renal failure associated with angiotensin-converting enzyme inhibitors in polycystic kidney disease. Ann. Intern. Med. 115, 769–773 (1991).

    Article  CAS  PubMed  Google Scholar 

  125. Lantinga, M. A. et al. International multi-specialty delphi survey: identification of diagnostic criteria for hepatic and renal cyst infection. Nephron 134, 205–214 (2016).

    Article  PubMed  Google Scholar 

  126. Lantinga, M. A., Drenth, J. P. & Gevers, T. J. Diagnostic criteria in renal and hepatic cyst infection. Nephrol. Dial. Transplant. 30, 744–751 (2015).

    Article  CAS  PubMed  Google Scholar 

  127. Lantinga, M. A., de Sevaux, R. G. & Drenth, J. P. 18F-FDG PET/CT during diagnosis and follow-up of recurrent hepatic cyst infection in autosomal dominant polycystic kidney disease. Clin. Nephrol. 84, 61–64 (2015).

    Article  PubMed  Google Scholar 

  128. Suwabe, T. et al. Intracystic magnetic resonance imaging in patients with autosomal dominant polycystic kidney disease: features of severe cyst infection in a case-control study. BMC Nephrol. 17, 170 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  129. Piccoli, G. B. et al. Positron emission tomography in the diagnostic pathway for intracystic infection in adpkd and “cystic” kidneys. a case series. BMC Nephrol. 12, 48 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  130. Lantinga, M. A. et al. Management of renal cyst infection in patients with autosomal dominant polycystic kidney disease: a systematic review. Nephrol. Dial. Transplant. 32, 144–150 (2017).

    CAS  PubMed  Google Scholar 

  131. Suwabe, T. et al. Cyst infection in autosomal dominant polycystic kidney disease: causative microorganisms and susceptibility to lipid-soluble antibiotics. Eur. J. Clin. Microbiol. Infect. Dis. 34, 1369–1379 (2015).

    Article  CAS  PubMed  Google Scholar 

  132. Nishiura, J. L. et al. Evaluation of nephrolithiasis in autosomal dominant polycystic kidney disease patients. Clin. J. Am. Soc. Nephrol. 4, 838–844 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Torres, V. E., Wilson, D. M., Hattery, R. R. & Segura, J. W. Renal stone disease in autosomal dominant polycystic kidney disease. Am. J. Kidney Dis. 22, 513–519 (1993).

    Article  CAS  PubMed  Google Scholar 

  134. Grampsas, S. A. et al. Anatomic and metabolic risk factors for nephrolithiasis in patients with autosomal dominant polycystic kidney disease. Am. J. Kidney Dis. 36, 53–57 (2000).

    Article  CAS  PubMed  Google Scholar 

  135. Umbreit, E. C. et al. Percutaneous nephrolithotomy for large or multiple upper tract calculi and autosomal dominant polycystic kidney disease. J. Urol. 183, 183–187 (2010).

    Article  PubMed  Google Scholar 

  136. Mallett, A., Patel, M., Tunnicliffe, D. J. & Rangan, G. K. KHA-CARI autosomal dominant polycystic kidney disease guideline: management of renal stone disease. Semin. Nephrol. 35, 603–606.e3 (2015).

    Article  PubMed  Google Scholar 

  137. Penniston, K. L., Wertheim, M. L., Nakada, S. Y. & Jhagroo, R. A. Factors associated with patient recall of individualized dietary recommendations for kidney stone prevention. Eur. J. Clin. Nutr. 70, 1062–1067 (2016).

    Article  CAS  PubMed  Google Scholar 

  138. Fink, H. A. et al. Medical management to prevent recurrent nephrolithiasis in adults: a systematic review for an American College of Physicians Clinical Guideline. Ann. Intern. Med. 158, 535–543 (2013).

    Article  PubMed  Google Scholar 

  139. Casteleijn, N. F. et al. Novel treatment protocol for ameliorating refractory, chronic pain in patients with autosomal dominant polycystic kidney disease. Kidney Int. 91, 972–981 (2017).

    Article  PubMed  Google Scholar 

  140. Miskulin, D. C. et al. Health-related quality of life in patients with autosomal dominant polycystic kidney disease and CKD stages 1-4: a cross-sectional study. Am. J. Kidney Dis. 63, 214–226 (2014).

    Article  PubMed  Google Scholar 

  141. Casteleijn, N. F. et al. A stepwise approach for effective management of chronic pain in autosomal-dominant polycystic kidney disease. Nephrol. Dial. Transplant. 29 (Suppl. 4), iv142–iv153 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. World Health Organisation. Cancer pain relief: with a guide to opiod availability — 2nd ed. (WHO, 1996).

  143. Ballantyne, J. C., Kalso, E. & Stannard, C. WHO analgesic ladder: a good concept gone astray. BMJ 352, i20 (2016).

    Article  PubMed  Google Scholar 

  144. Tellman, M. W., Bahler, C. D., Shumate, A. M., Bacallao, R. L. & Sundaram, C. P. Management of pain in autosomal dominant polycystic kidney disease and anatomy of renal innervation. J. Urol. 193, 1470–1478 (2015).

    Article  PubMed  Google Scholar 

  145. PKD Foundation forum. Living with PKD: pain relief and medical marijuana. PKD Foundation http://forums.pkdconnection.org/viewtopic.php?f=3&t=109 (2017).

  146. Walsh, N. & Sarria, J. E. Management of chronic pain in a patient with autosomal dominant polycystic kidney disease by sequential celiac plexus blockade, radiofrequency ablation, and spinal cord stimulation. Am. J. Kidney Dis. 59, 858–861 (2012).

    Article  PubMed  Google Scholar 

  147. Loukas, M. et al. A review of the thoracic splanchnic nerves and celiac ganglia. Clin. Anat. 23, 512–522 (2010).

    Article  PubMed  Google Scholar 

  148. Casteleijn, N. F., de Jager, R. L., Neeleman, M. P., Blankestijn, P. J. & Gansevoort, R. T. Chronic kidney pain in autosomal dominant polycystic kidney disease: a case report of successful treatment by catheter-based renal denervation. Am. J. Kidney Dis. 63, 1019–1021 (2014).

    Article  PubMed  Google Scholar 

  149. Valente, J. F., Dreyer, D. R., Breda, M. A. & Bennett, W. M. Laparoscopic renal denervation for intractable ADPKD-related pain. Nephrol. Dial. Transplant. 16, 160 (2001).

    Article  CAS  PubMed  Google Scholar 

  150. Chapuis, O., Sockeel, P., Pallas, G., Pons, F. & Jancovici, R. Thoracoscopic renal denervation for intractable autosomal dominant polycystic kidney disease-related pain. Am. J. Kidney Dis. 43, 161–163 (2004).

    Article  PubMed  Google Scholar 

  151. Bhatt, D. L. et al. A controlled trial of renal denervation for resistant hypertension. N. Engl. J. Med. 370, 1393–1401 (2014).

    Article  CAS  PubMed  Google Scholar 

  152. Haseebuddin, M. et al. Long-term impact of laparoscopic cyst decortication on renal function, hypertension and pain control in patients with autosomal dominant polycystic kidney disease. J. Urol. 188, 1239–1244 (2012).

    Article  PubMed  Google Scholar 

  153. Millar, M. et al. Surgical cyst decortication in autosomal dominant polycystic kidney disease. J. Endourol. 27, 528–534 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  154. Cook, N. R. et al. Long term effects of dietary sodium reduction on cardiovascular disease outcomes: observational follow-up of the trials of hypertension prevention (TOHP). BMJ 334, 885–888 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  155. Torres, V. E. et al. Dietary salt restriction is beneficial to the management of autosomal dominant polycystic kidney disease. Kidney Int. 91, 493–500 (2017).

    Article  CAS  PubMed  Google Scholar 

  156. McMahon, E. J., Campbell, K. L., Bauer, J. D. & Mudge, D. W. Altered dietary salt intake for people with chronic kidney disease. Cochrane Database Syst. Rev., CD010070 (2015).

  157. Dougher, C. E. et al. Spot urine sodium measurements do not accurately estimate dietary sodium intake in chronic kidney disease. Am. J. Clin. Nutr. 104, 298–305 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Thomas, M. C. et al. The association between dietary sodium intake, ESRD, and all-cause mortality in patients with type 1 diabetes. Diabetes Care 34, 861–866 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Mente, A., O'Donnell, M. J. & Yusuf, S. Sodium and cardiovascular disease — Authors' reply. Lancet 388, 2113–2114 (2016).

    Article  PubMed  Google Scholar 

  160. O'Donnell, M. et al. Dietary sodium and cardiovascular disease risk. N. Engl. J. Med. 375, 2404–2406 (2016).

    Article  PubMed  Google Scholar 

  161. O'Donnell, M., Mente, A. & Yusuf, S. Commentary: Accepting what we don't know will lead to progress. Int. J. Epidemiol. 45, 260–262 (2016).

    Article  PubMed  Google Scholar 

  162. Campbell, N. R. Dissidents & dietary sodium: concerns about the commentary by O'Donnell et al. Int. J. Epidemiol. 46, 362–366 (2017).

    PubMed  Google Scholar 

  163. Graudal, N., Jurgens, G., Baslund, B. & Alderman, M. H. Compared with usual sodium intake, low- and excessive-sodium diets are associated with increased mortality: a meta-analysis. Am. J. Hypertens. 27, 1129–1137 (2014).

    Article  CAS  PubMed  Google Scholar 

  164. Vegter, S. et al. Sodium intake, ACE inhibition, and progression to ESRD. J. Am. Soc. Nephrol. 23, 165–173 (2012).

    Article  CAS  PubMed  Google Scholar 

  165. Lambers Heerspink, H. J. et al. Moderation of dietary sodium potentiates the renal and cardiovascular protective effects of angiotensin receptor blockers. Kidney Int. 82, 330–337 (2012).

    Article  CAS  PubMed  Google Scholar 

  166. Maroni, B. J., Steinman, T. I. & Mitch, W. E. A method for estimating nitrogen intake of patients with chronic renal failure. Kidney Int. 27, 58–65 (1985).

    Article  CAS  PubMed  Google Scholar 

  167. Ko, G. J., Obi, Y., Tortorici, A. R. & Kalantar-Zadeh, K. Dietary protein intake and chronic kidney disease. Curr. Opin. Clin. Nutr. Metab. Care 20, 77–85 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Kalantar-Zadeh, K. et al. North American experience with low protein diet for non-dialysis-dependent chronic kidney disease. BMC Nephrol. 17, 90 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Ma, Y. et al. A dietary quality comparison of popular weight-loss plans. J. Am. Diet Assoc. 107, 1786–1791 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  170. Levey, A. S. et al. Effect of dietary protein restriction on the progression of kidney disease: long-term follow-up of the Modification of Diet in Renal Disease (MDRD) Study. Am. J. Kidney Dis. 48, 879–888 (2006).

    Article  CAS  PubMed  Google Scholar 

  171. Fouque, D. & Laville, M. Low protein diets for chronic kidney disease in non diabetic adults. Cochrane Database Syst Rev, CD001892 (2009).

  172. Boertien, W. E. et al. Short-term effects of tolvaptan in individuals with autosomal dominant polycystic kidney disease at various levels of kidney function. Am. J. Kidney Dis. 65, 833–841 (2015).

    Article  CAS  PubMed  Google Scholar 

  173. Wang, C. J., Grantham, J. J. & Wetmore, J. B. The medicinal use of water in renal disease. Kidney Int. 84, 45–53 (2013).

    Article  PubMed  Google Scholar 

  174. 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. 5, 693–697 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  175. Wang, C. J., Creed, C., Winklhofer, F. T. & Grantham, J. J. Water prescription in autosomal dominant polycystic kidney disease: a pilot study. Clin. J. Am. Soc. Nephrol. 6, 192–197 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. Higashihara, E. et al. Does increased water intake prevent disease progression in autosomal dominant polycystic kidney disease? Nephrol. Dial. Transplant. 29, 1710–1719 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. Lacquaniti, A. et al. Apelin and copeptin: two opposite biomarkers associated with kidney function decline and cyst growth in autosomal dominant polycystic kidney disease. Peptides 49, 1–8 (2013).

    Article  CAS  PubMed  Google Scholar 

  178. Kocer, D., Karakukcu, C., Ozturk, F., Eroglu, E. & Kocyigit, I. Evaluation of fibrosis markers: apelin and transforming growth factor-β1 in autosomal dominant polycystic kidney disease patients. Ther. Apher. Dial. 20, 517–522 (2016).

    Article  CAS  PubMed  Google Scholar 

  179. Helal, I. et al. Serum uric acid, kidney volume and progression in autosomal-dominant polycystic kidney disease. Nephrol. Dial. Transplant. 28, 380–385 (2013).

    Article  CAS  PubMed  Google Scholar 

  180. Kocyigit, I. et al. Serum uric acid levels and endothelial dysfunction in patients with autosomal dominant polycystic kidney disease. Nephron Clin. Pract. 123, 157–164 (2013).

    Article  CAS  PubMed  Google Scholar 

  181. Akiyama, K., Mochizuki, T., Kataoka, H., Tsuchiya, K. & Nitta, K. Fibroblast growth factor 23 and soluble Klotho in patients with autosomal dominant polycystic kidney disease. Nephrology http://dx.doi.org/10.1111/nep.12862 (2016).

  182. Pavik, I. et al. Soluble klotho and autosomal dominant polycystic kidney disease. Clin. J. Am. Soc. Nephrol. 7, 248–257 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  183. Pavik, I. et al. Secreted Klotho and FGF23 in chronic kidney disease Stage 1 to 5: a sequence suggested from a cross-sectional study. Nephrol. Dial. Transplant. 28, 352–359 (2013).

    Article  CAS  PubMed  Google Scholar 

  184. Meijer, E. et al. Association of urinary biomarkers with disease severity in patients with autosomal dominant polycystic kidney disease: a cross-sectional analysis. Am. J. Kidney Dis. 56, 883–895 (2010).

    Article  CAS  PubMed  Google Scholar 

  185. Parikh, C. R. et al. Evaluation of urine biomarkers of kidney injury in polycystic kidney disease. Kidney Int. 81, 784–790 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  186. Harskamp, L. R. et al. Urinary EGF receptor ligand excretion in patients with autosomal dominant polycystic kidney disease and response to tolvaptan. Clin. J. Am. Soc. Nephrol. 10, 1749–1756 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  187. Zschiedrich, S. et al. Secreted frizzled-related protein 4 predicts progression of autosomal dominant polycystic kidney disease. Nephrol. Dial Transplant 31, 284–289 (2016).

    Article  CAS  PubMed  Google Scholar 

  188. Ruggenenti, P. et al. Effect of sirolimus on disease progression in patients with autosomal dominant polycystic kidney disease and CKD stages 3b-4. Clin. J. Am. Soc. Nephrol. 11, 785–794 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

M.B.L. is supported by the American Society of Nephrology Jared J. Grantham fellowship.

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Authors and Affiliations

  1. Nephrology Division, Department of Medicine, McMaster University, St Joseph's Healthcare Hamilton, 50 Charlton Avenue E, Hamilton, L8N 4A6, Ontario, Canada

    Matthew B. Lanktree

  2. Department of Medicine, Section of Nephrology, University of Chicago, 5841 S Maryland Avenue, W503, Chicago, 60637, Illinois, USA

    Arlene B. Chapman

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A.B.C. declares an association with Otsuka Pharmaceutical Group through membership of the TEMPO steering committee. M.B.L. declares no competing interests.

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Lanktree, M., Chapman, A. New treatment paradigms for ADPKD: moving towards precision medicine. Nat Rev Nephrol 13, 750–768 (2017). https://doi.org/10.1038/nrneph.2017.127

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