Minimal-Change Disease Medication

Updated: Feb 08, 2023
  • Author: Abeera Mansur, MD; Chief Editor: Vecihi Batuman, MD, FASN  more...
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Medication Summary

Pharmacologic treatment in patients with minimal-change disease (MCD) includes the use of diuretics to decrease severe edema. Nonsteroidal anti-inflammatory drugs (NSAIDs) also can be used to decrease proteinuria.

MCD usually responds to corticosteroids. The response is defined in terms of proteinuria, as follows:

  • Complete remission - Complete resolution of proteinuria for at least 3-5 consecutive days
  • Partial remission - Reduction in the degree of proteinuria without complete clearing
  • Relapse - Reoccurrence of proteinuria for at least 3-5 consecutive days

A typical initial regimen in adults consists of oral prednisone in a daily dosage of 1 mg/kg of body weight for 8-16 weeks (or for 1 wk after remission has been induced). The patient is then placed on an alternate-day single-dose (1 mg/kg) regimen to minimize the incidence of adverse effects. If proteinuria disappears or falls to a very low level, high-dose alternate-day therapy is continued for several weeks to 1 month and prednisone is then slowly tapered over several months in an attempt to reduce the likelihood of relapse.

Patients with steroid-sensitive MCD have complete remission within 8-12 weeks with infrequent relapses. Children usually respond within 4-6 weeks. Adults tend to respond slowly, with more than 25% taking as long as 12-16 weeks to attain complete remission. Treatment usually is continued for another 6 weeks after complete remission of proteinuria occurs.

First-line treatment with tacrolimus proved an effective alternative to steroid therapy in a multicenter, prospective, open-label, randomized, controlled trial in 50 adult patients with MCD. Rates of complete remission at 8 weeks were 68% (17 of 25 patients) with tacrolimus versus 84% (21 of 25 patients) with prednisolone (P=0.32). In patiens who achieved complete remission, there was no significant difference between the two cohorts in relapse rates or in the time from complete remission to relapse. The authors conclude that tacrolimus is an effective alternative for patients with MCD who wish to avoid steroid therapy. [27]

If remission of MCD is followed by recurrence, a second course of steroids is given. Those patients who need steroids repeatedly are categorized as frequent relapsers or steroid dependent. Relapse in these patients can occur either during tapering of steroids or after cessation of therapy. In these patients, cytotoxic drugs (eg, cyclophosphamide, chlorambucil, or cyclosporine) can be considered to either induce a remission or decrease the adverse effects of continuous steroid use. Adults are particularly prone to the adverse effects of corticosteroids, but they do well on cyclophosphamide.

Studies in adults and children have shown that both cyclophosphamide and cyclosporine added to steroid treatment may induce remission. [28] Moreover, if these patients relapse at a later time, they tend to become steroid-sensitive.

Cyclophosphamide may be given in a dosage of 2 mg/kg/d for 8-12 weeks. Cyclosporine is given in a dosage of 4-6 mg/kg/d and also can be used in patients who continue to relapse or who are steroid-dependent.

Because cyclophosphamide is less expensive than cyclosporine and has a better response rate, it is preferable to cyclosporine in most patients with steroid-dependent or frequently relapsing MCD. However, cyclosporine may be used as an alternative to cyclophosphamide in order to avoid toxicities associated with the latter. [29] Keeping the dosage of cyclosporine at a minimum and carefully monitoring the drug’s levels have been shown to be helpful in avoiding cyclosporine-associated nephrotoxicity.

In children, repeat kidney biopsy can alter the treatment plan in a significant number of patients. Long-term follow-up of patients with MCD persisting after puberty shows that they are at increased risk of osteoporosis, myopia, and hypertension.

In patients who do not respond to treatment, follow-up biopsies have been found to show either IgM nephropathy or focal segmental glomerulosclerosis (FSGS). A study by Swartz et al of 55 children with steroid-resistant or steroid-dependent MCD determined that 23 of these patients also had mesangial IgM that was visible with immunofluorescence (one of the characteristics of IgM nephropathy). [30] The investigators also found that the children with MCD and immunofluorescently-visible IgM responded better to treatment with cyclosporine than to therapy with cyclophosphamide.

In cases where conventional immunosuppressive therapy has failed, the anti-CD20 antibody rituximab has demonstrated reasonable efficacy and an acceptable adverse effect profile. [31, 32, 33, 34]  Fenoglio et al reported successful use of rituximab as first-line therapy in six adult patients with MCD, and suggest that rituximab may be preferentially used in patients at high risk for adverse effects from corticosteroids. [35]  

Rituximab may be effective in relapsed MCD because relapse has been linked to the reappearance of B19 cells, which rituximab depletes. However, randomized controlled trials need to be conducted before guidelines can be issued. [32, 36, 37]  

In 20% of steroid-resistant patients, a genetic mutation may be responsible. One of these is the NPHS2 mutation; however, heterozygotes respond well to steroids. [38]

In children with steroid-resistant nephrotic syndrome, Gulati et al reported that those who received the calcineurin inhibitor tacrolimus and steroids had a higher complete/partial remission rate and increased chances of sustained remission with fewer adverse effects compared with those who received cyclophosphamide. [39] A Chinese study in patients with adult-onset minimal change nephrotic syndrome found that tacrolimus monotherapy after short-term intravenous methylprednisolone was noninferior to conventional glucocorticoid treatment. [40]

Mycophenolate mofetil (MMF) has been shown in limited studies to be beneficial in patients with steroid-dependent or frequently relapsing MCD. [41, 42, 43] Similarly, the immune modulator levamisole has shown benefit in small trials. [44]

For the treatment of frequently relapsing or steroid-dependent MCD, the Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group recommends cyclophosphamide in patients with no previous cyclophosphamide exposure and no treatment preference. For patients who received cyclophosphamide previously or who wish to avoid cyclophosphamide, treatment options are rituximab, calcineurin inhibitors, and MMF/sodium mycophenolate. [45]



Class Summary

These agents control volume overload.

Furosemide (Lasix)

Has potent diuretic effects by blocking the sodium reabsorption in the thick ascending limb of the loop of Henle.



Class Summary

For remission of proteinuria.

Prednisone (Sterapred)

Exerts anti-inflammatory effect via the inhibition of inflammatory mediator gene transcription.


Antineoplastic agents

Class Summary

For remission of nephrotic syndrome.

Cyclophosphamide (Cytoxan, Neosar)

Interferes with normal function of DNA by alkylation and cross-linking strands of DNA and by possible protein modification.


Immunosuppressant agents

Class Summary

For remission of nephrotic syndrome.

Cyclosporine A (Sandimmune, Neoral)

Inhibits production and release of IL-2, leading to inhibition of IL-2–mediated activation of T lymphocytes.

Chlorambucil (Leukeran)

To induce remission of proteinuria. Interferes with DNA replication and RNA transcription.

Tacrolimus (Astagraf XL, Envarsus XR, Hecoria)

Calcineurin inhibitor; inhibits T-cell activation and proliferation, humoral immunity.



Class Summary

To induce remission of nephrotic syndrome.

Levamisole (Ergamisol)

Stimulates formation of antibodies and enhances T-cell responses. Acts as a biochemical modulator of fluorouracil.

Mycophenolate mofetil (CellCept)

Inhibitor of de novo purine pathway with preferential inhibitory effects on T and B lymphocyte proliferation, has been used to treat steroid-dependent nephrotic syndrome.