UKidney Nephrology News and Insights

Some very disappointing news released today, as seen on Reuters:

Oct 18 (Reuters) - Abbott Laboratories Inc said its partner Reata Pharmaceuticals was discontinuing a late-stage trial of their potential blockbuster treatment for chronic kidney disease and diabetes based on safety concerns raised by an independent safety committee. The news for bardoxolone represents a major setback for Abbott just months before the planned Jan. 1 spinoff of its branded prescription drugs into a separate publicly traded company called AbbVie. Without the high-profile drug, Wall Street concerns about AbbVie's dependence on Abbott's $8 billion-a-year rheumatoid arthritis drug Humira could intensify. An independent data monitoring committee found excess serious adverse events and mortality in patients taking the oral anti-inflammatory drug, Abbott said in a regulatory filing.

Regulators were notified of the decision, and study participants were being informed, the company said.

Top-line results for the EVOLVE study using cinacalcet (Sensipar) in patients with end-stage renal disease (ESRD) were reported last week. In this phase 3 placebo-controlled randomized trial of 3,883 patients with secondary hyperparathyroidism, those on active treatment received a titrated dose of cinacalcet starting at 30 mg/day up to 180mg and were followed for approximately 4 years. Patients were evaluated for the composite primary outcome of all-cause mortality or first non-fatal cardiovascular event, including myocardial infarction, hospitalization for unstable angina, heart failure or peripheral vascular event. Despite very promising biochemical outcomes from earlier studies with cinacalcet, the reduction in the primary outcome, while numerically positive, was not statistically significant. A more detailed analysis of this study will be completed once the paper is published.

At the end of 2011, Novartis suspended the ALTITUDE Study, effectively ending the possibility that the direct renin inhibitor (DRI) Aliskiren will play a significant role in the management of patients with CKD already on an ACE or ARB. This development was disappointing but actually represents only part of a growing body of evidence that now casts major doubt on the use of microalbuminuria (MAU) as a treatment surrogate in patients with cardiovascular disease.

The use of MAU as a predictor of cardiovascular risk is sound and supported by a sizable evidence base. There is little doubt that patients with risks for cardiovascular disease who also have MAU are at far greater risk for adverse outcomes including death. In numerous studies, including the Heart Outcomes Prevention Evaluation (HOPE) Trial [7], MAU was the single most potent risk factor for adverse outcomes, with greater predictive power than diabetes, male gender, smoking and hypertension. The fascinating part of this observation is that even seemingly modest elevation in MAU was highly predictive of adverse events. It was very tempting then to anticipate a concomitant reduction in risk among patients whose MAU was targeted for therapeutic reduction with any of: (1) high dose ACE or ARB, (2) combination ACE and ARB, and most recently, (3) combination ACE or ARB with DRI. Unfortunately, recent prospective studies have essentially decimated this hypothesis and in all, proteinuria improved whereas patients did not or actually fared worse.

In a stunning development, Novartis said Tuesday that it will terminate the late-stage ALTITUDE study investigating Rasilez (aliskiren) in patients with type 2 diabetes and renal impairment on the recommendation of an independent data monitoring committee. The company indicated that the committee concluded that "patients were unlikely to benefit" from the addition of Rasilez to standard anti-hypertensives and also identified higher adverse events in this group (source: FirstWord).

On a personal and professional note, these results come as a great disappointment to me. Not only does it suggest no further protection for our patients prescribed this strategy in an effort to reduce the burden of cardiorenal disease, but I was a great believer in the hypothesis and taught about it extensively throughout my career.

Dr. Elizabeth Cohen, senior medical correspondent for CNN's Health, Medical and Wellness unit made a dangerously incorrect statement in her report on generic drugs in the US (Seen at approximately 1:37 of the following video).

Nephrology has become a field of medicine that is vastly expanding in knowledge and complexity. The number of students, residents considering the field of nephrology are declining every year. Lot of times the students consider nephrology as a difficult subject to grasp and hence have a "renal fear" to consider this field of medicine. To make nephrology more exciting and fun, and to add adjunctive tools of teaching, there have been attempts to develop interesting tools of teaching in nephrology. Websites like UKidney and others are one such example. E-learning can be used to enhance interest in nephrology. Other innovative tools have been tried as well ( crosswords, anagrams, role playing, concept maps) and we are hoping such tools will aid nephrology education and also enhancement of the field. Here are some links to publications that are reviewing some of these tools. Please give us your comments on these tools and how we can improve and make it more useful for all.

Refs: Link1, Link2, Link3, Link4, Link5, Link6

In this week's New England Journal of Medicine, Pergola et al report the results of a phase 2 randomized trial of an antioxidant inflammation modulator, bardoxolone, in patients with type 2 diabetes and chronic kidney disease (CKD). Over a period of 52 weeks, 227 adults with CKD (defined as an estimated glomerular filtration rate [GFR] of 20 to 45 ml per minute per 1.73 m2 of body-surface area) were randomized in a 1:1:1:1 ratio to receive placebo or bardoxolone methyl at a target dose of 25, 75, or 150 mg once daily. Primary outcome was a change from baseline in the estimated GFR with bardoxolone, as compared with placebo, at 24 weeks; a secondary outcome was the change at 52 weeks. The results were quite surprising.

The long awaited ROADMAP trial was recently published in the New England Journal of Medicine. This randomized controlled trial enrolled 4,447 patients to determine whether treatment with the angiotensin receptor blocker olmesartan could delay or prevent microalbuminuria.

In the study, blood pressure was targeted at less than 130/80 mmHg, yet patients randomized to the ARB group had a lower clinic blood-pressure by 3.1/1.9 overall. The time to onset of microalbuminuria was increased by 23% in the olmesartan group [hazard ratio for the onset of microalbuminuria 0.77; 95% confidence interval, 0.632 0.94; P=0.01]. However surprisingly, there was fewer cardiovascular deaths in the placebo group [3 versus 15, P=0.01].

This fascinating video discusses the concept of organ generation as a method of bridging the enormous gap between supply and demand that exists among patients who experience organ failure.

This may well move from science fiction to the mainstream in the not-too-distant future.

Click 'Read more' below to see the video