Table 2.

Antiproteinuric strategies (modified from Wilmer et al.⁷⁶)

Intervention	Goal/comment
Level 1
Control blood pressure (BP)	The greater the proteinuria, the greater the benefit of lowering BP
Angiotensin-converting enzyme inhibitor (ACEI) therapy	Use ACEI even if normotensive
Angiotensin II type 1-receptor blocker (ARB) therapy	Proven antiproteinuric and renoprotective therapy
Combination ACEI and ARB therapies	Adding ARB to maximum ACEI appears to reduce proteinuria further
Avoid dihydropyridine calcium-channel blockers (DHCCBs) unless needed for BP control	DHCCBs are excellent antihypertensive agents, but they are not antiproteinuric and may promote kidney disease progression; ARB therapy may mitigate these effects
β-Blocker therapy	β-Blocker therapy is antiproteinuric compared with DHCCB therapy
Control protein intake	Goal is 0.7–0.8 g/kg/day. Effect on proteinuria is nearly the same as that of the low BP goal
Level 2
Restrict NaCl intake	Goal is 80–120 mmol/day (≈2.0 to 3.0 g Na).
Control fluid intake	Goal is urine volume <2.0 l/day unless higher fluid intake is needed for specific reasons
Nondihydropyridine calcium-channel blocker therapy	This CCB class is considered antiproteinuric
Control blood lipids	Statins are considered antiproteinuric and renoprotective
Aldosterone antagonist therapy	Spironolactone is antiproteinuric in humans and in animal models independent of BP control
Smoking cessation	Cigarette smoking in humans increases proteinuria/albuminuria and is associated with faster kidney disease progression
Avoid estrogen/progestin replacement therapy in postmenopausal women with kidney disease	Estrogens may have renoprotective effects that explain slower progression of kidney disease in premenopausal women compared with men of the same age but may have adverse effects in postmenopausal women
Supine/recumbent posture when feasible.	Nephrotic-range proteinuria decreases by as much as 50% during recumbency.
Avoid severe exertion	Severe exercise may increase proteinuria substantially
Reduce obesity	Obesity apparently causes glomerulomegaly and proteinuria
Level 3
Decrease elevated homocysteine	Hyperhomocystinuria is associated with microalbuminuria and increased cardiovascular risks.
	Folic acid, B6, and B12 may lower homocysteine levels
Antioxidant therapies	Antioxidant therapies of several types reduce proteinuria in both experimental models and in patients with diabetic nephropathy
Sodium bicarbonate therapy to correct metabolic acidosis	NaHCO3 therapy is not antiproteinuric; however, it blocks complement activation in the tubular compartment and, therefore, may block tubular injury caused by proteinuria
NSAID therapy in severe untreatable nephrotic syndrome	NSAIDs (both COX 2 and nonspecific COX inhibitors) are antiproteinuric but are also nephrotoxic. Thus, NSAID use should be reserved for severe untreatable nephrotic syndrome
Other therapies based on animal studies	Avoid excessive caffeine, iron overload. Allopurinol, pentoxifylline, mycophenolate therapy