Spectrum of Kidney Pathology in Patients with Syphilis

Background: Syphilis has been associated with multiple kidney diseases, primarily studied within small series. A large cohort of patients with active syphilis who underwent kidney biopsy were examined to evaluate the histopathologic spectrum and clinicopathologic features of disease. Methods: Patients with syphilis who underwent a native kidney biopsy were identified from the renal pathology archives at Arkana Laboratories from 2006-2024. Patients were identified through a listed clinical history of syphilis in the medical record and/or positive laboratory testing for RPR or anti-treponemal antibodies. Patients with a remote or treated syphilitic infection were excluded. Results: A total of 111 patients with syphilis who underwent kidney biopsy were identified. The mean age was 42.0 ±14.5 years and there was male predominance (86.5%). The majority of patients presented with acute kidney injury with a mean serum creatinine of 4.4 ± 3.8 mg/dL. Co-infections were common, with HIV in 53 (47.7%), HBV in 9 (8.1%), and HCV in 9 (8.1%). The most common disease states, in descending order, included membranous nephropathy (MN) (n=29), HIV-associated diseases (n=21), acute interstitial nephritis (AIN, n=11), acute tubular injury (n=11), infection-associated glomerulonephritis (n=9), and IgA nephropathy (n=8). The remaining patients had various diagnoses unlikely to be associated with syphilitic infection, such as diabetic glomerulosclerosis (n=12) and arterionephrosclerosis (n=7), among others. Of 29 patients with MN (26.1%), 2 were PLA2R+, 2 were EXT+, and the remaining were PLA2R negative of unknown type. Staining for multiple immune reactants was common in MN cases with IgA staining in 24.1%, IgM in 34.5%, C3 in 89.7%, C1q in 44.8%, and 10.3% were 'full-house'. Of 21 patients with HIV-associated pathology (18.9%), 17 had collapsing glomerulopathy (HIVAN) and 7 had mesangial immune complex deposition (HIVICK). Of 11 patients with AIN, 5 were plasma cell rich, 1 was neutrophil rich, and the remaining had mixed infiltrates. Three of 8 patients with IgA nephropathy were secondary to liver disease related to viral hepatitis. Conclusion: The most common kidney biopsy diagnosis seen in patients with syphilis was membranous glomerulopathy. Disease associated with co-infections, particularly HIV and viral hepatitis, were also common in this setting.