Severity of anemia tied to specific kidney lesions in AAV patients

Low hemoglobin levels seen in 83% of study patients at time of kidney biopsy

Andrea Lobo, PhD avatar

by Andrea Lobo, PhD |

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The severity of anemia, or low levels of oxygen-carrying hemoglobin, is significantly associated with certain kidney lesions in people with ANCA-associated vasculitis (AAV) and kidney involvement, a study showed.

These findings “reflect an additional aspect of anemia pathophysiology [disease mechanisms] in ANCA-associated renal vasculitis,” the researchers wrote.

The study, “Low hemoglobin levels are associated with Bowman’s capsule rupture and peritubular capillaritis in ANCA-associated renal vasculitis: a link of vascular injury to anemia?,” was published in the Journal of Nephrology.

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AAV is a group of autoimmune diseases characterized by inflammation and damage to small blood vessels, most commonly those in the kidneys and lungs, due to self-reactive antibodies called ANCAs. These antibodies often target one of two proteins, proteinase 3 (PR3) and myeloperoxidase (MPO), at the surface of immune cells called neutrophils.

ANCA-associated renal vasculitis is a term for AAV-related kidney involvement, determined through a biopsy. This typically affects the blood vessels forming the glomeruli, which are the kidneys’ filtering units, and can cause tissue scarring and damage that ultimately leads to kidney failure.

Anemia refers to lower-than-usual levels of hemoglobin, the protein in red blood cells that carries oxygen throughout the body. It is a common and severe complication of ANCA-associated kidney involvement, and its severity has been associated with poorer kidney function and shorter survival.

Researchers at University Medical Center Göttingen, in Germany, previously identified a link between low hemoglobin levels and intensive care stays among hospitalized adults with ANCA-associated renal vasculitis.

However, the interplay between anemia and AAV-related kidney lesions remains unclear.

To better understand this, the researchers analyzed the medical records of 52 adults (29 men and 23 women) with ANCA-associated renal vasculitis who were hospitalized at their center between 2015 and 2020. All were positive for antibodies against PR3 or MPO, and had available hemoglobin levels at kidney biopsy.

Patients had a median age of 65, and most were newly diagnosed with the disease (75%), while 17.3% were experiencing a disease relapse. A total of 27 patients had PR3-ANCAs and 25 were positive for MPO-ANCAs.

Most patients (82.7%) had anemia at the time of their biopsy. Nine of them (17.3%) had anemia caused by kidney disease, which usually is due to a deficiency of erythropoietin, an essential hormone for the production of red blood cells.

Overall, 44.2% of the patients had severe acute kidney injury, classified as AKIN III based on blood and urine criteria.

Participants with MPO-ANCAs had more severe kidney damage than those with PR3-ANCAs, reflected by a higher rate of AKIN III (64% vs. 25.9%) and poorer kidney function based on higher creatinine levels (4.3 vs. 1.8 mg/dL). They also had a lower estimated glomerular filtration rate or eGFR (14 vs. 28.2 mL/min/1.73m2).

Regarding kidney lesions, patients with PR3-ANCA had significantly more normal glomeruli, while the MPO-ANCA group had significantly more total inflammation. Significant group differences also were seen in terms of shrinkage of the kidney’s tubules.

Further analyses showed that lower blood levels of hemoglobin significantly associated with lower eGFR, indicating worse kidney function. This association was observed in patients with MPO-ANCAs, but not in the PR3-ANCA group.

In all patients, lower hemoglobin levels significantly correlated with the presence of peritubular capillaritis — inflammation of tiny blood vessels in the kidney tubules — and rupture of the Bowman’s capsule that surrounds the glomerulus.

Although there was a tendency for similar associations in the MPO-ANCA group, these did not reach statistical significance in analyses accounting for several factors.

In patients with PR3-ANCAs, however, low levels of hemoglobin significantly associated with more damage to glomeruli.

“To the best of our knowledge, this is the first report of specific [tissue] lesions associated with anemia severity in ANCA-associated renal vasculitis,” the researchers wrote.

“The finding that peritubular capillaritis and Bowman’s capsule rupture correlate with low hemoglobin levels may add to the notion that [tissue] lesions might link inflammatory vascular injury to relative [erythropoietin] deficiency and renal anemia in ANCA-associated renal vasculitis,” they concluded.