Smaller changes in kidney filtration may predict end stage renal disease progression

1. A 57% decrease in estimated glomerular filtration rate (GFR), corresponding to a doubling of serum creatinine, is traditionally used as a measure of end stage renal disease progression. 

2. This study found that a smaller decrease in estimated GFR of 30% correlated with mortality and progression to end stage renal disease. 

Evidence Rating Level: 1 (Excellent)       

Study Rundown: The current standard endpoint for studies of end stage renal disease (ESRD) is a doubling in serum creatinine, which corresponds to a 57% reduction in glomerular filtration rate (GFR). While this is a useful benchmark, it often occurs late in the disease process. This study examined the risk of ESRD and mortality based on the change in GFR over 1, 2, and 3 years to try to establish additional useful endpoints for research and clinical use. Meta-analyses were performed using 22 studies (over 1.5 million individuals) with multiple creatinine measurements to study ESRD and 35 studies (over 1.7 million individuals) with mortality data. Included studies involved participants who were 18 years of age or older.

This study involved a very large total sample and cohort size. However, it was limited by characteristics inherent to metanalyses, including the difficulties of drawing conclusions based on many heterogeneous studies. The quality of each included study was not assessed. Nevertheless, this study contributes to our understanding of the prognosis and significance of decreases in GFR smaller than 57% and will be helpful both clinically and in designing future research studies.

Click to read the study, published today in JAMA

Relevant Reading: Short-term change in kidney function and risk of end-stage renal disease

In-Depth [meta-analysis]: This study performed meta-analyses on 22 studies with GFR data and 35 studies with mortality data to explore the risk of ESRD and mortality with decreases in GFR.  Over 2 years, of those with ESRD, 52% had a 30% decline in GFR and only 16% had a 57% decline in GFR. The HR for ESRD was 5.4 (95% CI 4.5-6.4) with a decrease in GFR of 30% at lower GFR and 6.7 (95% CI 3.9-11.1) at higher GFR.  A reduction of 57% in GFR was associated with an HR for ESRD of 32.1 (95% CI 22.3-46.3) at lower GFR and 57.2 (21.9-149.1) at higher GFR. There was a positive correlation between decrease in GFR and mortality and the adjusted HR for mortality was 1.8 (95% CI 1.6-1.9) with a decrease in GFR of 30%, 2.3 (95% CI 2.1-2.5) with a 40% decrease in GFR, and 3.7 (95% CI 3.2-4.4) for a 57% decrease in GFR.

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