Case Presentation: A 50-year-old woman with prior cerebrovascular accident, paroxysmal atrial fibrillation, hypertension, and diabetes who presented for her second syncopal episode in as many months. Her exam was unremarkable aside from chronic neurologic deficits and new lower extremity swelling. Initial labs revealed elevated creatinine and large protein on her urinalysis with a very low serum albumin. Subsequent urine protein/creatinine ratio revealed 26.7 grams of protein per gram of creatinine. Further workup revealed normal complement levels, as well as negative ANA, hepatitis serologies, Sjogren’s antibodies, and rheumatoid factor, but positive RPR (1:256) and treponemal antibodies. A lumbar puncture was done to rule out neurosyphilis as cause of prior CVA. VDRL-CSF studies came back negative. She was started on antiproteinuric agents and received a single dose of IM Penicillin G for secondary syphilis. On follow-up in Nephrology clinic 3 months post-treatment, her Cr down-trended back to baseline and her swelling was much improved.

Discussion: There are an estimated 6 million cases of syphilis annually in people aged 15 to 49 [1]. From 2015 to 2016, rates of primary and secondary syphilis increased in every age group over 15 years, in every race, ethnicity, and region [1]. In contrast, the incidence of nephrotic syndrome is much lower, as there are only three new cases per 100,000 adults per year [2]. However, recent reversal of syphilis incidence trends in western countries emphasizes the importance of considering secondary syphilis as a cause of acute nephrotic syndrome, though it does remain exceedingly rare, with roughly 10 cases documented from 1989 to 2014 [3]. Membranous nephropathy (MN) is the second most common cause of nephrotic syndrome in adults behind focal segmental glomerulosclerosis, and can be classified as primary or secondary [4]. Only approximately 20% of cases of MN can be classified as secondary, meaning they are associated with other systemic diseases or exposures [5]. The exact mechanism for syphilis triggering immune complex formation is unknown, but recent studies have revealed MN in syphilis is associated with a novel target antigen called neuron-derived neurotrophic factor (NDNF) [6, 7].

Conclusions: We present a case of acute nephrotic syndrome secondary to syphilis. This case demonstrates the importance of considering syphilis as a cause of MN, even with lack of patient reported history of primary syphilis. This case also demonstrates the acuity of very severe proteinuria, as the patient had normal renal function just three weeks prior. We postulate that the incidence syphilitic MN will continue to rise with the resurgence of syphilis in the western world.