Page 1348 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

CHAPTER 97: Acute Kidney Injury 921

cardiovascular events. The mortality is higher in patients who develop However, further doubt has been cast over these inconsistent findings
severe CI-AKI requiring dialysis compared to those not requiring by emerging experimental data that suggest that the apparent efficacy of
dialysis. In a study of 1896 patients undergoing coronary angiography, acetylcysteine in these studies may have been artifactual. Specifically, ace-
the hospital mortality was 7.1% in CI-AKI and 35.7% in patients who tylcysteine causes a decrement in serum creatinine (but not cystatin C)
required dialysis. 45 by a GFR-independent mechanism, perhaps by inhibiting creatinine
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The risk of nephrotoxicity due to contrast agents varies with the type phosphokinase function. In one of the largest randomized studies to
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and dose of agent. Low- or iso-osmolal agents are less nephrotoxic than date, involving 2308 patients assessing the utility of oral N-acetylcysteine
ionic high-osmolal agents. 46,47 The incidence of AKI due to radiocontrast to prevent CIN, the authors concluded that it did not lower the risk of
agents is less than 2% in patients with normal renal function, but is CI-AKI or other renal outcomes. However, the generalizability of this
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inversely related to GFR in patients with CKD; in high-risk patients the study may be limited; only 362 patients (15.7%) had a baseline serum
incidence is as high as 60%. There are several important risk factors for creatinine greater than 1.5 mg/dL, the median contrast volume was low
48
https://kat.cr/user/tahir99/
radiocontrast nephropathy, including CKD (the major risk factor; CI-AKI at 100 mL and there was imprecision regarding which patients received
is usually a form of AKI superimposed on CKD), diabetic nephropathy hydration and what volume was given. It may be more appropriate to
(see below), severe congestive heart failure, intravascular volume deple- conclude that N-acetylcysteine is not effective at preventing CI-AKI in
tion, high contrast dose, and multiple myeloma (Table 97-4). Of note, the low-risk groups; however, it may still have a role in preventing CI-AKI
risk of radiocontrast nephropathy at any GFR level in CKD is approxi- in patients at high risk.
mately double in diabetics compared to nondiabetics. The group at risk Other approaches such as vasodilation with dopamine or fenoldopam
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for radiocontrast nephropathy can be reliably identified, and a variety of failed to prevent radiocontrast nephropathy, and mannitol and furose-
prophylactic strategies have been used, several successfully. mide appeared to increase the rate of AKI postcontrast in one study.
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A number of measures are used for prevention of radio-contrast Prophylactic hemodialysis has not been shown to be beneficial in the
nephropathy. Alternative imaging approaches (ultrasound, noninfused prevention of contrast nephropathy. A recent meta-analysis looked at
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CT) are preferred to radiocontrast studies in patients with a high risk of nine randomized and two nonrandomized trials involving 1010 patients
radiocontrast nephropathy. Nonionic low-osmolal agents and nonionic who underwent RRT (hemodialysis or hemofiltration) to prevent
46
iso-osmolol agents are less nephrotoxic, and these agents are used to CI-AKI. RRT did not decrease CI-AKI incidence compared with stan-
47
decrease the incidence of AKI due to radiocontrast agents. Volume dard medical therapy (RR 1.02; 95% CI, 0.54-1.93). However, intertrial
expansion has been shown to reduce the incidence of CIN in a number heterogeneity was high. Limiting the analysis to trials involving hemo-
of studies, but the optimum solution and administration regimen has yet dialysis only (eight trials) reduced heterogeneity. Hemodialysis appeared
to be conclusively demonstrated. Isotonic saline (1 mL/kg per hour for to confer an increased risk of CI-AKI (RR 1.61; 95% CI, 1.13-2.28) and
12 hours pre- and postcontrast) was associated with a lower incidence of had no effect on need for permanent RRT or progression to ESRD (RR
CIN than a hypotonic saline regimen in a prospective randomized trial 1.47; 95% CI, 0.56-3.89). Since RRT is also expensive, associated with
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involving 1620 patients. It has been suggested that sodium bicarbonate a variety of risks, and a limited resource, we do not recommend this
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may be superior to normal saline, as urinary alkalinization may reduce approach to CI-AKI prevention.
free radical formation. The results of randomized controlled trials and A novel method of preventing CI-AKI is the RenalGuard system (PLC
meta-analyses have been variable with some reporting lower rates of Medical, Franklin, MA); a fluid management device which precisely
CIN and others equivalent rates. The largest meta-analysis published measures urine output and replaces the same amount of fluid intrave-
involved 14 trials and 2290 patients, but there was considerable clinical nously. The REMEDIAL II trial evaluated the effects of a forced diuresis
and statistical heterogeneity between trials (largely owing to variable induced by furosemide and replacement with saline as guided by the
trial size). Pooling the three large trials (1145 patients), there was no RenalGuard system. This strategy theoretically would reduce contrast
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difference between CI-AKI rates with sodium chloride or sodium bicar- exposure to tubular cells and increase its elimination. It evaluated the
bonate. The pooled relative risk of CI-AKI with sodium bicarbonate incidence of CI-AKI in 392 high-risk patients with an eGFR ≤30 mL/
was 0.50 (0.27-0.93) in the 12 smaller trials; however, these trials were of min. Patients randomized to the RenalGuard system achieved urinary
lower methodological quality. 50 flow rates of ∼350 mL/min. CI-AKI occurred in 30/146 (20.5%) of
In some studies, the administration of acetylcysteine, a thiol-containing patient in the control group (N-acetylcysteine and isotonic bicarbon-
antioxidant, in combination with saline hydration has been shown to ate solution) compared with 16/146 (11%) in the RenalGuard group
be beneficial in reducing the incidence of contrast nephropathy when (N-acetylcysteine, furosemide, and isotonic saline administration as
administered in various oral regimens (1200 mg once or 600 mg every controlled by the RenalGuard system), (OR, 0.47; 95% CI 0.24-0.92).
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12 hours before and after radiocontrast). 51-53 One successful study used However, concerns have been raised about the volume of fluid replace-
intravenous acetylcysteine for radiocontrast nephropathy prophylaxis. ment precipitating pulmonary edema in patients with cardiac dys-
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Although other studies did not show any benefit, a recent meta- analysis function, and the development of electrolyte abnormalities such as
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of eight randomized controlled trials involving 855 patients reported hypokalemia developing following diuretic use. Further research is
that the use of acetylcysteine reduced the risk of radiocontrast by 59%. required to determine the optimal approach to CI-AKI prevention.
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Nonsteroidal Anti-Inflammatory Drugs and Acute Renal Failure NSAIDs can cause
hemodynamically mediated AKI. Vasodilatory prostaglandins (prosta-
TABLE 97-4 Risk Factors for Radiocontrast Nephrotoxicity cyclin and prostaglandin E [PGE ]) are essential for the maintenance of
2
2
Preexisting renal failure renal blood flow and GFR in states of effective volume depletion, such as
congestive heart failure, cirrhosis of the liver, nephrotic syndrome, and
Diabetes mellitus
in states of true volume depletion. Prostaglandins counterbalance the
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Volume depletion effects of vasoconstrictors such as angiotensin II and catecholamines.
Previous contrast nephropathy NSAIDs inhibit prostaglandins and thus would lead to unopposed
effect of angiotensin II and catecholamines, leading to reduced GFR.
Multiple contrast procedures
Hyperkalemia may be prominent because NSAIDs impair renin secre-
High contrast dose (>2 mL/kg) tion. Patients with CKD are similarly at risk for NSAID-induced AKI,
Congestive heart failure because vasodilator prostaglandins maintain hyperfiltration in rem-
Elderly patient nant nephrons. Hemodynamically mediated AKI is seen within days
of taking NSAIDs in high-risk patients. Cyclooxygenase-2 (COX-2)
Multiple myeloma
selective drugs have the same renal effects as nonselective NSAIDs,

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