Prior to the discovery of the hepatitis C virus (viral particles shown on the left), there was an entity termed "essential cryoglobulinemia"--that is, cryoglobulinemia without an obvious explanation. While this term is still used, the true "essential cryoglobulinemia" is pretty rare, some cases of "hepatitis C-negative" cryoglobulinemia turned out instead to be positive: the cryoprecipitate can sequester hepatitis C antibody from the serum, so if there is a high suspicion for hepatitis C in a patient with detectable cryoglobulins, it is worthwhile to look for serologic evidence of hepatitis in the cryoprecipitate itself.Interestingly up to 50% of all patients with hepatitis C will show some evidence of circulating cryoglobulins. However, these antibodies only become clinically significant in about 5%. So the presence of renal failure in a patient with hepatitis C and positive cryoglobulins does not absolutely define the renal disease as being cryoglobulin-mediated; a renal biopsy is often needed to clarify the etiology.
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