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Renal transplantation is the treatment modality of choice for children with end-stage kidney disease since it decreases morbidity and mortality and improves quality of life. Children usually receive either living donor or deceased donor kidneys from adults. There are particular challenges to keep in mind while managing pediatric kidney transplant recipients in the post-operative period in the intensive care unit. This review focuses on the unique issues relating to maintaining fluid balance, current immunosuppression practices, prevention of graft thrombosis and expected complications of kidney transplant in children.

Kidney-allograft survival has improved tremendously over time, such that transplantation is now considered the best treatment for end stage kidney disease in children. Such progress can be attributed to multiple factors— refinements in pre transplantation preparation, enhanced surgical techniques, better choice of donors, more potent immunosuppressive medications, greater understanding of pediatric-specific pharmacokinetics, and use of evidence-based post- op management .Pediatric kidney transplantation is generally performed in specialized centers due to complex technical, metabolic, immunologic, and physiologic factors. Post-transplant care involves a integrated multidisciplinary team comprising pediatric transplant surgeons, pediatric nephrologists and pediatric intensivists along with trained paediatric transplant nurses.[1] Most children are cared for in the pediatric intensive care unit immediately post transplantation, in order to closely monitor hemodynamic stability, intake and output and optimise graft perfusion. The pediatric intensivist, thus should be familiar with the immediate post-operative management.Intra-operative Management
In children the adult sized donor kidney is placed either in the right or left iliac fossa, extraperitoneally or intraperitoneally in the case of a very small child. Vascular anastomoses with the donor vessels are with the iliac vessels in older children or directly with the aorta/ inferior vena cava in a smaller child. When the graft is perfused, a ‘vascular steal’ phenomenon occurs due to the large volume of blood that rapidly enters the transplanted adult sized kidney. This could lead to severe systemic hypotension which is deleterious to graft function. Therefore during vascular anastomoses, the child is given large volumes of fluids to expand the intravascular volume, build up the CVP and raise the blood pressure, above his/her 95th percentile. In a successful transplant the graft urine output begins immediately upon reperfusion. The child may arrive in the PICU passing large hourly quantities of urine.

Basics of Management in the Intensive Care unit
Immediate airway and hemodynamic support in Pediatric Intensive Care
The transplant team and paediatric intensivist should evaluate the patient on arrival from the operating room. The initial assessment should include hemodynamic and respiratory stability. Most patients are awake and could be extubated.[2] The systolic arterial blood pressure should be above 100 mmHg to provide adequate perfusion of the newly transplanted allograft in the first 24-48 hr. of intensive care. Crystalloids or albumin infusion should be infused to maintain adequate pressures. Rarely, inotropes may also be considered to achieve the target blood pressure.[3]

Monitoring
In addition to general pediatric perioperative care, the specific fluid, electrolyte and hypertension management in the first 24-48 hours after the transplant procedure requires close attention from the paediatric intensive care team, particularly for small children.[4]

Postoperative monitoring
Frequent hemodynamic evaluation is important. Vital signs (including temperature) should be checked every hour for 24 hours, then every 2 hours for 8 hours, then every 4 hours for stable patients.
Blood pressure (BP) monitored to maintain above 100 mmHg to provide adequate perfusion of the allograft in the first 24-48 hr. of intensive care and also for early recognition of hypertension .
Maintain urinary catheter patency and a closed system. Catheter patency is vital to keep the bladder decompressed and prevent pressure on suture lines.
Strict urine output should be monitored, initially every 30 to 60 minutes in first 24 hrs and fluids should be infused as explained in further detail below.
Monitoring of central venous pressures (CVP) is also beneficial in evaluating the recipient's intravascular volume status and guide fluid replacement and colloid .
Abdominal drain monitoring is helpful for early diagnosis and intervention. An increase in the drain output can indicate urinary fistula, lymphorrhea or bleeding.
Abdominal drains and bladder catheters are left in place for at least 5-7 days.[5]
No blood pressure, venipuncture in extremity with fistula or shunt.
Infection may not significantly elevate the temperature. Monitor for signs such as change in level of consciousness, cloudy or malodorous urine, or purulent drainage from the incision.
Postoperative Laboratory Orders
Upon arrival in PICU a CBC, serum creatinine and liver function tests should be obtained and then once daily
Regular monitoring of electrolytes, usually 2-3 times per day is essential in the first few postoperative days.
Other investigations included coagulation parameters, calcium, phosphorus and magnesium as these may become low and require intervention.
Management Fluid and Blood pressure
In small children, an adult graft can sequester a large proportion of the circulating blood volume, leading to systemic hypotension, poor graft function and the risk for graft thrombosis. Therefore, post-operative management in the ICU should ensure adequate systemic perfusion to the graft.[6] There is often copious urine production from a well-functioning graft due to the early lack of urinary concentrating ability. The hourly urine output may approach the patient's entire blood volume and therefore, close urine output monitoring is essential. A typical fluid infusion regimen consists of a combination of insensible losses (400ml/ m2/day of a dextrose containing crystalloid) along with hourly volume by volume urine replacements with either 0.45% or 0.9 normal saline. Within 24-48 hours, the graft regains urine concentrating ability and the urine output reduces.[7,8] At this stage, fluids may be reduced and given at a continuous fixed rate. Oral fluids should be encouraged as soon as the child is able to tolerate drinking.

Due to the large volumes of diuresis of dilute urine and intravenous replacements, electrolyte disturbances are common. Usually hyponatremia or hypernatremia occur and can be managed by changing the tonicity of the fluids being infused. Hypokalemia may also occur, although IV replacement of potassium should be very carefully provided, in a separate line. Hypophosphatemia and hypomagnesemia are not uncommon and managed with oral supplements.

Sedation & Pain Control
Postoperative pain is a significant source of distress in the immediate postoperative period and pain management is essential. As morphine is contraindicated in impaired renal function, post-operative analgesia may be provided with fentanyl and paracetamol.

Fentanyl synthetic opioid may be used in renal failure as continuous infusion. It provides good postoperative analgesia without respiratory depression.

Immunosuppression
Immunosuppression is essential for graft survival, although its use in pediatric transplant is tailored to each individual. The goal is to reduce the risk of rejection, promote good long term graft outcomes, but avoid over immunosuppression and drug toxicities.[7]

Induction therapy is provided during the perioperative period to prevent T cell activation that might lead to acute rejection. Most commonly high dose corticosteroids are used along with anti-IL2 receptor antibodies (basiliximab) or anti-lymphocyte antibodies, depending on the stratified risk of graft loss (sensitization history).

Maintenance immunosuppression consists of corticosteroids, anti-metabolites (azathioprine or mycophenolate) and calcineurin inhibitors (cyclosporine / tacrolimus). Although corticosteroids are usually administered intravenously in high dose for the first 2 days, the other medications are given orally or via naso-gastric tube, strictly timed, in order to maintain appropriate and steady therapeutic levels. Monitoring for drug interactions is required when introducing new medications and doses are adjusted only in consultation with nephrologist.

Infection in renal transplant
Post-transplant infections impact both on patient morbidity and mortality and allograft function There are 3 general time frames to consider, namely, the first month (i.e., the early perioperative period), the second through the sixth month, and the late post-transplant period (beyond the sixth month).[9]

In the early postoperative period, the most common infections are bacterial and involve the urinary tract, the wound, the respiratory tract, and central line infections. Infection in post kidney transplant recipients can be difficult to diagnose because concomitant immunosuppression and alterations in the immune response attenuate the usual clinical signs and symptoms of infection such as fever and leukocytosis. High index of clinical suspicion and prompt administration of empiric antimicrobial therapy based on site of infection are essential for effective treatment and prevention of infectious complications.[2]

Prevention of infection
Prophylaxis
Anti-infective prophylaxis is tailored to the intensity of immunosuppression, and history of exposure to infections in the recipient and donor. Cefazolin (vancomycin or clindamycin for those allergic to cefazolin) is used for 24 hr. for perioperative antibacterial prophylaxis. Ganciclovir or valganciclovir is used for 4 to 6 mo post-transplant for CMV prophylaxis in those patients at risk. Oral Nystatin (6–8 wk) and cotrimoxazole (6 mo) are used to prevent fungal and pneumocystis carinii infections. Cotrimoxazole also serves as prophylaxis in those patients at high risk for UTI.[10]

Anticoagulation
In order to prevent graft thrombosis, a dreaded complication leading to early graft loss, preoperative screening for risk factors for graft thrombosis is performed. Some of these include small recipient size, nephrotic syndrome and a history of previous thrombotic events.[11]

In some centres, prophylactic systemic anticoagulation with unfractionated heparin followed subsequently by low molecular weight heparin is performed. In these cases, monitoring for surgical bleeding is important in the ICU.

When unfractionated heparin is being used, ACT monitoring should be performed at regular intervals.[11]

Surgical Challenges in the Peri-operative Period
Structural urological abnormalities result in lower urinary tract dysfunction and contribute to 20-30% of End stage renal disease (ESRD) in children.[2]

It has been noted that an adequately treated bladder dynamics and reconstruction of an abnormal bladder does not adversely affect the outcome after renal transplantation. However proper pre-operative evaluation, select technical modifications during transplant surgery and post-operative care are necessary to avoid complications in transplanted children with abnormal bladders.[13] Native nephrectomy is required in 20-45% of pediatric recepients.[14] Nephrectomy of recipient is indicated only when there is no response to medical management. Occasionally it is preferred to do nephrectomy during transplant and in a few children unilateral pre-transplant nephrectomy is suffice.[15]

In those children who have undergone bladder augmentation, nephrectomy and anuria cause a dry augment necessitating bladder cycling to maintain bladder capacity.

Regular wound check for infection or dehiscence is mandatory. An increase in the drain output can indicate urinary fistula, lymphorrhoea or bleeding and need to be appropriately addressed.

Ultrasound including colour doppler is the mainstay in imaging of pediatric renal transplants. It effectively helps assess the vascular integrity, graft perfusion and immediate complications and also serves as baseline for future imaging.[16]

Medical Complications
Delayed graft function(DGF)
Although by strict definition, delayed graft function is diagnosed as the need for dialysis in the first week after transplant, DGF may also be indicated by a failure of the serum creatinine to return to the baseline.[6,7] This is clinically evident as a falling urine output, despite initial acceptable urine production and a biopsy of the graft typically reveals acute tubular necrosis. Management of the patient is supportive, with provision for dialysis when indicated, although a low threshold for suspecting acute rejection must be maintained.

Acute Rejection
Acute Rejection is a major cause of poor graft function, that typically occurs 5-7 days post transplant. Rejection may be cellular or antibody mediated and must be suspected when there is a rising trend in serum creatinine. A renal biopsy is essential to confirm the diagnosis, grade the severity of rejection and plan treatment. Rejection is managed by intensifying immunosuppression.

Drug Toxicity
Transplant recipients on multiple immunosuppressive medications require careful monitoring for drug toxicity in the intensive care unit. The side effects of corticosteroids in the ICU include hypertension. Blood sugars should also be monitored. Calcineurin inhibitors also cause hypertension due to vasoconstriction, nephrotoxicity, hyperkalemia and hypomagnesemia.[17] Therefore, therapeutic drug level monitoring and dosage adjustment is essential. Antimetabolite medications frequently cause leucopenia, and may require dosage reduction if there is neutropenia.

Recurrent Disease
Several diseases can recur in the transplanted kidney but only 2 appear in the immediate post-transplant course. The first is focal segmental glomerulosclerosis (FSGS) which may recur within 1-2 days after transplant. This should be suspected in a child whose original kidney disease was FSGS and develops a falling urine output, nephrotic range proteinuria, hypoalbuminemia and edema.[18] Such patients are usually managed with a combination of therapeutic plasma exchange and alteration of immunosuppression. Atypical haemolytic uremic syndrome (HUS) may also recur early, and should be suspected if a patient has evidence of thrombotic microangiopathy.

Hypertension:
Hypertension is common post-operatively and is due to a combination of intravascular volume expansion, high dose steroids and calcineurin inhibitor therapy. Moderate elevations of blood pressure are tolerated in the immediate post operative period to allow the adult graft to adjust to the child's lower perfusion pressure. Severe hypertension (BP persistently greater than 95th percentile after post-op day 2 or if the child has hypertensive symptoms) indicate that antihypertensive medications should be started. The usual safe choice are long acting agents such as amlodipine.[8] The use of rapidly acting agents like Nifedipine which could lead to an unsafe drop in BP should be avoided. ACE inhibitors are also contraindicated in the early post transplant period.

Conclusion
Success of pediatric renal transplantation depends on meticulous perioperative management by a dedicated multidisciplinary team with regular communication between pediatric nephrologists, intensivists and the surgical team.

Key Messages
Children with renal transplant face significant challenges that include risk for significant intravascular volume shifts, electrolyte disturbances, acute rejections, infections, and hypertension.
Care of pediatric renal transplant recipients require protocols in the ICU based on the specific challenges that children face in the post-operative period. Successful management involves a team based approach with excellent communication between the pediatric nephrologist, surgical team and the intensivist.