Dr. Smiley Thakur MD, FRCPC

GLG News by Dr. Smiley Thakur MD, FRCPC, Transplant Nephrologist

GLG News is now G+ Insights

G+ is a community for professionals, academics and entrepreneurs to connect through online discussions and in-person meetings. You will continue to see G+ Insights (formerly GLG News) here as well as on the G+ website, where you can share and discuss the G+ Insights you read.

Why the doctor can't see you now

December 2, 2008

Analysis of:Why the doctor can't see you now | seattlepi.nwsource.com

This article addresses government policy, taxation, insurance, and socialization implications on future patient access to physician care.

The silencing of the labs

June 19, 2006

Analysis of:Protecting Special Interests in the Name of “Good Science” | jama.ama-assn.org

The Data Quality Act (DQA) is a two sentence addition to a bill enacted in 2000. It directs the Office of Management and Budget (OMB) to provide a way for parties to impact the way government agencies review scientific research. This tool has been used primarily by industry to challenge and silence scientific results that affect their core business interests.

Recent examples include:

1. The tobacco industry creating “scientific uncertainty” regarding tobacco’s health effects and currently blocking actions on environmental smoke

2. Coal and oil industries blocking climate change legislation

3. Asbestos industry opposing asbestos regulation

4. The Salt Institute and US Chamber of Commerce challenging NIH data on reducing salt intake.

Can you tell the difference? AMGEN fears clinicians will view Aranesp and CERA as equivalent.

June 14, 2006

Analysis of:ITC agrees to investigate Roche’s importation of CERA | www.nephronline.com

AMGEN is vigorously opposing the arrival of Roche’s Continuous Erythropoetin Receptor (CERA) on American shores. CERA is currently in use in Europe. Roche’s approval with the FDA is pending.

CERA is a pegylated erythropoietin (peg-EPO). It incorporates a large polymer chain and has different receptor binding characteristics than Aranesp. This provides it with a longer half-life. AMGEN filed a patent infringement lawsuit November 8, 2005.

The US International Trade Commission has now weighed in and will evaluate whether Roche is violating six of AMGEN’s patents.

Niche for new phosphate binder unclear

May 24, 2006

Analysis of:Zerenex in Phase II Clinical Development for Treatment of Hyperphosphatemia in ESRD Patients | www.eneph.com

The need for another phosphate binder is debatable.  Genzyme’s DCOR trial claims ESRD patients taking calcium containing binders for more than two years or those over age 65 have increased mortality versus those taking sevelamer. TUMS is very inexpensive. PhosLo is more expensive than TUMS but is as well tolerated. Patients can develop calcium absorption from these binders and this can limit their usefulness, however. Sevelamer is an effective non-calcium containing binder and fits the niche of backup agent quite well. Its ability to cause acidosis is overrated and not a reason to discontinue therapy. For patients failing sevelamer, lanthanum, a rare earth metal, is a highly effective phosphate binder. Concern regarding the long term use of this agent lies in the history of using other metals i.e. aluminum, to bind phosphate. Aluminum accumulates in bones and may take up to ten years to be detected. The longest bone safety data available for humans on lanthanum is only for 4.5 years.

Zerenex is unlikely to be as inexpensive as TUMS/PhosLo and patients deserve a trial of this effective treatment first, in my opinion.  The DCOR trial results will be hotly debated when they are published in a peer reviewed journal, hopefully later this year.  If concerns rise regarding  the mortality risk of calcium binders and Zerenex is priced below sevelamer, it may effectively compete with sevelamer for market share. 

The doctor won’t see you now.

May 24, 2006

Analysis of:Medicare forecast renews calls for pay reform | www.amednews.com

Practicing physicians are caught in the spread between the rising cost of doing business and declining reimbursement for services. By the end of 2016, physicians may be earning 37% less than they currently do, according to projected reimbursement rate declines. Physicians may have to be satisfied with less of a planned decrease e.g. -3% instead of -4.7%, as the best compromise Congress can attain. Certainly, a net increase in physician payments isn’t something anyone is contemplating. The best physicians could hope for, in this author’s opinion, is for reimbursement to remain, on average, at its current level. A rise in the cost of doing business over the next nine years by 22% is an extension of slow increases physicians are already experiencing.

Never ask a barber whether you need a haircut – Confuscious

May 18, 2006

Analysis of:Reported Outcomes in Major Cardiovascular Clinical Trials Funded by For-Profit and Not-for-Profit Organizations: 2000-2005 | www.jama.com

Clinicians and financial analysts rely on trial data to guide decision making. Clinicians are well aware that positive trial results are more likely to be published than failures of treatment or neutral studies. While many are aware of the importance of trial design, the influence of funding source is rarely emphasized as having an influence on trial results. Data suppression, design bias, and data quality are other reasons for this discrepancy in publication. Rofecoxib (Vioxx, Merck) is a front-page media example of how suppression of drug company data can have fatal consequences.

It is important to be aware of the source of study funding as well as author affiliation when interpreting study results. Scepticism of drug company studies, even if high quality, well designed, and published in reputable journals, is still warranted.

 

Sensipar seeking upstream indication in stage 3 and 4 CKD markets

May 16, 2006

Analysis of:Cinacalcet hydrochloride is an effective treatment for secondary hyperparathyroidism in patients with CKD not receiving dialysis. | www.ajkd.org

Cinacalcet (Sensipar, AMGEN) was a wonder drug when it became available three years for the treatment of secondary hyperparathyroidism (SHPT) in end stage renal failure (ESRF). Patients with PTH levels greater than 800 pg/ml were well on their way to requiring surgical removal (parathyroidectomy) of the PTH glands. Oral cinacalcet is highly effective causing a predictable drop in PTH levels. Patients are spared parathyroidectomy as long as they continue therapy.

Data from the USRDS estimates 616,000 patients will be on dialysis (Stage 5) by 2010. Stage 3 patients will number 13,058,000 with stage 4 patients numbering approximately 657,000. An indication to use cinacalcet in stage 3 and 4 patients will substantially increase the market of patients suitable for treatment.

Weak data generates intriguing hypothesis

May 11, 2006

Analysis of:Antiproteinuric effect of oral paricalcitol in chronic kidney disease | www.nature.com.ezp1.harvard.edu

Treatment of stage 3 and 4 CKD patients with hyperparathyroidism prevents bone loss and improves morbidity. The ability to show a benefit in terms of actually preserving renal function would prove vitamin D is useful not only for treating the consequences of CKD (hyperparathyroidism), but also in favorably altering the course of CKD. Proteinuria is a marker for CKD progression. Treatments that decrease urine protein, protect renal function.

Block hypertension at the first step: Novartis’ novel renin inhibitor

May 3, 2006

Analysis of:New Drug Application for Rasilez (Aliskiren), an Innovative Oral Renin Inhibitor to Treat High Blood Pressure, Accepted for Review by the FDA | www.therapeuticsdaily.com

A brief lesson in physiology is required to understand the importance and concerns that arise from this novel compound that inhibits renin. Renin is formed from prorenin which is synthesized in the juxtaglomerular apparatus of the kidney filtering units, known as glomeruli. The stimuli for formation are renal hypoperfusion states, both real and perceived. Prorenin also circulates systemically but its role there is not clear. Both prorenin and renin are known to play a role in uterine function and especially in pregnancy, however. Renin causes the conversion of angiotensinogen to angiotensin I. Angiotensin converting enzyme (ACE) converts angiotensin I into angiotensin II. ACE is present in the lung, lining of blood vessels, in the glomeruli, as well as other organs.

Novel treatment of Alport Disease: Stem cell therapy repairs basement membrane defect

May 3, 2006

Analysis of:Bone-marrow-derived stem cells repair basement membrane collagen | www.pnas.org

In Alport Disease, defects in genes coding for type IV collagen are responsible for the resultant defective composition of the glomerular basement membrane (GMB). The GBM is responsible for retaining red blood cells and protein on the circulation side of the renal filtering units (glomeruli). Symptoms from this genetic disease develop in childhood. Affected patients progress to renal failure and experience symptoms in other organs dependent on these proteins ie hearing deficits, cataracts. There is no effective cure and patients require dialysis or renal transplantation, as renal failure progresses.

What is normal blood pressure? The line is a changin’.

May 3, 2006

Analysis of:Feasibility of Treating Prehypertension with an Angiotensin-Receptor Blocker | content.nejm.org

The current definition of hypertension is >140/90 mm of mercury. Being hypertensive increases one’s mortality risk from a variety of causes. Studies show “prehypertension”, that is having a blood pressure in the 130-139/85-89 range, increases one’s risk of stroke by 2.14 times and a fatal cardiac event by 1.61 times, when compared to individuals with more normal pressures. Thus the question arises of whether treating earlier is possible, beneficial, and produces a sustainable benefit.

The answer to this question will raise more significant issues:

a)What is the normal blood pressure that predicts no increased mortality risk?

b)What blood pressure is worth treating from a cost-effective point of view?

c)Does treating early actually cause a decrease in morbidity/mortality?

 

My analysis of the three oral Vitamin D analogs available for treatment of hyperparathyroidism in CKD

May 3, 2006

Analysis of:Paricalcitol capsule for the treatment of secondary hyperparathyroidism in Stages 3 and 4 CKD | journals.elsevierhealth.com

Hyperparathyroidism develops as renal function declines below a GFR of 60 ml/min. Early treatment preserves bone density. Three oral agents are currently available in the treatment of Stage 3 and 4 CKD patients. Calcitriol works in some patients without causing hypercalcemia or hyperphosphatemia. Paricalcitol and doxercalciferol are equally efficacious at lowering PTH. The latter has some concerns regarding the increased need for phosphate binders and increased calcium absorption from the gut.

GI bowel prep implicated in causing renal failure

April 19, 2006

Analysis of:Acute phosphate nephropathy following oral sodium phosphate bowel purgative: An underrecognized cause of chronic renal failure | www.jasn.org

Acute renal failure due to OSPS bowel prep is underrecognized and therefore underreported. The mechanism of injury is understood and risk factors have been identified to identify patients at risk of renal injury.

Defeating planned obsolescence: The science and politics of living forever

April 19, 2006

Analysis of:New Agers Live to 150 | www.barrons.com

The life expectancy of men(women) have increased from 46.3 years (48.3 years) in 1900 to 74.8 years (80.1 years) in 2003. Advances in sanitation, antibiotics, and disease management are largely responsible. Several obstacles lie ahead in the pursuit of prolonged life expectancy. Several companies are already working on drug therapies which have applications in prolonging longevity.

EXEL Phase II randomized trial enrolls diabetics with nephropathy

April 11, 2006

Analysis of:Phase II Clinical Program For XL784 For Diabetes Who Have Proteinuria | www.medicalnewstoday.com

Exelis, Inc. (EXEL) has initiated enrollment of diabetics with nephropathy in a randomized Phase II trial of XL784. This agent acts by inhibiting an enzyme involved in angiogenesis and cell proliferation.  Both processes are associated with renal fibrosis and disease.

What is keeping the Home Hemodialysis market from expanding?

April 11, 2006

Analysis of:A growing HHD market: Can it continue? | www.nephronline.com

Aksys and NxStage offer competing home hemodialysis (HHD) systems. Their market growth has little to do with product competition between the two. The limited number of patients suitable, the small percentage of patients who would choose it over PD, and the current reimbursement climate are more relevant factors.

Hemoglobin: More isn't better

April 11, 2006

Analysis of:Update on Erythropoietin Treatment: Should Hemoglobin Be Normalized in Patients with Chronic Kidney | www.jasn.org

Targeting a subnormal hemoglobin costs ~$55,000 per quality-adjusted life year gained. Attaining a normal hemoglobin requires ~$800,000/year. As the marketplace crowds with new ESP's, evidence shows market share can not be increased by justifying higher hemoglobin targets.

Urine Telomerase: A better TRAP to detect bladder cancer

April 10, 2006

Analysis of:Relevance of Urine Telomerase in the Diagnosis of Bladder Cancer | www.jama.com

60,000 new bladder cancer diagnoses are made each year in the USA. Bladder cancer is the 4^th common cause of cancer in men and the 10^th in women. 20% of patients die per year. Early diagnosis and treatment provides good survival. Current detection techniques include urine cytology and cystoscopy. 

A non-invasive, sensitive assay would aid in the detection of early tumors in at risk populations. 

Angiostatin: New possible early treatment of DN

April 6, 2006

Analysis of:Therapeutic potential of angiostatin in diabetic nephropathy (DN) | www.jasn.org

Our understanding of the early phases of diabetic nephropathy (DN) is imperative so as to provide intervention targets. DN will affect 20-40% of Type I and 10-20% of Type II diabetics. Growth factors and inflammatory mediators play significant roles in the development of DN. Angiostatin is a potent angiogenic inhibitor that inhibits the proliferation of vascular endothelial cells. This has proven implications in tumor regression, metastases, as well as retinal neovascularization. This animal study shows DN can be targeted early with a resultant decease in microalbuminuria, the precursor to DN.

Hepatorenal Syndrome: Terlipressin Phase III trial completes enrollment

April 6, 2006

Analysis of:PDL Biopharma completes patient enrollment in Terlipressin study | nephnews.com

Hepatorenal syndrome (HRS) is characterized by liver failure causing renal failure. A double blind trial is needed to identify an effective treatment. For these critically ill patients, there is no approved treatment short of liver transplantation.

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