Nephrotic Syndrome Treatment & Management

Updated: Dec 24, 2016
  • Author: Eric P Cohen, MD; Chief Editor: Vecihi Batuman, MD, FASN  more...
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Treatment

Approach Considerations

Specific treatment of nephrotic syndrome depends on its cause. These are detailed in the Medscape articles specific to each of these disorders. Treatment varies between adult and pediatric patients. Kidney Disease Improving Global Outcomes (KDIGO) issued guidelines in 2012 that include recommendations on treatment of nephrotic syndrome in adults and children. [39]

A study using the Cochrane database has put into question whether prednisone treatment is beneficial in adult minimal-change nephropathy. [40]  Nevertheless, treatment is needed when the nephrotic syndrome causes illness such as uncomfortable edema or associated coagulopathy.

The role of preventive anticoagulation in nephrotic syndrome has been reported, but there is no proof that it is beneficial.

Hyperlipidemia occurs in nephrotic syndrome, and it can be controlled with lipid-lowering agents. Older studies have reported a predisposition to atherosclerosis in patients with nephrotic syndrome, but there are no data to show that lipid-lowering drugs improve renal or patient outcomes.

Specific treatment

Children

In minimal-change nephropathy, glucocorticosteroids such as prednisone are used. [41] Rituximab, an antibody against B-cells, has proved an effective steroid-sparing agent in children with steroid-dependent idiopathic nephrotic syndrome. However, children dependent on both steroids and calcineurin inhibitors are less likely to achieve drug-free remission with rituximab. [42]  Rituximab may also be used in children with steroid-resistant disease.

The benefits of rituximab for nephrotic syndrome were shown in a study in 10 children and 20 adults with minimal-change disease/mesangial proliferative glomerulonephritis or focal segmental glomerulosclerosis who had suffered two or more recurrences over the previous year and were in steroid-induced remission for 1 month or longer. At 1 year after receiving one or two doses of rituximab, all patients were in remission: 18 had been fully weaned from steroids and 15 had never relapsed. In addition, rituximab halted disease-associated growth deficit in the children. [43]

A pilot study by Bonanni et al tested the new fully humanized anti-CD20 monoclonal antibody ofatumumab in four children with persistent proteinuria despite a full drug approach (including rituximab). The two patients with normal renal function experienced remission of proteinuria—transient in one patient and persistent in the other—while the two with impaired renal function failed to respond. This study used a low-dose two-infusion ofatumumab regimen (300+700 mg/1.73 m2 2 weeks apart); the authors suggest testing whether higher doses of ofatumumab may be effective in patients with renal impairment. [44]

In a retrospective study of 64 children with steroid-dependent nephrotic syndrome and 18 children with steroid-resistant nephrotic syndrome, treatment with cyclosporine A or cyclosporine A plus mycophenolate mofetil resulted in remission in 14 of the 18 steroid-resistant patients (eight with cyclosporine A and six with combination treatment). In the steroid-dependent group, 15 patients (23%) received no medication, cyclosporine A was effective in 31 of 38 patients (82%), and mycophenolate mofetil was effective in all patients in whom cyclosporine A treatment was not successful. [45]

Adults

Minimal change nephropathy in adults should respond to prednisone.

In lupus nephritis, prednisone with cyclophosphamide or mycophenolate mofetil should induce remission.

Secondary amyloidosis with nephrotic syndrome should improve with anti-inflammatory treatment of the primary disease.

In membranous nephropathy, management with angiotensin blockade but without immunosuppression can be used for the first 6 months in patients at low risk for progression (ie, those with serum creatinine level <1.5 mg/dL and less than 4 g of proteinuria per day). Patients with renal insufficiency (serum creatinine level >1.5 mg/dL) or those with higher amounts of urine protein are at risk for loss of kidney function and should receive immunosuppressive therapy. [46]  This includes regimens that combine prednisone with cyclophosphamide or chlorambucil. Mycophenolate mofetil is not helpful in membranous nephropathy. Rituximab is effective in membranous nephropathy in adults, but controlled trials are lacking. [47]

Diet and activity

The diet in patients with nephrotic syndrome should provide adequate caloric intake and adequate protein (1 g/kg/d). Supplemental dietary protein is of no proven value. A diet with no added salt will help to limit fluid overload. Fluid restriction per se is not needed.

There are no activity restrictions for patients with nephrotic syndrome. Ongoing activity, rather than bedrest, will reduce the risk of blood clots.

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Acute Nephrotic Syndrome in Childhood

With good parental and patient education and close outpatient follow-up care, hospitalization is not usually necessary. Hospitalization should be considered if any of the following are present:

  • Generalized edema severe enough to cause respiratory distress
  • Tense scrotal or labial edema
  • Complications such as bacterial sepsis, peritonitis, pneumonia, or thromboembolism
  • Failure to thrive
  • Uncertainty regarding patient or family compliance with treatment

Diuretics are needed. Furosemide (1 mg/kg/d) and spironolactone (2 mg/kg/d) will help when fluid retention is severe, provided no signs of renal failure or volume contraction are evident.

Achieving a satisfactory diuresis is difficult when the patient's serum albumin level is less than 1.5 g/dL. Albumin in a dose of 1 g/kg may be given intravenously (IV), followed by IV furosemide. Use of this approach is based on the premise that raising the serum albumin level will ‘pull’ fluid from the extravascular to the intravascular space. Albumin may also increase diuretic delivery to the kidney by keeping urosemide within the vascular space , decreasing its catabolism and facilitating its secretion into the tubular lumen.

Complications of using IV albumin may occur, including pulmonary edema.

Some evidence suggests that administration of albumin may delay the response to steroids and may even induce more frequent relapses, probably by causing severe glomerular epithelial damage. Fluid removal and weight loss remain transient unless proteinuria remits.

To prevent infection, oral penicillin can be prescribed for children with gross edema. Abdominal paracentesis should be performed if the patient develops signs of peritonitis, and any bacterial infection should be treated promptly. A non-immune patient with varicella should get immunoglobulin therapy if exposed to chickenpox, and acyclovir should be given if the patient develops chickenpox.

Depending on the cause of nephrotic syndrome, a patient may need specialty consultation. For example, an individual with lupus nephritis will benefit from rheumatologic consultation.

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Acute Nephrotic Syndrome in Adults

The principles for management of adults with acute nephrotic syndrome are similar to those for children. Diuretics will be needed; furosemide, spironolactone, and even metolazone may be used. Volume depletion may occur with diuretic use, which should be monitored by assessment of symptoms, weight, pulse, and blood pressure.

Anticoagulation has been advocated for use in preventing thromboembolic complications, but its use in primary prevention is unproven.

Hypolipidemic agents may be used, but if the nephrotic syndrome cannot be controlled, the patient will have persistent hyperlipidemia.

In secondary nephrotic syndrome, such as that associated with diabetic nephropathy, angiotensin-converting enzyme (ACE) inhibitors and/or angiotensin II receptor blockers are widely used. These may reduce proteinuria by reducing the systemic blood pressure, by reducing intraglomerular pressure, and also by direct action on podocytes.

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Long-Term Monitoring

Ongoing use and adjustment of diuretics and angiotensin antagonists are done according to the amount of edema and proteinuria that a patient has.

Follow-up care in patients with nephrotic syndrome also includes immunizations and monitoring for corticosteroid toxicity.

Routine immunizations should be delayed until the patient is free of relapses and has been off immunosuppression for 3 months. [48] Pneumococcal and influenza vaccines are recommended but are not routinely used, because their efficacy is not established. [49, 50] Children who have received immunosuppressive therapy in the preceding 3 months and are not immune to varicella should receive zoster immunoglobulin if they are exposed to chickenpox or shingles. These patients should also receive acyclovir if they develop chickenpox. [51]

Monitoring for steroid toxicity every 3 months in the outpatient clinic will detect adverse effects such as slowing of growth. Supplemental calcium and vitamin D may attenuate bone loss. A yearly checkup will detect cataracts. [52]

 

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Diet

A low-salt diet will limit the fluid retention and edema that occurs in nephrotic syndrome. A 24-hour urine collection is useful to quantify dietary intake of sodium. More than 88 mEq/day in the 24-hour urine suggests high salt intake. The help of a dietician will be useful to bring the daily sodium intake down to 2 g (88 mEq)/day or less.

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