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Edt - Slide Thaha MNHU Pentas Final
Edt - Slide Thaha MNHU Pentas Final
Edt - Slide Thaha MNHU Pentas Final
Mochammad Thaha
MNHU & PODIN
Malang
2021
M.Thaha
EPIDEMIOLOGY
& PATOPHYSIOLOGY
M.Thaha
What is diuretic resistance ?
M.Thaha Nature Reviews Nephrology 12, 610–623 (2016) doi:10.1038/nrneph.2016.113 Published online 30 August 2016
Change in body weight
at discharge based on ADHF
National Registry database
Amir Kazory. Cardiorenal Syndrome: Ultrafiltration Therapy for Heart Failure—Trials and Tribulations
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Diuretic dose and long-term outcomes in elderly
patients with heart failure after
hospitalization – Increased Mortality
━━ Low-dose
━━ Mid-dose
━━ High-dose
Survival rate (%)
Ultimately, lack of Transrenal Perfusion Pressure (TPP) will activate the NEUROHORMONAL ACTIVITY
Schefold JC, Filippatos G, Hasenfuss G, Anker SD, von Haehling S. Heart failure and kidney dysfunction: epidemiology, mechanisms and
Thaha management. Nat Rev Nephrol. 2016; 12:610-623
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EXCESSIVE NEUROHORMONAL ACTIVATION, RELEASE OF
VASOCONSTRICTING & SODIUM/WATER RETAINING
FACTORS & ACTIVATION OF THE SNS ARE THE HALLMARK
OF CRS
Verbrugge FH, Mullens W, Tang W. Management of cardio-renal syndrome and diuretic resistance. Curr Treat
Options Cardio Med. (2016)
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DIURETICS
MODE OF ACTIONS AND ISSUES
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Diuretic Options for Decongestions
IV Bolus Continuous
infusion
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2017 AHA Recommendations of Heart Failure
with PRESERVED EF
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2017 KDIGO Recommendations
of the treatments of AKI
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The DOSE Trial
Diuretic Optimization Strategies Evaluation
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Loop Diuretics
Furosemide
▪ Blocks the TAL Na/K/2Cl pump
▪ Better Efficacy in patients with reduced
GFR
▪ Better Bioavailability
▪ Primary Choice
▪ PG, less Neurohormonal, Fena >, less
rebound, switch oral, etc
▪ No current guideline dosing
Cautions: Chronic use -> cellular hypertrophy -> increased Na reabsorption -> Failure of diuresis
l-Qadir et al: Diuretics Dose and Long term Outcomes in Patients with Acute Decompensated Heart Failure.
M.Thaha American Heart Journal 160 (2), 265-271, 2010
EXCESSIVE NEUROHORMONAL ACTIVATION, RELEASE OF
VASOCONSTRICTING & SODIUM/WATER RETAINING
FACTORS & ACTIVATION OF THE SNS ARE THE HALLMARK
OF CRS
Verbrugge FH, Mullens W, Tang W. Management of cardio-renal syndrome and diuretic resistance. Curr Treat
Options Cardio Med. (2016)
M.Thaha
Neurohormonal Activity
Adenosine
Nijst P, Verbrugge FH, Grieten L, et al. The pathophysiological role of interstitial sodium in heart failure. J Am Coll Cardiol. 2015;65:378-388.
.
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What is Braking Phenomenon?
• is an appropriate
homeostatic response
that prevents excessive
volume depletion during
continued diuretic
therapy
• Decreased response to the
action of a diuretic that
results from increased
sodium reabsorption in
other nephron segments
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Efforts in treating diuretic Resistant
Combination of two or more diuretics from different classes may produce an additive or
synergistic mechanism of action and diuretic response, and can be an effective approach in
resistant cases
Without Hypokalemia:
• add metolazone (5 to 10 mg once daily initially, increased to a maximum dose of 20 mg
once daily), hydrochlorothiazide (25 to 50 mg twice daily initially, increased to a
maximum dose of 200 mg per day) is same effective.
• hydrochlorothiazide is given orally in patients treated with an IV loop diuretic, the
thiazide diuretic should precede the loop diuretic by 2-5 hours, since the peak effect of
the thiazide is 4-6 hours after ingestion
With Hypokalemia:
• add a potassium-sparing diuretic first (eg, amiloride or a mineralocorticoid receptor
antagonist). Potassium-sparing diuretics, such as mineralocorticoid receptor
antagonists and amiloride, can help limit potassium wasting, although data
demonstrating their efficacy in reducing extracellular fluid volume are limited
• ESC recommended the dose of spironolactone is 25 to 50 mg once daily.
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Brater and Ellison, 2019
Unproven Strategies that We Should not use
Dopamine
Addition of low dose dopamine on 360 ADHF patients in the large randomized
ROSE-HF trial. The addition of low-dose dopamine did not significantly increase
urine volume or improve decongestion compared with placebo, although it did
increase the incidence of arrhythmias (7% in the dopamine group vs 1% in the
placebo group, P<0.001)
Albumin
Jentzer JC, Chawla LS, et al. A clinical approach to the acute cardiorenal syndrome. Crit Care Clin. 2015; 31: 658-703
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When should we initiate UF?
Ultrafiltration in patients
with heart failure appears
to be indicated primarily
when dialytic treatment is
indicated in patients with
combined heart failure &
kidney failure.
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ROLE OF AVP ANTAGONIS
Tamaki, 2017
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Vasopressin Regulation
of Water Reabsorption from Renal Tubular Cells
Collecting duct
Vasa recta
ATP
GTP AQP2 Exocytic
(Gs) Insertion
cAMP
PKA
Recycling Endocytic
vesicle Retrieval
57.7%
(n = 15)
26.9%
(n = 7)
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