Acute Rejection, Kidney
GENERAL PRINCIPLES
Most episodes of acute rejection occur within the first year after transplantation. The low incidence of acute rejection today necessitates a careful search for inadequate drug levels, nonadherence, or less common forms of rejection (such as antibody-mediated rejection or plasma cell rejection).
Late acute rejection (gt;1 year after transplantation) is often a result of inadequate immunosuppression or patient nonadherence.Definition
An immunologically mediated acute deterioration in renal function associated with specific pathologic changes on renal biopsy including lymphocytic interstitial infiltrates, tubulitis, and arteritis (cellular rejection) and/or glomerulitis, capillaritis, and positive staining of the peritubular capillaries for the complement component C4d (antibody-mediated rejection).
Epidemiology
Kidney allograft rejection currently occurs in ~10% of patients. Patients who do not receive induction therapy have a 20%-30% incidence of acute rejection.
DIAGNOSIS
Diagnosis of acute renal allograft rejection is made by percutaneous renal biopsy after excluding prerenal azotemia, CNI nephrotoxicity (trough and/or peak levels and associated signs), infection (urinalysis and culture), obstruction (renal ultrasound), and surgical complications such as urine leak (renal scan). Newer techniques evaluating early markers of acute rejection in the blood and urine are under investigation.
Clinical Presentation
Manifestations include an elevated serum creatinine, decreased urine output, increased edema, or worsening hypertension. Initial symptoms are often absent, only laboratory evaluation will show a rise in creatinine. Constitutional symptoms (fever, malaise, arthralgia, painful or swollen allograft) are uncommon in current practice.
Differential Diagnosis
Differential diagnosis varies with duration after transplantation (Table 17-2).
TABLE 17-2
DIFFERENTIAL DIAGNOSIS OF RENAL ALLOGRAFT DYSFUNCTION
| gt;1 wk After Transplant | lt;3 mo After Transplant | gt;3 mo After Transplant |
| Acute tubular necrosis | Acute rejection | Prerenal azotemia |
| Hyperacute rejection | Calcineurin inhibitor toxicity | Calcineurin inhibitor toxicity |
| Accelerated rejection | Prerenal azotemia | Acute rejection (nonadherence, low levels) |
| Obstruction | Obstruction | Obstruction |
| Urine leak (ureteral necrosis) | Infection | Recurrent renal disease |
| Arterial or venous thrombosis | Interstitial nephritis | De novo renal disease |
| Atheroemboli | Recurrent renal | Renal artery stenosis (anastomotic or |
disease atherosclerotic)
BK virus nephropathy BK virus nephropathy