UKidney Nephrology News and Insights

AUG
06
0

Fascinating new therapy for PCKD on the horizon

While the nephrology community awaits the outcome of a much awaited study of tolvaptan on progression of polycystic kidney disease (PCKD), a new story is emerging with very intriguing possibilities.
 
Previously on UKidney, we reported the disappointing outcomes with mTOR-based treatments on PCKD outcomes. While in one study with everolimus, cyst volume was blunted, renal functional loss was unchanged at the expense of greater side effects. The problem with this approach in treating PCKD is one that plagues drug therapy for many other conditions, namely that one must expose all tissues to a drug in the hope that target organ, receives adequate therapeutic exposure. The result of this strategy is overdosing the bystander organs and potentially under-dosing the target organ.
 
A new drug is emerging that could change all of this. FC-rapa conjugates rapamycin with folate, capitalizing on the observation that PCKD cells express high levels of folate receptors. The result is that this chimeric compound delivers a greater concentration of the drug to its target while sparing a greater number of bystander tissues. According to Dr. Jonathan M. Shillingford, who is lead investigator in this work, the uptake of FC-rapa by tissues other than the kidney would be negligible and in their studies, only kidney cells were shown to take up the chimeric compunds (see commment below). Endocyte, the company behind the congujgated rapamycin specializes in this technique which is being studied increasingly in cancer treatments as well. It is very early in the life-cycle of FC-rapa, but in one study seen in the Journal of the Amercian Society of Nephrology, the drug was highly effective at limiting cyst growth in mice while side effects are much fewer than with conventional rapamycin.
 
Along with the possibility of using tolvaptan to treat PCKD, this resurgence in mTOR-based treatments further brightens the horizon for patients with this disorder.
Continue reading
JUN
20
3

Cinacelcet and cardiovascular outcomes: neutral study underscores a fundamental problem in nephrology research

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.

Continue reading
JAN
16
8

Treating microalbuminuria to reduce cardiovascular disease: an increasingly dangerous strategy

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.

Continue reading
DEC
20
10

No benefit of Aliskiren added on to ACE or ARB: a disappointing development

Plasma Renin ActivityIn 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.

Continue reading
JUL
26
0

Generic drugs: a dangerous public misunderstanding?

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).

Continue reading
JUL
14
2

Novel Tools to Teach Nephrology

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

Continue reading
JUL
02
2

Bardoxolone in Chronic Kidney Disease: A major breakthrough?

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.

Continue reading
MAR
12
2

Olmesartan delays the onset of microalbuminuria, but more deaths seen

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].

Continue reading
MAR
04
0

Growing new kidneys? An idea whose time may have come

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

Continue reading
FEB
17
0

Chloroquine in Lupus: Prevents flares and saves lives

This is a great post on chloroquine in lupus. It appears as below on Skin and Allergy News. A great and promising read:

SNOWMASS, Colo. – The past 12 months have brought a slew of studies making a persuasive case for hydroxychloroquine as a far more important drug in lupus than previously thought. Indeed, the drug could now even be considered essential.

"In 2011, all lupus patients should receive hydroxychloroquine," Dr. David Wofsy flatly declared at a symposium sponsored by the American College of Rheumatology.

"The indication for hydroxychloroquine in lupus is lupus," added Dr. Wofsy, professor of medicine and microbiology/immunology at the University of California, San Francisco.

There is now solid evidence that hydroxychloroquine (Plaquenil) prevents lupus flares, treats the skin manifestations of the disease, protects against thromboembolic events, prevents cardiac neonatal lupus, and prolongs life.

"It will be a very long time before we've proven that any biologic therapy can do all those things," Dr. Wofsy, who is also chief of rheumatology at the San Francisco Veterans Affairs Medical Center.

Continue reading
ukidneyisup