Case Published: November 2019
Diagnosis: Acute Cellular Rejection or Acute T-Cell Mediated Rejection (TCMR)
Case Summary: Well done! Let’s review this case.
Here we have a case of a kidney transplant with HIV within one year post-transplant, who received basiliximab (IL-2 receptor antagonist) induction therapy. On presentation, her tacrolimus is subtherapeutic (trough level only 2 mg/dL). Her creatinine is increased to 1.95 mg/dL, consistent with acute kidney injury (AKI).
Rejection & recurrent native kidney disease
Anatomical problem (e.g. obstructive nephropathy)
BK nephropathy & other viruses
Of course, we must also think about other causes of AKI that affect native allografts (i.e. pre-renal AKI). As the history did not suggest pre-renal AKI and the kidney allograft ultrasound did not reveal evidence of obstruction, allograft biopsy was performed. So what did the biopsy tell us?
The biopsy shows us significant interstitial inflammation, tubulitis (inflammatory cells that might look like eggs with deep blue yolks within the tubular wall) with normal glomeruli and arteries (importantly no arteritis, or inflammatory cells within the arterial wall). This raises suspicion for acute cellular rejection (ACR) or BK nephropathy. In this case, the absence of BK viremia, low tacrolimus trough, basiliximab, and HIV infection suggests ACR or T-cell mediated rejection (TCMR). Though HIV-infected kidney transplant recipients may have excellent allograft outcomes, higher rates of rejection have been reported.
So how to we grade types of rejection? Look to the Banff Criteria (updated every 2 years, 2019 TBD)! The Banff Criteria describes pathologic findings – specifically, for ACR, the degree of interstitial inflammation, tubulitis, and presence or absence of arteritis (the presence of inflammatory cells, mainly lymphocytes and monocytes, in the subendothelial space of 1 or more arteries). There are separate criteria to describe acute antibody mediated rejection (AMR) that we won’t address here, but you can find them here.
i1: 10-25% inflammation of unscarred cortex
i2: 26-50%
i3: > 50%
*t score (tubulitis)
t1: foci with 1 to 4 mononuclear cells/tubular cross section
t2: Foci with 5 to 10 mononuclear cells/tubular cross section
t3: Foci with >10 mononuclear cells/tubular cross section or the presence of ≥2 areas of tubular BM destruction accompanied by i2/i3 inflammation and t2 elsewhere
*v score (arteritis)
v1: mild to moderate INTIMAL arteritis
v2: severe arteritis
t>0 AND i ≤ 1 OR
t1 AND i ≥ 2
*ACR IA
i2 or i3 AND t2
*ACR IB
i2 or i3 AND t2
ACR IIA
v1 (regardless of i or to score)
*ACR IIB
v2 (regardless of i or to score)
*ACR III
v3 (regardless of i or to score)
As seen above, the grade of ACR (borderline, IA, IB, IIA, IIB, or III) is determined by the degree of interstitial infiltration (percentage of interstitial involvement), tubulitis (number of inflammatory cells in the tubular wall), and presence or absence of arteritis (also known as endothelialitis or endarteritis). We won’t cover the details here, but in general, the higher the grade of ACR, the more intensive the therapy. For example, borderline ACR may be treated with corticosteroids alone while a IIA ACR would likely be treated with T-cell depleting therapy (e.g. anti-thymocyte globulin) in addition to corticosteroids.
Stay tuned for a case of ANTIBODY mediated rejection!
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