Perioperative Care of Patients Undergoing Kidney Transplantation

Cardiovascular Complications

The two main cardiovascular complications of chronic renal failure are arterial hypertension and atherosclerosis, both of which predispose the patient to ischemic heart disease. The prevalence of preoperative hypertension in patients undergoing renal transplantation ranges from 50% to 80%. Hypertension in chronic renal disease develops as a consequence of volume expansion secondary to salt and water retention. Other factors that contribute to the pathophysiology of hypertension in chronic kidney disease include dysregulation of the renin-angiotensin-aldosterone system, sympathetic overactivity, imbalance of endothelium-derived vasoactive substances (endothelin-1 and nitric oxide), erythropoietin replacement therapy, and secondary hyperparathyroidism. If untreated, elevated systemic pressure within the kidney can cause sclerotic changes in the renal vasculature that further contribute to a vicious cycle of increasing hypertension and accelerated kidney injury.

The combination of fluid overload and increased systemic vascular resistance leads to increased myocardial afterload and wall stress. The heart is able to partially compensate with left ventricular (LV) hypertrophy. However, LV hypertrophy and elevated wall stress result in increased myocardial oxygen requirements. At the same time, a rise in LV end-diastolic pressure reduces subendocardial coronary perfusion, reducing myocardial oxygen supply. Together, these forces increase the risk of myocardial ischemia.

Cardiac dysfunction may improve with the initiation of dialysis and the appropriate antihypertensive therapy. In patients in whom the hypertension cannot be controlled by dialysis alone, an abnormal relationship may exist among plasma renin activity, intravascular fluid volume, blood pressure, and inappropriate levels of sympathetic activity. Patients needing antihypertensive therapy in addition to dialysis are often refractory to single antihypertensive drug regimens and require a combination of antihypertensive drugs, which can have significant implications for the perioperative period. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB) are two of the most commonly used antihypertensive agents in renal disease. Other commonly used antihypertensives include loop and thiazide diuretics, dihydropyridine calcium channel blockers, beta blockers, and hydralazine. A prospective study by Sear et al. demonstrated no difference in hemodynamic response to the induction of anesthesia and laryngoscopy between patients with mild to moderate hypertension on different single antihypertensive drug regimens. However, more recent studies have shown an increase in the incidence of intraoperative hypotension in patients taking ACE inhibitors or ARBs. Furthermore, patients with poorly controlled hypertension or requiring several antihypertensive agents often experience significant hemodynamic lability during general anesthesia.

Chronic kidney disease can accelerate the progression of atherosclerosis, including coronary artery disease (CAD), likely via modulation of lipid metabolism, which leads to dyslipidemia and accumulation of atherogenic particles. Cardiac disease is particularly prominent in ESRD patients with diabetes mellitus (DM). DM type 2 is the cause of ESRD in nearly 40% of patients. Patients with ESRD and DM have higher cardiovascular risk than do patients with uremia alone because of the acceleration of small-vessel atherosclerosis associated with DM and the frequently concomitant metabolic syndrome.

The prevalence of CAD in patients with ESRD has been reported in the range of 42% to 80%. Acute myocardial infarction (MI), cardiac arrest of unknown etiology, cardiac arrhythmia, and cardiomyopathy account for over 50% of deaths in patients maintained on dialysis. Cardiac mortality in dialysis patients increases with age. It is approximately two times higher for 45-to 64-year-olds and four times higher in patients older than 65 compared with younger patients in the 20-to 44-year-old range.

Cardiovascular disease remains one of the largest causes of death even after successful KTx, accounting for 17% to 50% of deaths in KTx recipients. Humar and colleagues reported a 6.1% overall perioperative cardiac complication rate among 2694 KTx recipients. Another large study by Gill and Pereira reported a 4.6% first-year all-cause mortality rate in 23,546 adult KTx patients, with greater than 25% of these being secondary to cardiac causes. The main predictors of adverse outcome were a history of pretransplant cardiac disease or MI within the previous 6 months and age older than 40 years.

When echocardiography is performed on dialysis patients as a screening tool, a high incidence of abnormalities is found. In one study, left or right ventricular hypertrophy or pericarditis was detected in 60% of autopsies performed on dialysis patients. Both dilated cardiomyopathy and concentric hypertrophy are seen in dialysis patients. The accumulation of uremic toxins and metabolic acids also contributes to poor myocardial performance. Fluid overload and congestive heart failure occur when the kidneys cannot excrete the daily fluid. Other cardiac conditions, such as pericardial disease and arrhythmia, may be encountered in patients with ESRD. Pericarditis, which may coexist with hemorrhagic pericardial effusion, may reverse with dialysis. Arrhythmias may result from electrolyte abnormalities or MI.

Hematologic Abnormalities

Patients in renal failure most often have normochromic, normocytic anemia due to decreased erythropoietin synthesis and release. Other factors contributing to anemia in renal failure include a decreased red blood cell lifespan, increased hemolysis and bleeding, repeated blood loss during hemodialysis, aluminum toxicity, uremia-induced bone marrow suppression, and iron, folate, and vitamin B ₆ and B ₁₂ deficiencies. Treatment with recombinant erythropoietin can frequently raise hemoglobin levels to 10 to 13 g/dL, which reduces symptoms of fatigue and improves cerebral and cardiac function. Pretransplant treatment with recombinant erythropoietin in anemic patients improves long-term graft survival compared with blood transfusion, which causes allostimulation. However, preexisting hypertension can worsen with erythropoietin therapy in some patients.

An association between renal failure and bleeding tendency has long been recognized. Uremia produces a qualitative defect in platelet function wherein decreased levels of platelet factor III impair platelet adhesion. A prolonged bleeding time is seen (although with poor clinical utility), although prothrombin and partial thromboplastin time are usually normal. Treatments for uremic coagulopathy include dialysis, platelet transfusion, cryoprecipitate, and desmopressin (0.3 mcg/kg). Recent studies suggest a prothrombotic state may in fact exist with uremia. A thromboelastographic study of whole blood clotting found increased coagulability and decreased fibrinolysis in uremic patients versus controls. Platelet-derived procoagulant microparticles may be involved in clinical thrombogenesis.

Uremia

Uremia can cause central nervous system disturbances ranging from drowsiness, memory loss, and decreased concentration to myoclonus, seizures, stupor, and coma. However, severe uremic central nervous system disturbances are rarely seen in patients when appropriately dialyzed. Chronic uremia may also cause delayed gastric emptying. Although the mechanism is not understood, gastric dysrhythmia with discoordinated myoelectrical activity has been found in uremic patients on maintenance hemodialysis. In addition, renal failure patients have an increase in acidity and gastric volume unrelated to Helicobacter pylori infection. There appears to be no difference in gastric emptying time between patients undergoing peritoneal dialysis and hemodialysis.