Non-invasive ²³Na MRI Identifies Functionally Distinct Cyst Phenotypes in Autosomal Dominant Polycystic Kidney Disease
²³Na MRI can identify different cyst phenotypes in ADPKD based on sodium content, which may influence disease understanding and treatment strategies.
Where it sits
this study against the rest of the vasopressin corpusSummary and findings
This study examined cyst sodium concentration in autosomal dominant polycystic kidney disease (ADPKD) using ²³Na MRI in 20 patients. Two distinct cyst phenotypes were identified: high-[Na⁺] cysts and low-[Na⁺] cysts, with high-[Na⁺] cysts being 1.8-fold more frequent overall. The presence of vasopressin V2 receptors was exclusively noted in low-[Na⁺] cysts.
Abstract
Autosomal dominant polycystic kidney disease (ADPKD) is characterized by cysts from different nephron segments, yet their origin remains inaccessible to in vivo imaging. Building on ex vivo studies that cyst sodium concentration ([Na⁺]) may reflect tubular origin, we developed a non-invasive 23 Na magnetic resonance imaging (MRI) approach at 7 Tesla to phenotype ADPKD cysts in vivo based on cyst sodium. In nephrectomized ADPKD kidneys, cyst fluid [Na + ] closely matched 23 Na MRI signal intensities, revealing two distinct cyst phenotypes: serum-like high-[Na + ] cysts and low-[Na + ] cysts. High-[Na + ] cysts expressed the proximal tubular marker sodium-glucose cotransporter-2, whereas low-[Na + ] cysts expressed markers of distal tubules and collecting ducts. The vasopressin V2 receptor (V2R), the therapeutic target of tolvaptan, was detected exclusively in low-[Na + ] cysts, linking sodium phenotype to therapeutic target expression. In vivo, ²³Na MRI enabled classification of 2,299 cysts in 20 ADPKD patients. High-[Na + ] cysts were 1.8-fold more frequent overall. Anatomical cyst localization did not predict sodium phenotype, underscoring the need for functional imaging rather than structural inference. Patients exhibited marked interindividual variation in cyst composition, with low-[Na + ] cysts comprising 4.6% to 83.9% of all cysts. Given the exclusive expression of V2R in low-[Na + ] cysts, this heterogeneity may influence disease progression and therapeutic responsiveness. These findings establish ²³Na MRI as a non-invasive method to phenotype ADPKD cysts in vivo and provide a functional imaging approach with potential relevance for stratifying patients and guiding future therapeutic interventions.
Background
Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the development of cysts from different nephron segments, yet their origins are not easily accessible through in vivo imaging techniques. Previous ex vivo studies suggested that cyst sodium concentration ([Na⁺]) may reflect the tubular origin of these cysts. This study aimed to develop a non-invasive ²³Na MRI approach to phenotype ADPKD cysts based on their sodium content, which could have implications for understanding disease progression and treatment response.
Methods
The study utilized a non-invasive ²³Na MRI technique at 7 Tesla to evaluate cysts in nephrectomized ADPKD kidneys. A total of 20 ADPKD patients were included, and ²³Na MRI was used to classify 2,299 cysts based on sodium concentration. The primary outcome was the identification of distinct cyst phenotypes based on their sodium content.
Results
The primary endpoint revealed that high-[Na⁺] cysts were 1.8-fold more frequent overall. The study found that low-[Na⁺] cysts expressed the vasopressin V2 receptor exclusively, while high-[Na⁺] cysts expressed markers of proximal tubules. The interindividual variation in cyst composition was significant, with low-[Na⁺] cysts ranging from 4.6% to 83.9% of total cysts.
Interpretation
These findings suggest that ²³Na MRI can effectively differentiate between cyst phenotypes in ADPKD, which may have implications for understanding the disease and its treatment. However, the clinical significance of the sodium phenotype and its impact on disease progression remains unclear. The study's limitations include a small sample size and the lack of long-term follow-up, which may affect the generalizability of the results.
Key findings
- Cyst fluid [Na⁺] closely matched ²³Na MRI signal intensities.
- High-[Na⁺] cysts were 1.8-fold more frequent overall.
- Low-[Na⁺] cysts comprised 4.6% to 83.9% of all cysts in individual patients.
- Vasopressin V2 receptor (V2R) detected exclusively in low-[Na⁺] cysts.
- 2,299 cysts were classified in 20 ADPKD patients.
Limitations
- Small sample size of 20 patients.
- No long-term outcomes reported.
- Potential confounding from nephrectomized kidneys.
- Not reported in abstract.