Association between HbA1c variability and disease prognosis in chronic kidney disease patients: a systematic review
Wanhaier Abudoureheman1, Fan Zhang1, Liuyan Huang1
1Department of Nephrology, Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Insights
Glycaemic instability, measured by HbA1c variability, is linked to higher risks of cardiovascular events and mortality in chronic kidney disease (CKD) patients. The impact on kidney disease progression requires further investigation.
Area of Science:
- Nephrology
- Endocrinology
- Cardiology
Background:
- Glycaemic variability, indicated by HbA1c variability, is a key factor in diabetes management.
- Chronic kidney disease (CKD) is a significant comorbidity associated with diabetes.
- Understanding the interplay between glycaemic instability and CKD outcomes is crucial for patient care.
Purpose of the Study:
- To investigate the association between HbA1c variability and clinical outcomes in patients with CKD.
- To evaluate the risk of CKD progression, cardiovascular events, and all-cause mortality in relation to glycaemic instability.
Main Methods:
- A systematic review and meta-analysis of cohort studies were performed.
- Literature search conducted across PubMed, Embase, and Scopus databases.
- Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for clinical outcomes.
Main Results:
- Eight cohort studies involving 59,018 CKD patients were analyzed.
- Increased HbA1c variability was significantly associated with a higher risk of cardiovascular events (HR 1.82) and all-cause mortality (HR 2.18).
- A non-significant trend towards increased CKD progression risk was observed (HR 1.49), with considerable heterogeneity.
Conclusions:
- Greater HbA1c variability is a significant predictor of adverse cardiovascular events and all-cause mortality in CKD patients.
- The association between HbA1c variability and CKD progression remains uncertain.
- Long-term glycaemic instability may hold prognostic value in CKD, warranting further research into its renal effects.
Aims:
To evaluate the association between HbA1c variability, a marker of long-term glycaemic instability, and clinical outcomes in patients with chronic kidney disease (CKD).
Methods:
We conducted a systematic review and meta-analysis of cohort studies. PubMed, Embase, and Scopus were searched from inception to 11 February 2026. Studies assessing HbA1c variability and reporting CKD progression, cardiovascular events, or all-cause mortality were included. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using fixed- or random-effects models as appropriate.
Results:
Eight cohort studies comprising 59,018 CKD patients were included. Higher HbA1c variability was significantly associated with increased risk of cardiovascular events (HR 1.82, 95% CI 1.52-2.20) with no significant heterogeneity. A significant association was also observed for all-cause mortality (HR 2.18, 95% CI 1.16-4.07), although substantial heterogeneity was present. For CKD progression, a non-significant trend toward increased risk was observed (HR 1.49, 95% CI 0.87-2.55) with considerable heterogeneity and wide prediction intervals.
Conclusion:
Greater HbA1c variability is associated with increased risks of cardiovascular events and all-cause mortality in CKD, whereas its association with renal progression remains inconclusive. These findings highlight the potential prognostic value of long-term glycaemic instability, although further studies are needed to clarify its role in renal outcomes.
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