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Published on: July 3, 2013
Citrate therapy for polycystic kidney disease in rats
1Department of Physiology and Biophysics, Indiana University School of Medicine, Indianapolis, Indiana, USA. gtanner@iupui.edu
Insights
Potassium citrate (KCitr) treatment in rats with autosomal dominant polycystic kidney disease (PKD) preserved glomerular filtration rate (GFR) and extended lifespan. This study investigated citrate and ammonia handling in PKD kidneys.
Area of Science:
- Nephrology
- Biochemistry
- Animal Models
Background:
- Autosomal dominant polycystic kidney disease (PKD) leads to renal failure with limited treatment options.
- A previous study showed potassium citrate plus citric acid (KCitr) prevented glomerular filtration rate (GFR) decline in young rats with PKD.
- This study aimed to assess the sustained effect of KCitr and explore renal citrate and ammonia metabolism in PKD.
Purpose of the Study:
- To determine if early KCitr treatment sustains GFR preservation in rats with PKD.
- To investigate the renal handling of citrate and ammonia in normal versus cystic kidneys.
- To evaluate the impact of KCitr on the survival rate of rats with PKD.
Main Methods:
- Rats with PKD were administered tap water or various citrate solutions for drinking.
- Glomerular filtration rate (GFR) and survival studies were conducted.
- Plasma and renal citrate levels, citrate consumption, and ammonia synthesis/excretion were measured.
Main Results:
- Long-term KCitr treatment maintained normal GFR in rats with PKD and extended average lifespan from 10 to 17 months.
- Rats with PKD showed altered citrate and ammonia handling, including higher plasma/renal citrate and lower citrate consumption/ammonia synthesis.
- Alkalinizing citrate salts (Na3 citrate or K3 citrate) prevented GFR decline, but ammonium citrate did not.
Conclusions:
- Rats with PKD exhibit abnormal renal citrate and ammonia metabolism.
- Alkalinizing citrate salts are effective in preserving GFR and extending survival in a rat model of PKD.
- Citrate supplementation represents a potential therapeutic strategy for managing PKD progression.
Background:
Few treatments are available to slow the progression to renal failure in autosomal dominant polycystic kidney disease (PKD). In an animal model of PKD, the male heterozygous Han:SPRD rat, intake of a solution of potassium citrate plus citric acid (KCitr) from age one to three months prevented a decline in glomerular filtration rate (GFR). The present study tested whether this beneficial effect is sustained and explored handling of citrate and ammonia in normal and cystic kidneys.
Methods:
Rats were provided with tap water or citrate solutions to drink, and clearance and survival studies were performed.
Results:
The GFRs of rats with PKD that consumed KCitr from one month of age were normal at six months of age, while those of their counterparts on water were about one third of normal. Long-term KCitr treatment extended the average life span of rats with PKD from 10 to 17 months. Compared with normal rats, water-drinking rats with PKD had higher plasma [citrate], renal cortical [citrate], and fractional excretion of citrate, and lower rates of renal citrate consumption, ammonia synthesis, and ammonia excretion. Cortical PNH3 was not elevated in cystic kidneys. Intake of Na3 citrate/citric acid solution or K3 citrate solution, but not ammonium citrate/citric acid solution, prevented a decline in GFR in three-month-old rats with PKD.
Conclusions:
Rats with PKD show abnormal renal handling of citrate and ammonia. Citrate salts that have an alkalinizing effect preserve GFR and extend survival.
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