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Diagnostic and Prognostic Comparison of Immune-Complex-Mediated Membranoproliferative Glomerulonephritis and C3
Marja Kovala1, Minna Seppälä2, Anne Räisänen-Sokolowski1
1Department of Pathology, University of Helsinki and Helsinki University Hospital, 00290 Helsinki, Finland.
Abstract:
Membranoproliferative glomerulonephritis (MPGN) is subdivided into immune-complex-mediated glomerulonephritis (IC-MPGN) and C3 glomerulopathy (C3G). Classically, MPGN has a membranoproliferative-type pattern, but other morphologies have also been described depending on the time course and phase of the disease. Our aim was to explore whether the two diseases are truly different, or merely represent the same disease process. All 60 eligible adult MPGN patients diagnosed between 2006 and 2017 in the Helsinki University Hospital district, Finland, were reviewed retrospectively and asked for a follow-up outpatient visit for extensive laboratory analyses. Thirty-seven (62%) had IC-MPGN and 23 (38%) C3G (including one patient with dense deposit disease, DDD). EGFR was below normal (≤60 mL/min/1.73 m2) in 67% of the entire study population, 58% had nephrotic range proteinuria, and a significant proportion had paraproteins in their serum or urine. A classical MPGN-type pattern was seen in only 34% of the whole study population and histological features were similarly distributed. Treatments at baseline or during follow-up did not differ between the groups, nor were there significant differences observed in complement activity or component levels at the follow-up visit. The risk of end-stage kidney disease and survival probability were similar in the groups. IC-MPGN and C3G have surprisingly similar characteristics, kidney and overall survival, which suggests that the current subdivision of MPGN does not add substantial clinical value to the assessment of renal prognosis. The high proportion of paraproteins in patient sera or in urine suggests their involvement in disease development.
Insights
Membranoproliferative glomerulonephritis (MPGN) subtypes, immune-complex-mediated (IC-MPGN) and C3 glomerulopathy (C3G), show similar clinical features and survival outcomes. This suggests their current classification may not significantly impact renal prognosis assessment.
Area of Science:
- Nephrology
- Immunology
- Pathology
Background:
- Membranoproliferative glomerulonephritis (MPGN) is classified into immune-complex-mediated glomerulonephritis (IC-MPGN) and C3 glomerulopathy (C3G).
- Histological patterns can vary, complicating traditional classification based on morphology alone.
Purpose of the Study:
- To investigate whether IC-MPGN and C3G represent distinct disease entities or a spectrum of the same process.
- To evaluate the clinical utility of the current MPGN subdivision in predicting renal prognosis.
Main Methods:
- Retrospective review of 60 adult MPGN patients diagnosed between 2006-2017.
- Follow-up outpatient visits with extensive laboratory analyses, including complement studies.
- Analysis of clinical characteristics, histological findings, treatment responses, and survival outcomes.
Main Results:
- A classical MPGN pattern was observed in only 34% of patients.
- No significant differences in renal function (eGFR), proteinuria, paraprotein prevalence, treatment, or complement levels were found between IC-MPGN and C3G groups.
- End-stage kidney disease risk and overall survival were similar for both groups.
Conclusions:
- IC-MPGN and C3G exhibit remarkably similar clinical characteristics and prognoses.
- The current subdivision of MPGN may lack substantial clinical value for assessing renal prognosis.
- A high prevalence of paraproteins suggests their potential role in disease pathogenesis.
