Hypertension, as mentioned previously, is the second most common cause of ESRD. The incidence of hypertensive patients developing ESRD is increased in those with elevated diastolic pressures, specifically men, older adults, and African-Americans [22]. A thorough review of hypertensive medications is important preoperatively. Hypertensive candidates for renal transplant are controlled with a variety of antihypertensive medications. Among these are diuretics, α-blockers, β-blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors (ACE-I), and angiotensin receptor blockers (ARB). Depending on the degree of renal impairment, lower dosages of these drugs may be required. Additionally, abrupt discontinuation of various classes of antihypertensive drugs, specifically α-blockers and β-blockers, can cause rebound hypertension and tachycardia. Continuation of antihypertensive drugs is therefore warranted to minimize such complications during the perioperative period. Despite consensus on the benefits of continuing most antihypertensive drugs in the perioperative period, controversy exists regarding the optimal timing of ACE-I and ARB administration. While different institutions have varying practice methods regarding this issue, most experts in the field recognize that a significant risk is posed of post-induction hypotension when either an ACE-I or ARB is given. ARBs tend to pose a greater risk than ACE-I, while the risk of both classes is abated with discontinuation greater than 10 h prior to the induction of anesthesia [23, 24]. Care should also be taken to monitor serum potassium levels of patients who are taking diuretics or ACE-I, as severe hypokalemia or hyperkalemia can occur with these drugs. Pulmonary hypertension, in addition to systemic hypertension, is of concern for a select group of patients with ESRD. Patients on long-term dialysis through an arteriovenous fistula were found to have a higher incidence of pulmonary hypertension than a control group of patients receiving peritoneal dialysis [25]. Although in most patients pulmonary pressures return to normal after renal transplantation, careful evaluation is necessary preoperatively to guide intraoperative anesthetic management.

Cardiovascular disease (CVD) is common in patients with ESRD. Prevalence rates of 35–50% have been observed in dialysis patients while even higher rates (50–85%) affect those older than 45 years who have diabetes [26, 27]. The high incidence of CVD, left ventricular hypertrophy, and congestive heart failure found in ESRD patients places them at a higher risk of adverse cardiovascular events perioperatively. Consistent with this finding is the fact that cardiovascular events are the leading cause of death after kidney transplantation. However, despite the potential morbidity and mortality of renal transplants in those with ESRD and/or diabetes, rarely is CVD a contraindication to renal transplantation. An exception to this contraindication is a patient with severe ventricular dysfunction causing low cardiac output. In this instance, a low cardiac output state may compromise viability of the newly transplanted kidney due to poor blood flow.

Evaluation of CVD typically begins with a history and physical examination to assess symptoms, signs, risk factors, and physical status. While such an evaluation would be revealing for most patients, it must be kept in mind that many diabetic patients, despite severe coronary disease, may have asymptomatic or silent disease. Consequently a detailed history of these diabetic patients may have limited value. Noninvasive screening consisting of electrocardiography, echocardiography, and/or stress testing should be performed to detect coronary ischemia in patients with symptoms or signs of CVD or in those with the potential for occult CVD. Those at risk of occult disease include patients older than 50 years, non-insulin-dependent diabetics older than 45 years, diagnosis of diabetes for greater than 25 years, patients with severe peripheral vascular disease, or those who have smoked more than 5 years [28, 29]. The sensitivity and predictive accuracy of an exercise stress test is low in diabetic patients. In these patients, greater benefit may therefore be obtained from a stress test with imaging [30]. Patients with a positive stress test should be referred to a cardiologist and coronary angiography should be considered. Nonischemic cardiomyopathy, such as uremic cardiomyopathy, is no longer considered an absolute contraindication to renal transplantation [31]. Not only do such conditions improve with aggressive dialysis, but more importantly the cardiomyopathy found in these patients is reversible with renal transplantation. Studies on the effects of renal transplantation on cardiac function in patients with severe nonischemic cardiomyopathy have found initial ejection fractions of 20–35% improve to almost 70% within 1–2 weeks of the transplanted kidney [32, 33]. Despite improvement in cardiovascular disease following renal transplantation, the anesthesiologist should be aware of and prepared for the potential of intraoperative hemodynamic instability and tailor the anesthetic plan accordingly. The use of invasive monitoring, such as arterial and central venous monitoring, should be considered as well as the use of intraoperative echocardiography in experienced hands. Alternatively, establishing a specific hemodynamic goal and using a goal-directed approach to fluid replacement instead of a liberal administration of fluids may be as effective. Studies have not only shown decreased perioperative morbidity with goal-directed fluid therapy but also decreased length of hospital stay [34].

While the optimal form of transplant for the diabetic ESRD patient is important and should be thoroughly discussed, perioperative concerns for the anesthesiologist revolve around the complications of the disease itself. As mentioned previously, transplantation offers a greater life expectancy than does continuation on dialysis. Despite this fact, risks of renal transplantation remain. Acute coronary syndrome (acute myocardial infarction) remains the most common cause of mortality for diabetic patients who have had renal transplants. Indeed, vascular complications in general plague the success of renal transplants in the diabetic patient. Almost half the diabetic patients with preexisting coronary artery disease and/or congestive heart failure who have undergone renal transplantation die of vascular complications within three posttransplant years [29]. Vascular complications include multiple surgeries for amputations, as well as myocardial infarctions and cerebrovascular accidents.

Another significant concern for ESRD patients with long-standing diabetes is the development of stiff joint syndrome. The syndrome is characterized by joint rigidity and tight waxy skin. Type I diabetic patients may also be short statured in addition to having the previous findings. The fourth and fifth proximal phalangeal joints are most commonly involved. Patients with diabetic stiff joint syndrome have difficulty approximating their palms and cannot bend their fingers backwards as noted by the “prayer sign.” The condition is caused by nonenzymatic glycosylation of collagen and subsequent deposition into joints. When the cervical spine is involved, direct laryngoscopic intubation may be difficult due to limited atlanto-occipital joint motion. Consideration of alternate means of securing the airway, such as fiberoptic intubation, is therefore warranted.

Diabetic autonomic neuropathy (DAN) is also a serious complication of diabetes. It can affect multiple organ systems including the gastrointestinal (GI) and cardiovascular systems. Up to 20% of randomly selected asymptomatic diabetic patients have been found to have abnormal cardiovascular autonomic function [35]. Some of the clinical findings of DAN include gastroparesis, constipation, a resting bradycardia or tachycardia, exercise intolerance, orthostatic hypotension, “brittle diabetes,” and labile blood pressures under anesthesia. If GI problems related to DAN are suspected or are present, precautions against aspiration should be instituted. While drugs such as H₂-blockers, sodium citrate, and metoclopramide have been used to reduce or neutralize gastric acidity and facilitate gastric emptying, aspiration-prevention medications should be tailored to individual patient history and disease severity. A study by Jellish et al. shows little difference in gastric volumes of fasting patients across a spectrum that includes those with severe diabetic autonomic neuropathy unless a history of poor glucose control was elicited [36].

Chronic kidney disease promotes an increase in tissue factor, von Willebrand factor, fibrinogen, factor VIII, lupus anticoagulant, activated protein C and S, and antithrombin II, in addition to causing platelet hyperactivity [37, 38]. These factors, along with other hemostatic abnormalities, promote a procoagulant state even in mild CKD. As kidney dysfunction progresses to end-stage renal disease, patients exhibit platelet dysfunction, which can present as cutaneous, mucosal, or serosal bleeding [37]. The procoagulant state as well as platelet function improve with renal transplantation [36, 39]. Preoperative correction of hemostatic factors is important not only to minimize intraoperative and postoperative blood loss but also to decrease the potential of a hematoma from poor hemostasis progressing to an infectious source. The mainstay of treatment in correcting hemostatic abnormalities is dialysis for the improvement of platelet function and cryoprecipitate or desmopressin.

Chronic anemia is a common problem in patients with ESRD due to decreased erythropoietin production from the kidneys. While chronic anemia causes a right shift of the oxygen–hemoglobin dissociation curve, thereby causing increased oxygen unloading and delivery to tissues, comorbid conditions and surgical stress typically warrant higher hemoglobin levels. Ideally, recombinant erythropoietin therapy should be started in patients who show signs of clinical compromise from low hemoglobin levels. Preoperative blood transfusions have fallen out of favor due to the risks associated with transfusions compared to minimal advantages.

While the goal for patients in general is to correct electrolytes prior to surgery, obtaining those normal values is often difficult in patients with CKD. The goal therefore should be to achieve electrolyte levels that are within baseline for each individual patient. Hyperkalemia specifically is a common feature of CKD and ESRD, and levels are typically elevated at a set point higher than the range found in those with normal kidney function. The current level as well as the trend in potassium levels should therefore be carefully noted. Steady-state levels in the range of 5–5.5 mmol/L are common and acceptable, while higher levels typically require treatment with dialysis or pharmacologic agents. Calcium is given to antagonize cardiac toxic effects and to stabilize cardiac membrane, magnesium can be given to prevent or suppress torsades de pointes, and glucose, insulin, β-agonists (such as albuterol), and sodium bicarbonate can be given to shift potassium intracellularly.