Nonimmunologic Complications After Kidney Transplantation

Sagar Gupta

Tarek Alhamad

General Principles

Differential diagnosis for post-transplant allograft dysfunction depends on many factors; importantly, the timing after transplantation (please see Table 30-1).
For allograft dysfunction in the early perioperative period, urologic and vascular surgical complications should be investigated and the possibility of rejection considered; other common etiologies include hypovolemia, hyperglycemia, drug toxicity (commonly calcineurin inhibitor [CNI] toxicity), and infection.
Acute rejection, recurrent disease, chronic allograft nephropathy, CNI toxicity, BK virus nephropathy (BKVN), and transplant renal artery stenosis are transplant-specific causes of renal dysfunction. However, it is important to recognize that renal failure can also ensue from all causes affecting nontransplant patients.

TABLE 30-1 DIFFERENTIAL DIAGNOSIS OF RENAL ALLOGRAFT DYSFUNCTION

First Week Post-Transplant	<3 Months Post-Transplant	>3 Months Post-Transplant
Acute tubular necrosis	Acute rejection	Acute rejection
Accelerated rejection	Calcineurin inhibitor toxicity	Chronic rejection
Hypovolemia	Hypovolemia	Calcineurin inhibitor toxicity
Obstruction	Hyperglycemia, hypercalcemia	Hypovolemia
	Obstruction	Obstruction
Urinary leak	Infection	Recurrent or de novo renal disease
Vascular thrombosis	Infectious (e.g., BKVN) or drug-induced interstitial nephritis	Infection
Atheroemboli	Recurrent renal disease	Transplant renal artery or iliac stenosis
Infections	Malignancy (allograft PTLD)	Malignancy
Thrombotic microangiopathy	Thrombotic microangiopathy	Thrombotic microangiopathy
BKVN, BK virus nephropathy; PTLD, post-transplant lymphoproliferative disorder.

Surgical Complications

Postoperative complications range between 5% and 10% (please see Table 30-2)
Arterial surgical complications include bleeding, renal artery thrombosis, and renal artery stenosis
Venous surgical complications include bleeding and renal vein thrombosis
Ureteral surgical complications include urinary leak and ureteral obstruction
Other complications are lymphocele, seromas, and infections

Infections

General Principles

A wide spectrum of potential pathogens infects immunocompromised hosts; many are infrequent pathogens in normal individuals.
Fever and physical signs of infection (e.g., erythema) are often diminished.
Risk factors for infections include:
- Prior therapies (chemotherapy or antimicrobials)
- Immunosuppressive therapy: type, temporal sequence, and intensity
- Mucocutaneous barrier integrity (catheters, lines, drains)
- Neutropenia, lymphopenia, hypogammaglobulinemia (often drug induced)
- Technical complications (graft injury, fluid collections, wounds)
- Underlying immune defects (e.g., genetic polymorphisms, autoimmune disease)
- Metabolic conditions: uremia, malnutrition, diabetes, alcoholism, cirrhosis, advanced age
- Viral infection (e.g., herpesviruses, hepatitides B and C, HIV, respiratory syncytial virus [RSV], influenza)

Cytomegalovirus (CMV)

General Principles

It is the human herpesvirus 5 (HHV-5).
Seroprevalence of CMV is around 60% in the general population and it varies according to the age and race.¹
Transmission is through blood, sexual intercourse, and transplanted organs.
Active infection in kidney transplant recipients is 30% to 70% without prophylaxis at 1 month from transplant with the highest rate in patients with donor CMV IgG positive into recipient CMV IgG negative.²
CMV infection leads to increased morbidity, mortality, and allograft failure.
Risk factors for CMV infection:
- Highest risk: CMV donor positive into recipient-negative serostatus
- Comorbid illnesses
- Neutropenia
- Lack of CMV prophylaxis
CMV infection is uncommon in CMV negative into recipient-negative serostatus.
Often considered as a disease of overimmunosuppression.

TABLE 30-2 SURGICAL COMPLICATIONS AFTER TRANSPLANTATION: CAUSES, SYMPTOMS, AND MANAGEMENT

Surgical Complication	Causes/Risk factors	Signs and Symptoms	Evaluation and Treatment
Arterial bleeding	Anastomotic leak Systemic anticoagulation Bleeding diathesis	Hypotension Tachycardia Drop in hematocrit Allograft dysfunction from compression	Blood transfusion Imaging (US/CT) Conservative management Surgical exploration and evacuation (if not a brisk or significant bleed and/or allograft dysfunction)
Venous bleeding	Anastomotic leak Systemic anticoagulation Bleeding diathesis	Hypotension Tachycardia Drop in hematocrit Allograft dysfunction from compression	Blood transfusion Imaging (US/CT) May need surgical exploration and evacuation
Renal artery thrombosis	Hypotension Hyperacute or unresponsive acute rejection Hypercoagulable state Multiple renal arteries Unidentified intimal flaps	Occurs early after transplant Sudden-onset oliguria/anuria (often complete) AKI Hyperkalemia	US Doppler shows no flow Radionuclide renal scan shows no uptake Immediate return to operation room for thrombectomy, but may need allograft nephrectomy
Renal vein thrombosis	Hypercoagulable state Hematomas or lymphoceles causing compression Anastomotic stenosis Extension of a DVT	Occurs early after transplant Tender swollen allograft Hematuria	US Doppler shows decreased flow in vein Attempt at thrombectomy, but may need allograft nephrectomy if unsuccessful
Urinary leak	Ureteral necrosis Disrupted anastomosis	Decreased urine output Pain due to urine irritation AKI	US, nuclear scan or CT shows fluid collection If Jackson–Pratt (JP) drain is present, JP fluid Cr will be elevated (equals urine creatinine) Treat with Foley catheter, nephrostomy, or surgical revision of anastomosis
Ureteral obstruction	Extrinsic: fluid collection or mass compressing the ureter Intrinsic: ureteral stenosis, structure, renal calculi Late stricturing can be seen in BK nephropathy	Decreased urine output AKI	US dilation of ureter Nuclear scan shows poor flow/retained tracer Treat with percutaneous nephrostomy with stenting and dilation, surgical revision of anastomosis
Lymphocele		Decreased urine output AKI (if compresses allograft) Suprapubic pressure Scrotal edema Unilateral leg edema Possible DVT	US or CT will show fluid collection, compression of allograft, or hydronephrosis. Drain lymphocele (percutaneous in VIR or laparoscopic) Peritoneal window to prevent recurrence
Renal artery stenosis	Difficulties in harvesting and operative techniques Atherosclerotic disease CMV infection Delayed graft function	Most commonly between 3 months and 2 years Difficult to control or acute increase in BP Fluid retention Flash pulmonary edema Allograft dysfunction which worsens with ACEi/ARB	Screening with US Doppler: shows increased velocity at stenosis site Confirmatory tests: MR/CT angiography Arteriography is ideal but invasive—diagnose and treat at same time Treat with endovascular stenting Rarely surgical redo of anastomosis may be needed
ACEi, angiotensin-converting enzyme inhibitor; AKI, acute kidney injury; ARB, angiotensin receptor blocker; BP, blood pressure; CMV, cytomegalovirus; CT, computed tomography; DVT, deep venous thrombosis; US, ultrasound; VIR, vascular interventional radiology.