Younger Age, Race and Low Complement Levels Seen to Raise Risk of Kidney Problems in Lupus Patients

Older patients with systemic lupus erythematosus (SLE) have a low risk of future renal involvement, researchers report. The risk factors they identified with lupus nephritis onset included young age, low complement levels, and non-Caucasian ethnicity.

The study, “Predictors of incident proteinuria among patients with SLE,” was published in the journal Lupus Science & Medicine.

Lupus nephritis, an inflammation in the kidneys caused by lupus antibodies, is a common manifestation in lupus patients. Despite advances in therapies, the condition is still associated with higher morbidity and mortality.

Proteinuria
 – higher content of proteins in the urine – is the clinical sign of lupus nephritis. However, few studies look at factors predictive of proteinuria in a prospective setting, and fewer have looked at time-varying predictors.

To identify factors that predict lupus nephritis, researchers analyzed patients enrolled in the Hopkins Lupus Cohort, run through the Johns Hopkins University School of Medicine. This large clinical cohort includes lupus patients from different ethnic backgrounds and offers regular follow-up, where protein measurements were performed on a quarterly basis throughout nine years (2006-2015).

Researchers defined incident proteinuria as “two or more measures of urine protein to creatinine ratio (or 24-hour protein measure) greater than 0.5 in two visits separated by more than 30 days and less than 180 days.”

In total, they analyzed 895 patients, most were women (94 percent), 58 percent were Caucasian and 34 percent African-American. Patients’ mean age when enrolled in the cohort was 42.

During the follow-up of 4,669 person-years, researchers identified 57 cases of incident proteinuria, according to their definition.

Results showed that the rate for incident proteinuria was significantly lower in older patients and among Caucasian patients. Also, very low levels of complement 3 (C3) and complement 4 (C4) — a hallmark of lupus — and high levels of autoantibodies, such as anti-dsDNA, associated with incident proteinuria.

“In those with a very low C3 measure in a previous cohort visit, the rate was increased by a factor of 16.1, and in those with a very low C4 by 16.3,” the researchers wrote.

But while the low complement is predictive, how low was actually what most influenced the risk of incident proteinuria. Researchers observed that a combination of low C3, C4, and high anti-dsDNA carried predictive value.

“If a patient has a C3 below 9, C4 below 4 and an anti-dsDNA higher than 80, their risk of proteinuria at the next visit is increased by an estimated factor of 60,” they wrote.

Patients prescribed either Plaquenil (hydroxychloroquine), a common therapy to treat symptoms associated with lupus, or blood pressure medications (ACE inhibitors/ARB treatment), showed the same risk as patients without them.

“Older patients with SLE are at low risk for developing proteinuria. There was not strong evidence that hydroxychloroquine or angiotensin-converting-enzyme (ACE) inhibitor reduced the risk of proteinuria. The highest rates of incident proteinuria were among those with recent low complement,” the study concluded.