What are the indications for thromboprophylaxis, diuretics (such as furosemide), and albumin infusion in a newly diagnosed child with nephrotic syndrome?

Management of Newly Diagnosed Nephrotic Syndrome in Children

In newly diagnosed nephrotic syndrome in children, thromboprophylaxis should be initiated when serum albumin is <20-25 g/L with additional risk factors such as proteinuria >10 g/d, while diuretics should be used cautiously only in cases of intravascular volume overload, and albumin infusions should be administered based on clinical indicators of hypovolemia rather than serum albumin levels alone. 1

Thromboprophylaxis Indications

• Prophylactic anticoagulation should be considered when serum albumin is <20-25 g/L AND any of the following risk factors are present: proteinuria >10 g/d, BMI >35 kg/m², heart failure (NYHA class III or IV), recent surgery, or prolonged immobilization 1
• Full anticoagulation is required for children who have already developed thromboembolic events (venous thrombosis, arterial thrombosis, pulmonary embolus) in the context of nephrotic syndrome 1, 2
• Membranous glomerulonephritis carries a particularly high risk of thromboembolic events compared to other causes of nephrotic syndrome 1, 3
• When central venous access is required for repeated albumin infusions, prophylactic anticoagulation should be administered for as long as the line is in place 1

Anticoagulation Options and Dosing

• Low-dose anticoagulation with low molecular-weight heparin (with dose reduction for creatinine clearance <30 ml/min) or unfractionated heparin 5000 U subcutaneously twice daily is recommended for prophylaxis 1
• For established thromboembolic events, full warfarin anticoagulation is preferred, with intravenous heparin followed by bridging to warfarin 1
• Higher than usual heparin dosing may be required due to antithrombin III urinary loss in nephrotic syndrome 1
• Target INR should be 2-3 for warfarin therapy with frequent monitoring due to fluctuating serum albumin levels 1
• Factor Xa inhibitors have not been systematically studied in nephrotic syndrome and should be avoided due to variable protein binding and urinary clearance 1

Diuretics Indications and Administration

• Diuretics should be used with caution and only in cases of intravascular fluid overload (evidenced by good peripheral perfusion and high blood pressure) 1, 4
• Furosemide is indicated for treatment of edema associated with nephrotic syndrome, particularly when greater diuretic potential is desired 4
• Consider an intravenous bolus of furosemide (0.5-2 mg/kg) at the end of albumin infusions in the absence of marked hypovolemia and/or hyponatraemia 1
• For severe edema, furosemide can be initiated at 0.5-2 mg/kg per dose intravenously or orally up to six times daily (maximum 10 mg/kg per day) 1
• High doses of furosemide (>6 mg/kg/day) should not be given for periods longer than 1 week to avoid hearing loss 1
• In stable patients, oral furosemide at 2-5 mg/kg per day can be combined with a thiazide or potassium-sparing diuretic 1
• If potassium-sparing diuretics are used, ENaC blockers like amiloride are preferable to spironolactone due to direct activation of ENaC by urinary proteases in nephrotic syndrome 1

Albumin Infusion Indications

• Albumin infusions should be administered based on clinical indicators of hypovolemia (oliguria, acute kidney injury, prolonged capillary refill time, tachycardia, hypotension, abdominal discomfort) or failure to thrive, NOT based on serum albumin levels alone 1, 5
• Rapid referral to a specialized pediatric nephrology unit is recommended due to the complexity of fluid management in nephrotic syndrome 1
• Intravenous fluids and saline should be avoided; oral fluid intake should be concentrated if necessary to avoid marked edema 1
• When albumin infusions are necessary, they can be administered at 0.5-1 g/kg over 1-4 hours followed by furosemide to enhance diuresis 5, 6

Monitoring and Complications

• Careful monitoring is required during diuretic therapy, including assessment of fluid status, electrolytes (particularly for hypokalemia or hyponatraemia), blood pressure, and kidney function 1
• Albumin infusions can cause hypertension (requiring acute antihypertensive therapy in up to 46% of cases), electrolyte disturbances, and respiratory distress 7
• The effect of albumin and furosemide therapy on plasma volume is transient, with initial increase in plasma volume returning to baseline within 24 hours 8
• Central venous lines should be avoided when possible due to the high risk of thrombosis in nephrotic syndrome 1
• Furosemide must be stopped in case of anuria 1

Additional Management Considerations

• Anti-proteinuric agents such as ACE inhibitors or ARBs may be considered to reduce glomerular protein loss 1
• Stable patients can be managed on an outpatient basis with spacing or even stopping of albumin infusions 1
• Pneumococcal and influenza vaccines are recommended for patients with nephrotic syndrome 1