Combination pegylated interferon and ribavirin therapy precipitating acute renal failure and exacerbating IgA nephropathy

Sir,

Combination pegylated interferon (Peg-interferon) and ribavirin therapy attains higher sustained virological response rates in chronic hepatitis C (CHC) than combination standard interferon and ribavirin and is fast becoming the standard of care for CHC. Renal dysfunction relating directly to this treatment is rare. We report a case of Peg-interferon and ribavirin therapy for CHC giving rise to macroscopic haematuria and acute renal failure.

A 54-year-old man with genotype 1 CHC and metavir stage 2 hepatic fibrosis and no prior history of renal disease was commenced on Peg-interferon alpha-2a 180 mcg subcutaneously weekly and ribavirin 600 mg b.d. orally. Nine days after commencing treatment the patient presented with macroscopic haematuria. Examination revealed jaundice but no pallor. Blood pressure was 130/90 mmHg and pulse rate 65/min. The abdomen was soft and non-tender. While urinalysis prior to treatment was normal, repeat urinalysis showed ++ proteinuria and +++ haematuria. Urine microscopy showed >1000 x 106/l erythrocytes and >1000 x 106/l leucocytes. Urine culture was negative. There was evidence of acute renal failure with a rise in serum creatinine from 0.09 to 0.19 mmol/l (0.04–0.13) (Figure 1). A 24-h urine collection showed 1.78 g/day proteinuria (<0.15 g/day). Immunological tests including cryoglobulins, ANA, dsDNA, ANCA were negative and complement levels normal. There was evidence of haemolysis secondary to ribavirin with a reduction in haemoglobin from 172 g/l at baseline to 140 g/l (128–175), increased bilirubin of 44 mmol/l (<21), lactate dehydrogenase 741 U/l (0–250), and haptoglobin <0.06 g/l (0.36–1.95) with a negative direct Coombs test. Liver chemistries remained otherwise stable with serum albumin 39 g/l (35–52), alanine aminotransferase 102 U/l (0–40), {gamma}-glutamyltransferase 79 U/l (0–60) and alkaline phosphatase 98 U/l (<110). Leucocyte and platelet counts remained normal.



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Fig. 1. Change in serum creatinine post-commencement of combination drug therapy.

 
A renal biopsy demonstrated acute tubular necrosis (ATN) characterized by tubular dilatation, sloughing of epithelial cells and minimal mononuclear cell inflammatory infiltrate, suggestive of drug toxicity. There was glomerular IgA deposition as well as mild mesangial proliferation consistent with IgA nephropathy with no evidence of haemolysis-induced renal injury. Peg-interferon and ribavirin therapy were ceased with gradual resolution of renal dysfunction, urinalysis abnormalities and haemolysis (Figure 1).

CHC is associated with a number of renal conditions including mesangiocapillary glomerulonephritis and chronic liver disease (CLD)-related IgA nephropathy. Secondary IgA nephropathy has been observed in up to 56% of patients with CLD [1]. Treatment with combination interferon and ribavirin is effective in the management of CHC-related mesangiocapillary glomerulonephritis [2]. However, the present case indicates that Peg-interferon based combination therapy has the potential to exacerbate IgA nephropathy as evidenced by macroscopic haematuria and the deterioration in renal function. Both the manufacturer and the Australian Therapeutic Goods Administration have confirmed that no similar cases have been reported with this product. Standard interferon therapy has previously been implicated in the development of ATN [3]. As Peg-interferon has a similar side effect profile to standard interferon it is not surprising that ATN may also occur with this treatment, although to date this has not been reported.

This case demonstrates the importance of monitoring renal function during treatment of CHC with combination therapy as treatment may precipitate ATN and in some instances lead to an exacerbation of CLD-related IgA nephropathy.

The results presented in this paper have not been published previously in whole or part.

Conflict of interest statement. None declared.

Adam Gordon1, Solomon Menahem2, Joanne Mitchell1, Peter Jenkins1, John Dowling3 and Stuart K. Roberts1

1 Department of Gastroenterology2 Department of Renal Medicine3 Department of Anatomical Pathology Alfred Hospital Commercial Road Prahran 3181 Victoria Australia Email: solomon.menahem{at}med.monash.edu.au

References

  1. Axelsen RA, Crawford DH, Endre ZH et al. Renal glomerular lesions in unselected patients with cirrhosis undergoing orthotopic liver transplantation. Pathology 1995; 27: 237–246[ISI][Medline]
  2. Naarendorp M, Kallemuchikkal U, Nuovo GJ, Gorevic PD. Long-term efficacy of interferon-a for extrahepatic disease associated with Hepatitis C virus infection. J Rheumatol 2001; 28: 2466–73[ISI][Medline]
  3. Dimitrov Y, Heibel F, Marcellin L, Chantrel F, Moulin B, Hannedouche T. Acute renal failure and nephrotic syndrome with alpha interferon therapy. Nephrol Dial Transplant 1997; 12: 200–203[Abstract]




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