[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Conditions](https://durgical.com/en/conditions/) › Kidney transplant rejection

[Conditions](https://durgical.com/en/conditions/) · [Nephrology and urology](https://durgical.com/en/conditions/)

# Kidney transplant rejection

Rejection is the recipient's immune system attacking a transplanted [kidney](https://durgical.com/en/anatomy/kidney/). It can be sudden or slow and is the main threat to graft survival.

Updated 2026-11-01

## Structures involved

Tap one to see what it is and open it in 3D.

- [Kidneys](https://durgical.com/en/anatomy/kidney/)
- [Common iliac arteries](https://durgical.com/en/anatomy/common-iliac-artery/)
- [Common iliac veins](https://durgical.com/en/anatomy/common-iliac-vein/)
- [Ureters](https://durgical.com/en/anatomy/ureter/)
- [Urinary bladder](https://durgical.com/en/anatomy/urinary-bladder/)
- [Right renal artery](https://durgical.com/en/anatomy/renal-artery-abdomen/)
- [Right renal vein](https://durgical.com/en/anatomy/right-renal-vein-abdomen/)

## Why it happens

- [Fibrosis in organs: TGF-β and the myofibroblast](https://durgical.com/en/general-pathology/fibrosis-in-organs-tgf-and-the-myofibroblast/)
- [Innate and adaptive immunity: overview](https://durgical.com/en/physiology/innate-and-adaptive-immunity-overview/)
- [Blood groups, transfusion and transfusion reactions](https://durgical.com/en/physiology/blood-groups-transfusion-and-transfusion-reactions/)

## What it is

Immune-mediated injury of a transplanted kidney by the recipient's T cells and/or antibodies directed against donor antigens (mainly HLA). It is classified by timing and mechanism as hyperacute, acute (T-cell-mediated or antibody-mediated) or chronic.

## Who gets it

Kidney transplantation is the preferred treatment for end-stage kidney disease and is performed in Colombia and other Latin American countries from living and deceased donors, although waiting lists are long. Acute rejection is most frequent in the first months; chronic graft loss accumulates over years. Poor access to or adherence with immunosuppressants is a key driver everywhere.

## Causes

- HLA mismatch between donor and recipient
- Preformed anti-donor antibodies (previous transplants, pregnancies or transfusions); ABO incompatibility
- Insufficient immunosuppression: missed doses, drug interactions or deliberate reduction
- Donor-specific antibodies that appear after transplant (de novo)

## Risk factors

- Non-adherence to immunosuppressive therapy, the leading preventable cause
- High panel-reactive antibody level (sensitised recipient) and repeat transplant
- Greater number of HLA mismatches
- Delayed graft function after surgery
- Younger recipient age and some infections (e.g. CMV) that trigger immune activation

## Pathophysiology

Donor HLA molecules on graft cells are recognised as foreign. In hyperacute rejection, preformed antibodies bind the endothelium within minutes, activate complement and thrombose the graft vessels. In acute cellular rejection, recipient T cells infiltrate the interstitium and tubules (tubulitis); in antibody-mediated rejection, donor-specific antibodies injure capillaries (C4d deposition). Chronic rejection is a slow immune and non-immune injury with arterial intimal thickening, interstitial fibrosis and tubular atrophy.

## Classification

- Hyperacute: minutes to hours, preformed antibodies (ABO or HLA); graft becomes mottled and thrombosed
- Acute T-cell-mediated (cellular): usually days to months; interstitial lymphocytes and tubulitis
- Acute antibody-mediated: donor-specific antibodies, peritubular capillaritis, C4d positivity
- Chronic (mainly chronic active antibody-mediated rejection; the old term 'chronic allograft nephropathy' is no longer used): months to years; vascular intimal fibrosis, interstitial fibrosis and tubular atrophy

## Symptoms and signs

- Often silent: detected only by a rise in serum creatinine on routine monitoring
- Reduced urine output and weight gain or oedema
- Pain, tenderness or swelling over the graft in the iliac fossa
- Fever and malaise (less common with modern immunosuppression)
- New or worsening hypertension
- Chronic rejection: slow decline in kidney function with proteinuria

## Red flags

- Sudden fall in urine output or anuria after transplant
- Rapid creatinine rise, especially in someone who has missed immunosuppressant doses
- Graft pain with fever (rejection versus graft infection)
- Hyperkalaemia or fluid overload with breathlessness
- Fever, sore throat or other signs of infection in an immunosuppressed patient

## Diagnosis

**Clinical**
Suspected when creatinine rises or urine output falls in a transplant recipient; review adherence, drug levels and recent infections, and rule out other causes of graft dysfunction.

**Tests**
Serum creatinine and electrolytes, trough immunosuppressant levels (e.g. calcineurin inhibitors), urinalysis and protein, donor-specific antibody testing, and viral testing (CMV, BK virus). Percutaneous graft biopsy graded by the Banff classification is the gold standard and separates cellular from antibody-mediated rejection.

**Imaging**
Doppler ultrasound of the graft to exclude obstruction, fluid collections (lymphocele, urinoma) and [renal artery](https://durgical.com/en/anatomy/renal-artery/) or vein thrombosis or stenosis; it also guides biopsy.

## Differential diagnosis

- Calcineurin-inhibitor nephrotoxicity
- Acute tubular necrosis or delayed graft function
- Urinary obstruction or urine leak
- Transplant renal artery stenosis or graft vessel thrombosis
- BK virus nephropathy or graft pyelonephritis
- Recurrence of the original kidney disease (e.g. FSGS)

## Goal of treatment

Prevent rejection with lifelong immunosuppression balanced against infection and cancer risk; when rejection occurs, reverse it quickly to preserve graft function.

## Treatment

**Medical**
Maintenance immunosuppression, usually a calcineurin inhibitor (tacrolimus or ciclosporin) plus an antiproliferative agent (mycophenolate or azathioprine) with or without corticosteroids; mTOR inhibitors and belatacept are alternatives.

**Acute**
Acute cellular rejection is treated with high-dose intravenous corticosteroids and, if resistant, T-cell-depleting antibodies (anti-thymocyte globulin).

**Procedure**
Antibody-mediated rejection may be treated with plasmapheresis and intravenous immunoglobulin, sometimes with anti-CD20 therapy. Hyperacute rejection cannot be reversed and requires removal of the graft.

**Follow-up**
Nursing and follow-up: strict timing of immunosuppressants, trough drug levels, daily weight, urine output and blood pressure, creatinine trends, and watching for infection and drug side effects (hyperglycaemia, tremor, hyperkalaemia).

**Lifestyle**
Patient education on adherence, avoiding interacting drugs and some foods (such as grapefruit), sun protection and [skin](https://durgical.com/en/anatomy/skin/) checks, and live-vaccine avoidance.

## Drugs for this condition

- [Basiliximab](https://durgical.com/en/pharmacology/basiliximab/)

## Complications

- Graft loss and return to dialysis
- Opportunistic infections from immunosuppression (CMV, BK virus, Pneumocystis, fungal)
- Post-transplant lymphoproliferative disorder (often EBV-related) and skin cancers
- Drug toxicity: nephrotoxicity, new-onset diabetes after transplant, hypertension, dyslipidaemia
- Cardiovascular disease, the leading cause of death with a functioning graft

## Prognosis

Most acute cellular rejection episodes respond to treatment. Antibody-mediated and chronic rejection respond less well and are the main causes of late graft loss. Graft survival is longer with living donors, good HLA matching and consistent adherence.

## Prevention

- ABO and HLA matching and a negative crossmatch before transplant
- Induction immunosuppression at the time of surgery in higher-risk recipients
- Lifelong adherence to maintenance immunosuppression with regular drug-level monitoring

## Test yourself

Think of the answer, then tap the question to see it.

## What causes hyperacute kidney transplant rejection?

Preformed recipient antibodies (ABO or anti-HLA) that bind graft endothelium within minutes, activating complement and thrombosing the vessels.

## What is the gold standard test to confirm kidney transplant rejection?

A graft biopsy graded by the Banff classification.

## Which histologic finding defines acute T-cell-mediated rejection?

Interstitial lymphocytic infiltrate with tubulitis (lymphocytes invading tubular epithelium).

## What is the first-line treatment of acute cellular rejection?

Pulse high-dose intravenous corticosteroids, with T-cell-depleting antibodies if steroid resistant.

## What is the leading preventable cause of late graft rejection?

Non-adherence to maintenance immunosuppressive therapy.

[Add to my cards (5)](https://durgical.app/estudiar/?add=/en/conditions/kidney-transplant-rejection/)

## Related conditions

- [Chronic kidney disease](https://durgical.com/en/conditions/chronic-kidney-disease/)
- [Acute kidney injury](https://durgical.com/en/conditions/acute-kidney-injury/)
- [Cytomegalovirus infection](https://durgical.com/en/conditions/cytomegalovirus-infection/)
- [Diabetic kidney disease](https://durgical.com/en/conditions/diabetic-kidney-disease/)
- [Focal segmental glomerulosclerosis](https://durgical.com/en/conditions/focal-segmental-glomerulosclerosis/)
- [Non-Hodgkin lymphoma](https://durgical.com/en/conditions/non-hodgkin-lymphoma/)
- [Acute pyelonephritis](https://durgical.com/en/conditions/acute-pyelonephritis/)
- [Hyperkalaemia](https://durgical.com/en/conditions/hyperkalaemia/)

Educational information, not medical advice. For any symptom, see a health professional.

Sources: [Transplant rejection: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/000815.htm) (MedlinePlus (U.S. National Library of Medicine), 2024); [Kidney Transplant](https://www.niddk.nih.gov/health-information/kidney-disease/kidney-failure/kidney-transplant) (NIDDK (National Institutes of Health), 2024).

[← All conditions](https://durgical.com/en/conditions/)

## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake

Representative model, for educational purposes only.

---
Source: https://durgical.com/en/conditions/kidney-transplant-rejection/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/conditions/kidney-transplant-rejection/