A usually harmless and common group of bacteria found in soil, water and shower heads has been associated with an increased risk of dying in people whose kidneys have failed. The “opportunistic” pathogens, which have even been found in dialysis machines, tend to cause serious problems when a patient has a compromised lung or immune system function.
Investigators at the Medical College of Georgia and Charlie Norwood VA Medical Centre in Augusta looked in the US Renal Data System at patients with end-stage renal disease, or ESRD, who also had a diagnosis of infection with the nontuberculous mycobacteria, or NTM, group, finding a significant increase in mortality with an NTM diagnosis in these patients. This indicated, they reported in the Journal of Investigative Medicine, that early diagnosis and treatment of an NTM infection might improve survival in ESRD patients.
“It’s important to be alert that certain patients can be at higher risk for NTM, which carries a risk for mortality,” said Dr Stephanie Baer, infectious disease physician and chief of Infection Control and Epidemiology at the Charlie Norwood VA Medical Centre.
The study team looked at the 0.3% of the 1.1m patients in the database with ESRD and an NTM diagnosis over a decade that ended in 2015. Patients were either on dialysis or had a kidney transplant.
“We looked for risk factors for the bacterium … at the different diseases it causes, like lung disease, skin disease, and disseminated disease, and at the mortality of those patients,” said Baer, corresponding author.
With a few exceptions like skin disease, NTM infection always increased mortality in patients with ESRD, she says.
The investigators said their findings highlight the need for physicians to remain vigilant for NTM infections in ESRD patients.
“This is showing an association,” says co-author Wendy Bollag, PhD, cell physiologist in the MCG Department of Physiology. “We don’t know if NTM directly causes the mortality or is more of a red flag to physicians to treat that patient aggressively in that moment.”
It does mean patients with ESRD may need testing for NTM, if there are symptoms that indicate it may be present, and treatment with the appropriate antibiotics, they say. It may also need them to be screened for infection with HIV, which directly targets the immune system, and those who have received a kidney transplant might need adjustments in the medications they take to keep their immune system from attacking the transplanted organ.
To ensure they were looking specifically at the association between ESRD and NTM, the investigators controlled for other known risk factors for NTM infection, such as being black, having diabetes or liver disease, or being HIV positive. The database did not contain information on other potentially confounding factors like BMI and blood levels of pro-inflammatory factors.
They found a higher risk of NTM infection with peritoneal dialysis versus hemodialysis. Peritoneal dialysis can be done at home and uses a cleansing fluid and the lining of the abdomen to filter waste products, compared to machine-based hemodialysis, but exactly why there was a difference was not clear. Rheumatologic diseases like arthritis, which may require medicine suppressing the immune response and painful inflammation, also increased the NTM risk, as did a history of organ transplant.
The investigators said patients with kidney transplants who had NTM infections were less likely to die, potentially because of factors like restored kidney function, closer follow-up with health care providers and that patients selected for transplant might be more generally healthy than those on dialysis.
The database did not specify which NTM was most prevalent, but suspect it was the M. avium complex, by far the most common type in the Southeastern United States, Baer said.
There are more than 70 identified species of NTM. These bacteria wrap themselves in a protective biofilm and are becoming increasingly disinfectant and antibiotic resistant.
NTM infection can produce non-specific symptoms like fever, weight loss, night sweats and lethargy. Lung nodules and lymph nodes that don’t resolve can be telltale signs.
“The good news is it’s everywhere and most of us are never bothered by it, until our immune system becomes compromised,” Bollag added.
ESRD and NTM infections are both increasing, with rates of ESRD more than tripling between 1990 and 2018, said the US Centres for Disease Control and Prevention. The increase in NTM is possibly due to an ageing population with COPD and an increasing number of people with a compromised immune response.
The National Institute of Diabetes and Digestive and Kidney Diseases said nearly 786 000 people in the US have ESRD, 71% are on dialysis and 29% had a kidney transplant.
Mycobacteria are a large group of organisms known to cause serious conditions like leprosy and tuberculosis. NTMs are part of that group, minus those causing leprosy and tuberculosis.
Study details
Non-tuberculous mycobacterial infections in patients with end-stage renal disease: prevalence, risk factors, and mortality.
Eszter Toth, Jennifer L Waller, Wendy B Bollag, Budder Siddiqui, Azeem Mohammed, Mufaddal Kheda, Sandeep Padala, Lufei Young, Stephanie L Baer, Sarah Tran.
Published in the Journal of Investigative Medicine on 6 October 2022.
Abstract
Non-tuberculous mycobacterial (NTM) disease has increased in prevalence in the USA, however, little is known on NTM in the population with end-stage renal disease (ESRD). Thus, we investigated patients with ESRD to determine risk factors for NTM disease and mortality. We queried the United States Renal Data System from 2005 to 2015 using International Classification of Diseases (ICD)-9/ICD-10 codes to identify NTM and risk factors. Logistic regression was used to examine the association of risk factors with NTM and Cox proportional hazards modelling was used to assess the association of NTM with mortality. Of 1,068,634 included subjects, 3232 (0.3%) individuals were identified with any NTM diagnosis. Hemodialysis versus peritoneal dialysis (OR=0.10, 95% CI=0.08 to 0.13) was protective for NTM, whereas black (OR=1.27, 95% CI=1.18 to 1.37) or other race compared with white race (OR=1.39, 95% CI=1.21 to 1.59) increased the risk of NTM. HIV (OR=15.71, 95% CI=14.24 to 17.33), history of any transplant (OR=4.25, 95% CI=3.93 to 4.60), kidney transplant (OR=3.00, 95% CI=2.75 to 3.27), diabetes (OR=1.32, 95% CI=1.23 to 1.43), rheumatologic disease (OR=1.92, 95% CI=1.77 to 2.08), and liver disease (OR=2.09, 95% CI=1.91 to 2.30) were associated with increased risk for NTM diagnosis. In multivariable analysis, there was a significant increase in mortality with any NTM diagnosis (HR=1.83, 95% CI=1.76 to 1.91, p≤0.0001). Controlling for relevant demographic and clinical risk factors, there was an increased risk of mortality associated with any diagnosis of NTM. Early diagnosis and treatment of NTM infection may improve survival in patients with ESRD.
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