Kidney Week

Abstract: SA-PO568

Kidney Prognosis in Patients with TSC2/PKD1 Contiguous Gene Deletion Syndrome

Session Information

• Cystic Kidney Diseases: Genetic Causes, Modifiers, and Extrarenal Manifestations
  October 26, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1201 Genetic Diseases of the Kidneys: Cystic

Authors

• Guerreiro, Mateus, Universidade de Sao Paulo Faculdade de Medicina, São Paulo, São Paulo, Brazil

Mateus Guerreiro, MD

• Valle, Eduardo, Universidade de Sao Paulo Faculdade de Medicina, São Paulo, São Paulo, Brazil

Eduardo Valle, MD

• Reusing, Jose Otto, Serviço de Transplante Renal, Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, São Paulo, Brazil

Jose Otto Reusing, MD, PhD

• Watanabe, Elieser H., Universidade de Sao Paulo Faculdade de Medicina, São Paulo, São Paulo, Brazil

Elieser H. Watanabe, MD, PhD

• Onuchic, Luiz F., Universidade de Sao Paulo Faculdade de Medicina, São Paulo, São Paulo, Brazil

Luiz F. Onuchic, MD, PhD

Group or Team Name

• Disciplinas de Nefrologia e Medicina Molecular.

Background

Patients with TSC2/PKD1 contiguous gene deletion syndrome (CGS) have classically been associated with a much more severe kidney phenotype than observed in isolated autosomal dominant polycystic kidney disease (ADPKD), displaying childhood onset and progression to end-stage kidney disease (ESKD) within the three first decades of life. Recent reports, however, revealed a more variable clinical course.

Methods

A survey of all reports of CGS was conducted using the terms "TSC2" and "PKD1" or "tuberous sclerosis" and "polycystic" on Pubmed. Thirty studies including patients with genetically confirmed CGS were selected, comprising 74 such cases. The addition of 11 cases from two novel pedigrees totalized 85 evaluated patients, who were analyzed at the demographic, clinical, and genetic levels.

Results

The median kidney survival of CGS patients was 35 (28-43) years. The age of ESKD onset did not differ between patients with germline deletion and cases in whom germline deletion could not be confirmed and mosaicism could not be excluded (Unknown group) (28 [20-37] vs 33 [31-43] years, respectively; p=0.09). Mosaic patients did not reach ESKD during the follow-up. Deletion extension did not affect kidney survival. The relative prevalences of TSC manifestations did not differ between CGS and TSC patients, except for higher frequencies of lymphangioleiomyomatosis and retinal hamartomas in CGS.

Conclusion

CGS patients have a slower progression to ESKD than previously believed, though usually faster than severe ADPKD cases (Figure 1). Thereby, CGS should be considered in ADPKD or significantly cystic TSC patients with severe CKD progression, particularly before the 5th decade. Our data suggest that the frequencies of most TSC clinical features do not significantly differ between CGS and TSC individuals.

Figure 1. Cumulative kidney survival according to the variant type/classification (adapted from Cornec-Le Gall et al, J AmSoc Nephrol, 24:1006-1013, 2013). The ESKD onset age overlap between the most severe ADPKD cases and the milder CGS cases is depicted by the black bar.

Funding

• Government Support – Non-U.S.