My patient with renal insufficiency developed hyponatremia after an IV contrast study.  Is there a connection between hyponatremia and iodinated contrast media?

There are several reports in the literature of hyponatremia (sometimes severe) developing in patients undergoing coronary angiography or routine IV contrast CT studies. 1-3 Although generally asymptomatic, severe hyponatremia with symptoms may also occur, particularly in those at risk of hyponatremia due to other factors.  

In a case series of 5 patients with advanced renal disease who underwent cardiac catheterization and developed post-procedure hyponatremia, the mean plasma sodium concentration decreased from 138.6 mEq/L to 122.6 mEq/L within 2-22 hours post-procedure; no patient had any neurological symptoms associated with hyponatremia. There was a strong correlation between dose of contrast administered and change in sodium level. 2

Severe symptomatic hyponatremia (confusion, stupor) was also reported in an elderly woman with blood creatinine of 0.9 mg/dL following coronary angiography (baseline plasma sodium 142 mmo/L vs. 115 mmol/L >16 hours post-procedure).  The authors suggested that a diagnosis of hyponatremia be considered in any patient who develops behavioral or neurologic manifestations after coronary angiography.3

Aside from coronary angiography, a prospective study among 103 adults (mean serum creatinine 0.79 mg/dl) undergoing contrast-enhanced CT found a drop in serum sodium from a mean concentration of 136 mmol/L to 132 mmol/L 24 hours after the procedure without any associated symptoms.1

Potential mechanisms for the development of hyponatremia after IV contrast studies include hemodilution due to translocation of fluid from intracellular space caused by high osmolality of the contrast media.1  

Bonus Pearl

Did you know that even the newer “low osmolar contrast” agents are more than 3 times the osmolality of blood?4

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References

  1. Sankaran S, Saharia GK, Naik S, et al. Effect of iodinated contrast media on serum electrolyte concentrations in patients undergoing routine contrast computed tomography scan procedure. Int J Appl Basic Med Res 2019;9:217-220. https://www.ijabmr.org/article.asp?issn=2229-516X;year=2019;volume=9;issue=4;spage=217;epage=220;aulast=Sankaran
  2. Sirken G, Raja R, Garces J, et al. Contrast-induced translocational hyponatremia and hyperkalemia in advanced kidney disease. Am J Kidney Dis 2004;43:e9.1-e9.5. https://www.sciencedirect.com/science/article/abs/pii/S0272638603013854?via%3Dihub
  3. Jung ES, Kang WC, Jang YR, et al. Acute severe symptomatic hyponatremia following coronary angiography. Korean Circ J 2011;41:552-554. https://europepmc.org/article/pmc/pmc3193049
  4. Bucher AM, De Cecco CN, Schoefpf UJ, et al. Is contrast medium osmolality a causal factor for contrast-induced nephropathy? BioMed Res International 2014; Volume 2014, article ID 931413. https://www.hindawi.com/journals/bmri/2014/931413/

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Massachusetts General Hospital, Harvard Catalyst, Harvard University, its affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

My patient with renal insufficiency developed hyponatremia after an IV contrast study.  Is there a connection between hyponatremia and iodinated contrast media?

Can my patient with renal insufficiency safely undergo gadolinium-based contrast MRI?

It may be possible for patients with renal insufficiency, including those with end-stage kidney disease (ESKD), to undergo MRI using potentially safer preparations of gadolinium-based contrast agents (GBCAs) with “very low, if any” risk of the feared nephrogenic systemic sclerosis (NSF). 1

In contrast to the so called “linear” chelates of gadolinium (eg, gadodiamide, gadopentetate), “cyclic” GBCA’s (eg, gadoteridol) have not been clearly associated with NSF. 2 A Veterans Administration study involving gadoteridol identified no cases of NSF among the 141 patients on hemodialysis following 198 exposures. 2 In fact, the 2017 American College of Radiology (ACR) Manual on Contrast Media reports the risk of NSF with cyclic chelates as “very low, if any”. 1 Even when a cyclic GBCA is used in patients with ESKD, however, hemodialysis is recommended as soon as possible after MRI. 3

GBCAs are chelates with 2 major components: gadolinium and either a linear or cyclic ligand. Cyclic ligands bind to gadolinium more avidly, resulting in lower probability of circulating renally-cleared free gadolinium which when deposited in tissue is thought to potentially trigger NSF.2

Although NSF is characterized by progressive fibrosis of skin and soft tissue, it may involve multiple organs with an estimated 30% mortality rate. 4

 Bonus Pearl: Did you know NSF is really a new disease, with no evidence of its existence before 1997?

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References

  1. “Nephrogenic Systemic Fibrosis”. In ACR Manual on Contrast Media; Version 10.3; May 31, 2017. https://www.acr.org/-/media/ACR/Files/Clinical-Resources/Contrast_Media.pdf
  2. Reilly RF. Risk for nephrogenic systemic fibrosis with gadoteridol (ProHance) in patients who are on long-term hemodialysis. Clin J Am Soc Nephrol 2008;3:747-51. https://www.ncbi.nlm.nih.gov/pubmed/18287249
  3. Wang Y, Alkasab TK, Nari O, et al. Incidence of nephrogenic systemic fibrosis after adoption of restrictive gadolinium-based contrast agent guidelines. Radiology 2011;260:105-111.  https://www.ncbi.nlm.nih.gov/pubmed/21586680
  4. Schlaudecker JD, Bernheisel CR. Gadolinium-associated nephrogenic systemic fibrosis. Am Fam Physician 2009;80:711-14. https://www.aafp.org/afp/2009/1001/p711.pdf

 

Contributed by Richard Newcomb, MD, Mass General Hospital, Boston, MA.

Can my patient with renal insufficiency safely undergo gadolinium-based contrast MRI?

How strong is the evidence for IV contrast-induced nephropathy (CIN) following CT scans?

Not as strong as one might expect with an increasing number of investigators questioning the causative role of IV contrast in precipitating CIN.

A 2013 meta-analysis involving observational—mostly retrospective— studies concluded that the risks of AKI, death, and dialysis were similar between IV contrast and non-contrast patients, including those with diabetes or underlying renal insufficiency1.

Two retrospective studies2,3 designed to control for a variety of factors that may affect the risk of AKI by propensity matching found divergent results with the larger and better designed study finding no significant difference in AKI between the 2 groups3. A 2017 retrospective cohort analysis of emergency department patients utilizing a similar propensity-score analysis also failed to find a difference in post-CT AKI between those receiving and not receiving IV contrast4.

Further shedding doubt on the role of IV contrast in causing AKI, a study involving patients with chronic kidney disease found no difference in the rates of excretion of 2 biomarkers of AKI (neutrophil gelatinase-associated lipocalin-NGAL, and kidney injury molecule-1-KIM-1) between patients with and without presumed CIN5.

This is not to say that IV CIN does not exist. Among many findings, in vitro and animal studies have demonstrated that iodinated contrast media exerts cytotoxic effects on renal tubular epithelial cells and promotes hemodynamic changes through renal vasoconstriction to severe renal damage and cellular apoptosis (6). However, some have have criticized experimental animal studies supporting the existence of CIN due to their poor applicability to human renal disease. 1

After all these years, it’s still important to keep an open mind about the pathophysiology and epidemiology of CIN. Stay tuned!

Fun pearl: Did you know that the first case of CIN was described in a patient with multiple myeloma undergoing IV pyelography (before the CT era)?

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References

  1. McDonald JS, McDonald RJ, Comin J, et al. Frequency of acute kidney injury following intravenous contrast medium administration: a systematic review and meta-analysis. Radiology. 2013;267(1):119-128. https://www.ncbi.nlm.nih.gov/pubmed/23319662
  2. Davenport MS, Khalatbari S, Dillman JR, et al. Contrast material-induced nephrotoxicity and intravenous low-osmolality iodinated contrast material. Radiology. 2013;267(1):94-105. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3606541/pdf/121394.pdf
  3. McDonald RJ, McDonald JS, Bida JP, et al. Intravenous contrast material-induced nephropathy: causal or coincident phenomenon? Radiology 2013;267:106-18. https://www.ncbi.nlm.nih.gov/pubmed/23360742
  4. Hinson JS, Ehmann MR, Fine DM, et al. Risk of acute kidney injury after intravenous contrast media administration. Ann Emerg Med 2017; 69:577-586. https://www.ncbi.nlm.nih.gov/pubmed/28131489
  5. Kooiman J, van de Peppel WR, Sijpkens YWJ, et al. No increase in kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin excretion following intravenous contrast enhanced-CT. Eur Radio 2015;25:1926-34. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4457910/pdf/330_2015_Article_3624.pdf
  6. Mamoulakis C, Fragkiadoulaki I, Karkala P, et al. Contrast-induced nephropathy in an animal model: evaluation of novel biomarkers in blood and tissue samples. Toxicol Rep 2019;6:395-400. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6506864/ 

Original contribution by Ginger Jiang, Medical Student, Harvard Medical School

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis or its affiliate healthcare centers, Mass General Hospital, Harvard Medical School or its affiliated institutions. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

How strong is the evidence for IV contrast-induced nephropathy (CIN) following CT scans?