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Journal Club: Aggrenox and AVG for TZDs in HD

Dixon et al. Effect of dipyridamole plus aspirin on hemodialysis graft patency. N Engl J Med (2009) vol. 360 (21) pp. 2191-201 (PDF)

Randomized placebo controlled double blind trial of patients on hemodialysis or to start hemodialysis in the next 6 months with a new AVG.

Primary outcome was loss of primary unassisted graft patency. thrombosis, 50% stenosis. Patients underwent regular site monitoring and referred for angiography if qB was less than 600 or less than 1000 and a greater than 25% reduction of qB.

Power analysis required 1054 patients.

results: 321 randomized to Aggrenox
328 assigned to placebo

No difference in bleeding or cardiovascular events.

Take home message: modest benefit from expensive drug in underpowered but well designed and executed study.

Brunelli et al. Thiazolidinedione use is associated with better survival in hemodialysis patients with non-insulin dependent diabetes. Kidney Int (2009) vol. 75 (9) pp. 961-8 (pdf)

Thiazolidinediones (TZDs)

  • bind peroxisome proliferator-activated receptor gamma
  • increase insulin sensitivity in peripheral tissues
  • increase HDL
  • decrease triglycerides
  • decrease visceral fat
  • improve endothelial function

This study is a retrospective analysis of hemodialysis patients in the ArMORR cohort.
ArMORR is a cohort of incident dialysis patients at FMC units. The total cohort includes 10,044 patients.

This analysis restricted to patients with diabetes surviving at least 30 days on dialysis.

Patients on pioglitazone (Actos) or rosiglitazone (Avandia) were placed in the TZD group. Primary outcome was time to death from any cause. Maximum follow-up was one year.

Results: 5,290 patientss were eligible for inclusion.
9.6% were treated with a TZD


Improved survival was seen among patients on TZDs, especially patients not also on insulin. Interestingly the survival benefit came from a reduction of non-CV end-points.

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Cool site on eGFR and proteinuria

2009 Annual Evidence Update on Proteinuria and eGFR

This Annual Evidence Update has been created to update the evidence presented last year for the 2008 National Knowledge Week on Proteinuria and eGFR. You can read commentaries on the latest systematic reviews, randomised controlled trials and the 2008 NICE guideline on Chronic Kidney Disease, as well as see what evidence has been produced in the last 12 months for the different topics presented last year. Drs David Goldsmith and Edward Sharples have also picked out the Treatment Uncertainties from the evidence, which have been added to the UK DUETs database.

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UpToDate evidence based medicine or not? Not.

A few months ago medical blogger Laika wrote an insightful blog entry summarizing a meme which had been bouncing around twitter regarding whether UpToDate was evidence based medicine or some other entity.


I found the whole excercise to be a bit too philosophical for me. Regardless of what you call it I think everyone would agree that UpToDate is useful. It is a great starting place but usually insufficient as a single source.

I was reminded about it today when I came across this paragraph:

In the card on “Clinical manifestations, diagnosis, and natural history of primary biliary cirrhosis.” (Link for subsribers)

Regardless of the merits of UpToDate, nothing breaks the illussion of evidence based medicine like an author throwing out a random statistic like “approximately 15% of the 1,200 patients who I have seen…” without a reference. This is the epitome of expert oriented experiential medicine and has no place in EBM.

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I am doing Grand-Rounds on the relationship of uric acid and hypertension

About three years ago I had the privledge to attend a day long seminar on gout put together by Jerry Yee from Henry Ford Hospital. The highlight of the day was a lecture by Richard Johnson from the University of Florida. I had learned about Johnson at my fellowship as the principle discoverer of the link between hepatitis C and membranoproliferative glomerulonephritis (review), in my mind, among the most significant discoveries in nephrology in the last twenty years. Before seeing him I had not made the connection between Richard Johnson and the author of the deservedly popular nephrology text Comprehensive Clinical Nephrology, but it is one and the same.

At that seminar Dr. Johnson gave the greatest lecture I have ever heard. The lecture was on uric acid and its etiologic role in hypertension, obesity and diabetes.

When I heard that he was writing a book on the subject I purchased it and have been reading it on and off for the last 8 months or so. Unfortunately, the book doesn’t have nearly the punch as his 90 minute lecture. My sense is that he writes to the level of the typical purchaser of diet books and comes across more as a carnival barker than one of the most respected researchers in nephrology today.

As I get ready for my grand rounds I am going to blog about uric acid, fructose and the epidemics of diabetes, obesity and hypertension as presented by Dr. Johnson in his book: The Sugar Fix. Should be an interesting ride as the subject is blessed with lots of data, industry influence, huge health implications and a likely Nobel prize if Johnson has really discovered the cause of the bulk of essential hypertension.

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PBFluids has been a little quiet recently

In the past few weeks I have been working on two presentations. The first was to Genzyme’s scientists and the second was grand rounds at Providence. I have been spending way too much time working on those two talks. Thankfully the bones of both talks were the same. I spoke on the problem of chronic kidney disease on the elderly, specifically whether CKD was over diagnosed (yes it is) in this population and can it be safely ignored (no it can’t).

I’m not completely through the gauntlet yet. I still have to provide a chapter on lifestyle modification for the control of blood pressure.

But I can’t describe the awesome feeling of relief from delivering the grand rounds this morning.

For those of you with iWork and Keynote here is the presentation:

The Two Faces of Geriatric CKD

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Cool new (to me) word: Anamnesis

Learned a new word: anamnesis.

Synonym for medical history.

Apparently, if you are considering the diagnosis of HCl intoxication no fancy flow chart needed just ask the patient if she’s been swigging hydrochloric acid.

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Sterile Pyuria [updated]

Patient came in yesterday with a three month history of frequent UTIs. These UTIs were diagnosed when the patient presented to her doctor with back/flank pain and the U/A was positive for leukocyte esterase and white cells but was always nitrate negative and the cultures never revealed more than low colony counts of skin flora.

The patient’s pain repeatedly responded to a few days of quinolone therapy.

Differential for sterile pyuria:

  • Renal TB: patient’s husband had a history of active TB
  • Interstitial nephritis: patient was taking a significant amount of NSAIDs and ASA for the back pain
  • Nephrolithiasis: patient had calcifications in the kidney on the U/S
  • Urogenital cancer
  • Vaginal contamination
  • Glomerulonephritis
  • Chlamydia, mycoplasma, ureaplasma (thanks Jim)

Others?

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Weight loss and blood pressure


Hmm, that’s an interesting question. When I counsel patients on controlling blood pressure I mention weight loss but don’t perseverate on it because of the general futility of of achieving lasting weight loss. Most diets deliver only modest weight loss and that weight loss is depressingly short lived:
The figure above is the primary results from a trial of various strategies to preserve weight loss. 1,685 patients were enrolled, only 1,032 lost the require 10 lbs to begin Phase 2. In Phase 2 patients were randomized to 1) minimal intervention 2) web-based interaction 3) monthly contact with an interventionist. Patients with monthly contact regained 3 lbs less than the patients with self-directed maintenance. Svetkey et al. Comparison of strategies for sustaining weight loss: the weight loss maintenance randomized controlled trial. JAMA (2008) vol. 299 (10) pp. 1139-48 (PDF)

Second study looking at Weight Watchers compared to a self-help program for weight loss. Same pattern, modest weight loss followed by rebound to regain much of the lost weight. Heshka et al. Weight loss with self-help compared with a structured commercial program: a randomized trial. JAMA (2003) vol. 289 (14) pp. 1792-8 (PDF)

I focus my limited office time on changing patients’ diet to reduce blood pressure. I recommend the DASH diet (PDF) to all of my patients without significant metabolic bone disease or hyperkalemia because I believe the data shows that it is the most effective life-style intervention to ameliorate hypertension. Unfortunately those two exclusions (bone disease and potassium) exclude many of my patients. I usually don’t recommend the low sodium version of of DASH because I feel that the reduction in palatability is not supported by the rather modest additive effects (an additional 3 mmHg reduction in SBP). Most of my patients recognize that they eat too much and have been trying to reduce calories, and lose weight for years prior to seeing me. I feel that by discussing the DASH diet and not rehashing the same tired dietary advice that every doctor has been promoting, I provide them with a novel view of dietary changes that they are willing to try.

Still, I think The Kidney Group has an interesting question, what is more important weight loss or diet changes?

NephSAP recently reviewed hypertension. On page 98 they had this table which compared various lifestyle interventions and their effect on blood pressure:
Unfortunately they grouped diet and weight loss in one group so it does not allow me to separate out the effect of changing diet from changing weight. Regardless, the effect on blood pressure looks modest compared to the findings of the DASH diet or DASH sodium intervention. From the abstract of the DASH-Sodium trial (PDF):

As compared with the control diet with a high sodium level, the DASH diet with a low sodium level led to a mean systolic blood pressure that was 7.1 mm Hg lower in participants without hypertension, and 11.5 mm Hg lower in participants with hypertension.

The Archive published this meta-analysis (PDF) in 2008 looking at weight loss by diet or drugs with respect to mortality and blood pressure control.


They found that weight loss did result in blood pressure reductions but the reduction was modest. Additionally not all methods were equal, with silbutamide (Meridia) resulting in an increase in blood pressure despite being effective at reducing weight. They were unable to find any studies which showed a reduction in weight reducing mortality.

The above systemic review mentioned that the TONE study was one that was particularly well done. The TONE trial (PDF) was published in JAMA in 1998 and compared sodium restriction to weight loss to usual care in a two by two factorial design. The enrolled 585 obese patients to be randomized to either weight loss, no weight loss, salt restriction or not. Another 390 were randomized to either salt restriction or usual diet.
The investigators achieved nice separation of the groups with regard to weight loss. The study began with every patient weaning off their antihypertensive medication and the primary end-point was the fraction resuming their pharmacologic blood pressure medications and the time to resumption. Weight loss was more effective than no intervention and about equally efficacious as sodium restriction:

Note the lower starting blood pressure for sodium intake, this accounts for some of the difference in the effect on blood pressure.

Though TONE showed no difference between weight loss and sodium restriction, I feel that diet is probably more important because sodium restrictionis not the most effective dietary change to reduce blood pressure, the DASH diet is. I feel that if the TONE trial was rerun with the DASH diet replacing sodium restriction we might see that diet is more important than weight loss.

One thing I am doing in my clinic more and more is recommending bariatric surgery. Medical and behavioral changes have a poor track record at providing lasting and significant weight loss. Bariatric surgery shows lasting weight loss 10 years out and it allows patients to recover from hypertension and diabetes. Sjöström et al. Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery. N Engl J Med (2004) vol. 351 (26) pp. 2683-93. (PDF)