Hydration for contrast induced nephropathy
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Transcript of Hydration for contrast induced nephropathy
Hydration for Contrast-Induced Acute Kidney Injury (CI-AKI) Prevention
Wisit Cheungpasitporn
August 8, 2014
Disclosure• None
Definition and frequency of CI-AKI
Lameire NH. Nephrol Dial Transplant. 2006 Jun;21(6):i11-23.
Definition in number of trials
Lameire NH. Nephrol Dial Transplant. 2006 Jun;21(6):i11-23.
CI-AKI: Definition
• An increase in SCr generally occurs within 3 days after contrast exposures (in a minority of cases, the peak increase of SCr may occur up until 5 days).
• Definition varies, increase in Cr of >25% from baseline and/or ≥0.5 mg/dL after 48 hrs is widely used in the literature.
• Individuals with increases of SCr compatible with the definition of AKI after administration of contrast media be also evaluated for other possible causes of AKI.
KDIGO Clinical Practice Guideline for Acute Kidney Injury 2012
CI-AKI: Incidence
• The reported incidence varies depending on risk factors, the amount and type of contrast, and the type of radiologic procedure.
• Among patients who have no risk factors, the risk of contrast nephropathy is negligible (ie, ≤1%).
• Among high risk patients (especially those with diabetes and CKD), the reported risk following percutaneous angiography with or without intervention is 10 to 20%.
Solomon RJ et. al. Clin J Am Soc Nephrol 2009; 4:1162.
Factors involved in CI-AKI pathogenesis
?Not well understood
Dangas G et al. Am J Cardiol. 2005;95:13-19.
Risk factors for CI-AKI• Patient-related
• Renal insufficiency • Diabetes mellitus• Intravascular volume depletion• Reduced cardiac output• Concomitant nephrotoxins
• Procedure-related• ↑ volume of radiocontrast• Multiple procedures w/i 72 hours• Intra-arterial administration• Type of radiocontrast
} additive risk
McCullough PA et al. Am J Med. 1997;103:368-375.
Risk models
McCullough et al. Am J Cardiol 2006
Mehran Risk Score for CIN post PCI
.
Mehran et al. JACC 2004
Weisbord SD et al. Clin J Am Soc Nephrol. 2013 Sep;8(9):1618-31.
• CCB
• Loop diuretics*
• Mannitol*
• Dopamine*
• Fenoldopam*
• ANP
• Hemodialysis*
• NAC
• Theophylline
• Aminophylline
• Ascorbic acid
• Statins
• Hemofiltration
• IVF• Choice of
contrast
Ineffective EffectiveUnclear benefit
* Possibly harmful
Preventive strategies for CI-AKIPreventive strategies for CI-AKI
Weisbord SD et al. Clin J Am Soc Nephrol. 2013 Sep;8(9):1618-31.
Contrast AgentsNameName TypeType Iodine Iodine
ContentContentOsmolalityOsmolality
IonicIonic Diatrizoate (Hypaque 50)Diatrizoate (Hypaque 50) Ionic Ionic MonomerMonomer
300300 15501550 High High OsmolarOsmolar
Metrizoate (Isopaque Metrizoate (Isopaque Coronar 370)Coronar 370)
IonicIonic 370370 21002100
Ioxaglate (Hexabrix)Ioxaglate (Hexabrix) Ionic dimerIonic dimer 320320 580580 Low Low OsmolarOsmolar
Non-Non-IonicIonic
Iopamidol (Isovue 370)Iopamidol (Isovue 370) Non-ionic Non-ionic monomermonomer
370370 796796
Iohexal (Omnipaque 350)Iohexal (Omnipaque 350) Non-ionicNon-ionicmonomermonomer
350350 884884
IopromideIopromide Non-ionicNon-ionicmonomermonomer
Iodixanol (Visipaque 320)Iodixanol (Visipaque 320) Non-ionic Non-ionic dimerdimer
320320 290290 Iso Iso OsmolarOsmolar
Pannu N et. al. JAMA 2006; 295:2765.
Clinical trials of volume Clinical trials of volume expansionexpansion
• 1994 → present
• Provide clinical basis for:• Protective effect of IVF• Deleterious effect of furosemide• Superiority of isotonic IVF• Superiority of IVF to pt-directed oral
fluids• Potential benefit of oral NaCl
Rate of CIN: 11% 28% 40%
Solomon R et al. N Engl J Med. 1994;331:1416-1420.
RCT 78 patients
Isotonic v. hypotonic saline Isotonic v. hypotonic saline
Mueller C, et al. Arch Int Med. 2002; 162:329-336
RCT 1,620 patients
Elective+emergency PCILow osmolar non-ionic contrast
Saline vs. Bicarbonate IV fluidSaline vs. Bicarbonate IV fluid
13.6%
1.7%
0%
2%
4%
6%
8%
10%
12%
14%
NaCl (n=59) NaHCO3(n=60)
rate of CIN
(8/59)
(1/60)
Merten et al. JAMA 2004;291:2328-2334
P = 0.02
RCT 119 patients
All procedures with contrast exposureLow osmolar non-ionic contrastPatients with Creatinine > 1.1 mg/dL
Weisbord SD et al. Clin J Am Soc Nephrol. 2013 Sep;8(9):1618-31.
Weisbord SD et al. Clin J Am Soc Nephrol. 2013 Sep;8(9):1618-31.
KDIGO 2012: CI-AKI
KDIGO Clinical Practice Guideline for Acute Kidney Injury 2012
KDIGO 2012: CI-AKI
KDIGO Clinical Practice Guideline for Acute Kidney Injury 2012
Brar SS et. al. Lancet. 2014 May 24;383(9931):1814-23.
LEFT VENTRICULAREND DIASTOLIC PRESSURE
( LVEDP )
What does LVEDP mean anyway?
• LVEDP is the left ventricular end-diastolic pressure, and serves as a measure of the pre-load and thus that of circulating blood volume.
• Direct measurement of LVEDP is routinely performed during cardiac catheterization.
Kern MJ. The Cardiac Catheterization Handbook, 5th ed2011
Clinical Measurement of Preload
• LVEDP is measured just before the start of the systole ( i.e : End of the diastole )
• LVEDP; normal = 4 - 12 mmHg• Cardiogenic pulmonary edema: LVEDP ≥ 18 mmHg
Kern MJ. The Cardiac Catheterization Handbook, 5th ed2011
Brar SS et. al. Lancet. 2014 May 24;383(9931):1814-23.
Objective
• To investigative different rates of fluid administration guided by the LVEDP to prevent CI-AKI in patients undergoing cardiac catheterization.
ParticipantsInclusion criteria
• ≤ GFR* 60 ml/min/1.73 m2
• ≥ 18 years
And at least one of the following
• DM
• CHF
• HTN
• Age ≥ 75 years
Exclusion criteria
• No consent
• Emergency cardiac catheterization
• RRT
• Exposure to contrast within 2 days
• Contrast allergy
• Acute decompensated HF
• Severe valvular disease
• Mechanical aortic prosthesis
• LV thrombus
• Hx of kidney or heart Tx
• Change in eGFR ≥ 7.5%/d or a cumulative change ≥ 15% during the preceding 2 days
* GFR was calculated using MDRD formula
Intervention – Fluid therapy
Standard hydration
3 ml/kg in 1 hour before procedure
Measure LVEDP
Randomization(1:1 ratio)
LVEDP-guided hydration
LVEDP •< 13 5ml/kg/h•13-18 3ml/kg/h•> 18 1.5 ml/kg/h
Fluid - NSS
1.5 ml/kg/h
Fluid started right before procedure and continued until 4 hours after procedure
Intra-arterial ioxilan (350 mg iodine/ml)
Non-ionic, low – osmolar
Randomization and masking• Stratified by DM status and NAC use
• NAC use • 600 mg twice daily for 2 days• Starting the day before index procedure • Use was at the discretion of the physician.
• Permuted block sized of 4
• Partly blinded• Patient masked• Lab personnel masked• Physician not masked
Outcomes
• Primary endpoint• ≥ 25% or 0.5 mg/dl increase in the SCr• Only patients with ≥ 2 SCr values between day 1-4 were included• Calculated with a baseline value obtained before procedure
and the highest post-procedure value on days 1-4
• Secondary endpoint• Components of primary endpoint• Occurrence of major adverse events
• A composite of all-cause mortality, MI, and RRT at 30 days and 6 months
• Safety endpoint• Clinical sequelae of fluid administration and LVEDP measurement• All adverse events were confirmed by personnel who were
masked to treatment assignment
Post-hoc analysis
• Rate of contrast-induced AKI• Increase in SCr ≥ 0.3 mg/dl
• The frequency of persistent renal impairment• ≥ 15% increase in SCr above baseline• SCr samples were obtained 2-8 weeks after the index procedure
and the 1st SCr value during this period was used in analysis
Statistical analysis
• Primary outcome• Relative risk, absolute risk reduction, number needed to treat
• Power calculation• Superiority trial• 18% in control group and 8% in LVEDP• 390 patients needed for 80% power and a two-sided alpha of 0.05
Outpatient/ambulatory procedure-58% overall-61% in LVDP-guided group -56% in control group P = 0.29
1727 (583) 812 (142)
P < 0.001
Incidence of contrast-induced AKI 11.4%NNT = 11 for LVEDP-guided treatment
No significant interaction between treatment assignment by subgroup
Result: contrast-induced AKI
Outcomes LVEDP –guided hydration
Control RR (95% CI) P-value
Contrast-induced AKI
5/60 (8%) 14/61 (23%) 0.36 (0.14-0.95)
0.03
In patients GFR ≤ 45 ml/min/1.73 m2
NNT = 7
Result: contrast-induced AKI
LVEDP level LVEDP- guided Control RR (95% CI) P-value
< 18 mmHg 8/152 (5.3%) 21/146 (14.4%) 0.37 (0.17-0.80)
0.008
≥ 18 mmHg 4/26 (15.4%) 7/26 (26.9%) 0.57 (0.19-1.72)
0.31
Result: contrast-induced AKI
Volume of NSS received Rate of contrast-induced AKI
Tertile 1 (448-874 ml) 20/117 (17%)
Tertile 2 (874-1512 ml) 13/117 (11%)
Tertile 3 (1512-3055 ml) 7/116 (6%)
OR = 0.91 (95% CI 0.89 – 0.94); P = 0.01 for every additional 100 ml of NSS administered
P = 0.03
Increasing volume of NSS administered were associated with reduced rates of contrast-induced AKI
Result: persistent renal impairment
Outcome LVEDP- guided Control RR (95% CI) P-value
Persistent renal impairment
6/178 (3.4%) 12/172 (7.0%) 0.48 (0.19-1.26)
0.13
Outcome LVEDP- guided Control RR (95% CI) P-value
Persistent renal impairment
6/12 (50%) 12/27 (44%) 1.13 (0.56-2.28)
0.75
patients who developed contrast-induced AKI – persistent renal impairment occurred in 46%
NNT for LVEDP for prevention of one major adverse event at 6 mo = 16
Result
At 6 month Contrast-induced AKI
No contrast-induced AKI
RR (95% CI)
P-value
All-cause mortality
higher 0.002
Myocardial infarction
higher 0.02
Need for RRT higher <0.001
Cumulative major adverse event
10/40 (25%) 11/310 (3.5%) 7.1 (3.2-15.5) <0.001
Result- Safety
• 6 patients terminated the IV fluid early due to SOB• 3 in LVEDP-guided LVEDP 3, 7 and 26 mmHg• 3 in control LVEDP 3, 23 and 31 Hg
• No ventricular arrhythmias or other complication associated with LVEDP measurements reported
Result
Outcome Risk ratio (95% CI)
Contrast-induced AKI OR = 0.37 (0.18-0.74)Adjusted OR = 0.40 (0.19-0.81)
Major adverse events at 6 months
HR = 0.31 (0.13-0.78)Adjusted HR = 0.35 (0.14-0.89)
*adjusted for history of CHF and PCI status
Discussion
• Pts with stable renal insufficiency undergoing cardiac catheterization and followed up for 6 months:
• LVEDP-guided fluid administration as compared with standard treatment resulted in 68% relative reduction in CI-AKI, and 59% relative reduction in major adverse clinical events.
Discussion
• LVEDP group was able to receive roughly twice the volume of NSS with a similar rate of fluid termination than the control group.
• Despite more IV fluid with LVEDP-guided therapy than with standard hydration, IV fluids were terminated at a similarly low rate in both study groups, which suggests that higher rates can be tolerated.
Discussion
• Pts with CI-AKI had a 7-fold increase in the rate of the composite major adverse events endpoint, and a significant increase in each of the components including death, MI, and RRT.
• These findings emphasize the importance of longer term follow-up in patients with CI-AKI.
• The study population was at a moderate to high risk of CI-AKI • all patients had eGFR ≤ 60 mL/min/ 1.73 m2 and one additional CI-
AKI risk factor
Limitations
• The study was single-blinded (patients, and not investigators) which is understandable as the rate of fluid infusion would be difficult to mask.
• Patients with acute decompensated heart failure or severe valvular heart disease were excluded from the study.
• LVEDP assessment of intravascular volume status, it is only available in patients undergoing cardiac catheterization.
Conclusion
• IV NSS guided by LVEDP is well tolerated and could substantially reduce the incidence of CI-AKI and major adverse clinical events in patients undergoing cardiac catheterization.
My ConclusionMore IV fluid is better!!!
PRESERVE
Weisbord SD et al. Clin J Am Soc Nephrol. 2013 Sep;8(9):1618-31.
Questions & Discussion