TRANSIENT INCREASE IN WATER INTAKE IS SUFFICIENT TO REDUCE LONGTERM CARDIORENAL PROGRESSION IN LPK RATS

PS SAGAR1, M LUCIUK1, C MANNIX1, J ZHANG1, ATY WONG1, GK RANGAN1,2

1Centre for Transplant and Renal Research, Westmead Institute for Medical Research, University of Sydney, Sydney, New South Wales; 2Department of Renal Medicine, Westmead Hospital, Sydney, New South Wales.

Aim: To determine the chronic effects of increased water intake on the progression of polycystic kidney disease (PKD).

Background: Vasopressin promotes renal cyst growth in PKD, and its level can be reduced by increasing water intake. However, there are no long-term data on the renal and cardiac effects of increased water in experimental PKD.

Methods: Male and female LPK (Nek8/NPHP9 ortholog; n=64) and Lewis (n=36) rats were assigned to either normal water intake (NWI) or high water intake (HWI; water supplemented with 5% glucose) from postnatal weeks 3 to 16. Groups were sacrificed at week 10 or 16 to assess different time-points of renal and cardiac disease progression.

Results: Water intake increased 3.5 fold in LPK rats over time due to polyuria. Between weeks 3 to 10, LPK+HWI rats had up to 32% higher water intake vs LPK+NWI, but at week 16 there was no difference between the two groups. Kidney to body weight ratio in the LPK+HWI group was markedly reduced at week 10 (54%) and week 16 (42%) (p<0.01) with no significant difference between genders. This was accompanied by a reduction in serum urea (54% at week 10, 42% at week 16; p<0.01) and a reduction in urinary protein to creatinine at week 16 (70%; p<0.01), but no improvement in serum creatinine or creatinine clearance. At week 16, LPK+HWI males had a reduction in the heart to body weight ratio (21%; p<0.01) and systolic blood pressure (HWI:134+9mmHg; NWI:159+14mmHg; p<0.01).

Conclusions: Increased water intake consistently reduced the progression of renal cyst growth, cardiac enlargement and hypertension in PKD. These effects were observed even if the increase in water intake was not sustained.

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