A 47 year-old African American female who presented for routine annual check-up, was found to have abnormal labs; Creatinine(Cr) of 4.7 and Blood urea nitrogen(BUN) of 37. Her creatinine was 0.8, 6 years prior. Review of systems was non-contributory except for recent bilateral leg swelling, which started 2 months prior and has since resolved after stopping Amlodipine. Her past medical history is significant for multiple sclerosis and hypertension, both diagnosed in the last 5years. She is on daily verapamil and Avonex (Interferon-1β), once weekly. Physical exam showed young woman, in no obvious distress. Her BMI was 48.9. There was no periorbital or pedal edema. Cardiovascular exam was normal, S1 S2 only. Clear lungs bilaterally. Abdomen was soft and no organomegaly. In the hospital, her labs revealed; BUN/Cr 37/4.7, Hemoglobin 12g, Albumin 3.3, LDL of 142mg/dl. Urinalysis showed proteinuria and spot protein/creatinine was 4.5g. Kidney ultrasound scan showed chronic medical disease with no evidence of obstructive uropathy. Diabetes, Lupus, amyloidosis, vasculitis, HIV and hepatitis were all ruled out from serological testing, and ultimately, a kidney biopsy was done. This showed focal segmental glomerulosclerosis (FSGS) and Minimal change disease (MCD).
Review of literature showed that our patient had an additional risk factor that is rare. Interferon has been linked to development of Nephrotic syndrome. We, stopped her Interferon- 1β and consequently, her creatinine has trended down from 4.7 to 3.6 over 2 months. Interferon therapy has been shown to be associated with the development of Minimal Change Disease (MCD) 1,2
In another study done in Columbia, New York, collapsing FSGS was observed in 11 patients on Interferon (IFN-α,-β, or-γ) therapy (1). Nine out of 10 patients, who followed up, had improvement in their renal function at a mean of 23.6months. Mean proteinuria also declined from 9.9 to 3.0g/d (1). In our case, the biopsy showed both FSGS and MCD features. Our patient had been on interferon-1β for the past 5 years. Massive Proteinuria/nephrotic syndrome is a rare adverse effect of any interferon therapy. Physicians using these agents should pay careful attention to new clinical symptoms and laboratory findings. Nephrotic-range proteinuria could develop after several years of the therapy with optimal management being early recognition and cessation of therapy.
Interferons are cytokines which play a central role in the inflammatory response, and have proven useful in the treatment of several chronic diseases. With its increasing use, has come the realization that they can have an unusual renal side effect-nephrotic range proteinuria.
1.Markowitz, G. S., Nasr, S. H., Stokes, M. B., & D’Agati, V. D. (2010). Treatment with IFN-α,-
β, or-γ is associated with collapsing focal segmental glomerulosclerosis. Clinical Journal of the
American Society of Nephrology, 5(4), 607-615.
2. Kumasaka R, Nakamura N, Shirato K, Fujita T, Murakami R, Shimada M, Nakamura M, Osawa
H, Yamabe H, Okumura K.(2006). Nephrotic syndrome associated with interferon-beta-1b
therapy for multiple sclerosis. Clinical and Experimental Nephrology, 10: 222–225.