Hematology, Oncology & Immunology · Topic 23 of 26

Solid Organ Transplant Recipient

Transplant · solid organ recipient

Solid Organ Transplant Recipient

A failing graft is rejection until biopsy says otherwise; every new drug can swing calcineurin inhibitor levels; the month after transplant predicts the infection.

Key numbers

Months 1–6: opportunistic infections peakmonths 1–6

Acute CNI nephrotoxicity: supratherapeutic troughtrough > 20 ng/mL

01 · FirstGraft dysfunction: biopsy separates rejection from toxicity

Rising creatinine in a kidney recipient (or rising liver tests in a liver recipient) means looking for rejection; graft biopsy confirms it and separates it from CNI toxicity, BK virus, obstruction or vascular compromise.

02 · AvoidCYP3A4 inhibitors raise, inducers lower tacrolimus

Tacrolimus and cyclosporine are CYP3A4 substrates: azoles, clarithromycin/erythromycin, diltiazem, verapamil, ritonavir and grapefruit raise levels (toxicity); rifampin, phenytoin, carbamazepine and St John's wort lower them (rejection). Recheck troughs within days.

03 · CauseMonths 1–6: opportunistic infections peak

Infection timeline: first month — surgical, nosocomial and donor-derived infection; months 1–6 — opportunistic and reactivated infection (CMV, Pneumocystis, Listeria, Nocardia, Toxoplasma, BK virus); after 6 months — mostly community pathogens unless immunosuppression is intensified.

Causes & risk factors

Why it happens

Skin cancer and EBV-driven lymphoma riseRecipients have 2–4 times the general cancer risk: skin cancer becomes common (sun protection, skin checks), and post-transplant lymphoproliferative disorder, driven by EBV and highest in EBV-seronegative recipients, is the key lymphoma risk.

Presentation

What you'll see

Acute kidney rejection: fever, rising creatinine, tender graftAcute kidney rejection (days to weeks) brings fever, rising creatinine, hypertension, weight gain and a swollen, tender graft; hyperacute rejection (minutes to hours, HLA incompatibility) means graft failure. Most episodes occur by 3–4 months.

Diagnosis & monitoring

Work-up

Acute CNI nephrotoxicity: supratherapeutic troughAcute CNI nephrotoxicity is dose-related — typically tacrolimus troughs above 20 ng/mL (cyclosporine above 400) — from afferent arteriolar vasoconstriction; it reverses when exposure is reduced.

Do right now

In this order

First moves

Graft dysfunction: biopsy separates rejection from toxicity

→

Acute CNI nephrotoxicity: supratherapeutic troughtrough > 20 ng/mL

→

Acute rejection: pulse methylprednisolone or ATG

Why each step

Graft dysfunction: biopsy separates rejection from toxicityRising creatinine in a kidney recipient (or rising liver tests in a liver recipient) means looking for rejection; graft biopsy confirms it and separates it from CNI toxicity, BK virus, obstruction or vascular compromise.

Acute rejection: pulse methylprednisolone or ATGAcute or accelerated rejection usually reverses with intensified immunosuppression: high-dose pulse IV glucocorticoids (methylprednisolone) or antithymocyte globulin, the usual escalation for severe or steroid-resistant episodes.

Management

Orders

Induction, then tacrolimus + mycophenolate + steroidsStandard immunosuppression: an induction agent (antithymocyte globulin, alemtuzumab or basiliximab) at surgery, then a calcineurin inhibitor (usually tacrolimus) with mycophenolate and glucocorticoids tapered over the following weeks.

TMP-SMX prophylaxis covers Pneumocystis and moreMost centers give TMP-SMX after transplant for Pneumocystis, which also prevents Listeria, Nocardia, Toxoplasma and some urinary infections; antivirals prevent HSV and VZV reactivation.

Red flags & don'ts

Avoid harm

CNI toxicity: kidney, potassium, magnesium, glucose, nerves complicationCalcineurin inhibitors cause nephrotoxicity, hyperkalemia, hypomagnesemia, hypertension, new-onset diabetes after transplant, and neurotoxicity from tremor and headache to seizures and PRES; dose by whole-blood trough levels.

Add nephrotoxins or potassium-raisers with caution interactionNephrotoxicity rises when tacrolimus is combined with aminoglycosides, amphotericin B, ganciclovir, cisplatin or some antiretrovirals; ACE inhibitors, ARBs and potassium-sparing diuretics add to CNI hyperkalemia — monitor creatinine and potassium.

CNI thrombotic microangiopathy: lower or switch complicationCalcineurin inhibitors can cause thrombotic microangiopathy (systemic HUS/TTP picture or graft-limited TMA) in about 1–3% of kidney recipients; reduce or switch the CNI.

CMV: commonest opportunist; valganciclovir prophylaxis complicationCMV is the most common opportunistic infection after transplant, highest risk in seronegative recipients of seropositive organs; prevent with valganciclovir prophylaxis or PCR-guided preemptive therapy, and treat disease with IV ganciclovir (myelosuppressive, renally dosed).

BK nephropathy: reduce immunosuppression complicationBK polyomavirus nephropathy causes progressive kidney-graft dysfunction with viruria and viremia; biopsy separates it from rejection, and reducing immunosuppression is the first and most important treatment.

No live vaccines on tacrolimus avoidAvoid live vaccines in recipients taking tacrolimus or other maintenance immunosuppression; give inactivated vaccines instead.

Rising creatinine: rejection or CNI toxicity?

Commonly confused

Clues	Fever, hypertension, weight gain, graft swelling or tenderness
Tacrolimus trough	May be low (e.g., after an inducer such as rifampin)
Biopsy	T-cell or antibody-mediated injury
Treatment	Pulse glucocorticoids or antithymocyte globulin

More detail

Reference

Show 7 reference facts

Early liver-graft complications include biliary leaks and strictures, bleeding needing reoperation, hepatic artery or portal vein thrombosis, and primary nonfunction (3–6%) requiring urgent retransplant; rejection shows as abnormal liver tests confirmed by biopsy.

Tacrolimus label troughs for kidney recipients depend on the regimen: 7–20 ng/mL (months 1–3) then 5–15 ng/mL (months 4–12) with azathioprine; 4–11 ng/mL with mycophenolate plus basiliximab. Centers individualize.

Tacrolimus prolongs the QT interval; monitor ECG and electrolytes when combined with other QT-prolonging drugs or with low potassium, calcium or magnesium.

Kidney transplant: 1-year graft survival 95–98%; median graft survival about 19 years for living-donor and 12 years for deceased-donor kidneys. About 5–15% have a rejection episode in year 1.

Red cell transfusion before or soon after kidney transplant can sensitize the recipient to HLA antigens and is linked to antibody-mediated rejection; avoid it when possible.

Chronic allograft nephropathy (graft dysfunction ≥ 3 months after transplant) affects most kidney recipients by 10 years and is mostly due to CNI toxicity, diabetic or hypertensive injury, or BK virus.

Tacrolimus with sirolimus is not recommended in liver and heart transplant because of serious adverse reactions; cannabidiol also raises tacrolimus levels.

Pearl

Before you prescribe for a transplant recipient, ask what it does to the tacrolimus level.

Sources · Merck Manual Professional — Kidney Transplantation (Sept 2026) · Merck Manual Professional — Liver Transplantation · Prograf (tacrolimus) prescribing information — DailyMed · Calcineurin Inhibitor Associated Nephrotoxicity in Kidney Transplantation — A Transplant Nephrologist's Perspective. Acta Physiol 2025 (PMC12005075) · Management of Infection in Patients With Kidney Transplant (infection timeline after Fishman; PMC7152491) · Merck Manual Professional — Approach to the Patient With Suspected Immunodeficiency (no live-virus vaccines) · Starter sheet built from the verified AGACNP fact map (facts reviewed 2026-10-15).