Combined Furosemide and Human Albumin Treatment for Diuretic-Resistant Edema

Elwell, Rowland J.; Spencer, Ann P; Eisele, George

doi:10.1345/aph.1c320

Cited by 45 publications

(31 citation statements)

References 12 publications

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“…In that regard, it is noted that Agarwal et al (2) showed that displacing furosemide from plasma proteins with a sulphonomide (sulfisoxazole) did not correct resistance in nephrotic patients. There is still controversy about whether and how albumin infusion could increase the natriuretic actions of furosemide in the nephrotic state (45). Taken together, diminished reabsorption, increased T½, and high-grade proteinuria in patients with CKD could limit the natriuretic response.…”

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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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

View full text Add to dashboard Cite

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“…The reasons proposed for the lack of patient response to diuretics include a decreased delivery of the diuretics into the tubular lumen, hypoalbuminemia, and binding of the diuretics to urinary albumin. Lack of compliance with oral medications, impaired bioavailability, and reduced glomerular filtration rate also lead to a suboptimal response to diuretics [7,8].…”

Section: Introductionmentioning

confidence: 99%

“…The contribution of hypoalbuminemia to impaired diuretic responsiveness can be overcome by administering larger doses of loop diuretics, either orally or intravenously (IV) [8][9][10][11]. This approach results in the excretion of a larger amount of the drug in the urine and, consequently, a greater natriuretic response.…”

Section: Introductionmentioning

confidence: 99%

“…Another clinical option is to infuse loop diuretics in combination with salt-poor human serum albumin. Such concomitant infusions of human albumin mixed with a loop diuretic are effective in enhancing the delivery of the loopacting diuretic to the luminal sites where their action on reabsorption of NaCl occurs [8]. As hypoalbuminemia lowers the amount of the albumin-bound fraction of the diuretic, it also decreases the amount of diuretic delivered to its site of action in the nephron.…”

Section: Introductionmentioning

confidence: 99%

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Randomized cross-over trial comparing albumin and frusemide infusions in nephrotic syndrome

2009

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The contribution of hypoalbuminemia to impaired diuretic responsiveness can be overcome by administering larger doses of loop diuretics. However, the clinical efficacy of the combination of loop-acting diuretics with human albumin remains controversial. In the study reported here, 16 children with nephrotic syndrome and refractory edema were randomized in a cross-over trial to receive either the combination of 20% human albumin and frusemide infusion (HA+FU infusion group) or frusemide infusion alone (FU infusion group). At the end of study, median urine volume was 3.27 [95% confidence interval (CI) 2.04-4.50] ml/kg per hour in the HA+FU infusion group and 1.33 (95% CI 0.79-1.88) ml/kg per hour in the FU infusion group (P = 0.01); the median daily sodium excretion was 58 (95% CI 30-366) mEq and 30 (95% CI 10-122) mEq (P = 0.08), respectively The changes in other variables included weight loss [HA+FU 5.2% (95% CI 3.1-8.8); FU 0.8% (95% CI -1.9 to 4.1); P = 0.006]; urine osmolality [HA+FU 315 (95% CI 220-426) mOsm/kg; FU 368 (95% CI 318-446) mOsm/kg; P = 0.13]; osmolal clearance [HA+FU 1600 (95% CI 916-4140) ml/day; FU 880 (95% CI 510-2105) ml/day; P = 0.01; free water clearance [HA+FU -190 (95% CI -960 to 280) ml/day; FU -162 (95% CI -446 to -70) ml/day; P = 0.18]. The findings from this study suggest that the co-administration of albumin and frusemide infusions is more effective than the administration of frusemide infusion alone in inducing diuresis and natriuresis in patients with nephrotic syndrome.

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“…Therefore, this combination should be reserved for specific groups of patients whose doses of diuretics have been maximized or for cases of severe hypoalbuminemia. 17 The findings from the review by Caraceni et al 34 show that use of human albumin alone for correcting hypoalbuminemia is not backed by scientific evidence. This confirms the stance taken in the guidelines, i.e.…”

Section: Discussionmentioning

confidence: 99%

Economic evaluation of human albumin use in patients with nephrotic syndrome in four Brazilian public hospitals: pharmacoeconomic study

et al. 2017

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CONTEXT AND OBJECTIVE: In 2004, the Brazilian National Health Surveillance Agency (Agência Nacional de Vigilância Sanitária, ANVISA) published a resolution establishing guidelines for albumin use. Although the published data do not indicate any definitive conclusions about the benefits of albumin use in patients with nephrotic syndrome (NS), the guidelines recommend this procedure only in cases of edema that is refractory to use of diuretics.The aim here was to analyze albumin use among patients with nephrotic syndrome. DESIGN AND SETTING: Pharmacoeconomic study conducted in four large public referral hospitals for nephrology services in northeastern Brazil. METHOD: Cost-effectiveness and cost-utility economic evaluations were performed on a concurrent cohort of patients with nephrotic syndrome, who were divided into two groups according to compliance or noncompliance with the guidelines. Quality-of-life data were obtained from the SF36 and CHQ-PF50 questionnaires.RESULTS: This study enrolled 109 patients (60% adults and 56% women); 41.3% were using albumin in accordance with the guidelines. The weight, diuresis and fluid balance parameters were more cost-effective for patients who adhered to the guidelines. Regarding days of hospitalization avoided, the incremental ratio showed a daily cost of R$ 55.33, and guideline-compliant patients were hospitalized for five days or fewer. The quality of life improved by 8%, and savings of R$ 3,458.13/QALY (quality-adjusted life year) for the healthcare system were generated through guideline compliance. CONCLUSION:The economic analyses of this study demonstrated that there were greater cost benefits for patients whose treatment followed the guidelines. RESUMO

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Combined Furosemide and Human Albumin Treatment for Diuretic-Resistant Edema

Cited by 45 publications

References 12 publications

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

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

Randomized cross-over trial comparing albumin and frusemide infusions in nephrotic syndrome

Economic evaluation of human albumin use in patients with nephrotic syndrome in four Brazilian public hospitals: pharmacoeconomic study

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