Clinical Outcomes of C3 Glomerulopathy and IC-MPGN in Russia: Hybrid Retrospective - Prospective Study

Complete response is defined as proteinuria <0.5 g/24 h with stable eGFR (less than 20% decline in eGFR from baseline without the need for renal replacement therapy).

Partial response is defined as reduction of proteinuria at stable eGFR (no decrease of >20% of baseline value): >50% (from baseline) (in those with proteinuria <3.5 g/day or >3.5 g/day but without nephrotic syndrome (NS)) OR in ≥50% from baseline accompanied by a regression of NS (NS <3.5 g/day and blood albumin ≥30 g/L).

Complete remission was defined as proteinuria <0.5 g/24 h with a stable eGFR (less than 20% decline in eGFR from baseline without the needs for renal replacement therapy).

Partial remission was defined as a reduction in proteinuria at stable eGFR (no decrease of >20% of baseline): >50% (from baseline) (in those with proteinuria <3.5 g/day or >3.5 g/day but without nephrotic syndrome (NS)) OR in ≥50% from baseline accompanied by a regression of NS (NS: <3.5 g/day and blood albumin ≥30 g/L)

Clinical relapse was defined as a proteinuria >3.5 g/24h after achieving complete remission or, in those with partial remission, as an increase of proteinuria >50% compared with the lowest value during remission with recurrence of NS

Composite progression defined as 40% eGFR decline from the baseline and/or eGFR <15 mL/min per 1.73 m2 and/or renal replacement therapy

Number and proportion of patients with progression to end-stage kidney disease from index-date up to 12 months

Number and proportion of patients who died from index date up to 12 months

Time in months from index date to start of maintenance dialysis

Time in months from the diagnosis date to the start date of dialysis

Time in months from first treatment date to the start date of dialysis

Time in months from the diagnosis date to transplantation

Time in months from the diagnosis date to the date of complete remission

Time in months from the diagnosis date to the date of partial remission

Time in months from the diagnosis date to the date of overall remission (complete and partial remission)

Time in months from the diagnosis date to progression

Number and proportion of patients with a) an increase in eGFR by ≥15% from the baseline; b) decrease in eGFR by ≥15% from the baseline; c) stable eGFR (change up to 15%) from index date up to 12 months

Time in months from index date to 30%, 40% and 50% decline in eGFR

Number and proportion of patients with proteinuria >1 g/24 h and eGFR ≥30 mL/min per 1.73 m2 from index date up to 12 months

Number and proportion of patients with nephrotic syndrome from index date up to 12 months

Number and proportion of patients by age, gender, BMI, BSA, family history of kidney disease, transplant status, blood pressure, laboratory markers: serum creatinine level (µmol/L), eGFR, urinary blood cell (RBCs/hpf), proteinuria (g/24h), serum albumin (g/L); eGFR rate of change; chronic kidney disease (CKD) stage; proteinuria ≥1 g/24 h AND eGFR ≥30 mL/min per 1.73 m2

Morphologically verified disease form: DDD (subject to electron microscopy), C3GN (subject to electron microscopy), C3G (in the absence of informative electron microscopy data), IC-MPGN.

Number of patients with presence of serum complement markers (C3, C4, CH50, C5a), serum factor H, rare genetic variants at baseline

Number and proportion of patients stratified by treatment sequence and specific regimen of treatment

Number and proportion of patients that discontinued a specific regimen of treatment at each line of therapy at any time during follow-up and reason for discontinuation for each cohort

Number of exposed doses for non-continuous treatments (e.g., pulse therapy, rituximab infusion) in each cohort

• mesangial proliferation (% of glomeruli),
• endocapillary hypercellularity (% of glomeruli),
• membranoproliferative morphology (thickening and/or double contouring of the capillary basement membranes),
• leukocyte infiltration,
• proportion of completely intact glomeruli (%)
• proportion of cellular (%), fibrous (%), fibrocellular (%) crescents,
• fibrinoid necrosis,
• interstitial infiltration,
• interstitial fibrosis (%),
• tubular atrophy (%),
• global and segmental glomerulosclerosis (quantitatively, % of all glomeruli)
• arteriosclerosis and arteriolosclerosis

Number of patients with signs of thrombotic microangiopathy in the biopsy specimen at baseline

Number of patients with acute tubular necrosis at baseline

Number of patients with presence of C1q, IgA, IgM, IgG, C3, kappa chain, lambda chain deposits at baseline

• Descriptive adherence data based on question score
• Patient-reported outcomes, SF-36 (RAND)

Number of patients (%) with adverse events/serious adverse events by treatment option from index date up to 12 months

Change from baseline of systolic and diastolic blood pressure (BP) (with percentiles for children) at 6 and 12 month

Change from baseline serum creatinine level (µmol/L) at 6 and 12 months

Change from baseline estimated glomerular filtration rate (eGFR) at 6 and 12 months

Change from baseline eGFR rate of change over time (eGFR slope) at 6 and 12 months

Change from baseline chronic kidney disease (CKD) stage (number of patients, %) at 6 and 12 months

Change from baseline red blood cell (RBC) count at 6 and 12 months

Change from baseline RBC casts at 6 and 12 months

Change from baseline daily proteinuria (proteinuria in g/24 hours) at 6 and 12 months

Change from baseline proteinuria >1 g/24 h at 6 and 12 months

Change from baseline eGFR ≥30 mL/min per 1.73 m2 at 6 and 12 months

Change from baseline number of patients with nephrotic syndrome (%) at 6 and 12 months