Glomerulonephritis

Publication Date: June 1, 2012
Last Updated: March 14, 2022

Recommendation Statements

Prednisone and prednisolone are equivalent, used in the same dosage, and have both been used in RCTs depending on the country of origin. All later references to prednisone in this chapter refer to prednisone or prednisolone. All later references to oral corticosteroids refer to prednisone or prednisolone.

Steroid-sensitive nephrotic syndrome in children

Treatment of the initial episode of SSNS

We recommend that corticosteroid therapy (prednisone or prednisolone)* be given for at least 12 weeks. (Level 1, B)
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We recommend that oral prednisone be administered as a single daily dose (Level 1, B)
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starting at 60 mg/m2 /d or 2 mg/kg/d to a maximum 60 mg/d. (Level 1, D)
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We recommend that daily oral prednisone be given for 4–6 weeks (Level 1, C)
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followed by alternate-day medication as a single daily dose starting at 40 mg/m2 or 1.5 mg/kg (maximum 40 mg on alternate days) (Level 1, D)
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and continued for 2–5 months with tapering of the dose. (Level 1, B)
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Treatment of relapsing SSNS with corticosteroids

Corticosteroid therapy for children with infrequent relapses of SSNS:
We suggest that infrequent relapses of SSNS in children be treated with a single-daily dose of prednisone 60 mg/m2 or 2 mg/kg (maximum of 60 mg/d) until the child has been in complete remission for at least 3 days. (Level 2, D)
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We suggest that, after achieving complete remission, children be given prednisone as a single dose on alternate days (40 mg/m2 per dose or 1.5 mg/kg per dose: maximum 40 mg on alternate days) for at least 4 weeks. (Level 2, C)
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Corticosteroid therapy for frequently relapsing (FR) and steroid-dependent (SD) SSNS:
We suggest that relapses in children with FR or SD SSNS be treated with daily prednisone until the child has been in remission for at least 3 days, followed by alternate-day prednisone for at least 3 months. (Level 2, C)
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We suggest that prednisone be given on alternate days in the lowest dose to maintain remission without major adverse effects in children with FR and SD SSNS. (Level 2, D)
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We suggest that daily prednisone at the lowest dose be given to maintain remission without major adverse effects in children with SD SSNS where alternate-day prednisone therapy is not effective. (Level 2, D)
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We suggest that daily prednisone be given during episodes of upper respiratory tract and other infections to reduce the risk for relapse in children with FR and SD SSNS already on alternate-day prednisone. (Level 2, C)
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Treatment of FR and SD SSNS with corticosteroid-sparing agents

We recommend that corticosteroid-sparing agents be prescribed for children with FR SSNS and SD SSNS, who develop steroid-related adverse effects. (Level 1, B)
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We recommend that alkylating agents, cyclophosphamide or chlorambucil, be given as corticosteroid-sparing agents for FR SSNS. (Level 1, B)
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We suggest that alkylating agents, cyclophosphamide or chlorambucil, be given as corticosteroid-sparing agents for SD SSNS. (Level 2, C)
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We suggest that cyclophosphamide (2 mg/kg/d) be given for 8–12 weeks (maximum cumulative dose 168 mg/kg). (Level 2, C)
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We suggest that chlorambucil (0.1–0.2 mg/kg/d) may be given for 8 weeks (maximum cumulative dose 11.2 mg/kg) as an alternative to cyclophosphamide. (Level 2, C)
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We suggest that second courses of alkylating agents not be given. (Level 2, D)
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We recommend that levamisole be given as a corticosteroid-sparing agent. (Level 1, B)
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We suggest that levamisole be given at a dose of 2.5 mg/kg on alternate days
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for at least 12 months (Level 2, C)
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since most children will relapse when levamisole is stopped.
We recommend that the calcineurin inhibitors cyclosporine or tacrolimus be given as corticosteroid-sparing agents. (Level 1, C)
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We suggest that cyclosporine be administered at a dose of 4–5 mg/kg/d (starting dose) in two divided doses. (Level 2, C)
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We suggest that tacrolimus 0.1 mg/kg/d (starting dose) given in two divided doses be used instead of cyclosporine when the cosmetic side-effects of cyclosporine are unacceptable. (Level 2, D)
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Monitor CNI levels during therapy to limit toxicity. (NG)
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We suggest that CNIs be given for at least 12 months, as most children will relapse when CNIs are stopped. (Level 2, C)
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We suggest that MMF be given as a corticosteroid-sparing agent. (Level 2, C)
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We suggest that MMF (starting dose 1200 mg/m2 /d) be given in two divided doses for at least 12 months, as most children will relapse when MMF is stopped. (Level 2, C)
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We suggest that rituximab be considered only in children with SD SSNS who have continuing frequent relapses despite optimal combinations of prednisone and corticosteroid-sparing agents, and/or who have serious adverse effects of therapy. (Level 2, C)
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We suggest that mizoribine not be used as a corticosteroid-sparing agent in FR and SD SSNS. (Level 2, C)
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We recommend that azathioprine not be used as a corticosteroid-sparing agent in FR and SD SSNS. (Level 1, B)
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Indication for kidney biopsy

Indications for kidney biopsy in children with SSNS are:
  • late failure to respond following initial response to corticosteroids;
  • a high index of suspicion for a different underlying pathology;
  • decreasing kidney function in children receiving CNIs.
(NG)
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Immunizations in children with SSNS

To reduce the risk of serious infections in children with SSNS:
  • Give pneumococcal vaccination to the children.
  • Give influenza vaccination annually to the children and their household contacts.
  • Defer vaccination with live vaccines until prednisone dose is below either 1 mg/kg daily (<20 mg/d) or 2 mg/kg on alternate days (<40 mg on alternate days).
  • Live vaccines are contraindicated in children receiving corticosteroid-sparing immunosuppressive agents.
  • Immunize healthy household contacts with live vaccines to minimize the risk of transfer of infection to the immunosuppressed child but avoid direct exposure of the child to gastrointestinal, urinary, or respiratory secretions of vaccinated contacts for 3–6 weeks after vaccination.
  • Following close contact with Varicella infection, give nonimmune children on immunosuppressive agents varicella zoster immune globulin, if available.
(NG)
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Steroid-resistant nephrotic syndrome in children

Evaluation of children with SRNS

We suggest a minimum of 8 weeks treatment with corticosteroids to define steroid resistance. (Level 2, D)
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The following are required to evaluate the child with SRNS:
  • a diagnostic kidney biopsy;
  • evaluation of kidney function by GFR or eGFR;
  • quantitation of urine protein excretion.
(, )
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Treatment recommendations for SRNS

We recommend using a calcineurin inhibitor (CNI) as initial therapy for children with SRNS. (Level 1, B)
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We suggest that CNI therapy be continued for a minimum of 6 months and then stopped if a partial or complete remission of proteinuria is not achieved. (Level 2, C)
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We suggest CNIs be continued for a minimum of 12 months when at least a partial remission is achieved by 6 months. (Level 2, C)
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We suggest that low-dose corticosteroid therapy be combined with CNI therapy. (Level 2, D)
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We recommend treatment with ACE-I or ARBs for children with SRNS. (Level 1, B)
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In children who fail to achieve remission with CNI therapy:

be considered in children who fail to achieve complete or partial remission with CNIs and corticosteroids.
  • We suggest that mycophenolate mofetil,
(Level 2, D)
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  • high-dose corticosteroids,
(Level 2, D)
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  • or a combination of these agents
(Level 2, D)
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We suggest that cyclophosphamide not be given to children with SRNS. (Level 2, B)
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In patients with a relapse of nephrotic syndrome after complete remission, we suggest that therapy be restarted using any one of the following options: (Level 2, C)
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  • oral corticosteroids
(, )
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  • return to previous successful immunosuppressive agent
(Level 2, D)
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an alternative immunosuppressive agent to minimize potential cumulative toxicity. (Level 2, D)
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Minimal-change disease in adults

Treatment of initial episode of adult MCD
We recommend that corticosteroids be given for initial treatment of nephrotic syndrome. (Level 1, C)
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We suggest prednisone or prednisolone* be given at a daily single dose of 1 mg/kg (maximum 80 mg) or alternate-day single dose of 2 mg/kg (maximum 120 mg). (Level 2, C)
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We suggest the initial high dose of corticosteroids, if tolerated, be maintained for a minimum period of 4 weeks if complete remission is achieved, and for a maximum period of 16 weeks if complete remission is not achieved. (Level 2, C)
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In patients who remit, we suggest that corticosteroids be tapered slowly over a total period of up to 6 months after achieving remission. (Level 2, D)
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For patients with relative contraindications or intolerance to high-dose corticosteroids (e.g., uncontrolled diabetes, psychiatric conditions, severe osteoporosis), we suggest oral cyclophosphamide or CNIs as discussed in frequently relapsing MCD. (Level 2, D)
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We suggest using the same initial dose and duration of corticosteroids for infrequent relapses. (, )
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FR/SD MCD
We suggest oral cyclophosphamide 2–2.5 mg/kg/d for 8 weeks. (Level 2, C)
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We suggest CNI (cyclosporine 3–5 mg/kg/d or tacrolimus 0.05–0.1 mg/kg/d in divided doses) for 1–2 years for FR/SD MCD patients who have relapsed despite cyclophosphamide, or for people who wish to preserve their fertility. (Level 2, C)
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We suggest MMF 500–1000 mg twice daily for 1–2 years for patients who are intolerant of corticosteroids, cyclophosphamide, and CNIs. (Level 2, D)
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Corticosteroid-resistant MCD
Re-evaluate patients who are corticosteroid-resistant for other causes of nephrotic syndrome. (NG)
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Supportive therapy
We suggest that MCD patients who have AKI be treated with renal replacement therapy as indicated, but together with corticosteroids, as for a first episode of MCD. (Level 2, D)
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We suggest that, for the initial episode of nephrotic syndrome associated with MCD, statins not be used to treat hyperlipidemia, and ACE-I or ARBs not be used in normotensive patients to lower proteinuria. (Level 2, D)
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Idiopathic focal segmental glomerulosclerosis in adults

Initial evaluation of FSGS

Undertake thorough evaluation to exclude secondary forms of FSGS. (NG)
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Do not routinely perform genetic testing. (NG)
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Initial treatment of FSGS

We recommend that corticosteroid and immunosuppressive therapy be considered only in idiopathic FSGS associated with clinical features of the nephrotic syndrome. (Level 1, C)
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We suggest CNIs be considered as first-line therapy for patients with relative contraindications or intolerance to high-dose corticosteroids (e.g., uncontrolled diabetes, psychiatric conditions, severe osteoporosis). (Level 2, D)
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We suggest prednisone be given at a daily single dose of 1 mg/kg (maximum 80 mg) or alternate-day dose of 2 mg/kg (maximum 120 mg). (Level 2, C)
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We suggest the initial high dose of corticosteroids be given for a minimum of 4 weeks; continue high-dose corticosteroids up to a maximum of 16 weeks, as tolerated, or until complete remission has been achieved, whichever is earlier. (Level 2, D)
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We suggest corticosteroids be tapered slowly over a period of 6 months after achieving complete remission. (Level 2, D)
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Treatment for relapse

We suggest that a relapse of nephrotic syndrome is treated as per the recommendations for relapsing MCD in adults. (Level 2, D)
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Treatment for steroid-resistant FSGS

For steroid-resistant FSGS, we suggest that cyclosporine at 3–5 mg/kg/d in divided doses be given for at least 4–6 months. (Level 2, B)
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If there is a partial or complete remission, we suggest continuing cyclosporine treatment for at least 12 months, followed by a slow taper. (Level 2, D)
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We suggest that patients with steroid-resistant FSGS, who do not tolerate cyclosporine, be treated with a combination of mycophenolate mofetil and high-dose dexamethasone. (Level 2, C)
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Idiopathic membranous nephropathy

Evaluation of MN

Perform appropriate investigations to exclude secondary causes in all cases of biopsy-proven MN. (NG)
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Selection of adult patients with IMN to be considered for treatment with immunosuppressive agents.

We recommend that initial therapy be started only in patients with nephrotic syndrome AND when at least one of the following conditions is met:
  • Urinary protein excretion persistently exceeds 4 g/d AND remains at over 50% of the baseline value, AND does not show progressive decline, during antihypertensive and antiproteinuric therapy during an observation period of at least 6 months.
(Level 1, B)
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  • the presence of severe, disabling, or life-threatening symptoms related to the nephrotic syndrome
(Level 1, C)
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  • SCr has risen by 30% or more within 6 to 12 months from the time of diagnosis but the eGFR is not less than 25–30 ml/min/1.73 m2 AND this change is not explained by superimposed complications.
(Level 2, C)
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Do not use immunosuppressive therapy in patients with a SCr persistently >3.5 mg/dl (>309 lmol/l) (or an eGFR <30 ml/min per 1.73 m2 ) AND reduction of kidney size on ultrasound (e.g., <8 cm in length) OR those with concomitant severe or potentially life-threatening infections. (NG)
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Initial therapy of IMN

We recommend that initial therapy consist of a 6-month course of alternating monthly cycles of oral and i.v. corticosteroids, and oral alkylating agents. (Level 1, B)
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We suggest using cyclophosphamide rather than chlorambucil for initial therapy. (Level 2, B)
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We recommend patients be managed conservatively for at least 6 months following the completion of this regimen before being considered a treatment failure if there is no remission, unless kidney function is deteriorating or severe, disabling, or potentially life-threatening symptoms related to the nephrotic syndrome are present. (Level 1, C)
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Perform a repeat kidney biopsy only if the patient has rapidly deteriorating kidney function (doubling of SCr over 1–2 month of observation), in the absence of massive proteinuria (>15 g/d). (NG)
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Adjust the dose of cyclophosphamide or chlorambucil according to the age of the patient and eGFR. (NG)
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We suggest that continuous daily (noncyclical) use of oral alkylating agents may also be effective, but can be associated with greater risk of toxicity, particularly when administered for >6 months. (Level 2, C)
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Alternative regimens for the initial therapy of IMN: CNI therapy

We recommend that cyclosporine or tacrolimus be used for a period of at least 6 months in patients who meet the criteria for initial therapy, but who choose not to receive the cyclical corticosteroid/alkylating-agent regimen or who have contraindications to this regimen. (Level 1, C)
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We suggest that CNIs be discontinued in patients who do not achieve complete or partial remission after 6 months of treatment. (Level 2, C)
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We suggest that the dosage of CNI be reduced at intervals of 4–8 weeks to a level of about 50% of the starting dosage, provided that remission is maintained and no treatment-limiting CNI-related nephrotoxicity occurs, and continued for at least 12 months. (Level 2, C)
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We suggest that CNI blood levels be monitored regularly during the initial treatment period, and whenever there is an unexplained rise in SCr (420%) during therapy. (NG)
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Regimens not recommended or suggested for initial therapy of IMN

We recommend that corticosteroid monotherapy not be used for initial therapy of IMN. (Level 1, B)
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We suggest that monotherapy with MMF not be used for initial therapy of IMN. (Level 2, C)
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Treatment of IMN resistant to recommended initial therapy

We suggest that patients with IMN resistant to alkylating agent/steroid-based initial therapy be treated with a CNI. (Level 2, C)
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We suggest that patients with IMN resistant to CNI-based initial therapy be treated with an alkylating agent/ steroid-based therapy. (Level 2, C)
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Treatment for relapses of nephrotic syndrome in adults with IMN

We suggest that relapses of nephrotic syndrome in IMN be treated by reinstitution of the same therapy that resulted in the initial remission. (Level 2, D)
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We suggest that, if a 6-month cyclical corticosteroid/alkylating-agent regimen was used for initial therapy, the regimen be repeated only once for treatment of a relapse. (Level 2, B)
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Treatment of IMN in children

We suggest that treatment of IMN in children follows the recommendations for treatment of IMN in adults. (Level 2, C)
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We suggest that no more than one course of the cyclical corticosteroid/alkylating-agent regimen be given in children. (Level 2, D)
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Prophylactic anticoagulants in IMN

We suggest that patients with IMN and nephrotic syndrome, with marked reduction in serum albumin (<2.5 g/dl [<25 g/l]) and additional risks for thrombosis, be considered for prophylactic anticoagulant therapy, using oral warfarin. (Level 2, C)
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Idiopathic membranoproliferative glomerulonephritis

Evaluation of MPGN

Evaluate patients with the histological (light-microscopic) pattern of MPGN for underlying diseases before considering a specific treatment regimen. (NG)
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Treatment of idiopathic MPGN

We suggest that adults or children with presumed idiopathic MPGN accompanied by nephrotic syndrome AND progressive decline of kidney function receive oral cyclophosphamide or MMF plus low-dose alternateday or daily corticosteroids with initial therapy limited to less than 6 months. (Level 2, D)
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Infection-related glomerulonephritis

For the following infection-related GN, we suggest appropriate treatment of the infectious disease and standard approaches to management of the kidney manifestations:
  • poststreptococcal GN;
  • infective endocarditis-related GN;
  • shunt nephritis.
(Level 2, D)
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Hepatitis C virus (HCV) infection–related GN

For HCV-infected patients with CKD Stages 1 or 2 and GN, we suggest combined antiviral treatment using pegylated interferon and ribavirin as in the general population. (Level 2, C)
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Titrate ribavirin dose according to patient tolerance and level of renal function. (NG)
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For HCV-infected patients with CKD Stages 3, 4, or 5 and GN not yet on dialysis, we suggest monotherapy with pegylated interferon, with doses adjusted to the level of kidney function. (Level 2, D)
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For patients with HCV and mixed cryoglobulinemia (IgG/IgM) with nephrotic proteinuria or evidence of progressive kidney disease or an acute flare of cryoglobulinemia, we suggest either plasmapheresis, rituximab, or cyclophosphamide, in conjunction with i.v. methylprednisolone, and concomitant antiviral therapy. (Level 2, D)
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Hepatitis B virus (HBV) infection–related GN

We recommend that patients with HBV infection and GN receive treatment with interferon-α or with nucleoside analogues as recommended for the general population by standard clinical practice guidelines for HBV infection. (Level 1, C)
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We recommend that the dosing of these antiviral agents be adjusted to the degree of kidney function. (Level 1, C)
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Human Immunodeficiency virus (HIV) infection–related glomerular disorders

We recommend that antiretroviral therapy be initiated in all patients with biopsy-proven HIV-associated nephropathy, regardless of CD4 count. (Level 1, B)
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Schistosomal, filarial, and malarial nephropathies

We suggest that patients with GN and concomitant malarial, schistosomal, or filarial infection be treated with an appropriate antiparasitic agent in sufficient dosage and duration to eradicate the organism. (NG)
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We suggest that corticosteroids or immunosuppressive agents not be used for treatment of schistosomalassociated GN, since the GN is believed to be the direct result of infection and the attendant immune response to the organism. (Level 2, D)
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We suggest that blood culture for Salmonella be considered in all patients with hepatosplenic schistosomiasis who show urinary abnormalities and/or reduced GFR. (Level 2, C)
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We suggest that all patients who show a positive blood culture for Salmonella receive anti-Salmonella therapy. (Level 2, C)
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Immunoglobulin A nephropathy

Initial evaluation including assessment of risk of progressive kidney disease

Assess all patients with biopsy-proven IgAN for secondary causes of IgAN. (NG)
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Assess the risk of progression in all cases by evaluation of proteinuria, blood pressure, and eGFR at the time of diagnosis and during follow-up. (NG)
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Pathological features may be used to assess prognosis. (NG)
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Antiproteinuric and antihypertensive therapy

We recommend long-term ACE-I or ARB treatment when proteinuria is 41 g/d, with up-titration of the drug depending on blood pressure. (Level 1, B)
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We suggest ACE-I or ARB treatment if proteinuria is between 0.5 to 1 g/d (in children, between 0.5 to 1 g/d per 1.73 m2 ). (Level 2, D)
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We suggest the ACE-I or ARB be titrated upwards as far as tolerated to achieve proteinuria <1 g/d. (Level 2, C)
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In IgAN, use blood pressure treatment goals of <130/80 mmHg in patients with proteinuria <1 g/d, and <125/75 mmHg when initial proteinuria is >1 g/d. (NG)
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Corticosteroids

We suggest that patients with persistent proteinuria ≥1 g/d, despite 3–6 months of optimized supportive care (including ACE-I or ARBs and blood pressure control), and GFR ≥50 ml/min per 1.73 m2 , receive a 6-month course of corticosteroid therapy. (Level 2, C)
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We suggest not using immunosuppressive therapy in patients with GFR <30 ml/min per 1.73 m2 unless there is crescentic IgAN with rapidly deteriorating kidney function. (Level 2, C)
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Immunosuppressive agents (cyclophosphamide, azathioprine, MMF, cyclosporine)

We suggest not treating with corticosteroids combined with cyclophosphamide or azathioprine in IgAN patients (unless there is crescentic IgAN with rapidly deteriorating kidney function.) (Level 2, D)
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We suggest not using MMF in IgAN. (Level 2, C)
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Other treatments

Fish oil treatment
We suggest using fish oil in the treatment of IgAN with persistent proteinuria ≥1 g/d, despite 3–6 months of optimized supportive care (including ACE-I or ARBs and blood pressure control). (Level 2, D)
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Antiplatelet agents
We suggest not using antiplatelet agents to treat IgAN. (Level 2, C)
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Tonsillectomy
We suggest that tonsillectomy not be performed for IgAN. (Level 2, C)
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Atypical forms of IgAN

MCD with mesangial IgA deposits
We recommend treatment as for MCD in nephrotic patients showing pathological findings of MCD with mesangial IgA deposits on kidney biopsy. (Level 2, B)
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AKI associated with macroscopic hematuria
Perform a repeat kidney biopsy in IgAN patients with AKI associated with macroscopic hematuria if, after 5 days from the onset of kidney function worsening, there is no improvement. (NG)
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We suggest general supportive care for AKI in IgAN, with a kidney biopsy performed during an episode of macroscopic hematuria showing only ATN and intratubular erythrocyte casts. (Level 2, C)
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Crescentic IgAN
Define crescentic IgAN as IgAN with crescents in more than 50% of glomeruli in the renal biopsy with rapidly progressive renal deterioration. (NG)
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We suggest the use of steroids and cyclophosphamide in patients with IgAN and rapidly progressive crescentic IgAN, analogous to the treatment of ANCA vasculitis. (Level 2, D)
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Henoch-Schönlein purpura nephritis

Treatment of HSP nephritis in children
We suggest that children with HSP nephritis and persistent proteinuria, >0.5–1 g/d per 1.73 m2, are treated with ACE-I or ARBs. (Level 2, D)
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We suggest that children with persistent proteinuria, >1 g/d per 1.73 m2 , after a trial of ACE-I or ARBs, and GFR 450 ml/min per 1.73 m2, be treated the same as for IgAN with a 6-month course of corticosteroid therapy. (Level 2, D)
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Treatment of crescentic HSP nephritis in children
We suggest that children with crescentic HSP with nephrotic syndrome and/or deteriorating kidney function are treated the same as for crescentic IgAN. (Level 2, D)
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Prevention of HSP nephritis in children
We recommend not using corticosteroids to prevent HSP nephritis. (Level 1, B)
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HSP nephritis in adults
We suggest that HSP nephritis in adults be treated the same as in children. (Level 2, D)
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Lupus nephritis

Class I LN (minimal-mesangial LN)
We suggest that patients with class I LN be treated as dictated by the extrarenal clinical manifestations of lupus. (Level 2, D)
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Class II LN (mesangial-proliferative LN)
Treat patients with class II LN and proteinuria <1 g/d as dictated by the extrarenal clinical manifestations of lupus. (Level 2, D)
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We suggest that class II LN with proteinuria >3 g/d be treated with corticosteroids or CNIs as described for MCD. (, )
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Class III LN (focal LN) and class IV LN (diffuse LN)—initial therapy
  • We recommend initial therapy with corticosteroids
(Level 1, A)
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combined with either cyclophosphamide (Level 1, B)
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or MMF (Level 1, B)
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We suggest that, if patients have worsening LN (rising SCr, worsening proteinuria) during the first 3 months of treatment, a change be made to an alternative recommended initial therapy, or a repeat kidney biopsy be performed to guide further treatment. (Level 2, D)
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Class III LN (focal LN) and class IV LN (diffuse LN)—maintenance therapy
We recommend that, after initial therapy is complete, patients with class III and IV LN receive maintenance therapy with azathioprine (1.5–2.5 mg/kg/d) or MMF (1–2 g/d in divided doses), and low-dose oral corticosteroids (≤10 mg/d prednisone equivalent). (Level 1, B)
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We suggest that CNIs with low-dose corticosteroids be used for maintenance therapy in patients who are intolerant of MMF and azathioprine. (Level 2, C)
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We suggest that, after complete remission is achieved, maintenance therapy be continued for at least 1 year before consideration is given to tapering the immunosuppression. (Level 2, D)
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If complete remission has not been achieved after 12 months of maintenance therapy, consider performing a repeat kidney biopsy before determining if a change in therapy is indicated. (NG)
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While maintenance therapy is being tapered, if kidney function deteriorates and/or proteinuria worsens, we suggest that treatment be increased to the previous level of immunosuppression that controlled the LN. (Level 2, D)
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Class V LN (membranous LN)
We recommend that patients with class V LN, normal kidney function, and non–nephrotic-range proteinuria be treated with antiproteinuric and antihypertensive medications, and only receive corticosteroids and immunosuppressives as dictated by the extrarenal manifestations of systemic lupus. (Level 2, D)
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We recommend that patients with class V LN, normal kidney function, and non–nephrotic-range proteinuria be treated with antiproteinuric and antihypertensive medications, and only receive corticosteroids and immunosuppressives as dictated by the extrarenal manifestations of systemic lupus. (Level 2, D)
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We suggest that patients with pure class V LN and persistent nephrotic proteinuria be treated with corticosteroids plus an additional immunosuppressive agent:
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  • or MMF
(Level 2, D)
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  • or azathioprine
(Level 2, D)
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General treatment of LN
We suggest that all patients with LN of any class are treated with hydroxychloroquine (maximum daily dose of 6–6.5 mg/kg ideal body weight), unless they have a specific contraindication to this drug. (Level 2, C)
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Class VI LN (advanced sclerosis LN)
We recommend that patients with class VI LN be treated with corticosteroids and immunosuppressives only as dictated by the extrarenal manifestations of systemic lupus. (Level 2, D)
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Relapse of LN
We suggest that a relapse of LN after complete or partial remission be treated with the initial therapy followed by the maintenance therapy that was effective in inducing the original remission. (Level 2, B)
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If resuming the original therapy would put the patient at risk for excessive lifetime cyclophosphamide exposure, then we suggest a non–cyclophosphamide-based initial regimen be used. (Level 2, B)
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Consider a repeat kidney biopsy during relapse if there is suspicion that the histologic class of LN has changed, or there is uncertainty whether a rising SCr and/or worsening proteinuria represents disease activity or chronicity. (NG)
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Treatment of resistant disease
In patients with worsening SCr and/or proteinuria after completing one of the initial treatment regimens, consider performing a repeat kidney biopsy to distinguish active LN from scarring. (NG)
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Treat patients with worsening SCr and/or proteinuria who continue to have active LN on biopsy with one of the alternative initial treatment regimens. (NG)
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We suggest that nonresponders who have failed more than one of the recommended initial regimens may be considered for treatment with rituximab, i.v. immunoglobulin, or CNIs. (Level 2, D)
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Systemic lupus and thrombotic microangiopathy
We suggest that the antiphospholipid antibody syndrome (APS) involving the kidney in systemic lupus patients, with or without LN, be treated by anticoagulation (target international normalized ratio [INR] 2–3). (Level 2, D)
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We suggest that patients with systemic lupus and thrombotic thrombocytopenic purpura (TTP) receive plasma exchange as for patients with TTP without systemic lupus. (Level 2, D)
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Systemic lupus and pregnancy
We suggest that women be counseled to delay pregnancy until a complete remission of LN has been achieved. (Level 2, D)
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We recommend that cyclophosphamide, MMF, ACE-I, and ARBs not be used during pregnancy. (Level 1, A)
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We suggest that hydroxychloroquine be continued during pregnancy. (Level 2, B)
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We recommend that LN patients who become pregnant while being treated with MMF be switched to azathioprine. (Level 1, B)
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We recommend that, if LN patients relapse during pregnancy, they receive treatment with corticosteroids and, depending on the severity of the relapse, azathioprine. (Level 1, B)
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If pregnant patients are receiving corticosteroids or azathioprine, we suggest that these drugs not be tapered during pregnancy or for at least 3 months after delivery. (Level 2, D)
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We suggest administration of low-dose aspirin during pregnancy to decrease the risk of fetal loss. (Level 2, C)
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LN in children
We suggest that children with LN receive the same therapies as adults with LN, with dosing based on patient size and GFR. (Level 2, D)
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Pauci-immune focal and segmental necrotizing glomerulonephritis

Initial treatment of pauci-immune focal and segmental necrotizing GN

We recommend that cyclophosphamide and corticosteroids be used as initial treatment. (Level 1, A)
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We recommend that rituximab and corticosteroids be used as an alternative initial treatment in patients without severe disease or in whom cyclophosphamide is contraindicated. (Level 1, B)
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Special patient populations

We recommend the addition of plasmapheresis for patients requiring dialysis or with rapidly increasing SCr. (Level 1, C)
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We suggest the addition of plasmapheresis for patients with diffuse pulmonary hemorrhage. (Level 2, C)
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We suggest the addition of plasmapheresis for patients with overlap syndrome of ANCA vasculitis and anti-GBM GN, according to proposed criteria and regimen for anti-GBM GN. (Level 2, D)
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We suggest discontinuing cyclophosphamide therapy after 3 months in patients who remain dialysisdependent and who do not have any extrarenal manifestations of disease. (Level 2, C)
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Maintenance therapy

We recommend maintenance therapy in patients who have achieved remission. (Level 1, B)
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We suggest continuing maintenance therapy for at least 18 months in patients who remain in complete remission. (Level 2, D)
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We recommend no maintenance therapy in patients who are dialysis-dependent and have no extrarenal manifestations of disease. (Level 1, C)
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Choice of agent for maintenance therapy

We recommend azathioprine 1–2 mg/kg/d orally as maintenance therapy. (Level 1, B)
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We suggest that MMF, up to 1 g twice daily, be used for maintenance therapy in patients who are allergic to, or intolerant of, azathioprine. (Level 2, C)
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We suggest trimethoprim-sulfamethoxazole as an adjunct to maintenance therapy in patients with upper respiratory tract disease. (Level 2, B)
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We suggest methotrexate (initially 0.3 mg/kg/wk, maximum 25 mg/wk) for maintenance therapy in patients intolerant of azathioprine and MMF, but not if GFR is <60 ml/min per 1.73 m2 . (Level 1, C)
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We recommend not using etanercept as adjunctive therapy. (Level 1, A)
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Treatment of relapse

We recommend treating patients with severe relapse of ANCA vasculitis (life- or organ-threatening) according to the same guidelines as for the initial therapy. (Level 1, C)
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We suggest treating other relapses of ANCA vasculitis by reinstituting immunosuppressive therapy or increasing its intensity with agents other than cyclophosphamide, including instituting or increasing dose of corticosteroids, with or without azathioprine or MMF. (Level 2, C)
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Treatment of resistant disease

In ANCA GN resistant to induction therapy with cyclophosphamide and corticosteroids,
  • we recommend the addition of rituximab
(Level 1, C)
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  • and suggest i.v. immunoglobulin
(Level 2, C)
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  • or plasmapheresis
(Level 2, D)
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as alternatives.

Treatment of anti-glomerular basement membrane antibody glomerulonephritis

Treatment of anti-GBM GN

We recommend initiating immunosuppression with cyclophosphamide and corticosteroids plus plasmapheresis in all patients with anti-GBM GN except those who are dialysis-dependent at presentation and have 100% crescents in an adequate biopsy sample, and do not have pulmonary hemorrhage. (Level 1, B)
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Start treatment for anti-GBM GN without delay once the diagnosis is confirmed. If the diagnosis is highly suspected, it would be appropriate to begin high-dose corticosteroids and plasmapheresis (Table 31) while waiting for confirmation. (NG)
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We recommend no maintenance immunosuppressive therapy for anti-GBM GN. (Level 1, D)
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Defer kidney transplantation after anti-GBM GN until anti-GBM antibodies have been undetectable for a minimum of 6 months. (NG)
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Recommendation Grading

Overview

Title

Glomerulonephritis

Authoring Organization

Publication Month/Year

June 1, 2012

Last Updated Month/Year

June 21, 2023

Supplemental Implementation Tools

Document Type

Guideline

External Publication Status

Published

Country of Publication

US

Inclusion Criteria

Female, Male, Adolescent, Adult, Child, Infant, Older adult

Health Care Settings

Ambulatory, Hospital, Outpatient

Intended Users

Nurse, nurse practitioner, physician, physician assistant

Scope

Management, Treatment

Diseases/Conditions (MeSH)

D005921 - Glomerulonephritis

Keywords

KDIGO, glomerulonephritis, nephrotic syndrome

Methodology

Number of Source Documents
765
Literature Search Start Date
January 1, 2011
Literature Search End Date
November 1, 2011