The influence of a low sodium diet on polycystic kidney disease progressionand the efficacy of a Vasopressin V2 Receptor Antagonist

Melsert, B. (Belle) (2015) The influence of a low sodium diet on polycystic kidney disease progressionand the efficacy of a Vasopressin V2 Receptor Antagonist. thesis, Medicine.

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Abstract

Background: Autosomal Dominant Polycystic Kidney Disease (ADPKD), also known as polycystic kidneys, is the most common hereditary renal disease. The disease is caused by a mutation the PKD1 or PKD2 gene, which leads to massive cyst development in both kidneys. The progression of cyst development leads to a decreased concentrating ability of the kidneys which leads to an increase in vasopressin levels in the blood. It is known that in chronic kidney disease these increased levels of vasopressin are harmful and lead to further deterioration of kidney function. Treatment with Tolvaptan, a Vasopressin V2 Receptor Antagonist (V2RA), has shown to be effective. Because of side-effects such as polyuria this treatment is not optimal. Beside blocking the V2 receptor, it is of great interest to investigate modifiable lifestyle factors which influence vasopressin. Vasopressin is released in response to a high blood osmolarity. Blood osmolarity is partially determined by the amount of sodium intake. In this respect, this study investigates whether it possible to delay polycystic kidney disease (PKD) progression in mice by a low sodium diet. On top of that this study investigates whether a low sodium intake positively influences the efficacy and side-effects of V2RA use. Research questions: 1- What is the effect of a low sodium diet on disease progression of PKD? 2- What is the effect of a low sodium diet on the efficacy of a V2RA? 3- Can side-effects of a V2RA be decreased by a low sodium diet? Materials and Methods: In this research the pups of the mouse strain Tam-KspCad-CreERT2;Pkd1lox2-11/lox2-11 are used. By administrating tamoxifen at the age of 10, 11 and 12 days these mice develop PKD, this is comparable to the human situation. Mice were divided into healthy controls, PKD mice and PKD mice with a V2RA in the diet. These groups are on a high sodium (HS) or low sodium (LS) diet during a 21 day experiment. During this experiment on certain time points weight, food and water intake was registered. At day 21 all the mice were terminated, hereafter kidney tissue was prepared to determine a cyst ratio. Results: A low sodium diet does not lead to a significant reduction in total kidney weight (TKW) but to an increase of TKW. A low sodium diet in PKD mice does not lead to a lower cyst ratio. A low sodium diet does also not lead to a lower TKW and cyst ratio in PKD-V2RA mice and does not lead to a lower water intake in PKD-V2RA mice. Conclusion: In this Pkd1 inducible mouse model a low sodium diet does not improve disease progression of PKD, a low sodium diet does not lead to a higher efficacy of a V2RA and a low sodium diet does not lead to less severe side-effects of a V2RA

Item Type:	Thesis (Thesis)
Supervisor name:	Faculty supervisor and Gansevoort, prof. dr. R.T. and Second supervisor and Gastel, M.D.A. van
Faculty:	Medical Sciences
Date Deposited:	25 Jun 2020 10:46
Last Modified:	25 Jun 2020 10:46
URI:	https://umcg.studenttheses.ub.rug.nl/id/eprint/740

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