Fig 1.
Kinetic model of the renal NKCC2 cotransporter.
kj’s, off-binding rate constants, on-binding rate constants not shown. kff, kbf, kfe, and kbe, translocation constant rates; Ej, contransporter density of state j.
Table 1.
Nephron segment lengths and luminal diameters.
Table 2.
Interstitial concentrations (in mM, unless stated otherwise).
Table 3.
Urine flow (per kidney) and composition, obtained under differing conditions.
*Model with human GFR and anatomical parameters, but rat transporter densities and permeabilities.
Fig 2.
Total delivery of key solutes (A–G) and fluid (H) to the beginning of individual nephron segments, given per kidney.
Model predicts that the majority of key solutes and volume are reabsorbed by the proximal tubule (PT). The distal tubular segments are responsible for the secretion of K+ and acid species. DL, descending limb; mTAL, medullary thick ascending limb; DCT, distal convoluted tubule; CNT, connecting duct; CCD, cortical collecting duct. TA, titratable acid. Insets reproduce distal segment and urine values.
Fig 3.
Profiles of tubular fluid solute concentrations (A–D), osmolality (E), and pH (F).
Solid black lines, superficial nephron. Solid line, luminal fluid solute concentrations, pH, and osmolality. Dashed lines, interstitial values. PT, proximal tubule; DL, descending limb; LDL/LAL, thin descending/ascending limb; TAL, thick ascending limb; DCT, distal convoluted tubule; CNT, connecting duct; CD, collecting duct.
Fig 4.
Impact of varying SNGFR on segmental delivery of Na+, K+, Cl−, and fluid, given per kidney.
A higher SNGFR enhances solute and volume deliveries, with the effect proportionally larger in distal segments. Notations are analogous to Fig 2. Insets reproduce distal segment and urine values.
Fig 5.
Impact of varying SNGFR on predicted transport of Na+, K+, Cl−, and fluid, given per kidney.
Positive values denote reabsorption. Notably, a 10% increase in SNGFR doubles K+ secretion along the connecting tubules. Insets reproduce distal segment and urine values.
Fig 6.
Fractional glucose flow along the proximal tubule (PT), obtained for baseline conditions and with SGLT2 inhibition.
Under baseline conditions, the SGLT2 reabsorbed ∼90% of the filtered glucose, with the remaining glucose reabsorbed via the SGLT1 along the S3 segment. With SGLT2 blockade, 56% of the filtered glucose is reabsorbed, primarily via the SGLT1.
Fig 7.
Impact of SGLT2 and NKCC2 inhibition on segmental delivery of Na+, K+, Cl−, and fluid, given per kidney.
Notations are analogous to Fig 2. SGLT2 inhibition lowers proximal convoluted tubular transport, whereas NKCC2 inhibition lowers thick ascending limb NaC; transport; both result in diuresis, natriuresis, and kaliuresis. Insets reproduce distal segment and urine values.
Fig 8.
Fractional Na+ flow along the thick ascending limb (TAL), obtained for baseline conditions and with NKCC2 inhibition.