Letter by Malhotra et al Regarding Article, “Neurons Over Nephrons: Systematic Review and Meta-Analysis of Contrast-Induced Nephropathy in Patients With Acute Stroke”
To the Editor:
We thank the authors Brinjikji et al for their study on contrast-induced nephropathy (CIN) in acute stroke patients.1 The study concludes that iodinated contrast for computed tomographic (CT) angiography/CT perfusion does not increase the risk of acute kidney injury (AKI) in patients with acute stroke. We have a few observations and questions. Do the authors have an explanation as to why AKI incidence was lower in patients who received contrast as noted in the meta-analysis results (2.3 versus 6.3% in case-controlled studies)?
Preexisting renal dysfunction is the most important risk factor for development of CIN.2 Baseline creatinine is not reliable enough to identify patients at risk for CIN, and creatinine clearance is more reliable to assess renal function.3 Closer scrutiny of the case-controlled studies included in the analysis shows significant differences in the 2 subsets—not just in terms of baseline creatinine but also age and risk factors, such as hypertension, diabetes mellitus, and heart failure. Accounting for baseline creatinine at admission by meta-regression may not completely account for the selection bias with patients, with higher estimated glomerular filtration rate preferentially getting contrast.
There is significant variability in the definition of AKI among included studies. Studies measuring creatinine at 24 to 48 hours may not be truly reflective of the extent of renal injury because previous studies have shown that creatinine levels typically peak at 3 to 5 days after contrast administration.4
The incidence of CIN may be influenced by hydration status at presentation and during admission. Only 2 studies in the analysis specified standardized hydration protocols for patients receiving CT angiography/CT perfusion and none for the control arm.
We would also like to point out a few observations about some of the included studies:
Ehrlich et al: 56/157 patients in contrast arm did not have 24- to 48-hour creatinine values recorded.
Ang et al: 41.4% of included 623 patients had chronic kidney disease with median estimated glomerular filtration rate in the study population of 65. Fifteen of 16 cases who met criteria for CIN had confounding factors, such as dehydration, urinary tract infection, or medications.
Lima et al: higher incidence of AKI was noted in the control arm at 24 hours, but results were not different in the 2 arms at 72 hours.
Bill et al: biggest study included. CIN was defined as increase in creatinine over 24 hours.
Aulicky et al: the contrast group was from 2003 to 2007. The control arm was from 1999 to 2003. More than 20% had abnormal creatinine at baseline. Multivariate analysis showed C-reactive protein to be most predictive of creatinine increase at 24 to 72 hours, and C-reactive protein was higher in control arm (indicative of sepsis as per authors, although it is not specified how many patients had sepsis).
Mehdiratta et al: of the 63 patients in control arm, 11% (7/63) had baseline creatinine >1.5 mg/dL. Thirty-four percent of patients in the study had glomerular filtration rate <60.
Yeo et al: baseline chronic kidney disease was seen in 12% of the control population.
Luitse et al: renal dysfunction on admission was found in 21.2% of patients.
The conclusion that contrast used for CT angiography/CT perfusion is not associated with increased risk of AKI in patients with stroke should be taken with caution given the limitations of the included studies, some of which we have mentioned.
Ajay Malhotra, MD, MMM
Xiao Wu, BS
Long H. Tu, MD
Department of Radiology and Biomedical Imaging
Yale School of Medicine
New Haven, CT
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- © 2017 American Heart Association, Inc.
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- Demchuk AM,
- Murad MH,
- Rabinstein AA,
- McDonald RJ,
- McDonald JS,
- et al
- Mehran R,
- Nikolsky E
- McCullough PA,
- Sandberg KR