AAV Patients With Low Complement Levels Experience Greater Kidney Damage, Study Reports

Patients with ANCA-associated vasculitis (AAV) with low levels of complement proteins develop greater kidney damage, according to new research.

The study, “Increased renal damage in hypocomplementemic patients with ANCA-associated vasculitis: retrospective cohort study,” appeared in the journal Clinical Rheumatology.

The complement system — a set of over 20 blood proteins that form part of the body’s immune defenses — plays an important role in AAV. Researchers note that, in the kidneys, complement protein deposits correlate with increased damage, greater disease activity, and proteinuria, or abnormal amounts of protein in the urine.

In addition, hypocomplementemia — low levels of complement proteins in the blood — at the onset of AAV has been linked with more extensive organ involvement, poorer prognosis, and greater mortality.

A team at the Hospital San Martín of La Plata, Argentina, hypothesized that AAV patients with hypocomplementemia — defined as C3 protein values lower than 80 mg/dL and C4 protein values below 15 mg/dL — would more commonly progress to end-stage renal disease and have more frequent morbidity.

The scientists primarily assessed the link between hypocomplementemia and clinical manifestations, laboratory findings, progression to renal insufficiency, and mortality. Their secondary aim was to test the correlation between disease alterations in the kidney, and renal function prognosis in patients with or without hypocomplementemia.

A total 93 patients, including 53 women, with a mean age at disease onset of 49 years, were evaluated between 2000 and 2017. The most common disease type was granulomatosis with polyangiitis (GPA; 44 patients) followed by microscopic polyangiitis (MPA; 23 patients). Patients were followed for an average of 46 months.

Among the 63 individuals whose complement levels were evaluated at diagnosis, seven presented hypocomplementemia. A majority of these patients (57.1%) had MPA.

The results showed a significant correlation between hypocomplementemia and kidney disease. Specifically, patients with low values more commonly showed proteinuria (57% vs. 23%) and active urinary sediment — normally with both red and white blood cells (71.4% vs. 41%). These individuals also were more likely to show high levels of creatinine, an established kidney function marker, than those without hypocomplementemia (71.4% vs. 32.1%).

Renal involvement was found in 58 of the 93 total patients (62.3%) — defined by a 24-hour urinary protein amount above 500 mg, active urinary sediment, and an increase of creatinine values over 1.4 mg/dL. A total 30 kidney biopsies were classified as pauci-immune glomerulonephritis, which is characterized by mild or absent detection of immunoglobulin and complement by microscopy.

Four of 14 tested patients showed immune complex, C3 complement, or fibrinogen deposits — a blood protein key in blood clotting. These patients had renal failure and needed hemodialysis until the end of follow-up.

“In conclusion, our results suggest that complement participates in renal damage of AAV patients,” the investigators said. “It is important to determine complement levels at the onset of the disease.”