Current drug development challenges in chronic kidney disease (CKD)-identification of individualized determinants of renal progression and premature cardiovascular disease (CVD)

Nephrology Dialysis Transplantation

Volumn 27, Issue SUPPL. 3, 2012, Pages

  Formentini, Ivan ^a   Bobadilla, Maria ^a   Haefliger, Carolina ^a   Hartmann, Guido ^a   Loghman Adham, Mahmoud ^b   Mizrahi, Jacques ^a   Pomposiello, Silvia ^a   Prunotto, Marco ^a   Meier, Matthias ^a  

^a F HOFFMANN LA ROCHE LTD   (Switzerland)

^b HOFFMANN LA ROCHE INC   (United States)

Author keywords

biomarker; chronic kidney disease; drug development; personalized medicine

Indexed keywords

ANGIOTENSIN RECEPTOR ANTAGONIST; BARDOXOLONE METHYL; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; ENDOTHELIN A RECEPTOR ANTAGONIST; ENDOTHELIN B RECEPTOR ANTAGONIST; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; IRBESARTAN; OLMESARTAN; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ANTAGONIST; PLASMINOGEN ACTIVATOR INHIBITOR 1;

ARTICLE; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; CHRONIC KIDNEY DISEASE; CLINICAL TRIAL (TOPIC); DIABETIC NEPHROPATHY; DISEASE COURSE; DRUG EFFICACY; DRUG MECHANISM; DRUG RESEARCH; DRUG SAFETY; DRUG TARGETING; GLOMERULUS FILTRATION RATE; HEART PROTECTION; HIGH RISK PATIENT; HIGH THROUGHPUT SCREENING; HUMAN; KIDNEY FAILURE; KIDNEY FUNCTION TEST; MICROALBUMINURIA; NONHUMAN; OUTCOME ASSESSMENT; PERSONALIZED MEDICINE; PHARMACODYNAMICS; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; QUALITY OF LIFE; RANDOMIZED CONTROLLED TRIAL (TOPIC); RENAL PROTECTION; RISK BENEFIT ANALYSIS;

BIOLOGICAL MARKERS; CARDIOVASCULAR DISEASES; DISEASE PROGRESSION; DRUG DESIGN; DRUG DISCOVERY; HUMANS; INDIVIDUALIZED MEDICINE; PROGNOSIS; RENAL INSUFFICIENCY, CHRONIC; RESEARCH DESIGN;

EID: 84868571581     PISSN: 09310509     EISSN: 14602385     Source Type: Journal    
DOI: 10.1093/ndt/gfs270     Document Type: Article

References (67)

1. Foley RN. Temporal trends in the burden of chronic kidney disease in the United States. Curr Opin Nephrol Hypertens 2010; 19: 273-277.
2. Stevens LA, Greene T, Levey AS. Surrogate end points for clinical trials of kidney disease progression. Clin J Am Soc Nephrol 2006; 1: 874-884.
3. Miyata T, Kikuchi K, Kiyomoto H et al. New era for drug discovery and development in renal disease. Nat Rev Nephrol 2011; 7: 469-477.
4. Casas JP, Chua W, Loukogeorgakis S et al. Effect of inhibitors of the renin-angiotensin system and other antihypertensive drugs on renal outcomes: systematic review and meta-analysis. Lancet 2005; 366: 2026-2033.
5. Opie LH, Kowolik H. The discovery of captopril: from large animals to small molecules. Cardiovasc Res 1995; 30: 18-25.
6. Novak JE, Inrig JK, Patel UD et al. Negative trials in nephrology: what can we learn? Kidney Int 2008; 74: 1121-1127.
7. US Food and Drug Administration. Guidance for industry: M3 (R2) nonclinical safety studies for the conduct of human clinical trials and marketing authorization for pharmaceuticals [online]. 2010.
8. Prunotto M, Gabbiani G, Pomposiello S et al. The kidney as a target organ in pharmaceutical research. Drug Discov Today 2011; 16: 244-259.
9. Azizi M, Menard J. Renin inhibitors and cardiovascular and renal protection: an endless quest? Cardiovasc Drugs Ther 2012. [Epub ahead of print March 6].
10. Al-Aly Z, Zeringue A, Fu J et al. Rate of kidney function decline associates with mortality. J Am Soc Nephrol 2010; 21: 1961-1969.
11. Laegreid IK, Aasarod K, Jordhoy M. End-stage renal disease and recruitment to randomized trials: why is it so difficult? Results from a survey among Norwegian nephrologists. Scand J Urol Nephrol 2011; 45: 285-289.
12. Ju W, Smith S, Kretzler M. Genomic biomarkers for chronic kidney disease. Transl Res 2012; 159: 290-302.
13. He JC, Chuang PY, Ma'ayan A et al. Systems biology of kidney diseases. Kidney Int 2012; 81: 22-39.
14. Hewitson TD, Ono T, Becker GJ. Small animal models of kidney disease: a review. Methods Mol Biol 2009; 466: 41-57.
15. Balakumar P, Chakkarwar VA, Kumar V et al. Experimental models for nephropathy. J Renin Angiotensin Aldosterone Syst 2008; 9: 189-195.
16. Brosius FC, 3rd, Alpers CE, Bottinger EP et al. Mouse models of diabetic nephropathy. J Am Soc Nephrol 2009; 20: 2503-2512.
17. Alpers CE, Hudkins KL. Mouse models of diabetic nephropathy. Curr Opin Nephrol Hypertens 2011; 20: 278-284.
18. Leelahavanichkul A, Yan Q, Hu X et al. Angiotensin II overcomes strain-dependent resistance of rapid CKD progression in a new remnant kidney mouse model. Kidney Int 2010; 78: 1136-1153.
19. Ledford H. Translational research: 4 ways to fix the clinical trial. Nature 2011; 477: 526-528.
20. Fassett RG, Venuthurupalli SK, Gobe GC et al. Biomarkers in chronic kidney disease: a review. Kidney Int 2011; 80: 806-821.
21. Stenvinkel P. Chronic kidney disease: a public health priority and harbinger of premature cardiovascular disease. J Intern Med 2010; 268: 456-467.
22. Beige J, Heipmann K, Stumvoll M et al. Paradoxical role for adiponectin in chronic renal diseases? An example of reverse epidemiology. Expert Opin Ther Targets 2009; 13: 163-173.
23. Kovesdy CP, Anderson JE. Reverse epidemiology in patients with chronic kidney disease who are not yet on dialysis. Semin Dial 2007; 20: 566-569.
24. Baigent C, Landray MJ, Reith C et al. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial. Lancet 2011; 377: 2181-2192.
25. Palmer SC, Strippoli GF. Cardiovascular diseases: lipid-lowering in CKD-at the SHARP end of the evidence? Nat Rev Nephrol 2011; 7: 609-611.
26. Pergola PE, Raskin P, Toto RD et al. Bardoxolone methyl and kidney function in CKD with type 2 diabetes. N Engl J Med 2011; 365: 327-336.
27. McMahon GM, Forman JP. Bardoxolone methyl, chronic kidney disease, and type 2 diabetes. N Engl J Med 2011; 365: 1746; author reply 1746-1747.
28. Li L, Astor BC, Lewis J et al. Longitudinal progression trajectory of GFR among patients with CKD. Am J Kidney Dis 2012; 59: 504-512.
29. Perkins RM, Bucaloiu ID, Kirchner HL et al. GFR decline and mortality risk among patients with chronic kidney disease. Clin J Am Soc Nephrol 2011; 6: 1879-1886.
30. Johnson CA, Levey AS, Coresh J et al. Clinical practice guidelines for chronic kidney disease in adults: Part II. Glomerular filtration rate, proteinuria, and other markers. Am Fam Physician 2004; 70: 1091-1097.
31. Ruggenenti P, Remuzzi G. Time to abandon microalbuminuria? Kidney Int 2006; 70: 1214-1222.
32. Basi S, Fesler P, Mimran A et al. Microalbuminuria in type 2 diabetes and hypertension: a marker, treatment target, or innocent bystander? Diabetes Care 2008; 31(Suppl 2): S194-S201.
33. Schiffrin EL, Lipman ML, Mann JF. Chronic kidney disease: effects on the cardiovascular system. Circulation 2007; 116: 85-97.
34. Lewis EJ, Hunsicker LG, Clarke WR et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 2001; 345: 851-860.
35. Brenner BM, Cooper ME, de Zeeuw D et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001; 345: 861-869.
36. Viberti G, Wheeldon NM. Microalbuminuria reduction with valsartan in patients with type 2 diabetes mellitus: a blood pressure-independent effect. Circulation 2002; 106: 672-678.
37. Haller H, Ito S, Izzo JL, Jr. et al. Olmesartan for the delay or prevention of microalbuminuria in type 2 diabetes. N Engl J Med 2011; 364: 907-917.
38. Ozer JS. A guidance for renal biomarker lead optimization and use in translational pharmacodynamics. Drug Discov Today 2010; 15: 142-147.
39. Perkins BA, Ficociello LH, Roshan B et al. In patients with type 1 diabetes and new-onset microalbuminuria the development of advanced chronic kidney disease may not require progression to proteinuria. Kidney Int 2010; 77: 57-64.
40. Perkins BA, Ficociello LH, Silva KH et al. Regression of microalbuminuria in type 1 diabetes. N Engl J Med 2003; 348: 2285-2293.
41. Levey AS, Cattran D, Friedman A et al. Proteinuria as a surrogate outcome in CKD: report of a scientific workshop sponsored by the National Kidney Foundation and the US Food and Drug Administration. Am J Kidney Dis 2009; 54: 205-226.
42. Thompson A. Proteinuria as a surrogate end point-more data are needed. Nat Rev Nephrol 2012; 8: 306-309.
43. Keith DS, Nichols GA, Gullion CM et al. Longitudinal follow-up and outcomes among a population with chronic kidney disease in a large managed care organization. Arch Intern Med 2004; 164: 659-663.
44. Matsushita K, Yasuda G, Shouda M et al. Evaluation of renal function and proteinuria based on mass health examinations in young Japanese obese adults. Clin Exp Nephrol 2009; 13: 316-324.
45. Rifkin DE, Shlipak MG, Katz R et al. Rapid kidney function decline and mortality risk in older adults. Arch Intern Med 2008; 168: 2212-2218.
46. Shlipak MG, Katz R, Kestenbaum B et al. Rapid decline of kidney function increases cardiovascular risk in the elderly. J Am Soc Nephrol 2009; 20: 2625-2630.
47. Elsayed EF, Tighiouart H, Griffith J et al. Cardiovascular disease and subsequent kidney disease. Arch Intern Med 2007; 167: 1130-1136.
48. Ronco C, Ronco F. Cardio-renal syndromes: a systematic approach for consensus definition and classification. Heart Fail Rev 2012; 17: 151-160.
49. Dieterle F, Sistare F, Goodsaid F et al. Renal biomarker qualification submission: a dialog between the FDA-EMEA and Predictive Safety Testing Consortium. Nat Biotechnol 2010; 28: 455-462.
50. Devarajan P. The use of targeted biomarkers for chronic kidney disease. Adv Chronic Kidney Dis 2010; 17: 469-479.
51. Spasovski G, Ortiz A, Vanholder R et al. Proteomics in chronic kidney disease: the issues clinical nephrologists need an answer for. Proteomics Clin Appl 2011; 5: 233-240.
52. Chen R, Mias GI, Li-Pook-Than J et al. Personal omics profiling reveals dynamic molecular and medical phenotypes. Cell 2012; 148: 1293-1307.
53. Strippoli GF, Craig JC, Schena FP. The number, quality, and coverage of randomized controlled trials in nephrology. J Am Soc Nephrol 2004; 15: 411-419.
54. Schulz KF, Altman DG, Moher D. CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. PLoS Med 2010; 7: e1000251.
55. Deo A, Schmid CH, Earley A et al. Loss to analysis in randomized controlled trials in CKD. Am J Kidney Dis 2011; 58: 349-355.
56. Gorman GH, Furth SL. Clinical research in pediatric nephrology: state of the art. Pediatr Nephrol 2005; 20: 1382-1387.
57. Cook T, DeMets DL. Review of draft FDA adaptive design guidance. J Biopharm Stat 2010; 20: 1132-1142.
58. Coffey CS, Kairalla JA. Adaptive clinical trials: progress and challenges. Drugs R D 2008; 9: 229-242.
59. Levin A, Beaulieu MC. Trials and tribulations of new agents, novel biomarkers, and retarding renal progression. J Am Soc Nephrol 2011; 22: 992-993.
60. Perico N, Benigni A, Remuzzi G. Present and future drug treatments for chronic kidney diseases: evolving targets in renoprotection. Nat Rev Drug Discov 2008; 7: 936-953.
61. Gagliardini E, Buelli S, Benigni A. Endothelin in chronic proteinuric kidney disease. Contrib Nephrol 2011; 172: 171-184.
62. Hahm K, Lukashev ME, Luo Y et al. Alphav beta6 integrin regulates renal fibrosis and inflammation in Alport mouse. Am J Pathol 2007; 170: 110-125.
63. Dolman ME, Harmsen S, Storm G et al. Drug targeting to the kidney: advances in the active targeting of therapeutics to proximal tubular cells. Adv Drug Deliv Rev 2010; 62: 1344-1357.
64. Iekushi K, Taniyama Y, Azuma J et al. Hepatocyte growth factor attenuates renal fibrosis through TGF-beta1 suppression by apoptosis of myofibroblasts. J Hypertens 2010; 28: 2454-2461.
65. Eddy AA, Fogo AB. Plasminogen activator inhibitor-1 in chronic kidney disease: evidence and mechanisms of action. J Am Soc Nephrol 2006; 17: 2999-3012.
66. Rodriguez HM, Vaysberg M, Mikels A et al. Modulation of lysyl oxidase-like 2 enzymatic activity by an allosteric antibody inhibitor. J Biol Chem 2010; 285: 20964-20974.
67. Song YR, You SJ, Lee YM et al. Activation of hypoxia-inducible factor attenuates renal injury in rat remnant kidney. Nephrol Dial Transplant 2010; 25: 77-85.