1. World Kidney Day 2016: Kidney Disease & Children
World Kidney Day 2016: Kidney Disease & Children. Act Early to Prevent It!

2. World Kidney Day 2016: Kidney Disease & Children
World Kidney Day 2016: Kidney Disease & Children. Act Early to Prevent It!
Kidney disease affects millions of people worldwide, including many children who may be at risk at an early age. It is therefore crucial that we encourage and facilitate education, early detection and a healthy life style in children, to fight the increase of preventable kidney diseases and to treat children with inborn and acquired disorders of the kidneys worldwide.

3. Pediatric Kidney Disease – An Update
Edited by the ASPN Clinical Affairs Committee

4. Kidney Transplant Mini Michael, MD, MMed (Clin Epi)
Texas Children’s Hospital, Baylor College of Medicine
Jodi M. Smith, MD, MPH
Seattle Children’s Hospital, University of Washington School of Medicine

5. Transplant: Objectives
Introduction
Epidemiology
Immunosuppression
Outcome: graft and patient survival
Unresolved issues in Pediatric Renal Transplantation (RTx)
Global Inequalities in Access to Pediatric RTx
Summary and future

6. Transplant: Introduction
Renal transplant is the optimal treatment for children with end-stage renal disease (ESRD)
Incidence of ESRD in children varies throughout the world
United States: ~14.8 cases per million
Japan: ~ 4 cases per million
Europe: ~ 8.3 cases per million but varies greatly among countries
Developing world: Limited data
Available estimates range from 3.4 pmcp (per million children population) in Turkey to a high of 35 pmcp in Kuwait
Higher incidence in US may be due to earlier initiation of renal replacement therapy

7. Transplant: Epidemiology
NAPRTCS (North American Pediatric Renal Trials and Collaborative Studies) Annual Report 2014:
Gender: Males 59%
Race: White 59%, Black 17% and Hispanics 17%
Age at transplant: age groups in years:
0-1: 5%; 2-5: 15%; 6-12: 32%; 13-17: 39% and >18 : 8%
Most common primary diagnosis:
Aplastic/hypoplastic/dysplastic kidneys (in 15.8%)
Obstructive uropathy (in 15.3%)
Focal segmental glomerulosclerosis (FSGS) is the third most common (11.7%) and continues to be the most prevalent acquired renal disease.
Based on NKF data 712 renal transplants performed in children <18 yrs in 2014 (470 DD RTx and 242 LD RTx)

8. Transplant: Epidemiology - Donor Type
50% of all transplants have involved a deceased donor (DD) source, 40% came from a parent and 10% from other living donors (LD)
Advantages of living donor renal transplant
Pre-emptive transplantation
Fewer rejection episodes
Incidence of delayed graft function is lower
Better graft survival
Better graft function

9. Transplant: Advantages
Improved growth and development
Improved patient survival
Improved quality of life
Cost effective

10. Transplant: Immunosuppression
Three general approaches:
To deplete circulating lymphocytes by destroying them
To use an inhibitor of lymphocyte activation (cyclosporine or tacrolimus)
To use various metabolic inhibitors (azathioprine, mycophenolate mofetil [MMF]) to interfere with lymphocyte proliferation essential for amplification of the response

11. Transplant: Site of Action of Immunosuppressive Drugs
Figure 2. Stages of T cell activation: multiple targets for immunosuppressive agentsSignal 1: Stimulation of T cell receptor (TCR) results in calcineurin activation, a process inhibited by cyclosporin (CyA) and tacrolimus. Calcineurin dephosphorylates NFAT (nuclear factor of activated T cells) enabling it to enter nucleus and bind to interleukin-2 promotor. Corticosteroids inhibit cytokine gene transcription in lymphocytes and antigen-presenting cells by several mechanisms. Signal 2: Costimulatory signals are necessary to optimise T cell interleukin-2 gene transcription, prevent T cell anergy, and inhibit T cell apoptosis. Experimental agents but not current immunosuppressive agents interrupt these intracellular signals. Signal 3: Interleukin-2 receptor stimulation induces cell to enter cell cycle and proliferate. Signal 3 may be blocked by interleukin-2 receptor antibodies or by sirolimus, which inhibits second messenger signals induced by interleukin-2 receptor ligation. Following progression into cell cycle, azathioprine and mycophenolate mofetil (MMF) interrupt DNA replication by inhibiting purine synthesis.
The Lancet. Vol 353. March 27, 1999

12. Transplant: Graft and Patient Survival
Both graft & patient survival significantly better in LD vs. DD recipients
In both donor types, improved graft and patient survival in most recent transplant era ( ) as compared to older eras
NAPTRCS 2014

13. Transplant: Major Issues
Medication non-adherence
Major cause of rejection and graft failure
Adolescents with poor social support more affected
Recurrence of FSGS post-transplant
Results in graft failure in >60%
Limited prevention/treatment options
High PRA: Major focus of new kidney allocation system
Recipients with CPRA of >80% receive additional priority points
Recipients with CPRA of 98, 99 and 100% receive local, regional, and national priority, respectively
Transplant in small children

14. Transplant: Global inequalities to access
Pediatric RTx performed in >60 countries worldwide but may cover no more than 10 % of global needs
In US, pediatric RTx incidence rate was >10 pmarp (per million age related population) in 2012
In developing world, incidence rates of pediatric RTx depend on country income
<1–2 pmarp in Pakistan, Arab countries, and South Africa
<4 pmarp in Brazil
Suggests a limited number of ESRD children have access to transplant
Access to pediatric RTx varies substantially within same country
Transplant outcome is generally poorer in low-income countries
Harambat J et al: Inequalities in access to pediatric ESRD care: a global health challengw; Pediatr Nephrol Dec 1
Rizvi et al: Pediatric Kidney Transplantation in the Developing World; AJT 2013; 13: 2441–2449

15. Transplant: Summary
Renal transplant is the optimal treatment for children with ESRD
Living donor RTx has superior graft and patient survival
Non-adherence is a major cause of graft failure
Adolescents with poor social support more affected
Major challenge is to reduce the inequality gap in access to optimal care for children with ESRD especially renal transplant worldwide
World Kidney Day 2016, dedicated to children, will help to deliver this message to governments, health-policy makers, the medical community, and the public at large

16. Happy World Kidney Day 2016!
Your pediatric nephrology community continues to work hard to improve clinical care, foster education, and advance the science regarding kidney disease in children! We appreciate your support and all you do for children’s health care!