Abnormal Function of the Vasopressin-cyclic-AMP-aquaporin2 Axis During Urine Concentrating and Diluting in Patients with Reduced Renal Function. A Case Control Study

Erling B Pedersen; Ingrid M Thomsen; Thomas G Lauridsen

Disclosures

BMC Nephrology. 2010;11(26) 

In This Article

Urine Concentration Test

Table 1 shows u-Osm, UV, CH2O, u-c-AMP and u-AQP2 during the urine concentrating test.

In all groups U-Osm increased during a 12 hours period of thirsting. The increase in u-Osm was significantly lower in Group 4 than in Group 1, and the increase was especially reduced in patients with decreased renal function (Group 1: 47%, Group 2: 65%, Group 3: 14%, and Group 4: 10%).

Urine volume decreased significantly in Groups 1 and 2 (Group 1: -49%, Group 2:- 49%), when comparison was made between the levels during 24 hours and during one hour after the 12 hours thirsting period. In addition, a tendency to decrease in UV was measured during the 12 hours thirsting period. Contrarily, in Groups 3 and 4, UV tended to increase during the 12 hours of thirsting, and at the end of the concentrating test, UV was not significantly changed in Group 3 (-15%), and was only borderline significantly reduced in Group 4 (-29%).

Free water clearances fell significantly in Group 1 (-17%) and in Group 2 (-40%), whereas the levels were approximately unchanged in Group 3 (-5%) and Group 4 (-7%), when comparison was made between the levels during 24 hours and during one hour after the 12 hours thirsting period.

The concentration of c-AMP was approximately at the same level in Groups 1–3 during 24 hours urine collection. U-c-AMP increased significantly in Group 1 (91%) and Group 2 (138%), when comparison was made between the levels during 24 hours and during one hour after the 12 hours thirsting period. There was no significant increase in u-c-AMP in groups 3 and 4, although a tendency to increase in u-c-AMP was measured in Group 3 (55%).

The concentration of AQP2 in urine increased significantly in Group 1 and 2 during the urine concentrating test. In Group 3 and 4, u-AQP2 was no significantly changed during water deprivation.

P-AVP was the same in Groups 1 to 3 (Group 1: 0.95 pmol/l (0.33), median with interquartile range, Group 2: 0.75 pmol/l (0.55), and Group 3: 1.00 pmol/l (0.83), NS). The level in Group 4 was significantly higher than in the other three groups (Group 4: 1.80 pmol/l (1.68), p < 0.000).

Urine Diluting Test

Table 2 shows UV, CH2O, u-osm, u-c-AMP, and u-AQP2 during the urine diluting test.

The amount of water given was in Group 1:1389 ml (371), in Group 2: 1581 (416), in Group 3: 1674 ml (416), and in Group 4: 1572 ml (374). The amount of water excreted during the first four hours after water loading was significantly lower in Group 4 than in the other three Groups (Group 1: 1376 ml/4 hours (465), median with interquartile range, 100% (44) of the water load, Group 2: 1210 ml/4 hours (662), 81% (30) of the water load, Group 3: 1536 ml/4 hours (524), 93% (32) of the water load, and Group 4: 797 ml/4 hours (363), 53% (17) of the water load).

Both UV and CH2O increased in all groups during the diluting test. UV and CH2O reached a significantly higher level during urine diluting in Groups 1, 2, and 3 compared with Group 4, i. e. UV (Group 1: 12 fold, Group 2: 9 fold, Group 3: 9 fold, and Group 4: 2 fold), and CH2O (Group 1: 9.0 ml/min, Group 2: 6.5 ml/min, Group 3: 9.8 ml/min, and Group 4: 1.9 ml/min). U-osm decreased significantly in all groups. In Group 4, u-osm was significantly higher than in the other groups during the second and third hour of the test.

U-c-AMP was unchanged during urine diluting test in all four groups. However, u-c-AMP was significantly lower in Group 4 than in the other three groups.

U-AQP2 decreased during urine diluting test in all groups. The statistical analyses showed that the level of u-AQP2 was significantly higher in Group 4 than in the other three groups during the different periods of the test. U-AQP2 was the same during the test in Groups 1, 2, and 3. The maximum decrease did not deviate significantly between the groups, u-AQP2 (Group 1: - 27%, Group 2: - 33%, Group 3: - 32%, and Group 4: - 19%).

Table 3 shows that p-AVP was significantly reduced in all four groups during urine diluting test. The maximum reduction was most pronounced in Group 1 (Group 1: - 40%, Group 2: - 11%, Group 3: - 14%, and Group 4: - 27%). The level of p-AVP was significantly higher in Group 4 than in the other three groups, in which p-AVP was approximately in the same level. P-osm decreased significantly in all groups and was normalized in the last period of the test in Groups 1 and 2.

Blood Pressure

Twenty-four hours BP was significantly different between the groups (Group 1: 123/74 (16/9.8) mm Hg, median and interquartile range, Group 2: 130/81 (12/7.0) mm Hg, Group 3:129/79 (13/8.0) mm Hg, Group 4: 140/83 (18/10) mm Hg) for both systolic and diastolic BP (0.004/0.005, Kruskal-Wallis test). The statistical analyses showed that the level in Group 4 was significantly higher than in the other groups. Pulse rate during 24 hours was the same in the groups (Group 1: 70 (13) beats/min, median and interquartile range, Group 2: 70 (12) beats/min, Group 3: 65 (15) beats/min, and Group 4: 69 (10) beats/min.

During the experimental procedure BP was measured seven times. The initial level was in Group 1: 107/62 (14/13) mm Hg, Group 2: 117/78 (24/15) mm Hg, Group 3: 123/74 (22/19) mm Hg, and Group 4: 126/77 (25/13) mm Hg. The BP and pulse levels did not deviate significantly from baseline level during the urine diluting test (Data not shown).

Relationship between e-GFR and AVP, c-AMP and AQP2

Correlation analyses were performed for the whole study population on data from baseline before the urine diluting test. E-GFR was significantly correlated with p-AVP (ρ = - 0.618, P < 0.000), u-c-AMP (ρ = 0.536, P < 0.000), and u-AQP2 (ρ = - 0.288, P < 0.05). The influence of e-GFR on effect variables were measured using a multiple regression analysis (Table 4). The dependent variable was the amount of water excreted during the first four hours after water loading in percent of the given water load during the urine diluting test (20 ml/kg/body weight). The independent variables were p-AVP, u-c-AMP, AQP2, 24 hours systolic and diastolic blood pressure, and e-GFR. The analysis showed that the partial regression coefficient was significant for e-GFR, but not for the other effect variables in the analysis.

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