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

primary FSGS

1st line – ACE inhibitor or angiotensin-II receptor antagonist

Back
ACUTE
|
primary FSGS
|
asymptomatic with proteinuria <3 g/24 hours
1st line – 

ACE inhibitor or angiotensin-II receptor antagonist

Required in all patients to reduce proteinuria to <0.5 g/24 hour and blood pressure to 125/75 mmHg or less.

ACE inhibitors are the preferred treatments. Angiotensin-II receptor antagonists can be used if ACE inhibitors are not tolerated.

Primary options

enalapril: 2.5 mg orally once daily initially, increase according to response, maximum 40 mg/day

OR

lisinopril: 2.5 mg orally once daily initially, increase according to response, maximum 80 mg/day

Secondary options

losartan: 25 mg orally once daily initially, increase according to response, maximum 100 mg/day

OR

irbesartan: 150 mg orally once daily initially, increase according to response, maximum 300 mg/day

Plus – dietary modification

Back
ACUTE
|
primary FSGS
|
asymptomatic with proteinuria <3 g/24 hours
Plus – 

dietary modification

Treatment recommended for ALL patients in selected patient group

Patients require sodium restriction, as high sodium intake can impair the benefits of renin-angiotensin system blockade.

A low-fat diet and exercise should also be considered in patients with hyperlipidemia.

Consider – statin

Back
ACUTE
|
primary FSGS
|
asymptomatic with proteinuria <3 g/24 hours
Consider – 

statin

Treatment recommended for SOME patients in selected patient group

High serum cholesterol and low-density lipoprotein produced by nephrotic syndrome contribute to the high vascular risk associated with proteinuria.

Normalization of lipid levels is required in any patient with lipid abnormalities.

Statins are the preferred agents. In addition to controlling hyperlipidemia, statins may have a small synergistic antiproteinuric effect when combined with ACE inhibitors.

Primary options

simvastatin: 40 mg orally once daily at night

OR

atorvastatin: 10 mg orally once daily at night

OR

pravastatin: 40 mg orally once daily at night

1st line – corticosteroid

Back
ACUTE
|
primary FSGS
|
symptomatic or proteinuria 3 g or more/24 hours
1st line – 

corticosteroid

According to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, high-dose corticosteroids are the immunosuppressant of choice.[25]

Therapy should be initiated with oral prednisone, which should be given for a minimum of 4 weeks and continued until complete remission is achieved (or up to a maximum of 16 weeks, whichever is earlier). After achieving complete remission, the dose should be tapered slowly over a 6-month period.[25]

20% to 50% of patients achieve complete remission (reduction in proteinuria to <300 mg/day). Others experience partial remission (reduction in proteinuria by 50% or more).[26][27][28][29]

Primary options

prednisone: 1 mg/kg orally once daily, maximum 80 mg/day; or 2 mg/kg orally on alternate days, maximum 120 mg/day

Plus – ACE inhibitor or angiotensin-II receptor antagonist

Back
ACUTE
|
primary FSGS
|
symptomatic or proteinuria 3 g or more/24 hours
Plus – 

ACE inhibitor or angiotensin-II receptor antagonist

Treatment recommended for ALL patients in selected patient group

Required in all patients to reduce proteinuria to <0.5 g/24 hours and blood pressure to 125/75 mmHg or less.

ACE inhibitors are the preferred treatments. Angiotensin-II receptor antagonists can be used if ACE inhibitors are not tolerated.

Primary options

enalapril: 2.5 mg orally once daily initially, increase according to response, maximum 40 mg/day

OR

lisinopril: 2.5 mg orally once daily initially, increase according to response, maximum 80 mg/day

Secondary options

losartan: 25 mg orally once daily initially, increase according to response, maximum 100 mg/day

OR

irbesartan: 150 mg orally once daily initially, increase according to response, maximum 300 mg/day

Plus – dietary modification

Back
ACUTE
|
primary FSGS
|
symptomatic or proteinuria 3 g or more/24 hours
Plus – 

dietary modification

Treatment recommended for ALL patients in selected patient group

Patients require sodium restriction, as high sodium intake can impair the benefits of renin-angiotensin system blockade. Sodium restriction also helps to reduce edema.

A low-fat diet and exercise should also be considered in patients with hyperlipidemia.

Consider – statin

Back
ACUTE
|
primary FSGS
|
symptomatic or proteinuria 3 g or more/24 hours
Consider – 

statin

Treatment recommended for SOME patients in selected patient group

High serum cholesterol and low-density lipoprotein produced by nephrotic syndrome contribute to the high vascular risk associated with proteinuria.

Normalization of lipid levels is required in any patient with lipid abnormalities.

Statins are the preferred agents. In addition to controlling hyperlipidemia, statins may have a small synergistic antiproteinuric effect when combined with ACE inhibitors. Concomitant use of a statin with cyclosporine may cause an increased risk of adverse effects, including myopathy and rhabdomyolysis, and is therefore contraindicated.

Primary options

simvastatin: 40 mg orally once daily at night

OR

atorvastatin: 10 mg orally once daily at night

OR

pravastatin: 40 mg orally once daily at night

Consider – furosemide ± thiazide diuretic

Back
ACUTE
|
primary FSGS
|
symptomatic or proteinuria 3 g or more/24 hours
Consider – 

furosemide ± thiazide diuretic

Treatment recommended for SOME patients in selected patient group

Diuretic therapy is required to treat edema.

Furosemide is the preferred agent. A thiazide diuretic may be added if the response to furosemide alone is inadequate.

Primary options

furosemide: 20-60 mg/day orally given in 2 divided doses

Secondary options

furosemide: 20-60 mg/day orally given in 2 divided doses

and

hydrochlorothiazide: 12.5 to 50 mg orally once daily

Consider – addition of corticosteroid-sparing agent (if corticosteroid-dependent)

Back
ACUTE
|
primary FSGS
|
symptomatic or proteinuria 3 g or more/24 hours
Consider – 

addition of corticosteroid-sparing agent (if corticosteroid-dependent)

Treatment recommended for SOME patients in selected patient group

A combination regimen of a calcineurin inhibitor (cyclosporine or tacrolimus) and low-dose prednisone can be used to reduce corticosteroid toxicity and maintain remission in patients with corticosteroid-dependent disease.

Calcineurin inhibitors can cause nephrotoxicity. Creatinine clearance must be checked before initiating this treatment. Prolonged use of a calcineurin inhibitor is associated with a significant increase in risk of tubulointerstitial fibrosis.[38] Renal function monitoring is essential. 

A cytotoxic alkylating agent (e.g., cyclophosphamide or chlorambucil) can also be used as a corticosteroid-sparing agent in combination with low-dose prednisone, if creatinine clearance permits, in those who have had an inadequate response to, or do not tolerate, a calcineurin inhibitor.

Primary options

cyclosporine non-modified: 3-5 mg/kg/day orally given in 2 divided doses, adjust dose according to serum cyclosporine level

or

tacrolimus: 0.05 to 0.1 mg/kg/day orally given in 2 divided doses, adjust dose according to serum tacrolimus level

-- AND --

prednisone: 0.15 mg/kg orally once daily

Secondary options

cyclophosphamide: consult specialist for guidance on dose

or

chlorambucil: consult specialist for guidance on dose

-- AND --

prednisone: 0.15 mg/kg orally once daily

2nd line – calcineurin inhibitor ± corticosteroid

Back
ACUTE
|
primary FSGS
|
symptomatic or proteinuria 3 g or more/24 hours
2nd line – 

calcineurin inhibitor ± corticosteroid

If no remission after 4 months of corticosteroid treatment, disease is defined as being corticosteroid resistant.[30]

According to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, these patients should be treated with a calcineurin inhibitor (cyclosporine or tacrolimus) for at least 4 to 6 months. If there is partial or complete remission, treatment should be continued for at least 12 months, followed by a slow taper over 6 to 12 months as tolerated.[25]

Cyclosporine can induce remission and preserve renal function, although relapse occurs in 60% of patients when cyclosporine alone is used.[31][32]​ ​

Cyclosporine plus low-dose prednisone in corticosteroid-resistant patients may be more effective than cyclosporine alone.[30][31][33][34]​ 

There is a lack of randomized controlled trials evaluating tacrolimus in the treatment of FSGS; however, several uncontrolled trials have demonstrated its suitability as an alternative to cyclosporine.[35][36]

Calcineurin inhibitors can cause nephrotoxicity. Creatinine clearance must be checked before initiating this treatment. Prolonged use of a calcineurin inhibitor is associated with a significant increase in tubulointerstitial fibrosis.[38] Renal function monitoring is essential.

Patients who develop significant toxicities with corticosteroid therapy should have corticosteroids rapidly tapered as tolerated.[25]​ Treatment with a calcineurin inhibitor should also be considered for this group.

Primary options

cyclosporine non-modified: 3-5 mg/kg/day orally given in 2 divided doses, adjust dose according to serum cyclosporine level

or

tacrolimus: 0.05 to 0.1 mg/kg/day orally given in 2 divided doses, adjust dose according to serum tacrolimus level

-- AND --

prednisone: 0.15 mg/kg orally once daily

Secondary options

cyclosporine non-modified: 3-5 mg/kg/day orally given in 2 divided doses, adjust dose according to serum cyclosporine level

OR

tacrolimus: 0.05 to 0.1 mg/kg/day orally given in 2 divided doses, adjust dose according to serum tacrolimus level

Plus – ACE inhibitor or angiotensin-II receptor antagonist

Back
ACUTE
|
primary FSGS
|
symptomatic or proteinuria 3 g or more/24 hours
Plus – 

ACE inhibitor or angiotensin-II receptor antagonist

Treatment recommended for ALL patients in selected patient group

Required in all patients to reduce proteinuria to <0.5 g/24 hours and blood pressure to 125/75 mmHg or less.

ACE inhibitors are the preferred treatments. Angiotensin-II receptor antagonists can be used if ACE inhibitors are not tolerated.

Primary options

enalapril: 2.5 mg orally once daily initially, increase according to response, maximum 40 mg/day

OR

lisinopril: 2.5 mg orally once daily initially, increase according to response, maximum 80 mg/day

Secondary options

losartan: 25 mg orally once daily initially, increase according to response, maximum 100 mg/day

OR

irbesartan: 150 mg orally once daily initially, increase according to response, maximum 300 mg/day

Plus – dietary modification

Back
ACUTE
|
primary FSGS
|
symptomatic or proteinuria 3 g or more/24 hours
Plus – 

dietary modification

Treatment recommended for ALL patients in selected patient group

Patients require sodium restriction, as high sodium intake can impair the benefits of renin-angiotensin system blockade. Sodium restriction also helps to reduce edema.

A low-fat diet and exercise should also be considered in patients with hyperlipidemia.

Consider – statin

Back
ACUTE
|
primary FSGS
|
symptomatic or proteinuria 3 g or more/24 hours
Consider – 

statin

Treatment recommended for SOME patients in selected patient group

High serum cholesterol and low-density lipoprotein produced by nephrotic syndrome contribute to the high vascular risk associated with proteinuria.

Normalization of lipid levels is required in any patient with lipid abnormalities.

Statins are the preferred agents. In addition to controlling hyperlipidemia, statins may have a small, synergistic, antiproteinuric effect when combined with ACE inhibitors. Concomitant use of a statin with cyclosporine may cause an increased risk of adverse effects, including myopathy and rhabdomyolysis, and is therefore contraindicated.

Primary options

simvastatin: 40 mg orally once daily at night

OR

atorvastatin: 10 mg orally once daily at night

OR

pravastatin: 40 mg orally once daily at night

Consider – furosemide ± thiazide diuretic

Back
ACUTE
|
primary FSGS
|
symptomatic or proteinuria 3 g or more/24 hours
Consider – 

furosemide ± thiazide diuretic

Treatment recommended for SOME patients in selected patient group

Diuretic therapy is required to treat edema.

Furosemide is the preferred agent. A thiazide diuretic may be added if the response to furosemide alone is inadequate.

Sodium restriction also helps to reduce edema.

Primary options

furosemide: 20-60 mg/day orally given in 2 divided doses

Secondary options

furosemide: 20-60 mg/day orally given in 2 divided doses

and

hydrochlorothiazide: 12.5 to 50 mg orally once daily

3rd line – mycophenolate + corticosteroid

Back
ACUTE
|
primary FSGS
|
symptomatic or proteinuria 3 g or more/24 hours
3rd line – 

mycophenolate + corticosteroid

If calcineurin inhibitors are contraindicated because of creatinine clearance or they are poorly tolerated, agents such as mycophenolate can be considered for corticosteroid-resistant disease. However, adequate randomized studies supporting this approach are lacking.[39]

If mycophenolate is being considered, calcineurin inhibitors should be discontinued.

The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines suggest that treatment should be with a combination of mycophenolate plus high-dose dexamethasone.[25] Patients should also be considered for clinical trial enrollment and referral to specialized centers for potential rebiopsy.[25]

Primary options

mycophenolate mofetil: 1 g orally twice daily

and

dexamethasone: consult specialist for guidance on dose

Plus – ACE inhibitor or angiotensin-II receptor antagonist

Back
ACUTE
|
primary FSGS
|
symptomatic or proteinuria 3 g or more/24 hours
Plus – 

ACE inhibitor or angiotensin-II receptor antagonist

Treatment recommended for ALL patients in selected patient group

Required in all patients to reduce proteinuria to <0.5 g/24 hours and blood pressure to 125/75 mmHg or less.

ACE inhibitors are the preferred treatments. Angiotensin-II receptor antagonists can be used if ACE inhibitors are not tolerated.

Primary options

enalapril: 2.5 mg orally once daily initially, increase according to response, maximum 40 mg/day

OR

lisinopril: 2.5 mg orally once daily initially, increase according to response, maximum 80 mg/day

Secondary options

losartan: 25 mg orally once daily initially, increase according to response, maximum 100 mg/day

OR

irbesartan: 150 mg orally once daily initially, increase according to response, maximum 300 mg/day

Plus – dietary modification

Back
ACUTE
|
primary FSGS
|
symptomatic or proteinuria 3 g or more/24 hours
Plus – 

dietary modification

Treatment recommended for ALL patients in selected patient group

Patients require sodium restriction, as high sodium intake can impair the benefits of renin-angiotensin system blockade. Sodium restriction also helps to reduce edema.

A low-fat diet and exercise should also be considered in patients with hyperlipidemia.

Consider – statin

Back
ACUTE
|
primary FSGS
|
symptomatic or proteinuria 3 g or more/24 hours
Consider – 

statin

Treatment recommended for SOME patients in selected patient group

High serum cholesterol and low-density lipoprotein produced by nephrotic syndrome contribute to the high vascular risk associated with proteinuria.

Normalization of lipid levels is required in any patient with lipid abnormalities.

Statins are the preferred agents. In addition to controlling hyperlipidemia, statins may have a small synergistic antiproteinuric effect when combined with ACE inhibitors.

Primary options

simvastatin: 40 mg orally once daily at night

OR

atorvastatin: 10 mg orally once daily at night

OR

pravastatin: 40 mg orally once daily at night

Consider – furosemide ± thiazide diuretic

Back
ACUTE
|
primary FSGS
|
symptomatic or proteinuria 3 g or more/24 hours
Consider – 

furosemide ± thiazide diuretic

Treatment recommended for SOME patients in selected patient group

Diuretic therapy is required to treat edema.

Furosemide is the preferred agent. A thiazide diuretic may be added if the response to furosemide alone is inadequate.

Sodium restriction also helps to reduce edema.

Primary options

furosemide: 20-60 mg/day orally given in 2 divided doses

Secondary options

furosemide: 20-60 mg/day orally given in 2 divided doses

and

hydrochlorothiazide: 12.5 to 50 mg orally once daily

secondary FSGS

1st line – treatment of underlying cause

Back
ACUTE
|
secondary FSGS
1st line – 

treatment of underlying cause

Mainstay of managing secondary FSGS is treating the underlying cause.

Weight loss can induce a significant decrease of proteinuria in obese patients.[40]

Antiretroviral therapy improves renal survival in patients with HIV-associated FSGS.[41][42]

Drug-induced FSGS should resolve when the causative agent is discontinued.

Patients with heroin addiction require detoxification followed by maintenance therapy with opioid agonists and psychosocial interventions; heroin-induced FSGS will only start to resolve when detoxification is successful.

Plus – ACE inhibitor or angiotensin-II receptor antagonist + sodium restriction

Back
ACUTE
|
secondary FSGS
Plus – 

ACE inhibitor or angiotensin-II receptor antagonist + sodium restriction

Treatment recommended for ALL patients in selected patient group

Required in all patients to reduce proteinuria to <0.5 g/24 hours and blood pressure to 125/75 mmHg or less.

ACE inhibitors are the preferred treatments. Angiotensin-II receptor antagonists can be used if ACE inhibitors are not tolerated.

Patients require sodium restriction, as high sodium intake can impair the benefits of renin-angiotensin system blockade.

Primary options

enalapril: 2.5 mg orally once daily initially, increase according to response, maximum 40 mg/day

OR

lisinopril: 2.5 mg orally once daily initially, increase according to response, maximum 80 mg/day

Secondary options

losartan: 25 mg orally once daily initially, increase according to response, maximum 100 mg/day

OR

irbesartan: 150 mg orally once daily initially, increase according to response, maximum 300 mg/day

Consider – statin

Back
ACUTE
|
secondary FSGS
Consider – 

statin

Treatment recommended for SOME patients in selected patient group

High serum cholesterol and low-density lipoprotein produced by nephrotic syndrome contribute to the high vascular risk associated with proteinuria.

Hyperlipidemia in patients with obesity is primarily related to the underlying condition and can be exacerbated by nephrotic syndrome.

Normalization of lipid levels is required in any patient with lipid abnormalities.

Statins are the preferred agents. In addition to controlling hyperlipidemia, statins may have a small synergistic antiproteinuric effect when combined with ACE inhibitors.

A low-fat diet and exercise should also be encouraged.

Primary options

simvastatin: 40 mg orally once daily at night

OR

atorvastatin: 10 mg orally once daily at night

OR

pravastatin: 40 mg orally once daily at night

Consider – furosemide ± thiazide diuretic

Back
ACUTE
|
secondary FSGS
Consider – 

furosemide ± thiazide diuretic

Treatment recommended for SOME patients in selected patient group

Diuretic therapy is required to treat edema.

Furosemide is the preferred agent. A thiazide diuretic may be added if the response to furosemide alone is inadequate.

Sodium restriction also helps to reduce edema.

Edema is much less common in secondary FSGS than in primary FSGS.

Primary options

furosemide: 20-60 mg/day orally given in 2 divided doses

Secondary options

furosemide: 20-60 mg/day orally given in 2 divided doses

and

hydrochlorothiazide: 12.5 to 50 mg orally once daily

Consider – immunosuppressants

Back
ACUTE
|
secondary FSGS
Consider – 

immunosuppressants

Treatment recommended for SOME patients in selected patient group

May be required as part of primary management of some underlying causes, including FSGS arising in a transplanted kidney, drug-induced FSGS that does not resolve with discontinuation of the causative agent, and cases due to a maladaptive response to reduced renal mass.

Corticosteroid therapy can also be used in patients with advanced HIV-induced FSGS to improve renal function and reduce or delay the need for dialysis. As these patients are already immunosuppressed, the risks and benefits of corticosteroid therapy need to be carefully weighed.

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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