contrast induced nephropathy
TRANSCRIPT
Contrast Induced Nephropathy: Predictors, Prevention, and Management
Dr Aris Tsalouchos Medico Specializzando in Nefrologia
Università Degli Studi di Firenze
AKI Definition
2.1.1: AKI is defined as any of the following (Not Graded):•Increase in SCr by ≥ 0.3 mg/dl (≥26.5lmol/l) within 48 hours; or•Increase in SCr to ≥ 1.5 times baseline, which is known or presumed to have occurred within the prior 7 days; or•Urine volume < 0.5 ml/kg/h for 6 hours.
KDIGO 2012
AKI Definition
2.1.2: AKI is staged for severity according to the following criteria (Table2). (Not Graded)
KDIGO 2012
CI-AKI DEFINITION
3 criteria: Iatrogenic disorder with absolute ( ≥ 0,5 mg/dl) or relative increase ( ≥ 25%) in sCr post-contrast exposure compared to baseline value.
Occur within 24-48 hours with peak sCr in 3-5 days.
Other alternative explanations for renal impairment have been excluded.
Murphy SW et. J Am Soc Nephrol. Jan 2000;11(1):177-82.
Slight (5%-10%) increments of serum creatinine compared with baseline 12 hours after angiography predict contrastinduced nephropathy.
A 5% increase of its value yielded 75% sensitivity and 72% specificity for early contrast-induced nephropathy detection.
Furthermore, it strongly correlated with the development of renal impairment at 30 days, sensitivity 87%, specificity 70%
The American Journal of Medicine (2010) 123, 755-763
Epidemiology of CI-AKICI-AKI is described as the third most common cause of new AKI in hospitalized patients (after decreased renal perfusion and nephrotoxic medications) and is responsible for 11% of cases.
Nash K et al. Am J Kidney Dis2002;39:930–936.
Reported incidence of 3.1-31%. The number varies depending on: the definition used for CIN the contrast agent characteristics, including the type, amount,
duration, and route of administration.preexisting risk factors.and length of follow-up (including the day of measurement of
postcontrast serum creatinine).
4.1.1: In individuals who develop changes inkidney function after administration of intra-vascular contrast media, evaluate for CI-AKIas well as for other possible causes of AKI.(Not Graded)
KDIGO 2012
‘‘Hospital-induced nephropathy’’ ?
‘‘Hospital-induced nephropathy’’ ?
Diagnostic Considerations
Conditions to consider in the differential diagnosis of CIN include the following:
Atheroembolic renal failure - More than 1 week after contrast, blue toes, livedo reticularis, transient eosinophilia, prolonged course, and lower recovery
Acute renal failure (includes prerenal and postrenal azotemia) - There may also be associated dehydration from aggressive diuresis, exacerbated by preexisting fluid depletion; the acute renal failure is usually oliguric, and recovery is anticipated in 2-3 weeks
Acute interstitial nephritis (triad of fever, skin rash, and eosinophilia) - Also eosinophiluria; the nephritis is usually from drugs such as penicillin, cephalosporins, and nonsteroidal anti-inflammatory drugs (NSAIDs)
Acute tubular necrosis- Ischemia from prerenal causes; endogenous toxins, such as hemoglobin, myoglobin, and light chains; exogenous toxins, such as antibiotics, chemotherapeutic agents, organic solvents, and heavy metals
Medscape Updated: Jul 10, 2012
Postulated Pathophysiology of CI-AKI
GR in soluzione ipertonica
Impilamento dei globuli rossi
all’interno dei piccoli vasi
Histopathology of CI-AKI
Vacuolar changes in the proximal convoluted tubular cells
Normal
ATN
Risk Factors for CINPatient-related Risk Factors
• Renal insufficiency• Diabetes mellitus with
renal insufficiency• Age > 70 years• Volume depletion• Hypotension• Low cardiac output• Class IV CHF• Other nephrotoxins• Renal transplant• Hypoalbuminemia (<35
g/l)
Procedure-related Risk Factors
• Multiple contrast media injection within 72 hrs
• Intra-arterial injection site
• High volume of contrast media
• High osmolality of contrast media
Lameire N et al. Am J Cardiol2006;98:21K–26K.
CMAJ • MAY 24, 2005; 172 (11)
Assessment of the population at riskfor CI-AKI
Screening for pre-existing impairment of kidney function A CI-AKI Consensus Working Panel agreed that the risk of CI-AKI becomes clinically important when the baseline SCr concentration is >1.3 mg/dl (>115mmol/l) in men and >1.0 mg/dl (>88.4mmol/l) in women, equivalent to an eGFR 60 ml/min per 1.73 m2. Lameire N et al. Am J Cardiol2006;98:21K–26K.
The incidence of ‘‘true’’ AKI became significant only between controls and contrast-media administered patients from a baseline SCr concentration of >1.8 mg/dl (>159mmol/l) onward and eGFR < 45ml/min per 1.73m2.
Bruce RJ et al. AJR Am J Roentgenol 2009;192:711–718.
American Journal of Kidney Diseases,Vol 55, No 6 (June), 2010: pp 1018-1025
Renal Insufficiency and Diabetes Mellitus
Creatinine Clearance (mL/min)
CIN Requiring Dialysis
Non-Diabetic Diabetic
50 0.04% 0.2%
40 0.3% 2%
30 2% 10%
20 12% 43%
10 48% 84%
McCullough PA et al. Am J Med. 1997;103:368-375.
Am Heart J. 2010;160(6):1170-1177.
•The FDA recommends withdrawing metformin on the day of the test and reintroducing it in 2 to 3 days
N Engl J Med 2006;354:2773-82.
Assessment of the population at riskfor CI-AKI
Risk-factor questionnaire
RiskScore
Riskof CIN
Risk ofDialysis
≤ 5 7.5% 0.04%
6 to 10 14.0% 0.12%
11 to 16 26.1% 1.09%
≥ 16 57.3% 12.6%
Mehran et al. JACC 2004;44:1393-1399.
Hypotension
IABP
CHF
Age >75 years
Anemia
Diabetes
Contrast media volume
Risk Factors5
5
5
4
3
3
Integer Score
1 for each 100 cc3
Scheme to Define CIN Risk Score
Serum creatinine > 1.5mg/dl 4
eGFR <60ml/min/1.73 m22 for 40 – 604 for 20 – 406 for < 20
eGFR < 60ml/min/1.73 m2 =186 x (SCr)-1.154 x (Age)-0.203
X (0.742 if female) x (1.210 if African American)
Calculate
OR
Nonpharmacological prevention strategies of CI-AKI Pharmacological prevention strategies of CI-AKI
PREVENTION
Nonpharmacological prevention strategies of CI-AKI
KDIGO 2012
4.2.2: Consider alternative imaging methods in patientsat increased risk for CI-AKI. (Not Graded)
Nonpharmacological prevention strategies of CI-AKI
4.3.1: Use the lowest possible dose of contrast medium in patients at risk for CI-AKI. (Not Graded)
4.3.2: We recommend using either iso-osmolar or low-osmolar iodinated contrast media, rather than high-osmolar iodinated contrast media in patientsat increased risk of CI-AKI. (1B)
KDIGO 2012
Maximum Radiographic Contrast Dose (MRCD)
Determine "maximum allowed contrast dose" for Coronary Angiography according to the following formula:
5cc x kg body weight/creatinine
Nyman U et al .Acta Radiol2008;49:658–667
g-I (grams iodine)/eGFR ratio
In patients undergoing coronary angioplasty calculated the probability of CI-AKI at various eGFR levels based on g-I (grams iodine)/eGFR ratios.
At a ratio< 1, the risk of CI-AKI was 3%, while it was 25% at a ratio>1.
Nyman U et al .Acta Radiol2008;49:658–667.
This, and other preliminary studies, indicate that a g-I/GFR ratio < 1 may be relatively safe in a patient without multiple risk factors.
Heinrich et al. Radiology 2009;250:68-86
Heinrich et al. Radiology 2009;250:68-86
Pharmacological prevention strategies of CI-AKI
4.4.1: We recommend i.v. volume expansion with either isotonic sodium chloride or sodium bicarbonate solutions, rather than no i.v. volume expansion, in patients at increased risk for CI-AKI. (1A)
KDIGO 2012
4.4.2: We recommend not using oral fluids alone in patients at increased risk of CI-AKI. (1C)
FLUID ADMINISTRATION
Most studies suggest that the fluids should be started at least 1 h before and continued for 3–6 hours after contrast-media administration.
A ‘‘good’’ urine output (>150 ml/h) in the 6 hours after the radiological procedure has been associated with reduced rates of AKI.
In order to achieve a urine flow rate of at least 150 ml/h > 1.0–1.5 ml/kg/h of i.v. fluid has to be administered for 3–12 hours before and 6–12 hours after contrast-media exposure.
Stevens MA et al .J Am Coll Cardiol1999;33:403–411.
FLUID ADMINISTRATION
Sodium Bicarbonate SolutionsFLUID ADMINISTRATION
Reactive oxygen species activate cytokine-induced inflammatory mediators, resulting in damage to proximal tubular cells.
Sodium bicarbonate infusion may decrease generation of free radicals mediated by the Haber-Weiss reaction by increasing tubular pH.
The Work Group concluded that there is a possible but inconsistent benefit of bicarbonate solutions based on overall moderate-quality evidence.
Merten et al. JAMA 2004;291:2328–2334.
Sodium Bicarbonate
Study N (Saline, Bicarb)
Procedure Baseline Function
(mL/min/1.73m2)
Fluid protocol CIN rate (%)
p
RANDOMIZEDBrar 353
(175, 178)Cardiac 48
48SalineBicarbonate
13.613.5
0.97
Briguori 219(108, 111)
Cardiac Peripheral
3235
SalineBicarbonate
9.91.9
0.02
Merten 119 (59, 60)
Cardiac Peripheral
4541
SalineBicarbonate
13.71.7
0.02
Masuda* 59(29, 30)
Emergency cardiac
3940
SalineBicarbonate
357
0.01
NON-RANDOMIZEDCARE 414
(246, 168)Cardiac 50
50Bicarbonate (-NAC)Bicarbonate (+NAC)
10.6
11.9
NS
ROLE OF NAC IN THE PREVENTION OF CI-AKI
4.4.3: We suggest using oral NAC, together with i.v. iso-tonic crystalloids, in patients at increased risk of CI-AKI. (2D)
KDIGO 2012
Pharmacological prevention strategies of CI-AKI
NAC might reduce the nephrotoxicity of contrast through antioxidant and vasodilatory effects. Fishbane S et al. J Am Soc Nephrol 2004;15:251–260.
Combination studies of NAC with bicarbonate administration have found a moderate benefit for this combination, compared to the combination of NAC-saline.
The overall benefit of NAC is not consistent or overwhelming. On the other hand, oral NAC has a low risk of adverse events and usually a low cost.
ROLE OF NAC IN THE PREVENTION OF CI-AKI
Briguori C et al.Circulation2007;115:1211–1217
N= 90578
Effects of hemodialysis or hemofiltration
4.5.1: We suggest not using prophylactic intermittent hemodialysis (IHD) or hemofiltration (HF) for contrast-media removal in patients at increased risk for CI-AKI. (2C)
KDIGO 2012
NSF: Speculative Pathogenesis
cF, circulating fibrocyte; Cyto, cytokinesPerazella MA. Clin J Am Soc Nephrol. 2007;2:200-202.
1
2
3
4 5
NSF: Clinical appearance
Occurs days to many months after exposure to GBCA
Marckmann P et al. Clin Nephrol. 2008;69:161-168
