Primary membranous nephropathy Urological and Genital Diseases
Conditions
Interventions
Intervention arm - Rituximab injection 500mg IV given on days 1 and 15
Control arm - Modified Ponticelli regimen (cyclical steroids/cyclophosphamide for 6 months)
Mont
Sponsors
Muljibhai Patel Urological Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients older than 18 years who provide written informed consent. 2. Biopsy-proven primary MN within 2 years of enrolment with nephrotic range proteinuria denoted by 24-hour urine protein =3.5 g or UPCR (urine protein:creatinine ratio) =3500 mg/g as well as the following: 2.1. Serology or biopsy positive for AntiPLA2R 2.2. Serology or biopsy negative for AntiPLA2R and secondary causes ruled out 2.3. Evaluation for secondary causes was done in all patients, even in patients who were positive for Anti-PLA2R antibodies on serology or PLA2R antigen on biopsy because these have also been found in some cases of secondary MN 3. Estimated GFR =30 ml/min/1.73m². The CKD-EPI creatinine equation was used for the calculation of the eGFR 4. Treatment with an ACEI or ARB for at least 3 months before enrolment
Exclusion criteria
Exclusion criteria: 1. Secondary MN 2. Active serious infections 3. Pregnant women 4. Suspected or known hypersensitivity to either interventional drug 5. Patients with persistently low estimated GFR <30 ml/min/1.73m² in the absence of acute causes such as acute tubular injury, renal vein thrombosis and others
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The proportion of patients reaching complete or partial remission at 6 months, defined according to the 2012 KDIGO guidelines as follows: Complete remission: a reduction of proteinuria to <0.3 g/24 h (uPCR <300 mg/g) with normal serum albumin concentration and normal serum creatinine Partial remission: a reduction of proteinuria to <3.5 g/day (uPCR <3500 mg/g) and a 50% or greater reduction from peak values accompanied by an improvement or normalisation of serum albumin concentration and stable serum creatinine 1. Proteinuria measured using the urine protein creatinine ratio (using Pyrogallol red and Jaffe kinetic reaction test methodology) at baseline and 6 months 2. Serum albumin concentration measured using the Bromocresol green test at baseline and 6 months 3. Serum creatinine measured using the Jaffe kinetic test at baseline and 6 months | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. The proportion of patients reaching either complete or partial remission at 12 months after therapy (measured as per the primary outcome measure) 2. The proportion of patients with relapsing nephrotic syndrome measured among patients who previously underwent partial remission or complete remission at any time during the study period as determined by proteinuria (measured as per the primary outcome measure) 3. The time to relapse of nephrotic syndrome after initial remission as determined by proteinuria (measured as per the primary outcome measure) 4. Serum anti-PLA2R levels measured using EUROIMMUN Anti-PLA2R ELISA (quantitative method) before treatment and at 6 and 12 months post-therapy 5. Efficacy outcome variables during the study period including the trend of the magnitude of proteinuria, serum albumin, serum proteins, serum creatinine and estimated GFR (measured by the CKD-EPI formula) at baseline, 6 and 12 months 6. Proportion of patients developing the following adverse events during the study period, as determined by clinical evaluation including patient interviews and patient notes and lab investigations: 6.1. Infections: symptoms such as fever, cough, dysuria; signs of infection such as fever, respiratory system signs including rales/crepitations, skin lesions of Tinea; lab investigations including total white blood cell (WBC) count (by automated cell counter machine), urine routine analysis (using Multistix and microscopic examination of urine sediment after centrifugation), chest X-ray 6.2. Leucopenia determined by total WBC count (by automated cell counter machine) 6.3. Infusion reaction determined by clinical evaluation 6.4. Acute kidney injury after the start of therapy determined by measuring serum creatinine using the Jaffe kinetic reaction | — |
Countries
India
Outcome results
None listed