Research: Kidney disease caused by autoimmune disease lupus may be twice as lethal in children

Kidney disease caused by the autoimmune disease lupus may be twice as lethal in children as kidney disease caused by other disorders, according to research led by Johns Hopkins Children's Center investigators.

The findings, published online in the journal Pediatric Nephrology, are based on analysis of records of more than 98,000 children and adults with various forms of end-stage kidney disease (ESKD).

Systemic lupus erythematosus, or lupus, is a chronic autoimmune disorder that affects one or more organs, including the kidneys, eyes, joints, skin and heart. Although the causes remain unknown, triggers of the disease and its characteristic flare-ups have been linked to genetics, sun exposure, infections, injuries and stress. In up to 80 percent of children with lupus, the disease attacks the kidneys. Lupus-induced kidney disease can vary from mild to life-threatening. Progressive kidney damage requires dialysis and, eventually, kidney transplantation.

In the new Johns Hopkins study, lupus emerged as a consistent predictor of death from all causes, regardless of age, in those with ESKD. Although children with kidney disease triggered by lupus were no more likely than adults to die from it, the investigators found that both children and adults with lupus-related kidney disease had higher death rates from all causes than patients with kidney disease stemming from other disorders.

Specifically, children with lupus kidney disease had more than twice (2.4 times) the risk of dying compared to children with other forms of kidney disease. Adults with lupus kidney disease had 1.7 times higher risk of dying than adults with other forms of ESKD.

The most common cause of death in both groups was heart disease, the research showed. And even though heart disease was the overall number-one cause of death no matter what form of kidney disease the patients had, it was far more common in those with lupus-induced kidney disease. Three-quarters of the children with lupus kidney disease who died did so from heart problems, mostly of heart attacks. By comparison, 26 percent of children with non-lupus kidney disease died from heart problems. Of the 98,483 patients, 1,513 were patients with lupus kidney disease, and 171 of them were children. Of the 171 children with lupus-induced kidney disease, 29 died, most of them (75 percent) of heart-related problems. In the non-lupus group, 316 of the 3,276 children with end-stage kidney disease died, 26 percent of them from heart problems. In the adult group, 559 of the 1,342 patients with lupus-induced kidney disease died, compared to 58,336 of the 93,694 adults with other forms of kidney disease.

Lupus patients seem more likely to develop high blood pressure and high cholesterol at unusually early age, the researchers say, and, like other autoimmune conditions, lupus triggers chronic inflammation, which is well known for its ability to cause heart trouble.

Heart disease was also the top cause of death among adults with lupus kidney disease and remained the overall number-one cause of death in both children and adults with all types of kidney disease.

The finding suggests that although heart monitoring is critical in all people with kidney disease, it is even more so in patients with lupus-induced forms of the condition, the investigators said. The suspected mechanism behind the high heart-disease mortality may be the interplay between lupus and kidney disease, both of which take a toll on the cardiovascular system, the investigators said.

"What we may be seeing here is a double whammy of cardiovascular damage — on one hand, there's the damage caused by lupus itself, further compounded by the resulting kidney disease," says lead investigator Sangeeta Sule, M.D., Ph.D., a pediatric nephrologist and lupus expert at Hopkins Children's.

To prevent heart damage in lupus patients, with and without kidney disease, the researchers urge regular heart checkups even in the youngest among them. Such tests should include standard EKGs and cholesterol checks, but also periodic ultrasound of the heart to evaluate heart muscle function and size.

Lupus is believed to affect between 5,000 and 10,000 children in the United States.