Consult the medical resource doctors trust

UpToDate is one of the most respected medical information resources in the world, used by over 360,000 doctors and thousands of patients to find answers to medical questions.

  • Content written by a faculty of over 4,000 physicians from leading medical institutions
  • Unbiased: free of advertising or pharmaceutical funding
  • Evidence-based treatment recommendations
  • Continuously updated to incorporate new medical findings

Course and treatment of autosomal dominant polycystic kidney disease

INTRODUCTION

Polycystic kidney disease (PKD) is an inherited disease that causes an irreversible decline in kidney function. PKD may be inherited as an autosomal dominant or recessive trait. The autosomal dominant form (ADPKD) is the most common genetic cause of chronic kidney disease [1,2]. The majority of individuals with PKD eventually require renal replacement therapy [1].

The course and treatment of ADPKD in adults are discussed here. The diagnosis, genetics and pathogenesis of ADPKD, and autosomal recessive PKD in children are discussed elsewhere. (See "Diagnosis of and screening for autosomal dominant polycystic kidney disease" and "Genetics of autosomal dominant polycystic kidney disease and mechanisms of cyst growth" and "Autosomal recessive and dominant polycystic kidney disease in children".)

EPIDEMIOLOGY

Autosomal dominant PKD (ADPKD) occurs in virtually all races and has a reported prevalence of 1:400 to 1:1000 [3]. ADPKD is the underlying cause of kidney disease in approximately five percent of patients who initiate dialysis annually in the United States [4,5].

ADPKD is caused by mutations of either PKD1 (which encodes polycystin-1) on chromosome 16 or PKD2 (which encodes polycystin-2) on chromosome 4 [4]. PKD1 mutations are more common (approximately 85 percent) than PKD2 mutations (approximately 15 percent) although the relative frequency of PKD1 and PKD2 mutations depends on the age of the population that is being studied since patients with PKD2 mutations present at an older age and progress more slowly than patients with PKD1 mutations. As a result, PKD2 mutations may be relatively underreported in a greater number of individuals compared to PKD1, and the frequency of PKD2 underestimated among populations in which only symptomatic individuals are tested. This is demonstrated by the following:

  • PKD1 mutations were present in 85 and PKD2 15 percent of cases respectively in one study of patients who had known PKD [6]. By contrast, the frequency of PKD2 mutations was higher in population-based studies that included individuals who were at risk for ADPKD but had no evidence of clinical renal disease [3,6].
  • Since patients with PKD1 reach end stage renal disease or die at a younger age compared to those with PKD2 [7], studies of older patients with ADPKD demonstrate a higher proportion of disease attributable to PKD2 [2,8]. In one study of 46 patients with ADPKD who had not yet started dialysis by age 63, 18 had mutations of PKD2. This is in contrast to only 4 of 40 patients with ADPKD younger than age 63 who served as a control group [8]. (See "Genetics of autosomal dominant polycystic kidney disease and mechanisms of cyst growth".)
To continue reading this article you need to subscribe.

Read the rest of this article and others like it

The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use (click here) ©2010 UpToDate, Inc.
References Top
  1. Patel, V, Chowdhury, R, Igarashi, P. Advances in the pathogenesis and treatment of polycystic kidney disease. Curr Opin Nephrol Hypertens 2009; 18:99.
  2. Barua, M, Cil, O, Paterson, AD, et al. Family history of renal disease severity predicts the mutated gene in ADPKD. J Am Soc Nephrol 2009; 20:1833.
  3. Torres, VE, Harris, PC. Autosomal dominant polycystic kidney disease: the last 3 years. Kidney Int 2009; 76:149.
  4. Torres, VE, Harris, PC, Pirson, Y. Autosomal dominant polycystic kidney disease. Lancet 2007; 369:1287.
  5. Harris, PC, Torres, VE. Polycystic kidney disease. Annu Rev Med 2009; 60:321.
  6. Rossetti, S, Consugar, MB, Chapman, AB, et al. Comprehensive molecular diagnostics in autosomal dominant polycystic kidney disease. J Am Soc Nephrol 2007; 18:2143.
  7. Hateboer, N, v Dijk, MA, Bogdanova, N, et al. Comparison of phenotypes of polycystic kidney disease types 1 and 2. Lancet 1999; 353:103.
  8. Torra, R, Badenas, C, Perez-Oller, L, et al. Increased prevalence of polycystic kidney disease type 2 among elderly polycystic patients. Am J Kidney Dis 2000; 36:728.
  9. de Almeida, E, Prata, MM, de Almeida, S, Lavinha, J. Long-term follow-up of a family with autosomal dominant polycystic kidney disease type 3. Nephrol Dial Transplant 1999; 14:631.
  10. Igarashi, P, Somlo, S. Genetics and pathogenesis of polycystic kidney disease. J Am Soc Nephrol 2002; 13:2384.
  11. Rossetti, S, Harris, PC. Genotype-phenotype correlations in autosomal dominant and autosomal recessive polycystic kidney disease. J Am Soc Nephrol 2007; 18:1374.
  12. Bergmann, C, Bruchle, NO, Frank, V, et al. Perinatal deaths in a family with autosomal dominant polycystic kidney disease and a PKD2 mutation. N Engl J Med 2008; 359:318.
  13. Peters, DJ, Breuning, MH. Autosomal dominant polycystic kidney disease: Modification of disease progression. Lancet 2001; 358:1439.
  14. Gabow, PA, Johnson, AM, Kaehny, WD, et al. Factors affecting the prognosis of renal disease in autosomal-dominant polycystic kidney disease. Kidney Int 1992; 41:1311.
  15. Johnson, AM, Gabow, PA. Identification of patients with autosomal dominant polycystic kidney disease at highest risk for end-stage renal disease. J Am Soc Nephrol 1997; 8:1560.
  16. Fick-Brosnahan, GM, Tran, ZV, Johnson, AM, et al. Progression of autosomal-dominant polycystic kidney disease in children. Kidney Int 2001; 59:1654.
  17. Fick-Brosnahan, GM, Belz, MM, McFann, KK, et al. Relationship between renal volume growth and renal function in autosomal dominant polycystic kidney disease: A longitudinal study. Am J Kidney Dis 2002; 39:1127.
  18. King, BF, Torres, VE, Brummer, ME, et al. Magnetic resonance measurements of renal blood flow as a marker of disease severity in autosomal-dominant polycystic kidney disease. Kidney Int 2003; 64:2214.
  19. Rizk, D, Chapman, AB. Cystic and inherited kidney diseases. Am J Kidney Dis 2003; 42:1305.
  20. Grantham, JJ. Clinical practice. Autosomal dominant polycystic kidney disease. N Engl J Med 2008; 359:1477.
  21. Yium, J, Gabow, P, Johnson, A, et al. Autosomal dominant polycystic kidney disease in blacks: clinical course and effects of sickle-cell hemoglobin. J Am Soc Nephrol 1994; 4:1670.
  22. Schrier, RW, McFann, KK, Johnson, AM. Epidemiological study of kidney survival in autosomal dominant polycystic kidney disease. Kidney Int 2003; 63:678.
  23. Dicks, E, Ravani, P, Langman, D, et al. Incident renal events and risk factors in autosomal dominant polycystic kidney disease: a population and family-based cohort followed for 22 years. Clin J Am Soc Nephrol 2006; 1:710.
  24. Brook-Carter, PT, Peral, B, Ward, CJ, et al. Deletion of the TSC2 and PKD1 genes associated with severe infantile polycystic kidney disease--a contiguous gene syndrome. Nat Genet 1994; 8:328.
  25. Rossetti, S, Burton, S, Strmecki, L, et al. The position of the polycystic kidney disease 1 (PKD1) gene mutation correlates with the severity of renal disease. J Am Soc Nephrol 2002; 13:1230.
  26. Rossetti, S, Chauveau, D, Kubly, V, et al. Association of mutation position in polycystic kidney disease 1 (PKD1) gene and development of a vascular phenotype. Lancet 2003; 361:2196.
  27. Hateboer, N, Veldhuisen, B, Peters, D, et al. Location of mutations within the PKD2 gene influences clinical outcome. Kidney Int 2000; 57:1444.
  28. Magistroni, R, He, N, Wang, K, Andrew, R. Genotype-renal function correlation in type 2 autosomal dominant polycystic kidney disease. J Am Soc Nephrol 2003; 14:1164.
  29. Hateboer, N, Lazarou, LP, Williams, AJ, et al. Familial phenotype differences in PKD1. Kidney Int 1999; 56:34.
  30. Connor, A, Lunt, PW, Dolling, C, et al. Mosaicism in autosomal dominant polycystic kidney disease revealed by genetic testing to enable living related renal transplantation. Am J Transplant 2008; 8:232.
  31. Consugar, MB, Wong, WC, Lundquist, PA, et al. Characterization of large rearrangements in autosomal dominant polycystic kidney disease and the PKD1/TSC2 contiguous gene syndrome. Kidney Int 2008; 74:1468.
  32. Rossetti, S, Kubly, VJ, Consugar, MB, et al. Incompletely penetrant PKD1 alleles suggest a role for gene dosage in cyst initiation in polycystic kidney disease. Kidney Int 2009; 75:848.
  33. Fain, PR, McFann, KK, Taylor, MR, et al. Modifier genes play a significant role in the phenotypic expression of PKD1. Kidney Int 2005; 67:1256.
  34. Persu, A, Duyme, M, Pirson, Y, et al. Comparison between siblings and twins supports a role for modifier genes in ADPKD. Kidney Int 2004; 66:2132.
  35. Baboolal, K, Ravine, D, Daniels, J, et al. Association of the angiotensin I converting enzyme gene deletion polymorphism with early onset of ESRF in PKD1 adult polycystic kidney disease. Kidney Int 1997; 52:607.
  36. O'Sullivan, DA, Torres, VE, Gabow, PA, et al. Cystic fibrosis and the phenotypic expression of autosomal dominant polycystic kidney disease. Am J Kidney Dis 1998; 32:976.
  37. Persu, A, Devuyst, O, Lannoy, N, et al. CF gene and cystic fibrosis transmembrane conductance regulator expression in autosomal dominant polycystic kidney disease. J Am Soc Nephrol 2000; 11:2285.
  38. Gabow, PA, Chapman, AB, Johnson, AM, et al. Renal structure and hypertension in autosomal dominant polycystic kidney disease. Kidney Int 1990; 38:1177.
  39. Chapman, AB, Guay-Woodford, LM, Grantham, JJ, 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 2003; 64:1035.
  40. King, BF, Reed, JE, Bergstralh, EJ, et al. Quantification and longitudinal trends of kidney, renal cyst, and renal parenchyma volumes in autosomal dominant polycystic kidney disease. J Am Soc Nephrol 2000; 11:1505.
  41. Grantham, JJ, Torres, VE, Chapman, AB, et al. Volume progression in polycystic kidney disease. N Engl J Med 2006; 354:2122.
  42. Torres, VE, King, BF, Chapman, AB, et al. Magnetic resonance measurements of renal blood flow and disease progression in autosomal dominant polycystic kidney disease. Clin J Am Soc Nephrol 2007; 2:112.
  43. Pei, Y. Nature and nurture on phenotypic variability of autosomal dominant polycystic kidney disease. Kidney Int 2005; 67:1630.
  44. Chapman, AB, Johnson, AM, Gabow, PA, Schrier, RW. Overt proteinuria and microalbuminuria in autosomal dominant polycystic kidney disease. J Am Soc Nephrol 1994; 5:1349.
  45. Sharp, C, Johnson, A, Gabow, P. Factors relating to urinary protein excretion in children with autosomal dominant polycystic kidney disease. J Am Soc Nephrol 1998; 9:1908.
  46. Grantham, JJ, Chapman, AB, Torres, VE. Volume progression in autosomal dominant polycystic kidney disease: the major factor determining clinical outcomes. Clin J Am Soc Nephrol 2006; 1:148.
  47. Bae, KT, Tao, C, Zhu, F, et al. MRI-based kidney volume measurements in ADPKD: reliability and effect of gadolinium enhancement. Clin J Am Soc Nephrol 2009; 4:719.
  48. O'Neill, WC, Robbin, ML, Bae, KT, et al. Sonographic assessment of the severity and progression of autosomal dominant polycystic kidney disease: the Consortium of Renal Imaging Studies in Polycystic Kidney Disease (CRISP). Am J Kidney Dis 2005; 46:1058.
  49. Perrone, RD, Ruthazer, R, Terrin, NC. Survival after end-stage renal disease in autosomal dominant polycystic kidney disease: Contribution of extrarenal complications to mortality. Am J Kidney Dis 2001; 38:777.
  50. Fick, GM, Johnson, AM, Hammond, WS, Gabow, PA. Causes of death in autosomal dominant polycystic kidney disease. J Am Soc Nephrol 1995; 5:2048.
  51. Chapman, AB, Johnson, AM, Gabow, PA. Pregnancy outcome and its relationship to progression of renal failure in autosomal dominant polycystic kidney disease. J Am Soc Nephrol 1994; 5:1178.
  52. K/DOQI Clinical Practice Guidelines on Hypertension and Antihypertensive Agents in Chronic Kidney Disease. Am J Kidney Dis 2004; 43:5(Suppl 1):S1.
  53. Chobanian, AV, Bakris, GL, Black, HR, Cushman, WC. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 Report. JAMA 2003; 289:2560.
  54. Schrier, RW. Renal volume, renin-angiotensin-aldosterone system, hypertension, and left ventricular hypertrophy in patients with autosomal dominant polycystic kidney disease. J Am Soc Nephrol 2009; 20:1888.
  55. Namli, S, Oflaz, H, Turgut, F, et al. Improvement of endothelial dysfunction with simvastatin in patients with autosomal dominant polycystic kidney disease. Ren Fail 2007; 29:55.
  56. Bremmer, MS, Jacobs, SC. Renal artery embolization for the symptomatic treatment of adult polycystic kidney disease. Nat Clin Pract Nephrol 2008; 4:236.
  57. Grantham, JJ. Lillian Jean Kaplan International Prize for advancement in the understanding of polycystic kidney disease. Understanding polycystic kidney disease: A systems biology approach. Kidney Int 2003; 64:1157.
  58. Calvet, JP. Strategies to inhibit cyst formation in ADPKD. Clin J Am Soc Nephrol 2008; 3:1205.
  59. Torres, VE, Wang, X, Qian, Q, et al. Effective treatment of an orthologous model of autosomal dominant polycystic kidney disease. Nat Med 2004; 10:363.
  60. Wang, X, Wu, Y, Ward, CJ, et al. Vasopressin directly regulates cyst growth in polycystic kidney disease. J Am Soc Nephrol 2008; 19:102.
  61. Grantham, JJ. Therapy for polycystic kidney disease? It's water, stupid!. J Am Soc Nephrol 2008; 19:1.
  62. Bennett, WM. V2 Receptor Antagonists in Cystic Kidney Diseases: An Exciting Step towards a Practical Treatment. J Am Soc Nephrol 2005; 16:838.
  63. Torres, VE. Role of vasopressin antagonists. Clin J Am Soc Nephrol 2008; 3:1212.
  64. Torres, VE, Bankir, L, Grantham, JJ. A case for water in the treatment of polycystic kidney disease. Clin J Am Soc Nephrol 2009; 4:1140.
  65. Grantham, JJ, Uchic, M, Cragoe, EJ, Jr, et al. Chemical modification of cell proliferation and fluid secretion in renal cysts. Kidney Int 1989; 35:1379.
  66. Gardner, KD Jr, Burnside, JS, Skipper, BJ, et al. On the probability that kidneys are different in autosomal dominant polycystic disease. Kidney Int 1992; 42:1199.
  67. Belibi, FA, Wallace, DP, Yamaguchi, T, et al. The effect of caffeine on renal epithelial cells from patients with autosomal dominant polycystic kidney disease. J Am Soc Nephrol 2002; 13:2723.
  68. Ruggenenti, P, Remuzzi, A, Ondei, P, et al. Safety and efficacy of long-acting somatostatin treatment in autosomal-dominant polycystic kidney disease. Kidney Int 2005; 68:206.
  69. Shillingford, JM, Murcia, NS, Larson, CH, et al. The mTOR pathway is regulated by polycystin-1, and its inhibition reverses renal cystogenesis in polycystic kidney disease. Proc Natl Acad Sci U S A 2006; 103:5466.
  70. Longa, L, Scolari, F, Brusco, A, et al. A large TSC2 and PKD1 gene deletion is associated with renal and extrarenal signs of autosomal dominant polycystic kidney disease. Nephrol Dial Transplant 1997; 12:1900.
  71. Wuthrich, RP, Serra, AL. Mammalian target of rapamycin and autosomal dominant polycystic kidney disease. Transplant Proc 2009; 41:S18.
  72. Qian, Q, Du, H, King, BF, et al. Sirolimus reduces polycystic liver volume in ADPKD patients. J Am Soc Nephrol 2008; 19:631.
  73. Woo, DD, Miao, SY, Pelayo, JC, Woolf, AS. Taxol inhibits progression of congenital polycystic kidney disease. Nature 1994; 368:750.
  74. Cowley, BD Jr, Gudapaty, S, Kraybill, AL, et al. Autosomal-dominant polycystic kidney disease in the rat. Kidney Int 1993; 43:522.
  75. Gile, RD, Cowley, BD Jr, Gattone, VHI, et al. Effect of lovastatin on the development of polycystic kidney disease in the Han:SPRD rat. Am J Kidney Dis 1995; 26:501.
  76. Keith, DS, Torres, VE, Johnson, CM, Holley, KE. Effect of sodium chloride, enalapril, and losartan on the development of polycystic kidney disease in Han:SPRD rats. Am J Kidney Dis 1994; 24:491.
  77. Gattone, VHI, Cowley, BD Jr, Barash, BD, et al. Methylprednisolone retards the progression of inherited polycystic kidney disease in rodents. Am J Kidney Dis 1995; 25:302.
  78. Nomura, H, Turco, AE, Pei, Y, et al. Identification of PKDL, a novel polycystic kidney disease 2-like gene whose murine homologue is deleted in mice with kidney and retinal defects. J Biol Chem 1998; 273:25967.
  79. Tao, Y, Kim, J, Schrier, RW, Edelstein, CL. Rapamycin markedly slows disease progression in a rat model of polycystic kidney disease. J Am Soc Nephrol 2005; 16:46.
  80. Wahl, PR, Serra, AL, Le Hir, M, et al. Inhibition of mTOR with sirolimus slows disease progression in Han:SPRD rats with autosomal dominant polycystic kidney disease (ADPKD). Nephrol Dial Transplant 2006; 21:598.
  81. Sweeney, WE Jr, Hamahira, K, Sweeney, J, et al. Combination treatment of PKD utilizing dual inhibition of EGF-receptor activity and ligand bioavailability. Kidney Int 2003; 64:1310.
  82. Muto, S, Aiba, A, Saito, Y, et al. Pioglitazone improves the phenotype and molecular defects of a targeted PKD1 mutant. Hum Mol Genet 2002; 11:1731.
  83. Omori, S, Hida, M, Fujita, H, et al. Extracellular signal-regulated kinase inhibition slows disease progression in mice with polycystic kidney disease. J Am Soc Nephrol 2006; 17:1604.
  84. Smith, LA, Bukanov, NO, Husson, H, et al. Development of polycystic kidney disease in juvenile cystic kidney mice: insights into pathogenesis, ciliary abnormalities, and common features with human disease. J Am Soc Nephrol 2006; 17:2821.
  85. Bukanov, NO, Smith, LA, Klinger, KW, et al. Long-lasting arrest of murine polycystic kidney disease with CDK inhibitor roscovitine. Nature 2006; 444:949.
  86. Lederman, ED, McCoy, G, Conti, DJ, Lee, EC. Diverticulitis and polycystic kidney disease. Am Surg 2000; 66:200.
  87. Hadimeri, H, Johansson, AC, Haraldsson, B, Nyberg, G. CAPD in patients with autosomal dominant polycystic kidney disease. Perit Dial Int 1998; 18:429.
  88. Hadimeri, H, Norden, G, Friman, S, Nyberg, G. Autosomal dominant polycystic kidney disease in a kidney transplant population. Nephrol Dial Transplant 1997; 12:1431.
  89. 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.
  90. Pirson, Y, Christophe, JL, Goffin, E. Outcome of renal replacement therapy in autosomal dominant polycystic kidney disease. Nephrol Dial Transplant 1996; 11 Suppl 6:24.
  91. Abbott, KC, Agodoa, LY. Polycystic kidney disease at end-stage renal disease in the United States: Patient characteristics and survival. Clin Nephrol 2002; 57:208.
  92. Hamer, RA, Chow, CL, Ong, AC, McKane, WS. Polycystic kidney disease is a risk factor for new-onset diabetes after transplantation. Transplantation 2007; 83:36.
  93. Andreoni, KA, Pelletier, RP, Elkhammas, EA, et al. Increased incidence of gastrointestinal surgical complications in renal transplant recipients with polycystic kidney disease. Transplantation 1999; 67:262.
  94. Wijdicks, EF, Torres, VE, Schievink, WI, Sterioff, S. Cerebral hemorrhage in recipients of renal transplantation. Mayo Clin Proc 1999; 74:1111.
  95. Stiasny, B, Ziebell, D, Graf, S, et al. Clinical aspects of renal transplantation in polycystic kidney disease. Clin Nephrol 2002; 58:16.
  96. Glassman, DT, Nipkow, L, Bartlett, ST, Jacobs, SC. Bilateral nephrectomy with concomitant renal graft transplantation for autosomal dominant polycystic kidney disease. J Urol 2000; 164:661.
  97. Fuller, TF, Brennan, TV, Feng, S, et al. End stage polycystic kidney disease: indications and timing of native nephrectomy relative to kidney transplantation. J Urol 2005; 174:2284.
  98. Whitten, MG, Van der, Werf W, Belnap, L. A novel approach to bilateral hand-assisted laparoscopic nephrectomy for autosomal dominant polycystic kidney disease. Surg Endosc 2006; 20:679.
white circle LOG IN
white circle DEMO