How are steroid-resistant nephrotic syndrome (SRNS) and focal segmental glomerulosclerosis (FSGS) treated?

Updated: Mar 04, 2020
  • Author: Jerome C Lane, MD; Chief Editor: Craig B Langman, MD  more...
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Answer

Genetic considerations play an important role in the treatment of SRNS and FSGS; approximately 30% of children with SRNS may have a single-gene cause of their disease. [3] Monogenic SRNS and FSGS are generally unresponsive to immunosuppressive medications, and identification of monogenic cases may avoid unnecessary treatment.

Calcineurin inhibitors (CSA and TAC) are the mainstay of treatment for SRNS and FSGS. In response to CNI treatment, SRNS without a clear genetic link may show complete remission in up to 60% of patients and partial remission in 19% of patients. [56] In one study, the response rate (complete and partial remission) to CSA for non-genetic SRNS was 68% versus 17% (partial remission only) for genetic SRNS. [84]  In a study by Büscher et al, 60% of patients with non-genetic SRNS achieved complete remission and another 19% had partial remission with CSA treatment, compared with 16% of patients with genetic SRNS who had only partial remission. [85]

The efficacy of TAC seems similar to that of CSA. As mentioned above, TAC may have the advantage of avoiding the gingival hyperplasia and hypertrichosis associated with CSA. [75]

Initial dosing recommendations for CSA and TAC in SRNS and FSGS are similar to those for FRNS and SDNS: CSA, 3-5 mg/kg/d divided every 12 hours; TAC, 0.1 mg/kg daily divided every 12 hours. Higher doses may be needed in SRNS and FSGS, and the dose may need to be titrated up carefully until a response is seen or adverse effects warrant a reduction in dose or discontinuation of treatment. [41]

An early, controversial protocol involved high-dose, intravenous methylprednisolone tapered over 78 weeks, in combination with alternate-day oral prednisone; CYP or chlorambucil was added if remission was not achieved in the first 10 weeks. The authors reported a 52% remission rate in SRNS. [86] However, subsequent studies using this protocol have not duplicated the initial success. The risk of steroid toxicity and infection, as well as the lack of sufficient evidence for the effectiveness of this protocol, has dampened enthusiasm for this treatment.

Most studies have shown no clear benefit to the use of alkylating agents in FSGS and SRNS. [60, 87]

In a nonrandomized study of children with SRNS, approximately half responded to MMF. Of 34 patients treated with CSA prior to MMF, 20% achieved complete remission, 39% achieved partial remission, and 41% had no response. Among 18 patients treated only with MMF, 27% achieved complete remission, 33% partial remission, and 40% had no response. [88] The MMF regimen used in this study was 500-600 mg/m2/day or 18 mg/kg/day (maximum, 1 g) for a minimum of 6 months.

In the largest prospective, randomized trial to date in pediatric FSGS, 138 children and adults (aged 2-40 years) received treatment with CSA or MMF with dexamethasone (dexa). Thirty-three percent of patients treated with MMF/dexa and 45% of patients treated with CSA achieved partial or complete remission, which was not statistically different in response rate. No difference was noted between the 2 treatment arms in the rate of sustained remission. [89]

The data are limited regarding the efficacy of rituximab in SRNS and FSGS. Case series indicate that rituximab may be effective in SRNS. [56] However, in an open-label, randomized, controlled trial in 31 children with SRNS resistant to steroids and CNI, no reduction in proteinuria was observed with the addition of rituximab. [10]

Two randomized trials in SRNS have shown a reduction in proteinuria with enalapril or fosinopril. Therefore, ACE inhibitors or ARBs should be considered for all patients with SRNS and FSGS, except when limited by hyperkalemia or significantly reduced kidney function. [56] Additionally, ACE inhibitor and ARB treatment may also have a renoprotective effect and slow progression of renal disease by inhibiting pathways of fibrosis. [90]


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