Advances in Pediatric Nephrology

Dr. Hilda E. Fernandez

Progress in solid organ transplantation has led to better long‐term patient and allograft survival rates for children with end‐stage organ failure. It has been thought that transferring care to adult oriented services is associated with non-adherence and worse allograft outcomes. Transfer is the actual occurrence of moving from pediatric to adult healthcare, whereas transition suggests a process of increasing patient independence and decreasing caregiver responsibility. Previous studies of youth transferring to adult care in most cases have looked at graft loss as the primary outcome and have shown limited data on the clinical course prior to the transfer.

With this in mind, Hilda E. Fernandez, MD, Interim Medical Director, Pediatric Kidney Transplant Program in the Division of Pediatric Nephrology at NewYork-Presbyterian Morgan Stanley Children’s Hospital, led a study to examine whether risk factors for graft loss, such as a decline in estimated glomerular filtration rate (eGFR) and high variability in tacrolimus (TAC), could be detected among youth cared for in a single pediatric kidney transplant center before their transfer to adult services. Dr. Fernandez, who is also Assistant Professor of Medicine (in Pediatrics) at Columbia, in collaboration with colleagues at Children’s Hospital of Philadelphia, University of Pennsylvania, and University of Virginia School of Medicine, theorized that youth who experienced health crises such as loss of kidney function or variable TAC levels during their well-supported pediatric care would be at greater risk for allograft loss after transferring to the generally higher-volume adult healthcare setting with perhaps less resources available to them.

The authors found that transfer was not independently associated with acceleration in eGFR decline, but rather they noted an improvement in allograft function, with a decline in eGFR preceding changes in healthcare settings, and stabilized or improved eGFR after transfer.

The researchers conducted a single center, retrospective cohort review of pediatric transplant recipients transplanted before the age of 18 from January 1, 1999, to December 31, 2011, who transferred to care at two adult transplant centers. Subjects must have had laboratory and clinical data available 1 year ± 120 days prior to and following the last pediatric visit, with at least two serum creatinine measurements pre‐ and post‐transfer.

The researchers conducted pre- and post-transfer analysis of eGFR and coefficient of variation of tacrolimus (CV TAC) in patients who were on TAC as part of their immunosuppression regimen, and determined the difference between means of CV TAC in subjects with and without allograft loss following transfer of care.

Study findings, which were published in the September 2019 issue of Pediatric Transplantation, showed:

• Of the 138 patients who transferred to adult care, 47 patients with data pre‐ and post‐transfer demonstrated an approximately 80 percent decrease in eGFR decline from 8.0 mL/min/1.73 m2 per year to 2.1 mL/ min/1.73 m2 per year
• Of the 24 patients who had CV TAC data pre‐ and post‐transfer of care, pre-transfer CV TAC for those with allograft loss post‐transfer was significantly higher (49 percent) than in patients without allograft loss (26 percent)

Overall, the authors found that transfer was not independently associated with acceleration in eGFR decline, but rather they noted an improvement in allograft function, with a decline in eGFR preceding changes in healthcare settings, and stabilized or improved eGFR after transfer.

Dr. Fernandez and the research team note that the results of their study demonstrated unexpectedly the stability of kidney allograft function. The investigators also suggest that CV TAC may be helpful in identifying patients with increased risk of allograft loss after transfer. They note, for example, in a clinic setting, increased CV TAC could trigger an assessment by a social worker, pharmacist, or psychologist to identify and discuss adherence barriers with the patient prior to transfer. This would also be key information to communicate to receiving adult providers who could increase monitoring for patients with high CV TAC.