© Borgis - Postępy Nauk Medycznych 9/2016, s. 672-676
*Jolanta Małyszko1, Dominika Musiałowska1, Anna Tomaszuk-Kazberuk2, Hanna Bachórzewska-Gajewska3, Jacek Małyszko4
Cardiovascular disease in patients qualified to kidney transplantation**
Choroby układu sercowo-naczyniowego u chorych zgłaszanych do przeszczepienia nerki
12nd Department of Nephrology, Medical University in Białystok
Head of Department: Professor Jolanta Małyszko, MD, PhD
2Department of Cardiology, Medical University in Białystok
Head of Department: Professor Włodzimierz Musiał, MD, PhD
3Department of Invasive Cardiology, Medical University in Białystok
Head of Department: Professor Sławomir Dobrzycki, MD, PhD
41st Department of Nephrology and Transplantation with Dialysis Unit, Medical University in Białystok
Head of Department: Professor Beata Naumnik, MD, PhD
Streszczenie
Choroby sercowo-naczyniowe są główną przyczyną zgonu chorych z przewlekłą chorobą nerek, w tym pacjentów po transplantacji nerki. Zatem istotną częścią kwalifikacji pacjenta do zbiegu transplantacji nerki jest ocena kardiologiczna. Dodatkowym utrudnieniem jest brak ogólnie przyjętych zaleceń. W procesie kwalifikacji kardiologicznej bierze się pod uwagę: wywiad, badanie przedmiotowe, elektrokardiografię, zdjęcie rentgenowskie klatki piersiowej, ocenę profilu lipidowego, glikemię na czczo, następnie test wysiłkowy oraz badanie echokardiograficzne. Angiografię tętnic wieńcowych należy rozważyć u pacjentów z dodatnim testem wysiłkowym po przebytym ostrym zespole wieńcowym, z niestabilną chorobą niedokrwienną serca, wysokim ryzykiem sercowo-naczyniowym. Innym problemem w tej grupie chorych są zaburzenia rytmu, w tym migotanie przedsionków, które jest najczęstszą patologią. Chorzy z migotaniem przedsionków i upośledzoną funkcją nerek mają znacznie większe ryzyko powikłań zakrzepowych, szczególnie udaru niedokrwiennego mózgu, a jednocześnie większe zagrożenie krwawieniami. Ze względu na nowe możliwości terapeutyczne należy zwracać szczególną uwagę na funkcję nerek, co warunkuje możliwości zastosowania nowych leków przeciwkrzepliwych oraz ich potencjalne interakcje z lekami immunosupresyjnymi.
Summary
Cardiovascular diseases are the leading causes of mortality in patients with chronic kidney diseases, including kidney transplant recipients. Thus, proper cardiological evaluation is crucial to yield the best possible outcomes. Anamnesis, physical examination, electrocardiography, chest x-ray, serum lipids, fasting glucose, then stress and echocardiography is performed in potential kidney transplant recipients. Coronary angiography should be considered in patients with positive stress test after acute coronary syndrome, with unstable angina and high cardiovascular risk. The other problem in this group are rhythm disturbances, with atrial fibrillation being the most common. Patients with atrial fibrillation and impaired kidney function are at the significantly higher risk of thrombotic complications, in particular ischemic stroke on one hand, and bleeding complications on the other hand (linearly to the stage of kidney diseases). Kidney transplant recipients treated with novel oral anticoagulants should be monitored in regard to kidney function and potential interactions with immunosuppressive therapy should be taken into account.
Following the progress in kidney transplantation and post-transplantation care the mortality rate among kidney transplant recipients was significantly reduced in the 60’s and 80’s of last century. It was the result of reduced number of deaths caused by infectious complications (1). On the other hand, the increase of cardiovascular (CV) mortality (1) resulted that the number of deaths remained constant in subsequent years. Currently, death among patients with functioning graft is the leading cause of graft loss and CV diseases are the major cause of death in that population (2, 3). It refers to approximately 50-60% of deaths, including 47% of deaths in the first 30 days after the transplantation by the incidence of coronary artery disease estimated on 1 per 100 patient-years of risk (2-5).
It should be noticed, that successfully completed kidney transplantation improves renal function and causes patient transfer from stage 5 in the KDIGO classification (eGFR < 15 ml/min) to stage 3, rarely to stage 1 or 2. It has been proven, that the risk of cardiovascular diseases increases with the stage of chronic kidney disease and is the highest in the population of dialysis patients (6). Cardiovascular diseases cause from 40 to over 60% of all deaths in this population (7, 8) as also in the population of kidney transplant recipients. The risk of death from cardiovascular diseases is higher among younger patients if compared to general population. Mortality among hemodialysis patients aged 25-44 years is comparable to those over 75 years old with normal renal function (8). It is associated with the occurrence of classic risk factors in the general population (Framingham Heart Study) such as: older age, male gender, hypertension, diabetes mellitus, hypercholesterolemia, smoking, no physical activity, charged family history of cardiovascular diseases (9, 10). There are also additional, specific for chronic kidney disease risk factors, predisposing to the development of cardiovascular diseases. They include: deterioration of renal function, resulting the recurrence of the primary disease, genetic predisposition to progression of chronic renal disease or abnormalities occurring secondary to renal disease, such as hypoalbuminemia, fluid overload, anemia, malnutrition, lipid disorders, chronic inflammation, calcium – phosphate hemostasis disorders (11-14).
They become very important by beginning chronic graft dysfunction, which causes progression of chronic kidney disease, leading to end-stage renal disease and dialysis. Moreover, the majority of kidney transplant recipients was dialyzed for many months or years before transplantation, that was associated with accelerated atherosclerosis progress in those population (15). Cardiovascular diseases diagnosed before transplantation were the strongest predictor of cardiovascular complications after transplantation (15, 16). On the other hand, the presence of blood vessels calcifications before transplantation correlated with higher mortality after transplantation – although no direct relationship was observed (17, 18).
Therefore classic, as also non-classic risk factors of cardiovascular diseases influence directly or indirectly the progression of chronic kidney disease (19). Among kidney transplant recipients there are also factors related to the transplantation, such as: graft loss, obesity, acute kidney rejection, delayed function of the graft, proteinuria, viral infections (e.g.: Cytomegalovirus) or side effects of immunosuppressive therapy (e.g. post--transplantational diabetes mellitus, hypertriglyceridemia, hypercholesterolemia).
Coronary artery disease (CAD) in patients with end-stage renal disease (ESRD) occurs more often than in the general population. Mortality in dialysis patients is extremely high; nearly every fourth patient dies during the annual observation. Most deaths occur from cardiovascular causes (20-22). The most important prognostic factor in patients with CAD is the evaluation of myocardial ischemia. However, the determination of the ischemia in dialysis patients is complicated. Non-invasive diagnostic is extremely difficult, because additional tests are characterized by low sensitivity and specificity. The sensitivity of non-invasive tests according to various sources were assessed from 52 to 95% and specificity of 71 to 94% (23, 24).
The symptoms of coronary artery disease in dialysis patients are often atypical. Atypical clinical symptoms, constantly increased levels of myocardial necrosis markers in patients with chronic kidney disease, including dialysis patients as also difficulties in ECG interpretation make the proper diagnosis difficult (24).
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