To the best of our knowledge, this is the first study including pre-procedural glycemia in a risk model for CI-AKI prediction in the specific setting of PCI. We found that: 1) pre-procedural hyperglycemia is associated with an increased incidence of CI-AKI; 2) adding FPG to a pre-existing model for CI-AKI prediction such as the Mehran score to form the new GlyMehr score improves the performance in predicting this procedural complication.
Hyperglycemia and CI-AKI
In our analysis, FPG alone significantly discriminated between patients with/without CI-AKI; furthermore, those with pre-procedural hyperglycemia (≥124 mg/dl) reported a higher incidence of this complication. Of note, the same glycemic cut-off (≥124 mg/dl) was previously found as the best value for CI-AKI prediction in a cohort of 421 patients with diabetes, pre-diabetes and normal fasting glucose undergoing coronary angiography (18).
Of course, these results highlight the importance of optimal glycemic control before and during PCI, regardless of the presence of diabetes. Previous studies have already demonstrated the relationship between hyperglycemia and CI-AKI among patients with acute myocardial infarction undergoing primary PCI (12-14); nevertheless, to date few data were available in those receiving elective procedures.
Pathophysiological mechanisms underlying the association between elevated FPG and acute renal damage are not completely recognized. Therefore, whether hyperglycemia is a marker of increased comorbidity burden or the direct cause of CI-AKI is undetermined. Several investigations reported direct renal effects mediated by acute hyperglycemia. Acute hyperglycemia may reduce endothelial-mediated vasodilation and worsen medullary hypoxia due to a lower availability of nitric oxide (19). Acute hyperglycemia could also stimulate inflammation and reactive oxygen species synthesis, increasing contrast-induced injury on renal tubular cells (20).
Of note, in our population, the causes of hyperglycemia were unknown. While in diabetic patients high FPG could account for a not well-controlled diabetic status, different explanations may be considered in patients without diabetes, such as the lack of a previous diagnosis of the metabolic disorder or an acute response to stress, ischemia, infections or other chronic conditions. However, the focus of our investigation was to demonstrate the predictive value of pre-procedural glycemia on the incidence of CI-AKI, regardless of its specific cause.
CI-AKI prediction models: Mehran and GlyMehr
In our study, the Mehran score was able to effectively identify patients who developed CI-AKI both in the Derivation and Validation cohorts. This was expected since it represents a proven score for CI-AKI prediction (10,11). However, several other predictive models have been validated for this purpose (21-25). Some of these scores integrated an impressive number of variables needing complex algorithms to be calculated and have been proved in cohorts of patients undergoing primary PCI (21,22,24). Thus, we focused on the Mehran score taking into account its favorable balance between prediction accuracy and feasibility that represents one of the reasons for its widespread application in clinical practice.
However, in our analysis, combining FPG with the Mehran score in the new GlyMehr model revealed an even higher predictive ability for CI-AKI. Higher values of GlyMehr score mean greater predicted probability and observed incidence of CI-AKI. This is especially attractive if we consider that we obtained this result by adding a simple and easy parameter such as FPG.
Of note, like the Mehran score, most of the previously reported scores for CI-AKI prediction do not include FPG. Whether adding FPG to these models may also improve their performance is unknown and could be assessed in further studies. Nowadays, only one model counting FPG along with another twelve biochemical variables has recently been proposed, albeit based on a cohort of Chinese patients undergoing intra-arterial and intra-venous contrast administration for angiography and computer tomography (25).
The performance of the GlyMehr was greater compared with the original Mehran score also in the Validation cohort and in the overall population. Interestingly, according to the results of the subgroup analysis, the higher predictive ability of the new score was maintained both in diabetic and non-diabetic patients, suggesting that glycemic status might have a significant impact on outcomes also in those without an established diagnosis of diabetes. Similarly, previous studies reported a higher incidence of CI-AKI in hyperglycemic patients without known diabetes in the setting of acute myocardial infarction (12,13).
CI-AKI represents one of the most common and serious non-cardiac complications in patients undergoing PCI, together with bleeding. Despite a noteworthy decline of CI-AKI incidence over time, its negative prognostic impact has remained unchanged (4). This is even more important in view of the growing number of frail patients undergoing percutaneous procedures, who are potentially at higher risk of this complication.
On this background, the results of our analysis might be interesting. Considering a timely risk allocation for CI-AKI as an important goal, the use of the new score including FPG may improve the identification of patients at higher risk. Secondly, our findings might suggest a potential new strategy for the prevention of CI-AKI, since pre-PCI glycemia may represent a modifiable intervention target.
Only a few pharmacological preventive strategies are currently available for CI-AKI prevention. Intense hydration still remains the cornerstone approach (26), whereas pre-treatment with high-dose statins has been shown to protect against the development of CI-AKI in several randomized trials (27). The potential benefit of other agents has also been investigated with conflicting results (e.g., N-acetylcysteine, sodium bicarbonate, ascorbic acid, xanthine) (28). Of note, none of these strategies has been demonstrated to lower the CI-AKI risk in patients with diabetes mellitus (28).
Hence, restoring optimal glycemic control before PCI in order to provide a new prophylactic approach in preventing CI-AKI is worthy of further investigation. Strict glycemic control with insulin has been demonstrated to reduce the occurrence of acquired kidney injury (29). More recently, sodium-glucose transport protein 2 (SGLT2) inhibitors, a new class of glucose-lowering agents acting by promoting glycosuria, have demonstrated protective renal effects (30-32). Furthermore, these agents seem to significantly decrease the risk of acute kidney injury in diabetic patients (33). However, no data are available on a possible benefit regarding CI-AKI, and it is also unknown whether SGLT2 inhibitors may exert their renoprotective effects also in patients without diabetes.