Potassium excretion during antinatriuresis: perspective from a distal nephron model

Weinstein, Alan M.

doi:10.1152/ajprenal.00528.2011

Cited by 20 publications

(22 citation statements)

References 63 publications

(70 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…*In addition to changes in entering concentrations, the cell-surface expression of ENaC channels and Na ϩ -K ϩ -ATPase pumps was increased twofold for the "furosemide and high aldosterone" and "volume depletion" simulations. luminal concentration of Na ϩ at the DCT2 entrance was diminished by 40% (and that of Cl Ϫ was adjusted accordingly), and the cell-surface expression of ENaC and Na ϩ -K ϩ -ATPase was increased twofold, as suggested by a recent model of the distal nephron (66). As a consequence of increased Na ϩ reabsorption and the Na ϩ /Ca 2ϩ coupling, the predicted J Ca then increased to 3.0 pmol·min Ϫ1 ·mm Ϫ1 , and the Ca 2ϩ load delivered downstream to the CCD was negligible (Table 6).…”

Section: Effects Of Furosemide and Volume Depletionmentioning

confidence: 88%

Calcium reabsorption in the distal tubule: regulation by sodium, pH, and flow

Bonny

Edwards

2013

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

We developed a mathematical model of Ca(2+) transport along the late distal convoluted tubule (DCT2) and the connecting tubule (CNT) to investigate the mechanisms that regulate Ca(2+) reabsorption in the DCT2-CNT. The model accounts for apical Ca(2+) influx across transient receptor potential vanilloid 5 (TRPV5) channels and basolateral Ca(2+) efflux via plasma membrane Ca(2+)-ATPase pumps and type 1 Na(+)/Ca(2+) exchangers (NCX1). Model simulations reproduce experimentally observed variations in Ca(2+) uptake as a function of extracellular pH, Na(+), and Mg(2+) concentration. Our results indicate that amiloride enhances Ca(2+) reabsorption in the DCT2-CNT predominantly by increasing the driving force across NCX1, thereby stimulating Ca(2+) efflux. They also suggest that because aldosterone upregulates both apical and basolateral Na(+) transport pathways, it has a lesser impact on Ca(2+) reabsorption than amiloride. Conversely, the model predicts that full NCX1 inhibition and parathyroidectomy each augment the Ca(2+) load delivered to the collecting duct severalfold. In addition, our results suggest that regulation of TRPV5 activity by luminal pH has a small impact, per se, on transepithelial Ca(2+) fluxes; the reduction in Ca(2+) reabsorption induced by metabolic acidosis likely stems from decreases in TRPV5 expression. In contrast, elevations in luminal Ca(2+) are predicted to significantly decrease TRPV5 activity via the Ca(2+)-sensing receptor. Nevertheless, following the administration of furosemide, the calcium-sensing receptor-mediated increase in Ca(2+) reabsorption in the DCT2-CNT is calculated to be insufficient to prevent hypercalciuria. Altogether, our model predicts complex interactions between calcium and sodium reabsorption in the DCT2-CNT.

show abstract

Section: Effects Of Furosemide and Volume Depletionmentioning

confidence: 88%

Calcium reabsorption in the distal tubule: regulation by sodium, pH, and flow

Bonny

Edwards

2013

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

show abstract

“…Although the underlying mechanism for the K + -induced downregulation of NCC is unclear, it likely contributes to the maintenance of K + balance because it augments Na + delivery to the ENaC-expressing ASDN in which then more luminal Na + is available for electrogenic Na + reabsorption in exchange for K + secretion. 5,52 Nevertheless, a recent renal clearance study with thiazide-treated mice pointed out that lowered NCC activity per se is not sufficient to activate electrogenic Na + reabsorption in the ASDN and to induce a significant kaliuresis. 53 Other renal adaptation mechanisms, including an activation of ROMK and ENaC, might be needed as well.…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of Renal Control of Potassium Homeostasis in Complete Aldosterone Deficiency

Todkar

Picard²,

Loffing‐Cueni³

et al. 2015

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Aldosterone-independent mechanisms may contribute to K + homeostasis. We studied aldosterone synthase knockout (AS 2/2 ) mice to define renal control mechanisms of K + homeostasis in complete aldosterone deficiency. AS 2/2 mice were normokalemic and tolerated a physiologic dietary K + load (2% K + , 2 days) without signs of illness, except some degree of polyuria. With supraphysiologic K + intake (5% K + ), AS 2/2 mice decompensated and became hyperkalemic. High-K + diets induced upregulation of the renal outer medullary K + channel in AS 2/2 mice, whereas upregulation of the epithelial sodium channel (ENaC) sufficient to increase the electrochemical driving force for K + excretion was detected only with a 2% K + diet. Phosphorylation of the thiazide-sensitive NaCl cotransporter was consistently lower in AS 2/2 mice than in AS +/+ mice and was downregulated in mice of both genotypes in response to increased K + intake.Inhibition of the angiotensin II type 1 receptor reduced renal creatinine clearance and apical ENaC localization, and caused severe hyperkalemia in AS 2/2 mice. In contrast with the kidney, the distal colon of AS 2/2 mice did not respond to dietary K + loading, as indicated by Ussing-type chamber experiments. Thus, renal adaptation to a physiologic, but not supraphysiologic, K + load can be achieved in aldosterone deficiency by aldosteroneindependent activation of the renal outer medullary K + channel and ENaC, to which angiotensin II may contribute. Enhanced urinary flow and reduced activity of the thiazide-sensitive NaCl cotransporter may support renal adaptation by activation of flow-dependent K + secretion and increased intratubular availability of Na + that can be reabsorbed in exchange for K + secreted.

show abstract

“…We assume that interstitial concentrations vary linearly between the cortico-medullary junction and the OM-IM boundary and between the OM-IM boundary and the papillary tip. The interstitial fluid in the cortex is taken to be homogeneous, with one exception: following the approach of Weinstein (54,55), we assume that there is a NH 3 /NH 4 ϩ concentration gradient in the cortex. The total interstitial concentration of ammonia (NH 3 ϩ NH 4 ϩ ) is taken to increase from 0.2 mM in the upper cortex to 1.0 mM at the corticomedullary boundary.…”

Section: Other Model Assumptionsmentioning

confidence: 99%

Predicted consequences of diabetes and SGLT inhibition on transport and oxygen consumption along a rat nephron

Layton

Vallon

Edwards

2016

American Journal of Physiology-Renal Physiology

129

152

View full text Add to dashboard Cite

Diabetes increases the reabsorption of Na(+) (TNa) and glucose via the sodium-glucose cotransporter SGLT2 in the early proximal tubule (S1-S2 segments) of the renal cortex. SGLT2 inhibitors enhance glucose excretion and lower hyperglycemia in diabetes. We aimed to investigate how diabetes and SGLT2 inhibition affect TNa and sodium transport-dependent oxygen consumption [Formula: see text] along the whole nephron. To do so, we developed a mathematical model of water and solute transport from the Bowman space to the papillary tip of a superficial nephron of the rat kidney. Model simulations indicate that, in the nondiabetic kidney, acute and chronic SGLT2 inhibition enhances active TNa in all nephron segments, thereby raising [Formula: see text] by 5-12% in the cortex and medulla. Diabetes increases overall TNa and [Formula: see text] by ∼50 and 100%, mainly because it enhances glomerular filtration rate (GFR) and transport load. In diabetes, acute and chronic SGLT2 inhibition lowers [Formula: see text] in the cortex by ∼30%, due to GFR reduction that lowers proximal tubule active TNa, but raises [Formula: see text] in the medulla by ∼7%. In the medulla specifically, chronic SGLT2 inhibition is predicted to increase [Formula: see text] by 26% in late proximal tubules (S3 segments), by 2% in medullary thick ascending limbs (mTAL), and by 9 and 21% in outer and inner medullary collecting ducts (OMCD and IMCD), respectively. Additional blockade of SGLT1 in S3 segments enhances glucose excretion, reduces [Formula: see text] by 33% in S3 segments, and raises [Formula: see text] by <1% in mTAL, OMCD, and IMCD. In summary, the model predicts that SGLT2 blockade in diabetes lowers cortical [Formula: see text] and raises medullary [Formula: see text], particularly in S3 segments.

show abstract

Potassium excretion during antinatriuresis: perspective from a distal nephron model

Abstract: Weinstein AM. Potassium excretion during antinatriuresis: perspective from a distal nephron model.

Cited by 20 publications

References 63 publications

Calcium reabsorption in the distal tubule: regulation by sodium, pH, and flow

Calcium reabsorption in the distal tubule: regulation by sodium, pH, and flow

Mechanisms of Renal Control of Potassium Homeostasis in Complete Aldosterone Deficiency

Predicted consequences of diabetes and SGLT inhibition on transport and oxygen consumption along a rat nephron

Contact Info

Product

Resources

About