Original investigation: Pathogenesis and treatment of kidney disease and hypertension
Hepatitis C virus-associated tubulointerstitial injury

https://doi.org/10.1016/S0272-6386(03)00024-6Get rights and content

Abstract

Background: Tubulointerstitial damage is recognized as a determinant of the prognosis of kidney disease. Various types of viral infection have been reported to induce tubulointerstitial lesions; however, that caused by hepatitis C virus (HCV) remains unclear, although glomerular lesions caused by this viral infection have been well documented. Methods: To identify any association, we retrospectively investigated 320 patients who underwent renal biopsy and did not have extrarenal diseases causing tubulointerstitial nephritis. Results: Of these patients, 13 patients had HCV infection and 307 patients did not. In a case-control study, HCV infection showed a significant association with the prevalence of tubulointerstitial injury. To offset the secondary tubulointerstitial change caused by advanced glomerulopathy, we performed a glomerular stage-matched comparison of patients with membranous nephropathy (MN). Nine patients with MN among the 13 HCV-infected patients and 18 HCV-negative patients with electron microscopic glomerular stage-matched MN were randomly selected from the overall pool of patients. Comparing areas of interstitial fibrosis and inflammatory cell infiltration, both were greater in HCV-infected than HCV-negative patients. In biopsy tissues from HCV-infected patients, positive signal for HCV was observed in the perinuclear area of tubular epithelial cells and infiltrating cells on immunohistochemistry and in situ hybridization. By a strand-specific reverse-transcription polymerase chain reaction for HCV, both genomic- and replicative-strand RNA were detected in renal tissues. Conclusion: These results suggest that HCV infection is a potent pathogenic factor of tubulointerstitial injury.

Section snippets

Patients

We define a patient as a person who underwent percutaneous renal biopsy for the investigation and treatment of renal diseases at Kyoto University Hospital (Kyoto, Japan) between 1992 and 2000 and did not have diseases causative of TIN, such as infectious diseases other than HCV, congenital diseases, collagen diseases, cryoglobulinemia, diabetes mellitus, malignant diseases, and drug-induced TIN. A full history was obtained from each patient before the investigation. No patient had a history of

Case-control study

Of the 320 patients without extrarenal diseases causative of TIN, 13 patients had HCV infection and 307 patients did not. Case subjects with HCV infection included a significantly larger population with tubulointerstitial damage (10 of 13 patients) than HCV-negative controls (104 of 307 patients; Fisher's exact P = 0.0024; Table 4). These data suggest that HCV infection is associated with the prevalence of tubulointerstitial lesions.

Typical picture of TIN in HCV-infected patients

Frequent tubulointerstitial changes were observed in these

Discussion

Renal involvement of HCV infection has been documented as cryoglobulinemic nephropathy and various types of glomerulonephritis. We have identified an association between HCV infection and prevalence of tubulointerstitial injury in a case-control study. Compared with glomerular stage-matched controls with MN in another study, frequent tubulointerstitial inflammatory cell infiltration and fibrosis were observed in HCV-infected patients. In these patients, factors that affect tubulointerstitial

Acknowledgements

The authors thank Dr Kunitada Shimotohno (Institute for Viral Research, Kyoto University, Japan) for providing rabbit anti-HCV core antigen antisera; Yukiko Ano for technical assistance; Fumie Uemura for secretarial assistance; and Daniel Mrozek for help preparing the manuscript.

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