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To systematically review the literature on the use of cardiac troponin levels in patients with chronic kidney disease (CKD) regarding four Key Questions (KQ): (1) diagnosis of acute coronary syndrome (ACS), (2) management decisions for ACS, (3) prognosis after presenting with ACS, and (4) risk stratification in patients without symptoms of ACS.
MEDLINE®, Embase®, and the Cochrane Central Register of Controlled Trials from January 1990 through September 2013.
We included studies that compared a cardiac troponin elevation with a nonelevation in terms of diagnostic accuracy, mortality, or cardiovascular events among patients with CKD. Two reviewers evaluated studies for eligibility; abstracted data using standardized forms; and independently evaluated study quality and graded strength of evidence (SOE). We conducted meta-analyses when there were sufficient data and studies were sufficiently homogenous.
We included 124 studies (130 articles). KQ 1: Fourteen studies evaluated diagnostic accuracy. The sensitivity of troponin T for ACS diagnosis in CKD patients ranged from 71 to 100 percent, and specificity from 31 to 86 percent (6 studies; low SOE). The sensitivity of troponin I for ACS diagnosis ranged from 43 to 94 percent, and specificity from 48 to 100 percent (8 studies; low SOE). KQ 2: One study indirectly addressed management decisions. We could not draw any conclusions about whether troponin levels affect management strategies, such as timing of intervention, in CKD patients with ACS (SOE: insufficient). KQ 3: Twelve studies examined the prognostic value of troponin in CKD patients. Elevated troponin I and T were associated with higher risk of short-term mortality and cardiac outcomes (low SOE). A similar trend was observed for long-term mortality with troponin I (low SOE), but less evidence was found for long-term cardiac events for troponin I and long-term outcomes for troponin T (insufficient SOE). Patients with advanced stages of CKD tended to have worse prognosis with elevated troponin I than those without elevation (moderate SOE). KQ 4: Ninety-eight studies met inclusion criteria. Elevated troponin was associated with all-cause and cardiovascular mortality among dialysis patients with moderate SOE. Hazard ratios (HR) adjusted at least for age and coronary artery disease or risk equivalents were pooled: All-cause mortality, troponin T (HR 3.0 [95% CI 2.4 to 4.3]), troponin I (HR 2.7 [1.9 to 4.6]); Cardiovascular mortality, troponin T (HR 3.3 [95% CI 1.8 to 5.4]), troponin I (HR 4.2 [2.0 to 9.2]). Findings were similar for non-dialysis CKD patients, with fewer studies. No study tested management strategies by troponin cut-points. KQs 1–4: Few studies evaluated high-sensitivity troponin T and I assays in CKD patients. KQs 1–4: We found substantial heterogeneity across studies in terms of study design, troponin assays, troponin cutpoints, patient populations, and adjustment for potential confounders. For ACS populations, the studies varied in the pretest probability descriptions and ACS definitions and adjudication. We found no studies that carried out direct a priori comparisons of troponin testing in patients with CKD versus patients with normal renal function.
Cardiac troponin elevations are associated with a worse prognosis for CKD patients with and without suspected ACS. However, the wide variation in assays and cutoffs, along with the lack of comparative studies, prevents clear conclusions about how this association should change management, compared with management based on clinical factors or evidence derived from the non-CKD population. Future research should compare various management strategies that incorporate measuring cardiac troponins in their algorithms, including using different cutoffs or assays. For this research to be effective, troponin assays and cutpoints need to be standardized and harmonized so that results can be pooled, compared, and applied in practice.
Michos ED, Wilson LM, Yeh H, Berger Z, Suarez-Cuervo C, Stacy SR, et al. Prognostic Value of Cardiac Troponin in Patients With Chronic Kidney Disease Without Suspected Acute Coronary Syndrome: A Systematic Review. Ann Intern Med. [Epub ahead of print 12 August 2014] doi:10.7326/M14-0743