Revisiting post-infectious glomerulonephritis in the emerging era of C3 glomerulopathy

Abstract

Background: Post-infectious glomerulonephritis (PIGN) is an immune complex-mediated glomerular injury that typically resolves. Dominant C3 deposition is characteristic of PIGN, but with the emergence of C3 glomerulonephritis (C3GN) as a distinct entity, it is unclear how the pathologic similarities between PIGN and C3GN should be reconciled. Therefore, nephrologists and nephropathologists need additional guidance at the time of biopsy.

Methods: We studied 23 pediatric and young adult patients diagnosed with PIGN. Patients were divided into two groups, one with co-dominance between C3 and immunoglobulins and the other meeting proposed diagnostic criteria for C3GN. Clinical and pathological features were compared.

Results: No clinical and/or pathological features could distinguish between those with C3-co-dominant deposits and those with C3 dominance. Nearly all patients in both groups regained their baseline renal function without clinical intervention.

Conclusions: Although the identification of abnormalities of the alternative pathway of complement is characteristic of C3GN, testing is not widely available and the turnaround time often exceeds 1 month. Our study found that PIGN with either co-dominant or dominant C3 deposition in a cohort of young patients has excellent short-term outcomes. Close clinical observation for persistent abnormalities, such as hypocomplementemia, prolonged hematuria or proteinuria, is recommended to single out patients that may harbor intrinsic complement abnormalities.

Keywords: alternative pathway; complement.

Fig. 1.

A glomerulus from a patient with C3-dominant deposits shows an exudative glomerulonephritis with abundant intracapillary neutrophils (hematoxylin and eosin stain).

Fig. 2.

(A) The ‘starry-sky’ IF pattern shows distinct granular staining of mesangial areas and capillary walls (C3 IF). (B) The ‘garland’ pattern of staining shows densely packed deposits with frequent confluent staining around capillary loops (C3 IF).

Fig. 3.

(A) By electron microscopy, all cases showed at least focal subepithelial ‘hump’-shaped deposits. (B) Intramembranous deposits were frequently identified, most of which were ovoid in shape and oriented perpendicular to the glomerular basement membrane (arrow). (C) A minority of cases in the C3-dominant group showed segmental elongated intramembranous deposits (arrow), reminiscent of dense deposit disease.