Pediatric renal transplantation

Pearls

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Kidney transplantation is the treatment of choice for children with end-stage renal disease; children have high priority in the deceased donor allocation policy.
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Upon arrival in the pediatric intensive care unit, key goals regarding blood pressure, central venous pressure (CVP), and urine output for the initial 24 to 48 hours are important to guide care.
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Awareness of the child’s pretransplantation blood pressure and antihypertensive regimens and native urine output is important to help guide posttransplantation management.
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Urine output is a critical marker of renal function; any drop in urine output should be addressed immediately. The first step in addressing low urine output is to assess the patient’s intravascular volume status (CVP, blood pressure), in addition to ensuring patency of the Foley catheter. The most common reason for a decrease in urinary output is volume depletion. The most catastrophic reason for a decrease in urine output is vascular thrombosis, which is assessed by a renal Doppler ultrasound.
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Hypotension and underperfusion of the adult-sized kidney in the pediatric patient is associated with delay in renal recovery. The treatment of choice for hypotension posttransplantation is volume expansion with crystalloid and/or colloid.

Transplantation is the treatment of choice in children with end-stage renal disease (ESRD) due to the beneficial impact on growth and development and quality of life. Significant progress has been made in pediatric kidney transplantation. Advances in immunosuppression have dramatically decreased rates of acute rejection, leading to improved short-term graft survival, but similar improvements in long-term graft survival remain elusive. Changes in allocation policy provide the pediatric population with timely access to transplant grafts, but there remains concern about the impact of less human leukocyte antigen (HLA) matching and a decrease in living donors. There are between 700 and 800 pediatric kidney transplants performed each year in the United States. The majority of transplantations (58%) occur in children between the ages of 11 and 17 years and in males (58%). Congenital anomalies of the kidney and urinary tract are the leading cause of kidney disease (35%), followed by focal segmental glomerulosclerosis (FSGS) and glomerulonephritis related to chronic renal failure and need for kidney transplantation.

Donor source: Living donor versus deceased donor

Living donor transplantation

Living donor kidney transplantation is well established as the optimal treatment for children and adults with ESRD due to superior graft and patient survival. ^, Despite these advantages, rates of living kidney donation are declining. In the United States, only 36% of pediatric kidney transplants were from living donors in 2018. Potential reasons for this decline in living donation in the United States include deterioration in the health of the general population, changing ethnic/racial characteristics, financial barriers, more stringent living donor criteria, and misconceptions about living donation. ^, In addition, differences in activity level of deceased donor transplantation programs in the region or country, cultural variations, and the manner in which parents are solicited for donation may contribute.

Deceased donor transplantation

If no living donor is available, a child is placed on the deceased donor waiting list. Children have long been recognized as a deserving priority in kidney allocation. Candidates listed before their 18th birthday are considered pediatric until they undergo transplantation or are otherwise removed from the waiting list. In 1993, the Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) formed an Ad Hoc Pediatric Advisory Committee. The committee prepared a white paper summarizing evidence of the detrimental effects of ESRD and dialysis on growth and development and describing technical problems with dialysis in pediatric patients. Congress passed the Children’s Health Act of 2000, which was incorporated as an amendment to the National Organ Transplant Act (NOTA). This Act specifies that organ allocation policy is to recognize the differences in health and organ transplant issues between children and adults throughout the system, and adopt criteria, policies, and procedures that address the unique healthcare needs of children.

A new kidney allocation policy (KAS) was implemented in 2015. The new allocation policy risk stratifies deceased donors using the kidney donor profile index (KDPI). The KDPI takes into account donor age, height, weight, ethnicity, history of hypertension and diabetes, cause of death, serum creatinine level, hepatitis C status, and donation after circulatory death status. Lower KDPI kidneys are associated with better posttransplantation survival. Similarly, transplantation candidates on the waiting list are risk stratified based on estimated posttransplant survival (EPTS), which considers candidate age, dialysis duration, prior solid organ transplant, and diabetes status. Generally, older age, longer dialysis duration, prior solid organ transplantation, and presence of diabetes are associated with higher EPTS scores and shorter expected posttransplantation survival. The new allocation policy prioritizes candidates in the top 20th EPTS percentile to receive kidneys with a KDPI of 0.20 or less. Children receive priority for kidneys with KDPI scores less than 0.35.

Deceased donors are categorized into two groups: donation after brain death (DBD) and donation after circulatory death (DCD). DCD, previously referred to as donation after cardiac death or non-heart-beating organ donation, refers to the retrieval of organs for the purpose of transplantation from patients whose death is diagnosed and confirmed using cardiorespiratory criteria (see also Chapter 20 ). There are two principal types of DCD: controlled and uncontrolled. Uncontrolled DCD refers to organ retrieval after a cardiac arrest that is unexpected and from which the patient cannot or should not be resuscitated. In contrast, controlled DCD takes place after death that follows the planned withdrawal of life-sustaining treatments that have been considered to be of no overall benefit to a critically ill patient in the intensive care unit (ICU) or emergency department. DCD kidneys were used in 4% of pediatric kidney transplant recipients from 2015 to 2017 in contrast to 20% of adult kidney transplant recipients. Another category of donor is the Public Health Service (PHS) Increased Risk Donor. The transplant center receives notification from the Organ Procurement Organization that the donor organ meets criteria for PHS increased risk. The phrase increased risk refers to the donor characteristics that could place the potential recipient at increased risk of disease transmission. A potential organ donor may be labeled as increased risk for a variety of different exposures, which carry different risks of transmitting recent infection with human immunodeficiency virus, hepatitis B virus, or hepatitis C virus. The phrase is not a reference to organ quality, nor should it be interpreted to be a predictor of graft survival. At the time of the organ offer, if a donor is identified as being at increased risk, the transplantation team should include this risk information in the informed consent discussion with the transplantation candidate or medical decision-maker.

Timing of transplantation

In the United States, adult candidates can be placed on and accrue wait time on the deceased donor wait list when the glomerular filtration rate (GFR) is 20 mL/min or less or when they are receiving chronic dialysis therapy. In contrast, there is no GFR cutoff for listing the pediatric candidate. Once the estimated GFR declines to less than 30 mL/min per 1.73 m ² , it is generally time to start preparing the child and the family for renal replacement therapy. Although there have been many advances in conservative renal replacement therapy, renal transplantation is the best treatment for children with ESRD. The majority of children in the United States have been on dialysis prior to transplantation, 22% for less than 1 year and 30% for 1 to 3 years. Preemptive transplantation refers to transplantation in a patient who has not been on dialysis, which occurred in 30% of pediatric kidney transplant recipients in 2018.

Histocompatibility

ABO blood group considerations

The ABO blood group consists of four common categories (A, B, AB, and O), with types A and O most frequently found in the US population. Antigen is expressed on red blood cells, lymphocytes, and platelets, as well as epithelial and endothelial cells. Formation of blood-group isoantibodies occurs against those antigens not native to the host. Thus, antibodies to both A and B are found in an individual with blood type O, while an individual with blood type AB has no antibodies to A or B antigens. Blood group A consists of two subtypes, A1 and A2. Approximately 80% of individuals in the United States with blood group A express A1. The antigenic expression of A2 is quantitatively and qualitatively less than that of A1, and the overall immunogenic risk based on antigen expression alone is A1 > B > A2. Given the lower immunogenic risk of the A2 antigen, donor A2 kidneys can generally be successfully transplanted into recipients with low pretransplantation anti-A titers without the use of desensitization. It is important to understand that a blood type O donor is a universal donor, and a blood type AB recipient is a universal recipient. In general, ABO-incompatible transplantation is rare in kidney transplantation, occurring in less than 1% of the pediatric population.

HLA matching

Traditionally, it has been shown that the greater the HLA mismatch, the greater the risk for acute and chronic rejection. Over time with newer immunosuppressive agents, HLA mismatching has been found to have less impact on the development of acute rejection and on early graft loss. However, it is still well established that better matching results in a better long-term outcome following renal transplantation and that mismatch is a factor that contributes to the development of chronic allograft rejection. Thus, the advantage of a perfect match is longer graft survival following renal transplantation. The disadvantage of perfect matching is the potential that it will be more difficult to achieve, as waiting for an appropriate donor will be longer.

Pretransplantation crossmatch testing

Pretransplant crossmatch between T cells and B cells is related to the presence of circulating anti-HLA class I and anti-HLA class II antibodies. In general, B-cell crossmatches do not impact transplant rejection. However, T-cell crossmatches do. Once an antibody binds to a T cell, it is generally an indication that this antibody is an anti-HLA class II alloantibody. It also suggests that this antibody has high potential to be pathologic and result in hyperacute rejection. For this reason, a positive T-cell crossmatch is a contraindication to transplantation. Newer techniques and studies have been developed such as Luminex to further define this alloantibody, and new therapeutic protocols may enable patients to be desensitized such that a transplantation can be performed in the future.

Sensitized recipient

The presence of preformed HLA antibodies is likely to result in severe antibody-mediated rejection and early allograft loss. Several different assays are available to determine the sensitivity (i.e., presence of HLA antibodies) of a potential transplant recipient to donor HLA antigens. These assays typically test for the presence of HLA antibodies by testing the serum from the recipient to a panel of HLA antigens or lymphocytes from different donors. Patient sensitization is classically reported as the percent panel reactive antibody (PRA) and is an estimate of the likelihood of a positive crossmatch to a pool of potential donors. The PRA is reported as historical (the highest value recorded on previous testing) and as current PRA. Leading causes of the sensitized recipients include blood transfusion, pregnancy, and prior transplantation.

Surgical procedure

The transplanted kidney is usually placed in an extraperitoneal location when possible to allow for easier clinical monitoring and access to the graft. In an infant or small child, it may be placed intraperitoneally. Occasionally, native nephrectomy is needed at the time of transplantation. Indications for nephrectomy include (1) need for space, such as in the case of polycystic kidney disease, especially in patients with massively enlarged kidneys; (2) uncontrolled renal-related hypertension; (3) persistent recurrent infections in native kidneys; (4) polyuria; and (5) nephrotic syndrome. Native nephrectomy is often needed in patients with nephrotic syndrome, either congenital or acquired. In this case, nephrectomies need to be done at least 3 months before transplantation so that the nephrotic hypercoagulable physiology corrects in order to minimize the risk of vascular thrombosis.

The aorta and inferior vena cava are usually used for anastomosis to ensure adequate blood flow, but smaller vessels may be used. These anastomoses may be difficult in children who have had previous hemodialysis accesses in the lower extremities. A thorough evaluation of the vasculature is important prior to transplantation. Cold ischemia time refers to the period of cold storage or machine perfusion. Cold ischemia time of more than 24 hours is associated with an increased risk of delayed graft function. Surgical teams make every effort to minimize cold ischemia time. Warm ischemia time refers to the period between circulatory arrest and commencement of cold storage, with a goal of less than 60 minutes.

Serious urologic anomalies are present in many children who undergo renal transplantation, the most common being posterior urethral valves and vesicoureteral reflux. Some of these children have undergone urinary diversion or bladder augmentation as a consequence of these malformations. In children with significant bladder abnormalities, urology should be part of the pre- and postoperative multidisciplinary transplantation team caring for these patients in order to optimize outcomes.

Multiorgan transplantation

In general, genetic or anatomic disease that affects both the kidney and one other organ, such as polycystic kidney disease (may affect both liver and kidney) can serve as an indication for multiorgan transplantation. Each transplantation can be performed simultaneously or at different time points. In some circumstances, a liver-kidney transplantation can be performed for diseases resulting from abnormalities in liver function that affect kidney function. These include primary hyperoxaluria and forms of atypical hemolytic uremic syndrome in which the disease may result from deficiency in factor H. Kidney disease following heart transplantation is rare in pediatric practice, but there have been cases in which ESRD can require treatment with renal transplantation. Kidney-pancreas transplantation is very rare in children; however, there are cases in which diabetic nephropathy results in ESRD in older children and young adults.

Immediate arrival to the pediatric intensive care unit ( boxes 76.1 , 76.2 , and 76.3 )

Initial assessment of patients upon arrival to the pediatric intensive care unit (PICU) includes assessment of routine respiratory and hemodynamic stability. The majority of children are extubated, with the occasional exception of the youngest recipients who weigh around 10 kg. Sign out from the anesthesia and OR team should include details on the intraoperative blood pressures, central venous pressure (CVP), volume administered, metabolic correction, urine output, and any bleeding or need for transfusion. The surgeon reports the cold and warm ischemia times and any surgical concerns. It is at this time that the PICU team, along with the surgery and nephrology team, establish goals for the next 24 hours; target low and high blood pressure goals for which fluid boluses or as needed antihypertensives should be administered. Target CVP goals are established at this time in addition to goals for urine output (e.g., call for urine output less than 1 mL/kg per hour or a decrease in 50% from the previous hour). Awareness of the child’s pretransplantation blood pressure and antihypertensive regimens and native urine output is important to help guide posttransplantation management. Anticoagulation management plans are discussed, with target levels depending on the patient’s thrombosis risk. The immunosuppression plan, with details on the timing of induction and maintenance medication initiation, is reviewed. Renal Doppler ultrasound is performed within the first hour of arrival to the PICU to confirm graft vascular flow.

• BOX 76.1

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