Evaluation of the Renal and Cardiovascular Effects of Long-Term Tolvaptan Treatment in Autosomal Dominant Polycystic Kidney Disease.

INTRODUCTION: Cardiovascular diseases constitute a significant cause of morbidity and mortality in individuals with autosomal dominant polycystic kidney disease (ADPKD). This study aimed to assess the long-term effects of tolvaptan on the kidneys and heart in rapidly progressing ADPKD. METHODS: Among 354 patients diagnosed with ADPKD, 58 meeting the eligibility criteria for tolvaptan were included in the study. The study comprised two groups with similar demographic and clinical characteristics: 29 patients receiving tolvaptan treatment and 29 in the control group. Several included genetic analysis, magnetic resonance imaging, and echocardiography. Clinical and cardiac changes were recorded in both groups after a 3-year follow-up. RESULTS: Tolvaptan treatment demonstrated a significant reduction in the rate of eGFR decline compared to the control group. Furthermore, it was observed that tolvaptan could prevent the development of cardiac arrhythmias by inhibiting an increase in QTc interval and heart rate. CONCLUSION: These findings suggest that, in addition to slowing kidney progression in ADPKD management, tolvaptan may potentially benefit in preventing cardiac complications.

Predicting Progression of Autosomal Dominant Polycystic Kidney Disease by Changes in the Telomeric Epigenome.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited cause of chronic kidney disease with Polycystin (PKD) 1 and 2 gene mutation. However, the intra-familial variability in symptoms further suggests a non-Mendelian contribution to the disease. Our goal was to find a marker to track the epigenetic changes common to rapidly progressing forms of the disease. The risk of ADPKD increases with age, and aging shortens the telomere length (TL). Telomeres are a nucleoprotein structure composed mainly of three complexes, shelterin, CST and RNA-containing telomere repeat(TERRA), which protects the ends of chromosomes from degradation and fusion, and plays a role in maintaining cellular stability and in the repair of telomeric damage. TERRAs are transcribed from telomeric regions and a part of them is engaged in a DNA/RNA hybrid (R-loop) at each chromosome end. We tracked TL and TERRA levels in blood samples of 78 patients and 20 healthy control. Our study demonstrates that TL was shortened and TERRA expression levels in the DNA-attached fraction increased in autosomal dominant polycystic kidney patients with mutations in PKD1 and PKD2 compared to the control group. Moreover, it was observed that the expression of TERRA engaged in the R-loop was higher and the length of telomeres shorter in patients with ADPKD who showed rapid disease progression. Intrafamilial variation in TL and TERRA levels with the same mutation would indicate reliable epigenetic potential biomarkers in disease monitoring.