Prevention of Contrast-induced Nephropathy

This has been asked about a few times:

The answer to these questions gradually  evolved into a massive table of comparisons, which is reproduced below without any modification.

For selected definitive resources among the (massive amount of) relevant published material, the time-poor reader is directed to the following references:

This question was written in 2009, which was a time when it seems contrast-induced nephropathy was a unquestioned fact. These days, things are less clear. Pulmcrit have an excellent review of this controversy. Their summary of the modern-day data can be summarised in one statement:

There is no evidence that contrast dye causes patient-centered outcomes such as death or dialysis. Many studies of contrast nephropathy may have been measuring random fluctuations in creatinine rather than genuine kidney injury.

Which renders the table below somewhat meaningless.

Nevertheless, there it is.

Protective Strategies against Contrast-Induced Nephropathy
Strategy Theoretical rationale Evidence
Identification of patients with non-modifiable risk factors

If these patients are identified early, perhaps for some a contrast-free imaging option could be appropriate

The risk of contrast induced nephropathy in the general population is about 0.6-2.3%; in the at-risk population it is as high as 20%.

Identification of patients with modifiable risk factors

If these patients are identified early, in a non-urgent situation some of the risk factors can be attended to prior to the imaging study.

Use of nonionic contrast media

High-osmolarity ionic contrast media are thought to be responsible for the tubule-damaging increase in tubular fluid viscosity

Some reviewers disagree- their data suggests that there does not seem to be very much difference in nephrotoxicity between modern contrast media of different osmolarities and ionicities. A 2014 meta-analysis found some differences in renal safety between different low-osmolar and iso-osmolar contrast media. High-osmolar contrast media are no longer used; their nephrotoxicity was indeed significant.

Use of a smaller volume of contrast media

The harm is thought to be dose-related

Use of automated injectors seems to deliver less contrast, and thus seems to be associated with less AKI.

N-acetylcysteine

Antioxidant effects of N-Ac (and its vasodilating tendency to regenerate nitric oxide) are thought to decrease the oxidative damage in the tubules and improve renal blood flow.

One meta-analysis had identified 22 trials of N-Ac in this setting, and complained that they are too heterogeneous and there is no way to generate a conclusion from them. Others however, performing similar searches have arrived at fewer trials, and have found some benefit.

Overall, there is no stong evidence to support the ongoing use of N-acetylcysteine. In fact some go as far as to say that ongoing use is"against principles of evidence-based clinical medicine".

Pre and post-hydration

This is a fairly benign therapy; the theoretical benefit depends on diluting the tubular fluid. and increasing the volume of distribution for the contrast agent, as well as increasing the rate of its clearance by the kidneys, and improving the renal blood flow by volume expansion.

Many trials (such as this recent one) have used saline as the control for comparison to an agent thought to be protective against CIN. The outcomes of such trials have thus far been largely negative, supporting the idea that crystalloid is at least as good as any other agent.

Knowing that dehydration is a risk factor for CIN, one is left to conclude that rehydration must be beneficial.

Interestingly, oral hydration may be at least as effective as IV hydration (though this is not a consistent finding).

The Australian College of Radiologists recommend an IV regimen of 1ml/kg/hr for a minimum of 6 hours.

Dopamine / fenoldopam

There is a theoretical benefit associated with increasing renal blood flow; and these agents theoretically increase renal blood flow. Ergo, they might be protective.

There is no good evidence to support the use of either dopamine or fenoldopam as protective agents for contrast-induced nephropathy.

Mannitol

Forced diuresis with mannitol was at one stage thought to improve the removal of toxic oxidants from the tubule by forcing large volumes of fluid through it.

RCTs have abundantly demonstrated that this strategy is without merit.

Frusemide

Similarly to mannitol, frusemide was though to protect the tubules both by forcing dilute fluid through them, and by decreasing their oxygen consumption (by inhibiting ATP-expensive ion pumps).

RCTs have shown that in this setting frusemide is either useless or actually harmful, and its use cannot be recommended.

Sodium bicarbonate

Apart from stimulating diuresis and natriuresis, sodium bicarbonate is thought to protect tubule cells by buffering the reactive oxygen species in the tubular fluid.

An early (2009) meta-analysis found some benefit, but no change in the risk of needing dialysis. A subsequent (2011) meta-analysis supported this finding. Trials released more recently have refuted it. Confusion remains.

At least one country's Consensus Guidelines support this strategy while admitting that the evidence for it is not very strong. Local guidelines make no mention of it.

Statins

The endothelium-protective antioxidant properties of statins may extend to protecting the tubular lumen.

A recently published meta-analysis of 8 trials found evidence of a significant protective effect. A similar meta-analysis had confirmed these findings. The effect size is considerable (halved RR) but the NNT is high, 26.

Prophylactic CVVHDF

The forcible evacuation of contrast from the body fluids seems an inelegant solution, but it certainly removes the contrast and thus theoretically decreases the kidney's exposure to it..

The use of this strategy has only been assessed in a few small trials, with inconsistent findings.

It seems CVVHDF may be cost-effective as a prophylactic post-exposure measure in patients with a very high baseline creatinine (Cr > 265 mcg/L)

Vitamin C

The mechanism of the theoretical benefit of Vitamin C is based on its antioxidant effect and renal clearance. Plus, its a relatively benign substance.

One small 2004 trial investigated this, and found some benefit. Since then, there has been little interest in ascorbic acid as a nephroprotective agent.

It is not included in any guidelines.

Question 19 from the second paper of 2017 had asked for six risk factors:

Risk Factors for Contrast-Induced Nephropathy
Non-modifiable risk factors Modifiable risk factors
  • Old age (over 75)
  • NIDDM
  • Existing renal dysfunction
    • Nephrotic syndrome
  • Poor cardiac systolic function
  • Peripheral vascular disease
  • Acute coronary syndrome
  • Renal transplant recipient
  • Multiple myeloma
  • Liver cirrhosis
  • Volume of contrast
  • Vintage of contrast (1st generation agents)
  • Hypotension
  • Anaemia
  • Dehydration
  • ACE-inhibitors
  • Diuretics
  • NSAIDs
  • Nephrotoxic antibiotics
  • IABP counterpulsation

 

References

UpToDate has an excellent article on this, for the paying public.

Mehran, R., and E. Nikolsky. "Contrast-induced nephropathy: definition, epidemiology, and patients at risk." Kidney International 69 (2006): S11-S15.

Kelly, Aine M., et al. "Meta-analysis: effectiveness of drugs for preventing contrast-induced nephropathy." Annals of internal medicine 148.4 (2008): 284-294.

Minsinger, Kristopher D., et al. "Meta-analysis of the effect of automated contrast injection devices versus manual injection and contrast volume on risk of contrast-induced nephropathy." The American journal of cardiology 113.1 (2014): 49-53.

Solomon, Richard. "Contrast Media: Are There Differences in Nephrotoxicity among Contrast Media?." BioMed research international 2014 (2014).

Thayssen, Per, et al. "Prevention of Contrast-Induced Nephropathy With N-Acetylcysteine or Sodium Bicarbonate in Patients With ST-Segment–Myocardial Infarction A Prospective, Randomized, Open-Labeled Trial."Circulation: Cardiovascular Interventions 7.2 (2014): 216-224.

Sadat, Umar. "N-acetylcysteine in contrast-induced acute kidney injury: clinical use against principles of evidence-based clinical medicine!." Expert review of cardiovascular therapy 12.1 (2014): 1-3.

Mahmoodi, Khalil, et al. "The efficacy of hydration with normal saline versus hydration with sodium bicarbonate in the prevention of contrast-induced nephropathy." Heart Views 15.2 (2014): 33.

Wu, Mei-Yi, et al. "The effectiveness of N-acetylcysteine in preventing contrast-induced nephropathy in patients undergoing contrast-enhanced computed tomography: a meta-analysis of randomized controlled trials." International urology and nephrology 45.5 (2013): 1309-1318.

Albabtain, Monirah A., et al. "Efficacy of Ascorbic Acid, N‐Acetylcysteine, or Combination of Both on Top of Saline Hydration versus Saline Hydration Alone on Prevention of Contrast‐Induced Nephropathy: A Prospective Randomized Study." Journal of interventional cardiology 26.1 (2013): 90-96.

Solomon, Richard, et al. "Effects of saline, mannitol, and furosemide on acute decreases in renal function induced by radiocontrast agents." New England Journal of Medicine 331.21 (1994): 1416-1420.

Dussol, Bertrand, et al. "A randomized trial of saline hydration to prevent contrast nephropathy in chronic renal failure patients." Nephrology Dialysis Transplantation 21.8 (2006): 2120-2126.

Weinstein, J-M., S. Heyman, and M. Brezis. "Potential deleterious effect of furosemide in radiocontrast nephropathy." Nephron 62.4 (1992): 413-415.

Navaneethan, Sankar D., et al. "Sodium bicarbonate therapy for prevention of contrast-induced nephropathy: a systematic review and meta-analysis."American Journal of Kidney Diseases 53.4 (2009): 617-627.

Kunadian, Vijayalakshmi, et al. "Sodium bicarbonate for the prevention of contrast induced nephropathy: a meta-analysis of published clinical trials."European journal of radiology 79.1 (2011): 48-55.

Mahmoodi, Khalil, et al. "The efficacy of hydration with normal saline versus hydration with sodium bicarbonate in the prevention of contrast-induced nephropathy." Heart Views 15.2 (2014): 33.

Saint-Laurent, Qc. "Consensus Guidelines for the Prevention of Contrast Induced Nephropathy." Canadian Association of Radiologists, 1740 Côte-Vertu, Saint-Laurent, Qc

Barbieri, Lucia, et al. "The role of statins in the prevention of contrast induced nephropathy: a meta-analysis of 8 randomized trials." Journal of thrombosis and thrombolysis (2014): 1-10.

Kapadia, Carl Behram, et al. "EFFICACY OF SHORT TERM, HIGH DOSE STATINS FOR PREVENTING CONTRAST-INDUCED ACUTE KIDNEY INJURY IN PATIENTS UNDERGOING CORONARY ANGIOGRAPHY AND/OR PERCUTANEOUS CORONARY INTERVENTION: A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS." Journal of the American College of Cardiology 63.12_S (2014).

Spargias, Konstantinos, et al. "Ascorbic acid prevents contrast-mediated nephropathy in patients with renal dysfunction undergoing coronary angiography or intervention." Circulation 110.18 (2004): 2837-2842.

Biondi-Zoccai, Giuseppe, et al. "Nephropathy after administration of iso-osmolar and low-osmolar contrast media: evidence from a network meta-analysis." International journal of cardiology 172.2 (2014): 375-380.