Inflammation Associated with Mortality in Kidney Transplant Recipients

Anders Åsberg, PhD

Investigators observed strong association between low-grade systemic inflammation in the 10 weeks following kidney transplantation and long-term mortality in a recent cohort study from Norway.

Generally, low-grade systemic inflammation has been established as a risk factor for all-cause mortality as has been known to increase the severity and risk of diseases including cardiovascular disease and cancer.

Kidney transplant recipients in particular face higher mortality rates often caused by CVD, malignancy, and infectious diseases, with investigators citing inflammation as an important marker in the pathogenesis of CVD in this patient group.

Investigators led by Anders Åsberg, PhD, Oslo University Hospital, evaluated the effect of general systemic inflammation measured 10 weeks after kidney transplants on long-term mortality.

All patients who received a kidney transplant at Oslo University Hospital between April 2007 and October 2012 were eligible for inclusion in the study. A total of 1349 adult patients underwent a kidney transplant at this time, after which they were tasked with performing a 10-weeks surveillance investigation.

Patients with early graft loss (22) or those with other reasons for not attending the investigation (136) and patients not examined due to lab accessibility (147) were excluded.

A total of 1044 patients remains, 1001 of whom had measure of all biomarkers included in the overall inflammation score.

Investigators measured inflammation 10 weeks after transplantation via composite inflammation scores based on 21 biomarkers. An overall inflammation score and 5 pathway-specific inflammation scores were featured including fibrogenesis, vascular inflammation, metabolic inflammation, growth/angiogenesis, and leukocyte activation.

Mortality was assessed via Cox regression models adjusted for common risk factors.

The Findings

The median follow-up time was 10.3 years, and a total of 312 (29.9%) patients died during the study period. Median time to death was 6.4 years.

Investigators observed that the overall sum of inflammation score varied from -39 to 38, and CVD was the cause of death for 100 (32.1%) patients.

Meanwhile, infections were the cause of 82 (26.3%) deaths and 130 (41.7%) of patients died of malignancy and other causes.

A total of 409 (39.2%) overall graft losses were observed during the study. Among these, 144 (35.2%) were death-censored graft loss.

Regarding patients in the highest quartile of the overall inflammation score featured in the study, the team observed that the hazard ratio for death was 4.71 (95%CI:2.85-7.81) (P<0.001). For patients in the intermediate groups, the hazard ratios were 2.35-2.54 (95%CI:1.40-3.96, 1.52-4.22) (P:0.001).

Investigators noted that the results were persistent when the score was analyzed as a continuous variable. Additionally hazard ratios ranging from 1.19 to 2.70 were recorded for all pathway-specicifc analyses, and a strong and consistent association between low-grade systemic inflammation following kidney transplantation and long-term mortality was recorded.

Importantly, no specific inflammatory pathway was considered causative.

“The results also give insight into why KTRs have high long-term mortality rates, and this could be targeted in future studies,” the team wrote.

The study, “Inflammation in the early phase after kidney transplantation is associated with increased long-term all-cause mortality,” was published online in the American Journal of Transplantation.