Kidney outcomes in long-term studies of ruboxistaurin for diabetic eye disease - PubMed (original) (raw)
Randomized Controlled Trial
doi: 10.2215/CJN.00840207. Epub 2007 May 30.
Affiliations
- PMID: 17699475
- DOI: 10.2215/CJN.00840207
Randomized Controlled Trial
Kidney outcomes in long-term studies of ruboxistaurin for diabetic eye disease
Katherine R Tuttle et al. Clin J Am Soc Nephrol. 2007 Jul.
Abstract
Background: A pilot study showed that ruboxistaurin (RBX), a protein kinase C beta inhibitor, significantly decreased albuminuria and stabilized kidney function over 1 yr in patients who had diabetic nephropathy and persistent macroalbuminuria despite receiving the current standard of care, including renin-angiotensin system inhibition. In contrast, in a trial of patients with diabetic retinopathy, investigators reported the adverse event "diabetic nephropathy" more frequently in patients who received RBX.
Design, setting, participants, and measurements: The purpose of this study was to evaluate long-term effects of RBX on kidney outcomes among patients with diabetic eye disease in three diabetic retinopathy trials (n = 1157). Baseline-to-study end changes in estimated GFR (eGFR) were calculated. Kidney outcomes included doubling of serum creatinine, development of advanced chronic kidney disease (stages 4 to 5), and death.
Results: Baseline eGFR was 81.6 +/- 26.0 ml/min per 1.73 m(2). In the combined placebo and RBX treatment groups, eGFR decreased by 11.0 +/- 19.6 ml/min per 1.73 m(2) during median follow-up of 33 to 39 mo. At least one kidney outcome occurred in 11.3% of patients. Frequency of doubling of serum creatinine was 6.0%, progression to advanced chronic kidney disease was 4.1%, and death was 4.1%. Kidney outcome rates did not differ by treatment assignment.
Conclusions: Long-term kidney outcomes in patients with diabetic eye disease were similar in placebo and RBX groups. In conclusion, large-scale, prospective trials in patients with diabetic nephropathy are needed to confirm safety and potential benefits of RBX on clinical outcomes.
Comment in
- Protein kinase C-beta inhibition: a promise not yet fulfilled.
Bakris GL. Bakris GL. Clin J Am Soc Nephrol. 2007 Jul;2(4):619-20. doi: 10.2215/CJN.01940507. Epub 2007 May 30. Clin J Am Soc Nephrol. 2007. PMID: 17699472 No abstract available.
Similar articles
- Treatment of symptomatic diabetic peripheral neuropathy with the protein kinase C beta-inhibitor ruboxistaurin mesylate during a 1-year, randomized, placebo-controlled, double-blind clinical trial.
Vinik AI, Bril V, Kempler P, Litchy WJ, Tesfaye S, Price KL, Bastyr EJ 3rd; MBBQ Study Group. Vinik AI, et al. Clin Ther. 2005 Aug;27(8):1164-80. doi: 10.1016/j.clinthera.2005.08.001. Clin Ther. 2005. PMID: 16199243 Clinical Trial. - Oral protein kinase c β inhibition using ruboxistaurin: efficacy, safety, and causes of vision loss among 813 patients (1,392 eyes) with diabetic retinopathy in the Protein Kinase C β Inhibitor-Diabetic Retinopathy Study and the Protein Kinase C β Inhibitor-Diabetic Retinopathy Study 2.
Aiello LP, Vignati L, Sheetz MJ, Zhi X, Girach A, Davis MD, Wolka AM, Shahri N, Milton RC; PKC-DRS and PKC-DRS2 Study Groups. Aiello LP, et al. Retina. 2011 Nov;31(10):2084-94. doi: 10.1097/IAE.0b013e3182111669. Retina. 2011. PMID: 21862954 Clinical Trial. - Effect of ruboxistaurin on visual loss in patients with diabetic retinopathy.
PKC-DRS2 Group; Aiello LP, Davis MD, Girach A, Kles KA, Milton RC, Sheetz MJ, Vignati L, Zhi XE. PKC-DRS2 Group, et al. Ophthalmology. 2006 Dec;113(12):2221-30. doi: 10.1016/j.ophtha.2006.07.032. Epub 2006 Sep 20. Ophthalmology. 2006. PMID: 16989901 Clinical Trial. - Protein kinase C-beta inhibition for diabetic kidney disease.
Tuttle KR. Tuttle KR. Diabetes Res Clin Pract. 2008 Nov 13;82 Suppl 1:S70-4. doi: 10.1016/j.diabres.2008.09.041. Diabetes Res Clin Pract. 2008. PMID: 18977550 Review. - Ruboxistaurin, a protein kinase C beta inhibitor, as an emerging treatment for diabetes microvascular complications.
Joy SV, Scates AC, Bearelly S, Dar M, Taulien CA, Goebel JA, Cooney MJ. Joy SV, et al. Ann Pharmacother. 2005 Oct;39(10):1693-9. doi: 10.1345/aph.1E572. Epub 2005 Sep 13. Ann Pharmacother. 2005. PMID: 16160002 Review.
Cited by
- Recent Advances in the Management of Diabetic Kidney Disease: Slowing Progression.
Wang N, Zhang C. Wang N, et al. Int J Mol Sci. 2024 Mar 7;25(6):3086. doi: 10.3390/ijms25063086. Int J Mol Sci. 2024. PMID: 38542060 Free PMC article. Review. - An Update on Protein Kinases as Therapeutic Targets-Part I: Protein Kinase C Activation and Its Role in Cancer and Cardiovascular Diseases.
Silnitsky S, Rubin SJS, Zerihun M, Qvit N. Silnitsky S, et al. Int J Mol Sci. 2023 Dec 18;24(24):17600. doi: 10.3390/ijms242417600. Int J Mol Sci. 2023. PMID: 38139428 Free PMC article. Review. - A protein kinase C α and β inhibitor blunts hyperphagia to halt renal function decline and reduces adiposity in a rat model of obesity-driven type 2 diabetes.
Wang J, Casimiro-Garcia A, Johnson BG, Duffen J, Cain M, Savary L, Wang S, Nambiar P, Lech M, Zhao S, Xi L, Zhan Y, Olson J, Stejskal JA, Lin H, Zhang B, Martinez RV, Masek-Hammerman K, Schlerman FJ, Dower K. Wang J, et al. Sci Rep. 2023 Oct 7;13(1):16919. doi: 10.1038/s41598-023-43759-7. Sci Rep. 2023. PMID: 37805649 Free PMC article. - Diabetic Nephropathy: Update on Pillars of Therapy Slowing Progression.
Naaman SC, Bakris GL. Naaman SC, et al. Diabetes Care. 2023 Sep 1;46(9):1574-1586. doi: 10.2337/dci23-0030. Diabetes Care. 2023. PMID: 37625003 Free PMC article. Review. - Intrarenal Mechanisms of Sodium-Glucose Cotransporter-2 Inhibitors on Tubuloglomerular Feedback and Natriuresis.
Koh ES, Kim GH, Chung S. Koh ES, et al. Endocrinol Metab (Seoul). 2023 Aug;38(4):359-372. doi: 10.3803/EnM.2023.1764. Epub 2023 Jul 24. Endocrinol Metab (Seoul). 2023. PMID: 37482684 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Research Materials
Miscellaneous