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GFR at initiation of dialysis and mortality in CKD: a meta-analysis
Paweena Susantitaphong1, Sarah Altamimi, Motaz Ashkar
1Department of Medicine, Division of Nephrology, Kidney and Dialysis Research Laboratory, St. Elizabeth's Medical Center, Boston, MA 02135, USA.
Insights
Higher estimated glomerular filtration rate (GFR) at dialysis initiation is linked to increased mortality risk in advanced chronic kidney disease (CKD) patients. This association persists regardless of nutritional status, warranting further investigation into GFR measurement methods.
Area of Science:
- Nephrology
- Epidemiology
- Clinical Research
Background:
- Increasing trend of advanced chronic kidney disease (CKD) patients initiating dialysis at higher glomerular filtration rates (GFRs).
- Emerging evidence suggests a potential association between higher GFR at dialysis initiation and increased mortality.
Purpose of the Study:
- To investigate the association between glomerular filtration rate (GFR) at the initiation of dialysis therapy and all-cause mortality in patients with advanced chronic kidney disease (CKD).
- To analyze the impact of different GFR determination methods (estimated vs. calculated) on mortality risk.
Main Methods:
- Systematic literature search across multiple databases (MEDLINE, Cochrane, ClinicalTrials.gov, ASN abstracts) and bibliographies.
- Meta-analysis of 16 identified studies (15 cohorts, 1 RCT) including over 1 million patients with advanced CKD.
- Analysis focused on the association between GFR at dialysis initiation (predictor) and all-cause mortality (outcome), with adjustments for nutritional covariates in a subset of studies.
Main Results:
- Higher GFR at dialysis initiation was associated with a significantly higher risk of all-cause mortality (pooled adjusted HR: 1.04; 95% CI, 1.03-1.05).
- This association remained significant even after adjusting for nutritional covariates (HR: 1.03; 95% CI, 1.02-1.04).
- A notable contrast was observed: higher mortality risk with estimated GFR, but lower mortality risk with calculated GFR, indicating a significant impact of GFR determination method.
Conclusions:
- Higher estimated GFR at dialysis initiation is independently associated with increased mortality risk in advanced CKD patients.
- Substantial heterogeneity across studies and the impact of GFR measurement methods (estimated vs. calculated) are key considerations.
- Further research is needed to clarify these associations, particularly given the paucity of randomized controlled trials and methodological variations.
Background:
The proportion of patients with advanced chronic kidney disease (CKD) initiating dialysis therapy at a higher glomerular filtration rate (GFR) has increased during the past decade. Recent data suggest that higher GFR may be associated with increased mortality.
Study Design:
A meta-analysis of cohort studies and trials.
Setting & Population:
Patients with advanced CKD.
Selection Criteria For Studies:
We performed a systematic literature search in MEDLINE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, American Society of Nephrology abstracts, and bibliographies of retrieved articles to identify studies reporting on GFR at dialysis therapy initiation and mortality.
Predictor:
Estimated or calculated GFR at dialysis therapy initiation.
Outcome:
Pooled adjusted hazard ratio (HR) of continuous GFR for all-cause mortality.
Results:
16 cohort studies and 1 randomized controlled trial were identified (n = 1,081,116). By meta-analysis restricted to 15 cohorts (n = 1,079,917), higher GFR at dialysis therapy initiation was associated with a higher pooled adjusted HR for all-cause mortality (1.04; 95% CI, 1.03-1.05; P < 0.001). However, there was significant heterogeneity (I(2) = 97%; P < 0.001). The association persisted among the 9 cohorts that adjusted analytically for nutritional covariates (HR, 1.03; 95% CI, 1.02-1.04; P < 0.001; residual I(2) = 97%). The highest mortality risk was observed in hemodialysis cohorts (HR, 1.05; 95% CI, 1.02-1.08; P < 0.001), whereas there was no association between GFR and mortality in peritoneal dialysis cohorts (HR, 1.04; 95% CI, 0.99-1.08, P = 0.1; residual I(2) = 98%). Finally, higher GFR was associated with a lower mortality risk in cohorts that calculated GFR (HR, 0.80; 95% CI, 0.71-0.91; P = 0.003), contrasting with a higher mortality risk in cohorts that estimated GFR (HR, 1.04; 95% CI, 1.03-1.05; P < 0.001; residual I(2) = 97%).
Limitations:
Paucity of randomized controlled trials, different methods for determining GFR, and substantial heterogeneity.
Conclusions:
Higher estimated rather than calculated GFR at dialysis therapy initiation is associated with a higher mortality risk in patients with advanced CKD, independent of nutritional status. Although there was substantial heterogeneity of effect size estimates across studies, this observation requires further study.
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