Background/Purpose: Apolipoprotein L1 (APOL1) mediated kidney disease with focal segmental glomerulosclerosis (FSGS) is a severe form of renal disease with risk of progressing towards end stage renal failure. The burden of coexisting inflammatory disease, whether autoimmune or autoinflammatory, on these select patients’ progression to renal failure has been postulated but remains unclear.

Methods: Case series of two pediatric patients with G1/G2 APOL1 risk alleles for FSGS and renal biopsy proven collapsing FSGS and other underlying severe inflammatory disease burden who developed progressive renal disease, one to end stage renal disease (ESRD) requiring dialysis and transplantation.  Both patient’s clinical kidney disease predated their respective autoimmune and autoinflammatory disease diagnosis, melanoma differentiation-associated protein 5 juvenile dermatomyositis (MDA5+ JDMS) and Hyper IgD syndrome (homozygous pathogenic variant in the mevalonate kinase gene) respectively.

Results: Both patient’s renal disease progressed to chronic renal failure. Case 1, a 16 year old male, required dialysis and renal transplantation. Case 2, a 14 year old male, is currently undergoing evaluation for future transplant. Case 1 suffered from recurrent fevers since age 4 requiring frequent courses of corticosteroids. Genetic testing revealed a homozygous c.1129G >A(p.Val377IIe) pathogenic variant in the mevalonate kinase gene, diagnostic for the autoinflammatory disease Hyper-IgD syndrome / mevalonate kinase deficiency. Case 2 suffered from concomitant difficult to treat MDA5+ JDMS. In addition to myositis, calcinosis, and dermatitis, his JDMS phenotype included pancreatic involvement, not previously described in MDA5+ JDMS. Case 1 was started on canakinumab and recently successfully received a kidney transplant. For case 2, his JDMS responded to rituximab therapy after having received many years of corticosteroids and tacrolimus for his FSGS disease followed by mycophenolate.

Conclusion: Our case series exemplifies the importance of both early and accurate diagnosis and effective treatment of existing autoimmune and autoinflammatory diseases in pediatric patients with underlying APOL1 and FSGS. Larger retrospective case series and future prospective trials will be important to better understand the inflammatory disease triggers of APOL1 mediated renal disease progression with FSGS pathology, in an effort to improve patient outcomes in this select population.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/apol1-focal-segmental-glomerulosclerosis-requiring-renal-transplant-the-burden-of-childhood-onset-autoimmune-and-autoinflammatory-disease/