Pediatric Renal Transplantation



Pediatric Renal Transplantation


Gerald C. Mingin

Jeffrey A. Stock



I. OVERVIEW

In children with end stage renal disease (ESRD), renal transplantation represents the current optimal standard of care for renal replacement. Despite the effectiveness of hemodialysis and peritoneal dialysis, even with the addition of recombinant erythropoietin and growth hormone for the prevention of anemia and lack of growth to the armamentarium, neither of these options has proven more effective than renal transplantation. The success of renal transplantation in children has steadily improved over the past three decades.

The North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) was established in 1987 to collect and distribute clinical data regarding pediatric transplantation in North America. One-year graft survival (GS) from living related donors (LRD) has increased from 91% (1987 to 1995) to 96.4% (2007 to 2013), while cadaver donor survival has increased from 81% to 95.8% during the same interval. In fact, most recent patients appear to be exhibiting equal 1-year allograft survival rates, regardless of whether the donor source of the allograft was living or cadaveric. This is of added importance since allograft half-lives, that is, long-term transplant kidney survival, directly correlate well with 1-year survival rates. In the 2003 to 2010 cohort, 5-year allograft survival for LRD was 84.3% and 78% in the deceased donor cohort.

Between 2008 and 2014 the incidence of ESRD has been decreasing annually in the United States. In 2014, a total of 1,398 children were diagnosed with new onset ESRD, which was 6% less than in 2013. In 2014, 1,312 children were waitlisted for a kidney transplant (896 listed for the first time and 425 listed for repeat transplant). Since 1997 there has been a decrease in the median wait time for those listed for their first transplant. The median waiting time for children receiving their first kidney transplant has ranged between 150 and 220 days. Children receiving a repeat transplant have been waiting 3 to 4 times longer than those awaiting their first transplant. A total of 1,018 children received a kidney transplant in 2014. Prior to 2005, the source of kidney grafts in pediatric transplant recipients was most commonly from living donors. There has been a steady decline in the number of children receiving living donor kidneys since 2009. In 2014, living donors accounted for 40% of kidney transplants, which is a 21% decrease since 2009.

It has been recognized that preemptive transplantation decreases the morbidity associated with chronic dialysis, thus potentially improving physical health, statural growth, and mental well-being. During 2010 to 2014, 36% of children received a kidney transplant within the first year of being diagnosed with ESRD. In recognition of the overt benefits of transplantation, pediatric patients with ESRD are given special consideration in the
allocation of organs; despite this, waiting times remain long for the fixed source of cadaveric organs and this problem is not likely to be solved in the near future.

Currently increased graft survival is dependent on identifying the most appropriate donor recipient characteristics while employing ongoing improvements in immunosuppressive therapy. This chapter highlights some of the recent and important changes in pediatric renal transplantation.


II. ETIOLOGY AND DEMOGRAPHICS

The etiologies of renal failure in pediatric patients differ significantly from that of adult patients (older than 18 years of age) in that urologic etiologies and/or comorbidities can be found in 30% to 40% of children compared to less than 10% of adults. The major urologic conditions associated with ESRD in pediatric patients requiring renal replacement include obstructive uropathy (16%), hypoplastic/dysplastic kidney disease (15%), and reflux nephropathy (5%). The most common medical causes of ESRD include: focal glomerular sclerosis, membranous nephropathies, autoimmune disease, metabolic defects, diabetes, and tumor.

While these etiologies have remained relatively constant, the demographics have shifted significantly. This is most pronounced in the ethnic mix, where Caucasian recipients have decreased. In turn, the number of African-American and Hispanic patients has increased from 28% in 1987 to almost 40% in 2007. In 2013, 55% of pediatric kidney recipients were Caucasian down from 72% in 1987.


III. SELECTION OF RENAL DONORS

Although the short-term survival of deceased donor (DD) allografts have been shown to be nearly equal to that of LRD allografts, the use of a LRD or LURD (living unrelated donor) is still preferable in children because long-term graft survival is superior. With live donors, families are better able to plan and prepare for the surgery; in addition there is a potential psychological benefit to the recipient knowing the source of the organ and to the donor by virtue of being a good Samaritan. However, this must be weighed against the knowledge that if the graft is lost, there can be considerable anguish, grief, and guilt from both the donor and recipient. Recently, computerized matching algorithms have been designed to identify maximal sets of donor/recipient pairs, generally forming “chains” from large sets of able donors who are either not compatible with their intended recipient or, in some cases, when greater compatibility can be achieved through this “donor” exchange pool.

Donor-recipient compatibility is based on several immunologic factors. The “cytotoxic crossmatch,” in which donor lymphocytes are mixed with recent recipient sera, is performed prior to any transplant. A positive crossmatch where recipient preformed reactive antibodies attack specific antigens on recipient cells is a contraindication to transplantation as it will lead to hyperacute (immediate) rejection. The matching process now includes more sensitive means of predicting rejection as well, including detection of low-level incompatibility by flow cytometry. Donor-specific antibodies (DSA) can now be detected with high sensitivity by immunofluorescence.

The two primary antigen systems associated with graft rejection are the ABO and human leukocyte antigen (HLA) systems. Similar to blood transfusions, type O represents the universal blood donor while type AB represents the universal recipient. Hence an appropriate match should be
assured to avoid hyperacute rejection. The Rh status appears to be a minor antigen system that does not influence the risk of rejection. The short-term and long-term survival of a transplanted kidney appear to be related with HLA compatibility at the A, B, and D (DR) loci primarily, though other loci are clearly relevant and figure in some matching decisions if not to define basic compatibility. Ideally a “zero antigen mismatch” is desired. In a LRD from parent to child there is at worst a 1 haplotype or up to 3 HLA mismatch. An identical twin should be a 2 haplotype (same maternal and paternal alleles)/0 mismatch donor; consanguineous parents may also share full haplotypes with their offspring. In a sibling group, there is a 50% chance of sharing 1 haplotype (1 maternal or 1 paternal) and a 25% chance of being either a full haplotype or totally mismatched. Clearly in the DD the chance of obtaining a perfect match is far less due to the HLA distributions in various populations and ethnic/cultural groups.

All donors are screened for systemic infections such as AIDS and hepatitis as well as malignancy (with the exception of some primary brain tumors). In rare individual cases, the criteria have been expanded to include kidneys from non-heart-beating donors, donors younger than 5 years or older than 60 years and in exceptional cases, a kidney from a deceased donor with diabetes or hypertension. Among adults, some recipients with hepatitis or HIV may elect donors with the same infection due to the availability of highly effective antiviral therapy. Any LD should be healthy, free of systemic illness or malignancy, and be freely willing to donate. The perioperative donor risk is small with a mortality rate between 0.03% and 0.06%. Long-term data have substantiated that while the attributable risk of ESRD or other significant long-term morbidity or mortality from becoming uninephric is nonzero, the absolute risk is extremely low and it is considered acceptably safe. Live donors may experience age-related development of hypertension sooner than they would have otherwise, and there is a somewhat higher risk of developing gout, pregnancy-induced hypertension, and preeclampsia.


IV. PRETRANSPLANT RECIPIENT PREPARATION

A. Metabolic Diseases

The activity of systemic diseases such as systemic lupus erythematosus and vasculitis require a stable and quiescent state prior to transplantation. Often times, the autoimmune responses in these diseases can be controlled with the same immunosuppression required for antirejection therapy and maintenance.

Metabolic and systemic diseases such as atypical hemolytic uremic syndrome (HUS), cystinosis, and primary hyperoxaluria require adequate medical therapy prior to transplantation. Specific therapy for these diseases exist, though in some cases, particularly primary hyperoxaluria type 1 with infantile ESRD, combined liver-kidney transplantation may be considered. Other specific diseases such as autosomal recessive polycystic kidney disease (ARPKD) and other “ciliopathies” that potentially affect both kidney and liver require specific evaluation for potential liver transplantation as well. Patients with cancer (such as bilateral Wilms tumor) require a disease-free waiting period before immunosuppression.

B. Upper Urinary Tract

Clinical conditions that require pretransplant nephrectomy are few and far between. However, consideration for nephrectomy(ies) includes those children who have severe polyuria with electrolyte wasting and patients with significant proteinuria. Polyuria, dehydration and electrolyte
disturbances, and importantly, a reduced circulating volume can lead to a hypercoagulable state. It should be emphasized that the child often receives a larger donor kidney that requires a significant cardiac output and perfusion pressure. Thus a low recipient volume status can precipitate thrombosis, a surgical complication more prevalent in pediatric patients than adults, and often thought to be technical in etiology.

As opposed to years gone by when routine nephrectomies were performed in patients with a history of obstructive uropathy and vesicoureteral reflux, this is rarely an indication today, unless the patient is prone to relapsing recurrent infections that can be attributed to the kidney. Renal hypertension that cannot be controlled with medication may be considered a rare indication for nephrectomy in order to improve blood pressure control. In children who have an associated predisposition to the development of malignant renal neoplasms, such as those with Denys-Drash syndrome, nephrectomies should be performed as these tumors tend to occur early in life.

Only gold members can continue reading. Log In or Register to continue

Sep 29, 2018 | Posted by in UROLOGY | Comments Off on Pediatric Renal Transplantation

Full access? Get Clinical Tree

Get Clinical Tree app for offline access