Renal allograft-related inflammation and accelerated coronary- artery disease: a case report

Background: Although persistent systemic inflammation is considered to be predictive for future cardiovascular events, it remains unclear whether or not Creactive protein (CrP) plays an active role in coronary-plaque instability. Here, we report a case of a patient with failed and super-infected renal allograft as a source for systemic inflammation presenting with repeat acute coronary syndromes. Case presentation: A 52-years-old male type-2 diabetic with a failed kidney transplant who was hospitalized for acute urinary-tract infection. In the presence of other, classic cardiovascular risk factors, peak values of CrP coincided with episodes of unstable angina treated by cardiologic interventions. Besides pyelonephritis, the histological examination of the kidney transplant revealed signs of chronic rejection and the presence of a renal cell carcinoma in situ. Once the renal allograft has been removed, systemic inflammation was attenuated, the patient was not rehospitalized for acute-coronary syndrome within the next 12 months. Conclusion: In this case, systemic inflammation was paralleled by instability of coronary plaques as documented by repeat coronary angiograms.


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Background C-reactive protein (CrP), a surrogate of systemic inflammation, is considered to be a predictor for cardiovascular risk in the general population (1-3) as well as for the outcome in patients with acute myocardial infarction (4) or unstable angina [5].
However, it remains unclear, whether or not CrP plays an active role in atherothrombosis or solely represents an epiphenomenon (6).
Here we report a patient with end-stage renal disease (ESRD) due to a failed, super-infected renal allograft hospitalized for repeat episodes of acute coronary syndrome. The role of systemic inflammation for coronary-artery disease outcomes is discussed.

Case presentation
A 52-years-old, obese male patient with ESRD due to diabetic nephropathy was admitted to a nephrology department of a tertiary referral hospital because of haematuria, leukocyturia and oligo-anuria in the presence of a failed renal allograft.
The patient received the renal allograft of a deceased donor 4 years earlier after 7 years of hemodialysis treatment. Hemodialysis treatment had to be resumed 6 months prior to hospitalization. Comorbidities include the full range of type-2-  Figure 1A). There, a direct bare-metal stent was deployed.
One week later, the kidney-transplant removal surgery had to be performed urgently due to urosepsis. Within the explanted renal allograft, the histological analysis revealed abscess formation and a prevalent vasculitis as sign of chronic vascular rejection (Figure 2A). As a new finding, a moderately differentiated renalcell carcinoma (G2, pT1a, pN0, L0, V0) with a diameter of 2.5 cm was found (

Discussion and Conclusion
This case suggests that peak systemic inflammation may coincide with acute coronary syndromes. Once the renal allograft ceased to function due to pyelonephritis and due to chronic allograft rejection, increased systemic inflammation may have facilitated the occurrence of plaque ruptures leading to acute coronary syndromes. This view is supported by sequential coronary angiograms within 3 weeks. As soon as systemic inflammation was consolidated, the patient remained event-free, as far as acute coronary syndromes are concerned. After kidney transplantation, medical immunosuppressive therapy may predispose to infections. Once the main source of infection has been identified, other secondary sources of infection, e.g. hemodialysis catheter (7) and/or infective endocarditis need to be ruled out, if systemic inflammation still persists.
In the present case, there was no clinical sign of arteriovenous-fistula infection, no secondary source of inflammation was found.
As a limitation, no cause-consequence relationship between inflammation and acute coronary syndromes may be established from a single case. However, the timely coincidence points to the possibility of a contribution of systemic inflammation to the occurrence of cardiovascular events. Coronary plaque rupture is known to be facilitated by pro-inflammatory cytokines (8). Besides local inflammatory processes leading to coronary-plaque instability, a more generalized inflammatory response may affect the whole coronary tree. There, CrP synthesized in the liver upon interleukin-6 stimulation, represents a candidate mediator linking inflammation with occurrence of acute coronary syndromes (9). In an animal model of atherosclerosis, CrP transgene expression accelerated aortic atherosclerosis (10), while therapeutic inhibition of CrP improved outcome of experimental myocardial infarction (11). Functional studies on neutrophils and human endothelial cells indicate that monomeric CrP, but not pentameric or native CrP, leads to neutrophil-granulocyte (12) and to endothelial-cell activation (13).
Increased systemic inflammation adversely affects mortality in patients with chronic kidney disease, stage 3 or 4 of (14). In addition, overall and cardiovascular mortality correlate with the estimated glomerular filtration rate (15). Future research needs to determine the individual roles and mechanisms of uremic toxins and inflammation for cardiovascular outcomes. To contain a possible role of CrP on acute coronary-artery disease progression, adsorptive techniques to therapeutically lower plasma CrP may be employed on an individual basis (16).
In summary, from this case a contributory role of inflammation on acute progression of coronary heart disease is assumed. Anti-inflammatory strategies, such as the removal of a failed, super-infected renal allograft, need to be considered in patients with therapy-resistant systemic inflammation to avoid cardiovascular complications.

Consent for publication
Written informed consent to publish patient-related information was obtained from the patient. The signed informed consent is on file. A copy of the consent form is available for review by the Editor of the journal.

Availability of data and material
All relevant data were included in the manuscript.