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Core Concepts in Parenchymal Kidney Disease pp 87–103Cite as

Cryoglobulinemias

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Abstract

The clinical symptoms of mixed cryoglobulinemia range from mild palpable purpura, arthralgias, and fatigue to severe vasculitis with skin necrosis, as well as peripheral neuropathy and, less frequently, involvement of the central nervous system, gastrointestinal tract, lungs, and myocardium. Cryoglobulinemic nephritis, a diffuse membranoproliferative glomerulonephritis in most cases, is a unique nephropathy which is pathogenetically related to HCV infection. Patients’ biochemical analyses usually reveal type II cryoglobulins (IgM–k, polyclonal IgG), increased IgM RF, and low C4 values.

Significant prognostic variables include age, male gender, proteinuria at the time of renal biopsy, number of syndromic relapses, and poor blood pressure control. Kaplan–Meier survival curves are worsened by baseline creatinine value >1.5 mg/dL (133 μ[mu]mol/L). Cardiovascular disease is the cause of death in over 60 % of cases.

Combined antiviral therapy with PEG-interferon and ribavirin appears logical, targets the viral trigger, and can be favorably used to control mild to moderate manifestations including mesangial glomerulonephritis with moderate signs of inflammation. Standard therapy for chronic hepatitis C, however, does not achieve sustained effects. Depending on the genotype, a 1-year schedule (for genotypes 2 and 3) or a 1 and a half-year schedule (for genotypes 1 and 4) are needed in cryoglobulinemic patients.

In acute immunological flares, antiviral treatment cannot be used alone, and in some cases, it can even be deleterious. Steroids and immunosuppressive drugs, mainly cyclophosphamide, and plasma exchange are needed. Besides the concerns on the use of immunosuppressants in a virus-triggered multiorgan disease, several patients complain of one or more of the several side effects of conventional immunosuppressive drugs.

Rituximab has earned a definite role in these cases, but its appropriate position in the treatment strategy of mixed cryoglobulinemia remains controversial. The main indications for its use include severe worsening of renal function, mononeuritis multiplex, extensive skin ulcers, and distal necrosis. While antiviral drugs administered with Rituximab may possibly be synergic, they multiply the adverse effects thereby making treatment poorly tolerated.

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Acknowledgments

The authors are indebted with Dr. Andrea De Marchi, San Giovanni Bosco Hospital of Turin, for providing the picture of cryoglobulinemic leukocytoclastic vasculitis, and Prof. Gianna Mazzucco, University of Turin, and Dr. Sanjeev Sethi, Mayo Clinic Institute, Rochester, for providing the pictures of renal histology.

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There are no conflicts of interest to declare.

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Authors and Affiliations

  1. Department of Rare, Immunologic, Haemathologic, Immunohaemathologic Diseases, Giovanni Bosco Hospital and University of Turin, Turin, Italy

    Dario Roccatello M.D.

  2. Division of Nephrology (Renal Unit), Azienda Ospedialiera G. Brotzu, Cagliari, Sardegna, Italy

    Antonello Pani M.D.

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  1. Dario Roccatello M.D.
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  2. Antonello Pani M.D.
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Correspondence to Dario Roccatello M.D. .

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Editors and Affiliations

  1. Div. Nephrology & Hypertension, Mayo Clinic Dept. Internal Medicine, Rochester, Minnesota, USA

    Fernando C. Fervenza

  2. Renal Division, Brigham and Women's Hospital, Boston, Massachusetts, USA

    Julie Lin

  3. Mayo Clinic, Rochester, Minnesota, USA

    Sanjeev Sethi

  4. Renal Division, Brigham and Women's Hospital Harvard Medical School, Boston, Massachusetts, USA

    Ajay K. Singh

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Roccatello, D., Pani, A. (2014). Cryoglobulinemias. In: Fervenza, F., Lin, J., Sethi, S., Singh, A. (eds) Core Concepts in Parenchymal Kidney Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-8166-9_7

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