A 45-year-old woman comes to the office due to polyuria and nocturia. She has no fever, dysuria, or abdominal pain. The patient has no significant medical problems and takes no medications. Her temperature is 36.7 C (98 F), blood pressure is 120/80 mm Hg, and pulse is 76/min. The patient's mucous membranes appear dry. The remainder of her physical examination is normal. Her urine output and osmolality remain unchanged with water deprivation for several hours, but after administration of desmopressin, urine output decreases and urine osmolality increases. Renal clearance of which of the following substances would decrease the most after this patient's injection?
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Polyuria that resolves with the administration of desmopressin (DDAVP, synthetic analogue of vasopressin) is likely secondary to deficient vasopressin secretion (central diabetes insipidus). Vasopressin produces a V2 receptor-mediated increase in water permeability within the cortical and medullary collecting ducts. As water leaves the tubular fluid, urea concentration greatly increases in these tubular segments. Although the cortical collecting duct is impermeable to urea, vasopressin activates urea transporters in the medullary collecting duct, increasing urea reabsorption and decreasing renal urea clearance. This passive reabsorption of urea into the medullary interstitium in the presence of ADH significantly increases the medullary osmotic gradient, allowing the production of maximally concentrated urine.
(Choice A) The majority of filtered calcium is passively absorbed in the proximal tubule and ascending limb of Henle's loop. Further calcium reabsorption by the distal and collecting ducts is stimulated by parathyroid hormone (not vasopressin).
(Choice B) Creatinine is freely filtered by the glomerulus, and a small amount is also secreted by the proximal tubule. No further secretion or reabsorption occurs beyond the proximal tubule.
(Choice C) Glucose is filtered in the glomerulus and fully reabsorbed in the proximal tubule as long as the filtered glucose is lower than the transport maximum (Tm). Sodium-glucose cotransporter-2 (SGLT-2) receptor inhibitors act on the tubular receptors to lower the Tm of glucose and may be used as third-line agents in type 2 diabetes mellitus.
(Choice D) Para-amino hippuric (PAH) acid is filtered in the glomerulus and nearly completely secreted by the proximal tubules without significant tubular reabsorption. PAH clearance depends on renal plasma flow. Unlike vasopressin, desmopressin selectively activates V2 receptors and does not cause vasoconstriction (mediated by V1 receptors).
Educational objective:
Vasopressin and desmopressin cause a V2 receptor-mediated increase in water and urea permeability at the inner medullary collecting duct. The resulting rise in urea reabsorption (decreased urea clearance) enhances the medullary osmotic gradient, allowing the production of maximally concentrated urine.