Expression pattern of aquaporins in patients with primary nephrotic syndrome with edema.

The association between the expression of aquaporins (AQPs) in kidney tissues and the occurrence of edema in nephrotic syndrome (NS) remains unclear. The current study aimed to investigate this association. A total of 54 patients with primary glomerular disease, diagnosed by renal biopsy, were divided into three groups: Control, NS without edema and NS with edema. The expression of AQP1, AQP2, AQP3 and AQP4 in kidney tissues from these patients was assessed using immunohistochemistry, and urinary AQP concentrations were quantified by ELISA. Comparison of the three groups was conducted using one way analysis of variance, independent samples t­test or the Chi­square test. AQP1 was strongly expressed in the proximal tubules. The proportion of the AQP1­positive area in kidney tissues from patients with NS with edema was significantly reduced, in comparison with the other two groups. By contrast, the proportion of the AQP2­positive area in the NS with edema group was significantly higher than that of the other two groups; significant differences were also observed between the control and NS without edema groups for this parameter. Urinary AQP2 concentrations in patients with NS (with and without edema) were significantly higher than that of the control group, and exhibited a significant positive correlation with kidney tissue AQP2 concentrations. The present study demonstrated the abnormal expression pattern of AQP1­AQP4 in the kidney tissues of patients with NS, providing a basis for an improved understanding of the role of AQP in the pathogenesis of NS.

Changes in the pharmacokinetics of digoxin in polyuria in streptozotocin-induced diabetic mice and lithium carbonate-treated mice.

In humans, digoxin is mainly eliminated through the kidneys unchanged, and renal clearance represents approximately 70% of the total clearance. In this study, we used the mouse models to examine digoxin pharmacokinetics in polyuria induced by diabetes mellitus and lithium carbonate (Li(2)CO(3)) administration, including mechanistic evaluation of the contribution of glomerular filtration, tubular secretion, and tubular reabsorption. After digoxin administration to streptozotocin (STZ)-induced diabetic mice, digoxin CL/F increased to approximately 2.2 times that in normal mice. After treatment with Li(2)CO(3) (0.2%) for 10 days, the CL/F increased approximately 1.1 times for normal mice and 1.6 times for STZ mice. Creatinine clearance (CLcr) and the renal mRNA expression levels of mdr1a did not differ significantly between the normal, STZ, and Li(2)CO(3)-treated mice. The urine volume of STZ mice was approximately 26 mL/day, 22 times that of normal mice. The urine volume of Li(2)CO(3)-treated mice increased approximately 7.3 times for normal mice and 2.3 times for STZ mice. These results suggest that the therapeutic effect of digoxin may be significantly reduced in the presence of polyuria either induced by diabetes mellitus or manifested as an adverse effect of Li(2)CO(3) in diabetic patients, along with increased urine volume.

Urinary aquaporin-2 in children with acute pyelonephritis.

Children with acute pyelonephritis develop polyuria and have reduced maximum urinary concentration capacity. We studied whether these abnormalities are associated with altered urinary excretion of the water channel aquaporin-2 (AQP2) in the renal collecting duct. AQP2 is the main target for antidiuretic action of arginine vasopressin (AVP), and the urinary excretion of this protein is believed to be an index of AVP signaling activity in the kidney. Children with acute pyelonephritis, aged 5-14 years, were examined for urinary flow rate, creatinine clearance, unchallenged urine osmolality, and urinary ion excretion. Urinary excretion of AQP2 was measured by dot immunoblotting technique. Studies were performed in the acute phase of pyelonephritis, in the same children after treatment, and in control patients. At the onset of pyelonephritis, urinary flow rate and solute excretion were increased, but the urinary osmolality was unchanged. The urinary level and urinary excretion of AQP2 was increased in acute pyelonephritis and decreased after treatment. Excretion of aquaporin-3 was unchanged, suggesting that the increase in AQP2 urinary excretion was not due to a shedding of collecting duct cells. The results suggest that a mechanism proximal to the collecting duct may be responsible for the polyuria observed in children with acute pyelonephritis. Increased urinary AQP2 levels suggest that a compensatory activation of apical plasma membrane targeting of AQP2 may occur in pyelonephritis.