Chronic kidney disease (CKD) is increasingly recognized as a global public health problem. CKD affects 10 to 16% of the adult population in Asia, Australia, Europe, and USA. There is now convincing evidence that CKD can be detected using simple laboratory tests, and that treatment can prevent or delay complications of decreased kidney function, slow the progression of kidney disease, and reduce the risk of cardiovascular disease. Data from the CKD Prognosis Consortium has provided a comprehensive evaluation of the associations of eGFR and albuminuria with mortality and kidney outcomes. The Consortium currently consists of 45 cohorts, including 1,555,332 people, from either general, high-risk, or CKD populations (CKD- PC) details here.

Summary of key results:

 1.  Albuminuria and GFR

• Both eGFR and albuminuria are associated independently with risk for mortality, cardiovascular disease mortality, ESRD, AKI and progressive CKD. The incidence rates were higher for mortality than kidney outcomes, but the risk relationships have a similar pattern for all outcomes. In general, the relative risks are higher for kidney outcomes than for mortality, reflecting a greater specificity of association of eGFR and ACR with these outcomes.

• There is a graded in increase in risk for lower levels of eGFR, independent of albuminuria. The risk for all outcomes is relatively constant between eGFR of 75 and 105 ml/min/1.73 m2, with a suggestion of a U-shaped curve for some outcomes. Even for the group with the lowest value of albuminuria, the increased relative risk for all outcomes is significant for eGFR of 60 ml/min/1.73 m2 in the continuous analysis and in the range of 45–59 ml/min/1.73 m2 for the categorical analysis, consistent with the current threshold value of GFR for the definition of CKD (<60 ml/min/1.73 m2). In the range of eGFR 30–59 ml/min/1.73 m2, there is a steep rise in risk with lower eGFR. In the range of eGFR >60 ml/min/1.73 m2, the risk for most outcomes is higher for eGFR between 60 and 74 ml/min/1.73 m2 than for eGFR >75 ml/min/1.73 m2.

• There is a graded increase in risk for higher levels of albuminuria, independent of eGFR, without an apparent threshold value. Increased relative risk is statistically significant for urine ACR >30 mg/g for mortality and kidney outcomes, even when GFR is >60 ml/min per 1.73m2, consistent with the current threshold value for albuminuria (>30 mg/g) as a marker of kidney damage. Increased relative risk at urine ACR of 10–29 mg/g is also apparent, suggesting that levels below the threshold may also warrant increased attention.

2.  Age Effects

Chronic kidney disease (CKD) is prevalent in older individuals, but the risk implications of low eGFR and high albuminuria across the full age range are controversial. The increase in CKD prevalence with age has led some individuals to question whether loss of kidney function is a normal part of the natural aging process and whether the definition of CKD should be modified according to age. Data from CKD-PC found that both low eGFR and high albuminuria are independently associated with mortality and ESRD regardless of age across a wide range of populations. Mortality showed lower relative risk but higher absolute risk differences at older age.

3. eGFR: CKD EPI versus MDRD Study equations

The Modification of Diet in Renal Disease (MDRD) Study equation is widely used for estimating GFR, but the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation is now recommended from KDIGO for estimation of GFR (link to GFR page). Data from the CKD-PC was used to compare the prognosis based on eGFR calculated using the CKD-EPI vs. MDRD Study equation for 90,750 study participants. The CKD-EPI creatinine equation classifies fewer individuals as CKD and more accurately categorizes the risk for mortality and ESRD than does the MDRD Study equation across a broad range of populations.

4. eGFR: Cystatin C versus Creatinine equations

eGFR computed using the combination of creatinine and cystatin C (eGFRcr-cys) is more accurate than eGFR computed using either alone (eGFRcr or eGFRcys) (link to GFR page). Data from the CKD-PC was used to compare the prognosis based on eGFR calculated with the use of cystatin C to that of the creatinine-based eGFR in more than 90,000 study participants across a broad range of populations. eGFRcr-cys classifies few individuals as CKD and than does eGFRcr alone. eGFRcys alone or in combination with eGFRcr-cys strengthens the association between the eGFR and the risks of death and end stage renal disease across these diverse populations. The risk of death is increased when the value for both cystatin C based eGFRcr and eGFR are based on combined creatinine and cystatin measurements that are below a threshold of approximately 85 ml per minute per 1.73m2, which is higher than the threshold of 60 ml/min per 1.73 m2 used in the definition of CKD.

Last Updated: July 2014