Two more NephTalk Podcasts

I was given the opportunity to work with Satellite Healthcare on their NephTalk podcast and hosted three episodes. The first one, on infection in dialysis units, was posted via RSS and picked up by iTunes. But the next two episodes I hosted were not posted to the RSS feed and so won’t show up in your podcast player of choice (by which I mean Overcast).

So you you’ll have to listen to them like your grand father did, as he walked to school bare foot, through the snow, uphill, both ways, via a web player. Sorry.

Joel Topf, M.D. interviews Steven D. Weisbord, M.D., lead researcher on a study recently published in the New England Journal of Medicine.

Joel Topf, M.D. interviews Linda F. Fried, M.D., lead researcher on a study recently completed for the U.S. Department of Veterans Affairs.

How I used my newly acquired PubMed skills

Yesterday I gave one of my favorite lectures, Renal Adventures in Imaging.

After I finished the lecture I spent some minutes playing with my new skills on PubMed and found this article: N-acetylcysteine effect on serum creatinine and cystatin C levels in CKD patients that completely goes against one of the figures and points of my newly scribed chapter:

[The inability of acetylcysteine to prevent dialysis or mortality] maybe because acetylcysteine alters creatinine handling in the proximal tubule. Acetylcysteine, actually accelerates the excretion of creatinine resulting in decreased serum creatinine.

After Tepel published his original work on acetylcysteine in 2000 everyone went a little crazy drinking the Mucomyst cool-aid. Here was a cheap, safe and already approved, remedy to the pervasive problem of contrast nephropathy. Everyone was so drunk with the excitement that they didn’t note that the 85% reduction in contrast nephropathy was not associated with a reduction in the need for acute dialysis or a reduction in patient morbidity and mortality.

In 2004, Hoffmann Et al. published the above quoted article which showed a modest but significant reduction in serum creatinine following ingestion of acetylcysteine. This seemed to me to be the best explanation for why a therapy could prevent an increase in creatinine but not prevent dialysis. (Data on the lack of prevention of dialysis from Miner et al. Am Heart J 2004.)

Apparently the patron saint of contrast nephropathy, Richard Solomon, recently reevaluated this theory and found it lacking. He took 30 patients with GFR < 60 mL/min and given 1,200 mg of acetylcysteine every 12 hours for four doses. Creatinine and cystatin C were measured at baseline, 4 and 48 hours after the last dose of acetylcysteine. They found:

Serum creatinine and cystatin C levels did not change significantly at either 4 h or 48 h following the last dose of NAC compared with the baseline values (Table 2; Figures 1 and 2). However, a small but statistically significant reduction in the ratio of serum creatinine to cystatin C was observed at 4 h but not 48 h.

click to enlarge
Solomon postulates that in patients with chronic kidney disease (a population that better represents the people who actually are given contrast nephropathy prophylaxis) the proximal tubule secretion of creatinine may already be maximized so that it cannot be further upregulated by acetylcysteine.
The end result is that changes in creatinine found during acetylcysteine administration likely represent changes in GFR and are not merely artifactual.

Noon conference St John Macomb: Renal Adventures in Imaging

Yesterday I gave one of my favorite lectures, Renal Adventures in Imaging.
It is a lecture on three issues in nephrology that are not normally put together in a single lecture:
  1. Phosphate nephropathy
  2. Nephrogenic fibrosing dermopathy (I’ll never get used to calling it nephrogenic systemic fibrosis because, despite what the literature states, all five patients I have seen had purely dermatologic manifestations)
  3. Contrast nephropathy
I like the lecture because it is not a typical nephrology lecture. 
I gave the lecture Seder-style and had crammed for the last three days getting the booklet ready. It’s the longest booklet by one sheet (32 pages rather than my standard 28). It turned out pretty good, though the acetylcysteine section needs to be built up and I need to comb through it for typos.

The highest urine specific gravity I have ever seen

1.050 is really high. Even the healthiest kidneys can’t concentrate urine past a specific gravity of 1.030. To get this high the urine must contain another substance.

In this patient’s case she had just undergone a heart catheterization. IV contrast is rapidly cleared by the kidney and increased the density of the sample. Proteinuria and glucosuria are other conditions which can cause an abnormally high urine specific gravity.


ACEi, ARBs and Aldo Antagonists and the risk of Contrast Nephropathy

This is a question that comes up during almost every consult in patients with CKD about to receive contrast exposure. Should we stop ACEi and ARBs prior to exposure?

The data is confusing as summarized in the introduction to this latest analysis:

…Some studies have demonstrated that chronic medication with angiotensin-converting enzyme inhibitors (ACE-I) or AT-1 blockers was a risk factor for CIN [19,20], whereas other studies [21,22] found a protective effect in patients with CKD when exposed to CM.

If that doesn’t meet the definition of equipoise, I don’t know what does.

There still isn’t any prospective data but a recent reanalysis of a large (negative) trial on the use of hemodialysis to prevent contrast nephropathy attempts to answer the question.

When the baseline characteristics are separated by the presence of contrast nephropathy it reads like a rogues gallery of risk factors of contrast:

All of the following were significantly more frequent (or more extreme, i.e. greater age, higher Cr, more contrast, lower eGFR) in patients who developed contrast induced nephropathy:

  • Age
  • Diabetes
  • Insulin dependent
  • Creatinine
  • eGFR
  • Hemoglobin (that’s new)
  • RAAS blockade (ACEi, ARB, and aldo antagonist)
  • Loop diuretic
  • Contrast dose

The multivariate analysis showed RAAS blockade and hemoglobin to be independent predictors of contrast induced nephropathy:

The data is sure suggestive of an effect but given that both CKD and CHF are risk factors for contrast nephropathy and RAAS blockade is a first line therapy for both diseases I fear we could be looking at a classic bias by indication.
This is a question that is begging for an interventional trial. I’d let my patients be randomized to d/c ACEi/ARB versus no discontinuation. It sure would be better than another damn study on loop diuretics, mannitol and IV fluids 2009 (Hey AJKD! 1994 is on the phone and they say they’d like their study back).

Contrast and residual renal function

In a previous entry I reviewed the iPhone app PubMedOnTap. I used this application to find articles regarding the question of whether iodinated radiocontrast media harms residual renal function for patients on dialysis. I came up with two “hits.”

The Palevski study is a retrospective analysis of PD patients with residual renal function who underwent coronary angiograms. They compared residual renal function after the angiogram to previous residual renal function. They also looked at mortality, change of modality and peritonitis. They created a control group composed of patients matched for time of initiation of PD, age, and diabetic status.

29 patients met the enrollment criteria. Residual renal function was assessed an average of 14.7 weeks following the procedure. 1 patient became permanently anuric following the angiogram.

The average loss of renal function for the cases was 0.09 ml/min/month versus 0.07 ml/min/month for the controls (p=0.53). Average decline in residual renal function for PD patients is said to be 0.1 mL/min/month.

5 patients had no residual renal function measured after the angiogram and a medical record review could not document why this happened. They were censored from the final analysis.

The Janousek study is a more rigorous design, as it is controlled. They did a matched cohort study of hemodialysis patients who underwent a endovascular procedures and matched them to similar patients who did not receive contrast.

All the participants had to have at least 500 mL of urine production per day.

The contrast patients received an average of 99 mL of iodixanol (isoosmolar contrast, Visipaque) with a range of 60-180 mL.

The authors specifically state that

Our aim was not to evaluate the immediate effect of contrast medium on residual renal function during the several days after application. Rather, we wanted to evaluate its long-term clinical effect. This is why we compared the volume of daily diuresis and RREC 3 months before and 3 months after ICA administration.

They found no difference in the rate of loss of residual renal function whether they measured it by urine volume (p=0.855) or creatinine clearance (p=0.573).

From the change in urine volume (the top chart), the value of a placebo group becomes clear. The contrast group does lose urine volume, but they lose it at roughly the same rate as the control group.
One of my concerns about the study is that since it was retrospective they purposefully restricted their analysis to patients who survived for the entire 6 month follow up period. From the Materials and Methods section:

Only clinically stable patients with no serious concomitant disease and who survived for a 6- month follow-up period with an unchanged dialysis strategy were evaluated.

So if contrast caused pre-mature death in dialysis patients, subjects having that outcome would not have been studied.

In the discussion the authors mention three other articles on the same subject:

They found two in NDT in addition to the pavlesky article. None showed a deleterious long term effect of contrast.

  • The first was a prospective trial by Dittrich el at. of 10 peritoneal dialysis patients with 8 patients as controls. They found a temporary drop in residual renal function that was erased after 30 days.

  • The second was a prospective cohort trial by Morrane et al. of 72 peritoneal dialysis patients, half of which were exposed to contrast. After two weeks there was no difference between the two groups or from baseline figures in regards to CrCl, urine volume or residual renal function.

Patient information: Contrast nephropathy

I am writing some patient information articles to go on our SCSP’s website,

I am including them here as I fine tune them. I have been in contact with Dr. Shah, a nephrologist who has produced some gorgeous patient information booklets that we will be posting online also.

I have heard that getting a dye for a cardiac catheterization or CAT scan can damage my kidneys. Is that true?

Yes. X-ray dye is usually made with iodine and is sometimes called iodinated contrast. The dye allows doctors to see the blood vessels and used when using x-rays to diagnose a number of medical problems. The dye that can damage the kidneys is always given intravenously. Another type of dye is given as a oral liquid. This oral contrast is not harmful to the kidneys.

If you have healthy kidneys the IV dye is almost never harmful; however if you have weak kidneys (chronic kidney disease stage 3, 4 or 5) and especially if you also have diabetes or are also over the age of 65 you are at risk of kidney damage from the contrast.

The kidney damage is called radiocontrast nephropathy. The damage is usually temporary (7-10 days) but sometimes it can cause permanent renal failure requiring dialysis.

There are ways to reduce the risk of developing radiocontrast nephropathy, though even in expert haqnds the risk cannot be eliminated. Protective strategies include:
1. Stopping diuretics
2. Hydrating the patient with saline solution
3. Taking an anti-oxidant called N-acetyl cysteine
4. Reducing the dose of contrast
5. Using a contrast agent with less toxicity

It is important, that if you are at risk of radiocontrast nephropathy and are going to get IV contrast that you notify your nephrologist beforehand so she can coordinate the protective strategy to spare your kidneys.

Renal Adventures in Imaging

One of my favorite lectures. I’m supposed to give an hour lecture on contrast nephropathy but I find that the residents have excellent knowledge and instincts on this topic so I expand it in two other areas they are less well versed:

  1. Oral sodium phosphorous and nephrocalcinosis
  2. Nephrogenic fibrosing dermopathy

iPhone version
Booklet for printing

Journal Club: Bicarb for contrast nephropathy and calcitriol for CKD 3 and 4

The first article was a retrospective study on the use of calcitriol in patients with CKD stage 3 and 4. The outcome was mortality and mortality plus dialysis. The authors were able to demonstrate a significant reduction in both outcomes with the use of calcitriol. Some interesting points were the lack of a dose effect and the effect was independent of PTH. The authors suggest that the benefit of activated vitamin D therapy is not due to its affect on PTH.

Association of oral calcitriol with improved survival.

The second article was the latest study on contrast nephropathy.

Sodium bicarbonate vs sodium chloride.

This well done randomized, single-blinded, controlled trial showed no difference between isotonic NaCl and nearly isotonic bicarbonate.