Radiocontrast Nephrotoxicity: A Myth?!

Written by Meguid El Nahas on Friday, 07 October 2016. Posted in OLA Blog

Radiocontrast Nephrotoxicity: A Myth?!
J Am Soc Nephrol. 2016 Sep 29. pii: ASN.2016010021. [Epub ahead of print]

Estimating the Risk of Radiocontrast-Associated Nephropathy.

Abstract

Estimates of the incidence of radiocontrast-associated nephropathy vary widely and suffer from misclassification of the cause of AKI and confounding. Using the Nationwide Inpatient Sample, we created multiple estimates of the risk of radiocontrast-associated nephropathy among adult patients hospitalized in the United States in 2009. First, we stratified patients according to the presence or absence of 12 relatively common diagnoses associated with AKI and evaluated the rate of AKI between strata. Next, we created a logistic regression model, controlling for comorbidity and acuity of illness, to estimate the risk of AKI associated with radiocontrast administration within each stratum. Finally, we performed an analysis stratified by the degree of preexisting comorbidity. In general, patients who received radiocontrast did not develop AKI at a clinically significant higher rate. Adjusted only for the complex survey design, patients to whom radiocontrast was and was not administered developed AKI at rates of 5.5% and 5.6%, respectively. After controlling for comorbidity and acuity of illness, radiocontrast administration associated with an odds ratio for AKI of 0.93 (95% confidence interval, 0.88 to 0.97). In conclusion, the risk of radiocontrast-associated nephropathy may be overstated in the literature and overestimated by clinicians. More accurate AKI risk estimates may improve clinical decision-making when attempting to balance the potential benefits of radiocontrast-enhanced imaging and the risk of AKI.

Copyright © 2016 by the American Society of Nephrology.

Commentary

Excellent analysis of the incidence of radiocontrast associated nephropathy (RCN). To start with it is NOT a "Nephropathy" instead most often a transient rise in serum creatinine that is transient and by definition reversible...so to call it a nephropathy is a misnomer as serum creatinine values rise transiently after a number of interventions including a cooked meat meal, ingestion of an H2blocker or some antibiotics...these dont become Meat Associated Nephropathy, or Cimetidine Associated Nephropathy etc...although some have attributed a "Nephropathy" to Warfarin....that is as ill conceived !

Back to the RCN, the strength of the current analysis is the adjustment for comorbidities, and the actual impact of comorbidities themselves on changes in serum creatinine rather than the associated interventions; radiocontrast administration in this publication or warfarin overanticoagulation (INR >3) elsewhere.

Secondly, the definitions of these entities often depend on variable cut off points for changes in the measured parameter, serum creatinine, that defines the "Nephropathy"...mostly arbitrarily chosen with no consideration for clinical severity, reversibility or enhanced morbidity/mortality, and/or the underlying CKD stage.

Finally, RCN has been a fertile ground for research and interventions. Mechanistic research that led to a number of interventions, most of which have shown little advantage over a bag of normal (or half normal) saline before and after the administration of RC material... 

Nephrology has to guard itself from embarking on research for the sake of research, rather than prioritise research that has clinical relevance, clinical impact and ultimately research that benefit patients...

If we ask of RCN whether it fulfils the 5 WHATs, it is unlikely to meet any of the 5 Whats criteriae:

1. What is the clinical relevance of RCN: Negligible!

2. What is the validity of the data supporting this entity: As shown by the publication under discussion, Minimal!

3. What is the Usefulness/Utility of identifying RCN: Optimise Hydration

4. Risk versus Benefit of RCN: too much emphasis, too much research, too much investments for little return: a bag of Saline would do...

5. Cost benefit analysis: same as 4!

So can we conclude from this publication and my commentary that RCN is an irrelevance?

Perhaps not, except that more attention needs to be paid to radiological investigations, specially those that are aggressive and invasive, in patients with significant comorbidities as these are at higher risk of acute on chronic kidney disease...regardless of the coadministration of potentially nephrotoxic agents!

 

 

 
Meguid El Nahas

Professor Meguid El Nahas PhD, FRCP

Chief Editor, OLA Director

Professor El Nahas was born in Cairo, Egypt and undertook his undergraduate medical education in...
Posted: 7 months 2 weeks ago by tukaram #21056
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People at bedside were always aware of this. With AKI case load of >100 per month (underlying CKD excluded), I am still to find a case of significant AKI or AKI requiring dialysis that can be solely attributed to intravenous contrast.
Research for the sake of research!
Posted: 7 months 2 weeks ago by saja71 #21057
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i agree about the overestimation of CIN BUT still in real practice we can see very few cases of AKI requiring dialysis especially on background of CKD and the frequent exposure to contrast
Posted: 7 months 2 weeks ago by upalinpgi #21058
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The issue is not giving RC in any population.The clinical relevance comes to a case which is already stage 3 or 4 CKD. Where there is a serious risk of initiation of dialytic modalities with actually very little deterioration of renal function with radiocontrast or per se any other renal insult.
We need to use an uniform score stating the probable risk which will probably dissect the myth of RCN under more scientific probabilistic light.
Posted: 7 months 2 weeks ago by elnahas #21059
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Medical practice is all about RISK v BENEFIT analysis and asking oneself:

HOW WILL THIS INVESTIGATION BENEFIT or HARM THE PATIENT?

So this also applies to RCM administration!

Most often investigations are done to satisfy the doctor's curiosity or fill gaps in his ignorance...at the expense of patients' risk exposure.

And this applies to RCM administration; for example, needless coronary CT angiograms requested by cardiologists for asymptomatic and older individuals with unrelated symptoms...needless angiographies in elder T2DM patients who undoubtedly have severe atherosclerotic vascular disease...Pulmonary CT angiogram in people with good oxygen saturation and no tangible signs suggestive of pulmonary embolism...not to mention renal vascular imaging, when reparative interventions for atherosclerotic renal artery disease (ARAD) is futile...these are common examples I have encountered over the years in susceptible older individuals often receiving inappropriately high doses of RCM, with inadequate prophylactic hydration!

Once more, MEDICINE IS NOT BLACK or WHITE....NEPHROTOXIC or SAFE....it is SHADES OF GREY...where the doctor has to navigate and practice, to the best interest of the patient he cares for.

BEING WELL INFORMED GOES A LONG WAY IN PROVIDING OPTIMAL CARE.

Following Myths and Dogmas can do harm!
Posted: 7 months 2 weeks ago by arif.khwaja #21060
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The risk of clinically significant contrast nephropathy is negligible in CKD3/4 and non dialysis CKD 5 as long as you take appropriate step of hydration etc as highlighted by this very large series of coronary angiograms done for transplant work up on CKD 4/5 patients
www.ncbi.nlm.nih.gov/pmc/articles/PMC3359544/
Posted: 7 months 2 weeks ago by tukaram #21061
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Even if it exists, it's likely to be a very small risk that can be purely attributed to contrast. Not only medical, this has other far reaching implications. KDIGO devotes full guideline chapters (1/5 th of the all recommendations)on CIN, without even mentioning other important and specific AKI settings like post cardiac surgery, obstetric AKI, tropical infection related AKI etc-each has unique management issues. Many fellows have spent (of course under guidance of their uncritical mentors) there years in replicating various protocols of CIN prevention, diagnosis, etc.
Posted: 7 months 2 weeks ago by elnahas #21063
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Of note, to induce experimental RCM Nephrotoxicity in rodents (rats), they often require:
Multiple simultaneous Insults:

Uninephrectomy (CKD),
coadministration of diuretics (dehydration)
coadministration of NSAIDs (additional nephrotoxins)

Radiocontrast material alone doesnt cause renal impairment in experimental animals!

I wonder if this may also be the case in humans:

Older age +
CKD
Renal Ischemia; Atherosclerotic vascular disease
Dehydration or inadequate hydration
Intake of NSAIDs; often undeclared!
or
ACE Inhibitors?!
etc...

This may explain discrepancies in reporting of incidence of CIN/renal impairment and highlights the importance of comorbidities and associated renal insults in the expression of RCM induced renal damage!?
Posted: 7 months 6 days ago by abutalebN #21081
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Thank you El Nahas and all colleagues.. Helpful study and discussions that further lower the threshold for carrying necessary (when truly indicated and with potential Rx) investigations in our sick /advanced CKD patients..

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