Slide 2 Prevention of Contrast-Induced Nephropathy (CIN) Sepehr
Khashaei, MD Assistant professor Department of Internal Medicine
Slide 3 What will be covered today? Definition of CIN Why is
prevention of CIN important? Some other information/statistics
about CIN Who is at high risk for CIN? Information and conclusions
based on outcomes from clinical trials Simple measures for
prevention Cost to patients. References. Questions and discussion.
Slide 4 Please save all your questions and discussions for the end.
Slide 5 Definition of CIN CIN is defined as an increase in baseline
serum creatinine level of 25% or an absolute increase of 0.5 mg/dL,
2 to 5 days after radiocontrast administration. Slide 6 Why is
prevention of CIN important? Radiocontrast administration is a
common cause of hospital-acquired acute renal failure (10% of
cases). In its severe form, CIN is associated with clinically
significant morbidity and mortality, including prolonged
hospitalization, requirement for dialysis, and an increased risk
for death. CIN increases the costs of medical care by at least
extending the hospital stay. There is no specific treatment once
CIN develops, and management must be as for any cause of ATN, with
focus on maintaining fluid and electrolyte balance. The best
treatment of CIN is prevention. Slide 7 Some other
information/statistics about CIN Individuals with pre-existing
renal insufficiency and diabetes are much more likely to experience
contrast-induced nephropathy. Typically, serum creatinine levels
begin to increase at 48-72 hours, peak at 3 to 5 days, and return
to baseline within another 3-5 days. In most cases there is no
permanent sequelae. Slide 8 Some data from 2004 More than a million
radiocontrast procedures were performed annually. Incidence of CIN
was 150,000/yr. 1% of CIN required dialysis and caused prolongation
of hospital stay to an average of 17 days. For episodes that did
not require dialysis, there was prolongation of hospital stay by 2
days on an average. Slide 9 Total CT scans with contrast done in
2009 at all UNM facilities where 18,350. Slide 10 Who is at high
risk? Patients with GFR 1.0 for a female and >1.3 for a male as
definition of a high risk patient. Slide 11 Proposed interventions
studied in literature Saline hydration Diuretics Mannitol
Intravenous bicarbonate Saline plus Mannitol Saline plus diuretics
Oral hydration Calcium channel antagonists (i.e. nifedipine)
Theophylline Endothelin receptor antagonists Dopamine Fenoldopam
(dopamine-1 receptor) Antioxidant N-acetylcysteine Iso-osmolar or
low-osmolal contrast agents Hemodialysis Hemofiltration Use of MRI
in place of CT Atrial natriuretic peptide Statins Ascorbic acid
Slide 12 Simple measures for prevention The use of lower doses of
contrast. Avoidance of repetitive contrast studies that are closely
spaced (within 48-72 hours). Avoidance of volume depletion
Avoidance of NSAIDS Avoidance of nephrotoxic drugs Slide 13
Information and conclusions based on outcomes from clinical trials
Slide 14 Patients with near-normal kidney function are at little
risk for CIN (about 3%) and few precautions are necessary other
than avoidance of volume depletion. Slide 15 The patients at
increased risk for contrast- induced nephropathy are diabetics
(especially insulin-dependent diabetics) and patients with
underlying renal insufficiency (12-50% incidence). Slide 16 The
effects of poor hydration and the volume of contrast medium
administered are less clear but are possible risk factors. Slide 17
Risk factors may be additive. Slide 18 The risk for CIN does not
appear to be influenced by the patients age or sex. Slide 19
Absence of risk factors does not preclude the development of CIN.
Slide 20 Although theoretically beneficial, there is little
evidence in support of vasodilators (such as nifedipine, captopril,
prostglandin E, low-dose dopamine, fenoldopam, endothelin receptor
antagonists, and theophylline) in reducing risk of CIN. Slide 21
Infuse NS (Grade 1B) at a rate of 1ml/Kg per hour starting at least
two and preferably 6-12 hours prior to the procedure, and
continuing for 6 to 12 hours after contrast administration. The
duration of administration of fluid should be directly proportional
to the degree of renal impairment (e.g., should be longer for
individuals with more severe renal impairment). Dose should be
adjusted depending on patients underlying medical condition and
their level of hydration. Hydration with NS was superior to 1/2NS
at least in one clinical trial. Slide 22 Intravenous hydration is
superior to oral hydration. Oral hydration with water alone should
not be used. Slide 23 Use, if possible, ultrasonography, MRI
without gadolinium contrast, or CT scanning without radiocontrast
agents. Slide 24 Based on limited literature, it is difficult to be
certain that gadolinium used in MRI scanning is completely free of
nephroxicity in high-risk patients. Also, gadolinium-based imaging
should not be performed, if at all possible, in patients with
GFRSlide 25 Oral acetylcysteine administed as 1200mg twice daily
the day before and the day after the procedure (Grade 2B). Do not
use iv acetylcysteine for prevention of CIN (Grade 2B). Slide 26 Do
not use mannitol or other diuretics prophylactically (Grade 1B).
However, diuretics may be required to treat volume overload. Slide
27 Do not use high osmolal agents (1400 to 1800 mosmol/KG) (Grade
1A). Slide 28 Use nonionic isoosmolar agents such as iodixanol
(Visipaque) or nonionic low-osmolal agents such as iopamidol
(Isoview) (Grade 1B) if a contrast study is necessary. Slide 29 Low
or iso-osmolar nonionic contrast Decreased incidence of CIN. Cost
reductions Increased patient tolerability Decreased
hypersensitivity reactions The benefit is higher in diabetics with
renal insufficiency Now administered for the majority of radiologic
procedures that use iv contrast media. There appears to be little
or no advantage in the prevention of CIN when compared to ionic
hyperosmolar agents in patients with normal renal function. At UNM
we use iopamidol (a low-osmolar non-ionic agent) on all adults who
have contrast studies regardless of their GFR. Slide 30 Among
patients with stage 3 and 4 CKD do not perform prophylactic
hemofiltration (see below) or hemodialysis (Grade 1B).
Hemofiltration is expensive, logically cumbersome and associated
with significant risks, its effectiveness compared to other less
expensive strategies is not well established, and the reported
benefits are implausible. Therefore currently prophylactic
hemofiltration is not recommended. Slide 31 Among patients with
stage 5 CKD, most suggest hemodialysis after contrast exposure if
there is already a functioning access (Grade 2C) (although there is
lack of sufficient data). Do not place a temporary access for
prophylactic hemodialysis in these patients. Slide 32 The
effectiveness of sodium bicarbonate treatment to prevent CIN
remains uncertain. Earlier reports probably overestimated the
magnitude of any benefit, whereas larger, more recent trials have
had neutral results. Large multicenter trials are required to
clarify whether sodium bicarbonate has value for prevention of CIN
before routine use can be recommended. Slide 33 Cost to patients
One bag of NS (1000cc) = $40.00 1200mg of acetylcysteine = $5.00
One day on 4-W = $5,489 (Medicine Subacute) One day on 4-E = $7,129
(Med/surg Subacute) One day on 4-S = $6, 863 (Orthopedics) One day
on 5-W = $ 4,049 (General Medicine) One day on 5-S = $6,152
(NeuroScience) One day on 6-S = $7,580 (General Surgery) One day on
7-S = $8,517 (Cardiothoracic) One day on Medical ICU = $7,747 Slide
34 References 1.Asif, A, Epstein, M. Prevention of
Radiocontrast-Induced Nephropathy. AM J Kidney Dis 2004; 44:12-24
2.Rudnick, M, Feldman, H. Contrast-Induced Nephropathy: what are
the true clinical consequences?. Clin J Am Soc Nephrol 2008; 3:263.
3.Rudnick, MR, Goldfarb, S, Wexler, L, et al. Nephrotoxicity of
ionic and nonionic contrast media in 1196 patients: A randomized
trial. Kidney Int 1995; 47:254. 4.Barrett, BJ. Contrast
nephrotoxicity. J Am Soc Nephrol 1994; 5:125 5.Shwab, SJ, Hlatky,
MA, Pieper, KS, et al. Contrast nephrotoxicity: a randomized
controlled trial of a nonionic and an ionic radiographic contrast
agent. N Engl J Med 1989; 320:149. 6.Solomon, R, Werner, C, Mann,
D, et al. Effects of saline, mannitol, and furosemide on acute
decreases in renal function induced by radiocontrast agents. N Engl
J Med 1994; 331: 1416. Slide 35 7.Weisbord, SD, Palevsky, PM.
Prevention of contrast-induced nephropathy with volume expansion.
Clin J Am Soc Nephrol 2008; 3:273. 8.Taylor, AJ, Hotchkiss, D,
Morse, RW, McCabe, J. PREPARED: Preparation for Angiography in
Renal Dysfunction: a randomized trial of inpatient vs outpatient
hydration protocols for cardiac catheterization in mild-to-moderate
renal dysfunction. Chest 1998; 114:1570. 9.Kshirsagar, AV, Poole,
C, Mottl, A et al. N-acetylcysteine for prevention of radiocontrast
induced nephropathy: a meta-analysis of prospective controlled
trials. J Am Soc Nephrol 2004; 15:761. 10.Alonso, a, Lau, J, Jaber,
BL, Weintraub, A. Prevention of radiocontrast nephropathy with
N-acetylcysteine in patients with chronic kidney disease: a
meta-analysis of randomized controlled trials. Am J Kidney Dis
2004; 43:1. 11.Gonzales, DA, Norsworthy, KJ, Kern, SJ, et al. A
meta-analysis of N- acetylcysteine in contrast-induced
nephrotoxicity: unsupervised clustering to resolve heterogeneity.
BMC Med 2007; 5:32. 12.Trivedi, H, Daram, S, Szabo, A, et al.
High-dose N-acetylcysteine for the prevention of contrast-induced
nephropathy. Am J Med 2009; 122:874. Slide 36 13.Klarenbach, SW,
Pannu, N, Tonelli, MA, Manns, BJ. Cost- effectiveness of
hemofiltration to prevent contrast nephropathy in patients with
chronic kidney disease. Crit Care Med 2006; 34:1044. 14.Lee, PT,
Chou, KJ, Liu, CP, et al. Renal protection for coronary angiography
in advanced renal failure patients by prophylactic hemodialysis. A
randomized controlled trial. J Am Coll Cardiol 2007; 50:1015.
15.Ledneva, E, Karie, S, Launay-Vacher, V, et al. Renal safety of
gadollinium-based contrast media in patients with chronic renal
insufficiency. Radiology 2009; 250:618. 16.Kurnik, BR, Allgren, RL
Genter, FC, et al. Prospective study of atrial natriuretic peptide
for the prevention of radiocontrast-induced nephropathy. Am J
Kidney Dis 1998; 31:674. 17.Patti, G, Nusca, A, Chello, M, et al.
Usefulness of statin pretreatment to prevent contrast-induced
nephropathy and to improve long-term outcome in patients undergoing
percutaneous coronary intervention. Am J Cardiol 2008; 101:279.
18.Briguori, C, Airoldi, F, DAndrea, D, et al. Renal Insufficency
Following Contrast Media Administration Trial (REMEDIAL): a
randomized comparison of 3 preventive strategies. Circulation 2007;
115:1211. Slide 37 19. Zoungas, S, Ninomiya, T, Huxley R, et al.
Systemic review: sodium bicarbonate treatment regimens for the
prevention of contrast-induced nephropathy. Ann Inern Med. 2009 Nov
3; 151 (9): 631-8 20. Stone GW, McCullough PA, Tumlin JA, et al:
Fenoldopam mesylate for prevention of contrast-induced nephropathy:
a randomized controlled trial. CONTRAST Investigators. JAMA
290:2284-2291,2003. 21. Kuhn, K, Chen, N, Dushyant, VS, et al: The
PREDICT study: A randomized double-blind comparison of
contrast-induced nephropathy after low- or isoosmolar contrast
agent exposure. AJR 191: 151-157, July 2008. 22. Lautin, EM,
Freeman, NJ, et al: Radiocontrast-associated renal dysfunction:
incidence and risk factors. AJR 157: 49-58, July 1991. Slide 38
Questions and discussion
