Spectrum of Kidney Diseases in Patients With Hepatitis C Virus Infection

A 10-Year Study

Shunhua Guo, MD; Meghan E. Kapp, MD; Diego M. Beltran, MD; Cesar Y. Cardona, MD; Dawn J. Caster, MD; Ronald R. Reichel, MD; Agnes B. Fogo, MD


Am J Clin Pathol. 2021;156(3):399-408. 

In This Article

Materials and Methods

The medical kidney biopsy database in the Department of Pathology, Microbiology and Immunology at Vanderbilt University Medical Center (VUMC) was searched for patients with a history of HCV infection (HCV+) from January 2007 to December 2016. HCV infection history was defined as a clinical diagnosis of HCV hepatitis, HCV antibody positivity, or HCV RNA test positivity. Clinical history, laboratory results, and renal biopsy diagnoses were reviewed, including renal function, urinalysis, cryoglobulinemia test, HCV-related tests such as serology and viral load, antineutrophil cytoplasmic antibody (ANCA) test, antiviral therapy, and outcomes (eg, dialysis and kidney transplant), from requisition forms or electronic medical records. Follow-up forms for the referral cases were sent to the referring nephrologists requesting additional information, including HCV viral status after treatment and disease progression. The study was approved by the Institutional Review Board of VUMC.

Renal biopsy specimens were examined in every case by light microscopy (LM) with H&E, periodic acid–Schiff, and Jones's silver stains, as well as immunofluorescence (IF) and electron microscopy (EM). IF studies include staining for immunoglobulin G (IgG), immunoglobulin A (IgA), immunoglobulin M (IgM), C3, C1q, and κ and λ light chains. IF for phospholipase A2 receptor (PLA2R) was performed on the cases with a membranous pattern (PLA2R antibody: Sigma AMAb90772, clone CL0474). The intensity of IF was graded on a scale of 0 to 3+, and location of deposits was noted.

HCV-associated GN was defined based on integrated clinical, laboratory, and pathologic findings with clinical hepatitis C diagnosis, as well as laboratory tests including HCV serology, HCV RNA, and cryoglobulinemia tests. The pathologic findings of HCV-associated GN include LM patterns of renal injury—namely, mesangial proliferative, membranoproliferative, or membranous GN; pseudo-thrombi/cryo plugs; positive IF results with often IgM-dominant immune deposits; and immune complex–type electron-dense deposits, including characteristic short fibrillary or short microtubular substructure of deposits by EM.

For comparing two proportions, a z test was performed using R 3.5.1 (R Foundation for Statistical Computing). For comparing quantitative data, two-way analysis of variance was performed using SAS 9.4 (SAS Institute). For comparison of glomerulosclerosis and interstitial fibrosis, the Mann-Whitney U test was performed using SAS 9.4. A P value less than .05 was considered significant.