Autosomal dominant polycystic kidney disease and mTOR inhibitors: The narrow road between hope and disappointment

Nephrology Dialysis Transplantation

Volumn 25, Issue 12, 2010, Pages 3809-3812

  Ponticelli, Claudio ^a   Locatelli, Francesco ^b  

^a HUMANITAS CLINICAL AND RESEARCH CENTER   (Italy)

^b A MANZONI HOSPITAL   (Italy)

Author keywords

CKD; everolimus; mTOR; polycystic kidney; sirolimus

Indexed keywords

EVEROLIMUS; MAMMALIAN TARGET OF RAPAMYCIN; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 2; POLYCYSTIN 1; POLYCYSTIN 2; RAPAMYCIN;

AUTOSOMAL DOMINANT DISORDER; CHROMOSOME 16; CHROMOSOME 4; CLINICAL TRIAL; DISEASE COURSE; DRUG EFFECT; DRUG EFFICACY; DRUG MECHANISM; DRUG SAFETY; DRUG TOLERABILITY; GENE MUTATION; HUMAN; INFECTION; KIDNEY POLYCYSTIC DISEASE; LOW DRUG DOSE; MUCOSA INFLAMMATION; NOTE; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN FUNCTION;

ANIMALS; DISEASE MODELS, ANIMAL; DISEASE PROGRESSION; DOSE-RESPONSE RELATIONSHIP, DRUG; GLOMERULAR FILTRATION RATE; HUMANS; MUTATION; PHOSPHATIDYLINOSITOL 3-KINASES; POLYCYSTIC KIDNEY, AUTOSOMAL DOMINANT; RATS; SIROLIMUS; TOR SERINE-THREONINE KINASES; TRPP CATION CHANNELS;

EID: 78649503269     PISSN: 09310509     EISSN: 14602385     Source Type: Journal    
DOI: 10.1093/ndt/gfq527     Document Type: Note

References (30)

1. Torres V, Harris PC. Autosomal dominant polycystic kidney disease: the last 3 years. Kidney Int 2009; 76: 149-168
2. Fingar DC, Blenis J. Target of rapamycine (TOR): an integrator of nutrient and growth factor signals and coordinator of cell growth and cell cycle progression. Oncogene 2004; 23: 3151-3171
3. Bissler JJ, Kingswood JC. Renal angiomyolipomata. Kidney Int 2004; 66: 924-934
4. Shillingford JM, Murcia NS, Larson CH et al. The mTOR pathway is regulated by polycystin-1, and its inhibition reverses renal cystogen-esis in polycystic kidney disease. Proc Natl Acad Sci USA 2006; 103: 5466-5471
5. Parker E, Newby LJ, Sharpe CC et al. Hyperproliferation of PKD1 cystic cells is induced by insulin-like growth factor-1 activation of the Ras/Raf signalling system. Kidney Int 2007; 72: 157-162
6. Abraham RT. Mammalian target of rapamycin: immunosuppressive drugs uncover a novel pathway of cytokine receptor signalling. Curr Opin Immunol 1998; 10: 330-336
7. Bissler JJ, McCormack FX, Young LR et al. Sirolimus for angiomyo-lipoma in tuberous sclerosis complex of lymphangioleiomuomatosis. N Engl J Med 2008; 358: 140-151
8. Motzer RJ, Escudier B, Oudard S et al. Efficacy of everolimus in adVanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet 2008; 372: 449-456
9. Shida T, Kishimoto T, Furuya M et al. Expression of an activated mammalian target of rapamycin (mTOR) in gastroenteropancreatic neuroendocrine tumors. Cancer Chemother Pharmacol 2010; 65: 889-893
10. Tao Y, Kim J, Schrier RW et al. Rapamycin markedly slows disease progression in a rat model of polycystic kidney disease. J Am Soc Nephrol 2005; 16: 46-51
11. Wahl PR, Serra AL, Le Hir M et al. Inhibition of mTOR with siro-limus slows disease progression in Han:SPRD rats with autosomal dominant polycystic kidney disease (ADPKD). Nephrol Dial Transplant 2006; 3: 598-604
12. Wu H, Wahl PR, Le Hir M et al. Everolimus retards cyst growth and preserves renal function in a rodent model for polycystic kidney disease. Kidney Blood Press Res 2007; 30: 253-259
13. Wu M, Arcaro A, Varga Z et al. Pulse mTOR inhibitor treatment effectively controls cyst growth but leads to severe parenchymal glomerular hypertrophy in rat polycystic kidney disease. Am J Physiol Renal Physiol 2009; 297: F1597-F1605
14. Shillingford JM, Piontek KB, Germino GG et al. Rapamycin ameliorates PKD resulting from conditional inactivation of Pkd1. J Am Soc Nephrol 2010; 21: 489-497
15. WeiW,PopovV,WalochaJAet al. Evidence for angiogenesis andmicro-vascular regression in autosomal-dominant polycystic kidney disease kidneys: a corrosion cast study. Kidney Int 2006; 70: 1261-1268
16. Ponticelli C. The pleiotropic effects of mTOR inhibitors. J Nephrol 2004; 17: 762-768
17. Lane HA, Wood JM, McSheehy PM et al. mTOR inhibitor RAD001 (everolimus) has antiangiogenic/vascular properties distinct from a VEGFR tyrosine kinase inhibitor. Clin Cancer Res 2009; 15: 1612-1622
18. Edelstein CL. Mammalian target of rapamycin and caspase inhibitors in polycystic kidney disease. Clin J Am Soc Nephrol 2008; 3: 1219-1226
19. Serra AL, Kistler AD, Poster D et al. Safety and tolerability of sirolimus treatment in patients with autosomal dominant polycystic kidney disease. Nephrol Dial Transplant 2009; 24: 3334-3342
20. Perico N, Antiga L, Caroli A et al. Sirolimus therapy to halt the progression of ADPKD. J Am Soc Nephrol 2010; 21: 1031-1040
21. Serra AL, Poster D, Kistler AD et al. Sirolimus and kidney growth in autosomal dominant polycystic kidney disease. N Engl J Med 2010; 363: 820-829
22. Grantham JJ, Torres VE, Chapman AB et al. Volume progression in polycystic kidney disease. N Engl J Med 2006; 354: 2122-2130
23. Torres VVE, Boletta A, Chapman A et al. Prospects for mTOR inhibitor use in patients with polycystic kidney disease and hamarto-matous diseases. Clin J Am Soc Nephrol 2010; 5: 1312-1329
24. Kistler AD, Poster D, Krauer F et al. Increases in kidney volume in autosomal dominant polycystic kidney disease can be detected within 6 months. Kidney Int 2009; 75: 235-241
25. Walz G, Budde K, Mannaa M et al. Everolimus in patients with auto-somal dominant polycystic kidney disease. N Engl J Med 2010; 363: 830-840
26. Watnick T, Germino GG. mTOR inhibitors in polycystic kidney disease. N Engl J Med 2010; In press
27. Lloberas N, Cruzado JM, Franquesa M et al. Mammalian target of rapamycin pathway blockade slows progression of diabetic kidney disease in rats. J Am Soc Nephrol 2006; 17: 1395-1404
28. Vogelbacher R, Wittmann S, Braun A et al. The mTOR inhibitor ever-olimus induces proteinuria and renal deterioration in the remnant kidney model in the rat. Transplantation 2007; 84: 1492-1499
29. Schena FP, Pascoe MD, Alberu J et al. Sirolimus CONVERT Trial Study Group. Conversion from calcineurin inhibitors to sirolimus maintenance therapy in renal allograft recipients: 24-month efficacy and safety results from the CONVERT trial. Transplantation 2009; 87: 233-242
30. Daniel C, Renders L, Amann K et al. Mechanisms of everolimus-induced glomerulosclerosis after glomerular injury in the rat. Am J Transplant 2005; 5: 2849-2861