KDIGO Recommendations for Antihypertensive Management in Nephrotic Syndrome

RAS Blockade Optimization

The KDIGO 2021 guideline strongly recommends using an ACE inhibitor or ARB titrated to the maximally tolerated dose as first‑line therapy for patients with hypertension and proteinuria. 1, 2, 3
Losartan should be uptitrated from 25 mg to 50 mg daily, then to 100 mg daily over 2–4 weeks if tolerated, with serum creatinine and potassium checked 2–4 weeks after each increase. 4
Do not discontinue losartan when serum creatinine rises ≤30 % from baseline; this modest increase is acceptable and does not mandate stopping the drug. 1, 2, 3
Target systolic blood pressure < 120 mm Hg (120–130 mm Hg acceptable) using standardized office measurements in glomerular disease. 3, 5

KDIGO 2021 strongly recommends loop diuretics as first‑line therapy for edema in nephrotic syndrome, preferably given twice daily. 1, 2, 5, 6
Start furosemide 40 mg twice daily (or an equivalent dose of bumetanide/torsemide) as the initial loop diuretic. 1, 6
Titrate the loop diuretic upward progressively until a clinically significant diuresis is achieved or the maximal effective dose is reached. 1, 5
If edema remains resistant, add a thiazide‑type diuretic or spironolactone for synergistic effect, while monitoring for hyper‑kalemia when combined with losartan. 1, 2, 7

Hydralazine should be tapered and discontinued as losartan is uptitrated and loop diuretics are introduced. 1, 4

Check serum creatinine and potassium 2–4 weeks after each losartan dose increase. 4
If hyper‑kalemia develops, use potassium‑wasting diuretics (loop or thiazide) and/or potassium binders rather than reducing the ARB dose. 7, 8
Advise patients to hold losartan and diuretics during acute illness or any situation that risks volume depletion (sick‑day management). 7, 8
Monitor for hypo‑kalemia, hyponatremia, and volume depletion while on loop diuretic therapy. 1, 5, 6

Restrict dietary sodium to < 2.0 g/day (< 90 mmol/day); this enhances the antiproteinuric effect of RAS blockade and improves diuretic responsiveness. 1, 2, 5, 4, 8

Do not stop losartan for modest creatinine increases up to 30 % above baseline. 1, 2, 3
Do not combine ACE inhibitors with ARBs or direct renin inhibitors, as this raises adverse‑event risk without additional benefit. 4
Do not use thiazide or potassium‑sparing diuretics as monotherapy in nephrotic syndrome; loop diuretics remain first‑line. 1, 6