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Autosomal recessive polycystic kidney disease Citrate . Mouse models
Abstract
The kidney function in a model of autosomal dominant polycystic kidney disease (PKD), the Han:SPRD rat, is dramatically improved by chronic ingestion of a solution of potassium citrate and citric acid (KCitr). This study investigated whether this treatment would also be beneficial in the pcy/pcy mouse, a model of autosomal recessive PKD. Starting at 1 month of age, male CD-1 pcy/pcy and normal CD-1 mice were provided with a solution of 55 mM K3 citrate/67 mM citric acid or tap water to drink. The pcy/pcy mice on the KCitr solution failed to grow normally and showed elevated plasma urea levels when compared to water-drinking littermates. Growth of normal CD-1 mice was not affected by KCitr intake. The pcy/ pcy mice were then provided with a more dilute solution of KCitr to drink: this resulted in greater kidney wet and
dry weights and a higher kidney weight/body weight ratio, but no beneficial effects. We conclude that pcy/pcy mice cannot tolerate a high level of KCitr intake and that a lower level is of no benefit. Whether KCitr therapy would be helpful in patients with PKD is still an open question.
Introduction Polycystic kidney disease (PKD) is the most common inherited kidney disorder and accounts for about 8-10% of the patients on dialysis for end-stage renal disease. Unfortunately, there is currently no definitive therapy for halting or slowing progression of this disease in people [ 1 ]. We recently demonstrated in an animal model of autosomal dominant PKD, the Han:SPRD rat, that provision of potassium citrate and citric acid in drinking water led to preservation of a normal glomerular filtration rate in young heterozygous male animals with cystic disease [2]. In the present study, we investigated whether a beneficial effect of this treatment would also be seen in the pcy/pcy mouse which has a slowly progressive form of autosomal recessive PKD [3]. Materials and Methods Six homozygous mice (2 males and 4 females, all from one litter) in which pcy genes were present on a CD-1 background were kindly provided by Dr. Vincent Gattone II (University of Kansas Medical Center, Kansas City, Kans., USA) and were used as breeders. Normal...