Pediatric kidney transplantation isn’t a one-and-done endeavor. Unlike adults, whose life expectancy may fall in line with the life of their transplanted kidneys, children and teens typically outlive their transplanted organ—at least the first one.
“With pediatric patients, there is almost always a second transplant,” said Dechu Puliyanda, MD, director of Pediatric Nephrology at Cedars-Sinai Guerin Children’s. “That second transplant can happen while they’re still young or after they become adults. In either case, antibodies from the first transplant make a second transplant exponentially more complicated.”
For more than four decades, Stanley Jordan, MD, director of the Division of Nephrology at Cedars-Sinai, has been investigating how to adequately suppress post-transplant antibodies so patients can be successfully transplanted for a second time. It’s not an exact science (yet), but Jordan and Puliyanda—in concert with a multidisciplinary team of professionals at Guerin Children’s—have devised a comprehensive, multidisciplinary approach to help ensure that second transplantations stick even after pediatric transplant patients reach adulthood.
Suppressing Antibodies: A Tiered Approach
After a kidney transplant, the immune system releases a torrent of antibodies as the body acclimates to the new organ. With such a high burden of antibodies, many children and teens run the risk of organ rejection after a second transplant.
Indeed, studies show that only about half of patients receive a second transplant after a first graft failure, and only 36% receive another transplant after a second graft failure.
“A key reason behind these sobering statistics is the development of allosensitization with increased panel reactive antibodies (preformed HLA-antibodies) formed after first transplant,” Puliyanda said.
Now, with Cedars-Sinai’s tiered desensitization approach, even young patients who are 99% or 100% sensitized may have an opportunity to receive a transplant. Each tier features different interventions designed to adequately suppress antibodies and prepare children and teens to receive a successful second transplant.
Here’s how it breaks down:
Tier 1: Antibody removal with plasmapheresis and intravenous immunoglobulin (IVIg) infusions. There are several protocols, but the most typical includes five to seven sessions of plasmapheresis followed by IVIg and anti-CD20 therapy.
Tier 2: Using IVIg to reduce alloantibodies. Children and teens are always premedicated prior to infusion, and new formulations such as IsoLow have helped reduce the risk of hemolysis after IVIg infusions.
Tier 3: Using targeted therapeutics aimed at preventing antibody rebound after antibody depletion. Over the past seven years, several antibody-directed therapies have emerged as potential desensitization agents, including imlifidase, FcRn blockade, anti-CD20 monoclonal antibodies and obinutuzumab, among others.
“Even with this tiered approach, the expectation isn’t for antibody levels to drop to zero. Our goal is for antibodies to drop low enough to allow patients to get a fairly compatible transplant,” Puliyanda said. “At the same time, we use strong immunosuppressive medications to prevent patients from producing even more antibodies, further reducing the risk of organ rejection.”
This multidisciplinary, stepwise approach to desensitization has shown remarkable results in patients from all over the country. In fact, more than 80% of Guerin Children’s pediatric kidney transplant patients receive new organs within one year of desensitization therapy.
That impressive track record has gained the attention of clinicians around the world who are interested in replicating Guerin Children’s results. In the March 2024 issue of Pediatric Transplantation, Puliyanda and her team published “Management of the Sensitized Pediatric Renal Transplant Candidate,” detailing the specific approach for each tier.
Increasing Kidney Retention
Unfortunately, getting a working kidney is only one part of the equation for a successful, long-term transplant. Patients also need to effectively care for their new organ, and that can be a daunting process.
According to a 2019 study published in Pediatric Transplantation, more than one-quarter of kidneys are lost within seven years of transplant. Children and teens are especially vulnerable to organ rejection due to increased rates of medication nonadherence. In fact, national studies, including this study published in Transplantation, show that more than one-third of pediatric patients lose their kidneys when they transition to an adult provider, which typically happens at 18 years of age.
“That’s one reason why Guerin Children’s pediatric team cares for patients until they reach the age of 21,” Puliyanda said. “The teenage years are difficult to navigate even without a kidney transplant, so vigilance is key for these patients.”
To counteract those sobering statistics, Guerin Children’s pediatric nephrology team has established a multipronged approach aimed at kidney retention:
- Clinical monitoring. In addition to monitoring children’s antibody levels, care providers take steps to reduce the risk of infection since patients are taking immunosuppressive medications.
- Biomarker analysis. Guerin Children’s experts were the first to use biomarkers to determine the risk of organ rejection among pediatric transplant patients. “Now we can analyze a patient’s urine and immediately tell whether there’s a risk of rejection,” Puliyanda said.
- Education. Beginning at age 13, Guerin Children’s kidney transplant patients complete questionnaires to assess their knowledge of important issues related to their care. During these visits, physicians fill in the gaps for patients and ensure they know the signs of organ rejection and are well versed in how to best care for their new organ.
“With grant money from the L.L. Foundation for Youth, our clinical team is working to completely change the statistics related to lost kidneys,” Puliyanda said. “Our goal now is that zero kidneys are lost when our patients transition to an adult provider.”
An organ transplant is never an easy proposition, regardless of the age of the recipient. But with the focus on effective desensitization strategies, when young patients need a second (or third) transplant, the process is becoming more manageable.
Sources
Chua A, Cramer C, Moudgil A, Martz K, Smith J, Blydt-Hansen T, et al. Kidney transplant practice patterns and outcome benchmarks over 30 years: The 2018 report of the NAPRTCS. Pediatric transplantation. 2019;23(8):e13597. Epub 2019/10/28. doi: 10.1111/petr.13597. PubMed PMID: 31657095.
