The increasing incidence of PVD often mandates use of contrasted procedures in the form of diagnostic angiography or angioplasty. CIN has been reported in up to 9.2% of patients undergoing peripheral angiography and contributes to increased length of hospital stay, morbidity and mortality [14].
We defined CIN as an increase in serum creatinine by > 26.5 umol/L within 48 hours of contrast exposure as per the KDIGO workgroup [15].
Renal biomarkers are reported to rise earlier than serum creatinine in AKI. Serum and urine NGAL, cystatin C, urinary retinol binding protein (RBP) have all been investigated to detect AKI early. [10,16,17]. Wang et al in a recent meta-analysis, which include 1520 patients undergoing coronary angiography found urine and plasma NGAL had a sensitivity and specificity of 84% and 89% respectively in predicting contrast induced AKI. They reported NGAL determined 4 hours after exposure to contrast was an excellent predictor of contrast-induced AKI [17].
Conversely, Moledina et al studied the performance of serum creatinine and other kidney injury biomarkers like NGAL, in a group of deceased donors who had undergone kidney biopsy at the time of organ procurement. 155/581 (27%) deceased donors had histologically proven ATN. They reported NGAL lacked accuracy in the diagnosis of acute tubular injury with an area under the receiver operating characteristic curve (AUROC) for diagnosing acute tubular injury of 0.60 (95% CI, 0.55-0.66; P=0.005) [18].
Rise in serum creatinine post-contrast exposure remains the current gold standard in the diagnosis of CIN. We did not find any correlation between rise of NGAL or Cystatin C to serum creatinine. [Table 2]
Preventative strategies for CIN include hydration with saline, isotonic bicarbonate; N-Acetylcysteine, RIPC and Xanthine have been reported earlier. There is still discrepancy in literature as to which preventative strategy is best [19]. RIPC has been demonstrated to have a protective effect against AKI in those undergoing primarily cardiac procedures like surgery or coronary interventions. [20]
A prior study evaluating the protective effects of RIPC in patients undergoing contrasted abdominal CT scan reported a 65% risk reduction in rise of serum creatinine in the group subjected to ischemic pre-conditioning [21].
Menting et al studied a group of 76 patients at risk for development of CIN as per the Dutch guidelines. The inclusion criteria were, reduced eGFR and two additional risk factors like age, heart failure, use of diuretics etc. in those undergoing contrasted studies for diagnostic or interventional purposes [22].
While they found no difference in the change of serum creatinine from baseline to 48-72 hours, in sub-analysis of the group with a high Mehran score (>11) the rise in serum creatinine was statistically lower [22].
However, there is data, which also suggests protective measures against CIN may be ineffective. A recent network metanalysis reported on 124 trials with 28,240 patients undergoing coronary angiography, did not find either intravenous saline, isotonic bicarbonate, NGAL, xanthines or RIPC to be protective [23].
From our study of 40 patients, we did not find a significant difference in creatinine, NGAL or cystatin changes between those with and without RIPC at 48- and 72-hours post contrast exposure, and no significant correlation with change in creatinine, NGAL or cystatin from pre-op to 2 hours.
In our study population, 5 patients developed CIN, 3 from the control group and 2 from the RIPC group.
The major strengths of this study are related to its design as a blinded study with a previously registered protocol. The physicians and nursing staff were blinded to the allocation minimizing risk of bias because of adherence to preventative measures like saline infusion and the volume of contrast used.
Our study has several limitations, which may account for our findings:
- Our sample size was based on earlier studies, which investigated urinary biomarkers to detect AKI and was not based on rise in creatinine as defined by KDIGO. Hence, our sample size may have been an underestimate. This is a common problem when biomarkers are used as a surrogate marker for AKI.
- RIPC was added on to other protective measures like normal saline infusion and use of low osmolar contrast media. These preventative measures may have masked the development of CIN
- Our patient cohort had eGFR>45 ml/min. This group is less susceptible to CIN as compared to those with lower eGFR. Our results may therefore represent a significant type 2 error.
The reason for inability to enroll patients with eGFR 30 to <45ml/min as per our protocol is based on our local experience, as patients chose against contrast procedures when explained the risk of CIN. We also tend to use carbon dioxide as mode of contrast under IR guidance for these patients.
Should we be targeting RIPC to those with GFR < 45 in future studies? Authors who have found protective effect of RIPC have had majority of patients with eGFR of <45 ml/min. however in our study we did not find protective effect of RIPC in patients with eGFR of >45 ml/min.