Kidney transplant - acute inpatient care

Organisation and pre-admit of LIVE DONOR paediatric kidney transplant

Once date confirmed:

1. Send date to anaesthetics lead for paediatric kidney transplant to confirm anaesthetic availability.

2. PICU booking form submitted (CNS).

3. Ward 26b booking (if from out of town, admit 2/7 prior). Need for accommodation at Ronald McDonald House indicated here (CNS).

4. Pre-admit organized 2-4 weeks prior (document all results in patients transplant admission file):

   1. Final cross-match done within past 4 weeks – ensure result reviewed and signed off to proceed

   2. Routine bloods and viral serology (CMV, EBV, Hepatitis A, B, C, HIV, Varicella serology)

   3. Review that all necessary transplant workup investigations completed

   4. Urine volume quantification

   5. ECG

   6. Neck vessel imaging to be done (if not already) in < 5 year olds or those with previous lines

   7. Review of medications (timing of discontinuation of long acting antihypertensive plan/ optimization of EPO and Vitamin D doses)

   8. Last echocardiogram and iliac vasculature imaging reviewed

   9. Consider any potential anaesthetic concerns and need for additional discussion

   10. Book Transplant kidney Doppler ultrasounds on ROERs and email Radiology (ultrasound booking clerk).

   11. Complete the “Anaesthetic Update Sheet” that is within the patients personalized transplant admission file.

Paediatric kidney transplant recipient - admission

Pre-operative organisation of DECEASED DONOR kidney transplant

1. Contact family (SMO)

   1. ensure well

   2. ensure NBM order given

   3. confirm timing of last HD session if applicable

   4. confirm when last episode of peritonitis if applicable

   5. transport plan – local hospital duty manager to be contacted and make arrangements for transfer (usually via first available commercial flight)

   6. if family not contactable consider requesting local police assistance

2. Confirm acceptance with ODNZ within 2 HOURS of notification of offer (SMO)

3. SMO to call transplant surgeon (N:/GROUPS/On Call Rosters/Auckland/Liver-Kidney Transplant – consultant tab) – renal service to confirm with surgeon (may be doing retrieval, leave message on phone if necessary). Avoid calling surgeon between hours of 2300 and 0600 hours.

4. Book PICU (phone 021893885)

5. Organise Anaesthetics (to be done ASAP irrespective of time of day)

   1. Daytime hours: inform Starship anaesthetic coordinator (ph 021334344)

   2. After hours call: inform on-call anaesthetist 021334344, and then the coordinator at 0730

   3. SCOPE booking to be done online

   4. Complete the “Anaesthetic Update Sheet” and ensure it is provided to/discussed with anaesthetist.

6. Organise Level 8 theatres – BEFORE 7.30AM (if overnight offer)

   1. Inform level 8 theatre coordinator - 021 492 086

   2. Acute theatre (paper) booking form CR2789 (found in level 8 or SSH theatres, or in 'renal team documents' binder on 26b) required

   3. Level 8 fax number 24877

7. Inform Starship Clinical Nurse Manager – call 021539525

8. Book Ward 26b

   1. In hours: booking form to be done and given to shift coordinator/charge nurse

   2. After hours call ward 26b shift coordinator 021404934

9. Organise urgent HD session (heparin free) if needed/time allows (level 7 acute HD shift coordinator 23131)

10. Drug chart – Basiliximab kept in stock in PICU if out of hours

11. Book transplant kidney Doppler ultrasound on ROERs and email ultrasound booking clerk ( if on weekend will need on-call transplant sonographer to do).

12. On arrival of patient – as per admission below plus:

    1. Inform anaesthetics/L8 theatre coordinator/surgeon patient arrived

    2. Confirm NBM time

    3. Nursing staff to arrange RMH accommodation

Admission to Ward 26b (all recipients – for both deceased and live donor transplant)

1. Medical and nursing admission to Ward 26b under the care of Paediatric Nephrologist on call. Standard history and physical examination to be carried out by the House Surgeon/Registrar.

2. Record accurate height, weight, calculate BSA. Document these as well as 24 hour urine volume and pre-transplant fluid allowance clearly in the admission note. Document donor/recipient CMV status. Document tissue typing (D & R) and cross match results (living donor) – from NZBS.

3. IV line insertion and bloods as below.

4. Tests to be done at preadmission or admission (if at preadmission review if any require repeat):
   CMV, EBV, Hepatitis B, C, HIV, Varicella serologies
   Urine for microscopy, culture and protein:creatinine ratio (if not anuric)
   Liver function tests
   ECG
   25OH Vitamin D (if not done in past 6/12)
   To be done at admission:
   FBC, PR, APTT
   Cross match 2 adult units packed RBCs
   Electrolytes (U&E, Ca, PO4, Mg, creatinine)
   Urine MC&S
   CXR
   If on Peritoneal dialysis, peritoneal dialysate for microscopy and culture, leave EMPTY pre surgery. (Cloudy bag/peritonitis is a contraindication to surgery).

5. Confirm with PICU that patient will be admitted to unit after operation.

6. Inform transplant surgeon that patient /caregiver is on ward for consent.

7. The patient is to be seen by the Paediatric Anaesthetist that has been assigned to the operation. This person will consent and chart any anaesthetic pre-medication that is required. For deceased donor transplants, the on call paediatric anaesthetist must be informed. The combination of clinical and biochemical assessment will provide the grounds for determining if anaesthesia is safe, or whether surgery should be deferred. This decision will be made in conference by the Transplant Surgeon, Paediatric Nephrologist, and the Anaesthetist. Ensure Anaesthetic Update Sheet has been discussed with/provided to Anaesthetist.

8. Ensure day 0 doppler ultrasound has been organized.

9. Chart dialysis if on PD (no last fill) and medications, review dialysis prescription and regular medications with consultant (usually stop anti-hypertensives).

Pre-operative preparation

Obtain patient specific transplant admission flowsheet.

Chart medications and check doses with nephrologist on call:

• Give Tacrolimus 0.15mg/kg (max 8mg/dose) and Mycophenolate Mofetil, 600mg/m2 PO (max 1000mg/dose) early morning on day of operation. If admitted previous day, can commence these medications that evening in addition to above.
  
  Basiliximab induction – to be administered as IV bolus over 20 seconds by ward nurses when called for the operating room (day 0 and repeat dose given on day 4)
  Weight <35kg: 10mg IV
  Weight >35kg 20mg IV
  
  Medications to be given at the time patient is undergoing anaesthetic induction:
  
  Methylprednisolone 10mg/kg (max 1000mg) IV
  Cefazolin 30mg/kg IV (max 2 g unless > 120 kg increase to 3 g)

  Note if MRSA colonised add Vancomycin 10 mg/kg (max 2 g). If ESBL colonised discuss with paediatric ID service.
  If allergies to cefazolin consult surgical antimicrobial prophylaxis Starship guideline.
  
  Please ensure that these are charted on once only section of medications chart and send these medications with the patient to OR.

• Confirm with blood bank that cross-matched blood is available (2 adult units packed cells)

• IV fluids with Plasmalyte 148 to commence when nil by mouth. Infusion rate to be decided by renal team (depending on usual urine output and fluid intake, aim to have mild intravascular fluid expansion at time of going to OR).

• If on PD leave empty pre surgery.

Paediatric kidney transplant recipient - operation

Preparation

1. Operating theatre to be kept at >23°C, warming blanket on table

2. Blood warmer available for IV fluids

3. Instruments:
   As for Adult Kidney Transplant Recipients, plus:
   A variety of paediatric double lumen Central lines (held in Starship OR)

4. The Surgical Resident will prepare the patient as for a routine renal transplant except that:

   1. The neck and chest need to be prepared as well

   2. The patient must be positioned to allow insertion of central line and the image intensifier.

   3. The urinary catheter used should be of paediatric dimensions

   4. The volumes of neomycin solution used to wash out the bladder should be reduced according to the size of the patient (wash out with 3mL/kg and instill 4mL/kg to leave the bladder distended).

Anaesthetic management

(Refer for more detail to anaesthesia department guideline for paediatric kidney transplant)

1. All paediatric transplant recipients should be anaesthetised by a designated transplant paediatric Anaesthetist.

2. All patients will have an anaesthetic update sheet accompany them to theatre. It is expected this will be utilised to optimise intraoperative renal perfusion.

3. Monitoring equipment should involve measurements of:

   1. Central venous pressure

   2. Direct arterial blood pressure

   3. Oximetry

4. The Anaesthetist should check that the following drugs have been given:
   Methylprednisolone 10mg/kg IV (max 1g)
   Cefazolin 30mg/kg IV (max 2g unless > 120kg where max 3g) 0 - 60 minutes before knife to skin, if not allergic)

5. Preferred intravenous fluid choice is Plasmalyte 148.

6. Just prior to reperfusion of the kidney the Anaesthetist will be asked to administer 0.5-1gm/kg of mannitol (maximum 25g) and 2mg/kg of frusemide IV (maximum 100mg). CVP should be ≥ 8cm H20 just prior to release of vascular clamps.

7. The Anaesthetist will record the kidney weight and time that the kidney is removed from ice and the time that it is reperfused (WARM ISCHAEMIA TIME).

8. Sedation/analgesia choice should be titratable and lowest risk for hypotension.

9. The patient will be transferred to the PICU from Auckland City Hospital with direct handover to PICU staff and on call nephrologist.

Paediatric kidney transplant - PICU

The greatest early risk to graft function is renovascular thrombosis. This is particularly so in children who have low blood pressures, but are transplanted with an adult donor kidney, accustomed to an adult BP. The gold standard assessment of adequate volume status and mean arterial pressure for the newly transplanted kidney is renal Doppler. This is routinely performed on table at the end of surgery and/or on arrival to PICU +/- Day 1 post operatively. Renal Doppler may also be performed at any time of unexplained oliguria. If the renal perfusion is inadequate, then raising the MAP and CVP is indicated. The prevention of hypovolaemia in the first 48-72 hours after kidney transplant is essential in maintaining graft perfusion and therefore graft function. If the MAP/systolic blood pressure and CVP targets are difficult to achieve (excessive fluid volumes/high rates of inotrope required) discuss with renal consultant. Reducing the targets may be acceptable if the kidney doppler ultrasound and clinical findings suggest good perfusion (good urine output, falling creatinine).

1. Patients will be under the joint care of the Paediatric Nephrologist on call, the PICU Intensivist and the Renal Transplant Surgeon. Hour by hour changes in fluid and electrolyte management will be made by the PICU Registrar as per protocol and in conjunction with the Paediatric Nephrologist.

2. Vital signs: Abnormal observations must be discussed with the Paediatric Nephrologist on call. Blood pressure, pulse, central venous pressure will be monitored by continuous arterial and central venous pressure lines with hourly recordings.

3. Weight: Daily body weight on the same scales.

4. Fluids:

   1. Urine losses to be replaced mL for mL with Plasmalyte 148 (change to 0.45% if concern regarding hypernatraemia).

   2. If large surgical drain outputs consider need to include in fluid replacement volumes and inform transplant surgeon.

   3. Insensible water losses (400mL/m²/day) to be replaced with 5% glucose.

   4. If the haemoglobin concentration is less than 75 g/L then RBCs should be given (5-10 mL/kg over 2-4 hours). (Note: unless the haemogloblin is rapidly falling and oxgen delivery may be compromised, red cell transfusion should be avoided unless Hb <75g/L).
      
      NOTE: Maintain intravascular volume status with 5-10mL/kg boluses of Plasmalyte 148 or 4% albumin solution. The sufficiency of fluid replacement is assessed by the combination of vital signs, peripheral perfusion, CVP and urine output.

5. Urine output:

   1. If urine output is <1.5 mL/kg/hr the paediatric nephrologist is to be called immediately.

      1. check urinary catheter patency with sterile water flush

      2. check circulating volume status
         
         If urine output is <1.5 mL/kg/hr and CVP is >7cm H20, then an inotrope may be initiated. If this fails to produce an adequate urine output, give frusemide 1-2mg/kg. MUST discuss with renal team before starting inotropes or giving frusemide.
         
         If no response, obtain an URGENT Doppler scan to confirm blood flow to and from the kidney.

   2. If urine output 1.5-7mL/kg/hr, replace urine output 100% every hour with Plasmalyte 148.

   3. If urine output> 7mL/kg/hour, measure output every 30 minutes and replace mL for mL with Plasmalyte 148 every 30 minutes.

      1. Check gas electrolytes (2-4 hourly) as polyuric patients more likely to develop hyponatremia, hypokalemia and other electrolyte abnormalities.

6. Laboratory studies:
   
   On return from OR:
   Blood: Na, K, glucose, Ca, Mg, PO4, creatinine, urea, albumin, haemoglobin, acid base
   Thereafter:
   Blood - Every 6 hours: Haemoglobin, Na, K, glucose, albumin creatinine, urea
   Catheter urine specimen for MC&S daily if PICU stay >24 hours
   Urine PCR and ACR 12 hourly if primary cause of renal failure is history of FSGS

7. Imaging:

   1. Transplant kidney Doppler ultrasound scan by transplant sonographer as soon as possible after admission to PICU (mandatory for all)

   2. DTPA nuclear medicine scan will only be done if clinically indicated and ordered on advice of on call nephrologist

8. Medications:

   1. Immunosuppressive medications as per protocol

   2. Cefazolin 30 mg/kg I.V. (max 2g) q8-24hourly depending on GFR for 48 hours post-operatively

   3. Co-trimoxazole (nb. Suspension is 240 mg/5 ml, consider dose adjustment for GFR)
      <20kg 2.5mL (120mg) nocte
      20-40 kg 5mL (240mg) nocte
      >40kg 10mL or 1 tablet (480mg) nocte

   4. Nystatin oral suspension 1mL to swish and swallow QID, this is to be continued whilst inpatient. Can consider discontinuation at discharge on case by case basis. Otherwise if high risk (eg in nappies, stomas) continue until 4 weeks post transplant/stent removal.

   5. Omeprazole 1mg/kg/dose (max 40mg) once daily

   6. Valganciclovir as per protocol – to start day 1-3 post op

   7. Pain relief and sedation: To be managed by PICU/ pain service, preference of agent is for easily titratable and lowest risk for hypotension in first 24 hours. Dosing to be frequently adjusted as per GFR changes.

9. Blood pressure management:
   Avoid relative hypotension as adult allografts require higher perfusion pressures.
   Minimal and maximal BP limits to be discussed with Paediatric Nephrologist on return from OR. Discuss directly with Paediatric Nephrologist if outside these limits.

See section on transplant for Infants under 15 kg

Transfer to lower dependency care (Ward 26b)

When the need for intensive monitoring of vital signs and urine output has ceased, a decision will be made by the Paediatric Nephrologist, the Transplant Surgeon and the PICU in consultation with ward 26b charge nurse, to transfer the child to the ward. This will usually be on the 1st or 2nd post-transplant day.

Paediatric kidney transplant recipient - Ward 26b

1. Patients will be under the care of the Paediatric renal service. Day to day changes in orders will be written by the paediatric renal house surgeon or registrar.

2. Vital signs: BP, pulse and urine output will be measured 2 hourly unless otherwise instructed.

3. Weight: Daily body weight on the same scales before 0830hrs.

4. Urine losses (also include drain/gut losses if significant):
   To be replaced mL for mL (Plasmalyte 148 unless hypernatraemic). When the patient is tolerating a regular diet and drinking sufficient oral fluids, IV fluids will be discontinued provided the urine output is maintained at >1 mL/kg/hr.

5. Surgical drain and urinary catheter: Timing of the removal of the surgical drain (usually day 2 or 3) and of the urinary catheter (usually day 5) is determined by the transplant surgeon.

6. DAILY Laboratory Studies (minimum – increase frequency as clinically indicated): Na, K, Glucose, Ca, Creatinine, Urea, Mg, Phosphate, Haemoglobin
   Tacrolimus trough levels daily unless otherwise instructed
   Urine culture while catheter in situ and one day post removal, then weekly

7. Immunosuppression and medications: See medication section under PICU section above – ensure these medications are charted for ward and adjust doses as needed for changing GFR. Confirm all medications with SMO.

   1. Immunosuppression adjustments – see Immunosuppression section below

   2. Magnesium hydroxide for hypomagnesaemia (<0.60mmol/L) – solution 1.3mmol/mL starting dose 0.2mmol/kg/day in 3 divided doses

   3. Sandoz Phosphate 500mg tablets (16mmol phosphate/tablet) for hypophosphatemia (Starting dose suggestions: If <0.8mmol/L dose 0.25mmol/kg/day BD dosing; if <0.5mmol/L IV dose 0.33mmol/kg/dose over 6 hours recommended; if <0.3mmol/L 0.5mmol/kg/dose over 6 hours and recheck level one hour post infusion complete)

8. Pain relief: Pain team input. Paracetamol, 15mg/kg/ dose (maximum 90mg/kg/24hours)

9. Discharge Planning – please follow the checklist below:

Routine CMV prophylaxis - Valganciclovir

Commence valganciclovir once tolerating enteral medications - within first five days post transplant, if indicated, as per below:

Patients at high risk of contracting new onset/ reactivation of CMV infection (on special authority):

1. Prophylaxis in high risk categories for 3 months

   1. Donor CMV IgG positive/Recipient negative

   2. Donor CMV IgG positive/ Recipient positive

   3. Donor negative/ Recipient CMV IgG positive

2. Patients receiving ATG/ other polyclonal or monoclonal antibodies for 3 months

Valganciclovir Dose (Prophylaxis for 12 weeks)

Dose (mg/day) = 7 x GFR x Body surface area (max 900mg) [Max GFR to use 120mL/min/1.73m2]
GFR=36.5 x height (cm)/ creatinine (umol/L)

Ganciclovir IV for prophylaxis in those unable to tolerate valganciclovir

Immunosuppression

Pre-transplant and Intra-operative
Tacrolimus (0.15mg/kg/dose (max 8mg) q 12 hourly) and Mycophenolate Mofetil (MMF) (600mg/m2/dose (max 1000mg) q 12 hourly) to start from night prior to transplant for LD transplants.
Basiliximab on ward on call to operating room (<35kg 10mg, >35kg 20mg).
Methylprednisolone 10mg/kg IV (max 1g) intra-operatively.

Day 0 (arrival in PICU)
Ensure that patient received pre-operative basiliximab and intraoperative methylprednisolone 10mg/kg (max dose 1000mg).
For patients having intraoperative methylprednisolone prior to midday, repeat dose 10mg/kg IV (max dose 500mg) 12 hours after initial dose.
Tacrolimus 0.15mg/kg/dose (max 8mg/dose) PO q12 hourly
If tolerating enteral intake give MMF 600mg/m2 PO (maximum dose 1000mg).

Day 1
Methylprednisolone 10 mg/kg IV (max 500mg) q24 hours after intraoperative dose.
Mycophenolate Mofetil. 600mg/m2 q12 hourly PO (maximum 1000mg per dose)
Tacrolimus 0.15mg/kg/dose (max 8mg/dose) q12 hourly PO

Days 2-6

DAY 4 – Basiliximab (<35kg 10mg, >35kg 20mg)
Prednisone PO, see table below for dose.
Mycophenolate Mofetil as above.
Tacrolimus as above, dose adjusted according to Tacrolimus trough level.

Days 7-14
Prednisone PO, see table below for dose.
Mycophenolate Mofetil as above.
Tacrolimus dose adjusted according to trough levels.

Maintenance immunosuppressive regimen

1. Routine tacrolimus and mycophenolate dosing is at 0800 and 2000hrs with food.

2. Steroids as per table below.

3. Mycophenolate as above if WBC >3.0. Reduce dose temporarily if side effects develop.

4. Tacrolimus as per trough levels. Note there may be clinical factors leading to variation in trough target (eg. Viremia, rejection episodes). Frequency of trough level measurements to be decided by clinical circumstances and consultant.

Note: There is potential to run levels 3-5ug/L if stable graft function, low immunological risk (first transplant, rejection free, no DSA, low trough level variability, no concerns for non-adherence, adequate exposure to adjunctive anti-metabolite agent) and beyond 3 years post transplant at the paediatric nephrologists discretion.

Tacrolimus Dose Adjustments

• Drug dose changes should be made no more than every two days, unless drug levels are grossly outside of the target range.

• It may take several days to achieve therapeutic drug levels with increasing drug doses, and typically there is risk for over-shoot that then requires sequential reduction of dose.

• Always clarify exact timing of nightime tacroliumus dose and trough level blood tests to ensure it is a true trough level before making dose adjustments.

• Monitoring should be increased following sub-therapeutic drug levels to every week, until the therapeutic range is achieved.

• For outpatients > 4 months post transplant ensure repeat drug level is requested at a minimum within 5-7 days after every dose change.

• High trough level variability is associated with non-adherence, so periodic assessment of trough level variability (e.g. annually) should be incorporated into the longitudinal patient evaluation.

Steroid reduction regimen

Please note: Different steroid dosing schedules for patients < or ≥ 40kg. If patient is having a second transplant or ABO incompatible transplant, review steroid dosing regimen with Paediatric Nephrologist.

Schedule for Patients < 40kg

Schedule for Patients ≥ 40kg

Three months after transplantation, a renal transplant biopsy will be performed. Providing the biopsy is satisfactory, and a history of early acute rejection is absent, the patient will be switched to alternate day (or 4 x weekly if easier to remember for family/patient) prednisone (5mg alternate day if >40kg, 5mg/m2 alternate day if <40kg).

Cyclosporin

Cyclosporin will be the calcineurin inhibitor of choice in patients who have recurrence of focal segmental glomerulosclerosis in their graft.

Levels/Monitoring

AUC:
It is recognised that trough CsA levels correlate poorly with total exposure to the drug.

Abbreviated area under the curve (AUC0-4) is undertaken in all patients on CsA . Levels are measured at time 0. 2, 4 hours after the dose. Blood sample must be taken within 10 minutes of the dose when AUC is constructed.

AUC for 12 hourly dosing = 444+3.69xC0 + 1.71xC2+4.1 xC4
AUC for 8 hourly dosing = 129 +1.84xC2+4.39xC4

SUGGESTED AUC RANGES FOR TIME INTERVALS AFTER TRANSPLANTATION

Dosing intervals for Cyclosporin and Tacrolimus

3 x daily dosing for CYCLOSPORIN & TACROLIMUS to be considered in children <age 5 years

MYCOPHENOLIC ACID LEVEL TESTING: See additional guideline and worksheets re MPA testing.

Infant transplant < 15kg

Pre-transplant planning/evaluation

All will have pre transplant neck and iliac vasculature ultrasound to establish patency of vessels for both line placement and transplant anastomosis. At the transplant surgeons discretion, more extensive imaging of abdomen/pelvis +/- vasculature (CT/MRI) may be requested.

All patients will have had pre-transplant cardiac echocardiogram. If any known cardiac anomaly, specific pre-transplant plan regarding blood pressure targets and inotrope recommendations should be documented with cardiology input (and the cardiac related guidelines below may not apply*).

Surgical considerations

Small recipients are at increased risk of vascular complications including vascular stenosis and thrombosis. Transplant surgeon will likely place the allograft intra-abdominally (aortic/IVC anastomosis) instead of extraperitoneal (iliac vessel anastomosis) location. There may be increased risk of allograft torsion on vascular pedicle with this placement. Percutaneous needle transplant biopsy is usually still possible for intraperitoneal grafts but should be discussed with radiology.

If significantly large donor kidney and/or gut manipulation/handling there may be increased risk of ileus. There may be increased third space fluid losses.

Circulating volume/ Graft perfusion considerations*

• The added excess vascular circuit from transplantation increases requirements for cardiac output for perfusion. In smaller children, this may be in excess of normal capacity resulting in ischemia.

• Distal placement on the arterial vasculature reduces relative blood flow, compared with more proximal placement of native kidneys.

• Sympathetic denervation is requisite with transplantation, resulting in impairment of regulated vascular tone in the setting of hypovolemic stress.

• Calcineurin-inhibitor medications cause vasoconstriction, which may impair renal blood flow.

Large adult donor kidneys thus require adequate blood flow to avoid chronic ischemia, the shrinkage of adult kidney and early development of tubular atrophy and interstitial fibrosis. Sufficient cardiac output and volume overload is needed to ensure adequate perfusion of the graft. The cardiac output must double in order to perfuse an adult kidney adequately.

• Intraoperatively it is considered desirable to maintain CVP >10cmH2O prior to unclamping and the mean arterial pressure at >60mmHg.

• General target is minimum SBP > 100-110mmHg (absolute minimum MAP 60mmHg which is 25th percentile for age 12months) however donor and recipient pre transplant BP are important in determining this target which should be individualised and documented by oncall nephrologist.

• Intraoperative information regarding renal perfusion may also inform BP targets required for adequate graft perfusion.

• Preferential inotrope is dopamine.

• Midodrine, salt and fludrocortisone might be considered to support blood pressure rather than escalating doses of inotropes.

These patients need to have an early Transplant kidney Doppler ultrasound (on same day of surgery) when they arrive in PICU from the Operating Room. Correlation between Doppler appearances, arterial blood pressures and urine output at the time of the ultrasound should be noted and recorded. There should be a low threshold to requesting subsequent Doppler ultrasounds in the early post transplant period.

Measurement of peripheral to core temperature gradient may help assessment of adequate circulating volume.

Post PICU care

• Prolonged enteral fluid support is required, at least 3 months post transplant.

• 2500-3000mLs/m2/24hours of maintenance fluids is required to maintain adequate renal perfusion, this should be continued for at least 4 months post transplant.

• Gastrostomy access for nutrition and fluid support will usually be required to achieve these fluid requirements over 24 hours.

• Due to faster metabolism consideration may be given to TDS dosing of calcineurin inhibitor and mycophenolate mofetil. Immunosuppressive medication administration via G-tube is best avoided.

Rejection

Investigation and treatment of acute allograft rejection

The diagnosis of acute rejection will be made using clinical, biochemical, histological criteria. Patients with suspected rejection will be investigated with a number of different tests including BK, CMV, EBV PCR, transplant kidney ultrasound (+/- doppler) and allograft biopsy. If histological confirmation of rejection consider sending sample to NZBS for Luminex HLA antibody identification – ensure advise on request form that patient has current confirmed /suspected acute rejection. Consider need for adherence questionnaires/pharmacy input, dose and target level adjustment for immunosuppression, need for MPA/ Tac AUC.

Banff Grade 1:

Methylprednisolone 20mg/kg IV (max 1gm) daily for 3 days (if “borderline” 1A ACR may consider lower dose ie 10mg/kg).

If no response at this stage (by completion of 3rd dose), repeat biopsy and if rejection has not substantially improved, the episode will be regarded as steroid resistant. If response is satisfactory, the steroid dose will be tapered as follows:

Day 4 & 5 - Prednisone 2mg/kg/day (max 80mg)
Day 6 & 7 - Prednisone 1mg/kg/day
Day 8 & 9 – Prednisone 0.5mg/kg/day
Then return to pre-rejection prednisone dose with consideration of maintaining daily steroid in those whom non-adherence is suspected.

Post IV MP monitor EBV, CMV, BKV viral loads in 2 weeks then monthly for 3/12. Ensure timing of next renal function testing clarified and communicated to family/ local paediatrician.

If signs of severe rejection are present, i.e. high fever, oliguria, graft tenderness, a rise in creatinine of >50% in 24 hrs, or arteriolar damage on histology/ Banff Grade 2/3, then treatment will progress as if the episode were steroid resistant ie therapy with Thymoglobulin.

Steroid Resistant Rejection – Anti Thymocyte Globulin (Rabbit; rATG)

ATG is produced from rabbit serum immunised with human T-lymphoblasts. ATG rapidly depletes T cells in vivo, and has a short half-life such that return of T cells is rapid. It is non-specific, so other white cells may also be depleted and thrombocytopenia can occur.

Requirements before r-ATG can be administered:
CXR must be clear (no fluid overload)
CVL required (minimise thrombophlebitis)

Premedication: 1 hour prior to r-ATG dose
Methylprednisolone 20mg IV
Phenergan IV (0.2mg/kg/dose, max 12.5mg) day 1 and 2 then may give PO
Paracetamol 10mg/kg orally

Precautions:
Anaphylactic reactions – hypotension, fever, urticaria – if severe discontinue
Fever reaction – frequent on first day but usually subsides
Serum sickness – may occur after one week – infusion does not need to be discontinued

Administration:
Dilute 25mL (25mg) to minimum of 50mL sodium chloride 0.9%
Slow IV infusion into high flow large bore CENTRAL vein (CVL only)
Give over 6 hours for initial dose and if tolerated, can administer over 5 hours for subsequent doses
Use in line filter with pore size of 0.22u
Do NOT mix with glucose/dextrose solutions

Monitoring:
Daily FBC and differential – aim to keep lymphocyte count < 0.3
If neutrophils < 1.5x10⁹/L or PLT <50,000 the ATG should be witheld until they reach this level again when it should be reintroduced at a dose approx 2/3 of that previously prescribed.

Post Dose:
Tacrolimus is discontinued at start of r-ATG until 2 days prior to completion of thymoglobulin. Mycophenolate is continued at a normal dose.
All must restart valganciclovir (unless D-/R-) and co-trimoxazole prophylaxis for 3 months
Monthly EBV, BK and CMV viral loads for 3 months