Mechanism-based therapeutics for autosomal dominant polycystic kidney disease: Recent progress and future prospects

Nephron - Clinical Practice

Volumn 120, Issue 1, 2012, Pages

  Chang, Ming Yang ^a   Ong, Albert C M ^b,c  

^a CHANG GUNG UNIVERSITY   (Taiwan)

^b UNIVERSITY OF SHEFFIELD   (United Kingdom)

^c SHEFFIELD TEACHING HOSPITALS NHS FOUNDATION TRUST   (United Kingdom)

Author keywords

Autosomal dominant polycystic kidney disease; Calcium; cAMP; ERK; mTOR; PKD1; PKD2; Polycystic kidney disease; Therapeutics

Indexed keywords

ADENYLATE CYCLASE; ANGIOPEPTIN; BOSUTINIB; CALCIUM; CHLORIDE CHANNEL; CYCLIC AMP; EVEROLIMUS; LISINOPRIL; MAMMALIAN TARGET OF RAPAMYCIN; METFORMIN; MOZAVAPTAN; OCTREOTIDE; PHOSPHODIESTERASE; PIOGLITAZONE; POLYCYSTIN 1; POLYCYSTIN 2; PRAVASTATIN; RAPAMYCIN; ROSCOVITINE; ROSIGLITAZONE; SOMATOSTATIN; SOMATOSTATIN DERIVATIVE; SORAFENIB; TECALCET; TELMISARTAN; TOLVAPTAN; TRICHOSTATIN A; TRIPTOLIDE; UNINDEXED DRUG; VASOPRESSIN RECEPTOR ANTAGONIST;

ACNE; ANGIONEUROTIC EDEMA; APHTHOUS STOMATITIS; AUTOSOMAL DOMINANT DISORDER; CARDIOVASCULAR DISEASE; CELL PROLIFERATION; CLINICAL TRIAL (TOPIC); CONTROLLED CLINICAL TRIAL (TOPIC); DIARRHEA; DISEASE ASSOCIATION; FOLLICULITIS; GENE CONTROL; GENE MUTATION; GLOMERULUS FILTRATION RATE; GRANULOMA; HUMAN; HYPERLIPIDEMIA; HYPERTENSION; INJECTION SITE NODULE; KIDNEY CARCINOMA; KIDNEY CYST; KIDNEY FAILURE; KIDNEY POLYCYSTIC DISEASE; KIDNEY TRANSPLANTATION; KIDNEY TUBULE EXCRETION; LACTIC ACIDOSIS; LEUKOPENIA; LIVER CELL CARCINOMA; LIVER POLYCYSTIC DISEASE; LOOSE FECES; MUCOSA INFLAMMATION; MULTICENTER STUDY (TOPIC); NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PERIPHERAL EDEMA; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEINURIA; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; STOMATITIS; TREATMENT PLANNING;

ANILINE COMPOUNDS; ANTIHYPERTENSIVE AGENTS; BENZAZEPINES; CLINICAL TRIALS AS TOPIC; CYCLIC AMP; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; DEPRESSION, CHEMICAL; DISEASE MANAGEMENT; DOUBLE-BLIND METHOD; DRUGS, INVESTIGATIONAL; FORECASTING; HISTONE DEACETYLASE INHIBITORS; HUMANS; MULTICENTER STUDIES AS TOPIC; NITRILES; POLYCYSTIC KIDNEY, AUTOSOMAL DOMINANT; PURINES; QUINOLINES; RANDOMIZED CONTROLLED TRIALS AS TOPIC; SIGNAL TRANSDUCTION; SOMATOSTATIN; TOR SERINE-THREONINE KINASES; TRANSLATIONAL MEDICAL RESEARCH;

EID: 84859436061     PISSN: None     EISSN: 16602110     Source Type: Journal    
DOI: 10.1159/000334166     Document Type: Review

References (73)

1. Torres VE, Bankir L, Grantham JJ: A case for water in the treatment of polycystic kidney disease. Clin J Am Soc Nephrol 2009; 4: 1140-1150.
2. Chang MY, Ong AC: Autosomal dominant polycystic kidney disease: recent advances in pathogenesis and treatment. Nephron Physiol 2008; 108: 1-7.
3. Grantham JJ, Torres VE, Chapman AB, Guay-Woodford LM, Bae KT, King BF Jr, Wetzel LH, Baumgarten DA, Kenney PJ, Harris PC, Klahr S, Bennett WM, Hirschman GN, Meyers CM, Zhang X, Zhu F, Miller JP: Volume progression in polycystic kidney disease. N Engl J Med 2006; 354: 2122-2130. (Pubitemid 43736612)
4. Harris PC, Bae KT, Rossetti S, Torres VE, Grantham JJ, Chapman AB, Guay-Woodford LM, King BF, Wetzel LH, Baumgarten DA, Kenney PJ, Consugar M, Klahr S, Bennett WM, Meyers CM, Zhang QJ, Thompson PA, Zhu F, Miller JP: Cyst number but not the rate of cystic growth is associated with the mutated gene in autosomal dominant polycystic kidney disease. J Am Soc Nephrol 2006; 17: 3013-3019. (Pubitemid 44707761)
5. Newby LJ, Streets AJ, Zhao Y, Harris PC, Ward CJ, Ong AC: Identification, characterization, and localization of a novel kidney polycystin-1-polycystin-2 complex. J Biol Chem 2002; 277: 20763-20773. (Pubitemid 34967382)
6. Ong AC, Harris PC: Molecular pathogenesis of ADPKD: the polycystin complex gets complex. Kidney Int 2005; 67: 1234-1247. (Pubitemid 40463100)
7. Nauli SM, Alenghat FJ, Luo Y, Williams E, Vassilev P, Li X, Elia AE, Lu W, Brown EM, Quinn SJ, Ingber DE, Zhou J: Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells. Nat Genet 2003; 33: 129-137. (Pubitemid 36177063)
8. Streets AJ, Wagner BE, Harris PC, Ward CJ, Ong AC: Homophilic and heterophilic polycystin
9. interactions regulate E-cadherin recruitment and junction assembly in MDCK cells. J Cell Sci 2009; 122: 1410-1417.
10. Giamarchi A, Feng S, Rodat-Despoix L, Xu Y, Bubenshchikova E, Newby LJ, Hao J, Gaudioso C, Crest M, Lupas AN, Honore E, Williamson MP, Obara T, Ong AC, Delmas P: A polycystin-2 (TRPP2) dimerization domain essential for the function of heteromeric polycystin complexes. EMBO J 2010; 29: 1176-1191.
11. Tao Y, Kim J, Faubel S, Wu JC, Falk SA, Schrier RW, Edelstein CL: Caspase inhibition reduces tubular apoptosis and proliferation and slows disease progression in polycystic kidney disease. Proc Natl Acad Sci USA 2005; 102: 6954-6959. (Pubitemid 40675423)
12. Leuenroth SJ, Okuhara D, Shotwell JD, Markowitz GS, Yu Z, Somlo S, Crews CM: Triptolide is a traditional Chinese medicine-derived inhibitor of polycystic kidney disease. Proc Natl Acad Sci USA 2007; 104: 4389-4394. (Pubitemid 47186236)
13. Yamaguchi T, Wallace DP, Magenheimer BS, Hempson SJ, Grantham JJ, Calvet JP: 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: 40419-40430. (Pubitemid 39287631)
14. Yamaguchi T, Hempson SJ, Reif GA, Hedge AM, Wallace DP: Calcium restores a normal proliferation phenotype in human polycystic kidney disease epithelial cells. J Am Soc Nephrol 2006; 17: 178-187.
15. Parker E, Newby LJ, Sharpe CC, Rossetti S, Streets AJ, Harris PC, O'Hare MJ, Ong AC: Hyperproliferation of PKD1 cystic cells is induced by insulin-like growth factor-1 activation of the Ras/Raf signalling system. Kidney Int 2007; 72: 157-165. (Pubitemid 47067385)
16. Boone M, Deen PM: Physiology and pathophysiology of the vasopressin-regulated renal water reabsorption. Pflügers Arch 2008; 456: 1005-1024.
17. Magenheimer BS, St John PL, Isom KS, Abrahamson DR, De Lisle RC, Wallace DP, Maser RL, Grantham JJ, Calvet JP: Early embryonic renal tubules of wild-type and polycystic kidney disease kidneys respond to cAMP stimulation with cystic fibrosis transmembrane conductance regulator/Na(+),K(+),2Cl(-) co-transporter-dependent cystic dilation. J Am Soc Nephrol 2006; 17: 3424-3437. (Pubitemid 44865285)
18. Shillingford JM, Murcia NS, Larson CH, Low SH, Hedgepeth R, Brown N, Flask CA, Novick AC, Goldfarb DA, Kramer-Zucker A, Walz G, Piontek KB, Germino GG, 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: 5466-5471.
19. Boehlke C, Kotsis F, Patel V, Braeg S, Voelker H, Bredt S, Beyer T, Janusch H, Hamann C, Godel M, Muller K, Herbst M, Hornung M, Doerken M, Kottgen M, Nitschke R, Igarashi P, Walz G, Kuehn EW: Primary cilia regulate mTORC1 activity and cell size through Lkb1. Nat Cell Biol 2010; 12: 1115-1122.
20. Wahl PR, Serra AL, Le Hir M, Molle KD, Hall MN, Wuthrich RP: Inhibition of mTOR with sirolimus slows disease progression in Han:SPRD rats with autosomal dominant polycystic kidney disease (ADPKD). Nephrol Dial Transplant 2006; 21: 598-604. (Pubitemid 43372904)
21. Shillingford JM, Piontek KB, Germino GG, Weimbs T: Rapamycin ameliorates PKD resulting from conditional inactivation of Pkd1. J Am Soc Nephrol 2010; 21: 489-497.
22. Qian Q, Du H, King BF, Kumar S, Dean PG, Cosio FG, Torres VE: Sirolimus reduces polycystic liver volume in ADPKD patients. J Am Soc Nephrol 2008; 19: 631-638. (Pubitemid 351355407)
23. Perico N, Antiga L, Caroli A, Ruggenenti P, Fasolini G, Cafaro M, Ondei P, Rubis N, Diadei O, Gherardi G, Prandini S, Panozo A, Bravo RF, Carminati S, De Leon FR, Gaspari F, Cortinovis M, Motterlini N, Ene-Iordache B, Remuzzi A, Remuzzi G: Sirolimus therapy to halt the progression of ADPKD. J Am Soc Nephrol 2010; 21: 1031-1040.
24. Walz G, Budde K, Mannaa M, Nurnberger J, Wanner C, Sommerer C, Kunzendorf U, Banas B, Horl WH, Obermuller N, Arns W, Pavenstadt H, Gaedeke J, Buchert M, May C, Gschaidmeier H, Kramer S, Eckardt KU: Everolimus in patients with autosomal dominant polycystic kidney disease. N Engl J Med 2010; 363: 830-840.
25. Serra AL, Poster D, Kistler AD, Krauer F, Raina S, Young J, Rentsch KM, Spanaus KS, Senn O, Kristanto P, Scheffel H, Weishaupt D, Wuthrich RP: Sirolimus and kidney growth in autosomal dominant polycystic kidney disease. N Engl J Med 2010; 363: 820-829.
26. Grantham JJ, Bennett WM, Perrone RD: mTOR inhibitors and autosomal dominant polycystic kidney disease. N Engl J Med 2011; 364: 286-287; author reply 287-289.
27. Watnick T, Germino GG: mTOR inhibitors in polycystic kidney disease. N Engl J Med 2010; 363: 879-881.
28. Levey AS, Stevens LA: mTOR inhibitors and autosomal dominant polycystic kidney disease. N Engl J Med 2011; 364: 287; author reply 287-289.
29. Schrier RW: Randomized intervention studies in human polycystic kidney and liver disease. J Am Soc Nephrol 2010; 21: 891-893.
30. Canaud G, Knebelmann B, Harris PC, Vrtovsnik F, Correas JM, Pallet N, Heyer CM, Letavernier E, Bienaime 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 1701-1706.
31. Hogan MC, Masyuk TV, Page LJ, Kubly VJ, Bergstralh EJ, Li X, Kim B, King BF, Glockner J, Holmes DR 3rd, Rossetti S, Harris PC, LaRusso NF, Torres VE: Randomized clinical trial of long-acting somatostatin for autosomal dominant polycystic kidney and liver disease. J Am Soc Nephrol 2010; 21: 1052-1061.
32. van Keimpema L, Nevens F, Vanslembrouck R, van Oijen MG, Hoffmann AL, Dekker HM, de Man RA, Drenth JP: Lanreotide reduces the volume of polycystic liver: a randomized, double-blind, placebo-controlled trial. Gastroenterology 2009; 137: 1661-1668e1-e2.
33. Torres VE, Harris PC: Autosomal dominant polycystic kidney disease: the last 3 years. Kidney Int 2009; 76: 149-168.
34. Torres VE, Wang X, Qian Q, Somlo S, Harris PC, Gattone VH 2nd: Effective treatment of an orthologous model of autosomal dominant polycystic kidney disease. Nat Med 2004; 10: 363-364. (Pubitemid 38508512)
35. Wang X, Wu Y, Ward CJ, Harris PC, Torres VE: Vasopressin directly regulates cyst growth in polycystic kidney disease. J Am Soc Nephrol 2008; 19: 102-108.
36. Gattone VH 2nd, Wang X, Harris PC, Torres VE: Inhibition of renal cystic disease development and progression by a vasopressin V2 receptor antagonist. Nat Med 2003; 9: 1323-1326. (Pubitemid 37279858)
37. Torres VE: Role of vasopressin antagonists. Clin J Am Soc Nephrol 2008; 3: 1212-1218.
38. Nagao S, Nishii K, Katsuyama M, Kurahashi H, Marunouchi T, Takahashi H, Wallace DP: Increased water intake decreases progression of polycystic kidney disease in the PCK rat. J Am Soc Nephrol 2006; 17: 2220-2227. (Pubitemid 44141912)
39. Barash I, Ponda MP, Goldfarb DS, Skolnik EY: 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: 693-697.
40. Chapman AB, Guay-Woodford LM, Grantham JJ, Torres VE, Bae KT, Baumgarten DA, Kenney PJ, King BF Jr, Glockner JF, Wetzel LH, Brummer ME, O'Neill WC, Robbin ML, Bennett WM, Klahr S, Hirschman GH, Kimmel PL, Thompson PA, Miller JP: 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: 1035-1045. (Pubitemid 37013840)
41. Chapman AB, Torres VE, Perrone RD, Steinman TI, Bae KT, Miller JP, Miskulin DC, Rahbari Oskoui F, Masoumi A, Hogan MC, Winklhofer FT, Braun W, Thompson PA, Meyers CM, Kelleher C, Schrier RW: The HALT polycystic kidney disease trials: design and implementation. Clin J Am Soc Nephrol 2010; 5: 102-109.
42. Chang MY, Kuok CM, Chen YC, Ryu SJ, Tian YC, Wu-Chou YH, Tseng FJ, Yang CW: Comparison of intracerebral hemorrhage and subarachnoid hemorrhage in patients with autosomal-dominant polycystic kidney disease. Nephron Clin Pract 2010; 114:c158-164.
43. Jafar TH, Stark PC, Schmid CH, Strandgaard S, Kamper AL, Maschio G, Becker G, Perrone RD, Levey AS: The effect of angiotensin-converting-enzyme inhibitors on progression of advanced polycystic kidney disease. Kidney Int 2005; 67: 265-271. (Pubitemid 40019248)
44. Cadnapaphornchai MA, George DM, Masoumi A, McFann K, Strain JD, Schrier RW: Effect of statin therapy on disease progression in pediatric ADPKD: design and baseline characteristics of participants. Contemp Clin Trials 2011; 32: 437-445.
45. Sweeney WE Jr, von Vigier RO, Frost P, Avner ED: Src inhibition ameliorates polycystic kidney disease. J Am Soc Nephrol 2008; 19: 1331-1341.
46. Bukanov NO, Smith LA, Klinger KW, Ledbetter SR, Ibraghimov-Beskrovnaya O: Long-lasting arrest of murine polycystic kidney disease with CDK inhibitor roscovitine. Nature 2006; 444: 949-952. (Pubitemid 46025010)
47. Ibraghimov-Beskrovnaya O: Targeting dysregulated cell cycle and apoptosis for polycystic kidney disease therapy. Cell Cycle 2007; 6: 776-779. (Pubitemid 46572612)
48. Leuenroth SJ, Bencivenga N, Igarashi P, Somlo S, Crews CM: Triptolide reduces cystogenesis in a model of ADPKD. J Am Soc Nephrol 2008; 19: 1659-1662.
49. Leuenroth SJ, Bencivenga N, Chahboune H, Hyder F, Crews CM: Triptolide reduces cyst formation in a neonatal to adult transition Pkd1 model of ADPKD. Nephrol Dial Transplant 2010; 25: 2187-2194.
50. Natoli TA, Smith LA, Rogers KA, Wang B, Komarnitsky S, Budman Y, Belenky A, Bukanov NO, Dackowski WR, Husson H, Russo RJ, Shayman JA, Ledbetter SR, Leonard JP, Ibraghimov-Beskrovnaya O: Inhibition of glucosylceramide accumulation results in effective blockade of polycystic kidney disease in mouse models. Nat Med 2010; 16: 788-792.
51. Lukina E, Watman N, Arreguin EA, Banikazemi M, Dragosky M, Iastrebner M, Rosenbaum H, Phillips M, Pastores GM, Rosenthal DI, Kaper M, Singh T, Puga AC, Bonate PL, Peterschmitt MJ: A phase 2 study of eliglustat tartrate (Genz-112638), an oral substrate reduction therapy for Gaucher disease type 1. Blood 2010; 116: 893-899.
52. Schrier RW, Levi M: Lipids and renal cystic disease. Nephrol Dial Transplant 2010; 25: 3490-3492.
53. Yamaguchi T, Reif GA, Calvet JP, Wallace DP: Sorafenib inhibits cAMP-dependent ERK activation, cell proliferation, and in vitro cyst growth of human ADPKD cyst epithelial cells. Am J Physiol Renal Physiol 2010; 299:F944-F951.
54. Di Lorenzo G, Buonerba C, Biglietto M, Scognamiglio F, Chiurazzi B, Riccardi F, Carteni G: The therapy of kidney cancer with biomolecular drugs. Cancer Treat Rev 2010; 36(suppl 3):S16-S20.
55. Mao Z, Ong AC: Peroxisome proliferatoractivated receptor gamma agonists in kidney disease-future promise, present fears. Nephron Clin Pract 2009; 112:c230-c241.
56. Blazer-Yost BL, Haydon J, Eggleston-Gulyas T, Chen JH, Wang X, Gattone V, Torres VE: Pioglitazone attenuates cystic burden in the PCK rodent model of polycystic kidney disease. PPAR Res 2010; 2010: 274376.
57. Yoshihara D, Kurahashi H, Morita M, Kugita M, Hiki Y, Aukema HM, Yamaguchi T, Calvet JP, Wallace DP, Nagao S: PPAR-gamma agonist ameliorates kidney and liver disease in an orthologous rat model of human autosomal recessive polycystic kidney disease. Am J Physiol Renal Physiol 2011; 300:F465-F474.
58. Muto S, Aiba A, Saito Y, Nakao K, Nakamura K, Tomita K, Kitamura T, Kurabayashi M, Nagai R, Higashihara E, Harris PC, Katsuki M, Horie S: Pioglitazone improves the phenotype and molecular defects of a targeted Pkd1 mutant. Hum Mol Genet 2002; 11: 1731-1742. (Pubitemid 34812094)
59. Dai B, Liu Y, Mei C, Fu L, Xiong X, Zhang Y, Shen X, Hua Z: Rosiglitazone attenuates development of polycystic kidney disease and prolongs survival in Han:SPRD rats. Clin Sci (Lond) 2010; 119: 323-333.
60. Nofziger C, Brown KK, Smith CD, Harrington W, Murray D, Bisi J, Ashton TT, Maurio FP, Kalsi K, West TA, Baines D, Blazer-Yost BL: PPARgamma agonists inhibit vasopressin-mediated anion transport in the MDCK-C7 cell line. Am J Physiol Renal Physiol 2009; 297:F55-F62.
61. Mao Z, Streets AJ, Ong AC: Thiazolidinediones inhibit MDCK cyst growth through disrupting oriented cell division and apicobasal polarity. Am J Physiol Renal Physiol 2011; 300:F1375-F1384.
62. Yang B, Sonawane ND, Zhao D, Somlo S, Verkman AS: Small-molecule CFTR inhibitors slow cyst growth in polycystic kidney disease. J Am Soc Nephrol 2008; 19: 1300-1310.
63. Sonawane ND, Muanprasat C, Nagatani R Jr, Song Y, Verkman AS: In vivo pharmacology and antidiarrheal efficacy of a thiazolidinone CFTR inhibitor in rodents. J Pharm Sci 2005; 94: 134-143. (Pubitemid 40116377)
64. Albaqumi M, Srivastava S, Li Z, Zhdnova O, Wulff H, Itani O, Wallace DP, Skolnik EY: KCa3.1 potassium channels are critical for cAMP-dependent chloride secretion and cyst growth in autosomal-dominant polycystic kidney disease. Kidney Int 2008; 74: 740-749.
65. Ataga KI, Smith WR, De Castro LM, Swerdlow P, Saunthararajah Y, Castro O, Vichinsky E, Kutlar A, Orringer EP, Rigdon GC, Stocker JW: Efficacy and safety of the Gardos channel blocker, senicapoc (ICA-17043), in patients with sickle cell anemia. Blood 2008; 111: 3991-3997.
66. Bradding P, Wulff H: The K+ channels K(Ca)3.1 and K(V)1.3 as novel targets for asthma therapy. Br J Pharmacol 2009; 157: 1330-1339.
67. Emanuele S, Lauricella M, Tesoriere G: Histone deacetylase inhibitors: apoptotic effects and clinical implications (review). Int J Oncol 2008; 33: 637-646.
68. Cao Y, Semanchik N, Lee SH, Somlo S, Barbano PE, Coifman R, Sun Z: Chemical modifier screen identifies HDAC inhibitors as suppressors of PKD models. Proc Natl Acad Sci USA 2009; 106: 21819-21824.
69. Xia S, Li X, Johnson T, Seidel C, Wallace DP, Li R: Polycystin-dependent fluid flow sensing targets histone deacetylase 5 to prevent the development of renal cysts. Development 2010; 137: 1075-1084.
70. Takiar V, Nishio S, Seo-Mayer P, King JD Jr, Li H, Zhang L, Karihaloo A, Hallows KR, Somlo S, Caplan MJ: Activating AMP-activated protein kinase (AMPK) slows renal cystogenesis. Proc Natl Acad Sci USA 2011; 108: 2462-2467.
71. Gattone VH 2nd, Chen NX, Sinders RM, Seifert MF, Duan D, Martin D, Henley C, Moe SM: Calcimimetic inhibits late-stage cyst growth in ADPKD. J Am Soc Nephrol 2009; 20: 1527-1532.
72. Wang X, Harris PC, Somlo S, Batlle D, Torres VE: Effect of calcium-sensing receptor activation in models of autosomal recessive or dominant polycystic kidney disease. Nephrol Dial Transplant 2009; 24: 526-534.
73. Meijer E, Boertien WE, Nauta FL, Bakker SJ, van Oeveren W, Rook M, van der Jagt EJ, van Goor H, Peters DJ, Navis G, de Jong PE, Gansevoort RT: Association of urinary biomarkers with disease severity in patients with autosomal dominant polycystic kidney disease: a cross-sectional analysis. Am J Kidney Dis 2010; 56: 883-895.