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. 2022 Feb 28;2(2):CD003233.
doi: 10.1002/14651858.CD003233.pub3.

Interventions for focal segmental glomerulosclerosis in adults

Elisabeth M Hodson  1   2 , Aditi Sinha  3 , Tess E Cooper  1   2
Affiliations

Interventions for focal segmental glomerulosclerosis in adults

Elisabeth M Hodson et al. Cochrane Database Syst Rev. .

Abstract

Background: Focal segmental glomerulosclerosis (FSGS) can be separated into primary, genetic or secondary causes. Primary disease results in nephrotic syndrome while genetic and secondary forms may be associated with asymptomatic proteinuria or with nephrotic syndrome. Overall only about 20% of patients with FSGS experience a partial or complete remission of nephrotic syndrome with treatment. FSGS progresses to kidney failure in about half of the cases. This is an update of a review first published in 2008.

Objectives: To assess the benefits and harms of immunosuppressive and non-immunosuppressive treatment regimens in adults with FSGS.

Search methods: We searched the Cochrane Kidney and Transplant Register of Studies to 21 June 2021 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.

Selection criteria: Randomised controlled trials (RCTs) and quasi-RCTs of any intervention for FSGS in adults were included. Studies comparing different types, routes, frequencies, and duration of immunosuppressive agents and non-immunosuppressive agents were assessed.

Data collection and analysis: At least two authors independently assessed study quality and extracted data. Statistical analyses were performed using the random-effects model and results were expressed as a risk ratio (RR) for dichotomous outcomes, or mean difference (MD) for continuous data with 95% confidence intervals (CI). Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

Main results: Fifteen studies (560 participants) were included. No studies specifically evaluating corticosteroids compared with placebo or supportive therapy were identified. Studies evaluated participants with steroid-resistant FSGS. Five studies (240 participants) compared cyclosporin with or without prednisone with different comparators (no specific treatment, prednisone, methylprednisolone, mycophenolate mofetil (MMF), dexamethasone). Three small studies compared monoclonal antibodies (adalimumab, fresolimumab) with other agents or placebo. Six single small studies compared rituximab with tacrolimus, cyclosporin plus valsartan with cyclosporin alone, MMF with prednisone, chlorambucil plus methylprednisolone and prednisone with no specific treatment, different regimens of dexamethasone and CCX140-B (an antagonist of the chemokine receptor CCR2) with placebo. The final study (109 participants) compared sparsentan, a dual inhibitor of endothelin Type A receptor and of the angiotensin II Type 1 receptor, with irbesartan. In the risk of bias assessment, seven and five studies were at low risk of bias for sequence generation and allocation concealment, respectively. Four studies were at low risk of performance bias and 14 studies were at low risk of detection bias. Thirteen, six and five studies were at low risk of attrition bias, reporting bias and other bias, respectively. Of five studies evaluating cyclosporin, four could be included in our meta-analyses (231 participants). Cyclosporin with or without prednisone compared with different comparators may increase the likelihood of complete remission (RR 2.31, 95% CI 1.13 to 4.73; I² = 1%; low certainty evidence) and of complete or partial remission (RR 1.64, 95% CI 1.10 to 2.44; I² = 19%) but not of partial remission (RR 1.36, 95% CI 0.78 to 2.39, I² = 22%). In Individual studies, cyclosporin with prednisone versus prednisone may increase the likelihood of partial (49 participants: RR 7.96, 95% CI 1.09 to 58.15) or complete or partial remission (49 participants: RR 8.85, 95% CI 1.22 to 63.92) but not of complete remission. The remaining individual comparisons may make little or no difference to the likelihood of complete remission, partial remission or complete or partial remission compared with no treatment, methylprednisolone, MMF, or dexamethasone. Individual study data and combined data showed that cyclosporin may make little or no difference to the outcomes of chronic kidney disease or kidney failure. It is uncertain whether cyclosporin compared with these comparators in individual or combined analyses makes any difference to the outcomes of hypertension or infection. MMF compared with prednisone may make little or no difference to the likelihood of complete remission (33 participants: RR 1.05, 95% CI 0.58 to 1.88; low certainty evidence), partial remission, complete or partial remission, glomerular filtration rate, or infection. It is uncertain whether other interventions make any difference to outcomes as the certainty of the evidence is very low. It is uncertain whether sparsentan reduces proteinuria to a greater extent than irbesartan.

Authors' conclusions: No RCTs, which evaluated corticosteroids, were identified although the KDIGO guidelines recommend corticosteroids as the first treatment for adults with FSGS. The studies identified included participants with steroid-resistant FSGS. Treatment with cyclosporin for at least six months was more likely to achieve complete remission of proteinuria compared with other treatments but there was considerable imprecision due to few studies and small participant numbers. In future studies of existing or new interventions, the investigators must clearly define the populations included in the study to provide appropriate recommendations for patients with primary, genetic or secondary FSGS.

Trial registration: ClinicalTrials.gov NCT00065611 NCT01613118 NCT00193648 NCT00814255 NCT00135811 NCT03536754 NCT01665391 NCT00404833 NCT00302536 NCT01451489 NCT00801463 NCT00956059 NCT03649152 NCT03493685 NCT03298698 NCT02633046 NCT02592798.

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Conflict of interest statement

  1. Elisabeth M Hodson has declared they have no conflict of interest

  2. Aditi Sinha has declared they have no conflict of interest

  3. Tess E Cooper has declared they have no conflict of interest

Figures

1
1
Flow diagram.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1: Cyclosporin versus different comparators, Outcome 1: Complete remission of proteinuria
1.2
1.2. Analysis
Comparison 1: Cyclosporin versus different comparators, Outcome 2: Partial remission of proteinuria
1.3
1.3. Analysis
Comparison 1: Cyclosporin versus different comparators, Outcome 3: Complete or partial remission
1.4
1.4. Analysis
Comparison 1: Cyclosporin versus different comparators, Outcome 4: Chronic kidney disease
1.5
1.5. Analysis
Comparison 1: Cyclosporin versus different comparators, Outcome 5: Kidney failure
1.6
1.6. Analysis
Comparison 1: Cyclosporin versus different comparators, Outcome 6: Adverse effects: hypertension
1.7
1.7. Analysis
Comparison 1: Cyclosporin versus different comparators, Outcome 7: Adverse effects: infection
1.8
1.8. Analysis
Comparison 1: Cyclosporin versus different comparators, Outcome 8: Adverse effects: total hospitalisations
1.9
1.9. Analysis
Comparison 1: Cyclosporin versus different comparators, Outcome 9: Adverse effects: GI disturbances
2.1
2.1. Analysis
Comparison 2: Cyclosporin plus valsartan versus cyclosporin alone, Outcome 1: Remission
2.2
2.2. Analysis
Comparison 2: Cyclosporin plus valsartan versus cyclosporin alone, Outcome 2: Protein excretion at 6 months
2.3
2.3. Analysis
Comparison 2: Cyclosporin plus valsartan versus cyclosporin alone, Outcome 3: Biochemical outcomes at 6 months
3.1
3.1. Analysis
Comparison 3: Chlorambucil plus prednisone versus no specific treatment, Outcome 1: Kidney outcomes
4.1
4.1. Analysis
Comparison 4: Mycophenolate mofetil versus prednisone, Outcome 1: Kidney outcomes
4.2
4.2. Analysis
Comparison 4: Mycophenolate mofetil versus prednisone, Outcome 2: Adverse effects
4.3
4.3. Analysis
Comparison 4: Mycophenolate mofetil versus prednisone, Outcome 3: GFR
5.1
5.1. Analysis
Comparison 5: Dexamethasone: 2 weekly versus 4 weekly, Outcome 1: Partial remission at 48 weeks
5.2
5.2. Analysis
Comparison 5: Dexamethasone: 2 weekly versus 4 weekly, Outcome 2: GFR
5.3
5.3. Analysis
Comparison 5: Dexamethasone: 2 weekly versus 4 weekly, Outcome 3: 24‐hour urine protein excretion
5.4
5.4. Analysis
Comparison 5: Dexamethasone: 2 weekly versus 4 weekly, Outcome 4: Adverse effects
6.1
6.1. Analysis
Comparison 6: Rituximab versus tacrolimus, Outcome 1: Remission of proteinuria by 12 months
6.2
6.2. Analysis
Comparison 6: Rituximab versus tacrolimus, Outcome 2: Relapse by 12 months
6.3
6.3. Analysis
Comparison 6: Rituximab versus tacrolimus, Outcome 3: Adverse effects
7.1
7.1. Analysis
Comparison 7: Fresolimumab versus placebo, Outcome 1: Partial remission at 16 weeks
8.1
8.1. Analysis
Comparison 8: Sparsentan versus irbesartan, Outcome 1: Partial remission at 8 weeks
8.2
8.2. Analysis
Comparison 8: Sparsentan versus irbesartan, Outcome 2: Adverse effects
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References to other published versions of this review

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