Statins fail again

Statins have a tortured relationship with nephrology. Our patients have accelerated atherosclerosis and they die overwhelmingly of cardiovascular disease. So one of my primary jobs is to continually optimize cardiovascular risk factors to save my patients

Control blood pressure, start an aspirin, and maximize the statin are the lather, rinse, repeat of my world.

That said we have little data that this makes a whit of difference, at least in our dialysis patients.


  • No randomized trials have been done on the role of aspirin to prevent cardiovascular events among dialysis patients.
  • Aspirin was found to increase acute coronary syndrome in an unbadjusted analysis but was not significant in multivariate analysis.
  • Berger et al. (PDF), however found a dramatic reduction in 30-day mortality for patients with acute myocardial infarction given aspirin. Unfortunatly fewer dialysis patients received ASA and other standards of heart-attack care (beta-blocker and ACEi) than patients not on dialysis.
The survival of patients based on whether they received ASA for their acute MIThe use of standard therapies for acute myocardial infarction was lower among dialysis patients, even patients deemed ideal candidates for the therapy.

Blood pressure

  • Hypertension, along with cholesterol and obesity, is subject to reverse epidemiology in dialysis patients. This means that observed epidemiology trends are the opposite of what you would expect from data on non-dialysis patients. Lower blood pressure leads to high mortality, lower cholesterol leads to higher mortality, increased BMI yields better observed survival. The observational data, however, does not mean that interventions to lower blood pressure will lead to the same bad outcomes.
  • A recent meta-analysis (PDF) of 8 randomized trials of anti-hypertensive therapy gives credence to the practice of treating hypertension in dialysis patients.

  • One thing high lighted by the trial, though, is the paucity of evidence for this treatment: They were able to find only 1,679 patients. Terrible.


  • The 4D study is one of the few randomized controlled trials in dialysis patients and unfortunately did not show any improvement in mortality with atorvastatin. The study randomized 1,255 hemodialysis patients to either 20 mg of atorvastatin or placebo. After 4 years they found the statin was safe and effective in reducing the median serum LDL cholesterol level by 42%. However, the primary endpoint—cardiac death, nonfatal MI, and stroke—was reduced by insignificant 8% (P=0.37).

  • The authors found a significant increase in fatal strokes among the patients randomized to atorvastatin. (RR 2.03, P=0.04).
  • Today came word that another randomized controlled trial on statins among hemodialysis patients, AURORA, was also a bust. Published yesterday in The Journal, AURORA randomized 2,776 dialysis patients to 10 mg of rosuvastatin (Crestor) or matching placebo. The end-point was a composite of CV death, non-fatal MI, and non-fatal stroke. Average follow-up was 3.8 years and there was no difference in the primary outcome (396 outcomes with rosuvastatin versus 408 on placebo, P=0.51).

  • AURORA found no increased risk of strokes as found in the 4D study.

EKG Changes with hyperkalemia

Last week one of our second-year fellows was called into the ER for a potassium of 9.9 mEq/L. The EKG you see above was waiting for him. He arranged for emergent dialysis. In the morning the patients EKG looked like this:

Here is the time line of events:

  • 17:24 Na 128, HCO3 9, Cl 103, BUN 100, Cr 5.6 (no potassium was reported out on the initial labs)
  • 18:06 First EKG done
  • 18:28: K=9.9
  • 18:28: U/A Sp Grav 1.012, pH 5, random drug screen positive for opioids
  • 18:45: ABG 7.05/37/408/10
  • 18:45: urine Na 89, urine Cr 50.5, FENa 4.7%
  • 23:00 initiate dialysis: 2 hours on 1 K bath
  • 01:00 complete dialysis
  • 03:30 Na 140, K 5, Cl 107, HCO3 16, BUN 67, Cr 3.8, Ca 9.1, Phos 6.4, Mg 1.4, CPK 941
  • 03:30 ABG 7.22/40/117
  • 09:20 Na 142, K 4.8, Cl 111, HCO3 15, BUN 63, Cr 3.2
  • 10:00 ABG 7.20/42/96

This patient had AKI due to prolonged decreased po intake along with a loop diuretic and ACEi. The patient initially was anuric but rapidly began to recover and by the next morning was making over 100 mL of urine an hour.

His initial EKG is the best example of a sine wave from hyperkalemia I have ever seen. Below is a cardiac cycle from V4. With a quick glance it may look like a very wide QRS complex with the t wave somewhere to the right of the picture. In reality, the QRS duration is only 176 msec and the large upward thrust is the peaked T wave.

EKG Changes with hyperkalemia

  • Peaked T waves
  • Shortened QT interval
  • Widened QRS
  • Sine wave

Great article on the two new PSA studies in the NEJM

The New York Times has good coverage of the latest data (US Study, European study) on prostate cancer.

I loved this beat which covers the difference between relative and absolute risk and NNT:

[After discussing the 20% reduction in mortality found in the European study] But in terms of individual risk, even that is not a huge benefit. It means that a man who isn’t screened has about a 3 percent average risk of dying from prostate cancer. If that man undergoes annual P.S.A. screenings, his risk drops to about 2.4 percent.

And there is an important tradeoff. P.S.A. testing increases a man’s risk of being treated for a cancer that would never have harmed him in the first place. The European study found that for every man who was helped by P.S.A. screening, at least 48 received unnecessary treatment that increased risk for impotency and incontinence. Dr. Otis Brawley, chief medical officer of the American Cancer Society, summed up the European data this way: “The test is about 50 times more likely to ruin your life than it is to save your life.”

William Schwartz, the co-discoverer of SIADH has died

William Schwartz has died.

Every Monday at noon during fellowship we had the fluid and electrolyte conference with Dr. Fred Coe. Dr. Coe has extra-sensory powers for electrolytes. When you presented, you would give just the electrolytes and he would re-create the entire case from the metabolic panel. During the lecture he would ask you to explain a certain pathophysiology and then excoriate you if your thoughts were lazy and poorly organized.

If you ever blamed a poorly characterized hyponatremia on SIADH, Dr. Coe would look at you and ask “If Bartter and Schwartz were here, at this table, right now, and were looking at the same data that you have provided, would they agree that this is SIADH? Would they?”

JASN re-printed the original 1957 article describing SIADH in 2001.

Goodbye Dr. Schwartz, yours are the shoulders we stand-on in the daily grind of clinical nephrology.

How not to randomize a study

If you are designing a randomized study, make sure you actualize randomize your patients. Schiffl messed this up in his study of daily versus three days a week dialysis, for acute renal failure. Schiffl achieved randomization by alternating eligible patients to three days a week versus daily dialysis. One key aspect about randomization, especially in non-blinded studies, is that the investigators cannot know what arm of the study the patient will be in prior to enrolling the patient. With alternating patients every investigator knows which arm the next patient will end-up in and they can make subtle decisions on the appropriateness of the patient or in how they present the consent form to influence the composition of the study arms.

This comes up, because my fellow sent me a paper on prophylactic dialysis prior to CABG (PDF). From the paper comes this gem:

Repeat after me, “If you know what arm the patient will be in prior to enrolling the patient, you are not running a randomized trial.”

Urinary anion gap

My fellow remembers the urinary anion gap by saying:


So a negative urinary anion gap is due to gut losses as opposed to an RTA.


iPhone, Blackberry: Fight!

I have a resident in my Farmington office this month. His primary phone is a Blackberry but he also carries an iPod Touch for medical applications. It’s getting to the point that the battle for the mainstream medical computer platform is the iPhone OS.

iPhone OS 3.0 is another major nail in the coffin of the Blackberry, Palm Pre and Windows. With every revision Apple fills in the holes. The critics are running out of ammunition.