Role of Serum Cystatin C in the Prediction of Contrast-Induced Nephropathy After Intra-Arterial Interventions
Contrast-induced nephropathy (CIN) is a significant complication following the administration of iodine-based contrast media (CM) during intra-arterial interventions. It is characterized by an acute impairment of renal function, leading to increased morbidity, prolonged hospital stays, and higher healthcare costs. Traditionally, the diagnosis of CIN relies on changes in serum creatinine (sCr) levels. However, sCr is influenced by various factors such as age, sex, and muscle mass, making it a less sensitive biomarker for early detection of kidney injury. This study investigates the utility of serum cystatin C (sCysC) as a more reliable biomarker for predicting CIN after intra-arterial interventions.
Background and Significance
With the increasing use of image-guided interventional procedures, the incidence of CIN has risen, making it the third most common cause of hospital-acquired acute kidney injury (AKI). CIN is typically defined as an increase in sCr by 0.5 mg/dL or 25% within three days after CM administration, in the absence of other causes of renal impairment. However, sCr levels may remain normal despite significant kidney dysfunction, highlighting the need for a more sensitive biomarker.
Cystatin C, a low molecular weight protein produced by all nucleated cells, is freely filtered by the glomeruli and not reabsorbed by the renal tubules. Its levels are influenced by the glomerular filtration rate (GFR) but are unaffected by external factors such as inflammation, fever, sex, age, diet, and body composition. This makes sCysC a promising candidate for early detection of renal injury.
Study Design and Methods
This prospective observational study included 360 consecutive patients who underwent intra-arterial interventions using digital subtraction angiography. Patients with pre-existing renal failure, dehydration, recent surgery, or those receiving nephrotoxic drugs were excluded. The patients received either low-osmolar (iohexol) or iso-osmolar (iodixanol) CM during the procedures.
Serum creatinine (sCr), serum cystatin C (sCysC), and estimated GFR (eGFR) were measured at 1 to 2 days before the procedure and at 48 hours, 72 hours, and 7 days post-procedure. CIN was defined as an increase in sCr of more than 25% from baseline or an absolute increase of at least 0.5 mg/dL within three days after CM administration.
Results
Out of the 360 patients, 31 (8.61%) developed CIN. The study found that pre-operative sCysC levels had good discriminatory power for evaluating the risk of CIN, with an area under the curve (AUC) of 0.634, sensitivity of 53.33%, and specificity of 73.70%. A baseline sCysC cut-off value of 1.07 mg/L was established to rule out CIN, with a negative predictive value (NPV) of 94.37%.
Post-operative sCysC levels at 48 hours were also predictive of CIN, with an AUC of 0.735, sensitivity of 74.20%, and specificity of 63.90%. A cut-off value of 0.99 mg/L at 48 hours was determined to be the best threshold for ruling out CIN, with an NPV of 96.34%.
Discussion
The findings of this study underscore the utility of sCysC as a sensitive biomarker for early prediction of CIN. Unlike sCr, sCysC levels change earlier and reach a steady state faster, making it a more reliable indicator of renal injury. The study demonstrated that baseline sCysC levels before an intervention could provide a preliminary estimate of the risk of CIN, while post-operative sCysC levels at 48 hours could help identify patients at lower risk for early discharge.
Diabetes mellitus (DM) was identified as an independent risk factor for CIN, increasing the risk by 2.778-fold compared to non-diabetic patients. This highlights the need for preventive strategies in high-risk patients with DM, including the use of hydration protocols and minimizing CM volume during procedures.
Limitations and Future Directions
The study has some limitations, including its single-center design and the lack of long-term follow-up. Future studies should include multi-center designs, longer follow-up periods, and animal models to monitor renal pathology and function changes over time. Additionally, further research is needed to validate the cut-off values for sCysC and explore its use in conjunction with other biomarkers for a more comprehensive assessment of renal injury.
Conclusion
Serum cystatin C is a valuable biomarker for the early prediction of contrast-induced nephropathy following intra-arterial interventions. Baseline sCysC levels can provide a preliminary estimate of the risk of CIN, while post-operative sCysC levels at 48 hours can help rule out patients at lower risk for early discharge. The study highlights the importance of preventive strategies, particularly in high-risk patients with diabetes mellitus, to mitigate the risk of CIN and improve patient outcomes.
doi.org/10.1097/CM9.0000000000000641
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