By Prathiba Raju and Nisha Kumari
New Delhi: Kidney transplantation in children with chronic kidney disease (CKD) aims to improve their duration and quality of life compared to dialysis. However, several challenges exist in this process. Early diagnosis is crucial to initiate timely intervention and optimise transplant chances. Medication adherence is vital to prevent immunological risks and rejection episodes. Multiple transplants pose difficulties due to limited donor availability and increased risks with each subsequent procedure. Medical and surgical advancements have enhanced transplant outcomes through improved immunosuppression, surgical techniques, and care protocols.
A study published by PLOS ONE on June 8, 2022, titled ‘Chronic kidney disease causes and outcomes in children: Perspective from an LMIC setting’ states that chronic kidney disease (CKD) is a major public health challenge in children globally with the prevalence of 15–74.7 cases/million children.
To understand this, ETHealthworld interacted with experts to understand the benefits of early diagnosis, how irregular medication can increase immunological risks, some of the risks associated with multiple transplants, and how medical and surgical advancements have improved transplant outcomes.
Paediatric kidney failure causes
Kidney failure in children is often a result of congenital malformations, genetic conditions, or developmental abnormalities. Early detection through prenatal ultrasounds and careful monitoring of kidney function after birth is crucial to improve outcomes and prevent progression to complete kidney failure.
Dr Haresh Dodeja, Consulting Nephrologist and Transplant Physician, Fortis Hospital, Mulund mentioned that kidney failure does not happen overnight and one reason behind this is the low incidence rates, He said, “Very few have focal segmental glomerulosclerosis (FSGS) which is very significant in paediatric patients causing a lot of protein loss whereby the development and growth are totally retarded.”
Dr Shraddha Lohia, Paediatric Nephrologist, FMRI, Gurugram emphasised that many of these abnormalities can be detected through ultrasound during pregnancy after 18 weeks.
As per the guidelines by the Indian Academy of Paediatrics (2020-2021) titled ‘Care of a Child with Chronic Kidney Disease’ states that the decreased amniotic fluid (fluid around the baby on antenatal scans) is one of the earliest signs that could tell us that the kidney function of the baby may be affected. This is because the water around the baby is mostly urine expelled by the kidneys of the fetus. In such cases, kidney function tests and ultrasounds have to be done after the baby is born and monitored later on too. Any abnormality seen on the antenatal ultrasound scans such as a single kidney, widening of the urinary tract, one smaller kidney, or cysts in the kidneys needs to have careful monitoring of the kidney functions after birth and monitoring later.
If unidentified and untreated early, many do not survive till adolescence. Like in the case of glomerulonephritis (inflammation of the kidney tract), there is a slow progression to complete kidney failure. Dr Dodeja further explained, “These are the children who gradually progress to complete kidney failure, maybe in their teenage years or otherwise. Then there are some developmental abnormalities like posterior urethral valves. In such cases, in the urinary tract of males, there is a posterior lateral valve issue that can cause obstruction and little reflux nephropathy that can progress slowly leading to end-stage kidney disease much later. Not necessarily in the first 2-4 years of life.”
No registry, complications
According to Dr Bharat Shah, Director & Head, Department of Nephrology, Global Hospital, Mumbai, early diagnosis may facilitate kidney transplantation for children. However, he mentioned that the Indian Society of Paediatric Nephrology (ISPN) is currently working on establishing a registry for paediatric patients, and thus, specific data regarding transplantation rates for children in India is not currently available.
He noted, “In general only about 20 per cent of kidney patients get transplants, and the rest 80 per cent cannot afford it or have access to it. So I would presume a similar thing would happen to children.”
Dr Dodeja added, “The rate of paediatric kidney transplantation in children is less than 10 per cent of the adult transplant number.”
To address these challenges, raising awareness about organ donation in India is crucial. Dr Lohia highlighted various barriers associated with organ donation in the country, including lack of general population awareness, unwillingness to donate, social and cultural barriers, inadequate infrastructure in public hospitals, insufficient medical experts, and limited storage facilities for extracting and preserving donated organs.
When it comes to operating on paediatric patients receiving a living or deceased kidney transplant, there are certain risks involved. Dr Shyam Bihari Bansal, Secretary of the Indian Society of Nephrology, emphasised, “A thorough evaluation is done especially for paediatric recipients for their native disease, degree of sensitisation and risk of recurrence of the native disease. In India, most of the transplants are live-related.”
One challenge in paediatric transplantation is the accommodation of an adult donor kidney into a child’s body. Dr Lohia said, “Due to the relatively large adult donor kidney, a larger than usual quantity of blood flows into it causing a drop in blood pressure when the clamps are released. We prepare in advance by giving large amounts of fluids, crystalloids, and blood products to avoid this sudden drop in pressure. As for the size difference in the diameter of the blood vessels of the child and adult kidneys, there are multiple surgical techniques available with surgeons to be linked by anastomosis.”
Before performing kidney transplantation in paediatric patients, a comprehensive evaluation is conducted, considering the native disease, sensitisation levels, and risk of recurrence.
Dr Shah added that if a child has a history of autoimmune diseases, there is a possibility of disease recurrence after surgery. This highlights the need for careful monitoring and management of such cases. The above factors necessitate close attention and specialised care for paediatric kidney transplant recipients.
Significant risks involved
Paediatric transplant recipients face significant risks not only in the early post-transplant period but also during adolescence and young adulthood when the immunological risk is heightened. Non-adherence to medication and the risk of rejection are key concerns during this stage. Dr Bansal shared, “The adolescents especially need good counselling regarding adhering to medication schedules. They need higher doses/body weight and sometimes need thrice daily dosing of tacrolimus to maintain their levels.”
“Factors contributing to the high graft failure rates in this period include poor adherence to treatment, potentially exacerbated by the transfer of care from paediatric to adult-oriented care providers, and perhaps an increased potency of the immune response,” added Dr Lohia.
Adequate counselling and support are crucial during this transition to ensure medication adherence and minimise the risk of graft failure.
According to a study published in The New England Journal of Medicine, the median survival of transplanted kidney grafts is 11.7 years for organs from deceased donors and 19 years for organs from living donors. This indicates that most children who receive a kidney transplant will likely require multiple transplants during their lifetime.
Highlighting various factors that can contribute to the need for a second transplantation, Dr Dodeja remarked, “The body will attack the transplanted kidney so it is important to keep immunological responses under control. But that does not mean that it is always under control. So sometimes that may be the reason why it is damaging the kidney. Second, there are also drugs that we use to protect the kidney in the short term, but in the long term, they have side effects that can damage the kidney. Thirdly, there can be other factors like at the time of surgery if the size of the donated kidney does not match, so at the time of stitching them together, due to unequal sizes, there are chances of clotting. So one might lose a kidney.”
Dr Dodeja further discussed the immunological and non-immunological factors that increase the chances of requiring a second transplantation. Immunological factors include acute kidney rejection, where the body mounts an attack that medication cannot counteract, as well as chronic rejection, where the body slowly rejects the transplanted kidney. Drug-related factors such as tacrolimus can also contribute to chronic graft dysfunction, damaging the kidney. Non-immunological factors, such as high blood pressure and diabetes, can also play a role.
Advancements in molecular techniques, surgical procedures
With the advancement of molecular techniques, transplant outcomes have significantly improved. Dr Shah discussed the advancements, highlighting various techniques that contribute to better matching and lower the risk of rejection. He mentioned, “First, we check the matching level of donor and recipient. Better matching lowers the risk of rejection. In addition to this human leukocyte antigen (HLA) technique, complement-dependent cytotoxicity (CDC) crossmatch techniques and Flow Cytometry crossmatch techniques are also available.”
The HLA technique helps in tissue matching and identifies antibodies already present in the recipient’s body that could potentially harm the new kidney, thus reducing immunological risks. Complement-dependent cytotoxicity (CDC) cross-match techniques are used to detect donor-specific antibodies by examining T and B lymphocytes. Flow Cytometry cross-match technique is employed to ensure that the interaction between the immune components of the donor and recipient does not lead to adverse immunological responses.
In addition to molecular techniques, surgical advancements, such as robotic surgery, have greatly benefited the transplant industry. Dr Lohia concluded, “Robotic surgery for kidney transplants decreases the chances of complications as compared to open surgery, especially in immunocompromised and end-stage renal disease patients undergoing kidney transplants. It is safer and more efficacious for obese patients. It also shortens hospital stays due to early recovery,”
Overall, experts agree that transplantation is a safe option for children with CKDs. However, they emphasise the importance of early diagnosis, consistent medication, and proper care to improve the chances of survival and successful transplant outcomes for paediatric patients. These advancements in techniques and surgical procedures have significantly enhanced the field of kidney transplantation, providing hope for better outcomes for children in need.