Contrast-Induced Nephropathy: Prevention and Management
Michael A. Bettmann
Contrast-induced nephropathy (CIN) may occur after administration of any iodine-based contrast agent. Its importance is not that it leads to the need for temporary or permanent renal replacement therapy (i.e., dialysis—on the order of 1% even in those at risk) but rather that it is associated with increased all-cause morbidity and mortality (1,2,3,4). The incidence depends on risk factors and the definition of CIN. The incidence of CIN approaches zero in patients with truly normal renal function (glomerular filtration rate [GFR] >90 mL/min/1.73m2). In patients with stage 4 or 5 chronic kidney disease (CKD) (GFR <30), the incidence may be as high as 20% to 40%, in part as a function of contrast volume and associated risk factors. Arriving at an accurate definition of incidence is difficult for several reasons, in addition to the factors noted above. For example, particularly among hospitalized patients, there are many nephrotoxic risk factors other than contrast administration: age (related to decreased muscle mass), surgery, hypotension, congestive heart failure (CHF), and many medications. It is often difficult, therefore, to be certain that a specific occurrence of transient worsening of renal function is actually solely or even primarily related to contrast administration. Currently, criteria for the diagnosis of CIN vary widely. Until the pathophysiology is completely understood, however, prevention will not be completely effective. Both the risk for and the occurrence of CIN are best defined and evaluated by using an estimated GFR (eGFR). Although the overall accuracy of the eGFR may be limited, it remains a better indicator of both baseline risk and of the course of CIN than serum creatinine alone. The reader is directed to the e-book for an in depth discussion of this topic.
Diagnosis
CIN is defined most often as a 25% or 50%, or a 0.5 mg per dL increase in serum creatinine, or a 25% or greater decrease in eGFR. The best approach to making a clinically relevant diagnosis of CIN is nonetheless to obtain a baseline serum creatinine and eGFR, followed in those at risk by a serum creatinine at 24 and/or 48 hours, with repeated measurements for 7 to 14 days if an initial elevation is seen (5,6,7,8). Although a rise in serum creatinine at 24 hours has been shown to be the single best predictor for CIN currently, because there are normal day-to-day variations in serum creatinine, a single such measurement may not be either sufficiently sensitive or sufficiently accurate.
Natural History
In most cases, CIN is characterized by an increase in serum creatinine over 1 to 7 days after contrast administration, with a return to baseline renal function by 2 to 4 weeks. Development of end-stage renal disease is rare, even in patients with significantly compromised renal function (CKD grade 3 or worse, that is, GFR <60) (9).
Risk Factors
1. In patients with truly normal renal function (i.e., not just normal serum creatinine but also normal eGFR of >90 mL/min/1.73m2) the risk is very low, probably even absent. See the caveat later, however, regarding acute changes in renal function due to changes in renal perfusion.
2. Patients with preexisting renal dysfunction are at risk. Risk is very limited in patients with stage 1 or 2 CKD (GFR ˜60-89). Although it is logical to think that the risk increases with increasing dysfunction, it is not clear that this is true. The reason is that it is likely that numerous other risk factors play a role in the incidence and severity of CIN (e.g., nephrotoxic medications, poor cardiac output).
3. The risk is increased roughly by a factor of 2 in patients with diabetes mellitus (10). Again, the risk appears to be confined to those with CKD stage 3 or worse (GFR <60). This risk has been shown almost solely in patients with type I diabetes; the risk among the increasing population with type II diabetes is not clearly defined. There is likely to be an increased risk, as a function of the duration and severity of the diabetes.
4. Increasing age also is a risk factor, again only in those with compromised renal function. It is important to remember that renal function normally decreases with age, as reflected in both true GFR and eGFR but not necessarily in serum creatinine.
