Proteinuria Treatment & Management

Evaluation normally is conducted on an outpatient basis unless the patient develops a complication of severe nephrotic syndrome. All patients with evidence of glomerular disease or any reduction in renal function should be referred to a nephrologist.

• Medical care can be considered as having 2 components as follows:

  • Nonspecific treatment that is applicable irrespective of the underlying cause, assuming the patient has no contraindications to the therapy
  • Specific treatment that depends on the underlying renal or nonrenal cause
• Nonspecific treatment

  • The degree of proteinuria depends on the integrity of the GCW (charge and size selectivity) and the intraglomerular pressure. Intraglomerular pressure is controlled by both the afferent arteriole, which transmits systemic blood pressure to the glomerulus, and the efferent arteriole.
  • Normalization of systemic blood pressure in a patient with hypertension^[9] should result in a reduction in intraglomerular pressure and a fall in albuminuria.
  • Some vasodilatory antihypertensives (eg, hydralazine and nifedipine) dilate the afferent arteriole, which may attenuate the reduction in intraglomerular pressure despite the fall in arterial blood pressure.
  • As a consequence, these agents may not reduce proteinuria to the same degree, particularly if systemic blood pressure is not adequately reduced at the same time the afferent arteriole is dilated. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor antagonists (AT1-ra) reduce intraglomerular pressure by inhibiting angiotensin–II-mediated efferent arteriolar vasoconstriction.
  • These groups of drugs have a proteinuria-reducing effect independent of their antihypertensive effect.
  • Other hemodynamic and nonhemodynamic effects of ACEIs may partly explain the renoprotective properties of this group of drugs, such as reduced breakdown of bradykinin (an efferent arteriolar vasodilator), restoration of size and charge selectivity to the GCW, and reduced production of cytokines that promote glomerulosclerosis and fibrosis, such as TGF-beta.
  • Target blood pressure is less than 125/75 mm Hg. The dose of ACEI should be increased as tolerated until this blood pressure is achieved.
  • Normotensive patients with proteinuria also should be given ACEIs because low doses usually are well tolerated and do not usually cause symptomatic hypotension.
  • Patients who develop adverse effects from ACEIs, such as cough, should be given an AT1-ra. Patients also may develop angioedema due to the increase in bradykinin levels that accompany the use of ACEIs. This adverse effect also warrants cessation of treatment. An AT1-ra may be used instead. Patients with mild hyperkalemia should receive dietary counseling. Those with significant hyperkalemia should have the medication immediately discontinued and should be administered a potassium-binding resin.
  • Patients with edema should have salt and water restrictions (see Diet).
  • Patients with fluid overload should be treated with diuretics. The use of diuretics in patients with nephrotic syndrome requires careful attention because patients may be refractory to normal doses of diuretics due to reduced delivery to the renal tubule (reduced albumin transport). Use a combination of diuretics acting at different sites of the nephron (eg, loop diuretic ± thiazide ± spironolactone). These patients, at the same time, may have intravascular volume depletion and, as a consequence, may be at risk of acute renal failure due to exacerbation of volume depletion.
  • The routine use of albumin infusion combined with diuretics is not advocated in patients with nephrotic syndrome. Most patients diurese with a loop diuretic or a combination of diuretics. The addition of albumin may improve natriuresis in patients with refractory salt and water retention, but the potential benefits must be offset against cost and risks of albumin infusion, including the possibility of exacerbating fluid overload.
  • No evidence-based recommendations are available for the treatment of hyperlipidemia associated with nephrotic syndrome, and, as such, this is a controversial topic.
    • The lipid abnormalities in these patients usually are not responsive to dietary measures.
    • In patients in whom proteinuria is reduced, by specific or nonspecific treatment, dyslipidemia usually improves.
    • In patients with persistent proteinuria and lipid abnormalities, many nephrologists now treat the secondary lipid abnormalities, particularly if these patients have other risk factors for vascular disease. Unfortunately, patients with severe nephrotic syndrome frequently are only partially responsive to lipid-lowering agents (eg, statin group).^[10]
  • Recommendations on anticoagulation for patients with nephrotic syndrome also are not evidence-based and are equally controversial.
    • Due to urinary losses associated with coagulation inhibitors, such as antithrombin III and protein S and C, these patients are hypercoagulable.
    • The risk of thrombosis appears highest in patients with membranous glomerulonephritis. Numerous case reports have been published pertaining to the development of renal vein thrombosis (usually presents as acute onset of gross hematuria and back pain) in patients with membranous glomerulonephritis.
    • While some nephrologists advocate treating patients with Coumadin, most do not prophylactically anticoagulate these patients unless the patients have a second risk factor for venous thrombosis, such as immobility. Some nephrologists recommend the use of heparin (5000 U subcutaneously bid) as prophylactic anticoagulation in those patients with serum albumin levels of less than 2.5 mg/dL.
  • Patients with nephrotic syndrome are at increased risk of infection. The risk is greatest for bacterial infection (including spontaneous bacterial peritonitis) due to renal losses of immunoglobulin and complement components. No data, however, advocates the routine use of prophylactic antibiotics or immunoglobulin infusions.
• Specific treatment

  • This depends on the nature of the underlying glomerular injury and, in particular, whether or not the injury is immune mediated.
  • For details on specific treatment for the various glomerular diseases, see the relevant eMedicine articles.

• Nephrologist

• Patients with nephrotic syndrome and fluid overload should have a salt-restricted diet. A "no-added-salt" diet usually is sufficient, although some patients may need restrictions of up to 40 mmol/d.
• Vegter et al found that for nondiabetic patients with chronic kidney disease, high dietary salt (>14 g daily) appeared to blunt the antiproteinuric effect of ACE inhibitor therapy and increase the risk for end-stage renal disease (ESRD), independent of blood pressure control.^[11]
• The issue of dietary protein restrictions is controversial.

  • Evidence exists that indicates a protein restriction may slow down the rate of deterioration in the GFR in patients with glomerular diseases, including diabetic nephropathy. The presumed mechanism is a reduction in intraglomerular pressure.
  • However, concern exists that protein-restricted diets may increase the risk of protein malnutrition, and other methods of reducing intraglomerular pressure, such as the use of ACEIs, may be safer than protein restriction.
  • Most nephrologists recommend no restrictions or mild restriction in protein intake (0.8-1 g/kg/d).
• The role of cholesterol restriction is discussed in Medical Care.