Medicine:Contrast-induced nephropathy

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Contrast-induced nephropathy
SpecialtyNephrology, radiology

Contrast-induced nephropathy (CIN) is a purported form of kidney damage in which there has been recent exposure to medical imaging contrast material without another clear cause for the acute kidney injury.

Despite extensive speculation, the actual occurrence of contrast-induced nephropathy has not been demonstrated in the literature.[1] Analysis of observational studies has shown that radiocontrast use in CT scanning is not causally related to changes in kidney function.[2]


Given the increasing doubts about the contribution of radiocontrast to acute kidney injury, the American College of Radiology has proposed the name contrast-associated acute kidney injury (CA-AKI) (formerly referred to as post-contrast acute kidney injury; PC-AKI) because it does not imply a causal role, with the name contrast-induced acute kidney injury (CI-AKI) (formerly referred to as contrast-induced nephropathy; CIN) reserved for the rare cases where radiocontrast is likely to be causally related.[3]

Risk factors

There are multiple risk factors of contrast-induced nephropathy, whereof a 2016 review emphasized chronic kidney disease, diabetes mellitus, high blood pressure, reduced intravascular volume, and old age.[4]

Decreased kidney function

European guidelines classify a pre-existing decreased kidney function to be a risk factor of contrast-induced nephropathy in the following cases:[5]

  • Estimated glomerular filtration rate (eGFR) < 45 ml/min/1.73 m2 of body surface area before intra-arterial administration with first-pass renal exposure (not passing lungs or peripheral circulation before kidneys), or in the intensive care unit
  • eGFR < 30 ml/min/1.73 m2 before intravenous administration or intra-arterial administration with second-pass renal exposure
  • Known or suspected acute kidney injury

To calculate estimated GFR (a measure of kidney function) from creatinine, European guidelines use the CKD-EPI formula in adults ≥ 18 years, and the revised Schwartz formula in children.[5] Swedish guidelines recommends no specific formula in children because of lack of evidence, but on the other hand recommends GFR based on cystatin C rather than creatinine in those with abnormal muscle mass, liver failure, or cirrhosis.[5]

Mehran score

The Mehran score is a clinical prediction rule to estimate probability of CIN which includes the following risk factors: systolic blood pressure <80 mm Hg for at least one hour requiring inotropic support, intra-aortic balloon pump, congestive heart failure with New York Heart Association Functional Classification class III or worse, history of pulmonary edema, age >75 years, hematocrit level <39% for men and <35% for women, diabetes mellitus, contrast media volume, decreased kidney function (serum creatinine level >1.5 g/dL or decreased estimated glomerular filtration rate).[6][7]

Other factors

European guidelines include the following procedure-related risk factors:[5]

  • Large doses of contrast given intra-arterially with first-pass renal exposure
  • Use of contrast agents with high osmolality (limited use today)
  • Multiple contrast injections within 48–72 h. Swedish guidelines also include gadolinium MRI contrast agents in this aspect.

Swedish guidelines list the following additional risk factors:[5]


The main alternatives in people with a risk of contrast-induced nephropathy are:[citation needed]

  • Adjustment of the radiocontrast dose
  • Treating or mitigating risk factors
  • Using no intravenous contrast for the investigation.
  • Switching to another modality such as ultrasonography or MRI.

Dose adjustment

According to European guidelines, the ratio of the contrast dose (in grams of iodine) divided by the absolute estimated glomerular filtration rate (GFR) should be less than 1.1 g/(ml/min) for intra-arterial contrast medium administration with first-pass renal exposure (not passing lungs or peripheral tissue before reaching the kidneys).[5] Swedish guidelines are more restrictive, recommending a ratio of less than 0.5 g/(ml/min) in patients with risk factors and irrespective of route of administration, and even more caution in first-pass renal exposure.[5]

Treating or mitigating risk factors

Hydration by drinking or intravenous volume expander, either before or after contrast administration, decreases the risk of contrast-induced nephropathy.[8] Evidence also supports the use of N-acetylcysteine with intravenous saline among those getting low molecular weight contrast.[9][dubious ] The use of statins with N-acetylcysteine and intravenous saline is also supported.[9]

  • Oral hydration may be as effective as the intravenous route for volume expansion to prevent contrast-induced nephropathy, according to a review in 2013.[8]
  • Adenosine antagonists such as the methylxanthines theophylline and aminophylline, may help[10] although studies have conflicting results.[11]
  • N-acetylcysteine (NAC) by mouth twice a day, on the day before and of the procedure if creatinine clearance is estimated to be less than 60 mL/min [1.00 mL/s]) may reduce risk. Some authors believe the benefit is not overwhelming.[12] A systematic review concluded that NAC is "likely to be beneficial" but did not recommend a specific dose.[13][needs update]
  • Ascorbic acid may be protective against CIN, according to a systematic review of randomized controlled trials.[14]
  • Matched hydration, meaning infusion of a volume of normal saline equal to the urine output, has been found to reduce kidney injury, dialysis, adverse events and mortality compared to standard therapy.[15][16]


CIN is classically defined as a serum creatinine increase of at least 25% and/or an absolute increase in serum creatinine of 0.5 mg/dL[17] after using iodine contrast agent without another clear cause for acute kidney injury,[4] but other definitions have also been used.[2]

The American College of Radiology recommends the usage of the AKIN criteria for the diagnosis of CIN or PC-AKI. The AKIN criteria states that the diagnosis is made if within 48 hours from intravascular contrast medium exposure one of the following occurs:[18]

  1. Absolute serum creatinine increase of ≥0.3 mg/dl (>26.4 µmol/L)[18]
  2. Relative serum creatinine increase of ≥50 % (≥1.5-fold above baseline)[18]
  3. Urine output reduced to ≤0.5 mL/kg/hour for at least 6 hours[18]


The mechanism of contrast-induced nephropathy is not entirely understood, but is thought to include direct damage from reactive oxygen species, contrast-induced increase in urine output, increased oxygen consumption, changes in dilation and narrowing of the blood vessels to the kidneys, and changes in urine viscosity.[citation needed]


It is unclear if CIN causes persisting decline in renal function since few studies has followed patients for more than 72 hours.[18] In one meta-analysis the decline in renal function was shown to persist in 1.1 % of the patients with CIN.[19]

Clinical relevance

Doubts regarding the significance of the phenomenon appeared in the scientific literature. Several studies have shown that intravenous contrast material administration was not associated with excess risk of acute kidney injury, dialysis, or death, even among patients with comorbidities reported to predispose them to nephrotoxicity.[1] Moreover, hydration, the most established prevention measure to prevent contrast-induced nephropathy was shown to be ineffective in the POSEIDON trial,[20] raising further doubts regarding the significance of this disease state.[21] A meta-analysis of 28 studies of AKI after CT with radiocontrast showed no causal relationship between the use of radiocontrast and AKI.[2]


  1. 1.0 1.1 McDonald, Robert; McDonald, Jennifer S.; Carter, Rickey E.; Hartman, Robert P.; Katzberg, Richard W.; Kallmes, David F.; Williamson, Eric E. (December 2014). "Intravenous Contrast Material Exposure Is Not an Independent Risk Factor for Dialysis or Mortality". Radiology 273 (3): 714–725. doi:10.1148/radiol.14132418. PMID 25203000. 
  2. 2.0 2.1 2.2 Aycock, Ryan D.; Westafer, Lauren M.; Boxen, Jennifer L.; Majlesi, Nima; Schoenfeld, Elizabeth M.; Bannuru, Raveendhara R. (August 2017). "Acute Kidney Injury After Computed Tomography: A Meta-analysis". Annals of Emergency Medicine 71 (1): 44–53.e4. doi:10.1016/j.annemergmed.2017.06.041. PMID 28811122. 
  3. "10. Post-Contrast Acute Kidney Injury and Contrast-Induced Nephropathy in Adults". ACR Manual on Contrast Media. American College of Radiology. 2022. pp. 40–50. ISBN 978-1-55903-012-0. Retrieved 2022-08-02. 
  4. 4.0 4.1 Subramaniam, RM; Suarez-Cuervo, C; Wilson, RF; Turban, S; Zhang, A; Sherrod, C; Aboagye, J; Eng, J et al. (February 2016). "Effectiveness of Prevention Strategies for Contrast-Induced Nephropathy: A Systematic Review and Meta-analysis". Annals of Internal Medicine 164 (6): 406–16. doi:10.7326/M15-1456. PMID 26830221. 
  5. 5.0 5.1 5.2 5.3 5.4 5.5 5.6 Nyman, Ulf; Ahlkvist, Joanna; Aspelin, Peter; Brismar, Torkel; Frid, Anders; Hellström, Mikael; Liss, Per; Sterner, Gunnar et al. (2018). "Preventing contrast medium-induced acute kidney injury". European Radiology 28 (12): 5384–5395. doi:10.1007/s00330-018-5678-6. ISSN 0938-7994. PMID 30132106. 
  6. "A simple risk score for prediction of contrast-induced nephropathy after percutaneous coronary intervention: development and initial validation". J. Am. Coll. Cardiol. 44 (7): 1393–9. 2004. doi:10.1016/j.jacc.2004.06.068. PMID 15464318. 
  7. Kalgi Modi, Scott C. Dulebohn (2017). Contrast-Induced Nephropathy. StatPearls Publishing.  CC-BY-4.0
  8. 8.0 8.1 Yang, Xiaoming; Hiremath, Swapnil; Akbari, Ayub; Shabana, Wael; Fergusson, Dean A.; Knoll, Greg A. (2013). "Prevention of Contrast-Induced Acute Kidney Injury: Is Simple Oral Hydration Similar To Intravenous? A Systematic Review of the Evidence". PLOS ONE 8 (3): e60009. doi:10.1371/journal.pone.0060009. ISSN 1932-6203. PMID 23555863. Bibcode2013PLoSO...860009H. 
  9. 9.0 9.1 Subramaniam, RM; Suarez-Cuervo, C; Wilson, RF; Turban, S; Zhang, A; Sherrod, C; Aboagye, J; Eng, J et al. (15 March 2016). "Effectiveness of Prevention Strategies for Contrast-Induced Nephropathy: A Systematic Review and Meta-analysis.". Annals of Internal Medicine 164 (6): 406–16. doi:10.7326/m15-1456. PMID 26830221. 
  10. "Evidence-based emergency medicine review. Prevention of contrast-induced nephropathy in the emergency department". Annals of Emergency Medicine 50 (3): 335–45, 345.e1–2. 2007. doi:10.1016/j.annemergmed.2007.01.023. PMID 17512638. 
  11. "Theophylline for prevention of contrast-induced nephropathy: a systematic review and meta-analysis". Arch. Intern. Med. 165 (10): 1087–93. 2005. doi:10.1001/archinte.165.10.1087. PMID 15911721. 
  12. "Contrast-induced nephropathy". AJR Am J Roentgenol 183 (6): 1673–89. 2004. doi:10.2214/ajr.183.6.01831673. PMID 15547209. 
  13. "Renal failure (acute)". Clinical Evidence (15): 1191–212. 2006. PMID 16973048. 
  14. "Does ascorbic acid protect against contrast-induced acute kidney injury in patients undergoing coronary angiography: a systematic review with meta-analysis of randomized, controlled trials.". J Am Coll Cardiol 62 (23): 2167–75. 2013. doi:10.1016/j.jacc.2013.07.065. PMID 23994417. 
  15. Putzu, Alessandro; Berto, Martina Boscolo; Belletti, Alessandro; Pasotti, Elena; Cassina, Tiziano; Moccetti, Tiziano; Pedrazzini, Giovanni (2017). "Prevention of Contrast-Induced Acute Kidney Injury by Furosemide With Matched Hydration in Patients Undergoing Interventional Procedures". JACC: Cardiovascular Interventions 10 (4): 355–363. doi:10.1016/j.jcin.2016.11.006. PMID 28231903. 
  16. Mattathil, Stephanie; Ghumman, Saad; Weinerman, Jonathan; Prasad, Anand (2017-10-01). "Use of the RenalGuard system to prevent contrast-induced AKI: A meta-analysis" (in en). Journal of Interventional Cardiology 30 (5): 480–487. doi:10.1111/joic.12417. ISSN 1540-8183. PMID 28870002. 
  17. "Clinical practice. Preventing nephropathy induced by contrast medium". N. Engl. J. Med. 354 (4): 379–86. 2006. doi:10.1056/NEJMcp050801. PMID 16436769. 
  18. 18.0 18.1 18.2 18.3 18.4 Ellis, JH; Davenport, MS; Dillman, JR; Hartman, RP; Herts, BR; Jafri, SZ; Kolbe, AB; Laroia, A et al. (2017). ACR Manual on Contrast Media. American College of Radiology. pp. 35–46. ISBN 978-1-55903-012-0. Retrieved 20 November 2020. 
  19. Kooiman, Judith; Pasha, Sharif M.; Zondag, Wendy; Sijpkens, Yvo W. J.; Molen, Aart J. van der; Huisman, Menno V.; Dekkers, Olaf M. (2012-10-01). "Meta-analysis: Serum creatinine changes following contrast enhanced CT imaging" (in English). European Journal of Radiology 81 (10): 2554–2561. doi:10.1016/j.ejrad.2011.11.020. ISSN 0720-048X. PMID 22177326. 
  20. Brar, Somjot S.; Aharonian, Vicken; Mansukhani, Prakash; Moore, Naing; Shen, Albert Y.-J.; Jorgensen, Michael; Dua, Aman; Short, Lindsay et al. (2014-05-24). "Haemodynamic-guided fluid administration for the prevention of contrast-induced acute kidney injury: the POSEIDON randomised controlled trial". Lancet 383 (9931): 1814–1823. doi:10.1016/S0140-6736(14)60689-9. ISSN 1474-547X. PMID 24856027. 
  21. John Mandrola (2017-03-07). "Contrast-Induced Nephropathy: Signal or Noise?". 

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