Month: May 2016

So this is a little out of my wheelhouse, but yesterday this tweet came across my tweet stream:

If you had to pick seminal articles in health policy all residents should know, what would you choose?@RealCedricDark @AriBFriedman @MDaware

— Vidya Eswaran (@vidyaeswaran) May 16, 2016

Ari Friedman replied

Arrow 63, Pauly 68, Cutler Reber 98, Finkelstein *, Cohen 08, Burns Pauly 12. https://t.co/ayxlRhMoVU

— Ari Friedman (@AriBFriedman) May 16, 2016

Which was simultaneously a great answer and kind of useless. He then sent me a bibliography, here is his list with links:

There is a spirited debate in our hospital system about the use and availability of high flux membranes. Part of the debate centered around middle molecule clearance and its relationship to uremia. I fell back to my old standard the HEMO trial.

A study as long and as expensive as HEMO will not be let to rot after its first paper, and the research parasites extracted a number of tantalizing findings. In 2003 JASN published an analysis that looked at flux when patients were divided by vintage. Dialysis patients who have been on dialysis for more than 3.7 years had improved outcomes with high flux dialyzers:

In the subgroup that had been on dialysis for >3.7 yr, randomization to high-flux dialysis was associated with lower risks of all cause mortolity (RR, 0.68; 95% CI, 0.53 to 0.86; P = 0.001), and cardiac deaths (RR, 0.63; 95% CI, 0.43 to 0.92; P = 0.016), compared with low-flux dialysis.

Though the data is not so compelling when the vintage is divided by quintiles:

Even more damning ,was the fact that the longer the patients were randomized, the smaller the effect of high flux membranes:

Longer years of follow-up should show more protection from high-flux membranes (lower RR in the table) but the opposite is actually seen.

Additional post-hoc analysis was done here, showing decreased cerebrovascular disease for longer vintage patients:

I then came across the membrane permeability outcome study, MPO, published in 2009 in JASN. This European study was designed to answer the following question:

This prospective, randomized Membrane Permeability Outcome (MPO) study was designed to compare the impact of membrane permeability on survival in incident HD patients who had either low ( 4 g/dl) or normal albumin ( 4 g/dl) and were treated with a minimum dialysis dose (single-pool Kt/V [spKt/V]) of 1.2. 

Use of incident patients will eliminate the vintage advantage seen in the two post-hoc HEMO studies discussed above. Separating patients based on albumin at baseline seems a bit wonky. Lots of patients have low albumin at the start of dialysis. And I doubt there is an inherent biological reason for this. Turns out, the two tiers were due to pokey enrollment after 11 months and they changed enrollment rules.  They also changed the rules by extending the time patients could take to get to a spKt/V from 1 month to 3 months. The things we do for enrollment!

The top-line results showed no difference in survival by flux:

This isn’t just any pre-specified sub-group, this was supposed to be the entire cohort, and only became a sub-group after they amended the protocol.

Last week the Wearable Artificial Kidney reached some sort of new benchmark and a bunch of press ensued. I stumbled across this one.

Persons using catheters had increased risk of all-cause mortality (RR=1.38, 95% CI=1.25–1.52), fatal (RR=1.49, 95% CI=1.15–1.93) and nonfatal (RR=2.78, 95% CI=1.80–4.29) infection, cardiovascular event (RR=1.26, 95% CI=1.11– 1.43), and hospitalization (RR=1.51, 95% CI=1.30–1.75) compared with those individuals using grafts. From Ravani, JASN 24:465-73, 2013.