Rejection of the kidney transplant

1. How to evaluate acute kidney injury (AKI) in the kidney transplant patient?

See Fig. 58.1 . When deciding the baseline kidney function and using the serum creatinine (Scr), the clinician must be careful. The ideal baseline Scr is based on the most recent trend when the patient was in a steady state. Time after transplantation is also critical in sorting through the differential diagnosis of AKI. The differential changes when the patient is a recent transplant and could have surgical complications, such as a urine leak in the first few months as opposed to a patient several years after transplant in whom that is less likely.

2. What are the various types of rejection as defined by time?

There are three general types of organ rejection:

1.

Hyperacute
2.

Acute
3.

Chronic

Hyperacute rejection is a complement-mediated response by the recipient with preexisting donor specific antibodies (DSA). Hyperacute rejection occurs almost immediately following organ implantation and necessitates immediate explant of the organ. Hyperacute rejection is uncommon with pre-transplantation cross-matches and screening.

Acute rejection is associated with a sudden deterioration in allograft function that can occur as early as 1 week post-transplantation. Acute rejection may also be subclinical, associated with a more insidious rise in creatinine. Acute rejection has a major adverse effect on long-term graft survival.

Chronic rejection, better defined as chronic antibody-mediated rejection (AMR), is the main cause of late allograft loss and is histologically defined as transplant glomerulopathy (TG).

3. What are the two different types of acute rejection?

For diagnosis, both require a kidney transplant biopsy. A patient can have a mixed rejection with features of both cell-mediated acute cellular rejection and AMR ( Table 58.1 ).

Table 58.1.

Acute Rejection Types

CELL-MEDIATED REJECTION	ANTIBODY-MEDIATED REJECTION
Cell-mediated Adaptive immune system	B-cell mediated Innate immune system Can be activated by a T-cell response
Can occur within the first few weeks of transplant	Can occur within hours to days after transplant
Scr might be stable and can have subclinical rejection, though usually is elevated	When acute, more likely to cause rapid kidney allograft dysfunction Proteinuria
Lymphocyte infiltration, tubulits, arteritis Negative DSA Negative C4d in peritubular capillaries	Intimal arteritis, peritubular capillaritis and glomerulitis, microthrombi Positive DSA Positive C4d in peritubular capillaries (can be negative in AMR; however, have positive DSA and other histological changes consistent with acute AMR
Treatment involves shutting down T-cell response using steroids and lymphocyte-depleting agents Optimize maintenance immunosuppression	Treatment involves removing and shutting down antibody production using steroids, plasmapheresis, intravenous immunoglobulin, lymphocyte-depleting agents, and B-cell (rituxan, boertezomab) or compliment- specific therapies (eculizimab) Optimize maintenance immunosuppression

AMR , Antibody-mediated rejection; DSA , donor specific antibodies; Scr , serum creatinine.

4. What is the banff criteria for acute cell-mediated rejection?

The Banff classification of kidney allograft rejection grades acute tubulointerstitial rejection by severity of tubulitis and acute vascular rejection by severity of arteritis. Types of T-cell-mediated rejection are as follows:

•

Type IA: Cases with significant interstitial infiltration by lymphocytes (>25% of parenchyma affected) and foci of moderate tubulitis
•

Type IB: Cases with significant interstitial infiltration of lymphocytes (>25% of parenchyma affected) and foci of severe tubulitis
•

Type IIA: Cases with mild-to-moderate intimal arteritis
•

Type IIB: Cases with severe intimal arteritis
•

Type III: Cases with transmural arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic inflammation