Quiz Page March 2009: A 58-Year-Old Man With Chronic Hepatitis B, Nephrotic Syndrome, and a Papulosquamous Rash

What do you observe in the kidney biopsy specimen? 

Figure 2 shows an entire glomerulus with swelling of the epithelial cells, but an otherwise normal structure without thickening of the glomerular basement membrane. Figure 3A shows electron-dense deposits in the mesangium. Figure 3B shows electron-dense subepithelial deposits of the glomerular basement membrane without spike formation.

What is the most likely cause of the reduced kidney function and nephrotic syndrome? 

Our patient presented with nephrotic syndrome and kidney failure. Kidney biopsy showed membranous glomerulopathy, and serological tests showed active hepatitis B and secondary syphilis. Both infections are associated with nephrotic syndrome with similar kidney biopsy findings.1, 2

In our patient, nephrotic syndrome most likely is caused by the secondary syphilis, based on a recent syphilis infection with rapid disappearance of nephrotic syndrome and recovery of kidney failure after treatment with penicillin. The absence of spike formation on the glomerular basement membrane corresponds to a recent syphilis-induced disease process. Diagnostic criteria are considered by some investigators2, 3 to include: (1) a positive serological test result for syphilis, (2) nephrotic syndrome, (3) the presence of antitreponemal antibody and/or antigen in glomerular deposits, and (4) complete recovery after penicillin therapy. Our patient fulfilled criteria 1, 2, and 4. Only a small number of case reports can be found of patients with syphilis-associated reduced kidney function. Renal complications usually are seen a few weeks after a penile lesion and usually together with the papulosquamous skin rash typically seen in patients with secondary syphilis. Membranous glomerulopathy is the most commonly found pathological lesion. Granular deposition of immunoglobulins and complement fractions together with electron-dense humps on the epithelial side of the glomerular basement membrane are strongly suggestive of an immune complex–mediated disease. Although a pathogenetic role of hepatitis B cannot be excluded in this case, it was less likely the primary cause because the literature describes much slower recovery of hepatitis B–associated nephropathy even in the presence of active antiviral treatment.4 The deposition of HBeAg combined with anti-HBe antibodies on the glomerular basement membrane is the proposed pathogenic condition in hepatitis B–associated nephropathy.1 The absence of anti-HBe antibody formation in our patient therefore argues against a causal relationship between hepatitis B and the nephrotic syndrome and kidney failure observed. Our patient was treated with benzathine penicillin for his syphilis on day 4, lamivudine was started on day 6, and methylprednisolone pulse treatment was initiated for 3 days because of progressive kidney failure. Eight weeks after admission, no more proteinuria was found on dipstick analysis, kidney function had recovered to serum creatinine level of 1.2 mg/dL (110 μmol/L; estimated glomerular filtration rate, 66 mL/min/1.73 m2 [1.10 mL/s/1.73 m2]), albumin level had normalized to 38 g/L, and ascites had resolved. After 1 year of treatment, serum HBeAg test results were still positive.