Kidney transplantation and immunosuppression

01Purpose and principlesWhat the treatment does and how it fits into care.

Transplant evaluation asks whether expected graft and survival benefit outweigh peri-operative, infectious, malignant and cardiovascular risk for this individual. Chronological age alone is not decisive. The team defines the kidney disease and recurrence risk, evaluates urinary tract and vascular anatomy, treats active infection, assesses adherence barriers and explores living donation without coercion. Sensitisation from pregnancy, transfusion or previous transplant can produce HLA antibodies that alter compatibility and waiting time.

The donor kidney is usually placed extraperitoneally in the iliac fossa with vascular anastomoses to iliac vessels and the donor ureter implanted into the bladder; native kidneys commonly remain. Early complications include bleeding, thrombosis, urine leak, obstruction, lymphocele, infection and delayed graft function. Delayed function may require temporary dialysis and does not by itself prove rejection. Ultrasound with Doppler helps assess obstruction, collections and major perfusion, but biopsy is usually needed to classify suspected rejection after safer causes are considered.

Maintenance treatment commonly combines a calcineurin inhibitor, an antiproliferative agent and corticosteroid, modified by immunological risk, toxicity and centre protocol. This narrow balance changes over time: too little exposure permits rejection, while too much produces infection, cancer and organ toxicity. Primary-care, emergency and surgical clinicians should reconcile exact product, formulation, dose and timing, contact the transplant centre before alterations and screen new prescriptions for interactions.

Key points

Kidney transplantation is kidney replacement therapy, not a cure: recipients retain cardiovascular risk, need lifelong surveillance and usually require continuing immunosuppression while the graft functions.
Suitable people should be assessed before dialysis where possible; living-donor and deceased-donor routes require consent, infection and cancer screening, cardiovascular assessment, ABO and HLA work-up and a current crossmatch strategy.
A rising creatinine is graft dysfunction, not synonymous with rejection: dehydration, obstruction, vascular compromise, infection, calcineurin-inhibitor toxicity, recurrent disease and non-adherence must also be assessed urgently.
Rejection can be clinically silent and is often detected by surveillance blood tests; never wait for graft pain or fever before contacting the transplant centre about deteriorating function.
Tacrolimus has a narrow therapeutic window and major CYP3A interactions; take trough samples immediately before the scheduled dose and never switch formulation or brand casually.
Do not stop, double or empirically change anti-rejection medicines during vomiting, diarrhoea, infection or inability to swallow—obtain same-day transplant advice because both underexposure and toxicity threaten the graft.
Fever, shivering, severe headache, persistent diarrhoea or vomiting, breathlessness, chest pain, feeling markedly unwell, or little or no urine are NHSBT warning signs requiring transplant-team contact.
Immunosuppression increases opportunistic infection and malignancy risk; prophylaxis, non-live vaccination, sun protection and national cancer screening are part of graft care.
Mycophenolate is a major human teratogen; pregnancy must be planned with the transplant team so a safer regimen can be established without precipitating rejection.

02Indications, selection and cautionsWho may benefit, who needs urgent treatment and important alternatives.

Stable graft

Creatinine fluctuates within an individual baseline, urine output is maintained and immunosuppressant levels and surveillance results fit the transplant centre's targets.

Delayed graft function

Little urine and persistently high creatinine immediately after transplantation may require dialysis while ischaemia-reperfusion injury and other causes are evaluated.

Acute rejection

An otherwise unexplained creatinine rise, proteinuria or occasionally graft tenderness, fever and oliguria prompts urgent transplant assessment and often biopsy.

Calcineurin toxicity

Rising creatinine, tremor, headache, hypertension, hyperkalaemia, hypomagnesaemia or hyperglycaemia may accompany excessive tacrolimus or ciclosporin exposure.

Opportunistic infection

CMV, BK polyomavirus, Pneumocystis and fungal disease vary with time, donor-recipient serostatus and net immunosuppression and may present subtly.

Urological obstruction

Falling urine, rising creatinine and transplant hydronephrosis can result from ureteric oedema, stricture, stone, clot or extrinsic compression.

Long-term toxicity

Hypertension, diabetes, dyslipidaemia, skin cancer, post-transplant lymphoproliferative disease, bone disease and recurrent native disease contribute to late morbidity.

Red flags requiring action

Anuria or a rapid creatinine increase after transplantation requires same-day transplant-centre assessment for vascular occlusion, obstruction, rejection, sepsis and severe volume depletion.
Fever or rigors in an immunosuppressed recipient may progress with muted inflammatory signs; use urgent sepsis assessment and seek transplant or infection advice early.
Sudden graft-region pain, hypotension, falling haemoglobin or abrupt oliguria soon after surgery raises bleeding, vascular thrombosis or urine leak and needs surgical review.
Severe diarrhoea or vomiting risks dehydration, missed immunosuppression and unpredictable tacrolimus exposure; it is a same-day medicine and graft-safety problem.
New neurological symptoms with severe hypertension, headache, seizure or visual change may indicate calcineurin toxicity or posterior reversible encephalopathy and requires emergency assessment.
Pregnancy, suspected pregnancy or pregnancy planning during mycophenolate therapy needs urgent specialist review, but the patient must not stop treatment without a safe replacement plan.
Night sweats, unexplained weight loss, lymphadenopathy, persistent fever or a new skin lesion warrants prompt malignancy and infection investigation in a transplant recipient.

03Assessment before treatmentTests and checks that guide safe selection.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Serial creatinine and urine outputFirst step
Why
Detect graft dysfunction early and define tempo against the recipient's post-transplant baseline.
Interpretation and limitations
A small sustained change may be important; relate it to volume, medicines, diarrhoea, infection and timing rather than relying on population reference ranges.
02
Transplant ultrasound with Doppler
Why
Assess hydronephrosis, collections, kidney size and major arterial or venous flow.
Interpretation and limitations
Normal macroscopic perfusion does not exclude rejection or drug toxicity, while resistive indices are non-specific and need the full clinical context.
03
Tacrolimus or ciclosporin concentration
Why
Evaluate exposure, adherence, interaction and possible calcineurin-inhibitor toxicity.
Interpretation and limitations
Confirm exact formulation and sample timing; a trough is taken immediately before dosing, and targets vary by time, regimen and immunological risk.
04
Urinalysis, culture and protein quantification
Why
Identify infection, haematuria, proteinuria and recurrent or de novo renal disease.
Interpretation and limitations
Denervation may blunt urinary symptoms; proteinuria trajectory can signal chronic graft injury even when creatinine appears stable.
05
CMV and BK viral testing
Why
Detect viral replication when surveillance or graft, marrow or systemic findings raise concern.
Interpretation and limitations
Use centre-specific quantitative PCR thresholds and trends; reducing immunosuppression is a specialist balance against rejection.
06
Donor-specific HLA antibodies
Why
Support assessment of antibody-mediated rejection and immunological graft injury.
Interpretation and limitations
A positive result is integrated with graft function, pathology and timing; it is not a stand-alone mandate for a particular treatment.
07
Kidney allograft biopsy
Why
Classify rejection, drug injury, viral nephropathy, recurrent disease and other parenchymal pathology.
Interpretation and limitations
Check blood pressure, coagulation and imaging safety first; pathology guides specialist treatment and empirical steroids should not obscure avoidable differentials when the patient is stable.
08
Metabolic and malignancy surveillance
Why
Identify diabetes, lipids, hypertension, marrow suppression, liver toxicity and cancer risk from long-term therapy.
Interpretation and limitations
Frequency depends on time since transplant and regimen; continue national screening and add transplant-specific dermatology or viral surveillance as advised.

04Treatment approachPreparation, options, escalation and aftercare.

01ASSESSTransplant candidacyFirst stepAdvanced CKD is likely to progress to kidney failure and transplantation could be suitable.

1Refer early for multidisciplinary assessment, explaining living and deceased donation, waiting, surgery, lifelong medicines and realistic graft outcomes in accessible language.
2Define recurrence risk and evaluate cardiovascular health, infection, malignancy, urinary tract, iliac vessels, frailty, psychosocial needs and ability to manage the regimen.
3Perform ABO, HLA antibody and compatibility work-up under NHS Blood and Transplant and centre protocols, treating living donors as independent volunteers with separate advocacy.
4Optimise vaccination, dental and infection status, maintain regular wait-list reviews and provide clear instructions for illness or a potential organ offer.

02CREATRising transplant creatinineRenal function worsens beyond expected biological variation in a graft recipient.

1Contact the transplant team promptly and establish urine output, volume loss, fever, pain, blood pressure, recent illness, adherence and every prescription or non-prescription medicine.
2Repeat renal chemistry, urinalysis and culture and obtain a correctly timed calcineurin-inhibitor level, treating dangerous potassium or sepsis immediately.
3Arrange ultrasound for obstruction, collections and major vascular compromise, then pursue viral testing, antibodies or biopsy as the centre directs.
4Treat the established cause—such as fluid depletion, obstruction, infection, toxicity or rejection—without blind cessation of baseline immunosuppression.

03FEVERUnwell immunosuppressed recipientFever, rigors, respiratory symptoms, severe headache, gastrointestinal illness or systemic decline occurs after transplant.

1Use an urgent ABCDE and sepsis assessment while notifying the transplant service; normal temperature or white count does not safely exclude serious infection.
2Take cultures and source-directed tests, considering common bacterial illness alongside CMV, Pneumocystis, BK, herpesviruses and donor-derived or travel infections according to timing.
3Start appropriate renal- and interaction-adjusted antimicrobial therapy when indicated and involve microbiology; check for nephrotoxicity and effects on tacrolimus or ciclosporin.
4Change immunosuppression only through transplant advice, balancing infection control with rejection risk and arranging closer levels during interacting treatment.

04MEDSMedicine reconciliationA transplant recipient is admitted, starts a new treatment or cannot reliably take oral medicines.

1Record exact generic and brand names, immediate- or prolonged-release formulation, dose, schedule, last administration and usual transplant centre and pharmacy.
2Screen antibiotics, antifungals, anticonvulsants, herbal products, grapefruit, acid-suppressing therapy and other medicines for level-changing or nephrotoxic interactions.
3Contact the transplant pharmacist or clinician before omission, substitution, crushing, route change or dose adjustment, including peri-operative fasting.
4Arrange correctly timed levels and post-change renal, electrolyte, glucose, marrow and infection monitoring, giving the patient an updated written plan.

05Regimens, contraindications and interactionsTreatment details and the circumstances that modify them.

Provide calcineurin inhibition as a central component of many induction-to-maintenance regimens preventing cellular rejection.

Immediate-release tacrolimus

Use the transplant centre's weight- and level-guided oral regimen at consistent times, adjusting only against correctly timed trough concentrations.

Nephrotoxicity, tremor, neurotoxicity, hypertension, hyperkalaemia, hypomagnesaemia and diabetes occur; macrolides, azoles, rifamycins, anticonvulsants, grapefruit and formulation switches can dangerously alter exposure.

Inhibit lymphocyte proliferation as the antiproliferative component of maintenance immunosuppression.

Mycophenolate mofetil

Give the centre-prescribed oral dose, commonly divided across the day, with any reduction or interruption authorised by the transplant team.

Diarrhoea, nausea, leucopenia and infection can require review; it is a major teratogen, has strict pregnancy-prevention requirements and should be replaced before planned pregnancy under specialist supervision.

Suppress multiple immune pathways during induction, maintenance and selected specialist-treated rejection episodes.

Prednisolone

Follow the transplant protocol's initial and tapering oral schedule, using the lowest maintenance exposure compatible with rejection risk.

Infection, diabetes, hypertension, mood change, cataract, skin thinning, osteoporosis and adrenal suppression require prevention and monitoring; never stop prolonged therapy abruptly.

Block the interleukin-2 receptor on activated lymphocytes to reduce early acute rejection risk.

Basiliximab induction

Administer the protocol intravenous induction doses around transplantation alongside a calcineurin-inhibitor-containing regimen in eligible recipients.

This is transplant-centre therapy; hypersensitivity can occur, and induction choice changes with immunological risk, infection and the full planned regimen.

Prevent Pneumocystis jirovecii pneumonia and reduce selected bacterial infection risk during higher immunosuppression.

Co-trimoxazole prophylaxis

Use the centre's renal-adjusted oral schedule for its specified post-transplant duration, modified for allergy, cytopenia and graft function.

Rash, marrow suppression, creatinine secretion effect and hyperkalaemia can mimic or worsen graft problems; severe sulfonamide reactions and interactions need an alternative plan.

Prevent or treat cytomegalovirus disease in recipients selected by serostatus, immunosuppressive intensity and viral monitoring.

Valganciclovir prophylaxis or treatment

Dose strictly to current graft function and donor-recipient CMV risk under the transplant virology protocol, with repeated adjustment as filtration changes.

Neutropenia, anaemia and thrombocytopenia require blood counts; underdosing risks failure while accumulation causes toxicity, and pregnancy precautions apply.

06Complications, monitoring and follow-upAdverse effects, response and longer-term review.

Early after transplantation, follow creatinine, urine output, weight, blood pressure and surgical wound at the centre's close interval; spacing increases only after stable graft function.
Take calcineurin-inhibitor troughs at the correct pre-dose time and repeat after diarrhoea, interacting treatment, formulation change, adherence concern or unexplained dysfunction.
Monitor potassium, magnesium, glucose, liver profile, full blood count and urine protein for medicine toxicity and evolving graft disease.
Use CMV and BK surveillance according to donor-recipient status, time since transplant and immunosuppression, escalating quantitative trends rather than one isolated result.
Review vaccinations with the Green Book and transplant team, avoiding live vaccines during clinically significant immunosuppression and keeping household contacts appropriately immunised.
Check skin regularly, reinforce high-factor sun protection and ensure cervical, breast, bowel and other national cancer screening remains current.
Assess adherence without judgement, including timing complexity, supply, cost-free NHS entitlement processes, cognition, mental health, shift work and adverse effects.
Review cardiovascular risk, smoking, weight, activity, lipids and blood pressure because a functioning graft does not remove vascular disease.

07Special situationsVariants, exceptions and circumstances that change the usual approach.

Creatinine is the smoke alarm

Rejection often lacks pain or fever, making reliable surveillance blood tests central to early detection.

The graft is denervated

Urinary infection, obstruction and parenchymal injury may produce fewer localising symptoms than disease in a native kidney.

Trough timing creates meaning

A tacrolimus result drawn after the morning dose cannot be compared uncritically with a pre-dose target.

Diarrhoea changes two risks

It can cause dehydration and alter tacrolimus exposure while also preventing reliable immunosuppressant absorption.

Delayed function is not failure

Temporary post-operative dialysis can support a kidney recovering from ischaemia-reperfusion injury while other causes are excluded.

Cancer prevention is graft care

Skin protection and screening address a predictable consequence of sustained immune suppression rather than an unrelated lifestyle issue.

Pregnancy requires preparation

Stable graft assessment and planned substitution of teratogenic medicines are safer than either unplanned exposure or abrupt self-discontinuation.

08Common pitfallsFrequent interpretation and management errors.

01
Do not diagnose rejection from creatinine alone or give empirical high-dose steroids before the transplant team evaluates infection, obstruction, toxicity and biopsy need.
02
Do not omit tacrolimus because a patient is nil by mouth without arranging a specialist route and level plan.
03
Do not substitute immediate-release and prolonged-release tacrolimus formulations or switch brand by matching milligrams casually.
04
Do not prescribe clarithromycin, erythromycin, azole antifungals, rifampicin, carbamazepine or herbal products without checking major transplant-drug interactions.
05
Do not dismiss mild fever, diarrhoea or urinary symptoms because steroids and immunosuppression can blunt inflammatory presentation.
06
Do not give a live vaccine to a clinically immunosuppressed transplant recipient unless the responsible specialist has explicitly advised it.
07
Do not stop mycophenolate abruptly after a positive pregnancy test; secure urgent transplant and maternal-medicine advice for safe replacement.
08
Do not assume a functioning graft removes the need for CKD, cardiovascular, cancer and infection surveillance.