CI-AKI is closely associated with prolonged hospital stay, long-term morbidity, and mortality in patient undergoing PCI. The incidence of CI-AKI is about 2% in the general population and over 50% in high-risk population . Previous study supported the relationship between CI-AKI and higher incidence of adverse short- and long-term cardiovascular outcomes, including mortality . Patients with STEMI are likely to present with hypotension, or even cardiogenic shock, higher volume of contrast media, and impossibility of renal prophylactic therapy, which are associated with an increased risk of CI-AKI .
Advanced age, diabetes, dehydration, hypotension, sepsis, cardiovascular disease, underlying acute kidney injury, chronic kidney disease, and concomitant use of nephrotoxic drugs were identified as well-known risk factors for CI-AKI [3, 21]. In previous studies [5, 6], we reported that hyperuricemia was an independent risk factor for CI-AKI in PCI patients, which was consistent with other studies [7-12]. However, other studies did not show the same conclusion [13, 14]. Several studies explored the effect of serum uric acid (SUA) on CI-AKI among high-risk patients such as STEMI undergoing primary PCI. Elbasan et al. showed that SUA was associated with CI-AKI in STEMI patients undergoing pPCI (mean SUA=6.2±0.9 mg/dL, 95% CI, 1.877- 3.236; p=0.002) . In another study, Mendi MA et al. demonstrated that SUA ≥ 5.4 mg/dL was an independent risk factor for CI-AKI (OR 1.26, 95% CI, 1.10-1.42; p < 0.001) . Saritemur M et al. showed that elevated uric acid was lined with CI-AKI in multivariate analysis after adjusting for potential confounding factors (OR 1.01, 95% CI, 1.00-1.01; p = 0.01) . However, even though they reported that high SUA was an independent predictor of CI-AKI in STEMI patients, there was no uniform standard for the definition of hyperuricemia. In our study, we employed the definition consistent with our previous study.
In addition, these studies did not compare the prognosis between CI-AKI group and non-CI-AKI group in STEMI patients undergoing PCI. Some observational studies proved the relationship between hyperuricemia and clinical outcomes in the presence of gout, but not for asymptomatic hyperuricemia [22, 23]. Nevertheless, a recent study by Pagidipati et al, including the PLATO and TRACER study population, demonstrated a significant association between uric acid (UA) and short-term adverse outcomes, independent of the presence of gout . Regarding the relationship between UA and long-term prognosis, the data also supported the relationship between elevated UA and long-term prognosis in patient with acute coronary syndromes and treated with PCI . Therefore, whether hyperuricemia is still a predictor of poor long-term prognosis after adjusting for CI-AKI should be studied in STEMI patients receiving pPCI.
Although the pathophysiological mechanisms of adverse reactions to hyperuricemia has not been fully elucidated, it appears to be multifactorial. In experimental models, hyperuricemia was linked to a variety of proatherogenic processes, including increased oxidative stress , vascular smooth muscle cell proliferation , inflammation , and endothelial dysfunction .
Our current secondary analysis is subject to the following restrictions. First, its sensitivity was lower due to the definition of >0.5 mg/dL because it was less selective for patients with higher risk of mortality and morbidity. Second, a single baseline SUA measurements were used to predict CI-AKI and long-term mortality. However, a number of previous studies have used this method as well. Third, the measurement of serum creatinine (SCr) was standardized at 72 hours after pPCI rather than at random, which might lead to the ignorance at the increase in delayed SCr (>72 hours). Finally, it is a secondary analysis that is not capable of testify a causal relationship.
In conclusion, our study will determine the association between hyperuricemia and contrast-induced acute kidney injury (CI-AKI) after primary percutaneous coronary intervention (pPCI), and will identify if Hyperuricemia is a risk factor for long-term death after adjusting for CI-AKI.
The first patient was included in the RESCIND –1 ATTEMPT Trial (Protocol version 2.0, 11th June 2014) on 1st July 2014 and expected to complete recruitment in December 2018. As of October 24, 2018, recruitment is ongoing with 555 patients randomized at 15 centers in China.