The eGFR difference between creatinine-based and cystatin-C-based equations is also important in an Asian population within the J-CKD-DB-Ex

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Chronic Kidney Disease (n=1585). Intervention: Large negative eGFR difference (Q1 < -14.83 mL/min/1.73 m²) vs. Near-zero eGFR difference (Q3 -6.62 to <1.72 mL/min/1.73 m²). Primary outcome: Kidney composite outcome (progression to CKD stage G5 or ≥40% decline in eGFRcr) (HR 2.11, 95% CI 1.24-3.59).

Takaya Nakashima; Hajime Nagasu; Akira Hirano; Masao Iwagami; Tadahiro Goto; Naoki Kashihara; Masaomi Nangaku; Yosuke Hirakawa

doi:10.1038/s41598-026-57444-y

June 9, 2026Scientific ReportsOpen Access

The eGFR difference between creatinine-based and cystatin-C-based equations is also important in an Asian population within the J-CKD-DB-Ex

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Why the study?

A large negative eGFR difference is related to kidney events, but whether this association applies to the Japanese population remains unclear.

Does a large negative eGFR difference predict kidney disease progression in Japanese patients with CKD?

Key Points

This study evaluates the significance of a negative eGFR difference in predicting kidney events in the Japanese population.
Conducted a retrospective cohort study using the J-CKD-DB-Ex dataset.
Examined the association between baseline eGFR difference and kidney composite outcomes using Cox proportional hazards models.
Utilized restricted cubic splines to assess the nonlinearity of the association.
Q1 (eGFRdiff < −14.83) was associated with a higher risk of kidney disease progression compared to Q3 (HR 2.11; 95% CI 1.24–3.59).
Hazards increased sharply as eGFRdiff became more negative, with a flat risk near zero to positive values.
A large negative eGFR difference was independently linked to an increased risk of kidney disease progression.

Study Design

Type

Cohort (n=1,585)

Multicenter

Yes

Structured PICO

Does a large negative eGFR difference predict kidney disease progression in Japanese patients with CKD?

P

Population

1,585 Japanese adults with CKD stage G2-G4 and paired creatinine and cystatin C measurements, followed for up to 5 years.

E

Exposure

Large negative eGFR difference (eGFRdiff), defined as cystatin C-based eGFR minus creatinine-based eGFR (specifically Q1 < -14.83 mL/min/1.73 m²)

C

Comparator

Near-zero eGFR difference (Q3: -6.62 to < 1.72 mL/min/1.73 m²)

O

Outcome

Kidney composite outcome defined as progression to CKD stage G5 (eGFRcr < 15 mL/min/1.73 m²) or ≥ 40% decline in eGFRcr within 5 yearscomposite

Main Result

Hazard Ratio: 2.11 (95% CI 1.24–3.59)

Limitations

Retrospective observational design
Cystatin C measurement was not routine and left to physician judgment, introducing potential selection bias
Missing dipstick proteinuria data in 27.0% of patients
Measurement of serum cystatin C is not routine but left to the judgement of the treating physician
Quantitative albuminuria/proteinuria measures were missing in a substantial proportion of patients
Dipstick proteinuria was missing in 27.0% of patients

Implication

A large negative difference between cystatin C-based and creatinine-based eGFR is independently associated with a higher risk of kidney disease progression in a Japanese CKD cohort.

Abstract

Recent studies have shown that a large negative estimated glomerular filtration rate (eGFR) difference (eGFRdiff), defined as the cystatin C–based eGFR minus the creatinine-based eGFR, is related with kidney events. However, whether this association applies to the Japanese population remains unclear. This study assessed the importance of a negative eGFRdiff in the Japanese population. This was a retrospective cohort study using the J-CKD-DB-Ex. The association between baseline eGFRdiff and kidney composite outcome defined as progression to CKD stage G5 (eGFRcr < 15 mL/min/1.73 m 2 ) or ≥ 40% decline in eGFRcr within 5 years was examined with Cox proportional hazards models. Restricted cubic splines were used to assess nonlinearity. eGFRdiff quartiles were Q1 < − 14.83, Q2 − 14.83 to < − 6.62, Q3 − 6.62 to < 1.72, and Q4 ≥ 1.72 mL/min/1.73 m 2 . Compared with Q3, Q1 was associated with a higher risk of the composite outcome (HR, 2.11; 95% CI 1.24–3.59). Spline analyses showed that hazards increased sharply as eGFRdiff became more negative and were relatively flat around near-zero to positive values. A large negative eGFRdiff was independently associated with a higher risk of kidney disease progression in a Japanese CKD cohort, supporting its use as a prognostic marker.

Discussion

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Cite This Study

Nakashima et al. (2026) conducted a cohort in Chronic Kidney Disease (n=1,585). Large negative eGFR difference (Q1 < -14.83 mL/min/1.73 m²) vs. Near-zero eGFR difference (Q3 -6.62 to <1.72 mL/min/1.73 m²) was evaluated on Kidney composite outcome (progression to CKD stage G5 or ≥40% decline in eGFRcr) (HR 2.11, 95% CI 1.24-3.59).

synapsesocial.com/papers/6a2ba1ca8101cf8926f00fc1 https://doi.org/10.1038/s41598-026-57444-y

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The eGFR difference between creatinine-based and cystatin-C-based equations is also important in an Asian population within the J-CKD-DB-Ex

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

The eGFR difference between creatinine-based and cystatin-C-based equations is also important in an Asian population within the J-CKD-DB-Ex

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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