Clinical and morphologic spectrum of renal involvement in patients with HBV‐associated cryoglobulinaemia

Li, Shijun; Xu, Shutian; Chen, Huiping; Zhang, Mingchao; Xu, Feng; Cheng, Sheue-yann; Liu, Zhihong

doi:10.1111/nep.12795

Cited by 31 publications

(38 citation statements)

References 22 publications

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“…We observed microtubule structure in only one case on electron microscopy. These findings were consistent with the ultrastructural features of HBV related CryoGn reported in the literature [6,10]. In one previous study including 12 patients of CryoGn associated with HBV infection, only two cases were found microtubule substructure on electron microscopy [6].…”

Section: Discussionsupporting

confidence: 91%

“…This finding was consistent with that of Italian study which reported type II cryoglobulins accounted for 88% in HBV related cryoglobulinemic vasculitis [5]. However, result in another previous Chines study suggested that type III cryoglobulinemia was more frequently seen in HBV related CryoGn [6]. This discrepancy may reflect differences in the laboratory methods in detection of cryoglobulin as well as patient selection bias considering a limited sample size.…”

Section: Discussionsupporting

confidence: 90%

“…The morphologic pattern of HBV related CryoGn varied in the limited number of previous studies. Membranous nephropathy was the predominant pattern reported in one study including eight Chinese cases of CryoGn associated with HBV infection [10], while the result of another Chinese study demonstrated that membranoproliferative GN was the exclusive type of all 12 patients [6]. The discrepancy of the morphologic pattern of CryoGn among different studies could have been generated by limited sample size.…”

Section: Discussionmentioning

confidence: 99%

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Clinicopathological study of mixed cryoglobulinemic glomerulonephritis secondary to hepatitis B virus infection

et al. 2020

BMC Nephrol

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Background Cryoglobulinemic glomerulonephritis (CryoGn) caused by hepatitis B virus (HBV) infection was rarely reported. Our study aimed to investigate the clinical features, renal pathology findings, and prognosis in patients with HBV related CryoGn. Methods This was a retrospective study including seven Chinese patients with HBV related CryoGn in a tertiary referral hospital from April 2016 to March 2019. The clinical and pathological data were collected and analyzed. Results Age at renal biopsy was 47 ± 12 years, with female/male ratio 3/4. Urine protein was 5.6 (3.0, 6.6) g/d and five cases presented with nephrotic syndrome. The baseline eGFR was 23.5 (20.2, 46.3) ml/min per 1.73m2. The extrarenal manifestations included 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) %. Renal pathologic findings on light microscopy: endocapillary proliferative glomerulonephritis (Gn) (n = 3), membranoproliferative Gn (n = 3), and mesangial proliferative Gn (n = 1). On immunofluorescence microscopy, the predominant type of immunoglobulin deposits was IgM (n = 5). HBsAg and HBcAg deposits were found in one case. Ultrastructural studies showed granular subendothelial and mesangial electron-dense deposits in all patients and microtubules in one case. All patients received antiviral medications. 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 was 18 (6, 37) months. Four patients got remission, two patients died of pneumonia, and one progressed to end-stage renal disease (ESRD). At endpoint of follow-up, 24hUP was 2.1 (0.8–5.2) g/d, and eGFR was 55.3 (20.7, 111.8) ml/min per 1.73m2. The median cryocrit decreased to 1.0 (0, 5.75) %. Conclusions The etiology of mixed CryoGn should be screened for HBV infection. Endocapillary proliferative Gn and membranoproliferative Gn were the common pathologic patterns. Diagnosis and treatment in early stage benefit patients’ renal outcomes. Immunosuppressive therapy should be considered for severe renal disease, based on efficient antiviral therapy.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

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Clinicopathological study of mixed cryoglobulinemic glomerulonephritis secondary to hepatitis B virus infection

et al. 2020

BMC Nephrol

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show abstract

“…This nding was consistent with that of Italian study which reported type II cryoglobulins accounted for 88% in HBV related cryoglobulinemic vasculitis [5]. However, result in another previous Chines study suggested that type III cryoglobulinemia was more frequently seen in HBV related CryoGn [6]. This discrepancy may re ect differences in the laboratory methods in detection of cryoglobulin as well as patient selection bias considering a limited sample size.…”

Section: Treatment and Clinical Outcomessupporting

confidence: 90%

Clinicopathological study of mixed cryoglobulinemic glomerulonephritis secondary to Hepatitis B virus infection

LI²,

et al. 2020

Preprint

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Background Cryoglobulinemic glomerulonephritis (CryoGn) caused by hepatitis B virus (HBV) infection was rarely reported. Our study aimed to investigate the clinical features, renal pathology findings, and prognosis in patients with HBV related CryoGn. Methods This was a retrospective study including seven Chinese patients with HBV related CryoGn in a tertiary referral hospital from April 2016 to March 2019. The clinical and pathological data were collected and analyzed.Results Age at renal biopsy was 47±12 years, with female/male ration 3/4. Urine protein was 5.6(3.0, 6.6) g/d and five cases presented with nephrotic syndrome. The baseline eGFR was 23.5 (20.2, 46.3) ml/min per 1.73m2. The extrarenal manifestations included 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) %. Renal pathologic findings on light microscopy: endocapillary proliferative glomerulonephritis (Gn) (n=3), membranoproliferative Gn (n=3), and mesangial proliferative Gn (n=1). On immunofluorescence microscopy, the predominant type of immunoglobulin deposits was IgM(n=5). HBsAg and HBcAg deposits were found in one case. Ultrastructural studies showed granular subendothelial and mesangial electron-dense deposits in all patients and microtubules in one case. All patients received antiviral medications. 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 was 18 (6, 37) months. Four patients got remission, two patients died of pneumonia, and one progressed to end-stage renal disease (ESRD). At endpoint of follow-up, 24hUP was 2.1 (0.8-5.2) g/d, and eGFR was 55.3 (20.7, 111.8) ml/min per 1.73m2. The median cryocrit decreased to 1.0 (0, 5.75) %.Conclusions The etiology of mixed CryoGn should be screened for HBV infection. Endocapillary proliferative Gn and membranoproliferative Gn were the common pathologic patterns. Diagnosis and treatment in early-stage benefit patients’ renal outcomes. Immunosuppressive therapy should be considered for severe renal disease, based on efficient antiviral therapy.

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“…The majority of these patients (75%) presented after .10 years of HBV infection with predominantly type 3 cryoglobulinemia (polyclonal IgM -polyclonal IgG). This compares to a greater propensity (80%) of type 2 cryoglobulinemia (monoclonal IgM -polyclonal IgG) with type 1 MPGN in chronic HCV infection of .10-15 years (18). HBV patients with cryoglobulinemia may present with nephrotic syndrome, AKI, and systemic vasculitis with low C4 (92%) and low C3 (58%).…”

Section: Mpgnmentioning

confidence: 99%

Viral-Associated GN: Hepatitis B and Other Viral Infections

Kupin

2016

CJASN

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By definition, viral-associated GN indicates the direct pathogenic relationship between active viral replication and the development of acute GN. This definition is in sharp contrast to the semantic label and pathophysiologic foundation behind postinfectious GN that uniquely develops only during a period of resolved and absent active infection. The primary example of postinfectious GN are the glomerular lesions described after a pharyngeal or cutaneous streptococcal infection and do not represent the clinical or immunologic pattern seen with viralassociated GN. Hepatitis B (HBV) is the most common chronic viral infection in the world affecting >400 million people which is more than double the prevalence of chronic HIV and hepatitis C carriers combined. In addition, 10%-20% of HBV patients may be coinfected with hepatitis C and 5%-10% will have coinfection with HIV. Being able to distinguish the different types of GN seen with each viral infection is essential for the practicing clinician as each virus requires its own specific antiviral therapy. HBV-induced immune complex disease with renal injury lies on one end of the spectrum of disorders that occurs after a prolonged chronic carrier state. On the opposite end of the spectrum are renal diseases that develop from acute or subacute viral infections. One important glomerular lesion in this category is the association of collapsing FSGS with acute active cytomegalovirus, Epstein-Barr virus, and parvovirus B19 infection. The data supporting or disproving this relationship for each of these viruses will be discussed. A second renal manifestation of acute viral infections often occurs with many different sporadic or epidemic infections such as dengue and hantavirus and can lead to a transient proliferative GN that resolves upon viral clearance. The complex interplay of HBV and all viruses with the immune system provides conceptual lessons on the pathophysiology of immune complex GN that can be applied to all infection-related renal disease and plays an integral role in developing an approach to therapeutic intervention.

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Clinical and morphologic spectrum of renal involvement in patients with HBV‐associated cryoglobulinaemia

Cited by 31 publications

References 22 publications

Clinicopathological study of mixed cryoglobulinemic glomerulonephritis secondary to hepatitis B virus infection

Clinicopathological study of mixed cryoglobulinemic glomerulonephritis secondary to hepatitis B virus infection

Clinicopathological study of mixed cryoglobulinemic glomerulonephritis secondary to Hepatitis B virus infection

Viral-Associated GN: Hepatitis B and Other Viral Infections

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