Serum Creatinine Trajectories May Predict 28-Day Mortality in CKD

According to new research, among patients with acute kidney injury (AKI) on chronic kidney disease (CKD), moderate-stable, moderate-high stable, and high-decreasing serum creatinine trajectories were associated with an increased risk of 28-day mortality.1

“The serum creatinine trajectory can serve as an important indicator for assessing the short-term and long-term mortality risks of patients (especially critically ill or post-operative patients), and has significant reference value for clinical prognosis judgment,” wrote study investigator Jian Huag, MD, research director from the Zhejiang University School of Medicine, and colleagues.1

Serum creatinine, as a biomarker reflecting glomerular filtration function, has been widely used to assess renal function and diagnose kidney-related diseases. The latest evidence had suggested serum creatinine fluctuations were closely associated with the risk of death in CKD, but systematic trajectory typing research required further exploration.1,2

In a retrospective study, investigators aimed to explore the association between serum creatinine trajectories and 28-mortality in AKI on CKD patients through group-based trajectory modeling. They leveraged data from the Medical Information Mart for Intensive Care-IV (MIMIC) database, containing de-identified health-related information of Intensive Care Unit (ICU) patients from Beth Israel Deaconess Medical Center.1

Investigators measured and recorded serum creatinine > 3 times during the first 96 hours after admission to the ICU, and calculated the mean.1

The study included 7852 patients with CKD who developed AKI during hospitalization, defined as an increase in serum creatinine of ≥ 0.3 mg/dL within 48 hours, or an increase in serum creatinine of ≥ 50% from baseline within 7 days.1

Upon Group-Based Trajectory Modeling, investigators identified 5 trajectories:

• Serum creatinine low-stable (Group G1): with levels maintained at approximately 1 and showing a stable trend
  • (n=1761, 22.4%)
• Serum Creatinine High-Decreasing (Group G2): with baseline levels > 8 and showing a decreasing trend
  • (n=915, 11.7%)
• Serum Creatinine Moderate-Low Stable (Group G3) with levels maintained at approximately 1.3–1.5 and showing a stable trend
  • (n=2017, 25.7%)
• Serum Creatinine Moderate-Stable (Group G4) with levels maintained at approximately 2, and showing a stable trend
  • (n=1707, 21.7%)
• Serum Creatinine Moderate-High Stable (Group G5) with levels maintained at approximately 4 and showing a stable trend
  • (n=1451, 18.5%)1

In terms of comorbidities, group G5 had a significantly increased prevalence of diabetes and sepsis, G4 of chronic pulmonary disease and congestive heart failure, and G1 of cerebrovascular diseases. Regarding prognostic scores, group G1 had decreased Simplified Acute Physiology Score II and Sequential Organ Failure Assessment scores, while group G2 had a decreased Charlson Comorbidity Index Score.1

Investigators saw significant differences among the 5 groups in white blood cells, blood urea nitrogen, anion gap, total calcium, glucose, potassium, sodium, bicarbonate, and chloride levels. Group G2 had the highest serum creatinine baseline levels and estimated glomerular filtration rate (eGFR) percentage change.1

In fully adjusted analyses, compared with the low-stable trajectory group (G1), 28-day mortality risk was significantly increased in the high-decreasing group (G2) (Hazard Ratio [HR], 1.82; 95% Confidence Interval [CI], 1.18-2.82; P = .007), the moderate-stable group (G4) (HR, 1.45; 95% CI, 1.14-1.86; P = .003), and the moderate–high stable group (G5) (HR, 1.86; 95% CI, 1.36-2.54; P <.001).1

Investigators identified a significant interaction between baseline serum creatinine and trajectory group. The association between moderate-stable (G4) and moderate–high stable (G5) trajectories and 28-day mortality was only observed among patients with baseline serum creatinine ≤ 1.8 mg/dL, which investigators suggested may reflect preserved baseline renal filtration, making subsequent trajectory abnormalities more prognostically meaningful.1

“This finding provides a reference for clinical practice in formulating individualized prognostic assessment protocols for patients with different baseline serum creatinine levels,” concluded investigators.1

References

1. Ying J, Zhou H, Zhang Y, Zhu S, Zhang G, Huang J. Association of different serum creatinine trajectories with 28-day mortality in patients with acute kidney injury on chronic kidney disease: based on the MIMIC-IV database. European journal of medical research. Published online Autumn 2025:10.1186/s40001-02503632-x. doi:https://doi.org/10.1186/s40001-025-03632-x

2. Horne KL, Packington R, Monaghan J, Reilly T, Selby NM. Three-year outcomes after acute kidney injury: results of a prospective parallel group cohort study. BMJ Open. 2017;7(3):e015316. doi:https://doi.org/10.1136/bmjopen-2016-015316