New Immune Cell Marker Offers Clues to Kidney Disease Progression

A previously unrecognized immune-cell population that may serve as a sensitive indicator of kidney disease severity and future progression risk was uncovered by research from Japan.¹

The prospective observational study, published in Nephrology, introduces CD45 + C1q + CCR8+ cells as an emerging blood-based biomarker that reflects ongoing inflammation and fibrosis in chronic kidney disease (CKD) and acute kidney injury (AKI).

Despite advances in diagnostic imaging and serum markers, predicting which patients with CKD—the third fastest growing cause of death globally²—will experience rapid functional decline continues to challenge clinicians. Fibrosis is a common endpoint of both acute and chronic renal disorders, and researchers have long sought cellular indicators that mirror the biological processes driving fibrosis at an early stage.

Fibrosis occurs when inflammation activates immune cells and fibroblasts to release collagen and cytokines that remodel and damage tissue. Key molecules like C1q and CCR8 drive this process by promoting fibroblast activation and directing immune cells to sites of injury.

Researchers of the new study hypothesized that mononuclear immune cells expressing both molecules may represent a pro-fibrotic cell subset linked to renal injury. To test this, they used multicolor flow cytometry to quantify CD45 + C1q + CCR8+ cells in the peripheral blood of 44 patients diagnosed with kidney disease and compared the results with healthy volunteers.

The team included adults with biopsy-proven renal pathology or abnormal kidney function and used regression analysis to examine correlations between the percentage of CD45 + C1q + CCR8+ cells and clinical parameters, including serum creatinine (Cr), estimated glomerular filtration rate (eGFR), hemoglobin, and urinary protein levels.

Patients with kidney disease exhibited a significantly higher proportion of CD45 + C1q + CCR8+ cells compared with healthy controls (3.7% vs 1.5%). Levels were elevated in both CKD and AKI, with the highest percentages seen in acute injury. Statistical analyses demonstrated positive correlations between these cell percentages and serum creatinine and urinary protein, 2 core indicators of renal dysfunction, even after adjusting for age, sex, and hemoglobin.

Among the 21 patients who were followed for at least 3 months, nearly half experienced major kidney outcomes. Those with moderately increased baseline levels of CD45 + C1q + CCR8+ cells had a markedly higher risk of disease progression than those with lower levels, corresponding to a hazard ratio exceeding 27 in multivariate models.

Receiver-operating-characteristic analysis identified a 2.2% threshold that effectively distinguished high-risk from low-risk patients.

The results suggest that these triple-positive immune cells may act as intermediaries between inflammation and fibrosis. C1q-dependent cytokine production could amplify local injury, while CCR8 expression may drive migration of immune cells to renal tissue, explained the researchers. They note that together, these mechanisms may accelerate structural damage and functional loss. Elevated counts of CD45 + C1q + CCR8+ cells in blood could therefore mirror the intensity of fibrotic signaling occurring within the kidneys.

The discovery points to potential clinical applications in both prognosis and therapy. Measuring CD45 + C1q + CCR8+ cells may allow earlier identification of patients at risk of rapid renal decline, complementing established markers such as proteinuria and eGFR. Because these cells can be quantified with a minimally invasive blood test, they could serve as a practical tool for longitudinal monitoring. In parallel, targeting C1q- or CCR8-mediated pathways might represent a new therapeutic avenue for slowing fibrosis and preserving renal function.

The researchers acknowledged several constraints of their study, including the small sample size, limited number of healthy controls, and relatively short follow-up period averaging under ten months. Treatment data, such as use of renin–angiotensin inhibitors or SGLT2 inhibitors, were not analyzed, and causal relationships could not be established. They urge the need for larger, multicenter cohorts and mechanistic experiments to confirm whether CD45 + C1q + CCR8+ cells actively promote fibrosis or simply reflect its presence.

References

1. Sato K, Oshima M, Sakai N, et al. CD45 + C1q + CCR8+ cells as emerging indicators of kidney disease severity and progression risk. Nephrology. Published online September 16, 2025. doi:10.1111/nep.70126

2. Francis A, Harhay MN, Ong ACM, et al. Chronic kidney disease and the global public health agenda: an international consensus. Nat Rev Nephrol. Published online April 3, 2024. doi:10.1038/s41581-024-00820-6