Infection-related acute care events in children and adults with glomerular disease are common and associated with a number risk factors, according to a new study.

“We undertook this study to update our knowledge regarding the epidemiology of infections in patients with glomerular disease. This is especially important because our therapies and regimens have evolved since much of the literature in this area was published,” lead investigator Dorey A. Glenn, MD, an assistant professor in the Division of Nephrology and Hypertension at the University of North Carolina Kidney Center in Chapel Hill, North Carolina. “Patients with glomerular disease suffer from more frequent, and sometimes severe infections. We also have data showing that these patients worry about infections and that infections affect quality of life. Actually, I think we are all experiencing what it is like to worry about catching an infectious disease right now with the COVID pandemic.”

Dr Glenn and his colleagues examined risk factors for time to first infection-related acute care events (hospitalization or emergency department [ED] visit) in a prospective, multicenter study of 1741 children and adults who within 5 years of enrollment were diagnosed with biopsy sample–proven minimal change disease, focal segmental glomerulosclerosis (FSGS), membranous nephropathy, or IgA nephropathy/vasculitis. The study enrolled patients at 72 participating clinical sites in the United States, Canada, Italy, and Poland.

Of the 1741patients in the study, 372 (21%) subjects had minimal change disease, 411 (24%) had FSGS, 329 (19%) had membranous nephropathy, and 629 (36%) had IgA nephropathy/vasculitis. The cohort was 43% female, 68% white, and 41% were under age 18.


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The investigators excluded patients with kidney failure, a kidney transplant, diabetes mellitus, systemic lupus erythematosus, HIV infection, active malignancy, or hepatitis B or C at time of first kidney biopsy.

Of the 1741 patients, 163 (9%) experienced infection-related acute care events over a median follow-up period of 17 months. The unadjusted incidence rates of these events were 13.2 per 100 person-years among pediatric participants and 6.2 events per 100 person-years among adult participants.

“We found that infection-related ED visits and hospitalizations were associated with younger age, steroid exposure, and hypoalbuminemia with nephrotic range proteinuria,” Dr Glenn told Renal & Urology News. Infections were particularly frequent among those exposed to corticosteroids during the first year of study follow-up.”

The unadjusted incidence rates of infection-related acute care events during the first year of follow-up were 50.6 per 100 person-years among patients with corticosteroid exposure at enrollment compared with only 28.6 per 100 person-years among those without corticosteroid exposure.

Over a median follow-up time of 16 months, 537 all-cause acute care events occurred among pediatric participants. Of these, 134 (25%) were infection-related. The incidence rate of all infection-related acute care events (including first and recurrent infections) among pediatric participants was 13.2 per 100 person-years. Over a median follow-up time of 17 months, 507 all-cause acute care events occurred among 1027 adult participants, and 93 (18%) of the events were infection-related.

The study was limited by the lack of a control group and inability to estimate the risk of infection attributable to glomerular disease, Dr Glenn’s team noted. Additionally, the researchers were unable to account for infections managed at home or by a primary care physician.

“Our findings generally reinforce what nephrologists have thought for some time about risk of infection in this patient population,” Dr Glenn said. “Pediatric nephrologists need to counsel families regarding infection risk, especially during periods of steroid exposure and disease relapse. Apart from greater awareness, patient and family counseling strategies to reduce exposure to infectious agents and more diligent attention to recommended vaccination regimens are needed, especially for influenza and pneumococcal disease.”

Nephrologist Panduranga Rao, MD, who is professor of internal medicine at the University Michigan in Ann Arbor, said the study findings are clinically relevant because they better define the magnitude of infection risk as well as the burden of hospitalization in this patient population. “It also helps us in quantifying the risk imposed by various features of glomerular disease such as low serum albumin as well as level of proteinuria,” Dr Rao said. “I was a little surprised to see that children … had a greater risk of infection than adults, as normally you would expect adults to do worse in view of the many comorbidities they accumulate over time.”

The current study, he said, highlights the importance of tailoring therapy to the type of kidney disease. Noting that steroids are commonly used for many glomerular diseases, he added: “These treatments come with a broad range of side effects. If we are able to direct therapy to specific disease pathways, it is possible we may be able to reduce the morbidity associated with treatment. Until that time, it is important to be cognizant of the numerous side effects of the drugs we use and institute appropriate prophylaxis to decrease adverse events such as infection by effective use of either vaccines or prophylactic antimicrobials.”

Rakesh Gulati, MD, a clinical associate professor and the director of the Nephrology/Transplant Fellowship Programs at Jefferson Health in Philadelphia, Pennsylvania, said low serum albumin, as shown in the current study, is a marker of malnutrition and more aggressive disease, so it is not surprising that the study cohort had a relative high rate of infections. The study findings, he said, may be more relevant to pediatric glomerular disease cases. “Antibiotic prophylaxis as well as age-appropriate immunizations for respiratory illness in such subjects may prevent much morbidity and readmissions in such patients,” Dr Gulati said.

Reference

Glenn DA, Henderson CD, O’Shaughnessy M, et al. Infection-related acute care events among patients with glomerular disease. Published online October 20, 2020. Clin J Am Soc Nephrol. doi: 10.2215/CJN.05900420