Does increased water intake prevent disease progression in autosomal dominant polycystic kidney disease?

Abstract

Background: The clinical effects of increased water intake on autosomal dominant polycystic kidney disease (ADPKD) progression are unknown.

Methods: ADPKD patients with creatinine clearance ≧ 50 mL/min/1.73 m(2) were divided into high (H-, n = 18) and free (F-, n = 16) water-intake groups, mainly according to their preference. Prior to the study, 30 patients underwent annual evaluation of total kidney volume (TKV) and 24-h urine for an average of 33 months. During the 1-year study period, TKV and 24-h urine were analyzed at the beginning and end of the study and every 4 months, respectively.

Results: During the pre-study period, urine volume (UV) in the H-group was higher (P = 0.034), but TKV and kidney function and their slopes were not significantly different between the two groups. After the study commenced, UV further increased (P < 0.001) in the H-group but not in the F-group. During the study period, TKV and kidney function slopes were not significantly different between the two groups (primary endpoint). Plasma copeptin was lower (P = 0.024) in the H-group than in the F-group. TKV and kidney function slopes became worse (P = 0.047 and 0.011, respectively) after high water intake (H-group) but not in the F-group. High UV was associated with increased urine sodium, and urine sodium positively correlated with the % TKV slope (P = 0.014).

Conclusions: Although the main endpoint was not significant, high water intake enhanced disease progression in the H-group when compared with the pre-study period. These findings necessitate a long-term randomized study before drawing a final conclusion.

Keywords: autosomal dominant polycystic kidney disease; glomerular filtration rate; kidney volume; urine volume; vasopressin.

FIGURE 1:

Changes in urine volume from the pre-study period to water-study period (A), and during the water study period (B). Urine volume in the pre-study period is the mean of 24-h urine collected yearly for 2–3 years and that during the study period is the mean of four 24-h urine samples collected during the water study. Connected line represents the same patient and unconnected single points correspond to the participants without pre-study data. Single data were input to draw the figure but only paired data were used for statistical calculation. (A). In the pre-study period, urine volume was larger in the high water-intake group and further increased significantly from 2048 ± 648 to 2691 ± 710 mL/day (mean of paired samples). Higher urine volume was sustained for 1 year in the high water-intake group (B).

FIGURE 2:

Changes of plasma osmolality (A) and plasma copeptin (B) during the water study. The right-most column represents the mean of four measurements. High water intake accompanied with low plasma osmolality and low plasma vasopressin (copeptin) level.

FIGURE 3:

Changes of plasma sodium concentration (A) and urinary sodium excretion (B) during the water study. The right-most column represents the mean of four measurements. High water intake induced high urinary sodium excretion, which resulted in low plasma concentration.

FIGURE 4:

The relationships between urine volume and urine sodium excretion. Urine volume correlated positively with urine sodium excretion with a highly significant correlation coefficient. Although patients were directed to drink solute-free water, urine sodium increased concomitantly with increased urine volume.

FIGURE 5:

The relationships between urine sodium and % change of TKV (A) and between plasma copeptin level and TKV slope (B). Urine sodium had a positive correlation with % increase in TKV (A). Plasma copeptin had a positive but weak correlation with the increased rate of TKV (B), which is consistent with previous experimental findings.

FIGURE 6:

Changes in eGFR(Eq_cr) slope (A), TKV slope (B) and %TKV slope (C) between pre-study and during water study periods. The slopes in the pre-study period were calculated from 2 to 3 years of observation and those during the water study from 1-year observation. The lines connect individual data and unconnected single points correspond to the participants without pre-study data. Single data were input to draw the figure but only paired data were used for statistical calculation. Horizontal bar represents the mean. After increasing water intake in the high water-intake group, eGFR(Eq_cr) slope (A) became more negative (from −0.3 ± 3.0 to −7.1 ± 8.6) and TKV slope (B) became more positive (from 72 ± 89 to 149 ± 113). The %TKV slope (C) also increased (from 3.8 ± 5.7 to 9.1 ± 6.3) in the high water-intake group, but the changes did not reach statistical significance. (The data in parentheses are the means ± SD of paired data.)