Month: December 2009

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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).
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Plavix drug interaction

I know I’m a little late on this, but here is a sign we are using in our offices to alert patients to the problem with clopidogrel and omeprazole. Thought it might be useful for others.

Plavix Warning value=”http://d1.scribdassets.com/ScribdViewer.swf?document_id=24374327&access_key=key-2mnvhafk7m2nr8eu2ek9&page=1&version=1&viewMode=list”>            

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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.

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How to make a cool clinic diagnosis

I had a great case yesterday in clinic.

The patient was a 55 year old woman with HIV and a chief complaint of gradually climbing creatinine. Among her medications were Truvada and Norvir.

Truvada is one of three brand name drugs that contains tenofovir:

  1. Viread: tenofovir
  2. Truvada: emtricitabine-tenofovir
  3. Atripla: efavirenz-emtricitabine-tenofovir
Tenofovir rarely causes renal failure through proximal tubule toxicity. One of its hallmarks is a Fanconi syndrome, though the renal failure can occur without Fanconi’s. Fanconi’ syndrome is generalized dysfunction of the proximal tubule, so metabolites normally reabsorbed in the proximal tubule are wasted in the urine. Patients have amino aciduria, bicarbonaturia (RTA type II), inappropriate phosphaturia and glucosuria. Because of the increased phosphaturia, hypophosphatemia is a surprisingly sensitive indicator of tenofovir toxicity (20/20 cases).
This patient’s creatinine rose from 1.4 in March of ’09 to 1.7 in November. The primary care doctor that handles this patient’s HIV had checked an ultrasound (9 and 10 cm kidneys), and albuminuria (400 mcg/min).
Here are the results of his U/A we did in the clinic:
I focused on the glucosuria and concluded that if her blood sugars are normal then she must have proximal tubular dysfunction and likely tenofovir toxicity.
Her blood sugar was 87. The Tm for glucose is roughly 200, so a serum glucose of 87 should not cause any glucosuria.
The Truvada was stopped. The patient is also on ritonovir (Norvir). Ritonovir is found in 72% of patients with tonofovir induced Fanconi’s syndrome, so it maybe an important co-factor in the development of this condition. We did not stop the Norvir, should we?

 I will follow up with the patient in the month. Hopefully she will do well.

Here is a talk I gave on HIV and the Kidney:
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Great web service for making booklets

My favorite way to lecture is to pass out a personally written chapter on the subject and then collectively read the hand-out. I call this lecturing “Seder-style” named after the ritualistic dinner of the Jewish holiday Passover.

The booklets have four pages on each sheet of paper but you need a computer program to reorder the sheets so the booklets come out right. I used to have a print service that did this for me but it stopped working when I upgraded to Snow Leopard. I found this web service BookletCreator which does a great job with this.

Here are the original PDFs I uploaded:

Here are the bookletized PDF the website created:

Perfect.

UPDATE: No longer free.

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PubMed on Tap for the iPhone: the NLM in your pocket

Last week at the end of a morning conferance there was an impromptu discussion of the problem of residents ordering IV contrast for patients with acute kidney injury. The residents see a patient on dialysis and feel that its open season for contrast.

As part of the discussion one of the attendings mentioned this is also a problem with his PD patients with residual renal function and the residents need to know that contrast should be avoided in these patients to preserve residual renal function. I mentioned that actually the data doesn’t support the common sense notion that contrast accelerates the loss of residual renal function. Immediately all eyes were on me and the consensus was that no one else had seen that data and that I was way off the reservation. Pretty uncomfortable place to be.

I had buttoned holed Paul Palevsky at the 2006 ASN Renal Week after a talk on contrast nephropathy and in that hallway conversation he had mentioned that he had just finished research on this vary question. he only reason I remember it was that the results were so counter intuitive. Contrast has no measurable affect on residual renal function. I had actually never seen the article but now I had put up or shut up.

After the conference I had to run to an outside hospital but I stopped at a Tim Hortons (the best thing to come out of Canada since Douglas Coupland) and fired up PubMed on Tap (PMT).

PMT is an app dedicated to adapting the PubMed database to the constraints of a mobile platform. I used an app by the same name on my old Treo. Adding Palevsky as author, and then contrast and residual renal function as text words.

Bingo! One article:

You can pull up the abstract:
The PDF:
 :
and the PubMed listing:

I then did a less specific search by dropping the author name and found a higher quality study:

I was able to send the references to my colleagues right from the application. Sweet.

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What are the top nephrology stories of the last decade?

As we come to the end of the naughts, we naturally reflect back and think about how far we have come from in the last ten years. Here is my quick list:

  1. MYH9 gene for ESRD
  2. The failure of the normalization of hemoglobin and the wholesale reevaluation of ESAs
  3. The rise of aldosterone and its importance in hypertension and renal disease
  4. the failure of dialysis dose to improve out come in both chronic (HEMO) and acute dialysis (ATN).
  5. FGF-23, hey a whole new hormone and a major advancement in renal physiology
  6. Re-emergence of home dialysis
  7. Problems with the definition of CKD and the problems with eGFR
  8. discovering the antigen in idiopathic membranous nephropathy
I want to do a longer article about this but I’m sure I’m missing some stuff. I don’t have a transplant subject, seems like vitamin D belongs up there, what about the phos binder wars? Bundling? What about MMF in lupus nephritis and every other GN?
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week-end call and a pair of crazy numbers: Glucose and Calcium

Glucose
I saw the highest glucose I can remember in a patient without ESRD. I have seen the glucose go over 2,700 in a patient with the misfurtune to have both DKA and anuric ESRD. Without the osmotic diuresis to lower the glucose the glucose can shoot the moon. This patient had HyperOsmolar Non-Ketotic Coma (or HONK as my fellow calls it, love that) and baseline Cr of 0.83 and a peak glucose of 1,600 mg/dL.
I love the twin graphs showing the falling glucose and the simultaneous resolution of the pseudohyponatremia. The patient had enough pre-existing osmotic diuresis to cause hypernatremia which was masked by the hyperglycemia. As the glucose comes down the sodium goes up from 136 to 162.

Calcium
The other crazy number was the most severe hypercalcemia I have ever seen. The calcium was 18 mg/dL with an albumin of 3.7 g/dL. The patient is a kidney transplant recipient who was recently seen in the outpatient clinic with hypocalcemia. His calcium was 6.5 and his calcitriol was increased from 0.5 mcg to 1 mcg twice daily. He was also continued on his calcium carbonate.

Admission labs:

The other pertinent calcium labs:

  • PTH: 3.2 pg/mL
  • Vit D 1,25 dihydroxy: 36 pg/mL
  • SPEP/UPEP: unremarkable
  • PTHrp: pending
I think this is milk-alkali syndrome from the calcium carbonate exacerbated by the calcitriol. One supporting string of evidence supporting this is the fact that his calcium came down and has not reoccurred. If it was hypercalcemia of malignancy I would have expected his calcium to be resistant to conservative therapy.