Role of Renal Nerves in a Preclinical Model of Advanced Autosomal Recessive Polycystic Kidney Disease

• Published in: Physiology (Bethesda, Md.) Md.), 2023-05, Vol.38 (S1)
• Main Authors: Gauthier, Madeline, Encinas, Noah, Dennis, Melissa, Morales, Mark, Banek, Christopher
• Format: Article
• Language: English
• ISSN: 1548-9213; 1548-9221
• DOI: 10.1152/physiol.2023.38.S1.5733823

Abstract only Autosomal recessive polycystic kidney disease (ARPKD) is a rare genetic disease defined by the early and rapid renal cyst growth, which result in renal and cardiovascular dysfunction in early adulthood. Our lab has recently revealed a novel role for renal nerves in early phase of renal cystogenesis in the PCK rat model of ARPKD, where total renal denervation (T-RDNx) mitigated cystic progression from age week 4 (W4) through W10. Moreover, afferent-targeted renal nerve ablation (A-RDNx), which leaves sympathetic nerves intact, also suppressed renal cystogenesis, highlighting a pivotal role of renal afferent nerves in the PCK rat cystic progression. Whether renal nerves contribute to later phases of ARPKD progression remains unknown. In this study, we aimed to evaluate the role of renal nerves in cystogenesis and cardio-renal dysfunction in 24-week-old PCK rats. We hypothesized that T-RDNx but not A-RDNx, would improve renal function and decrease systolic blood pressure (SBP), but that intervention would not decrease cystogenesis. To test this hypothesis, PCK rats (age: Week 24; W4) were randomly treated with T-RDNx (n=12; 7M/5F), A-RDNx (n=15; 7M/8F), or sham (n=13; 6M/7F) surgical interventions. Animals were monitored biweekly for cardiovascular and renal function measurements through W30. SBP was collected via tail cuff. Renal function was assessed indirectly by serum creatinine (Cr) and blood urea nitrogen (BUN). At W30, kidney tissues were collected and assessed for cystic index (%cystic area). Treatment and sex effects were analyzed by two-way ANOVA with a Bonferroni post hoc test (p