Aminoglycosides such as gentamicin can induce ATN in up to 20% of cases. Among the frequently used agents, amikacin may be less nephrotoxic than gentamicin or tobramycin.
The drugs accumulate in the renal proximal tubule cells and cause cellular necrosis.49 Risk factors for nephrotoxicity are advanced age, liver failure, renal failure, peak concentration, and volume depletion.49, 50
With aminoglycoside nephrotoxicity, the serum creatinine concentration starts to rise a week to 10 days after beginning treatment. The AKI often is accompanied by hypokalemia, hypomagnesemia, and a non-anion-gap metabolic acidosis.
Prevention of aminoglycoside-induced AKI is best achieved by minimizing drug exposure, single daily dosing (in patients with normal baseline renal function), frequent pharmacokinetic monitoring, and daily serum creatinine concentration.49
The time course of AKI in this case is incompatible with aminoglycoside nephrotoxicity.
Radiocontrast-induced nephropathy (RCIN) is the third most common cause of AKI in hospitalized patients.51 Its exact incidence is reported to be quite variable, and it depends on the stringency of the definition of AKI and the number and severity of risk factors prevalent in the population under consideration.52 Risk factors for RCIN are shown in Table 41-6.52, 53, 54, 55, 56, 57 The incidence of RCIN in patients with mild CKD is less than 5%,58, 59 and as high as 50% in patients with advanced CKD with diabetes mellitus.60 All other factors being equal, it appears to be less common with intravenous than intra-arterial radiocontrast administration.61, 62 One retrospective study, using a liberal definition of AKI, found a 3% incidence of radiocontrast-induced injury in unselected patients with acute stroke undergoing CT angiography; none of the patients in that study required renal replacement therapy (RRT).63
Table 41-6.Risk Factors for RCIN
After injection of iodinated contrast, the glomerular filtration rate falls immediately, but the consequent accumulation of creatinine in the blood may be slow enough that a change in serum creatinine concentration is not detectable for 24 or 48 hours. The serum creatinine concentration usually reaches a plateau within a few days to a week, followed by resolution in 2 to 4 weeks. About 10% of patients require RRT to manage the consequences of AKI64; however, permanent dialysis dependence solely as a consequence of RCIN is rare.
Because RCIN results from a discrete, premeditated event, it has been considered the paradigm for prevention (Table 41-7). Notwithstanding decades of research into its prevention, however, few interventions have shown convincing benefit.55, 65 The only surefire way to prevent RCIN is to avoid contrast administration. Short of that, only two interventions have proven unequivocally effective: intravenous fluids and manipulation of the radiocontrast agents.
Table 41-7.Preventive Measures for Minimizing the Risk of RCIN ||Download (.pdf) Table 41-7. Preventive Measures for Minimizing the Risk of RCIN
We recommend the following:
Avoid high-osmolality contrast agents
Minimize volume of contrast injected
Optimize the patient's volume status:
Volume expansion with 0.9% NaCl (1 mL/kg) starting up to 12 h before and continuing up to 12 h after (adjusted for volume status; see text)
Stop intravenous diuretics before the procedure
Stop COX inhibitors
We do not discourage the use of:
Intravenous administration of sodium chloride reduces the risk of RCIN. Normal (0.9%) saline seems to be more effective than half-normal (0.45%) saline, when administered at 1 mL/kg/h starting before the contrast injection and continuing for 24 hours.66 There has been debate as to whether sodium bicarbonate is more effective than normal saline for the prevention of RCIN. Studies to date have yielded conflicting results,67, 68 so there is no basis for recommending sodium bicarbonate. Decompensated congestive heart failure probably is just as great a risk for RCIN as volume depletion. Thus, intravenous saline must be used cautiously in patients with impaired heart or renal function, and should be avoided in patients who are already fluid overloaded. The use of intravenous furosemide before contrast administration has been shown to be deleterious,69 and this has led to the recommendation that even oral diuretics be held before contrast procedures.
The risk of RCIN appears to be related to the chemistry of the radiocontrast agent, its route of administration, and its dose. Radiocontrast agents vary according to their osmolality. Conventional high-osmolality agents have an osmolality of about 1200 mOsm/kg, and so-called low-osmolality agents about 600 mOsm/kg. The newest, iso-osmolar agents have an osmolality of about 300 mOsm/kg. There is little doubt that high-osmolality agents are more nephrotoxic than low-osmolality agents.70, 71 The additional benefits of iso-osmolar agents in this regard are unclear.72, 73 Recent studies have shown that intra-arterial rather than intravenous administration of contrast is associated with a greater risk of ARF.61, 62 Finally, the risk of RCIN in high-risk patients seems to be proportional to the volume of contrast administered.53
Other interventions intended to prevent RCIN have failed to show a consistent benefit. N-acetylcysteine (NAC, Mucomyst) showed great promise early on,74 but subsequent studies have been equivocal.75, 76, 77, 78 Because oral NAC appears to have little if any toxicity, its use in this setting cannot be strongly discouraged. Other interventions shown to be of no benefit for prophylaxis of RCIN include natriuretic peptides,79 dopaminergic agents,55 and cessation of ACE inhibitors or angiotensin receptor blockers.80 A single-center study on the use of prophylactic hemofiltration showed a reduction in 1-year mortality,81 an outcome of dubious relationship to the intervention, and one that does not justify routine use of this invasive modality. Because COX inhibitors predispose animals to RCIN,82 it is prudent to withhold them in patients about to receive a radiocontrast infusion.
In the present case, radiocontrast administration is very likely to have contributed to the development of nephrotoxic ATN. The additional probable cause is sepsis leading to ischemic ATN. This sort of multifactorial AKI is quite typical of critically ill patients.
In support of the diagnosis of ATN, the urinalysis shows a specific gravity of 1.010 and more than 5 granular casts per high-power field. The patient's urine volume fell steadily, and over the next few days he became anuric.