Abstract

Abstract Background and Aims To describe the clinical features, renal pathology findings and prognosis in patients with mixed cryoglobulinemic glomerulonephritis (Gn) caused by hepatitis B virus (HBV) infection. Method This was a retrospective study including seven Chinese patients with HBV infection associated mixed cryoglobulinemic Gn in a tertiary referral hospital from April, 2016 to March, 2019. The demographic, clinical, pathological characteristics, treatment and follow-up data were collected and analyzed. Results Age at renal biopsy was 47±12 years, including three females and four males. 24hUP was 5.6(3.0, 6.6)g/d and five cases presented with nephrotic syndrome. The median baseline eGFR(CKD-EPI) was 23.5(20.2, 46.3) ml/min per 1.73m2. The extrarenal manifestations were: purpura (n=6), arthralgia (n=1), peripheral neuropathy (n=1), and cardiomyopathy (n=1). Six cases had type II cryoglobulinemia with IgMκ, the other one had type III. The median cryocrit was 4.0 (1.0, 15.0) %, rheumatoid factor was 368(117, 733) IU/ml, C3 was 0.48(0.41, 0.57) g/L, C4 was 0.013(0.003, 0.118) g/L. Renal pathologic findings on light microscopy: endocapillary proliferative Gn (n=3), membranoproliferative Gn (n=3), and mesangial proliferative glomerulonephritis(n=1). Hyaline thrombi were seen in four cases, while crescents were found in two cases. On immunofluorescence microscopy, the predominant types of immunoglobulin deposits were: IgM(n=5), IgA(n=1), and codominance of IgG and IgA(n=1). HBsAg and HBcAg deposits were found in only one case. Ultrastructural studies showed granular subendothelial and mesangial electron-dense deposits in all patients and organized microtubules was seen in only one case. All patients received antiviral medication (entecavir, n=6; lamivudine, n=1). They were given corticosteroid alone(n=2) or combined with cyclophosphamide(n=4) or mycophenolate mofetil(n=1). Two patients received plasmapheresis. The median follow-up time were 18 (6, 37) months. One patient died from pneumonia, and one progressed to end stage of renal disease (ESRD). At endpoint of follow-up, 24hUP was 2.1 (0.8-5.2) g/d, and eGFR (CKD-EPI) was 55.3 (20.7, 111.8) ml/min per 1.73m2. Conclusion Mixed cryoglobulinemic Gn should be screened for HBV etiologies, especially in HBV-endemic country. Endocapillary proliferative Gn was the common pathologic type, as well as membranoproliferative Gn. Diagnosis and treatment in early stage benefit patients’ renal outcome. Long-term prognosis should be investigated in further studies.

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