December 2015

Contrast Induced-Acute Kidney Injury: Predictable and potentially avoidable

Gemma Batten (Medical Student) and Yogita Aggarwal (SpR Renal Medicine)

Aim: Contrast media related renal insufficiency is a common, costly and avoidable cause of acute kidney injury (AKI) and related morbidity.  Timely risk stratification and subsequent implementation of protective or preventative therapeutic measures can directly result in lower rates of associated negative outcomes.     

We present a patient with chronic kidney disease (CKD) who developed AKI following contrast imaging and required short-term supportive renal replacement therapy.  We chose this case as it represents a typical patient phenotype at risk of developing contrast induced- acute kidney injury (CI-AKI) and demonstrates the risk factors exacerbating the severity of AKI.


Case: Day 0 – The admission

A 62 year-old gentlemen was referred to the Acute Medical Unit with decompensated heart failure, vomiting and lethargy.  10 days prior he had had an outpatient staging CT scan of his neck, chest, abdomen and pelvis following a malignant polyp that was found on colonoscopy.  The CT images showed an early Dukes’ C bowel cancer.  In outpatients 3 weeks earlier, his creatinine had been 150mmol/L.


His past medical history included the following:

  1. Well controlled type 2 Diabetes Mellitus of 4-5years with no evidence of retinal disease – last HBA1c 5.9%
  2. Controlled hypertension for over 2 decades with mean home readings of 130/75mmHg
  3. Ischaemic Heart Disease (3 previous myocardial infarctions and left anterior descending stent placed 7 years ago)
  4. Congestive cardiac failure (CCF) with a severely impaired biventricular function (EF 35%, NYHA stage III)
  5. Asymptomatic peripheral vascular disease
  6. Non-proteinuric CKD 3b – baseline creatinine 150mmol/L and eGFR 48ml/min/1.73m2.
  7. Life-long non-smoker

The patient was on the following medications and he denied the use of non-steroidal anti-inflammatory drugs (NSAIDs).

  1. Aspirin 75mg OD
  2. Atorvastatin 40mg OD
  3. Bisoprolol 5mg OD
  4. Furosemide 40mg OD
  5. Metformin 1g BD
  6. Ramipril 10mg OD


On examination the patient was fluid overloaded with relative hypotension 101/59mmHg.  He required 10L of oxygen to maintain oxygen saturations of 92%, and his respiratory rate was 19bpm.  His abdominal examination was unremarkable and there were no visible rashes.

Bedside investigations revealed a metabolic acidosis with pH 7.28, lactate 4 and bicarbonate 18.  ECG showed sinus rhythm and a CXR confirmed florid pulmonary oedema. His blood results, in SI units, were as follows:

A diagnosis of decompensated heart failure with an AKI due to cardiogenic shock was made and the patient was managed with predominantly oxygen, intravenous furosemide and glyceryl trinitrate.   Admission medications altering renal haemodynamics and nephrotoxics were stopped.  An ultrasound showed two normal sized kidneys and a urine dip was not available.

Over the next 36 hours, the patient did not improve and below is a summary of his observations and renal bloods:


Day 2: The Renal Opinion:  He was referred to the renal team as he had deteriorating renal function. 

After a detailed history and examination, it was apparent the patient had presented with Stage 3 AKI secondary to contrast media and exacerbated by pre-existing CKD, his presentation with hypotension and concomitant use of ACEi, diuretics and metformin.  Fluid retention had occurred due to the patient becoming anuric.   **The patient had not been pre-hydrated and had not stopped any medications pre-scan.  They type and volume of CM used was not available.**


The following important differential diagnoses were considered:

  1. AKI secondary to aggressive over diuresis
  2. Acute interstitial nephritis
  3. Acute tubular necrosis to other medications
  4. (Atheroembolic disease especially after intra-arterial contrast media as associated with intervention – not relevant to this case).


The following management occurred:

  • All medications altering renal haemodynamics and nephrotoxics were checked and had been definitely stopped.
  • Ward based renal replacement therapy was started as the patient was anuric with a severe persistent metabolic acidosis and hyperkalaemia.
  • A strict fluid balance assessment was continued.
  • Daily renal bloods were performed.



The patient received haemodialysis for 2 weeks and over this time he started to regain residual renal function.  Dialysis was withheld when he started to pass more than 1 L of urine a day and his renal blood results started to plateau.

4 weeks after becoming dialysis independent he was passing normal urine volumes and had a creatinine of 230mmol/L which was the same at 3 months.

In the recovery stages of acute tubular necrosis (ATN) – the tubules lose their ability to effectively filter electrolytes. A patient can develop polyuria and become hypo-electrolyte (serum magnesium, calcium, phosphate, potassium and chloride).  There is a risk of an additive hypovolaemic insult, and close observation and regular fluid assessment +/- intravenous hydration is required.  It is important to avoid nephrotoxics in this stage of ATN recovery.  ATN recovery can take up to 3 months and only thereafter can eGFR be used as a measure of renal function.



Incidence of CI-AKI

It is the third most common cause of acute kidney injury in patients admitted to hospital.  It is known to accelerate the onset of end-stage renal disease and has an estimated general incidence of 7%.  The true incidence of CI-AKI is difficult to capture for a number of reasons including patients having outpatient contrast imaging.

Its incidence increases to over 50% in the presence of risk factors such as chronic kidney disease (CKD), diabetes mellitus and nephrotoxic drugs.


Definition of CI-AKI

The clinical course of CI-AKI is a rise in blood urea and creatinine, or a decline in estimated glomerular filtration rate (eGFR) occurring typically 24–72 hours after administration of iodinated CM and usually recovering over the following five days to 3 weeks.

CI-AKI is associated with increased mortality and morbidity including coronary artery bypass grafting, packed red cell transfusions, sepsis, bleeding, coma, respiratory failure and renal replacement therapy.   

The Kidney Disease: Improving Global Outcomes (KDIGO) ( defines CI-AKI when one of the following criteria is met:

  • Serum creatinine rises by ≥ 26μmol/L within 48 hours
  • Serum creatinine rises ≥ 1.5 fold from the baseline value, which is known or presumed to have occurred within one week
  • Urine output is < 0.5ml/kg/hr for >6 consecutive hours


If a baseline serum creatinine is not available within 1 week the lowest serum creatinine value recorded within 3 months of the episode of AKI can be used.

If a baseline serum creatinine value is not available within the past 3 months, and AKI is suspected, repeat the serum creatinine within 24 hours.  A reference serum creatinine value can be estimated from the nadir serum creatinine value, if patient recovers from AKI.

It is important to exclude other causes of AKI as small rises in serum creatinine have been demonstrated to occur in 8-35% of patients admitted to hospital without exposure to contrast media.


The severity of CI-AKI can be graded by using the Kidney Disease: Improving Global Outcomes (KDIGO) staging classification* of acute kidney injury (AKI).

Stage Serum creatinine (Cr) criteria Urine output criteria

increase ≥ 26 μmol/L within 48hrs or

increase ≥1.5- to 1.9 X baseline Cr

<0.5 mL/kg/hr for > 6 consecutive hrs

increase ≥ 2 to 2.9 X baseline Cr


<0.5 mL/kg/ hr for > 12 hrs

increase ≥3 X baseline Cr or

* increase 354 μmol/L or

commenced on renal replacement therapy (RRT) irrespective of stage

<0.3 mL/kg/ hr for > 24 hrs or


Pathophysiology of CI-AKI

Contrast media (CM) generates reactive oxygen species (ROS) which exert a direct cytotoxic effects on renal tissue by inducing renal cell apoptosis – which is dose and time dependent.

CM also causes hypoperfusion, particularly in the medulla, by causing constriction of vasa recta. This results in a hypoxic injury to the medulla and results in ischaemia.

Further, CM slows down the flow of tubular fluid by increasing its viscosity and leading to prolonged renal retention of CM and subsequent exposure to CM cytotoxic effects.


Who is at risk of CI-AKI?

Risk factors for CI-AKI are best approached in terms of patient-related, CM-related and procedure-related.

Patient related risk factors:

  • Chronic kidney disease (CKD) eGFR < 60 mls/min/1.73m2
  • Older age (> 75 years old)
  • Cardiac failure
  • Diabetes
  • Hypertension
  • Concomitant use of aminoglycosides, NSAIDs, Amphotericin B
  • Hypovolaemia
  • Sepsis


CM-related risk factors:

  • High total dose
  • High osmolality
  • High ionic content
  • High viscosity of the contrast media
  • Possible intra-arterial administration (but risk may actually be related to the haemodynamic instability of the patient and the subsequent acute clinical need for the procedure)


High-osmolality CM (HOCM) are associated with a higher incidence of CI-AKI than low-osmolality CM (LOCM) and iso-osmolality CM (IOCM).  According to RCR guidelines ‘Non-ionic, low or iso-osmolar iodinated media are five to ten times safer than the older, high osmolar ionic contrasts’.  It is not clear whether IOCM are less nephrotoxic than LOCM.

Below are examples of HOCM, LOCM and IOCM and their relevant osmolar weights.


Procedure related risk factors:  Less than two days between the contrast-using procedures and an urgent/emergency procedure


Risk scoring systems: 

There are many scoring systems which remain largely unvalidated.  A favoured model is that offered by Mehran et al. but it uses a population who have CI-AKI after PCI and intra-atrial contrast injection.

Risk scoring system by Mehran et al.  (Figure taken from Sadat U, Usman A, Boyle J et al.  Contrast Medium-Induced Acute Kidney Injury. Cardiorenal Med 2015;5:219-228)


The effect of risk factors is additive.


Prevention and Measures to minimise the Risk of CI-AKI:

Prevention is important as there is no specific treatment and involves identification of patients at increased risk of CI-AKI. 

Measures which could be considered are: 

  1. Alternative imaging such as ultrasound or magnetic resonance angiography.
  2. Consider carbon dioxide and similar as a contrast media
  3. Stop/avoid renal insufficiency inducing medications such as non-steroidal anti-inflammatory drugs, aminoglycosides, angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin receptor blockers (ARBs).  It is unclear if there is any benefit in stopping ACEi and ARBs in stable outpatients but logically it makes sense to stop it
  4. Stop metformin for 48 hours if eGFR < 60 ml/min/1.73m2
  5. Acutely ill patients and those considered high risk of CI-AKI should have an assessment of their volume status and receive appropriate volume expansion pre-CM either:
    1. intravenous 0.9% sodium chloride at a rate of 1 mL/kg/hour for 12 hours pre- and post- procedure OR
    2. Isotonic sodium bicarbonate
    3. Oral volume expansion is not as effective as intravenous.
  6. Use LOCM and low volumes.HOCM should be avoided in high risk patients.It is unclear whether IOCM is superior to LOCM.
  7. Avoid repeat insults with CM spaced over 48-72 hours.
  8. Renal function should be checked up to 48-72 hours post-procedure in high risk patients.
  9. Reactive Oxygen Species - No evidence for N-acetylcysteine peri-procedure.


Learning points:

  1. CI-AKI is avoidable.
  2. Risk can be somewhat pre-empted with scoring tools
  3. High-risk patients should be pre-hydrated, and medications which alter renal haemodynamics should be suspended where possible, and other nephrotoxic inducing agents such as metformin should be stopped
  4. In the Emergency/Acute setting robust fluid resuscitation before contrast imaging should be consideredis useful
  5. The risk of CI-AKI in CKD patients is proportional to the level of CKD
  6. Involve the renal team as early as possible in cases of AKI stage 3



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