Hofstra 2010.

Study characteristics
Methods	Study design: parallel, open‐label RCT Study duration: May 1998 to May 2005 Duration of follow‐up: 72 ± 22 months; treatment group 1 (73 ± 20); treatment group 2 (71 ± 2)
Participants	Setting: multicentre Country: Netherlands Inclusion criteria: biopsy‐proven IMN with nephrotic syndrome and high risk for ESKD (urinary B2 microglobulin > 0.5 μg/min and urinary IgG > 125 mg/24 hours) Baseline characteristics Pathology stage: not reported Median proteinuria, range (g/10 mmol Cr): treatment group 1 (9.6, 5.9 to 14.4); treatment group 2 (12.0, 5.6 to 17.2) Mean serum albumin ± SD (g/L): treatment group 1 (22.6 ± 4.8); treatment group 2 (22.3 ± 3.8) Median SCr, range (µmol/L): treatment group 1 (94, 68 to 122); treatment group 2 (101, 75 to 126) Mean GFR ± SD (mL/min/1.73 m²): treatment group 1 (81 ± 17); treatment group 2 (76 ± 13) Baseline declining kidney function: no; SCr was < 135 μmol/L in all patients at randomisation Number: treatment group 1 (14); treatment group 2 (12) Mean age ± SD (years): treatment group 1 (48 ± 13); treatment group 2 (49 ± 10) Sex (M/F): treatment group 1 (13/1); treatment group 2 (11/1) Exclusion criteria: secondary cause of MN was suspected based on clinical or laboratory criteria; previously treated with immunosuppressive drugs; systemic diseases; pregnancy or inadequate contraception; active infection; unstable angina pectoris; DM, clinical evidence of renal vein thrombosis; liver function test abnormalities (> 2 times the upper limit of normal); use of NSAIDs; active peptic ulcer disease and gastrointestinal diseases that could impair the resorption of oral medication
Interventions	Treatment group 1 Early treatment: started immunosuppressive therapy immediately after randomisation Oral CPA: 1.5 mg/kg/day for 12 months IV methylprednisolone: 1 g on days 1, 2, 3, 60, 61, 62, 120, 121 and 122 Oral prednisone: 0.5 mg/kg/day for 6 months, and subsequently tapered by decreasing the dose by 5 mg/week For prevention of gastric symptoms, famotidine 1 daily dose 20 mg was added. From 1999 onwards, trimethoprim‐sulfamethoxazole was added 480 mg/day in the first 4 to 6 months, to prevent Pneumocystis jiroveci pneumonia. In young fertile patients, the treatment regimen was modified because of the infertility risk associated with the use of CPA; in these patients, after 3 months of treatment CPA was replaced by AZA 1.5 mg/kg/day for the remaining 9 months. Three patients were treated according to the modified treatment scheme with AZA Treatment group 2 Late treatment: started immunosuppressive treatment (as for early treatment) when kidney function deteriorated, defined as an increase of SCr with ≥ 25% reaching a level of ≥ 135 μmol/L or an increase of SCr with ≥ 50% Two patients received modified treatment with AZA after 3 months Co‐medication Use of ACEi or ARB during follow‐up: all patients were aggressively treated to decrease BP (target value 130/80 mm Hg), primarily by using ACEi and/or ARB
Outcomes	Death ESKD Partial or complete remission Final proteinuria Final SCr Final GFR Side effects leading to patient withdrawal or hospitalisation
Notes	Funding information: supported by grants from the Dutch Kidney Foundation (NSN OW08 and NSN PC152)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information to permit judgement
Allocation concealment (selection bias)	Unclear risk	No sufficient detail about concealment of the random allocation sequence before or during enrolment of participants
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open‐label study
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Insufficient information to permit judgement
Incomplete outcome data (attrition bias) All outcomes	Low risk	During the first year of the study, 3 patients were excluded because of the following reasons: discovery of a malignancy and withdrawal from the study within 3 months; protocol violation (start of prednisone by a physician in another hospital) and loss to follow‐up due to emigration 7 months after randomisation. Thus, the final analysis included 26 patients
Selective reporting (reporting bias)	Low risk	The study protocol was not available but it was clear that the published reports included all expected outcomes, including those that were pre‐specified
Other bias	Unclear risk	Insufficient information to permit judgement