A Rare Coexisting Presentation of Autosomal Dominant Polycystic Kidney Disease With Rapid Deterioration of Renal Function and Neurofibromatosis Type 1

TL;DR

A rare case of a young man with two genetic disorders, ADPKD and NF1, showed faster kidney decline than typical ADPKD cases.

Contribution

This case suggests that NF1 may accelerate the progression of ADPKD, a previously unreported interaction.

Findings

The patient's kidney function declined rapidly, with eGFR dropping from 71.9 to 56.7 mL/min/1.73m² in one year.

Kidney volume increased by 10.4% over one year, indicating accelerated cyst growth.

The patient's condition was more severe than his father's ADPKD alone, suggesting NF1 may worsen ADPKD progression.

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common hereditary kidney disorders, characterized by progressive cyst development. Neurofibromatosis type 1 (NF1) is another autosomal dominant disorder, characterized by café-au-lait spots, neurofibromas, and multisystem involvement. We report the case of an 18-year-old male with ADPKD and NF1, referred due to progressively worsening renal dysfunction. His initial estimated glomerular filtration rate (eGFR) was 71.9 mL/min/1.73m², with MRI showing bilateral cystic renal enlargement (total kidney volume: 758 mL). One year later, his eGFR declined to 56.7 mL/min/1.73m², and kidney volume increased by 10.4% over one year. Tolvaptan was initiated, and he remains under follow-up.

Mutations in the PKD1/PKD2, which are responsible for ADPKD, affect intracellular signaling, including the mammalian target of the rapamycin (mTOR) pathway, leading to cyst formation and progression, while NF1 mutations overactivate the Ras proteins. His disease progression was more severe than that of his father with ADPKD alone, suggesting NF1 may have accelerated cyst enlargement. The co-occurrence of ADPKD and NF1 is extremely rare, with only a few cases reported in the past.

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