Glomerulonephritis (GN) can result from a number of pathogenic processes that cause glomerular deposition of immune complexes and/or complement. Immune complex-mediated GN (due, for example, to chronic infections such as hepatitis C virus) is characterized by deposits of immunoglobulin, often accompanied by deposition of complement that includes C3 and/or C4 and, in some cases, C1q. Deposition of C3, C4, and C1q in immune complex-mediated GN is likely due to activation of the classical pathway of complement.

On the other hand, complement-mediated GN is usually characterized by deposition of C3 with minimal or no immunoglobulin deposits. The prototype of complement-mediated GN is C3 glomerulopathy, which includes C3 glomerulonephritis (C3GN) and dense deposit disease (DDD). Both C3GN and DDD result from overactivation of the alternative pathway of complement. In C3 glomerulopathy, C4 is typically absent on immunofluorescence microscopy.

In 2014, a new type of complement-mediated GN was identified that was characterized by deposition of C4 in the absence of C3, C1q, and immunoglobulin. This disorder was called C4 dense deposit disease (abbreviated as C4 DDD; if there were dense C4 deposits along the glomerular basement membrane documented by electron microscopy) or C4 glomerulonephritis (abbreviated as C4GN; if there were C4 deposits primarily in the mesangium with few capillary wall deposits). Thus, complement-mediated GN can be subdivided into C3 glomerulopathy (C3GN and DDD) and C4 glomerulopathy (C4GN and C4 DDD)

In C1q Nephropathy, the kidney filters can look absolutely normal under a standard (light) microscope (though they can also have visibly “scarred” areas as well- see FSGS). It is not until special “stains” specific for the C1q protein are added to the sample that the differences can be seen. These stains cause the areas of the biopsy where C1q has deposited to glow bright green under certain types of light. Also, if the biopsy is evaluated under an “electron microscope”(which can magnify an object over a million times), the C1q deposits themselves can be seen.

Symptoms

The most noticeable symptom of C1q Nephropathy is often edema, or swelling, which can be profound. This typically starts in the feet and legs, but can move into the hips and abdomen as well. Other symptoms include high blood pressure, high cholesterol, and a tendency to form blood clots.

Protein levels can be measured in a urine sample, and kidney function can be calculated from a blood test alone or measured more directly by adding a 24-hour urine collection. C1q Nephropathy can cause proteinuria alone or proteinuria and renal failure together.

Treatment

C1q Nephropathy is not an easy disease to treat, and anyone with this disease should be seen regularly by a kidney specialist. It is important to be on a medication that reduces the amount of protein in the urine. These medications are called ACE-inhibitors (angiotensin converting enzyme inhibitors) and ARBs (angiotensin II receptor blockers). If urine protein levels are high, the complications of the Nephrotic Syndrome should also be considered; patients should receive routine cholesterol screening/treatment, and their physicians should always remember their tendency to form clots. Finally, every patient with C1q Nephropathy must have their kidney function monitored regularly. If kidney function declines, certain other interventions may become necessary.

Conclusion

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