Abbreviations:

CAD- Coronary Artery Disease; CKD- Chronic Kidney Disease; CRP- C-Reactive Protein; CT- Computed Tomography; ECG- Electrocardiogram; EF- Ejection Fraction; ESRD- End-Stage Kidney Disease; KT- Kidney Transplant; PCT- Procalcitonin; STEMI- ST-Elevation Myocardial Infarction

1. Introduction

The immense increase in mortality of patients with end-stage kidney disease (ESRD) is mainly due to cardiovascular reasons [1]. Before potential kidney transplantation, non-invasive diagnostic workup is not validated and the current KDIGO guideline is discussed controversially [1]. In this paper, we describe the case of a previously heart transplanted male with chronic kidney disease (CKD) presenting a major complication during the pre-kidney transplant assessment phase. This rare case points out the need for individual cardiac diagnostic workup prior to KT based on specific risk and pretest probability. Additionally, we outline atypical symptoms, laboratory parameters and discuss the relevance of contrast-induced nephropathy.

2. Case Presentation

A 50-year-old heart transplanted male with CKD stage G4A3 was admitted for kidney transplant (KT) evaluation. Orthotropic heart transplantation had been performed 9 years earlier due to transposition of the great arteries. The etiologies of CKD were calcineurin inhibitor toxicity, cardio-renal syndrome and secondary focal segmental glomerular sclerosis. The patient was stable throughout the hospital stay and routine examinations were performed for evaluation as KT candidate, such as myocardial scintigraphy, chest x-ray, lung function test, urology, and gastrointestinal assessment which were all unremarkable. However, on the day of planned hospital discharge, elevated infection parameters including C-reactive protein (CRP), procalcitonin (PCT) as well as transaminases, creatine kinase and lactate dehydrogenase were detected (day 0, Table 1).

Table 1: Laboratory parameters.

Table 1 displays leucocyte counts (in 10³ cells/µl), PCT (in ng/ml) and CRP (in mg/l) levels for day -4, day 0 and day 1.

Interestingly, the patient had no fever, showed stable cardiovascular and respiratory conditions, clinical examination was unremarkable and urine assessment showed no sign for infection. The patient denied symptoms such as pain, coughing, shortness of breath and alguria. Urine and blood cultures were collected and sent out to microbiology. Aerococcus urinae was detected in the patient’s urine while blood culture tests remained negative. Antibiotic treatment with intravenous piperacillin/tazobactam was initiated. Since infectious parameters were further increasing on the next day (day 1, table 1), a thoracic and abdominal contrast-enhanced CT-scan was performed to find the focus of infection. The CT- scan showed myocardial infarction in the left anterior descending artery territory, a new apical aneurysm and a left ventricular thrombus (Figure 1). Repeated electrocardiogram (ECG) recordings showed newly elevated ST segments (Figure 2).

Figure 1: CT-scan. Representative images of the contrast-enhanced thoracic CT-scan. A Coronal image of the left ventricle revealing apical aneurysm and left ventricular thrombus (arrow). B and C Sagittal images of CT-based iodine imaging. The arrows depict hypoperfusion of the septal and apical myocardium.

Figure 2: ECG. Three consecutive ECG recordings. A Routine ECG recording from 4 days prior to the event. B ECG recording performed immediately after the CT-scan revealing myocardial infarction. ST-segment elevation is present in leads I, II, aVL, V1-V5 (day 1). C Follow-up ECG recording 30 days after the event.

Maximum Troponin levels were >125.000 pg/ml and creatine kinase >140 U/l. The ejection fraction (EF) decreased from >55% 4 days before to 25% in transthoracic echocardiogram. Treatment with aspirin and heparin was initiated immediately. Heart catheter was postponed because of the fear that contrast media would lead to CKD progression to ESRD and because myocardial infarction most likely ran its course somedays before. However, even without further contrast media the patient required hemodialysis treatment due to acute on chronic kidney injury because of impaired cardiac output. When heart catheter was finally performed, no stenosis but a potential former in-stent thrombosis was detected. A control echocardiography showed a slightly improved but still dramatically impaired EF of 30-35%. Upon hospital discharge, the patient still required dialysis treatment. Blood and urine cultures remained sterile.

3. Discussion and Conclusions

This case report has several teaching aspects: First, CKD is a major cardiovascular risk factor [1]. Therefore, prior to listing for KT patients with CKD often receive cardiac diagnostic workup which, however, is not validated for detection of coronary artery disease (CAD) in this population. Studies comparing invasive vs. non-invasive cardiac diagnostics prior to KT delivered controversial results and current pretransplant screening guidelines are only based on expert opinions [1]. Guidelines recommend non-invasive CAD screening for asymptomatic patients prior to listing for KT [2]. A meta-analysis found invasive coronary angiography and non-invasive measures to be comparable when detecting major adverse cardiac events. However, sensitivity and specificity were low for non-invasive diagnostics and a substantial number of people with negative test results went on to experience adverse cardiac events [3]. Therefore, in asymptomatic patients before and after KT, non-invasive diagnostics are not suitable to rule out CAD as all these tests do not have a sufficient likelihood ratio and no sufficient posttest probability can be achieved. Asymptomatic patients with high pretest probability should directly undergo angiography. For symptomatic patients coronary angiography is the first choice as well [4]. Regarding therapeutic approaches, coronary revascularization is not superior to optimal medical therapy in reducing mortality or major adverse cardiovascular events in waitlisted KT candidates with CAD [5].

Thus, more detailed algorithms based on risk stratification and therapy should be elaborated [6]. Second, CKD patients as well as heart transplanted patients may present with atypical symptoms when suffering from myocardial ischemia [7]. This calls for an increased awareness for more atypical signs such as abnormal laboratory findings. Third, elevation of infection parameters including PCT can be a sign of myocardial infarction in the absence of infection. PCT has been identified as an earlier marker than CK-MB and Troponin I, however, not necessarily correlating with the amount of myocardial tissue injury [8]. In patients with severe ST-elevation myocardial infarction (STEMI) and cardiogenic shock, PCT values are significantly increased [9]. Myocardial infarction leads to a sterile inflammation and reduced perfusion of the bowels can induce transient leakage of the intestinal barrier with transient bacteremia stimulating PCT and other infection parameters [8]. Fourth, whether contrast media causes AKI was lately called into question, even though CKD has been identified as major risk factor. However, the risk of contrast-associated AKI has been overestimated in the past and there is a risk of underusing otherwise necessary interventions such as percutaneous coronary intervention. Potential lifesaving diagnostics and intervention should not be delayed because of a risk of AKI [10].

Acknowledgement

N/A

Conflicts of Interest

The authors have declared that no conflict of interest exists.

References

1. Hart A, Weir MR, Kasiske BL. Cardiovascular risk assessment in kidney transplantation. Kidney Int 87 (2015): 527-534.
2. Chadban SJ, Ahn C, Axelrod DA, et al. KDIGO Clinical Practice Guideline on the Evaluation and Management of Candidates for Kidney Transplantation. Transplantation 104 (2020): S11-S103.
3. Wang LW, Masson P, Turner RM, et al. Prognostic value of cardiac tests in potential kidney transplant recipients: a systematic review. Transplantation 99 (2015): 731-745.
4. Pauker SG, Kassirer JP. The threshold approach to clinical decision making. N Engl J Med 302 (1980): 1109-1117.
5. Siddiqui MU, Junarta J, Marhefka GD. Coronary Revascularization Versus Optimal Medical Therapy in Renal Transplant Candidates With Coronary Artery Disease: A Systematic Review and Meta-Analysis. J Am Heart Assoc 11 (2022): e023548.
6. Kassab K, Doukky R. Cardiac imaging for the assessment of patients being evaluated for kidney transplantation. J Nucl Cardiol 29 (2022): 543-557.
7. Gao SZ, Schroeder JS, Hunt SA, et al. Acute myocardial infarction in cardiac transplant recipients. Am J Cardiol 64 (1989): 1093-1097.
8. Reindl M, Tiller C, Holzknecht M, et al. Association of Myocardial Injury With Serum Procalcitonin Levels in Patients With ST-Elevation Myocardial Infarction. JAMA Netw Open 3 (2020): e207030.
9. Picariello C, Lazzeri C, Chiostri M, et al. Procalcitonin in patients with acute coronary syndromes and cardiogenic shock submitted to percutaneous coronary intervention. Intern Emerg Med 4 (2009): 403-408.
10. Mehran R, Dangas GD, Weisbord SD. Contrast-Associated Acute Kidney Injury. N Engl J Med 380 (2019): 2146-2155.