Sometimes, the pattern of C3/C4 levels can give a clue as to the specific diagnosis. Disorders in which C3 is decreased but C4 is not include MPGN and post-infectious glomerulonephritis, indicating a tendency for the alternative pathway to be active moreso than the classical pathway. Activation of the classical pathway will typically result in lowering of both C3 and C4, and therefore disorders in which BOTH C3 and C4 are decreased include lupus nephritis and cryoglobulinemia. These rules may not be perfect, but can potentially give a hint as to the mechanism of inflammation in glomerulonephritis.
Although the complement cascade is an essential aspect of the response to infection, it unfortunately can be activated by a variety of means in several types of kidney disease. In common day clinical practice, most of the time we determine complement activity by assessing serum C3 and C4 levels; a decreased C3 level means that the alternative complement pathway has been activated whereas a decreased C4 level means that the classical complement pathway has been activated. This is especially important in the workup of glomerulonephritis of uncertain etiology.