Renal transplantation (paediatric): management of

SOP Group

The following SOP has been developed by the Paediatric Renal Transplant Group consisting of Dr Heather Maxwell, Mr Vlad Shumeyko, Mr Martyn Flett, Dr Ben Reynolds, Mrs Angela Lamb, Dr Alison Balfour, Dr Ann-Margaret Little, Dr Jocelyn Erskine and Dr Chris Kidson.

Please contact Dr B Reynolds if there are issues with this SOP or any suggested improvements.

SOP Development

The SOP has been developed after assessing current practice in the light of published evidence and guidelines. Much of the guidance is based on shared expert opinion and experience. This SOP should be used in conjunction with the following GGC NOPS

• NOP001 Donor and Organ Characterisation, Assessment and Allocation in Deceased and Living Donation and Transplantation
• NOP002 Verification of Donor Identity, Consent/Authorisation and Organ and Donor Characterisation in Deceased and Living Donation and Transplantation
• NOP003 Packaging, Labelling and Transport of Organs in Deceased and Living Donation Transplantation
• NOP004 Management of Procurement Material and Equipment in Deceased and Living Donation and Transplantation
• NOP005 Activities to Be Performed Under the Guidance of A Registered Medical Practitioner in Deceased and Living Donation and Transplantation
• NOP006 Transfer And Storage Of Donor and Organ Characterisation Information and Storage of Traceability Data
• SOP3888/1 Reporting an Organ Donation or Transplantation Incident to NHSBT

SOP Update

This SOP was updated June 2020, following work by the Paediatric sub-group of the Kidney Advisory Group for NHSBT.  Changes reflect the harmonization of immunosuppression and anti-infective regimes across the UK. A further update in August 2020 was incorporated to reflect changing anaesthetic practice.

Children will either receive a transplant from a relative (Living Donor - LD) or from a deceased donor (DD). An LD transplant will have been planned in advance; a DD transplant will take place when a suitable organ becomes available and often takes place out of hours. The duties of relevant personnel are outlined in NOP005 [external link].

2.1 Deceased Donor Kidney

The consultant paediatric nephrologist on call accepts a suitable kidney after phone calls from NHSB&T. The initial calls take place before the kidney has been harvested. 

• The consultant paediatric nephrologist will phone Ward 3C (0141 452 4521) to advise a kidney has been accepted, the expected arrival time (if known) and when the child should start fasting
• The nephrologist will contact the on call paediatric urologist for transplantation (rota available on Rotawatch)
• The urologist will contact the on call transplant surgeon from the Queen Elizabeth University Hospital (rota available on Rotawatch)
• The urologist will contact the duty anaesthetist and/or emergency theatre co-ordinator and inform them that there is a deceased donor transplant planned and give the estimated time of operation. This information may be needed at the daily ‘bed huddle’
• The nephrologist will update the ‘Emergency Renal Transplant’ channel on MS Teams to advise that a DD transplant is planned.
• Ward 3C nursing staff will let the family know that a kidney may be available for their child
• During this phone call, the ward 3C nursing staff will check if the patient has had any infections over the last 2 months and if they have had any recent blood transfusions.
• After the phone call, the ward 3C nursing staff will let the nephrologist know how the patient has been over the last two months
• If the patient is on the virtual cross-match (vXM) list (no preformed antibodies and up to date antibody testing on at least two independent samples), the nephrologist will then contact the Consultant Clinical Scientist on call (rota and numbers available on vXM Sheet) for confirmation that a vXM is acceptable. The laboratory crossmatch will be performed during working hours the next day. Contact should be made with the Histocompatibility and Immunogenetics (H&I) Laboratory during working hours to arrange transport of specimens (0141 301 7757/ 7755).
• If the patient is not on the vXM list and therefore requires a prospective crossmatch, Ward 3C staff will contact the H&I laboratory during working hours, or if it is out of hours the tissue-typist on call via switchboard. This needs to be in sufficient time for a cross-match to take place as soon as the kidney arrives in the ward. Consider whether to request for peripheral blood from the donor to be sent to the H+I lab via ODT Hub to permit ‘wet’ cross-matching in a timely fashion.
• Ward 3C nursing staff will inform PICU that a transplant is planned
• Once the arrival time of the kidney is confirmed by NHSB&T, the nephrologist will inform Ward 3C. If necessary, the nephrologist will speak to the most senior of the medical receiving team on call.

The patient should be fasted for 6 hours before the operation.

• The family should make their way to Ward 3C
• If the patient is on peritoneal dialysis they should be left with no last fill. The parents should bring a sample of PD fluid with them. If during the night, the treatment should be interrupted and a manual drain performed.
• If the patient is on haemodialysis they may require an extra haemodialysis session before the transplant goes ahead – discuss this with the on-call nephrologist.

• A copy of this SOP should be printed out for use by the attending medical staff. Further information relating to the child (The Transplant Plan) is held in Clinical Portal. Print out this information. For most patients information can also be obtained from the renal unit database (SERPR). Admit as below.

2.2 Living Related Transplants

Living related transplants are planned in advance and the final cross-match will have already been carried out. Admit the child as below. Information will be available in the transplant plan, available online and in a hard copy kept on the ward.

3.1 Admit the child directly to ward 3C

The patient should be clerked in by the most senior of the junior medical staff on call. Much of the past medical history will be documented in the transplant plan. Note any past medical history of hypertension, asthma or seizures.

Attention should be paid to recent infections including peritonitis in PD patients and HD line infections, and any contact with infectious diseases. If the child is unwell or there are concerns, please discuss with the consultant paediatric nephrologist on call immediately.

3.2 Investigations

• Other investigations as clinically indicated e.g. CXR, ECG
  
  

3.3 Arrival of Deceased Donor Kidney

The donor kidney should be kept in ward 3C. Nursing staff should inform both the transplant surgeon and the paediatric surgeon when it has arrived (rotas available). If a prospective cross-match is required, the donor lymph node or spleen should be sent to H&I Laboratory at Gartnavel* along with a clotted sample of the patient’s blood. This should be sent by taxi not courier. Ensure the H&I lab / on-call tissue-typist is aware of the estimated time of arrival of specimens. Check where sample is to be sent, and that a sample has not already been sent from the donor hospital. If a vXM is taking place, and samples arrive after 3pm (Mon-Fri), then they should be kept in the ward fridge ready for collection the next working day.
* Histocompatibility & Immunogenetics Service, Level 1, Laboratory Medicine Building, Gartnavel General Hospital, 21 Shelley Rd, Glasgow, G12 0ZD

The donor kidney will be taken out of ice, assessed by the operating surgeons to make sure that the kidney is suitable for grafting. This will take place before any immunosuppression has been given and before the patient is taken to theatre.

3.4 Medical Management

• Document anonymised deceased donor details in casenotes (Age, gender, blood group, tissue type, date and cause of death, weight, virology and creatinine)
• Fast for solids for 6 hours pre-operatively and for clear fluids for 3 hours (a cross match takes approximately 6 hours)
• Document the following: Weight, height, surface area and native urine output (mls/day) in the casenotes (Information available on Transplant Plan in Clinical Portal)
• Prescribe IV fluids once the child is fasting to cover measured urinary losses and insensible losses of 400ml/m². Use 0.9% saline/5% dextrose unless otherwise indicated. Children should be well hydrated at the time of operation. (However many CKD patients are polyuric and the use of large volumes of 0.9% saline can be associated with hypernatraemia).
• Document BP.  Withhold long-acting anti-hypertensives. If BP elevated, discuss with consultant nephrologist.
• Perform ischaemic pre-conditioning if appropriate (aged >5years, likely to tolerate procedure). Refer to Ischaemic pre-conditioning SOP (Appendix VII)
• Radiology. Order an ultrasound of the transplant kidney (to be performed during or just after surgery) and make radiology aware that a transplant is about to take place.
• Calculate medication doses that will be necessary pre and post op. Discuss with renal pharmacist.
  i. Prescribe immunosupression. The intended immunosuppression regimen will be documented in the transplant plan. Doses are given below and details of all medicines used post transplant are available at the end of this protocol. Basiliximab is generally the only immunosuppressant given pre-operatively; methylprednisolone is given during surgery and the rest start after theatre.
  ii. Prescribe antibiotic cover. Give Cefotaxime 50mg/kg at induction, to a maximum dose of 1.5g bd. This is for surgical prophylaxis and should be for a minimum of 24 hours or longer if indicated. This can be changed to a prophylactic oral dose to prevent UTIs whilst catheters remain in situ. If Co-trimoxazole has been started as PJP prophylaxis this will double as urinary prophylaxis.
  iii. Prescribe gastroprotection as below to start pre-op.
  iv. Check CMV status of recipient and If the recipient is negative and donor is positive the patient will require valganciclovir. This is started post op once the patient is taking oral medication.
  v. Aspirin is started on the day of transplant and is given prior to going to theatre. Any child deemed at increased risk of thrombosis will have a plan for low molecular weight heparin (LMWH) thromboprophylaxis outlined in their transplant plan.
  At the discretion of the operating surgeon, thromboprophylaxis may be administered intra-operatively or LMWH may be recommended post operatively (See appendix V).

• Review blood results

• Haemodialysis: children on haemodialysis will require dialysis pre-transplant unless they have had a satisfactory dialysis session within the previous 24 hours. Minimal anticoagulation should be used. Heparin should be used during haemodialysis NOT tinzaparin.  The line should be capped with a heparin lock (not alteplase) only (please document and label). Fluid removal should be minimal unless fluid overloaded. Discuss with consultant on call.

• Peritoneal Dialysis: children should receive their usual overnight dialysis. Depending on the time of transplantation and biochemistry results, further cycles may be required. When going to theatre, the abdomen should be empty (no last fill), and the catheter capped prior to transfer to theatre. Fluid removal should be minimal unless fluid overloaded. Aim to leave child at or above their dry weight i.e. limit the UF or allow time to catch up with IV fluids if fluid removal greater than expected. Discuss with consultant on call.
  
  

3.5 Surgical Considerations

• Consent will be obtained by the operating surgeons. Frequently consent will be taken by both Transplant and Paediatric Surgeons.
• Consideration should be given to the need for dialysis access (HD or PD) post operatively. Pre-emptive patients may need access inserted; for those with access in situ a decision needs to be made whether to keep the access or remove it (e.g. infected exit site or catheter). If dialysis is likely to be needed post op, replacement access may be necessary.
  
  

3.6 Deceased Donor Cross-Match results

The operation can go ahead if the cross-match result is negative. As soon as this result is known, the Basiliximab can be given, and once the infusion is complete, the patient should go promptly to theatre. 

3.7 Living Donor Transplantation

The donor nephrectomy takes place in the adult operating theatre suite. As soon as the retrieving surgeon is happy that the kidney is suitable for use, they will phone ward 3C to say the transplant is going ahead. Nursing staff on Ward 3C will then phone theatre to inform them that the operation is proceeding. The Basiliximab will be given promptly to the patient who will then go to theatre as soon as the infusion is complete.

The arrival of the donor organ needs to be recorded in the Transplant Log which is held in the ward and in theatre. See also NOP002 and NOP003 [External links]

See also NOP004 [External link]. The operating surgeon is responsible for the correct identification of the donor organ used.

Children need to be kept ‘well–filled’ throughout the procedure and recovery period. Children should be well hydrated prior to going to theatre, and long- acting anti-hypertensives will have been withheld. Many children are polyuric and their native 24 hour urinary output will be clearly documented. On the day of transplant, these 24 hour urinary losses will be given as intravenous therapy with a crystalloid solution, the concentration of which will depend upon the urine sodium concentration. This is their ‘maintenance’ fluid, individualised to their needs, which will be running when the child reaches theatre and should be continued. This is usually given as 0.9% saline and 5% dextrose but will depend on the individual child. 

The transplanted kidney needs to be well perfused. This is achieved by maintaining an adequate intra-vascular volume; as a guide, a central venous pressure in the range of 10-12 cm water and the absence of a core-peripheral temperature gradient. This is particularly important for small children receiving adult sized kidneys. When the clamps are released and the kidney is re-perfused, the child’s circulating volume will need to increase to be able to perfuse a large kidney at an appropriate pressure. A bolus of fluid should be given prior to the release of the clamps. Avoid using packed red cells if possible.

Blood pressure should be maintained at levels appropriate for donor age. Information regarding donor age will be available in patient’s casenotes. (See also appendix I).

Ensure dialysis access available if operative course suggests that dialysis is likely to be required. (see also section on Admission point 5). Consider removal of potentially infected dialysis access.

Human Tissue Authority Form B needs to be completed and faxed to NSHBT.

ANAESTHETIC MANAGEMENT (J.Erskine/J. Skuratova)

Close communication with renal physicians and surgeons is paramount. The following serves as a guide, developed after consultation with other UK and international centres. It is accepted that there will be variation in practice.

5.1 Preparation & Equipment

• Ensure PICU bed available
• Confirm cross-matched blood is in theatre fridge
• Fluid warmer primed with 0.9% NaCl (if clinical indication for Plasmalyte® discuss with renal physicians)
• Arterial line
• Central line if the patient does not already have a haemodialysis line. Consider a tunnelled line in children with sampling difficulties or other concerns.
• Minimum 2 Alaris® CC infusion pumps (may be worth using PICU/cardiac stack)
• Urinary catheter
• 18G epidural catheter and local anaesthetic infusion device for surgically sited for Transverse Abdominal Plane (TAP) block.
• 2 temperature probes
• Forced air warming device
• Theatre temperature >23ºC
• Gastrostomy extension (ask ward 3C to bring down with patient)
• Basiliximab will be given on the ward by the renal physicians prior to transfer to theatre.

5.2 Induction

• Premedication as indicated
• Aspirate gastrostomy
• Any suitable induction technique. Atracurium NMB of choice.
• Large bore IV access
• Invasive monitoring. If patient has existing HD line ensure sterile access and dead space heparin is discarded.
• Prophylactic antibiotics (often prescribed by renal physicians on drug kardex).

5.3 Maintenance

• Remifentanil is useful in maintaining cardiovascular stability
• Dopamine is usually required to optimise perfusion pressure. Start at 5mcg/kg/min and titrate as necessary.
• Consider additional boluses of phenylephrine
• Goal directed fluid management. These patients can often require (and tolerate) intraoperative fluids of 60mls/kg and upwards. The author uses SPV (see below).
• Regular blood gases (focusing on electrolytes, Hb, base excess, lactate)

5.4 Intraoperative goals

• The transplanted kidney needs to be well perfused
• Using systolic pressure variation (SPV) to direct fluid management is helpful. Maintain this parameter <10%. It can be selected on the GE monitor to be continually displayed in screen set up. Urine output is not measured during the majority of the case as the catheter is spigotted so SPV can provide valuable information and trends
• Replace the recipients native urine output plus insensible losses
• Use crystalloid/packed red cells/other blood products as clinically indicated
• Maintain CVP 10-12 cmH₂O
• Target core-peripheral temperature gradient <2°C
• Avoid hyperchloraemia. Consider using Plasmalyte® and discuss with renal team

5.5 Reperfusion

• Give immunosuppression. Methylprenisolone will come with the patient prescribed by renal physicians. Administer 600mg/m² (max 500mg) IV prior to release of vascular clamps
• Prepare for potential cardiovascular instability
• Aim to match donor blood pressure or appropriate blood pressure for donor age. This information will be available in the patient’s casenotes (see also Appendix I)
• Give a fluid bolus Initially 10mls/kg prior to release of vascular clamps but more may be required for large donor kidneys. 4.5% albumin is generally favoured however current evidence of clear advantage over crystalloids is lacking

5.6 Analgesia

• IV paracetamol, morphine bolus towards end of case.
• Morphine or oxycodone NCA/PCA as appropriate. Fentanyl may also be used especially if there are concerns over delayed graft function (requires discussion with PICU)
• TAP block catheter and initial block by surgeons. Local anaesthetic infusion device (usually a Pajunk® elastomeric pump). A Lockit Plus® epidural securement device is useful in securing the catheter

5.7 Recovery/postoperative care

• Decision to extubate dependent on various factors including length of procedure, haemodynamics, intraoperative events, volume of fluid administered and patient specific factors. The majority of LRD recipients are extubated.
• Extubated patients can be transferred to recovery or proceed directly to PICU. This is at the discretion of the anaesthetist but close communication with the entire team is essential to ensure the patient has the appropriate immediate postoperative management started.
• If planning to transfer to recovery first, the anaesthetist should ensure the recovery staff are aware and have IV fluids prepared. Anaesthetist should also consider taking initial postoperative bloods.
• IV fluids should replace both native and transplant urinary losses hourly until reaching PICU.
• Ensure accurate documentation of all fluids given
• Handover to PICU consultant and team.

The transplanted kidney needs to be well-perfused. Fluid management in the first 12 hours post operatively is critical and needs careful attention.  Please discuss any concerns with the nephrologist on call.

6.1 MEDICATION 

Prescribe the following medication in ITU.

6.1.1 Immunosuppression
The immunosuppression regimen will be documented in the drug chart from Ward 3C. Below is a summary of the usual medication used.

6.1.2 CMV status
If the recipient is CMV negative and the donor CMV positive, then oral valganciclovir is given for at least the first 3 months, and consider treatment for 6 months total. This should be started when the patient is tolerating oral fluids (usually day 1 or 2 post transplant).

6.1.3 Analgesia / Sedation
This will have been started in theatre and usually includes a TAP If further analgesia is required, consider:-

Further  information  about  medication  is  available  in  the  medication appendix of the protocol.

6.2 Investigations

On admission measure FBC, coagulation, U&E, LFTs, Bone, glucose, magnesium, CRP and urinalysis. Thereafter measure U&E, LFTs, glucose and FBC 4-6 hourly.

Monitor serum Na on blood gas machine 3-4 hourly.

Renal USS and Doppler shortly after admission to ITU if not already performed in theatre and repeated if clinical situation changes.

Daily Investigations

6.2.1 Check Tacrolimus level at 0800 each day. For Tacrolimus level send 1 x 0.5 ml K EDTA Tubes which must be filled accurately.

6.2.2 Send daily urine (boric acid container) for culture

6.2.3 Consider daily renal USS and doppler if concerns about renal blood flow.

6.3 Monitor CVP, urine output, BP and core-peripheral temperature gap

Aim to keep CVP at 8-10 cm H₂0

Aim to keep systolic BP > 50^th centile for donor age. For donors aged 17 and over this is 120/70. For younger donors age-specific centile charts are available (Appendix I). 

Aim to keep core-peripheral temperature gradient < 2^oC 

Measure the urine output hourly 

6.4 Fluid and Electrolytes

Replace urine output ml for ml on an hourly basis with 0.9% saline and 5% dextrose initially. (This is the combined transplant and native urine output from the bladder).

6.4.1 If serum sodium rises change to 0.45% saline and 5% dextrose

6.4.2 Send a urinary sodium level and dip urine for glucose

6.4.3 If combined urine output is greater than 150 ml/hr consider changing to 0.45% / 5% dextrose but be guided by urinary sodium losses

6.4.4 Measure serum sodium frequently

6.4.5 If combined urine output is greater than 200ml/hr, consider reducing the dextrose concentration. Solutions of 0.45% saline/2.5% dextrose are available.

6.4.6 K⁺ should not be added to replacement fluids until the serum K⁺ is normal and there is a good urine output

• Insensible losses will generally be covered by infusions of inotropes, morphine etc.
• Document drain losses - only replace, with 0.9% saline or blood, if losses are greater than 4-5 ml/kg/day (Discuss with nephrologist or surgeon on call.)

6.4.7 Blood transfusion can result in sensitisation, therefore transfuse only if actively bleeding or Hb < 80 g/l or if there are concerns regarding adequacy of tissue oxygen delivery. Do not administer blood without discussion with nephrologist

6.4.8 If clinically underfilled (CVP or BP low, large core-peripheral temp gap) Give 5% Albumin or 0.9% Saline at 5-10 ml/kg to keep CVP in the required range 8-10 cmH₂0. Measure serum albumin 6-8 hourly

6.4.9 If urine output falls to less than 1.5ml/kg/hr

• Check for a full bladder and flush urinary catheter (and stent if present).
• Check for hypovolaemia and give 5% albumin or 0.9% saline 5-10ml/kg as appropriate
• If well-filled then consider iv furosemide (initially 0.25 - 0.5 mg/kg). Start with a low dose as the response can be dramatic particularly with LD transplants. Discuss with renal consultant prior to first administration
  

6.5 Polyuria

Large urinary losses of sodium, calcium, magnesium and phosphate can occur with a high urine output. Monitor serum electrolytes closely. Check for glycosuria. SOPs are available for calcium, magnesium, and phosphate replacement.

6.6 Delayed Graft Function

If there is no urine output, mechanical or surgical causes should be discussed and ruled out. If there is no obstruction and no urine output despite adequate hydration and furosemide, then there is likely to be delayed graft function. Fluid replacement at this point should cover insensible losses, any other losses and any urine output that is present.

Time of transfer to ward 3C will depend on the patient’s clinical condition but ideally should take place during working hours. The patient should be nursed in a cubicle. Patients should have a daily weight, accurate 24 hour fluid balance and 4 hourly blood pressure. Monitor peripheral temperature and aim to keep this at or above 35^oC.

7.1 INVESTIGATIONS

On admission measure FBC, coagulation, U&E, LFTs, bone, glucose, magnesium, CRP, urinalysis and urine culture. Thereafter measure U&E and LFTs 12 hourly or more often if clinically indicated. Check that a Renal USS and Doppler has been carried out within the previous 24 hours. Consider handheld USS to assess graft on the ward (if appropriate)

7.2 FLUID AND ELECTROLYTES

Measure urinary sodium losses to guide fluid prescription.

Replace transplant and native urine output ml for ml with either 0.9% saline/5% dextrose or 0.45% saline and 5% dextrose on an hourly basis.
Insensible losses will generally be covered by infusions of morphine, antibiotics etc. and do not require a separate infusion.
Document drain losses – only replace, with 0.9% saline or blood, if losses are greater than 4-5 ml/kg/day.

If clinically underfilled (BP low, large core-peripheral temp gap) Give 4.5% Albumin or 0.9% Saline at 5-10 ml/kg to maintain intravascular volume. Measure serum albumin and keep within the normal range.

If urine output falls to less than 1.5ml/kg/hr, check for a full bladder and flush urinary catheter and stent. Check for hypovolaemia and give 5% albumin or 0.9% saline 5-10ml/kg as appropriate. If well-filled then consider iv furosemide (initially 0.25 - 0.5 mg/kg). Start with a low dose as the response can be dramatic particularly with LD transplants. Discuss with the consultant nephrologist who is on call.

If the urine output is large, urinary losses of sodium, calcium, magnesium and phosphate can occur. Monitor serum electrolytes closely and dip urine for glucose.

If there is delayed graft function with no transplant urine output, mechanical or surgical causes should discussed and ruled out. If there is no obstruction and no urine output despite adequate hydration and furosemide, then there is likely to be delayed graft function. Fluid replacement should cover insensible losses, any other losses and any urine output that is present.

7.3  MEDICATION

Immunosuppression
The immunosuppression regimen will be documented in the original drug chart from Ward 3C. Doses are available in the table below and in the section on medication at the end of the protocol.

Prescribe aspirin as below

Analgesia / Sedation
Most children will have a PCA in situ and a local TAP block around the wound site. If additional pain relief is required, consult with the pain service. For those not on a PCA, morphine can be given as below. Avoid non-steroidal analgesics.

Morphine:

Gastroprotection
Prescribe IV esomeprazole until tolerating oral medications, then switch to oral omeprazole.

Antibiotics
Prescribe iv cefotaxime or oral co-trimoxazole as detailed in the table below. Cefotaxime is usually given for the first 48 hours post op, then oral co-trimoxazole is given thereafter. Co-trimoxazole is given for Pneumocystis prophylaxis and can double as urinary prophylaxis for patients at risk for UTI. This is given for 6 months. If urinary prophylaxis is required thereafter, change to an appropriate antibiotic.

CMV Status
If the recipient is CMV negative and the donor CMV positive, then oral valganciclovir is given for at least the first 3 months, and preferably six. This should be started when the patient is tolerating oral fluids (usually day 1 or 2 post transplant). The dose is given in the medication table below. Further information is available in the medication section of the protocol.

Aspirin
Aspirin should be given as thromboprophylaxis for the first 3 months post transplant. For patients deemed to be at increased risk of clotting low molecular heparin may be used.

Prescribe the following medication

8.1 Daily Investigations

Check U+E, LFTs, Bone, Glu, CRP, Mag and FBC each day. Blood tests should be sent by 0800 so that results are available by midday at the latest.

In addition
Check Tacrolimus level at 0800 each day. For Tacrolimus levels send 1 x 0.5 ml K EDTA tubes which must be filled accurately. Samples need to reach the lab by 1000. Assays are performed routinely Mon to Fri.  If a level is required on a Saturday, discuss in advance with Dr Galloway or on call biochemist. Samples need to be in the RHSC biochemistry lab by 0900 on a Saturday.

Send daily urine for culture (boric acid container)

Consider daily renal USS if concerns about renal blood flow.

If the creatinine is elevated, it should be repeated (results to be back before 5pm) and the following considered:-

1. Tacrolimus toxicity
2. Urinary tract infection
3. Obstruction to urine outflow
4. Dehydration
5. Rejection

Serum levels of phosphate, magnesium and potassium can fall post transplant and should be supplemented when below the normal range (See Appendix IV).

8.2 Other tests 

Weekly (Monday)

• EBV / CMV / Adenovirus / Polyoma virus PCR (3-5 ml blood in EDTA tube to virology at South Sector Microbiology laboratory:)
• Urine protein/creatinine ratio

Post Transplant HLA antibody Monitoring
HLA antibody levels should be measured if there is suspected rejection, when performing a renal biopsy or if there is declining renal function. They should be checked 3 monthly until one year then yearly thereafter.

8.3 SURGICAL ISSUES 

The following apply to routine (extraperitoneal) procedures. Always check operative notes and discuss with surgeons involved in all cases. The surgical team will review the morning after surgery. As both local Paediatric surgeons and the Transplant surgeons are involved, decisions may require a discussion. Unless by prior agreement any deterioration or concern should be passed on to both operating surgeons to ensure a coordinated plan can be made.

In principal:

NG Tube / PEG

• If minimal and improving drainage over the first 24hrs with a soft flat abdomen and normal bowel sounds, then spigot NG tube.
• Sips to drink initially building up as tolerated
• If there is any abdominal distension or vomiting, then stop fluids, place NG on free drainage and discuss with surgeons
• Aim for fluids, light diet and all medication taken orally by 24-48 hours or earlier if tolerated
• Remove NG tube when tolerating fluids and drugs

Wound Drain

• If drainage minimal then consider removal at 48-72 hours
• If drainage volumes change dramatically then discuss with surgeon

Urethral catheter

• Should remain in situ until days 6-7 (remove after wound drain and external stent if present)

Ureteric Stent

• These will mainly be internal JJ stents which will be removed surgically after approximately 4-8 weeks. Theatre date to be arranged with the urologist prior to discharge. Often patients will be booked onto beginning of next LD list if possible. Patients may also need lines removed at that time.
• Occasionally external transplant ureteric stents are used which are usually of small calibre (4-6Fr) and therefore prone to blockage
• Flush 6 hourly with 5ml of 0.9% Sodium Chloride for first 24hours or longer if not draining well
• Aim to remove on day 5

HD or PD catheters, Internal JJ Stents

• Where PD or HD catheters remain in situ or an internal (JJ type) stent has been used patients should be booked for removal at about 4-6 weeks. This should be on the elective list of the operating paediatric surgeon or utilising the first hour of the LD Wednesday list. A booking should be made early to ensure patients are not delayed through waiting list pressures.

8.4 RADIOLOGY

• Renal USS as clinically indicated
• Use portable handheld Clarius USS (available on Ward 3C) if appropriate
• Consider USS pre and post catheter removal
• Consider Mag3 scan if there is persisting delayed graft function and concern about graft perfusion.

9.4 Rejection

Rejection is a diagnosis of exclusion and when suspected should be confirmed by renal biopsy (See Guideline for Renal Biopsy). If confirmed rejection should be treated with intravenous methylprednisolone (600mg/m², max 1gm) for 3 days followed by a prednisolone taper. Consideration should be given to augmenting baseline immunosuppression. Measure donor specific HLA antibody. If immunosuppression is increased consider CMV and PCP prophylaxis if these have already been discontinued.

9.5 Hypertension

High BP is common post transplant and often improves with time. Calcium channel blockers are often the first line agents to be used, except in IgA nephropathy. Please refer to the hypertension protocol and discuss with nephrologist on call.

10.1 The discharge planning summary sheet is held within the nursing documentation and should be reviewed to ensure all aspects of transplant care for discharge have been considered.

Before the child is ready for discharge, ensure the following have been completed:

• Discharge summary to GP and other medical personnel involved in the child’s The aim is for this to be received within 2-5 days of discharge. Refer to Discharge Summary Guideline for the information that needs to be included.  Copy the Trakcare IDL onto the renal database SERPR, and e-mail a copy (where relevant) to the local paediatrician on day of discharge.
• Supply of medications including where appropriate either
  • 5 and 1.0 mg of Tacrolimus (Prograf®) capsules OR
  • 2 and 1.0 mg Tacrolimus (Modigraf®) sachets
• Renal Medication Information Book with up to date medication,and update ALL medications on renal database (SERPR).
• Ensure booking confirmed for removal of PD or HD catheters and internal JJ stent.
• Consider dietary advice, sun protection advice (leaflet available), advice re vaccination etc…
• Co-trimoxazole should be used for the first 6 months post transplant.
• Prednisolone reducing schedule if appropriate (Avoid enteric coated prednisolone)
• Aspirin should be continued for the first 3 months
• Valganciclovir should be continued for the first 3-6 months

10.2   Review after Discharge

The following is a rough guide.

• If rejection episodes occur then visits will need to be more frequent.
• At each visit: Weight, BP, bloods, urinalysis +/- urine culture as required.
• Virology PCR screening as outlined below
• Virology: If EBV, CMV, varicella IgG negative – repeat serology 6 mthly during first year (clotted blood)
• Virology: If Hep BSAg and Hep C screen negative – repeat serology yearly unless indicated more frequently
• If creatinine elevated, measure viral PCRs and anti- HLA antibodies

10.3 Viral Screening

EBV, CMV, Adenovirus, Polyoma PCR - 3-5 ml EDTA blood sample
0 - 6 months post transplant: - monitor weekly or at each visit if seen less often
6- 12 months: monitor monthly to every 6 weeks
Thereafter only at annual transplant assessment unless there is clinical concern

Clinical concern of polyoma virus – send urine in a plain universal

For further discussion on this guideline, please contact a consultant within the Renal Unit.

This is only a guide. If results are abnormal then they may need to be checked more frequently.

BP Centiles available on ward or use mobile App Ped(z)

Start with IV therapy and convert to oral Prednisolone as soon as tolerated. Most patients receive only 5 days of steroid. 

Day 0                     as above in theatre
Day 1                     60 mg/m²/day (maximum dose 80mg)
Day 2                     40 mg/m²/day
Day 3                     30 mg/m²/day
Day 4                     20 mg/m²/day then stop.

IV treatment (0.06mg/kg/day continuous infusion) is associated with hypertension - where possible start with oral therapy. Can give NG by opening the capsules and dissolving the contents in at least 10 ml water. Flush with at least 10 ml water and clamp NG tube for 45 - 60 minutes.

• Aim for 12 hour trough levels of:
  
  

  1st 2 months 3 to 6 mths      6 mths to 1 year After 1 year

  8 - 12 ng/ml 5 - 10 ng/ml 4 – 8 ng/ml 3 - 6 ng/ml

• Trough level measured at 12 hours. One 0.5 ml EDTA is sufficient.
• Interaction can occur with erythromycin, fluconazole and other imidazoles, warfarin. Do not administer with grapefruit or cranberry juice.
• Prescribe as brand (Prograf® / Modigraf®) as other preparations are available
• Modigraf® sachets can be used for those who have difficulty swallowing capsules.

Dose reductions will be needed if there are low platelets, low WCC or low haemoglobin. Available as 250mg capsule and 500mg tablet. Use liquid preparation rather than splitting capsules for doses in between. Side effects can be lessened by splitting the same daily dose tds or qid. If side effects are problematic, drug levels can be measured as an MPA trough.

If used in combination with ciclosporin continue on 600mg/m2 bd after 2 weeks. Ciclosporin interacts with MMF and reduces the AUC.

Basiliximab is an IL-2 receptor blocking antibody, used at induction. It is generally well tolerated. Only 2 doses are needed causing IL-2 receptor blockade for up to 4-6 weeks.

The infusion: reconstitute with 5ml of water provided and then further dilute to a volume of 50 ml with 5% Glucose or 0.9% Sodium Chloride. Give over 20-30 minutes.

First dose is given on day 0 in ward 3C when it is known that the transplant is going ahead, dose 2 on day 4.

PROPHYLAXIS

Patients who are CMV seronegative at the time of transplantation, should receive oral valganciclovir after transplantation if the donor is CMV seropositive. Valganciclovir should be started when the patient is tolerating oral fluids and continued for a duration of at least 3 and preferably six months.

TREATMENT OF CMV DISEASE

CMV disease is diagnosed by evidence of CMV in the blood by PCR and systemic symptoms: fever, abnormal LFTs, anaemia etc. Treatment is with oral valganciclovir

The length of treatment will depend on the severity of the illness. 

Longer treatment may be required for gastrointestinal disease

Immunosuppressed patients are at risk of pneumocystis jirovecii pneumonia (previously pneumocystis carinii). This is particularly true for patients receiving augmented immunosuppression. Patients who develop CMV disease are susceptible to PJP.

If clinically indicated send a bronchial alveolar lavage (BAL) to Virology for CMV PCR and to confirm the diagnosis of PJP by direct immunofluorescence and PCR.

Prophylaxis

Co-trimoxazole 12 mg/kg nocte (max. 480 mg) to be given for a minimum of 6 months. Can ‘double’ as urinary prophylaxis.

Treatment

If the patient is deemed to be at increased risk of clotting then low molecular heparin may be used instead of aspirin. This is given as Dalteparin (Fragmin®) 40 units/kg bd by subcutaneous injection, starting within 2-4 hours post surgery. This is usually given at 1800 and 0600 and a heparin assay measuring the anti-Xa level is measured 4 hours after the second (usually morning) dose. If these times are missed, aim to give the first dose within 2-4 hours of surgery, the next at 10 to 14 hours and gradually work around to dosing at 0600 and 1800. Remember levels are only measured within working hours, but samples can be spun down and frozen.

Check  an  Anti-Xa  level  at  1000  each  day  (Purple  Sodium  Citrate  tube). Withhold next dose until this result is available.

Aim for Anti-Xa levels of between 0.2 - 0.4 iu/dl. Patients with a pro-coagulant tendency may require a different therapeutic range.

Once patients are ambulant (approx day 5) or as directed by the medical team, dalteparin can be discontinued and aspirin commenced.

WIG Protocol for Use of ATG ( Rabbit Anti T-lymphocyte Globulin/ Thymoglobuline)

Updated by Heather Black, Renal Pharmacist 6.2.12                            Reviewed by Neal Padmanabhan

Uses

Steroid resistant rejection in renal transplant patients. Use of ATG should only be on the instruction of the Consultant looking after the patient.

Supply

Dosage

The aim is to suppress absolute CD3 count to <0.05 x10⁹/L  (50,000 cells/ml) for 14 days.  On day 0 a test dose is administered, followed on day 1 by the first full dose of 1.5mg/kg. CD3 counts are monitored daily and further doses of 1.5mg/Kg are administered if the CD3 count is≥0.05 x10⁹/L. Usually 3 doses will be required over a 10-14 day period.  Length of treatment will be decided based on clinical status and laboratory results (approx 10-14 days) and may be suspended if total WCC falls to <2 x10⁹/L, platelet count < 50 x10⁹/L, or if unacceptable side effects intervene. To avoid over-immunosuppression,  tacrolimus dose is reduced to quarter dose and MMF is stopped during treatment.  Cumulative doses between 10.5-21mg/kg may be required. Use ideal weight not actual weight and round the dose to nearest 25mg.

Presentation and Administration

• Thymoglobuline is presented in vials of 25mg freeze dried purified immunoglobulin + 5ml vial of diluent. The vials should be stored in the fridge.
• Although not essential, many units give a test dose due to infusion related symptoms including anaphylaxis.
• Test dose: no test dose is generally required
• Full dose:
  Premedicate with hydrocortisone 100mg IV and chlorphenamine 10mg IV.
  Reconstitute vials as above.
  Administer in NaCl 0.9%, allowing 50mls for every 25mg vial (total volume 250-500mls).
  Administer via a central line over at least 6 hours (preferably 8-12 hours if infusion related reactions are an issue). Observe the patient checking BP, pulse and temperature frequently during the infusion.

Stability

Once reconstituted, the infusion is only stable for a maximum of 24 hours but should be used as soon as possible.

Contraindications

• Allergy to rabbit protein
• Acute viral illness
• Full anaphylactic reaction to test dose

Side Effects

Severe acute infusion associated reactions associated cytokine release and rarely anaphylaxis can occur. Symptoms include headache, fever, arthralgia, rigors and hypotension. Pulmonary oedema may occur in severe cases. Reducing infusion rate and pre med with paracetamol, hydrocortisone and chlorpheniramine can reduce incidence and severity of these reactions.

Caution if platelet count falls <50 or WBC<2- consider interrupting treatment.

Interactions

There is a risk of over-immunosuppression- review tacrolimus/ ciclosporin dose and stop mycophenolate.

Continue co-trimoxazole and valganciclovir prophylaxis for 3 months after treatment with ATG.

Dosing schedule

*CD3 Count 

Daily CD3 count. Further full dose if CD3 Count ≥0.05 x10⁹/L (50,000 cells/ml). No dose if total WCC <2 x10⁹/L or platelet count<50 x10⁹/L.

Tacrolimus/MMF

Reduce Tacrolimus to 0.025mg/Kg as 2 doses until day 14, then increase to 0.05mg/Kg bd (Target level 8-12)

Stop MMF during treatment then reintroduce at full dose  from day 14.

ⁱhttp://www.dh.gov.uk/health/2012/03/sabto/

Introduction

The potential for an ischaemic injury to reduce the impact of a subsequent ischaemic injury has been demonstrated in animal models since the 1990s.  This can occur directly (direct) or following an injury to a different part of the body (remote).   The effect also appears to occur if the ischaemic injury is applied before (pre-), at the same time (per-) or after (post-) the main injury.

A conditioning injury can be caused by inflation of a BP cuff impeding blood flow to the distal end of a limb.  Studies suggest that 3-4 cycles are sufficient to have a conditioning effect.  The exact timing of conditioning and whether it should be applied to donor, recipient or both remains under investigation.

Who it applies to
Paediatric patients due to receive a living related donor transplant
Paediatric patients due to receive a deceased donor transplant where there is sufficient time
Paediatric patients old enough to tolerate the procedure (practically, this has been >5 years)

Equipment required
‘Green light’ sphygmomanometer
Appropriate blood pressure cuff size
Stethoscop

Procedure

On morning of LRD transplant approx 0900 (or 2-3 hours pre-procedure for DD)

• Check blood pressure with manual (‘green light’) sphyg.
• Document blood pressure and note systolic
• Manually inflate cuff to 40mmHg above systolic BP and keep inflated for 5 minutes
• Deflate cuff and leave for 5 minutes
• Repeat 3) + 4 above for a total of FOUR inflations and deflations
• Document completion of procedure and time in notes.

Adverse Effects

Some pins and needles and discomfort in the arm is expected.  Mild bruising over the cuff area is frequently seen. 

Procedure must be completed 1-2 hours before called for theatre.