Evaluation of renal tubulointerstitial damage as a residual renal risk factor for adverse cardiac events in patients with myocardial infarction

Abstract

Background: Renal dysfunction, defined as a lower estimated glomerular filtration rate (eGFR), has been shown to be related to cardiovascular events in patients with myocardial infarction (MI). However, the contribution of renal tubulointerstitial damage to the predictive value for cardiovascular events has not been established. The aim of this study was to elucidate whether renal tubulointerstitial damage is associated with the occurrence of cardiac death and recurrence of MI in patients who have had MI.

Methods and results: Urinary β2-microglobulin (β2MG) was measured in 681 consecutive patients with MI in our hospital. All patients were followed up for <12 years or until the occurrence of cardiac death and MI. During a median follow-up period of 6 years, the cumulative cardiac death rate was 5.4%, and the MI rate was 3.1%. When outcomes were divided into two groups according to the β2MG levels, cardiac death and MI rates were lower in patients with lower levels of β2MG (<0.319 mg/gCre: determined by receiver operating characteristic analyses) than in those with β2MG ≥0.319 mg/gCre (5.9% versus 17.1%, p<0.01). When outcomes were stratified according to the β2MG levels in combination with eGFR levels, Kaplan-Meier analyses showed that cardiac death and MI rates increased depending on an increase in the β2MG levels (p<0.05). Moreover, multivariate Cox analyses revealed that high levels of β2MG were a significant independent predictor of adverse events (hazard ratio: 1.956; 95% confidence interval: 1.014-3.774; p = 0.045). The addition of high levels of β2MG to conventional risk factors, including eGFR and urinary albumin, improved the net reclassification improvement (NRI) and integrated discrimination improvement (IDI) (NRI 0.5447, p = 0.0002; IDI 0.0126, p = 0.0454).

Conclusion: Renal tubulointerstitial damage, as assessed by urinary β2MG, is associated with the occurrence of cardiac death and recurrence of MI independent of renal glomerular function in patients with MI.

Keywords: Myocardial infarction; Renal tubulointerstitial damage; Risk stratification; β2-microglobulin.