Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

initial presentation

1st line – corticosteroid or immunosuppressant

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ACUTE
|
initial presentation
1st line – 

corticosteroid or immunosuppressant

Corticosteroids are considered the mainstay of therapy, and are the initial treatment for all patients unless contraindicated.[3]

A child with nephrotic syndrome (NS) had about an 85% to 90% chance of a complete response to corticosteroid therapy within 4-6 weeks.[2]​ In adults with minimal change disease (MCD), the response to corticosteroids may take much longer than in children.[25][27]​​​​ 

The duration of corticosteroid treatment in children at onset of NS is debated. Flexibility in the duration of the initial treatment course of corticosteroids (8 or 12 weeks) is recommended depending on the child's response and clinical characteristics.[3][28]​ In adults, high-dose corticosteroid treatment for MCD should be given for no longer than 16 weeks.[3]​ 

Ensure adequate dietary calcium intake, or start calcium supplementation in those with inadequate intake, in all patients treated with corticosteroids.[2][37]

In patients in whom corticosteroids are contraindicated, an immunosuppressant agent may be given for initial therapy, such as cyclophosphamide or a calcineurin inhibitor (e.g., cyclosporine, tacrolimus).[3]

Primary options

prednisone: children: 2 mg/kg/day orally given in 1-3 divided doses for 4-6 weeks, followed by 1.5 mg/kg once daily on alternate days for 4-6 weeks, maximum 60 mg/day (daily dosing) or 50 mg/day (alternate day dosing); adults (standard dose): 1 mg/kg orally once daily for 4-16 weeks, taper over at least 24 weeks after remission, maximum 80 mg/day; adults (alternative dose): 2 mg/kg orally once daily on alternate days for 4-16 weeks, taper over at least 24 weeks after remission, maximum 120 mg/dose

Secondary options

cyclophosphamide: children: 2 mg/kg/day orally for 12 weeks, maximum cumulative dose 168 mg/kg; adults: 2 to 2.5 mg/kg/day orally for 8 weeks

OR

cyclosporine modified: children: 4-5 mg/kg/day orally given in 2 divided doses for at least 1 year; adults: 3-5 mg/kg/day orally given in 2 divided doses for 1-2 years

More

OR

tacrolimus: children: 0.1 mg/kg/day given in 2 divided doses for at least 1 year; adults: 0.05 to 0.1 mg/kg/day given in 2 divided doses for 1-2 years

More

Plus – low-salt diet ± fluid restriction

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ACUTE
|
initial presentation
Plus – 

low-salt diet ± fluid restriction

Treatment recommended for ALL patients in selected patient group

The mainstay in the management of edema is a low-salt diet and evaluation of the patient’s fluid status, with restriction of fluid intake if fluid overloaded.[1][2]​​

Fluid restriction is equivalent to daily output plus insensible water losses.

Consider – hypertonic albumin and furosemide

Back
ACUTE
|
initial presentation
Consider – 

hypertonic albumin and furosemide

Treatment recommended for SOME patients in selected patient group

Depending on stage of minimal change disease, rate of progression of hypoproteinemia, and absolute levels of plasma oncotic pressure; functional hypovolemia may develop, stimulating hemostatic mechanisms and secondary sodium retention.[36]

In the presence of massive anasarca or significant respiratory distress, hypertonic albumin and furosemide should be considered.[36]

Furosemide is given intravenously with each albumin infusion to promote diuresis.[36]

Blood pressure (BP) and respiratory status should be closely monitored during these infusions, as hypertension, worsening respiratory distress, and hypercoagulability can occur with aggressive diuresis.[36]

Although albumin and diuretic therapy results in fluid removal and weight loss in children with nephrotic syndrome, this effect is transient unless remission of proteinuria occurs.[36]

Primary options

albumin (human): (25%) children and adults: consult specialist for guidance on dose

and

furosemide: children and adults: consult specialist for guidance on dose

Plus – continue oral corticosteroid or switch to intravenous corticosteroid

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ACUTE
|
initial presentation
|
partial response to corticosteroid
Plus – 

continue oral corticosteroid or switch to intravenous corticosteroid

Treatment recommended for ALL patients in selected patient group

If partial remission is observed, continuation of the oral corticosteroid or a switch to a high-dose intravenous corticosteroid (e.g., methylprednisolone for 3 days) may be considered for a further 2 weeks, as some patients may be late responders.[3][32]

Primary options

prednisone: children: 2 mg/kg/day orally given in 1-3 divided doses for 4-6 weeks, followed by 1.5 mg/kg once daily on alternate days for 4-6 weeks, maximum 60 mg/day (daily dosing) or 50 mg/day (alternate day dosing); adults (standard dose): 1 mg/kg orally once daily for 4-16 weeks, taper over at least 24 weeks after remission, maximum 80 mg/day; adults (alternative dose): 2 mg/kg orally once daily on alternate days for 4-16 weeks, taper over at least 24 weeks after remission, maximum 120 mg/dose

Secondary options

methylprednisolone sodium succinate: children and adults: consult specialist for guidance on dose

Plus – immunosuppressant

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ACUTE
|
initial presentation
|
corticosteroid-resistant
Plus – 

immunosuppressant

Treatment recommended for ALL patients in selected patient group

In children, nephrotic syndrome (NS) is considered to be corticosteroid-resistant (SRNS) if there is not a complete response to the corticosteroid within 4 weeks of treatment.[3] ​SRNS is an indication for kidney biopsy.[3][32]​​ Genetic testing for a monogenic cause of NS is recommended, as immunosuppression may not be beneficial in some of these cases.[3][28]​ Treatment of SRNS in children has improved in the last decade but remains challenging. Most patients do not remain free of proteinuria and may show progressive kidney​ damage. In children with a nongenetic form of NS, treatment with a calcineurin inhibitor such as cyclosporine or tacrolimus can be used.[3][32]​​ If genetic and/or histopathology assessment is not available, immediate immunosuppressive treatment with a calcineurin inhibitor may be started.[32]​ If calcineurin inhibitors are not available, cyclophosphamide may be used.[32]​ After initiating the calcineurin inhibitor (or cyclophosphamide), the corticosteroid dose can be tapered to discontinuation or to the lowest dose possible.

Most published studies on SRNS are in children but in practice, treatment of SRNS is similar for adults. In adults with minimal change disease, only 50% respond to corticosteroids by 4 weeks, with 80% achieving remission by 16 weeks.[25]​ Between 10% and 20% of adults with minimal change disease are corticosteroid-resistant (defined as no response to 16 weeks of corticosteroid treatment).[1][3]​​ Repeat biopsy is likely to show lesions of focal segmental glomerulosclerosis, which reflects a pathologic shift in the course of the disease.[1][3][25]​​ See Focal segmental glomerulosclerosis.

Primary options

cyclosporine modified: children: 4-5 mg/kg/day orally given in 2 divided doses for at least 1 year; adults: 3-5 mg/kg/day orally given in 2 divided doses for 1-2 years

More

OR

tacrolimus: children: 0.1 mg/kg/day given in 2 divided doses for at least 1 year; adults: 0.05 to 0.1 mg/kg/day given in 2 divided doses for 1-2 years

More

Secondary options

cyclophosphamide: children: 2 mg/kg/day orally for 12 weeks, maximum cumulative dose 168 mg/kg; adults: 2 to 2.5 mg/kg/day orally for 8 weeks

ONGOING

infrequent relapse

1st line – corticosteroid

Back
ONGOING
|
infrequent relapse
1st line – 

corticosteroid

A relapse is defined as the reappearance of proteinuria for 3 days or more with or without edema, hypoalbuminemia, and hyperlipidemia.[3]

Infrequent relapses (<2 relapses per 6 months within 6 months of disease onset or <4 relapses per 12 months in any subsequent 12-month period) may be treated with corticosteroids in both children and adults.[3]

Patients who experience infrequent relapses are treated similarly to the initial presentation, but are converted to the lower corticosteroid dose when the urine has been free of protein for 3 days. They are then tapered off or maintained on this dose for 4 weeks or more, depending on the patient's history of relapses and incidence of adverse effects from corticosteroids.

Primary options

prednisone: children: 2 mg/kg/day orally given in 1-3 divided doses for 4-6 weeks, followed by 1.5 mg/kg once daily on alternate days for 4-6 weeks, maximum 60 mg/day (daily dosing) or 50 mg/day (alternate day dosing); adults (standard dose): 1 mg/kg orally once daily for 4-16 weeks, taper over at least 24 weeks after remission, maximum 80 mg/day; adults (alternative dose): 2 mg/kg orally once daily on alternate days for 4-16 weeks, taper over at least 24 weeks after remission, maximum 120 mg/dose

Plus – low-salt diet ± fluid restriction

Back
ONGOING
|
infrequent relapse
Plus – 

low-salt diet ± fluid restriction

Treatment recommended for ALL patients in selected patient group

The mainstay in the management of edema is a low-salt diet and evaluation of the patient’s fluid status, with restriction of fluid intake if fluid overloaded.[1]​​​[2]​​

Fluid restriction is equivalent to daily output plus insensible water losses.

Consider – hypertonic albumin and furosemide

Back
ONGOING
|
infrequent relapse
Consider – 

hypertonic albumin and furosemide

Treatment recommended for SOME patients in selected patient group

Depending on stage of minimal change disease, rate of progression of hypoproteinemia, and absolute levels of plasma oncotic pressure; functional hypovolemia may develop, stimulating hemostatic mechanisms and secondary sodium retention.[36]

In the presence of massive anasarca or significant respiratory distress, hypertonic albumin and furosemide should be considered.[36] Furosemide is given intravenously with each albumin infusion to promote diuresis.[36]

BP and respiratory status should be closely monitored during these infusions, as hypertension, worsening respiratory distress, and hypercoagulability can occur with aggressive diuresis.[36]

Although albumin and diuretic therapy results in fluid removal and weight loss in children with nephrotic syndrome, this effect is transient unless remission of proteinuria occurs.[36]

Primary options

albumin (human): (25%) children and adults: consult specialist for guidance on dose

and

furosemide: children and adults: consult specialist for guidance on dose

frequent relapse

1st line – corticosteroid

Back
ONGOING
|
frequent relapse
1st line – 

corticosteroid

Relapse is the reappearance of proteinuria (dipstick ≥ 3+) for 3 or more days with or without edema, hypoalbuminemia, and hyperlipidemia.[3]

Patients with frequent relapses (≥2 episodes per 6 months within 6 months of disease onset or ≥4 relapses per 12 months in any subsequent 12-month period) are treated similarly to the initial presentation but are converted to the lower corticosteroid dose when the urine has been free of protein for 3 days. They are then tapered off or maintained on this dose for 4 weeks or more, depending on the patient's history of relapses and incidence of adverse effects from corticosteroids.

In children with SSNS who subsequently fail to respond to corticosteroids, a kidney biopsy is indicated.[3]

Primary options

prednisone: children: 2 mg/kg/day orally given in 1-3 divided doses for 4-6 weeks, followed by 1.5 mg/kg once daily on alternate days for 4-6 weeks, maximum 60 mg/day (daily dosing) or 50 mg/day (alternate day dosing); adults (standard dose): 1 mg/kg orally once daily for 4-16 weeks, taper over at least 24 weeks after remission, maximum 80 mg/day; adults (alternative dose): 2 mg/kg orally once daily on alternate days for 4-16 weeks, taper over at least 24 weeks after remission, maximum 120 mg/dose

Plus – low-salt diet ± fluid restriction

Back
ONGOING
|
frequent relapse
Plus – 

low-salt diet ± fluid restriction

Treatment recommended for ALL patients in selected patient group

The mainstay in the management of edema is a low-salt diet and evaluation of the patient’s fluid status, with restriction of fluid intake if fluid overloaded.[1][2]​​

Fluid restriction is equivalent to daily output plus insensible water losses.

Consider – hypertonic albumin and furosemide

Back
ONGOING
|
frequent relapse
Consider – 

hypertonic albumin and furosemide

Treatment recommended for SOME patients in selected patient group

Depending on stage of minimal change disease, rate of progression of hypoproteinemia, and absolute levels of plasma oncotic pressure; functional hypovolemia may develop, stimulating hemostatic mechanisms and secondary sodium retention.[36]

In the presence of massive anasarca or significant respiratory distress, albumin and furosemide should be considered.[36]​ Furosemide is given intravenously with each albumin infusion to promote diuresis.[36]

BP and respiratory status should be closely monitored during these infusions, as hypertension, worsening respiratory distress, and hypercoagulability can occur with aggressive diuresis.[36]

Although albumin and diuretic therapy results in fluid removal and weight loss in children with nephrotic syndrome, this effect is transient unless remission of proteinuria occurs.[36]

Primary options

albumin (human): (25%) children and adults: consult specialist for guidance on dose

and

furosemide: children and adults: consult specialist for guidance on dose

Plus – immunosuppressant

Back
ONGOING
|
frequent relapse
|
severe corticosteroid adverse effects
Plus – 

immunosuppressant

Treatment recommended for ALL patients in selected patient group

Corticosteroid-sparing therapy is indicated for patients with frequent relapses who develop serious corticosteroid-related adverse effects (e.g., growth failure, significant weight gain, hypertension, diabetes, osteoporosis, behavioral concerns, or cataracts).[3][28]

Corticosteroid-sparing agents are ideally initiated while the patient is in remission with corticosteroid treatment and include the following agents: oral cyclophosphamide, mycophenolate, rituximab, or a calcineurin inhibitor (e.g., cyclosporine, tacrolimus).[2][3]​ There is no clear efficacy of one agent over the other and the decision for use is based on issues such as resources, adherence, adverse effect profile, and patient preferences.[3]​​[27][28]​​[34]​ After patients start the corticosteroid-sparing agent, the corticosteroid is often tapered and stopped, or tapered to the lowest possible dose.

Vitamin D levels should be assessed in patients with frequently-relapsing minimal change disease and supplementation guided by serum levels.[2][3]

Primary options

cyclophosphamide: children: 2 mg/kg/day orally for 12 weeks, maximum cumulative dose 168 mg/kg; adults: 2 to 2.5 mg/kg/day orally for 8-12 weeks

OR

cyclosporine modified: children: 4-5 mg/kg/day orally given in 2 divided doses for at least 1 year; adults: 3-5 mg/kg/day orally given in 2 divided doses for 1-2 years

More

OR

tacrolimus: children: 0.1 mg/kg/day given in 2 divided doses for at least 1 year; adults: 0.05 to 0.1 mg/kg/day given in 2 divided doses for 1-2 years

More

OR

mycophenolate mofetil: children: 600 mg/square meter of body surface area orally twice daily for at least 1 year; adults: 1000 mg orally twice daily for at least 1 year

OR

rituximab: children and adults: consult specialist for guidance on dose

corticosteroid-dependent

1st line – immunosuppressant

Back
ONGOING
|
corticosteroid-dependent
1st line – 

immunosuppressant

Corticosteroid-sparing therapy is indicated for patients who have corticosteroid dependence (relapses occur during corticosteroid tapering or within two weeks of discontinuation).[3][28]

Corticosteroid-sparing agents are ideally initiated while the patient is in remission with corticosteroid treatment and include the following agents: oral cyclophosphamide, mycophenolate, rituximab, or calcineurin inhibitors (e.g., cyclosporine, tacrolimus).[2][3] There is no clear efficacy of one agent over the other and the decision for use is based on issues such as resources, adherence, adverse effect profile, and patient preferences.[3]​​[27][28]​​[34]​ After patients start corticosteroid-sparing agents, corticosteroids are often tapered and stopped, or tapered to the lowest possible dose.

Primary options

cyclophosphamide: children: 2 mg/kg/day orally for 12 weeks, maximum cumulative dose 168 mg/kg; adults: 2 to 2.5 mg/kg/day orally for 8-12 weeks

OR

cyclosporine modified: children: 4-5 mg/kg/day orally given in 2 divided doses for at least 1 year; adults: 3-5 mg/kg/day orally given in 2 divided doses for 1-2 years

More

OR

tacrolimus: children: 0.1 mg/kg/day given in 2 divided doses for at least 1 year; adults: 0.05 to 0.1 mg/kg/day given in 2 divided doses for 1-2 years

More

OR

mycophenolate mofetil: children: 600 mg/square meter of body surface area orally twice daily for at least 1 year; adults: 1000 mg orally twice daily for at least 1 year

OR

rituximab: children and adults: consult specialist for guidance on dose

Plus – low-salt diet ± fluid restriction

Back
ONGOING
|
corticosteroid-dependent
Plus – 

low-salt diet ± fluid restriction

Treatment recommended for ALL patients in selected patient group

The mainstay in the management of edema is a low-salt diet and evaluation of the patient’s fluid status, with restriction of fluid intake if fluid overloaded.[1][2]​​

Fluid restriction is equivalent to daily output plus insensible water losses.

Consider – hypertonic albumin and furosemide

Back
ONGOING
|
corticosteroid-dependent
Consider – 

hypertonic albumin and furosemide

Treatment recommended for SOME patients in selected patient group

Depending on stage of minimal change disease, rate of progression of hypoproteinemia, and absolute levels of plasma oncotic pressure; functional hypovolemia may develop, stimulating hemostatic mechanisms and secondary sodium retention.[36]

In the presence of massive anasarca or significant respiratory distress, hypertonic albumin and furosemide should be considered.[36]​ Furosemide is given intravenously with each albumin infusion to promote diuresis.[36]

BP and respiratory status should be closely monitored during these infusions, as hypertension, worsening respiratory distress, and hypercoagulability can occur with aggressive diuresis.[36]

Although albumin and diuretic therapy results in fluid removal and weight loss in children with nephrotic syndrome, this effect is transient unless remission of proteinuria occurs.[36]

Primary options

albumin (human): (25%) children and adults: consult specialist for guidance on dose

and

furosemide: children and adults: consult specialist for guidance on dose

back arrow

Choose a patient group to see our recommendations

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

Use of this content is subject to our disclaimer