Predictive factors of renal involvement in cryoglobulinaemia: a retrospective study of 153 patients

Abstract

Background The course of cryoglobulinaemia varies widely, from asymptomatic patients to severe vasculitis syndrome. Renal involvement (RI) is the major prognostic factor, and frequently occurs several years after diagnosis. However, predictive factors for RI are not well known. The aim of our study was to identify RI predictive factors during cryoglobulinaemia. Methods We retrospectively reviewed the clinical charts of a consecutive series of 153 patients positive for cryoglobulinaemia in the University Hospital of Lyon (France). RI was defined either histologically or biologically if cryoglobulinaemia was the only possible cause of nephropathy. Results Among the 153 positive patients (mean age 55 years, 37% male), cryoglobulinaemia was associated with RI in 45 (29%) patients. Sixty-five percent of patients had Type II cryoglobulinaemia, 28% had Type III and 7% had Type I. Autoimmune diseases were the most common aetiology (48%), followed by infectious diseases (18%) and lymphoproliferative disorders (13%). Membranoproliferative glomerulonephritis was the main histological pattern (93% of the 14 histological analyses). A multivariable logistic regression showed that Type II cryoglobulinaemia, a high serum cryoglobulin concentration, the presence of an IgG kappa monoclonal component and diabetes were independently associated with the risk for developing RI. Conclusion We identified several factors predictive of RI in patients with cryoglobulinaemia, which were different from the diagnostic criteria for cryoglobulinaemic vasculitis. This could suggest a specific pathophysiology for RI. We suggest performing an extensive renal monitoring and ensure nephroprotection when a diagnosis of cryoglobulinaemia is made in patients with these predictive factors.

Renal Involvement and HBV Infection Are Common in Chinese Patients With Cryoglobulinemia

“…This may be the reason for the high prevalence of renal involvement. A retrospective study of 153 French patients, in which 45 patients had renal involvement, showed that type II cryoglobulinemia, a high serum cryoglobulin concentration, the presence of an IgG kappa monoclonal component, and diabetes were independently associated with the risk of renal involvement, and no particular etiology independently predicted renal involvement (13). In our cohort, we found no differences in clinical manifestations among the three groups of patients based on secondary causes.…”

“…Previous studies have shown that the most common renal pathology pattern in patients with cryoglobulinemia was MPGN, and other studies have reported mesangial proliferative glomerulonephritis (MsPGN), MN, FSGS, fibrillary or immunotactoid glomerulopathy, and thrombotic microangiopathy (TMA) ( 14 , 15 ). In a French cohort, 14 patients underwent renal biopsy, the majority of whom had MPGN (13/14) ( 13 ). Here in our study, MPGN was the most common renal pathology pattern, followed by lupus nephritis, MN, and RPGN.…”

“…Therefore, this study may have selection and referral biases, resulting in the inclusion of more severe patients with organ involvement, such as renal involvement, or the rare clinical manifestations of pulmonary and gastrointestinal involvement. Second, due to laboratory limitations, especially in the early years, cryoglobulinemia was not classified and the cryoglobulin concentration was not measured in some patients, which are important for determining the severity of cryoglobulinemia ( 13 ). Recently, we have started using the modified capillary immunotyping and immunofixation electrophoresis methods for identifying cryoglobulins and testing the absolute cryoglobulin concentration.…”

IgG subclasses in cryoglobulins: link to composition and clinical manifestations

“…These mouse models cannot be transferred to humans, because mouse IgG1 resembles human IgG4, not involved in type I CG pathophysiology. The involvement of one specific IgG subclass in renal manifestations in humans is not clear because renal manifestations appear several years after CG diagnosis [29]. This delay could explain differences in the reported results and justify a long follow-up study of patients.…”

Proteome profiling of Cryoglobulinemia

“…As the disease progresses, severe irreversible clinical manifestations such as glomerulonephritis, peripheral neuropathy, and skin ulcers occur, and the 10-year survival rate was significantly reduced. At the same time, patients with MC have poor response to treatment, high mortality rate and sequelae rate of chronic organ failure (such as chronic renal failure and lymphoma) [4,5] . Therefore, cryoglobulinemia is a disease with atypical symptoms and serious injury to patients.…”