Current Hypertens Reports 9:393-402, 2007.
Radica Alicic and Katherine R. Tuttle
Richard E. Gilbert, MD, PHD, Sandra A. Kim, MD, MSC, Katherine R. Tuttle, MD, George L. Bakris, MD, Robert D. Toto, MD, Janet B. McGill, MD, Douglas J. Haney, PHD, Darren J. Kelly, PHD and Pamela W. Anderson, MD
Blood Pressure, Volume 16, Issue 2 2007 , pages 80 - 86
Authors: Kenneth Jamerson a; George L. Bakris b; Björn Dahlöf c; Bertram Pitt a; Eric Velazquez d; Jitendra Gupte e; Martin Lefkowitz e; Allen Hester e; Victor Shi e; Sverre E. Kjeldsen af; William Cushman g; Vasilios Papademetriou h; Michael Weber - FOR THE ACCOMPLISH INVESTIGATORS
ACCOMPLISH is a "new-generation" hypertension trial assessing single-tablet combination therapy for initial treatment of high-risk hypertension. At baseline, 97% of subjects were treated with anti-hypertensive medication at entry, but only 37% of participants had blood pressure (BP) control (<140/90 mmHg). Single-tablet combination therapy may improve control rates. Methods. The mean BP change from baseline at the end of 6 months (the time point when subjects should have had all of the drug titrations to achieve BP control) was examined for 10,704 randomized patients. Within-group changes were examined using t-tests. Comparisons between subgroups were made using analysis of variance (ANOVA) and covariance (ANCOVA). Results. Mean (±SD) BP fell from 145±18/80±11 mmHg at randomization to 132±16/74±10 mmHg. The 6-month BP control rate was 73% in the overall trial (78% in the US), 43% in diabetics and 40% in patients with renal disease. Of the patients uncontrolled, 61% were not on maximal medications, suggesting potential increases in control rates. Serious hypotensive events occurred in 1.8% of participants. Conclusion. ACCOMPLISH BP control rates are the highest of any multi-national trial to date. Whereas current guidelines recommend combination therapy only for stage 2 hypertension, in this trial it is expedient and safe for both stage 1 and 2 hypertension.
American Journal of Kidney Diseases Volume 49, Issue 2, Supplement S2 (February 2007)
Tuttle, KR and Nelson RG (Eds.) for the K/DOQI Work Group.
Clinical Journal of The American Society of Nephrology 2:631-636, 2007.
Katherine R. Tuttle*, Janet B. McGill, Douglas J. Haney, Toni E. Lin, Pamela W. Anderson; for the PKC-DRS, PKC-DMES, and PKC-DRS 2 Study Groups
Journal of Pediatric Nursing 22:43-58, 2007
Bindler RC, Massey LK, Shultz JA, Mills PE, Short R.
Current Opinion in Nephrology & Hypertension. 16(5):397-402, September 2007.
Anderson, Pamela W; McGill, Janet B; Tuttle, Katherine R
Purpose of review: The prevalence of diabetes mellitus is increasing rapidly worldwide. The number of patients with diabetic nephropathy is also expected to increase considerably in the future despite currently available treatments that may prevent or slow kidney disease progression. Additional therapeutic agents are therefore urgently needed.
Recent findings: Ruboxistaurin mesylate is a bisindolylmaleimide that specifically inhibits the [beta]-isoform of protein kinase C. In animal models of diabetic nephropathy, ruboxistaurin normalized glomerular hyperfiltration, decreased urinary albumin excretion, preserved renal function and reduced mesangial expansion, glomerulosclerosis, and tubulointerstitial fibrosis. In humans with type 2 diabetes and nephropathy already treated with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, treatment with ruboxistaurin for 1 year reduced albuminuria and urinary transforming growth factor-[beta], and maintained estimated glomerular filtration rate. Ruboxistaurin has so far been shown to be well tolerated at the doses tested.
Summary: Inhibition of protein kinase C [beta] may represent a novel strategy to improve kidney outcomes in patients with diabetes mellitus. Large-scale, prospective trials are needed to confirm the safety and potential benefits of ruboxistaurin in patients with diabetic nephropathy.
Blood Purification 25:112-114, 2007
Robert G. Nelsona, Katherine R. Tuttle, for the National Kidney Foundation
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