Tag: heart failure

Posted on

More OUWB M2 questions and Answers

The question: I am going through the real well made sodium and water guide you made and there is a concept I am having trouble with regarding ADH stimulation by decreased BP. In the text, one of the reasons that ADH release is triggered is:

Decrease in blood pressure: ADH is a potent vasoconstrictor. 10% drops in blood pressure are required to release ADH. This drop in pressure is usually due to a drop in the blood volume from volume loss but can also be due to heart failure or cirrhosis. ADH is relatively insensitive to changes in pressure, this is why it takes a full 10% drop in pressure to start to stimulate ADH.

I thought blood pressure goes up with heart failure as hypertension is a risk factor for heart failure. How do we get decreased blood pressure from heart failure? 

The Answer: Hypertension can cause heart failure. Hypertension is a risk factor for hypertension. Heart failure can present with hypotension or hypertension. Regardless of the blood pressure, heart failure can cause poor perfusion, and stimulate ADH release, with or without a low blood pressure. Sometimes the heart pumps so poorly that blood backs up in the venous circulation, this venous congestion slows perfusion since the back pressure blocks flow, even though blood pressure it good.

So the important point is that heart failure, cirrhosis and volume depletion all stimulate ADH release through decreased perfusion/blood pressure predisposing to hyponatremia.

Posted on

The failure of creatinine as a marker of AKI

  • If you went to a national nephrology meeting in the 2000’s and walked into a lecture on clinical AKI there were two obligatory sections that would be part of the talk.
    1. The first would be how poor creatinine was as a marker for AKI. The expert at the front of the room would explain that creatinine was a lagging indicator and that by the time the creatinine had begun to climb the injury was yesterday’s news. Identifying AKI by a bump in the creatinine would force you to always be reactive rather than proactive. This discussion would then lead to a plea for better markers of AKI, followed by descriptions of NGAL, KIM-1, and other promising AKI assays of the future.The second would be a complaint about the lack of a consensus definition of AKI. The speaker would point to 35 different definitions of AKI in the literature, from highly sensitive (25% bumps in serum creatinine) to perfectly specific (need for acute dialysis during the hospitalization).
Oh 2002, how I miss you… (https://www.ncbi.nlm.nih.gov/pubmed/12454534)

Depending on the exact year of the talk, they would then talk about the RIFLE criteria, or to the AKIN modifications to the RIFLE criteria, or to KDIGO’s modifications to AKIN. The speaker would always point to a future where we had a consensus definition of acute kidney injury so that we could start to move forward with a cohesive literature where one paper could be compared to another. What was always odd about these talks was that the second part of the lecture, about the emerging creatinine-based consensus definitions of AKI must have been browsing Facebook during the earlier part of the lecture about the futility of creatinine-based definitions of AKI.

But the consensus did emerge. Despite all the experts warning us about the problems with small changes in creatinine defining AKI, that is the world we live in. One problem with this definition recently emerged in a discussion of cardiorenal syndrome. This article by Testani et al found that:

The group experiencing hemoconcentration received higher doses of loop diuretics, lost more weight/fluid, and had greater reductions in filling pressures (p<0.05 for all). Hemoconcentration was strongly associated with WRF (OR=5.3, p<0.001) whereas change in right atrial pressure (p=0.36) and change in pulmonary capillary wedge pressure (p=0.53) were not. Patients with hemoconcentration had significantly lower 180 day mortality (HR=0.31, p=0.013). This relationship persisted after adjustment for baseline

We should not have a situation where increased risk of AKI (yes, I know the definition of worsening renal function, WRF, does not perfectly overlap with Stage 1 AKI, but work with me) is also associated with improved 180 day mortality. By defining AKI around changes in AKI we have deputized nephrologists to be the creatinine police and make decisions on treating patients based on what effect it has on short-term changes in GFR which may or may not have anything to do with long-term outcomes. In the above study, using serum creatinine to guide therapy leads to insufficient diuresis, poor fluid removal, and poor 180 day outcomes.

The Twitter discussion about this was particularly enlightening. Take a look.

Posted on

Great article on the Nesiritide debacle

There has been some great articles regarding the expensive, waste of a decade induced by nesiritide.

I like this article the most because it’s written by someone who is not in medicine. It tackles many of the same issues I looked at in my post, The problems with numbers, namely when drugs are approved based on intermediate end-points bad things can happen.

The best thing we can say about niseritide is that when the definitive trial was finally done, the previous concerns about renal failure, were shown to be merely illusions created by the smoke and mirrors of meta-analysis.

Acute renal failure was an early concern regarding Nesiritide…

…but when the right placebo controlled trial was done, no renal failure.
So go and read Carolyn Thomas’ view of nesiritide and see how we have failed the people we are entrusted to care for.
Posted on

Cardiorenal syndrome

On the first Friday of every month I give a lecture to the residents at St. John Hospital and Medical Center. I like to do an electrolyte lecture but for March the chief resident asked me to talk about cardiorenal syndrome. In researching the lecture I came across this article by Claudio Ronco.

The article defines cardiorenal syndrome as any condition with simultaneous kidney and heart failure. He then goes on to subdivide cardiorenal syndrome into 5 types:

  1. Acute heart failure causing acute renal failure
  2. Chronic heart failure causing chronic kidney disease
  3. Acute kidney injury causing any type of acute cardiac dysfunction (including arrhythmia)
  4. Chronic kidney disease causing any chronic cardiac disease
  5. Any systemic condition that causes renal and cardiac dysfuction (e.g. sepsis)

This is terrible. Cardiorenal syndrome used to signify the unique cause of acute kidney injury where the decrease in function is due to apparent volume depletion in a patient that obviously overloaded. It named the only scenario where acute kidney injury responded to diuresis. It was unique and specific. Ronco comes along and says, yes I like your version of cardiorenal syndrome so I will make it type 1 in my new all purpose definition of cardiorenal syndrome. Now whenever there is cardiac dysfunction and simultaneous kidney dysfunction we can just call it cardiorenal syndrome.

It doesn’t have to be this way look at the example of hepatorenal syndrome. The syndrome does not refere to just any situation with simultaneous renal and liver dysfunction. It is a very specific diagnosis that only occurs with chronic liver disease and ascites. The patients must be oliguric, there is no non-oliguric HRS. Patients must be sodium avid and unresponsive to fluids and albumin. Additionally the patients cannot have laboratory or imaging evidence for an alternative cause of renal failure. Because of this definition hepatorenal syndrome identifies a very specific disorder, with a specific pathophysiology and unique prognosis and treatment options.

Ronco takes the beautiful and evocative name cardiorenal syndrome, strips it of all specificity and then tries to restore it by tacking on five different types. The fifth type 5 is the one that makes my brain explode. Sepsis, really? Acute kidney injury from sepsis that happens in the same patient who also suffers from sepsis induced cardiomyopathy should now be considered to have cardiorenal syndrome? Ronco is a man who has spent his life studying sepsis and acute renal failure, I can’t believe he is actually referring to that condition as CRS type 5.

I’m not buying what Ronco’s selling. Cardiorenal syndrome begins and ends with type 1 for me.

FYI: Here is the lecture (Keynote, PDF). It still needs some work. I’d like to add a section on ultrafiltration and I need to include the NEJM article on furosemide that was published yesterday.

Posted on

Journal Club: Aspirin and FGF-23

The first article was an intriguing look at various renal function parameters and how they respond to various doses of aspirin. All the patients were pre-treated with enalepril and a thiazide diuretic for 6 days. Then they were given one of four doses of aspirin:

  1. placebo
  2. 80 mg
  3. 160 mg
  4. 320 mg

They found decreased GFR, decreased sodium clearance, decreased solute clearance and decreased free water clearance with 160 mg and 320 mg but the effect was transient with all factors returning to baseline 4 hours after the aspirin was administered.

The article has a long introduction and discussion outlining all of the heart failure studies which have shown that aspirin can be harmful or can decrease the effectiveness of ACEi in heart failure.

The study is small (n=16, with each participant randomized to two doses of aspirin with a 2 week washout between doses) and the authors fail to fully describe the cohort. The primary weakness is the authors want to extrapolate there findings over 6 hours to the effect of aspirin taken chronically for years. Additionally they make the leap of using aspirin-induced changes in renal function to be a proxy for interference with ACEi effect on heart failure survival.

Nonetheless it will change the way I practice. I had previously given my patients (who essentially all are on diuretics and ACEi) the green light to take aspirin any way they want. I will now suggest they limit themselves to 81 mg for CAD protection.

The second article was the NEJM article on FGF-23 and the risk of mortality in hemodialysis patients. FGF-23, or fibroblast growth factor-23, is a newly discovered molecule which regulates the phosphorous in the body. It is one of the primary phosphatonins, signals which increase the renal excretion of phosphorous. Additionally they suppress 1-alpha hydroxylase lowering the amount of 1,25 dihydroxy-vitamin D.

This is prospective cohort with nested case-control of incident dialysis patients in the U.S. The investigators looked at 200 patients who died (cases) in the first year and compared them to 200 patients who survived one year (control). FGF-23 was measured on the first day of dialysis. They divided the cohort into quartiles based on phosphorous and found that patients who subsequently died had increased FGF-23. They found a graded increase in the risk of death with increased FGF-23 level that was signifigant in the whole cohort and inevery quartile of phosphorous except the highest.They also showed a dose responce of mortality to FGF-23 levels in the whole cohort in the crude data, case-mix adjusted and multivariate adjusted.


The authors in the discussion point out that the association of FGF-23 with mortality is stronger than that found with phosphorous and mortality. They found FGF-23 levels were 22% lower in African-Americans than in Caucasians. The authors leave a tease that this lower level of FGF-23 level may explain the improved survival found in African Americans on dialysis.