ABSTRACT
The discovery of aquaporin (AQP) membrane water channels by Peter Agre and co-workers answered a long-standing biophysical question of how water crosses biological membranes and provided insight, at the molecular level, into the fundamental physiology of water balance regulation and the pathophysiology of water balance disorders. In the kidney, AQP1-AQP4, AQP6-AQP8 and AQP11 are expressed and multiple studies
CONTENTS Abstract 125 7.1 Introduction 126 7.2Expression and Function of Aquaporins in the Kidney 127 7.3Vasopressin Regulation of Kidney Aquaporins 130 7.4Dysregulation of Renal Aquaporins in Water Balance Disorders 133
7.4.1Urinary Concentrating Defects 134 7.4.1.1Inherited Forms of Diabetes Insipidus 134 7.4.1.2Acquired Forms of NDI 135 7.4.1.3Lithium-Induced NDI 135 7.4.1.4Electrolytes Abnormality (Hypokalemia and Hypercalcemia) 139 7.4.1.5Ureteral Obstruction 140 7.4.1.6Acute and Chronic Renal Failure 142
7.5Conditions Associated with Water Retention 143 7.5.1Congestive Heart Failure 143 7.5.2Hepatic Cirrhosis 144 7.5.3Experimental Nephrotic Syndrome 145 7.5.4SIADH and Vasopressin Escape 145
References 145
have underscored the essential roles of AQP1-AQP4 in renal regulation of body water balance. Vasopressin regulates acutely the water permeability of the kidney collecting duct by regulation of AQP2 tra cking from intracellular vesicles to the apical plasma membrane. is involves complex signalling mechanisms. In addition, long-term regulation of AQP2 and AQP3 expression act in concert with acute regulation of AQP2 to tightly control collecting duct water reabsorption and hence body water balance. Importantly, mutations or dysregulation of renal AQPs is involved in water balance disorders. Mutations in AQP2 lead to nephrogenic diabetes insipidus (NDI). Downregulation of AQP2 expression and/or dysregulation of AQP2 tra cking leads to urinary concentrating defects seen in acute kidney injury, drug-induced polyuria (e.g. lithium-induced NDI), compulsive water drinking (polydipsia) and diseases associated with electrolyte disorders (hypokalemia and hypercalcemia). Conversely, upregulation and enhanced apical tra cking of AQP2 is involved in diseases associated with water retention such as congestive heart failure.
