A case of neuron-derived neurotrophic factor-positive, syphilis-related membranous nephropathy that achieved spontaneous remission

Abstract

Neuron-derived neurotrophic factor (NDNF) was discovered as a target antigen in membranous nephropathy (MN) caused by syphilis. However, there have been few reports of NDNF-positive MN in Japan. A 19-year-old female patient was admitted to our hospital with nephrotic syndrome and acute kidney injury. After admission, she presented with a skin rash and was serologically positive for syphilis. Kidney biopsy showed MN positive not only for immunoglobulin (Ig) G, but also for IgA and complement C1q. IgG subclass analysis revealed positivity for IgG1 and IgG3. Immunohistochemistry for glomerular NDNF was positive, and a diagnosis of syphilis-related MN was confirmed. Prior to treatment of the infection, her urinary protein decreased to achieve complete remission and her kidney function improved. Benzylpenicillin was administered, and no recurrence of nephrotic syndrome or kidney dysfunction was observed thereafter. This case illustrates the importance of considering syphilis infection when encountering a case of nephrotic syndrome with skin rash. In addition, urinalysis of syphilitic patients should be performed to avoid missing MN that may be in spontaneous remission. Further elucidation of the pathogenesis of NDNF-positive, syphilis-related MN in Japan is needed.

Keywords: Acute kidney injury; Jarisch–Herxheimer reaction; Membranous nephropathy; Neuron-derived neurotrophic factor; Spontaneous remission; Syphilis.

Fig. 1

Papules appeared after hospitalization. a Papules on the palms. Arrows indicate the rash. b Papules on the feet. Arrows indicate the rash. c Papules on the back. The rash is seen over the entire back

Fig. 2

Images of kidney biopsy. a Hematoxylin–eosin stain, 400 × magnification. b Periodic acid–Schiff stain, 400 × magnification. c Periodic acid–methenamine–silver stain, 400 × magnification. d Positive complement C3 immunofluorescent staining of the glomerular loop. e Positive complement C1q immunofluorescent staining of the glomerular loop. f Positive IgG immunofluorescent staining of the glomerular loop. g Positive IgA immunofluorescent staining of the glomerular loop. h Positive immunofluorescent staining for IgG subclass IgG1. i Negative immunofluorescent staining for IgG subclass IgG2. j Positive immunofluorescent staining for IgG subclass IgG3. k Negative immunofluorescent staining for IgG subclass IgG4. l Negative immunofluorescence image for phospholipase A2 receptor staining

Fig. 3

Electron microscopy image of a kidney biopsy. A small number of electron-dense deposits were observed in a subepithelial lesion of the glomerular basement membrane, equivalent to Ehrenreich–Churg stage I. Arrows indicate the electron-dense deposits

Fig. 4

Immunostaining for NDNF. a Immunostaining for NDNF with diaminobenzidine staining, 400 × magnification. b Immunofluorescence for nuclear DAPI staining. c Immunofluorescence for IgG staining. d Immunofluorescence for NDNF staining. e Merged immunofluorescence image shows co-localization of IgG and NDNF. NDNF, neuron-derived neurotrophic factor; DAPI, 4ʹ,6-diamidino-2-phenylindole

Fig. 5

Clinical course. Cr, creatinine; Up/UCr, urinary protein to creatinine ratio