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Background <p>Diabetes is the leading cause of chronic kidney disease (CKD) and end-stage kidney disease (ESKD), and glycemic assessment is complicated by altered glucose/insulin handling and biased glycated hemoglobin (HbA1c) values in advanced kidney disease. Beyond mean HbA1c, long-term visit-to-visit HbA1c variability has emerged as an additional dimension of risk. This review aims to summarize the definition, measurement, and clinical significance of long-term HbA1c variability in diabetes with CKD, and to discuss implications for risk stratification and management, including complementary biomarkers and continuous glucose monitoring (CGM).</p> Methods <p>We narratively reviewed observational cohorts, meta-analyses, and dialysis/advanced CKD studies evaluating metrics of long-term glycemic variability (e.g., HbA1c-standard deviation, HbA1c-coefficient of variation, HbA1c variability score) and their associations with renal outcomes, cardiovascular events, and mortality, alongside evidence on alternative biomarkers and CGM-derived indices.</p> Results <p>Across diverse populations, higher HbA1c variability is consistently associated with faster CKD progression, greater risk of ESKD, increased cardiovascular events, and higher all-cause mortality, often independent of mean HbA1c. In advanced CKD and dialysis, HbA1c limitations and treatment-related glucose swings heighten the value of CGM and, in selected settings, glycated albumin/fructosamine.</p> Conclusion <p>Long-term HbA1c variability is a robust prognostic marker in diabetic CKD and should complement mean HbA1c in clinical assessment; prospective trials are needed to test whether variability-targeted strategies improve hard outcomes.</p>

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Glycemic instability in renal decline: a review of HbA1c variability and outcomes in chronic kidney disease

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月21日

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  • Fan Zhang,
  • Rong Wu,
  • Yan Bai,
  • Yifei Zhong

摘要

Background

Diabetes is the leading cause of chronic kidney disease (CKD) and end-stage kidney disease (ESKD), and glycemic assessment is complicated by altered glucose/insulin handling and biased glycated hemoglobin (HbA1c) values in advanced kidney disease. Beyond mean HbA1c, long-term visit-to-visit HbA1c variability has emerged as an additional dimension of risk. This review aims to summarize the definition, measurement, and clinical significance of long-term HbA1c variability in diabetes with CKD, and to discuss implications for risk stratification and management, including complementary biomarkers and continuous glucose monitoring (CGM).

Methods

We narratively reviewed observational cohorts, meta-analyses, and dialysis/advanced CKD studies evaluating metrics of long-term glycemic variability (e.g., HbA1c-standard deviation, HbA1c-coefficient of variation, HbA1c variability score) and their associations with renal outcomes, cardiovascular events, and mortality, alongside evidence on alternative biomarkers and CGM-derived indices.

Results

Across diverse populations, higher HbA1c variability is consistently associated with faster CKD progression, greater risk of ESKD, increased cardiovascular events, and higher all-cause mortality, often independent of mean HbA1c. In advanced CKD and dialysis, HbA1c limitations and treatment-related glucose swings heighten the value of CGM and, in selected settings, glycated albumin/fructosamine.

Conclusion

Long-term HbA1c variability is a robust prognostic marker in diabetic CKD and should complement mean HbA1c in clinical assessment; prospective trials are needed to test whether variability-targeted strategies improve hard outcomes.