Changes in the Sodium and Potassium Transporters in the Course of Chronic Renal Failure

Kim, Sejoong; Heo, Nam Ju; Jung, Ji Yong; Son, Maeng-Hyun; Jang, Hye Ryoun; Lee, Jay Wook; Oh, Yun Kyu; Na, Ki Young; Joo, Kwon Wook; Han, Jin Suk

doi:10.1159/000314542

Cited by 23 publications

(25 citation statements)

References 61 publications

(46 reference statements)

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“…Plasma and urine osmolality were measured with a cryoscopic osmometer (Osmomat 030-D-M; Gonotec, Berlin, Germany). The glomerular filtration rate (GFR) was calculated using the average of urea clearance and creatinine clearance (7). …”

Section: Methodsmentioning

confidence: 99%

“…Selected bands from these gels were scanned (GS-700 Imaging Densitometry; Bio-Rad) to determine the density (Molecular Analyst version 1.5; Bio-Rad), and relative amounts of protein were loaded into each lane. Finally, protein concentrations were corrected to reflect these measurements and were subjected to immunoblot analysis, using a previously described method (7). …”

Section: Methodsmentioning

confidence: 99%

“…Affinity-purified polyclonal antibodies against NHE3, NKCC2, NCC, ENaC-α, ENaC-γ, NBC, pendrin, and H-ATPase were used as described in a previous study (7, 14). Affinity-purified polyclonal antibodies against Na-glucose cotransporter-1 (SGLT1; AB1352; Millipore Corp., Billerica, MA, USA), ENaC-β (sc-21013; Santa Cruz Biotechnology, Inc., Santa Cruz, CA, USA), and Na-K-ATPase (05-396; Millipore Corp.) were also used.…”

Section: Methodsmentioning

confidence: 99%

“…Luminal Na/H exchanger type 3 (NHE3) is responsible for a significant portion of renal Na + and HCO 3 - absorption (7). NHE3 is variably expressed depending on the pathologic condition and was increased in adriamycin-nephropathy models (8).…”

Section: Introductionmentioning

confidence: 99%

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Alkali Therapy Attenuates the Progression of Kidney Injury via Na/H Exchanger Inhibition in 5/6 Nephrectomized Rats

et al. 2014

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Metabolic acidosis is a cause of renal disease progression, and alkali therapy ameliorates its progression. However, there are few reports on the role of renal acid-base transporters during alkali therapy. We evaluated the effect of sodium bicarbonate therapy and the role of acid-base transporters on renal disease progression in rats with a remnant kidney. Sprague-Dawley rats consumed dietary sodium bicarbonate (NaHCO3) or sodium chloride (NaCl) with 20% casein after a 5/6 nephrectomy. After being provided with a casein diet, the NaHCO3-treated group had higher levels of serum bicarbonate than the control group. At week 4, the glomerular filtration rate in the NaHCO3 group was higher than that in the NaCl group, and the difference became prominent at week 10. The glomerulosclerosis and tubulointerstitial damage indices in the NaHCO3 group were less severe compared with controls at week 4 and 10. The expression of the Na/H exchanger (NHE) was decreased, and apical reactivity was decreased in the NaHCO3 group, compared with the NaCl group. Endothelin-1 levels in the kidney were also decreased in the NaHCO3 group. Dietary sodium bicarbonate has the effects of ameliorating renal disease progression, which may be related to the altered expression of NHE in the remaining kidney.Graphical Abstract

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Alkali Therapy Attenuates the Progression of Kidney Injury via Na/H Exchanger Inhibition in 5/6 Nephrectomized Rats

et al. 2014

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“…Data about CKD and expression of NKCC2 are limited. One study demonstrated an initial increase in NKCC2 expression after 5/6th nephrectomy in rats, later returning toward normal (85). Two studies in rats after uninephrectomy and salt loading demonstrated decreased expression of the NKCC2 (73,74).…”

Section: Does Kidney Disease Affect the Actions Of Furosemide?mentioning

confidence: 99%

Everything we always wanted to know about furosemide but were afraid to ask

Huang

Mees

Vos

et al. 2016

American Journal of Physiology-Renal Physiology

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Huang X, Dorhout Mees E, Vos P, Hamza S, Braam B. Everything we always wanted to know about furosemide but were afraid to ask. Am J Physiol Renal Physiol 310: F958 -F971, 2016. First published February 24, 2016 doi:10.1152/ajprenal.00476.2015.-Furosemide is a widely used, potent natriuretic drug, which inhibits the Na ϩ -K ϩ -2Cl Ϫ cotransporter (NKCC)-2 in the ascending limb of the loop of Henle applied to reduce extracellular fluid volume expansion in heart and kidney disease. Undesirable consequences of furosemide, such as worsening of kidney function and unpredictable effects on sodium balance, led to this critical evaluation of how inhibition of NKCC affects renal and cardiovascular physiology. This evaluation reveals important knowledge gaps, involving furosemide as a drug, the function of NKCC2 (and NKCC1), and renal and systemic indirect effects of NKCC inhibition. Regarding renal effects, renal blood flow and glomerular filtration rate could become compromised by activation of tubuloglomerular feedback or by renin release, particularly if renal function is already compromised. Modulation of the intrarenal renin angiotensin system, however, is ill-defined. Regarding systemic effects, vasodilation followed by nonspecific NKCC inhibition and changes in venous compliance are not well understood. Repetitive administration of furosemide induces short-term (braking phenomenon, acute diuretic resistance) and long-term (chronic diuretic resistance) adaptations, of which the mechanisms are not well known. Modulation of NKCC2 expression and activity in kidney and heart failure is ill-defined. Lastly, furosemide's effects on cutaneous sodium stores and on uric acid levels could be beneficial or detrimental. Concluding, a considerable knowledge gap is identified regarding a potent drug with a relatively specific renal target, NKCC2, and renal and systemic actions. Resolving these questions would increase the understanding of NKCCs and their actions and improve rational use of furosemide in pathophysiology of fluid volume expansion. extracellular fluid volume; natriuresis; renal function; chronic kidney disease; heart failure DIURETICS BLOCKING THE Na ϩ -K ϩ -2Cl Ϫ cotransporter (NKCC) have an important place in the treatment of fluid overload, specifically in the context of kidney disease and heart failure (64). Of the drugs that inhibit the NKCC2 in the loop of Henle (furosemide, bumetanide, torsemide, ethacrynic acid), furosemide is most commonly applied (66) and Ͼ40 million prescriptions are dispensed every year in the USA (66a). However, many uncertainties remain about intrarenal and systemic actions of furosemide, including its two main targets NKCC1 and NKCC2.Clinically, there are a number of undesirable consequences of the use of furosemide, of which the pathophysiological mechanisms have not been sufficiently investigated. Furosemide has been associated with worsening of kidney function in patients treated for volume overload admitted for acute heart failure (104) and even glomerular filtration rate (GFR) ...

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Optimizing SGLT inhibitor treatment for diabetes with chronic kidney diseases

Layton

2018

Biol Cybern

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Diabetes induces glomerular hyperfiltration, affects kidney function, and may lead to chronic kidney diseases. A novel therapeutic treatment for diabetic patients targets the sodium-glucose cotransporter isoform 2 (SGLT2) in the kidney. SGLT2 inhibitors enhance urinary glucose, [Formula: see text] and fluid excretion and lower hyperglycemia in diabetes by inhibiting [Formula: see text] and glucose reabsorption along the proximal convoluted tubule. A goal of this study is to predict the effects of SGLT2 inhibitors in diabetic patients with and without chronic kidney diseases. To that end, we applied computational rat kidney models to assess how SGLT2 inhibition affects renal solute transport and metabolism when nephron population are normal or reduced (the latter simulates chronic kidney disease). The model predicts that SGLT2 inhibition induces glucosuria and natriuresis, with those effects enhanced in a remnant kidney. The model also predicts that the [Formula: see text] transport load and thus oxygen consumption of the S3 segment are increased under SGLT2 inhibition, a consequence that may increase the risk of hypoxia for that segment. To protect the vulnerable S3 segment, we explore dual SGLT2/SGLT1 inhibition and seek to determine the optimal combination that would yield sufficient urinary glucose excretion while limiting the metabolic load on the S3 segment. The model predicts that the optimal combination of SGLT2/SGLT1 inhibition lowers the oxygen requirements of key tubular segments, but decreases urine flow and [Formula: see text] excretion; the latter effect may limit the cardiovascular protection of the treatment.

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Changes in the Sodium and Potassium Transporters in the Course of Chronic Renal Failure

Cited by 23 publications

References 61 publications

Alkali Therapy Attenuates the Progression of Kidney Injury via Na/H Exchanger Inhibition in 5/6 Nephrectomized Rats

Alkali Therapy Attenuates the Progression of Kidney Injury via Na/H Exchanger Inhibition in 5/6 Nephrectomized Rats

Everything we always wanted to know about furosemide but were afraid to ask

Optimizing SGLT inhibitor treatment for diabetes with chronic kidney diseases

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