Passage
Renal reabsorption of glucose is facilitated by sodium-glucose linked transporters (SGLTs) , which are secondary active transport proteins located in the apical membrane of the proximal tubular cells in the kidney. SGLT activity determines the transport maximum of glucose T_m, the maximum rate at which the kidneys can reabsorb glucose.Excretion of glucose in the urine (glycosuria) occurs when the glomerular filtration rate (GFR) of glucose exceeds the T_m. Glycosuria is a symptom of diabetes mellitus, a disease marked by hyperglycemia (elevated serum glucose) . Uncontrolled hyperglycemia can damage the nerves that innervate urinary tract musculature, resulting in urinary retention (inability to fully empty the bladder) or incontinence (involuntary urine leakage) .Canagliflozin is a SGLT inhibitor used for the treatment for diabetes. The effect of canagliflozin on renal glucose reabsorption was tested in a glucose infusion experiment in patients with type 2 diabetes mellitus (T2DM) . First, researchers measured the participants' fasting serum glucose levels (average ~80 mg/dL) and then began a continuous intravenous infusion of a glucose solution. The rate of glucose infusion was adjusted such that blood glucose concentration steadily rose to 300 mg/dL. Blood and urine glucose concentrations were measured at 30-minute intervals. The experiment was later repeated in the same patients following canagliflozin administration (100 mg, once a day for seven days) . The results of both trials are shown in Figure 1.
Figure 1 Mean urine glucose excretion versus blood glucose concentration in patients with T2DM, with and without canagliflozin treatmentResearchers then estimated the new T_m of glucose following canagliflozin treatment (Figure 2) . Canagliflozin was found to also lower fasting blood glucose in individuals with T2DM. Side effects included weight loss, increased urinary frequency, excessive thirst, and blood pressure reduction.
Figure 2 Mean rate of renal glucose reabsorption versus plasma glucose concentration in patients with T2DM, with and without canagliflozin treatment
-Administration of canagliflozin most directly increases urinary output by increasing the:

Question

Passage
Renal reabsorption of glucose is facilitated by sodium-glucose linked transporters (SGLTs) , which are secondary active transport proteins located in the apical membrane of the proximal tubular cells in the kidney. SGLT activity determines the transport maximum of glucose T_m, the maximum rate at which the kidneys can reabsorb glucose.Excretion of glucose in the urine (glycosuria) occurs when the glomerular filtration rate (GFR) of glucose exceeds the T_m. Glycosuria is a symptom of diabetes mellitus, a disease marked by hyperglycemia (elevated serum glucose) . Uncontrolled hyperglycemia can damage the nerves that innervate urinary tract musculature, resulting in urinary retention (inability to fully empty the bladder) or incontinence (involuntary urine leakage) .Canagliflozin is a SGLT inhibitor used for the treatment for diabetes. The effect of canagliflozin on renal glucose reabsorption was tested in a glucose infusion experiment in patients with type 2 diabetes mellitus (T2DM) . First, researchers measured the participants' fasting serum glucose levels (average ~80 mg/dL) and then began a continuous intravenous infusion of a glucose solution. The rate of glucose infusion was adjusted such that blood glucose concentration steadily rose to 300 mg/dL. Blood and urine glucose concentrations were measured at 30-minute intervals. The experiment was later repeated in the same patients following canagliflozin administration (100 mg, once a day for seven days) . The results of both trials are shown in Figure 1.

Figure 1 Mean urine glucose excretion versus blood glucose concentration in patients with T2DM, with and without canagliflozin treatmentResearchers then estimated the new T_m of glucose following canagliflozin treatment (Figure 2) . Canagliflozin was found to also lower fasting blood glucose in individuals with T2DM. Side effects included weight loss, increased urinary frequency, excessive thirst, and blood pressure reduction.

Figure 2 Mean rate of renal glucose reabsorption versus plasma glucose concentration in patients with T2DM, with and without canagliflozin treatment
-Administration of canagliflozin most directly increases urinary output by increasing the:

Quizplus · Accepted Answer

11ecba2d_0fa8_ad68_a3bf_857a83fac067_MD0008_00 Hydrostatic pressure and osmotic pressure are two opposing forces that regulate fluid movement between capillaries and the tissues that surround them. Hydrostatic pressure is the force exerted by a liquid on the walls of its container. Accordingly, the hydrostatic pressure of blood, or blood pressure (BP), is the force exerted by blood on the vessel walls. This pressure pushes fluid through capillary wall pores and into the interstitial fluid (the extracellular fluid surrounding cells of a tissue). The kidneys regulate BP by increasing water reabsorption (thereby increasing blood volume and, consequently, BP) when BP is low and by decreasing water reabsorption when BP is high. In contrast, osmotic pressure causes a solution to take in water by osmosis, the passive movement of water molecules from an area of low to an area of high solute concentration. Osmotic pressure increases as solute concentration (osmolarity) increases. When blood osmolarity is high, the kidneys respond by increasing water reabsorption and decreasing solute reabsorption. Conversely, when blood osmolarity is low, the kidneys react by decreasing water reabsorption and increasing solute reabsorption. The passage states that SGLTs transport glucose out of the proximal tubule so it can be returned to circulation through the peritubular capillaries. Administration of a SGLT inhibitor prevents glucose reabsorption, increasing solute concentration within the tubule and consequently increasing the osmotic pressure of the tubular filtrate. As a result, water is drawn back into the renal tubule, increasing urine output. (Choice B) Increasing the osmotic pressure of blood in the peritubular capillaries would increase water retention by osmosis and decrease urinary output. (Choice C) According to the passage, SGLT inhibitors can cause a decrease in blood pressure (ie, a decrease in hydrostatic pressure in the renal artery). Decreased hydrostatic pressure would reduce the amount of fluid being filtered into Bowman's capsule from the glomerular capillaries, thereby decreasing (not increasing) overall urine output. (Choice D) Hydrostatic pressure within the glomerulus pushes fluid into Bowman's space. This movement is opposed by the hydrostatic pressure in Bowman's space. Therefore, increasing the hydrostatic pressure in Bowman's space would impede fluid from entering the nephron and would decrease urinary output. Educational objective: The kidneys regulate blood osmolarity, and in turn blood pressure, by selectively modulating the reabsorption and secretion of water and solutes.

Passage Renal Reabsorption of Glucose Is Facilitated by Sodium-Glucose Linked Transporters