What are the guidelines to treat edema in nephritic syndrome for children and adults?

Guidelines for Treating Edema in Nephritic Syndrome

Note: The question asks about "nephritic syndrome," but the provided evidence exclusively addresses "nephrotic syndrome" - these are distinct clinical entities. Nephritic syndrome (characterized by hematuria, hypertension, and mild proteinuria) has different edema management than nephrotic syndrome (characterized by heavy proteinuria, hypoalbuminemia, and severe edema). The following recommendations are based on the available evidence for nephrotic syndrome, as no specific guidelines for nephritic syndrome edema were provided.

First-Line Treatment Approach

Start with loop diuretics as first-line therapy, combined with strict sodium restriction to <2.0 g/day (<90 mmol/day). 1

Initial Loop Diuretic Dosing

Adults:

• Begin furosemide with twice-daily dosing preferred over once-daily dosing 1
• Once-daily dosing may be acceptable if GFR is reduced 1
• Increase dose until clinically significant diuresis occurs or maximum effective dose is reached 1
• Switch to longer-acting loop diuretics (bumetanide or torsemide) if concerned about furosemide treatment failure or oral bioavailability issues 1

Children:

• Start furosemide at 0.5-2 mg/kg per dose intravenously or orally, up to 6 times daily (maximum 10 mg/kg/day) based on degree of edema and diuresis achieved 1
• Critical safety threshold: High doses >6 mg/kg/day should NOT be given for longer than 1 week due to ototoxicity risk 1
• Infusions must be administered over 5-30 minutes to avoid hearing loss 1
• In stable pediatric patients, oral furosemide 2-5 mg/kg per day can be used for maintenance 1

Sequential Escalation for Resistant Edema

When loop diuretics alone are insufficient, add mechanistically different diuretics for synergistic effect. 1

Combination Diuretic Therapy

Thiazide diuretics:

• All thiazide-like diuretics in high doses are equally effective; none is preferred 1
• Administer with oral or IV loop diuretic to impair distal sodium reabsorption and improve diuretic response 1

Potassium-sparing diuretics:

• Amiloride is preferable to spironolactone because urinary proteases (plasmin) directly activate the epithelial sodium channel (ENaC) independent of mineralocorticoid receptors 1
• Amiloride provides improvement in edema/hypertension, counters hypokalemia from loop or thiazide diuretics, and helps with metabolic alkalosis 1
• Spironolactone may be used but is less mechanistically appropriate 1

Acetazolamide:

• May be helpful for metabolic alkalosis but is a weak diuretic 1

Albumin Administration: When and How

Albumin should be reserved for specific clinical indications, NOT based on serum albumin levels alone. 1

Indications for Albumin Use

In children, use albumin infusions ONLY for clinical indicators of hypovolemia: 1

• Oliguria
• Acute kidney injury
• Prolonged capillary refill time
• Tachycardia
• Hypotension
• Abdominal discomfort
• Failure to thrive

Albumin dosing:

• In severe disease, daily albumin infusions of 1-4 g/kg may be initiated 1
• Consider IV furosemide bolus (0.5-2 mg/kg) at the end of each albumin infusion in absence of marked hypovolemia or hyponatremia 1

Evidence on Furosemide-Albumin Combination

The evidence for routine furosemide-albumin combination is mixed:

• A 2022 systematic review found greater urine excretion with furosemide plus albumin versus furosemide alone (SMD 0.85,95% CI 0.33-1.38), but results for sodium excretion were inconclusive 2
• Current evidence is insufficient to make definitive conclusions about routine albumin use 2

Critical Monitoring Requirements

Monitor closely for adverse effects: 1

• Hypokalemia with thiazide and loop diuretics 1
• Hyponatremia with thiazide diuretics 1
• Impaired GFR 1
• Hyperkalemia with spironolactone/eplerenone, especially if combined with RAS blockade 1
• Volume depletion, especially in pediatric/elderly patients 1

Required monitoring parameters: 1

• Fluid status
• Electrolytes (potassium, sodium)
• Blood pressure
• Kidney function (diuresis and estimated GFR)

Assessing Volume Status Before Treatment

Determining intravascular volume status is crucial for treatment strategy. 3

A 2009 prospective study demonstrated that fractional excretion of sodium (FeNa) can distinguish volume-contracted from volume-expanded patients:

• FeNa <0.2% indicates volume contraction 3
• Volume-contracted patients benefit from IV albumin plus furosemide 3
• Volume-expanded patients can be safely treated with diuretics alone (IV furosemide and oral spironolactone) 3
• Both approaches showed no difference in hospital stay or weight loss 3

Strategies for Diuretic-Resistant Patients

If standard therapy fails, escalate sequentially: 1

1. Amiloride (reduces potassium loss and may improve diuresis) 1
2. Acetazolamide (helps treat metabolic alkalosis) 1
3. Loop diuretics in combination with IV albumin 1
4. Loop diuretics (bolus or infusion) alone 1
5. Ultrafiltration 1
6. Hemodialysis 1

Critical Safety Warnings

Absolute contraindications to diuretics: 1

• Furosemide must be stopped in case of anuria 1
• Use diuretics with caution and only in intravascular fluid overload (good peripheral perfusion and high blood pressure) 1
• Diuretics could induce or increase hypovolemia and promote thrombosis 1

Pediatric-specific warnings:

• Avoid intravenous fluids and saline; concentrate oral fluid intake if necessary 1
• Avoid central venous lines when possible due to high thrombosis risk 1

Adjunctive Therapy

ACE inhibitors or ARBs should be used as first-line therapy for patients with both hypertension and proteinuria. 1

• Use maximally tolerated or allowed dose 1
• Do not stop with modest and stable increase in serum creatinine (up to 30%) 1
• Stop if kidney function continues to worsen or refractory hyperkalemia develops 1
• Do not start ACEi/ARB in patients with abrupt onset nephrotic syndrome as these can cause AKI, especially in minimal change disease 1