TOPLINE:

Patients with chronic kidney disease (CKD) stage G3 showed distinct inflammatory cytokine profiles that correlated with disease progression. Specific cytokine clusters were associated with a faster progression of CKD, increased cardiovascular events, and poor long-term outcomes, including kidney failure and mortality.

METHODOLOGY:

• Researchers conducted a prospective cohort study to evaluate associations between systemic inflammatory cytokine profiles and disease progression by comparing 165 patients with CKD stage G3 (median age, 68.0 years; 126 women) to 30 healthy control individuals.
• Plasma levels of 17 cytokines and urinary levels of 10 cytokines were measured using an automated immune analyser at baseline and 18 and 36 months.
• The primary outcome was a composite of kidney replacement therapy (KRT) or death within 10 years.
• Secondary outcomes included individual KRT and mortality rates, the progression of CKD (changes in the estimated glomerular filtration rate [eGFR] and urinary albumin-to-creatinine ratio [uACR]), and hospitalisations for cardiovascular events.

TAKEAWAY:

• Patients with CKD stage G3 had distinct cytokine profiles compared with control individuals: Plasma levels of 10 cytokines were elevated, and those of five cytokines were reduced; six urinary cytokine profiles were also different between those with CKD stage G3 and control individuals.
• At 36 months, urinary levels of interleukin (IL)-6 were negatively correlated with the eGFR slope; plasma levels of IL-8, IL-22, chemokine (C-X-C motif) ligand 13, and growth differentiation factor (GDF)-15 were correlated with the uACR slope.
• Plasma GDF-15 was identified as an independent predictor of KRT or death, and both plasma GDF-15 and tumour necrosis factor-alpha (TNF-α) predicted the requirement for KRT.
• A cluster analysis of plasma IL-8, IL-22, TNF-α, and GDF-15 identified six distinct patient phenotypes. Clusters 3 (elevated levels of TNF-α, GDF-15, and IL-22), 4 (elevated levels of all four cytokines), and 5 (elevated levels of GDF-15) were associated with worse kidney function, higher uACR, cardiovascular hospitalisations, and increased 10-year mortality.

IN PRACTICE:

"Specific plasma cytokine clusters consisting of four cytokines helped to condense the information contained in a larger cytokine panel and may inform research into novel pathophysiological pathways as well as risk stratification and response to therapy. These clusters may help design clinical trials of anti-inflammatory therapies targeting specific inflammatory cytokines," the authors wrote.

SOURCE:

This study was led by Alberto Martínez-Castelao, Hospital Universitari de Bellvitge, Hospitalet, Barcelona, Spain. It was published online on December 09, 2025, in Clinical Kidney Journal.

LIMITATIONS:

The sample size was small. Data on the temporal sequence between the initiation of KRT and death were not collected. Additionally, the healthy control group used for reference cytokine values was younger than the CKD cohort, which may have influenced the comparison of cytokine profiles.

DISCLOSURES:

Four authors reported receiving honoraria for lectures, consultancy fees, speaker fees, and travel support and having other ties with various pharmaceutical companies. Three authors reported being employees of Sysmex, and one author reported holding stocks in Telara Farma.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.