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


BMC Nephrology. 2010;11(26) 

In This Article


The capacity of the kidneys to concentrate and dilute urine is an important mechanism to maintain constant plasma osmolarity of the body fluid compartments. Defects in both urine concentrating and diluting ability have been measured in chronic kidney diseases, and in diseases outside the kidneys associated with either fluid retention as heart failure, liver cirrhosis and syndrome of inappropriate antidiuretic hormone secretion or dehydration as diabetes insipidus.[1–3] In addition, urine diluting capacity is reduced in hypothyreoidism and adrenal insufficiency with up regulation of AQP2,[4–6] and urine concentration capacity is reduced in thyrotoxicosis and glucocorticoid excess with down regulation of AQP2.[7,8]

A normal concentrating and diluting capacity demands delivery of fluid to the distal part of the nephron, hypertonicity of renal medullar interstitial tissue and intact water absorption in the collecting ducts of the nephron. In addition, GFR and filtered load are important factors in the process of urinary concentrating ability of the kidney, as they control the load delivered to the thick ascending limb, which generates and maintains a hypertonic medullary interstitium. One or more of these prerequisites might be abnormal during the development and progression of chronic kidney disease. The consequence is an abnormal water transport in the distal part of the nephron.

In the kidney, aquaporin-2 trafficking mediates water transport across the apical cell membrane in principal cells of the collecting ducts.[2] The short-term regulation by vasopressin implies activation of V2 receptors and subsequently trafficking of AQP-2 vesicles to the apical plasma membrane resulting in increased water permeability and absorption. The long-term regulation is due to a change in AQP-2 mRNA expression followed by AQP2 synthesis.[2] Mutation in the aquaporin2 gene causes nephrogenic diabetes insipidus. Thus, an abnormal up- or downregulation of the aquaporin2 water channels in the principal cells seems to be an important patophysiological factor in development of concentrating and diluting defects in progressive renal disesase.[3,9–11] However, it has never been studied to what extent the function of the principal cells is affected in patients with varying degrees of reduced renal function, when evaluated by simultaneous measurements of urinary excretions of aquaporin2 (u-AQP2) and cyclic-AMP (u-c-AMP), and plasma concentration of vasopressin (p-AVP) during urine concentrating and diluting.

In the present study, we wanted to test the hypothesis that u-AQP 2 and u-c-AMP were abnormal in chronic kidney disease Stages I-IV,[12] and that these variables responded abnormal during urine concentrating and dilution tests.

We performed urine concentrating test of 12 hours duration, and urine diluting test of 5 hours duration in healthy control subjects and patients with chronic kidney diseases. The effect variables were u-AQP 2, u-c-AMP, urine volume (UV), free water clearance (CH2O), and p-AVP.


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