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Nephrology

Advanced diuresis

Loops have a sigmoidal threshold. If no UOP, double the dose — do not give the same subthreshold dose q6h.

Spencer Flynn5 min6 questions2 trials

General principles

Daily standing weights. Sodium 2 g/day plus fluid restriction 1.5–2 L. Loops have a sigmoidal dose-response (a threshold effect) — if there is no UOP, double the dose. Do not give the same subthreshold dose every 6 hours and call it a failure.

  • If UOP is adequate but volume is not improving: tighten Na/fluid restriction and increase diuretic frequency.
  • Transient ↑ in serum Cr is common (~20% in DOSE-AHF, ) and can be tolerated if decongestion is working. Diuresis did not worsen renal function; it associated with better HF outcomes (; ).

Stepwise approach in heart failure

Sequential nephron blockade (NEJM 2017;377:1964)
  1. 1

    IV loop

    Start 2–2.5× the home dose as IV furosemide (e.g. home 80 mg PO → ~80–100 mg IV), or Cr × 40 as IV furosemide (Cr 3 → lasix 120 mg IV).

  2. 2

    Reassess in 1–2 h; double until it works

    Adequate dose = brisk diuresis, goal >100–150 mL/h. A gtt is allowed (bolus when you start and every time you uptitrate) but is not more effective than boluses in ADHF (DOSE, ).

  3. 3

    Augment (SNB)

    Pick the add-on by severity, setting, labs, and your ability to replete Mg/K. Chlorothiazide for a short inpatient challenge (also helps hypernatremia). Metolazone when you need longer augmentation, inpatient or outpatient (also helps hypernatremia). Acetazolamide 500 mg IV daily on top of a loop, especially if metabolic alkalosis is limiting diuresis (↑HCO3, pH >7.45) — () showed better decongestion; caution in COPD, acidosis, sulfa allergy. MRAs: spironolactone 12.5–200 mg or eplerenone 25–50 mg daily (CHF/cirrhosis); ↑K, gynecomastia ~10% with spironolactone only; useful if you need to raise K and only want minor augmentation. SGLT2i: modest diuretic effect, often started nearer discharge (); you may need to drop the maintenance loop. Caution with frequent UTIs, AUD, prior DKA, and poor PO intake.

  4. 4

    Ultrafiltration / RRT

    Nephrology for short-term UF/RRT as a to recovery or advanced therapies. : UF is not first-line.

  5. 5

    Discharge loop

    No strong evidence to prefer torsemide over PO furosemide (TRANSFORM-HF, ). Recalibrate the maintenance dose if they leave on an MRA or SGLT2i.

  6. 6

    Replete K and Mg

    Standing repletion or a higher MRA on the way out. Metolazone can crater K and Na — check labs.

Loops (diuretic > natriuretic)Thiazides (natriuretic > diuretic)
ExamplesFurosemide, torsemide, bumetanideChlorthalidone, HCTZ, metolazone (PO), chlorothiazide (PO/IV)
MechanismInhibit NKCC2 in the thick ascending limb → ↓Na reabsorption and “break” the medullary concentrating gradientInhibit NCC in the DCT → ↓Na reabsorption and prevent urinary dilution
PO bioavailabilityFurosemide 20–50%; torsemide 80–90%; bumetanide 80%Variable
DurationFurosemide ~6 h; torsemide 6–8 h; bumetanide 4–6 hHCTZ 6–12 h; chlorthalidone 24–48 h; metolazone 24 h; IV chlorothiazide 2 h
Dosing1 mg bumetanide IV/PO = 20 mg torsemide PO = 20 mg furosemide IV = 40 mg furosemide PO. Dose BID–QID to avoid the anti-natriuresis of once-daily dosing ( Fig. 2C).Metolazone 2.5–10 mg PO or chlorothiazide 500–1,000 mg IV 30 min before the loop to disable DCT Na reabsorption (sequential nephron blockade).
Side effects↑Na, ↓K, ↓Mg, ↓Ca, ↑urate, ↑HCO3, ototoxicity, allergy; bumetanide myalgias↓Na (avoid in SIADH), ↓K, ↓Mg, ↑Ca, ↑urate, ↑glucose, HLD, pancreatitis

Disease-specific resistance

ConditionMechanismTreatment
CKD / AKI↓GFR → ↓delivery of diuretic to the nephron. Organic acids accumulate, injure the PCT, and compete with diuretics → higher doses needed.High-dose loop ± thiazide. Prefer furosemide in CKD (renal excretion, long half-life).
Chronic diuretic use“Braking”: compensatory DCT hypertrophy → ↑ distal Na reabsorption.Add metolazone or chlorothiazide.
CHF / ADHFGI edema → ↓ absorption of PO diuretics. High sympathetic tone → ↑RAAS, Na reabsorption.Use IV. DOSE (): no difference in symptoms or renal function for drip vs bolus. Consider SNB.
↓ Albumin / nephrotic syndromeLoop diuretic (albumin-bound) leaks out of the vasculature (↑Vd) → ↓ delivery to the nephron.Consider bumetanide (less albumin-binding). No evidence that albumin plus a loop helps.
Cirrhosis↓ delivery with hypoalbuminemia. Splanchnic vasodilation → ↓EABV → renal hypoperfusion. SNS and RAAS → ↑Na reabsorption.Caution with IV diuretics unless respiratory distress — rapid fluid shifts. 5:2 spironolactone:furosemide ratio to stay eukalemic. See ESLD: Ascites.
Loop / thiazide allergyLarge sulfonamide groups, but limited cross-reactivity with other sulfa drugs.Rotate to a different loop or thiazide. If the reaction persists → ethacrynic acid (50 mg = bumetanide 1 mg).