Hyperacute rejection of renal transplants is a rapid rejection that occurs within minutes to hours after transplantation due to preformed antibodies against donor endothelium. These antibodies activate complement and platelets, causing cyanosis, swelling, hemorrhage and necrosis of the graft. Microscopy shows platelet and neutrophil margination in the peritubular capillaries within hours along with widespread thrombi formation within a day. Immunohistochemistry and immunofluorescence can detect C4d and complement deposition in the peritubular capillaries.
3. Mechanism
Preformed antibodies to donor endothelium
ABO, HLA, or others
Antibodies activate complement, endothelium,
and platelets
4. Clinical aspect
Incidence <0.5%
Decreased due to pretransplant testing
Primary nonfunction or loss of function within
hours after transplant
Anuria, lack of graft perfusion
No effective treatment
5. Macroscopic
Cyanosis of graft within minutes to hours
Swelling, hemorrhage, necrosis within a day
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12. Microscopy
Early (1-12 hr)
Platelet and neutrophil margination in PTC
Congested PTC
Scattered thrombi
Late (12-24 hr)
Widespread thrombi
Interstitial edema and hemorrhage
Cortical and medullary necrosis
Fibrinoid necrosis
Rare cases due to primed cytotoxic T cells, without complement or due to exogenous antithymocyte globulin or 3rd-party plasma
In cross section, this normal adult kidney demonstrates the lighter outer cortex and the darker medulla, with the renal pyramids into which the collecting ducts coalesce and drain into the calyces and central pelvis.
Nephrectomy Specimen With Hyperacute Rejection
This kidney is swollen, hemorrhagic, dusky, and has pale focal areas of necrosis .
Nephrectomy specimen with hyperacute rejection shows edema, as indicated by the glistening cut surface, and hemorrhage. The dark zones at the corticomedullary junction are due to marked congestion . The medullary areas are pale due to ischemia.
Hemorrhage and Necrosis
Cross section of a nephrectomy of an allograft with hyperacute rejection reveals pale medullary pyramids, which are necrotic . Foci of necrosis are also evident in the cortex .
Glistening due to edema, hemorrhage and necrosis (paler areas)
Note the swollen and hemorrhagic appearance of this entire kidney sectioned in half.
This is a normal glomerulus by light microscopy. The glomerular capillary loops are thin and delicate. Endothelial and mesangial cells are normal in number. The surrounding tubules are normal.
Glomerular Capillaritis
Shown here are neutrophils within glomerular capillaries within a few hours post implantation in hyperacute rejection. Capillaries are congested, and some have lost endothelial nuclei . These are the 1st histological signs of hyperacute rejection.
Glomerular Thrombi
H&E shows glomerular thrombi in hyperacute rejection. The differential is between thrombotic microangiopathy, possibly donor disease, or preservation injury. C4d, as well as testing for antidonor antibodies, helps distinguish these possibilities.
Peritubular Capillaritis
H&E shows neutrophils within peritubular capillaries in hyperacute rejection . This biopsy was taken a few hours after implantation. The peritubular capillaries are markedly congested. Similar but milder congestion may be due to ischemia reperfusion injury and may be present at the time of implantation.
Early Cortical Necrosis in Day 1 Biopsy
Loss of nuclei in proximal tubules indicates early cortical necrosis. Interstitial hemorrhage due to peritubular capillary destruction is also evident as well as glomerular thrombi . This graft was removed 3 days later.
Hyperacute Rejection in Day 1 Biopsy
This biopsy 1 day after transplantation shows the classic features of hyperacute rejection: Interstitial hemorrhage , glomerular thrombi and neutrophils in peritubular and glomerular capillaries, and focal tubular necrosis.
Cortical Necrosis
H&E shows a low-magnification view of a renal allograft with hyperacute rejection. Cortical necrosis and hemorrhage are widespread . C4d stain was negative in the necrotic areas, comprising 95% of the sample. Nonnecrotic areas were selected from the paraffin-embedded material for C4d staining .
Diffuse Hemorrhage and Necrosis
This nephrectomy specimen from a patient with hyperacute rejection 3 days post transplant shows congestion and necrosis involving all elements of the kidney.
C4d immunohistochemistry in a wedge biopsy of hyperacute rejection shows strong staining of peritubular capillaries focally . Necrotic areas are C4d(-) . C4d can be negative in early biopsies of hyperacute rejection, probably due to poor perfusion.
Postperfusion biopsy shows prominent CD61 staining in peritubular capillaries, indicating the presence of platelets . CD61 detects the platelet receptor for fibrinogen (IIb/IIIa) and may be a useful test to detect hyperacute rejection.
Diffuse, bright circumferential staining of PTCs for C4d by immunofluorescence (IF) is shown. A positive C4d stain is defined as linear endothelial staining of ≥ 10% of PTC by IF in frozen sections or > 0% of PTC by immunohistochemistry (IHC) in paraffin-embedded samples.
