Harmless group of bacteria associated with an increased risk of death in patients with end-stage renal disease

Harmless group of bacteria associated with an increased risk of death in patients with end-stage renal disease

A large group of bacteria found in our soil, water and showerheads are harmless to most of us, but a new study shows they are linked to an increased risk of death in people with kidney failure.

In what appears to be the first study of its kind, researchers from the Medical College of Georgia and the Charlie Norwood VA Medical Center in Augusta examined patients with end-stage renal disease (ESRD) in the United States Renal Data System who also had kidney disease and a diagnosis of infection with the nontuberculous mycobacteria, or NTM, group.

They found a significant and independent increase in mortality with an NTM diagnosis in these patients, suggesting that early diagnosis and treatment of NTM infection may improve the survival of ESRD patients, they report in the Journal of Investigative Medicine.

“It is important to note that certain patients are at higher risk of NTM and that NTM carries a risk of mortality,” says Stephanie L. Baer, ​​MD, MCG infectious disease physician and chief of the Division of Infection Control and Epidemiology at the Charlie Norwood VA Medical Center.

These “opportunistic” pathogens, which have even been found in dialysis machines, typically only cause serious problems when a patient has compromised lung or immune system function.

Patients with kidney failure are considered to be immunocompromised and generally have a higher risk of infection. Therefore, MCG and VA researchers wanted to better identify prevalence, risk factors and associated deaths in patients who also had an NTM infection.

They specifically looked at the 0.3% of the 1.1 million patients in the database with ESRD and an NTM diagnosis over a decade ending in 2015. Patients were either on dialysis or had a kidney transplant.

We looked at risk factors for the bacterium... and we looked at the different diseases it causes, like lung disease, skin disease, and disseminated disease, and we looked at the mortality of these patients.

Stephanie L. Baer, ​​MD, corresponding author

With a few exceptions, such as skin diseases, NTM infection pretty much always increased mortality in patients with ESRD, she says.

The researchers say their findings underscore the need for physicians to remain vigilant for NTM infections in ESRD patients.

“This shows an association,” says co-author Wendy B. Bollag, PhD, a cell physiologist in the MCG Department of Physiology. "We don't know whether NTM directly causes mortality or is more of a red flag for their doctor to treat this patient aggressively at this time."

It means patients with ESRD may need testing for NTM if there are symptoms that suggest it may be present and treatment with the appropriate antibiotics, it says. It may also indicate that they need to be checked for conditions such as HIV infection, which directly targets the immune system, and those who have received a kidney transplant may need to adjust the medications they take to prevent their immune system from attacking the transplanted organ.

To ensure that they were specifically examining the association between ESRD and NTM, investigators controlled for other known risk factors for NTM infection, such as: B. black skin color, diabetes or liver disease or HIV positive. The database did not contain information on other potentially confounding factors such as BMI and blood levels of pro-inflammatory factors.

They found a higher risk of NTM infection with peritoneal dialysis compared to hemodialysis. Peritoneal dialysis can be done at home and uses a cleansing fluid and the abdominal lining to filter waste products compared to mechanical hemodialysis, but exactly why there was a difference wasn't clear. Rheumatologic diseases such as arthritis, which may require medications that suppress the immune response and therefore painful inflammation, increased the risk of NTM, as did a history of organ transplants, and the investigators note that due care is needed in individuals with these additional risk factors.

They found that kidney transplant patients who had NTM infections were less likely to die, possibly due to factors such as recovery of kidney function, closer follow-up from health care providers, and that patients selected for transplant may generally be healthier than dialysis patients.

The database didn't specify which NTM was most prevalent, but they suspect it was the M. avium complex, which is by far the most common type in the southeastern United States, Baer says.

"It's all around us. It can cause an allergy called whirlpool cough or sneezing," says Baer.

There are more than 70 identified NTM species and the number is increasing. These bacteria coat themselves in a protective biofilm and are becoming increasingly resistant to disinfectants and antibiotics.

NTM infection can cause nonspecific symptoms such as fever, weight loss, night sweats, and lethargy. Lung nodules and lymph nodes that don't resolve can be telltale signs.

“The good news is that it is all around us and most of us are never bothered by it until our immune systems are compromised,” notes Bollag.

Both ESRD and NTM infections are increasing, with ESRD rates more than tripling between 1990 and 2018, according to the Centers for Disease Control and Prevention. The increase in NTM is likely due to an aging population with COPD and an increasing number of individuals with an impaired immune response, says Baer.

According to the National Institute of Diabetes and Digestive and Kidney Diseases, nearly 786,000 people in the United States have ESRD, 71% are on dialysis and 29% have had a kidney transplant.

Mycobacteria are a large group of organisms known to cause serious diseases such as leprosy and tuberculosis. NTMs belong to this group, apart from those that cause leprosy and tuberculosis.

The article's first author, Eszter Toth, is a medical student at MCG and is currently conducting a year of research in the laboratory of Steven Holland, MD, director of the Division of Intramural Research and chief of the Division of Immunopathogenesis at the National Institute of Allergy and Infectious Diseases.

Source:

Medical College of Georgia at Augusta University

Reference:

Toth, E., et al. (2022) Nontuberculous mycobacterial infections in patients with end-stage renal disease: prevalence, risk factors and mortality. Journal of Investigative Medicine. doi.org/10.1136/jim-2022-002462.

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