Age, Wasting, and IL-1 Type Raise Risk of Bacterial Infection for Dialysis Patients

Older age and wasting are risk factors for severe bacterial infections among patients with stage 5 chronic kidney disease (CKD), according to findings from a study by researchers at the Karolinska Instutet in Stockholm. Patients with a central dialysis catheter at the initiation of dialysis were more prone to infection, and patients with a particular single nucleotide polymorphism in the gene for interleukin-1β (IL-1β) were at markedly increased risk.

Because infectious complications are a major cause of morbidity and mortality in patients with CKD, Olof Heimbürger, MD, PhD, senior physician in the division of renal medicine, and colleagues at the institute investigated risk factors for infection. They presented their findings at the poster session “Dialysis: Non-Cardiovascular Outcomes and Clinical Trials.”

CKD patients commonly show signs of chronic inflammation, including elevated acute phase proteins and pro-inflammatory cytokines, one of which is IL-1β. A single base variation, a C/T polymorphism at nucleotide base position +3954 in the IL-1β gene, modulates production of the cytokine. The C/C allotype is linked to lower IL-1β production in monocytes in vitro.

In the study, 360 patients with severe stage 5 CKD were recruited before they started dialysis. About half the patients went on peritoneal dialysis (PD), a third on hemodialysis (HD) with peripheral vascular access, and the remainder on HD using a central dialysis catheter. The endpoint of the study was defined as hospitalization for bacterial infection, with a maximum follow-up period of three years. Patients were eliminated from the study at the time of transplantation or death.

The three most common infectious events were PD-related peritonitis (28 percent), respiratory tract infections (21 percent), and septicemia (14 percent). Forty-one percent of the patients had an infectious event leading to hospitalization. Staphylococci were the major causative organisms for both PD-related peritonitis and septicemia.

“The risk of being hospitalized for a bacterial infection was increased in the older patients [>55 years] and in the malnourished patients,” Heimbürger reported. These patients were also more likely to have diabetes mellitus (P <0.005) or cardiovascular disease (P <0.0005). Wasting (subjective global assessment score, SCG >1), inflammation (hsCRP >10 mg/L), and lower serum albumin levels were significantly more frequent in the presence of serious infectious diseases. Glomerular filtration rates did not differ significantly among patients with or without infections .

Forty-eight percent of PD patients had an infectious event versus 34 percent of the HD patients. There was no significant difference in the rates of septicemic events between the two groups.

“We found that patients with central dialysis catheters had an increased risk of infection [P <0.05], and I think we should avoid using central dialysis catheters if possible. Everyone agrees about that, but this is further evidence that this is important,” Heimbürger said.

The investigators also found an independent effect of the IL-1β genotype. The 139 patients who were low producers of this pro-inflammatory cytokine, that is, with the C/C genotype, had a higher risk for serious infectious events compared to patients with the C/T (n=71) or T/T (n=18) genotypes.

“So we see on one hand that patients on dialysis and in CKD 5 have increased levels of inflammatory cytokines, so they have a kind of constant pro-inflammatory state,” Heimbürger said. “But, on the other hand, they can’t respond in a good way when they are challenged by infection. So they have an overactivated but still blunted immune system.”

A multivariate analysis taking into account age, gender, diabetes mellitus, cardiovascular disease, wasting, and the IL-1β +3954 genotype yielded significant approximate odds ratios (OR) for risk of infection: age > 55 years, OR = 2.1; wasting, OR = 2.4; C/C genotype, OR = 1.9.

The investigators did not try to measure IL-1β levels in the blood because the molecule is short-lived and therefore difficult to evaluate. The study was too small to determine if specific types of bacteria were responsible for infections at particular sites.

In light of the finding of increased risk with central dialysis catheters, Heimbürger advised, “We should try to create a fistula, and I know the United States has been far behind Europe, but the United States is shifting very rapidly to have more fistulas, and I think it is the right way to go.”