Abstract: PO1264
The Impact of Salt Deficiency on Acid-Base Homeostasis in Autosomal Recessive Polycystic Kidney Disease
Session Information
- Cystic Kidney Disease - II
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1001 Genetic Diseases of the Kidneys: Cystic
Authors
- Mallory, Jonathan, Medical University of South Carolina, Charleston, South Carolina, United States
- Spicer, Morgan J., Medical University of South Carolina, Charleston, South Carolina, United States
- Domondon, Mark, Medical University of South Carolina, Charleston, South Carolina, United States
- Schibalski, Ryan, Medical University of South Carolina, Charleston, South Carolina, United States
- Spires, Denisha R., Medical University of South Carolina, Charleston, South Carolina, United States
- Fomin, Mikhail, Medical University of South Carolina, Charleston, South Carolina, United States
- Amoah, Thelma, Medical University of South Carolina, Charleston, South Carolina, United States
- Ilatovskaya, Daria, Medical University of South Carolina, Charleston, South Carolina, United States
Background
In healthy subjects, dietary salt restriction exacerbates imbalances of acid-base homeostasis. The disease progression of autosomal dominant PKD is associated with decreasing serum bicarbonate levels and metabolic acidosis, however very little is known about acid-base imbalance in autosomal recessive (AR) PKD, particularly, in response to dietary restrictions. Here we hypothesized that a salt-deficient (SD) diet leads to electrolyte and acid-base imbalance in ARPKD.
Methods
Male and female PCK/CrljCrlPkhd1pck/CRL (PCK) rats were fed a SD (0.01% NaCl, Dyets Inc) diet for 1, 3, 5, 7 and 9 weeks beginning at 4 weeks of age. Before each endpoint, urine was collected, and plasma and tissue samples were harvested. Urine and plasma creatinine, pH and electrolytes, BUN, and plasma aldosterone levels were measured. Cystic index was analyzed with ImageJ. Statistical analysis was performed with 2-way ANOVA.
Results
Two-kidney-to-body-weight, water consumption, plasma K+ and urine output decreased over the course of the SD diet in both sexes. Plasma Na+ and Cl- as well as creatinine increased; and BUN did not change. Plasma aldosterone increased from week 1 to week 5 (week 1: 2.6±1 (M) and 3.7±0.9 (F), week 5: 10.5±1.5 ng/ml (M) and 7.7±1.1 (F), p<0.001 (over time)), followed by a return to baseline by week 9 of the SD diet. There was a significant increase in cystogenesis in female rats from week 1 to week 9 of the SD diet (week 1: 14.2±1.9%, week 9: 36.3±2.4%). Further, we observed an increase in plasma pH (week 1: 6.98±0.08 (M) and 6.83±0.03 (F), week 9: 7.16±0.08 (M) and 7.13±0.02 (F), p<0.001 (over time)) and a decline in urine pH (week 1: 7.69±0.42 (M) and 8.75±0.08 (F), week 9: 5.80±0.07 (M) and 5.72±0.08 (F), p<0.001 (over time)) in both sexes throughout the dietary challenge.
Conclusion
PCK rats on a SD diet exhibit acidification of urine pH and an increase in plasma pH. We can speculate that acid base transporters such as NHE1, NBCe2, and pendrin are upregulated to conserve plasma sodium leading to a shift in acid-base homeostasis. Further studies aimed at elucidating the role of these transporters may add to the current knowledge regarding the pathogenesis and dietary management of ARPKD.
Funding
- NIDDK Support