Pediatric Nephrologists Reluctant to Offer Kidney Transplant in C3G, IC-MPGN

Burkhard Tönshoff, MD, PhD

Credit: European Rare Kidney Disease Reference Network

New research is shedding light on widespread reluctance among pediatric nephrologists to list patients with stage 5 chronic kidney disease (CKD) due to C3 glomerulopathy (C3G) or primary immune-complex membranoproliferative glomerulonephritis (IC-MPGN) for kidney transplantation.¹

Survey results from transplant centers of the European Society for Pediatric Nephrology highlight the medical dilemma faced by physicians treating patients with kidney failure due to C3G or IC-MPGN. Most participants indicated they would not list these patients for preemptive and/or living donor kidney transplantation, despite transplantation being the treatment of choice for kidney failure in children.¹

The prevalence of C3G is estimated to be 2-3 per 1,000,000 people.² For IC-MPGN, the prevalence is estimated to be 1-4 per 1,000,000 people.³ Both rare kidney diseases are often diagnosed during childhood and frequently progress to kidney failure but lack effective treatments.¹

“There is considerable uncertainty and variability among pediatric nephrologists regarding listing for transplantation and optimal post-transplant management in the absence of international consensus guidelines,” Burkhard Tönshoff, MD, PhD, a professor of pediatrics and pediatric nephrology at the University Children's Hospital Heidelberg in Germany, and colleagues wrote.¹

To define current practices and unmet clinical needs regarding the listing and donor selection of pediatric patients with C3G or IC-MPGN and stage 5 CKD, investigators from the Transplantation Working Group of the European Society for Paediatric Nephrology and the Cooperative European Paediatric Renal Transplant Initiative research network developed a questionnaire on center practice in the management of these patients.¹

All active members of kidney transplant centers of the European Society for Paediatric Nephrology were invited to participate in the survey, which was conducted from August 23 to November 25, 2023. The survey consisted of 17 questions addressing listing for deceased donation; living donation; preemptive kidney transplantation; and choice of immunosuppressive therapy post-transplant and in case of recurrence.¹

In total, 65 physicians representing 65 pediatric kidney transplant centers participated in the survey. Of these respondents, 49 (75%) indicated they had previously been responsible for the management of a child or adolescent with C3G or IC-MPGN who required kidney transplantation.¹

A total of 8 (12%) physicians reported they had on at least one occasion decided not to perform a kidney transplant in a child or adolescent with renal failure secondary to C3G or IC-MPGN based on the high risk of recurrent disease in the transplant for which no effective treatment was currently available.¹

Additionally, 17 (26%) physicians indicated they had on at least one occasion decided not to use a potentially suitable living related or unrelated donor because of a diagnosis of C3G or IC-MPGN, with most respondents citing the high risk of disease recurrence in the absence of effective treatment (88.2%) and concern about potential donor genetic mutations and/or a familial form of C3G or IC-MPGN (35.3%). In such a situation, 88% of participants said they would recommend listing for deceased donor transplantation only, and 12% decided not to proceed with transplantation at all.¹

Of note, all 65 respondents confirmed there was no specific written local or national guideline regarding the use of living donors for kidney transplantation in children and adolescents with C3G or IC-MPGN.¹

Results showed many physicians favored more intensive immunosuppressive therapy for patients undergoing transplantation, but the choice of immunosuppressant varied, with the most popular approach being the intensification of MMF therapy or MPA exposure. For patients who develop recurrent C3G or IC-MPGN, investigators noted complement factor 5 inhibition with either eculizumab or ravulizumab was the preferred approach, followed by plasma exchange and the intensification of steroid or MMF/MPA-based maintenance immunosuppressive therapy.¹

Investigators pointed out 28% of physicians would want to enroll these patients in a clinical trial, reflecting the growing interest and awareness of new medications in this disease area.¹

“This survey shows a considerable reluctance of pediatric nephrologists to list patients with CKD stage 5 due to C3G or IC-MPGN for preemptive and/or living donor kidney transplantation. This decision is based mainly on the fear of recurrence of the underlying disease combined with the lack of reliable treatment options,” investigators concluded.¹ “This limited access of affected patients to the best treatment option for kidney failure will hopefully change in the future with the approval of effective drugs for the prophylaxis and treatment of recurrent disease after transplantation.”

References

1. Patry C, Webb NJA, Meier M, et al. Kidney Transplantation in Children and Adolescents With C3 Glomerulopathy or Immune Complex Membranoproliferative Glomerulonephritis: An International Survey of Current Practice. Pediatric Transplantation. https://doi.org/10.1111/petr.70048

2. National Organization for Rare Disorders. C3 Glomerulopathy: Dense Deposit Disease and C3 Glomerulonephritis. January 19, 2023. https://rarediseases.org/rare-diseases/c3-glomerulopathy-dense-deposit-disease-and-c3-glomerulonephritis/

3. Wong EKS, Marchbank KJ, Lomax-Browne H, et al. C3 Glomerulopathy and Related Disorders in Children: Etiology-Phenotype Correlation and Outcomes. CJASN. doi:10.2215/CJN.00320121