Hearts in the Crossfire: Standard Hemodialysis Stuns Organs—But, There is Hope!

This blog post was made by Dori Schatell, MS, Executive Director, Medical Education Institute on February 26th, 2015.
Hearts in the Crossfire: Standard Hemodialysis Stuns Organs—But, There is Hope!

Dr. Chris McIntyre, newly moved from the UK to the shining dialysis beacon of London Ontario, Canada, became one of my favorite people on earth during his keynote address at the recent Annual Dialysis Conference (ADC)—and we’ve never even met!

In case you don’t know him either, the ADC program lists Dr. McIntyre as “Professor of Medicine, Robert Lindsay Chair of Dialysis Research and Innovation, Schulich School of Medicine and Dentistry, University of Western Ontario; Director of London Kidney Clinical Research Unit, London Health Sciences Centre, London, Ontario, Canada,” and goes on to say that he “leads a team of multidisciplinary researchers focused largely on the pathophysiology of the widespread abnormalities of cardiovascular function and body composition in CKD patients… these studies have increasingly focused on the adverse consequences resulting from dialysis therapy itself and the improvement in outcomes by the reduction of preventable harm .” (Now do you see why he is one of my new favorite people?!)

His talk was brilliant (STUNNING, actually, pardon the pun), and I truly wish it had been videotaped so CMS could see it, but sadly it wasn’t. So, read on if you’d like to make do with my notes—with apologies to Dr. McIntyre if I got anything wrong—and some of his team’s papers in PubMed.

Key Points

  1. Circulatory stress causes most of the complications of uremia. Dr. McIntyre referred to an intradialytic “chamber of horrors,” noting that intradialytic hypotension (IDH) occurs in up to 2/3 of standard in-center hemodialysis (HD) treatments . So, those all-too-common painful cramps, headaches, and wiped-out feelings are signs of a much larger and longer-term problem…
  2. Patients don’t just fade away: they tend to go quickly—due to sudden cardiac death. Myocardial stunning (first mentioned in 1983 in general,[1] and in 2006 in HD[2]) is the mechanism for fibrosis and left ventricular hypertrophy (LVH). In effect, the heart muscle is zapped by lack of oxygen each time blood flow drops, and the muscle does not return to normal after a treatment is over.[3]We can measure for stunning by testing blood for troponin T; higher levels correspond to more damage. [4] (NOTE: I would wager that this test is never done in the US outside, perhaps, of research studies—so, of course we don’t find what we don't look for…)
  3. So, what caused the stunning—did standard HD itself drive the process? Dr. McIntyre and his colleagues used a PET scanner DURING HD to look at patients’ hearts! In one study,[5] seven HD patients without diabetes or significant cardiac histories were scanned before treatment, 30 minutes in, and at 220 minutes (NOTE: this was done in the UK—in the US, most don't even get 220 minutes of in-center HD!). Global blood flow to the heart muscle dropped in all patients. At 30 minutes—without ultrafiltration—it fell by 13.5+11.5%. At 220 minutes, with ultrafiltration, it fell by 26.6+13.9% (both were significant). Two patients developed new regional heart wall abnormalities—and they had less blood flow to the heart muscle than the rest.
  4. The reduced blood flow was comparable to a heart attack,” emphasized Dr. McIntyre, who went on to say that, “Hemodialysis-induced stunning leads to myocardial hibernation and decreased systolic function. After stunning, patients’ blood pressure becomes less responsive. After 6 months, only a tiny fraction have normal hearts.” In a study of 30 patients who had hemodialysis-induced heart damage, just one year of dialysis led to a significant drop in left ventricular ejection fraction: their hearts pumped out 61.5+10.1% less blood. [6]
  5. But wait—it gets worse! The heart is NOT the only organ stunned by reduced blood flow during standard in-center HD. The gut is stunned, too. Apparently, Dr. McIntyre noted, each of our guts contains enough endotoxin to kill 2000 people. When endotoxin stays in the gut, it is excreted harmlessly from the body. If endotoxin leaks into the bloodstream, it triggers inflammation, or even sepsis. Papers from the team implicates circulating endotoxins as a novel factor in ESA-resistance[7] (!!!!! I’ve never believed that higher hemoglobin levels were lethal—but inflammation certainly can be, and none of the studies ever looks at it!) and heart disease.[8]
  6. The kidneys are stunned. Stunning is the likely reason for the faster loss of residual kidney function with standard in-center HD than with PD…
  7. The brain is stunned. Compared to people who are not on dialysis and have similar levels of arterial stiffness, those on dialysis have white matter injuries and very impaired cognitive function —including depression.[9]

The impact of stunning is even seen in children receiving standard in-center HD.[10]

So, Is There Hope to Avoid Damage from Stunning?

In a word: Yes.

Frankly, Dr. McIntyre’s talk would have been very depressing if he hadn’t gone one step further and described a FREE intervention that could start TODAY to help people on standard in-center HD: cool dialysate.


Using slightly cool dialysate can reduce the impact of organ stunning in a standard in-center HD setting . In a small randomized crossover trial, 10 patients who were prone to intradialytic hypotension (IDH) tested dialysate at 37°C (98.6°F) or 35°C (95°F). [11] Patients dialyzing with warmer fluid developed almost four times as many new heart muscle abnormalities as those dialyzing with cooler fluid. Patients tolerated the slightly cooler temperature well.

Changing the temperature did not affect the “adequacy” of dialysis. The team conducted a year-long study to follow 73 patients randomized to usual 37°C dialysate (98.6°F) vs. dialysate set to 0.5°C cooler than each person’s core body temperature (measured in the ear). Cooled dialysate made the treatments more tolerable—and completely prevented abnormal brain changes.[12]

There are other ways to reduce the risk of intradialytic hypotension and organ stunning with standard in-center HD that Dr. McIntyre did not address in his talk—though he was involved in both of the studies below:

  • Do PD. In ten patients observed on PD with echocardiogram, no stunning occurred. Heart muscle wall abnormalities were very rare. [13]
  • Remove less water at each treatment. Dialyzing more often than the seemingly magical three days per week paid for by Medicare reduces the risk of intradialytic hypotension and myocardial stunning on echocardiogram.[14] Though the study was small (N=46), there were trends toward lower troponin T levels, too.

If you have followed this blog, you may have seen Dr. Agar’s passionate defense of longer, gentler dialysis here, here, and here. Dialyzing more gently can avoid intradialytic hypotension—which can be so awful that some patients choose to stop dialysis and die rather than go through it again. When we can give patients back their lives while helping them avoid injury to their hearts, kidneys, guts, and brains—that is the biggest win of all.



[1] Bashour TT, Kabbani SS, Brewster HP, Wald SH, Hanna ES, Cheng TO. Transient Q waves and reversible cardiac failure during myocardial ischemia: electrical and mechanical stunning of the heart. Am Heart J. 1983 Oct;106(4 Pt 1):780-3

[2] Galetta F , Cupisti A,Franzoni F,Carpi A,Barsotti G, Santoro G. Acute effects of hemodialysis on left ventricular function evaluated by tissue Doppler imaging. Biomed Pharmacother 2006 Feb;60(2):66-70.

[3] McIntyre CW, Burton JO, Selby NM, Leccisotti L, Korsheed S, Baker CSR, Camici PG. Hemodialysis-Induced Cardiac Dysfunction Is Associated with an Acute Reduction in Global and Segmental Myocardial Blood Flow. Clin J Am Soc Nephrol 2008:3(1), 19–26

[4] Breidthardt T, Burton JO, Odudu A, Eldehni MT, Jefferies HJ, McIntyre CW. Troponin T for the Detection of Dialysis-Induced Myocardial Stunning in Hemodialysis Patients. Clin J Am Soc Nephrol 2012 7(8),1285–1292

[5] Dasselaar JJ, Slart RH, Knip M, Pruim J, Tio RA, McIntyre CW, de Jong PE, Franssen CF. Haemodialysis is associated with a pronounced fall in myocardial perfusion Nephrol Dial Transplant 2009 24:604–610

[6] Burton JO, Jefferies HJ, Selby NM, McIntyre CW. Hemodialysis-induced repetitive myocardial injury results in global and segmental reduction in systolic cardiac function. Clin J Am Soc Nephrol 2009 4(12):1925-31

[7] Harrison LE, Burton JO, Szeto CC, Li PK, McIntyre CW. Endotoxaemia in haemodialysis: a novel factor in erythropoetin resistance? PLoS ONE 2012 7(6):e40209

[8] McIntyre CW, Harrison LE, Eldehni MT, Jefferies HJ, Szeto CC, John SG, Sigrist MK, Burton JO, Hothi D, Korsheed S, Owen PJ, Lai KB, Li PK. Circulating endotoxemia: a novel factor in systemic inflammation and cardiovascular disease in chronic kidney disease. Clin J Am Soc Nephrol 2011 6(1):133-41

[9] Eldehni MT, McIntyre CW. Are there neurological consequences of recurrent intradialytic hypotension? Semin Dial 2012 25(3):253-6

[10] Hothi DK, Rees L, Marek J, Burton J, McIntyre CW. Pediatric myocardial stunning underscores the cardiac toxicity of conventional hemodialysis treatments. Clin J Am Soc Nephrol 2009 4(4):790-7

[11] Selby NM, Burton JO, Chesterton LJ, McIntyre CW. Dialysis-induced regional left ventricular dysfunction Is ameliorated by cooling the dialysate. 2006 Clin J Am Soc Nephrol 2006 1(6): 1216–1225

[12] Eldehni MT, Odudu A, McIntyre CW. Randomized Clinical Trial of Dialysate Cooling and Effects on Brain White Matter. J Am Soc Nephrol. 2014 Sep 18. [Epub ahead of print].

[13] Selby NM, McIntyre CW. Peritoneal Dialysis is not associated with myocardial stunning. Perit Dial Int 2011; 31:27-33

[14] Jefferies HJ, Virk B, Schiller B, Moran J, McIntyre CW. Frequent hemodialysis schedules are associated with reduced levels of dialysis-induced cardiac injury (myocardial stunning). Clin J Am Soc Nephrol 2011 6: 1326–1332

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Comments

  • Dori

    Jul 6, 10:06 AM

    A new abstract suggests that the unacceptably high mortality rate among children on HD may be related to their ultrafiltration rates.

    Pediatr Nephrol. 2015 Jun;30(6):859-63. doi: 10.1007/s00467-015-3086-6. Epub 2015 Mar 24.
    The interdialytic weight gain: a simple marker of left ventricular hypertrophy in children on chronic haemodialysis.
    Fischbach M1, Zaloszyc A, Shroff R.
    Author information
    Abstract
    Despite multiple advances in haemodialysis (HD) technology over the years, the morbidity and mortality of HD patients remain unacceptably high. Cardiovascular disease is the most common cause of death, and left ventricular hypertrophy (LVH), seen in two-thirds of children on dialysis, is a significant contributor. The importance of volume control is increasingly recognized by nephrologists and now considered to be as important as urea kinetics, both in the day-to-day management and the long-term outcome of dialysis patients. The results published by Paglialonga et al. ( 10.1007/s00467-014-3005-2 ) in this issue of Pediatric Nephrology clearly demonstrate that there is a significant correlation between interdialytic weight gain (IDWG) and LVH in oligoanuric children on chronic HD and that children with an IDWG of >4 % are at high risk of LVH. One common practice to achieve euvolaemia is to prescribe very high ultrafiltration rates. However, both volume overload and aggressive fluid removal can induce circulatory stress and multi-organ injury. In adults, ultrafiltration rates of >1.24 % body weight per hour, even if well tolerated, are associated with a significant increase in mortality. Nephrologists should be aware of the risk of a high ultrafiltration rate, especially if tolerance is obtained by a positive dialysate-to-plasma sodium gradient. Haemodiafiltration, which allows for higher ultrafiltration rates with greater intradialytic haemodynamic stability, or more frequent and longer dialysis sessions allow for safe and effective fluid removal.

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  • Matthew Hegg

    Mar 5, 5:21 PM

    I don't think there is any secret that longer, gentler dialysis is preferred from a clinical standpoint; But I would caution using it as a description with "improving patient's quality of life". It may be better tolerated with less side effects, but being tied to a machine longer than they already are is not an improvment of life quality in my opinion.

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    • Dori Schatell

      Mar 5, 9:45 PM

      Cooler dialysate will protect the organs from stunning. But, it won't remove more water from inside or between the cells, and it won't remove more of the middle molecules that build up over time and cause bone, joint, and nerve damage. In the short term, how someone feels on dialysis is almost entirely about the rate and amount of water removal. But, in the long term, failing to remove those middle molecules can markedly reduce quality of life and mobility. The question is, how many hours of dialysis do you want to trade for cleaner cells and a body that looks, works, and feels better? IMHO, the best approach is to do HD at night while you sleep, disconnect in the morning, and go about your day. This minimizes illness intrusion into life--IF you can sleep through the treatments (not everyone can). This is why I was so happy that the FDA FINALLY approved a machine explicitly for nocturnal HD--with, hopefully, more to come...

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  • Mary Beth Callahan, ACSW/LCSW

    Mar 1, 3:19 PM

    This is a very important article. Thank you so much for sharing.

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  • Vukotic Snezana

    Feb 28, 10:22 AM

    Good article!
    I can say that I use cool dialysate (36 C), from 1993., when I started HDF and HF on-line at home.I am now 34 years on hemodialysis and all the time with very low blood pressure, but with low temp., with on-line therapy and profiling of UF, Na and HCO3 I am very well all this years !I hope that somebody will include in the study Hf on-line treatment !!!! I run it from 1993. and it is the best !!!!!
    Thank you!

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    • pat

      Sep 7, 9:08 AM

      what is hf on line treatment??

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    • John Agar

      Feb 28, 11:29 PM

      You are absolutely right ... but as this site is predominantly US-oriented, and the US has yet to 'meet' HDF - it is almost exclusively an EU and ANZ modality, many will not know what HDF is and why it is different (and better) than HD ... at least that is what most of the trials would say.
      In my own unit, we have now fully converted all facility-based patients (and I know I shouldn't call them patients, but 'users') to HDF now. The only 'users' still on HD are our home HD group. That is a hurdle yet to be crossed. Indeed, I gave a talk at the recent ADC in New Orleans titled "HDF trumps HD" ... it was about how and why HDF is an improvement on HD.
      Dori ... I feel a blog on HDF coming on ... but, as it is not currently offered - except in tiny niche regions or units - in the US, one might argue that there is not yet a great deal of point and it may just confuse. I will take your advice ....

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  • Dori

    Feb 26, 6:36 PM

    Thanks, John! Normally I would ask you to read this before I posted it, but I didn't want to disturb your holiday. This topic is literally LIFE-AND-DEATH important. However much we want as many folks as possible to dialyze in the comforts of their homes, some can't or won't, and they need help. They need POLICIES that will protect them from overenthusiastic ultrafiltration--and too-warm dialysate.

    Of COURSE you use cooler dialysate fluid in Australia. I wonder if DOPPS has looked at differences in dialysate temps around the world? I'll have to ask...

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    • Dr. Steve Surrey

      Feb 27, 6:49 AM

      Excellent article .
      For the record , I already have been dialyzing at cooler temperatures at home after reading an article last year pertaining to the effects of warm dialysate on the brain. My dialysate temp. today when I checked was at 95 F .
      I follow Dr. Agars UF numbers and only remove 5ml /kg / hour . Very safe and gentle.
      Thank you .

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      • Dori

        Mar 1, 3:50 PM

        95 degrees Farenheit is pretty much right on the money as far as what Dr. McIntyre recommended. How cold does that make you feel during treatment? Is it tolerable? (I also noted that Joel Glickman wrote a very similar article. I bet he saw this keynote address, too! Good! Hopefully these messages will spread! http://www.medscape.com/viewarticle/762480#vp_1).

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    • John Agar

      Feb 26, 6:56 PM

      Hopefully ... but I wont hold my breath ... my suggested UFRmax KPI, if used co-incident with Kt/V urea, will help provide that protection by adding a volume-based target to what is currently only a solute-based one - and, even then, the solute one (Kt/Vurea) uses the wrong solute.

      But, I am sadly pessimistic that any will heed the message or consider ways to implement it.

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  • John Agar

    Feb 26, 4:45 PM

    Well written, Dori.
    Well written, well précised, and faithfully well-represented as a synopsis of Chris McIntyre's address at the ADC.
    As you will know, I have a paper coming out in Hemodialysis International (it has been accepted and is in press) around this very topic - one inspired and underpinned by Chris's work.
    In it, I call for a second (and more far more telling) 'Key Performance Indicator' - or KPI - in dialysis to work alongside my béte noir (Kt/Vurea) ... I call it UFRmax (or a maximum rate of fluid removal, set at 10ml/kg body weight/hour ... to limit the rate of intravascular fluid contraction during dialysis to a rate below that which Chris's work has shown to carry rising cardiovascular risk and myocardial damage.
    Incidentally, our facility-based dialysate temperature here has long been set at 35.5 for sessional runs of a mean 4.35 hours. Till recently, it had not really occurred to me that US dialysate temperatures were otherwise. However, we run our home patients at the higher temperature of 36.5, due to their longer (8 hour) and more frequent (4-5 night/week) sleep-phase schedules.
    So ... perhaps our patients have long gained a dual advantage: cooler dialysate and gentler, longer, and less circulatory-insulting therapy.
    Well, done Dori. Thank you, Chris. You are dual beacons for commonsense dialysis.

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