The most common etiologies of renal disease leading to kidney transplant are:

CKD has many potential causes that differ among the world populations. In developed countries, age, hypertension, cardiovascular disease, diabetes, increased body mass index (BMI), and smoking are associated with CKD. In the developing world, causes of kidney failure include infections due to bacteria, viruses, and parasites.

The global increase in CKD parallels the obesity epidemic. Obesity has been associated with a secondary focal segmental glomerulosclerosis coined obesity-related glomerulopathy (ORG). The accumulation of lipid in the cellular structure of the kidney is associated with structural and functional changes.

In recent years, Central America, Egypt, India, and Sri Lanka have reported a high prevalence of CKD of unknown etiology in agricultural communities, predominantly among male farmworkers. The dominant histopathologic diagnosis is chronic tubulointerstitial nephritis. There are associations reported with agricultural work, agrochemical exposure, dehydration, hypertension, homemade alcohol use, and family history of CKD.

CKD is defined as abnormalities of kidney structure or function that is present for more than 3 months, with implications for health. It is not dependent on the etiology leading to deteriorated kidney function.

The criteria for CKD include either of the following present for more than 3 months:

Early start of dialysis is initiated when GFR reaches ≤10 mL/min/1.73 m² in a patient without diabetes or ≤15 mL/min/1.73 m² in a patient with diabetes. Recent data indicate that the mortality while on dialysis may be higher with an early start and that there is no significant benefit in terms of quality of life. Some nephrologists support initiating dialysis at a lower GFR (<7.0 mL/min/1.73 m²) provided that patients are given careful clinical management, and at an even lower rate (<5 mL/min/1.73 m²) in selected elderly patients given a supplemented very low protein diet with careful management of the nutritional status, fluid and electrolyte balance, body weight, mineral metabolism, anemia, and blood pressure.

Patients with uremic symptoms (e.g., anorexia, vomiting, weight loss, pericarditis, and pleuritis) or fluid overload should be started on dialysis even if GFR is not at critically low levels. Other indications for dialysis in CKD include hyperkalemia that causes electrocardiogram (ECG) changes or that is persistent (K⁺ >6 mEq per L), heart failure poorly controlled with drugs, and metabolic acidosis that is difficult to control.

The common problems related to ESRD are the following:

Pain is extremely common in ESRD and can result from renal and nonrenal etiologies. In a prospective study of 205 hemodialysis patients, musculoskeletal pain was most common (63.1%), followed by dialysis-associated pain (13.6%), peripheral neuropathy (12.6%), and peripheral vascular disease claudication pain (9.7%). Polycystic kidney disease can cause chronic abdominal pain. Fentanyl and methadone are considered the safest opioids for use in patients with ESRD. Secondary hyperparathyroidism often results in bone pain.

Chronic renal insufficiency and ESRD are associated with abnormalities in sodium (Na), potassium, calcium, magnesium balance, and metabolic acidosis.

Na and water (H₂O) balance are closely related. The kidney has its own inherent circadian rhythm involved in the transcription genes for renal Na excretion and blood pressure control. This function is impaired in renal disease. In patients with chronic renal failure, the total body content of Na and H₂O may be increased. This can be due to glomerular disease promoting Na retention or excessive ingestion of Na leading to extracellular fluid (ECF) expansion. The ECF expansion and hyperosmolarity contributes to hypertension. Nonanuric patients may be treated with loop diuretics and salt restriction.

The renal mechanisms for conserving Na and H₂O are impaired in ESRD. Urine in nonoliguric patients is isosthenuric. This means the usual indices of prerenal azotemia (high urine osmolality, low urine Na, and low fractional excretion of sodium [FENa]) are not applicable. If additional fluid loss (vomiting, fever) is imposed, such patients become severely volumedepleted. These patients have to be hydrated carefully with normal saline.

Hyperkalemia rarely occurs in patients with a GFR greater than 25 mL/min/1.73 m² in the absence of an endogenous or exogenous potassium load. Patients are usually chronically hyperkalemic. Severe hyperkalemia increases cardiac and skeletal muscle excitability. The earliest changes begin with levels above 6.5 mEq per L. The ECG shows peaked T waves, flattened P waves, lengthened PR interval, disappearance of P waves, and a widened QRS complex that can progress to a “sine wave,” ventricular asystole, or ventricular fibrillation. Muscle weakness can cause respiratory failure. Membrane excitability is more dependent on the rate of increase in potassium than on potassium concentration per se. The treatment of hyperkalemia includes a combination of insulin, glucose, loop diuretics (nonanuric), sodium bicarbonate, calcium, and magnesium (Table 25.1). The anesthesiologist may also institute hyperventilation in mechanically ventilated patients. Hemodialysis or peritoneal dialysis is the definitive treatment for severe hyperkalemia.

Magnesium imbalance can accompany chronic renal failure. High blood magnesium levels cause dose-dependent neuromuscular toxicity and increased sensitivity to depolarizing and nondepolarizing neuromuscular blockers. Bradycardia, hypotension, and heart block are due to the calcium channel-blocking effects of magnesium. The acute toxicity can be antagonized by intravenous infusion of calcium. Conversely, decreased dietary intake and impaired intestinal absorption can lead to hypomagnesemia. Magnesium deficiency has been related to progression of atherosclerosis and low parathyroid hormone (PTH) levels.

Phosphate retention occurs when GFR begins to decline. Retained phosphate promotes secondary hyperparathyroidism by lowering ionized plasma calcium levels, decreasing renal formation of calcitriol (1,25 dihydroxyvitamin D), and stimulating PTH gene expression.

Ionized and protein-bound calcium levels are lower in uremic patients. This is the result of hyperphosphatemia and reduced gastrointestinal absorption secondary to the decreased production of vitamin D.

A mild-to-moderate acidosis is commonly noted when the GFR decreases to less than 20% to 25% of normal. The decreased renal mass results in decreased production and excretion of proton load. The plasma bicarbonate concentration ranges between 12 and 22 mEq per L, and blood pH remains greater than 7.20. This does not routinely require correction. It may gradually evolve into a high anion gap acidosis when the GFR is below 20 mL/min/1.73 m². Some patients with ESRD maintain close to normal acid-base parameters even when renal function is severely compromised. However, when exposed to an increased dietary acid load, these patients may have decreased ability to increase bicarbonate generation.

The correction of acidosis by oral sodium bicarbonate or a diet rich in fruits and vegetables can attenuate rate of decline of renal function.

ESRD is associated with an increased incidence and prevalence of a wide range of cardiovascular morbidities including hypertension, coronary artery disease, stroke, congestive heart failure, atrial fibrillation, sudden cardiac death, pulmonary hypertension, and valvular heart disease.

Extensive vascular calcification contributes to early onset cardiovascular disease and cardiovascular mortality. In addition to traditional cardiovascular risks, risk factors specific to CKD such as phosphate retention, hypercalcemia, history of dialysis, high-dose vitamin D therapy, and deficiency of calcification inhibitors promote arterial calcification. There is no specific therapy to reverse vascular calcification, but statin therapy is associated with decreased cardiovascular death. Additional measures such as reduction of calcium phosphate load, using non-calcium-containing phosphate binders, and moderate doses of active vitamin D may attenuate arterial hardening.

The rate of sudden cardiac death increases as the stage of CKD increases and could be responsible for 60% of cardiac deaths in patients undergoing dialysis. The uremic load results in cardiac fibrosis and in left ventricular systolic and diastolic dysfunction. The occurrence of conduction abnormalities and arrhythmias is exacerbated by electrolyte shifts, diabetes, and autonomic neuropathy. Cardioverter-defibrillator implantation decreases the risk of sudden death in patients with CKD.

Hypertension has been reported to occur in 85% to 95% of patients with CKD (stages 3 to 5). The relationship between hypertension and CKD is cyclic in nature. Uncontrolled hypertension is a risk factor for developing CKD and leads to a more rapid progression of CKD. In turn, renal disease exacerbates uncontrolled hypertension due to volume expansion and increased systemic vascular resistance. An imbalanced autonomic system results in an exaggerated sympathetic drive with a loss of vagal tone. Autonomic neuropathy creates a setting for silent myocardial ischemia.

Correction of the uremic state and improved GFR after kidney transplant may decrease the incidence and severity of cardiovascular complications.

Studies show that survival of a transplanted kidney is incrementally worse if the recipient has been on long-term dialysis. The best outcomes are seen for patients who are preemptively transplanted before dialysis is initiated. However, renal failure in some patients is slowly progressive so it is not practical to perform a transplant months or even years before it is needed. Also, there is a small fraction of patients diagnosed with “end-stage” kidney disease that regain kidney function. For example, patients with kidney injury from malignant hypertension may regain kidney function weeks or even months after hypertension control is established.

In general, a patient is a candidate for a kidney transplant if the estimated glomerular filtration rate (eGFR) is 20 mL/min/1.73 m² or less. The rate of progression to ESRD is also important. In diabetics, renal failure can develop rapidly. If it is obvious the patient will eventually require dialysis, and a living donor is available now, transplant is practical and cost-effective option.

Preparation for a transplant candidate can take several months. It involves thorough medical evaluation, with optimization of cardiac and pulmonary status. The workup for potential living donors also takes several months.

In order to decrease the incidence of graft rejection, several regimens of immunosuppressive agents have been devised. Centers throughout the world may use different combinations of these drugs, but the basic idea behind their use is to prevent acute and chronic T-cell alloimmune rejection. The regimens are separated into the induction phase and then a long-term maintenance phase. Four classes of immunosuppressive medications are used: corticosteroids, calcineurin inhibitors (cyclosporine and tacrolimus), antimetabolites (mycophenolate mofetil, mycophenolate sodium, and azathioprine), and the target-of-rapamycin (TOR) inhibitor (sirolimus). The maintenance phase involves a combination of two or three of these drugs, each from a separate class.

Immunosuppressant therapy is started in the immediate preoperative period. In the intraoperative period, induction therapy is targeted to eliminate lymphoid cells that may cause acute rejection of the graft. An induction agent may be withheld if immediate graft function occurs from a living donor kidney. After surgery, maintenance therapy is begun for the life of the recipient. Although lifelong immunosuppression helps prevent rejection of the allograft, it also increases the risk of malignancy and infectious diseases. The regimens may not prevent the slow deterioration associated with chronic graft rejection.

In an effort to reduce the long-term toxicities of immunosuppressant drugs, corticosteroid-and calcineurin inhibitor (CNI)-sparing protocols have become popular in managing kidney transplant patients. This is because the long-term use of steroids contributes to cardiovascular disease and/or infectious disease complications.

CNIs prevent acute rejection but are associated with reduced long-term allograft function. Protocols with agents such as mycophenolate mofetil, mycophenolate sodium, sirolimus, everolimus, and belatacept allow discontinuation of CNI within 6 months or avoid the CNIs.