Magnetic resonance–determined sodium removal from tissue stores in hemodialysis patients

Dahlmann, Anke; Dörfelt, Kathrin; Eicher, Florian; Linz, Peter; Kopp, Christoph W.; Mössinger, Irina; Horn, Stephan; Büschges-Seraphin, Beatrix; Wabel, Peter; Hammon, Matthias; Cavallaro, Alexander; Eckardt, Kai‐Uwe; Kotanko, Peter; Levin, Nathan W.; Johannes, Bernd; Uder, Michael; Luft, Friedrich C.; Müller, Dominik N.; Titze, Jens

doi:10.1038/ki.2014.269

Cited by 194 publications

(237 citation statements)

References 43 publications

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“…This situation manifests itself by the low intra-volunteer variance. It should be noted that residual partial volume effects are significantly lower compared to previous results reported for 3.0 T 23 Na MRI in skin (12)(13)(14).…”

Section: Discussioncontrasting

confidence: 45%

“…• 23 Na MRI with a volume RF coil at 3.0 T to resemble the setup reported in recent state-of-the-art 23 Na MR studies (12)(13)(14).…”

Section: Phantom Study: Snr Assessmentmentioning

confidence: 99%

“…We calibrated the method with human tissue that was then ashed and measured with atomic absorption spectrometry (12). We have shown that the proposed 3.0 T approach has clinical utility (12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

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Skin sodium measured with ²³Na MRI at 7.0 T

et al. 2014

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Objective: Skin-sodium storage, as a physiologically important regulatory mechanism for blood pressure, volume regulation, and indeed survival, has recently been rediscovered. This prompted the development of MRI methods to assess sodium storage in humans ( 23 Na-MRI) at 3.0 Tesla. This work examines the feasibility of high in-plane spatial resolution 23 Na MRI in skin at 7.0 T. Methods:A two-channel transceiver RF coil array tailored for skin MRI at 7.0 T (f=78.5MHz) is proposed. Specific absorption rate (SAR) simulations and a thorough assessment of RF power deposition were performed to meet the safety requirements. Human skin was examined in an in vivo feasibility study using 2D gradient echo imaging. Normal male adult volunteers (n=17, mean ± SD = 46 ± 18 years, range: 20-79 years) were investigated.Transverse slices of the calf were imaged with 23 Na MRI using a high in-plane resolution of (0.9 x 0.9) mm 2 . Skin Na + content was determined using external agarose standards covering a physiological-range of Na + concentrations. To assess the intra-subject reproducibility, each volunteer was examined three to five times with each session including a 5 min walk and repositioning/preparation of the subject. Age-dependence of skin Na + content was investigated. Results:The 23 Na RF coil provides improved sensitivity within a range of 1 cm from its surface versus a volume RF coil which facilitates high in-plane spatial resolution imaging of human skin. Intra-subject variability of human skin sodium content in the volunteer population was <10.3%. An age-dependent increase in skin Na + content was observed, r = 0.78). Short abstractThis work demonstrates the feasibility of sub-millimeter in-plane spatial resolution 23 Na MRI in skin at clinically acceptable acquisition times at 7.0 T. Intra-subject variability of human skin sodium content in the volunteer population was <10.3%. An age-dependent increase in skin Na + content was observed (r = 0.78). Assigning sodium stores with 23 Na-MRI techniques could be improved at 7.0 T compared to current 3.0 T technology.-6 -

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Section: Discussioncontrasting

confidence: 45%

“…• 23 Na MRI with a volume RF coil at 3.0 T to resemble the setup reported in recent state-of-the-art 23 Na MR studies (12)(13)(14).…”

Section: Phantom Study: Snr Assessmentmentioning

confidence: 99%

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Skin sodium measured with ²³Na MRI at 7.0 T

et al. 2014

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“…Reducing or individualizing dialysate sodium is now recommended as a means of improving control of sodium balance, volume, and BP in hypertensive patients on hemodialysis (16,18), and it has been shown to reduce IDWG and BP (19). Emerging data from investigations of patients on hemodialysis using magnetic resonance imaging suggest that osmotically inactive sodium is stored in body tissues (20). The potential mobilization of tissue sodium or the effects on whole-body sodium balance caused by reduced uptake of sodium from the gut during tenapanor treatment were not investigated as part of our study.…”

Section: Discussionmentioning

confidence: 99%

Effect of Tenapanor on Interdialytic Weight Gain in Patients on Hemodialysis

Block

Rosenbaum

Leonsson-Zachrisson

et al. 2016

CJASN

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Background and objectives Interdialytic weight gain in patients on hemodialysis is associated with adverse cardiovascular outcomes and increased mortality. The degree of interdialytic weight gain is influenced by sodium intake. We evaluated the effects of tenapanor (AZD1722 and RDX5791), a minimally systemically available inhibitor of the sodium/hydrogen exchanger isoform 3, on interdialytic weight gain in patients with CKD stage 5D treated with hemodialysis.Design, setting, participants, & measurements This phase 2, randomized, double-blind study (NCT01764854; conducted January to September of 2013) enrolled adults on maintenance hemodialysis with interdialytic weight gain $3.0% of postdialysis weight and $2 kg. Patients were randomly assigned (1:1) to receive tenapanor or placebo. The primary end point was change in mean interdialytic weight gain (percentage of baseline postdialysis weight) from baseline (mean across a 2-week run-in period) to week 4. In a subgroup of inpatients, 24-hour stool sodium and stool weight were assessed for 1 week.Results Sixteen patients received 1 week of inpatient treatment (tenapanor, eight; placebo, eight), and 72 patients received 4 weeks of treatment in an outpatient setting (tenapanor, 37; placebo, 35; completers: tenapanor, 31; placebo, 33). In the outpatient cohort, no significant effect on interdialytic weight gain was detected; least squares mean changes in relative interdialytic weight gain from baseline to week 4 were tenapanor, 20.26% (95% confidence interval, 20.57% to 0.06%) and placebo, 20.23% (95% confidence interval, 20.54% to 0.07%; P=0.46). During week 1 (inpatient cohort only), compared with placebo, tenapanor treatment resulted in higher stool sodium content (mean [6SD]: tenapanor, 36.6 [621.8] mmol/d; placebo, 2.8 [62.7] mmol/d; P,0.001) and higher stool weight (tenapanor, 172.5 [668.1] g/d; placebo, 86.3 [630.0] g/d; P,0.01). A similar safety profile was observed across treatment groups with the exception of diarrhea, which occurred more frequently with tenapanor treatment.Conclusions Tenapanor treatment increased stool sodium and weight over placebo in patients undergoing hemodialysis. However, over 4 weeks of treatment, there was no difference in interdialytic weight gain between patients treated with tenapanor and those receiving placebo.

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“…Gradually, evidence is accumulating that the subcutaneous sodium storage is expanded in different disease states, such as hypertension (97) and endstage renal disease (35). A question that is unanswered at this moment is whether any diuretic therapy can mobilize the subcutaneous sodium, and whether this would improve or deteriorate systemic hemodynamic function.…”

Section: F966mentioning

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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Magnetic resonance–determined sodium removal from tissue stores in hemodialysis patients

Cited by 194 publications

References 43 publications

Skin sodium measured with ²³Na MRI at 7.0 T

Skin sodium measured with ²³Na MRI at 7.0 T

Effect of Tenapanor on Interdialytic Weight Gain in Patients on Hemodialysis

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

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Magnetic resonance–determined sodium removal from tissue stores in hemodialysis patients

Cited by 194 publications

References 43 publications

Skin sodium measured with 23Na MRI at 7.0 T

Skin sodium measured with 23Na MRI at 7.0 T

Effect of Tenapanor on Interdialytic Weight Gain in Patients on Hemodialysis

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

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Skin sodium measured with ²³Na MRI at 7.0 T

Skin sodium measured with ²³Na MRI at 7.0 T