PMC5457925_01
Clinical course of the patient. Changes in the serum creatinine (SCr, continuous lines), urine protein-to-creatinine ratio (UPCR, dotted lines), and urine volume during hospitalization (A) and after discharge (B). A: The first kidney biopsy (KB) was performed on hospital day 2. Hemodialysis was initiated on hospital day 13 due to oliguria and congestion, and symptomatic therapy resulted in a gradual decrease in the SCr and increase in the urine volume, and hemodialysis was ceased on day 52. B: The second KB was performed due to transient recurrence of nephrotic-range proteinuria. BW: body weight, KB: kidney biopsy, UPCR: urine protein to creatinine ratio, SCr: serum creatinine
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The first kidney biopsy was performed on hospital day 2 (Fig. 1). On day 13 after admission, hemodialysis was initiated due to oliguria and congestion despite high-dose intravenous diuretics (Fig. 1).
Representative light microscopy. A: Diffuse proliferative and circumferential crescentic glomerulonephritis at the first kidney biopsy (Masson trichrome, x40). B: Mesangial and endocapillary proliferation with double contours along the capillary walls and a cellular crescent [periodic acid-methenamine-silver (PAM) stain, x200]. C: Increased global sclerosis with moderate tubular fibrosis at the second kidney biopsy (periodic acid-Schiff stain, x40). D: A glomerulus showing a fibular crescent and mesangial proliferation with double contours along the capillary walls (Masson trichrome, x400).
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Numerous circumferential cellular crescents and diffuse endocapillary and mesangial proliferation with double contour formation along the capillary walls were observed (Fig. 2A and B). A second kidney biopsy performed at that time showed markedly increased sclerotic or collapsing glomeruli (approximately 70% of all glomeruli) with fibrous crescents (15-20%), moderate tubular atrophy, and fibrosis (Fig. 2C). The remaining glomeruli showed mesangial proliferation with double contour formation along the capillary walls (Fig. 2D).
Immunofluorescence study. (A-H) Immunofluorescence staining for C3 and IgG subtypes showing monoclonal IgG1kappa predominantly along the capillary walls at the first kidney biopsy. A: IgG (+), B: C3 (++), C: IgG1 (+), D: IgG2 (-), E: IgG3 (-), F: IgG4 (-), G: kappa (+), and H: lambda (-). (I-L) Immunofluorescence staining for IgG subtypes showing weak monoclonal IgG1kappa deposition at the second kidney biopsy. I: IgG (+), J: C3 (++), K: IgG1 (+), and L: kappa (+).
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Immunofluorescence showed granular IgG, IgG1, kappa light chain, and C3 deposits predominantly along the capillary walls, with undetectable IgM, IgA, C1q, IgG2-4, and lambda light chain (Fig. 3A-H).
Electron microscopy. A: Electron-dense deposits (arrows) are predominantly seen in the subendothelium at the first kidney biopsy (x4,000). B: Subepithelial hump-shaped deposits (*). C: Electron microscopy showing subendothelial deposits at the second kidney biopsy (*, x4,000).
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Electron microscopy (EM) showed subepithelial and subendothelial deposits, including hump-like shaped deposits (Fig. 4A and B).
Glomerular staining for nephritis-associated plasmin receptor (NAPlr) and plasmin activity. A: NAPlr staining labeled with fluorescein isothiocyanate (green) at the first kidney biopsy. B: Plasmin activity by in situ zymography with localization similar to NAPlr staining. (C-H) Representative photomicrographs of double immunofluorescence staining for IgG1 or kappa (FITC; green) and NAPlr (Alexa Fluor 594; red). The distributions of IgG1 or kappa (C or F) and NAPlr (D or G) were different in the merged images (E or H). I: Staining for NAPlr was negative at the second kidney biopsy. J: Plasmin was also negative.
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Positive immunofluorescent staining for nephritis-associated plasmin receptor (NAPlr) and positive in situ zymography for plasmin (Fig. 5A and B) suggested a preceding infection as the etiology of glomerulonephritis, which could partially explain the spontaneous recovery of the renal function later observed in this case, similar to that observed in PIGN. NAPlr and plasmin deposits were absent (Fig. 5I and J). Nephrotic-range proteinuria spontaneously resolved, and the UPCR and SCr levels were within the ranges of 1-2 g/gCr and 1.2-1.5 mg/dL, respectively, for one year following discharge.
Serum and urine protein electrophoresis with immunofixation. Both serum (left) and urine (right) protein electrophoresis showed no bands within the IgG, IgA, IgM, kappa, or lambda columns.
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Repeated serum and urine electrophoresis showed no paraproteins (Fig. 6).