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Dietary potassium citrate does not harm the pcy mouse
Judith A Tanner1, George A Tanner
1Department of Cellular and Integrative Physiology, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, Indiana 46202, USA.
Abstract:
Formation of multiple cysts in the kidneys occurs in several inherited diseases and often leads to terminal kidney failure. Because there is no definitive therapy to halt or slow the progression of renal cystic disease in people, numerous studies have examined possible therapies in animal models. Autosomal-dominant polycystic kidney disease (ADPKD) in the Han:SPRD rat is ameliorated when alkalinizing citrate salts are provided in drinking solutions. By contrast, pcy mice with cystic disease fare worse with the same treatment. We tested the hypothesis that pcy mice ingesting citrate salts in the feed would not be adversely affected by this treatment. Male homozygous pcy mice were given regular feed or 6% potassium citrate-supplemented feed and ad libitum access to water starting at 3 weeks of age. The survival curves of the treated and untreated mice were not significantly different. We conclude that treatment with potassium citrate in the feed does not affect the progression of renal cystic disease in the pcy mouse. This model closely resembles human adolescent nephronophthisis (NPHP3). Based on these findings, citrate treatment cannot be recommended for NPHP3. The fact that it did no harm, however, removes a significant barrier to its consideration as a therapy for ADPKD.
Insights
Potassium citrate in feed did not worsen kidney disease in pcy mice, a model for human nephronophthisis (NPHP3). This finding suggests citrate therapy may still be viable for autosomal-dominant polycystic kidney disease (ADPKD).
Area of Science:
- Nephrology
- Genetics
- Pharmacology
Background:
- Inherited kidney diseases causing multiple cysts often lead to kidney failure.
- Current therapies lack definitive treatments to slow cystic kidney disease progression.
- Animal models are crucial for investigating potential therapeutic interventions.
Purpose of the Study:
- To evaluate the effect of potassium citrate supplementation in feed on renal cystic disease progression in pcy mice.
- To determine if citrate treatment, previously shown to benefit some models, adversely affects the pcy mouse model of nephronophthisis (NPHP3).
Main Methods:
- Male homozygous pcy mice were administered either regular feed or feed supplemented with 6% potassium citrate.
- Mice had ad libitum access to water and treatment began at 3 weeks of age.
- Survival rates of treated and untreated groups were compared to assess disease progression.
Main Results:
- Ingesting potassium citrate via feed did not significantly alter the survival curves of pcy mice.
- The progression of renal cystic disease in the pcy mouse model was not affected by dietary potassium citrate.
- This indicates citrate treatment is not detrimental to this specific model of cystic kidney disease.
Conclusions:
- Dietary potassium citrate does not impact renal cystic disease progression in the pcy mouse model, which resembles human nephronophthisis type 3 (NPHP3).
- Citrate treatment is not recommended for NPHP3 based on these findings.
- The lack of adverse effects removes a barrier for considering citrate therapy in autosomal-dominant polycystic kidney disease (ADPKD).
