Introduction:
Membranous nephropathy (MN), both primary and secondary, is one of the common causes of adult onset nephrotic syndrome. Renal biopsy can usually lead us to a confirmatory diagnosis in PLA2R negative cases. We present a case of a patient of secondary membranous nephropathy, the etiology of which was difficult to ascertain even with a renal biopsy and led us to face a diagnostic as well as a treatment dilemma.
Methods:
This was a case of a 30 year old male who was incidentally detected to be hepatitis B positive with high HBV DNA titres and started on Tenofovir. 3 months later, patient developed swelling of bilateral lower limbs, abdominal distension and passage of frothy urine. Investigations at that point revealed a serum creatinine of 0.82 and urinary dipstick protein being 3 + without any other active sediments. His HBV DNA PCR titres were still high at 28957. He was found to have nephrotic range proteinuria on follow up. His ANA was 3+ fine speckled, C3 and C4 were 60 and 8.9, respectively and dsDNA was positive. ANCA, MPO, PR3 were all negative. On his next monthly visit, his 24 hour urinary protein had almost doubled to 9840 mg/day. His repeat ANA was 2+, repeat C3 and C4 levels were persistently low. HBV DNA PCR titres came down to 3365. Serum urea and creatinine were 25 and 1.2. On his next visit, 24 hour urinary protein was even higher at 11884 mg/day. His PLA2R, C3,C4 and dsDNA were all negative this time. A provisional diagnosis of adult onset nephrotic syndrome likely due to membranous nephropathy secondary to either hepatitis B or lupus class V was made. So, we faced a diagnostic dilemma as this patient was on Tenofovir for 6 months and his HBV viral loads were reducing. However, proteinuria was seen to persistently on a high despite continuous Hepatitis B treatment. Lupus was a possibility as ANA was 3+, fine speckled pattern with persistence of low C3 and C4 for more than 2 months. So, he underwent a renal biopsy.
Results:
Renal biopsy revealed secondary membranous nephropathy. However, the etiology of secondary membranous nephropathy was still not clear despite renal biopsy. There were factors favouring both the etiologies. We, therefore, went for an immunohistochemistry (IHC) testing to establish our etiology. IHC for surface HBsAg, HBeAg and antiHBc were negative as depicted in the Figure 1. These findings were strongly in favour of Lupus nephritis related membranous nephropathy. The patient had a good response to oral Prednisolone along with Tacrolimus.
Conclusions:
To overcome similarities in terms of clinical, laboratory and biopsy parameters, we should, thus, look at the pathophysiology of the disease. Presence of glomerular HBV(Hepatitis B viral) antigens, especially HbeAg, helps in clinching the diagnosis of HBV MN in patients with overlapping lupus and, therefore, a negative HbeAg in the glomerular tissues negates the diagnosis of HBVMN. Immunohistochemistry (IHC), thus, helps us in solving this diagnostic dilemma as has been proved in our case. We, therefore, recommend more enthusiastic usage of IHC in overlapping cases where multiple etiologies are present and the routine available tests fail in establishing a definitive diagnosis.
I have no potential conflict of interest to disclose.
I did not use generative AI and AI-assisted technologies in the writing process.