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Small eGFR Drops May Predict Kidney Outcomes

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Declines in estimated glomerular filtration rate (eGFR) smaller than those that currently attract clinical attention may help predict the risk of end-stage renal disease (ESRD), researchers reported.

In an analysis of data from the , a 30% decline in eGFR over 2 years was tied to a five -fold increase in risk of ESRD, , of Johns Hopkins University, and colleagues reported online in the .

Action Points

  • In a meta-analysis with a large database, declines in estimated GFR smaller than a doubling of serum creatinine concentration -- a commonly used CKD progression endpoint -- occurred more commonly and were strongly and consistently associated with the risk of ESRD and mortality.
  • The data support consideration of lesser declines in estimated GFR than currently used (such as a 30% reduction over 2 years) as an alternative end point and indicator of risk for CKD progression.

They also simultaneously reported the findings at a meeting of the European Renal Association/European Dialysis and Transplant Association Congress.

The findings may "provide a basis for use [of smaller eGFR changes] as alternative outcomes for CKD progression," they wrote.

Both of the current markers used to predict outcomes in chronic kidney disease -- ESRD itself, or a doubling of serum creatinine -- are late events, and there is a need for another approach to determine prognosis, such as by using declines in eGFR, the researchers said.

To better characterize the decline in eGFR as it relates to progression to ESRD, Coresh and colleagues looked at data on 1.7 million patients from the CKD Prognosis Consortium. There were 12,344 cases of ESRD and 223,944 deaths.

Overall, they found that declines in eGFR that were smaller than a doubling of serum creatinine occurred more commonly and were strongly and consistently associated with the risk of ESRD and mortality.

Among patients with a baseline eGFR of less than 60 mL/min, the adjusted hazard ratios for ESRD were higher with greater declines in eGFR over 2 years:

  • 30% drop: HR 5.4 (95% CI 4.5 to 6.4)
  • 57% drop: HR 32.1 (95% CI 22.3 to 46.3)

They noted, however, that changes of 30% or more were more common, which provides "a basis for understanding the tradeoff between higher risk and lower prevalence in choosing a larger or smaller percentage change in estimated GFR as an outcome when studying CKD progression."

The association between eGFR decline and ESRD was strong and consistent across the length of the baseline period, baseline eGFR, age, diabetes status, or albuminuria, they reported.

The average adjusted 10-year risk of ESRD in patients with a baseline eGFR of 35 mL/min was:

  • 99% for 57% drop
  • 83% for 40% drop
  • 64% for 30% drop

Corresponding mortality risks were 77%, 60%, and 50%, respectively.

Coresh and colleagues concluded that the findings support the consideration of lesser declines in eGFR -- such as a reduction of 30% over 2 years -- as an alternative endpoint for CKD progression. This has the potential to shorten duration of follow-up, reduce costs, and increase the efficiency of clinical trials, they wrote.

At present for clinical practice, however, the study is useful for defining what level of change in the future can be considered important for a particular patient, and what the consequences would be, but "once the change has occurred, the relative importance of the change versus the last eGFR measure requires further analysis, and is beyond the scope of this study."

Disclosures

The CKD Prognosis Consortium is funded by the National Kidney Foundation and the National Institute of Diabetes and Digestive and Kidney Diseases.

A co-author disclosed relevant relationships with Matsushita, Mitsubishi Tanabe Pharma, Amgen, Novartis, and Alexion.

Primary Source

Journal of the American Medical Association

Coresh J, et al "Decline in estimated glomerular filtration rate and subsequent risk of end-stage renal disease and mortality" JAMA 2014; DOI: 10.1001/jama.2014.6634.