Kidney Transplants

Kidneys are the most frequently transplanted organ; more than 285,000 transplants have been performed through 2007, with over 16,000 transplants performed per year in the United States¹ (Table 196-1). Numerous causes of chronic renal failure result in the need for transplantation, the most common being diabetes mellitus and glomerular disorders (Box 196-1). The source of donors for renal transplantation are both cadavers and living donors. In 2009, there were 10,442 cadaveric donor transplants and 6387 living donor transplants performed.^1,2 The living donor pool consists of both living related donors, who have a higher likelihood for a favorable crossmatch, and living unrelated donors. Recent surgical innovations such as using laparoscopy to obtain the donor kidney have decreased morbidity for donors and decreased costs.³ The living donor pool may be expanded through the use of programs to utilize nonrelated donors (e.g., kidney paired donations, non-directed donation).

TABLE 196-1 Kidney, Pancreas, and Kidney-Pancreas Transplant Statistics

In most cases, the renal transplant operation is done through a retroperitoneal flank incision. An anastomosis is created between the recipient’s iliac artery and the donor kidney’s renal artery. Another anastomosis is fashioned between the iliac vein and the renal vein. The donor ureter is connected either to the recipient’s bladder using a ureteroneocystostomy or to the recipient’s ureter via ureteropyelostomy.

Pancreas Transplants

Pancreas transplantation for control of diabetes was first successfully reported by Lillehei and colleagues in 1970.⁴ The major indication for transplantation of this organ is diabetes mellitus. Because of the significant morbidity associated with immunosuppression, transplantation of this organ in isolation is uncommon; most pancreatic transplants are carried out in conjunction with a simultaneous or previous kidney transplant. In 2009, there were 854 simultaneous kidney-pancreas transplants and 379 pancreas-after-kidney transplants or solitary pancreas transplants.² Isolated pancreatic islet cell transplantation (autotransplantation) has been utilized as an adjunct to total pancreatectomy for patients with intractable pain due to chronic pancreatitis and is an active area of research using human and genetically modified animal islet cells to produce insulin while minimizing the risks of immunosuppression.⁵ However, these techniques are difficult to apply outside of specialized centers.

The surgical technique for pancreas transplantation involves anastomosis of the pancreatic vascular supply to the iliac artery and vein. A major issue in pancreatic transplantation is ensuring safe drainage of exocrine secretions. The two options employed are drainage of the pancreatic duct into the bladder and drainage of the duct into the small intestine. Bladder drainage has a lower infection rate, but it is associated with metabolic acidosis due to bicarbonate losses in the urine, as well as cystitis, urethral stricture, and hematuria. This has led to a recent increase in the use of enteric drainage.

Compared with other solid-organ transplant operations, rejection is more difficult to diagnose in pancreas transplantation for a number of reasons. Hyperglycemia is not manifested until a significant portion of the graft is lost. For grafts drained into the bladder, decreases in urinary amylase concentrations sometimes suggest that rejection is occurring, although this test is not very sensitive. Needle core biopsies under ultrasound guidance using 18- or 20-gauge needles have reduced complications associated with biopsies to 2% to 3%.⁶ The problem of detecting rejection of pancreatic grafts has prompted efforts to carry out simultaneous pancreatic and kidney transplants, using the kidney as a “canary” to detect rejection of both organs. This indicator of rejection is not as effective in pancreas-after-kidney transplants, because the two organs are immunologically distinct, as evidenced by higher pancreas graft loss rates after pancreas-after-kidney procedures as compared with simultaneous transplants (22% versus 15%).⁷ The advantage of early identification of rejection must be balanced against the increased risk of perioperative complications as a consequence of the more challenging simultaneous operation.

Postoperative Respiratory Failure

The majority of kidney and/or pancreas transplant patients admitted with a diagnosis of respiratory failure after surgery have a self-limited form of the condition secondary to the residual effects of general anesthesia. These patients can be extubated when awake, and recovery from the effects of neuromuscular blocking agents is complete or nearly so. Other causes of immediate postoperative respiratory failure include congestive heart failure from perioperative myocardial infarction (MI), pulmonary edema due to intravascular volume overload secondary to acute tubular necrosis, preexisting pneumonia, aspiration pneumonitis, pulmonary embolus, or (rarely) acute respiratory distress syndrome (ARDS) secondary to intraoperative events or posttransplant pancreatitis. In this setting, it is key to perform a rapid and thorough diagnostic workup to determine the etiology of more serious causes of respiratory failure. This evaluation should include electrocardiography (ECG), determination of circulating levels of cardiac enzymes, chest radiography, arterial blood gas analysis, and measurements of serum electrolytes and blood urea nitrogen (BUN)/creatinine concentration. Based on findings from history, physical examination, and the results of these initial tests, the clinician can obtain additional tests as needed to establish a diagnosis. Additional tests that may be helpful include duplex ultrasound scans of the lower extremities for deep venous thrombosis, spiral computed tomography (CT) of the chest to evaluate for pulmonary embolus, cardiac echocardiography, diagnostic bronchoscopy, and transplant ultrasound and/or biopsy.

Respiratory Failure Distant To Transplant

Occasionally, patients are admitted to the ICU with respiratory insufficiency or failure weeks or years after pancreatic and/or renal transplantation. The differential diagnosis is broadened in these patients because of the increased risk of infection associated with immunosuppression. The differential diagnosis for respiratory failure includes infectious causes, cardiogenic causes, and renal failure. It is important to glean from the patient, family, or records any features such as cytomegalovirus (CMV) status of the patient and donor, past history of cardiac disease, and recent changes in transplantation medications. A rapid workup should take place to evaluate the cause of decompensation. It is frequently necessary to intubate the patient, even in the absence of overt respiratory failure, to perform bronchoscopy for diagnostic evaluation. Initial evaluation should include chest radiography; complete blood cell count; determination of serum electrolytes, BUN/creatinine and cardiac enzymes; sputum sampling; and ECG. It is also prudent to include a rapid screen for CMV in this evaluation. Other tests, including diagnostic bronchoscopy, CT of the chest, echocardiography, and lower extremity Doppler examinations, should be carried out as clinically indicated. Typically, the noninfectious causes of respiratory failure, such as renal failure with fluid overload and myocardial dysfunction causing congestive heart failure, are more readily identified and treated, leaving the more subtle causes to sort through over the next several days of the patient’s ICU course. Exclusion of cardiac and renal failure mandates strong consideration for the possibility of an infectious cause of respiratory compromise.

Initial treatment for posttransplant respiratory failure distant to surgery requires broad-spectrum antibacterial, fungal, and viral therapy until a definitive diagnosis is reached. It is not unusual in such circumstances to have patients on agents that will cover common bacterial organisms, Candida and Aspergillus, and CMV (see also Chapter 195). Common regimens include broad-spectrum antibiotic agents with antipseudomonal and antianaerobic activity, an agent with gram-positive activity, a broad-spectrum antifungal agent, and ganciclovir to provide antiviral coverage for cytomegalovirus and other members of the herpesvirus family. Similarly to other work in the ICU care, delay to appropriate antibiotics in transplant patients has been associated with worsened outcomes.¹⁶ A number of appropriate agents for this purpose are listed in Table 196-6. In situations where Pseudomonas is strongly suspected, an additional agent should be added to provide double coverage of this organism. In situations where the patient has high risk for or has known vancomycin-resistant Enterococcus faecium, one of the new gram-positive agents should be chosen. Another key component of treatment in this setting is strong consideration for short-term discontinuation of most immunosuppressive medications. The practice at our institution is to hold all but maintenance doses of corticosteroids when infection is strongly suspected. It is frequently possible to tailor antimicrobial therapy as results return. For instance, in the setting of a patient with a low white blood cell count, diffuse pneumonitis, and positive screen for CMV, it is not unreasonable to discontinue antifungal therapy. It is important for the intensivist to be willing to revisit the diagnosis on at least a daily basis, especially if the clinical course is not consistent with the working diagnosis.

TABLE 196-6 Empirical Agents for Early Treatment of Infection in Kidney/Pancreas Transplant Patients

* Please note that doses given do not account for renal or hepatic insufficiency common in critically ill patients. Prior to choosing an empirical antibiotic regimen, the clinician should carefully consider the patient scenario and medication side effects related to the specific patient.

^† Rather than a single agent, combination agents covering both gram-negative organisms and anaerobes may be chosen (e.g., fluoroquinolone plus clindamycin or metronidazole). For cases with a strong suspicion for Pseudomonas aeruginosa infection, additional Pseudomonas coverage should be added (e.g., fluoroquinolone or aminoglycoside).

^‡ When vancomycin-resistant Enterococcus faecium infection is suspected, one of the latter 4 choices should be employed.

^§ Daptomycin is not indicated for treatment of pneumonia (package insert).

^|| Tigecycline is not indicated for treatment of hospital-acquired pneumonia (package insert).

^¶ Antiviral agents directed toward herpesvirus family (most commonly CMV). Adjust for other viruses.