Combining GFR and Albuminuria to Classify CKD Improves Prediction of ESRD

Despite the high prevalence of chronic kidney disease (CKD), relatively few individuals with CKD progress to ESRD. A better understanding of the risk factors for progression could improve the classification system of CKD and strategies for screening. We analyzed data from 65,589 adults who participated in the Nord-Trøndelag Health (HUNT 2) Study (1995 to 1997) and found 124 patients who progressed to ESRD after 10.3 yr of follow-up. In multivariable survival analysis, estimated GFR (eGFR) and albuminuria were independently and strongly associated with progression to ESRD: Hazard ratios for eGFR 45 to 59, 30 to 44, and 15 to 29 ml/min per 1.73 m² were 6.7, 18.8, and 65.7, respectively (P < 0.001 for all), and for micro- and macroalbuminuria were 13.0 and 47.2 (P < 0.001 for both). Hypertension, diabetes, male gender, smoking, depression, obesity, cardiovascular disease, dyslipidemia, physical activity and education did not add predictive information. Time-dependent receiver operating characteristic analyses showed that considering both the urinary albumin/creatinine ratio and eGFR substantially improved diagnostic accuracy. Referral based on current stages 3 to 4 CKD (eGFR 15 to 59 ml/min per 1.73 m²) would include 4.7% of the general population and identify 69.4% of all individuals progressing to ESRD. Referral based on our classification system would include 1.4% of the general population without losing predictive power (i.e., it would detect 65.6% of all individuals progressing to ESRD). In conclusion, all levels of reduced eGFR should be complemented by quantification of urinary albumin to predict optimally progression to ESRD.Since the publication of the Kidney Disease Outcomes Quality Initiative (K/DOQI) clinical practice guidelines on the classification of chronic kidney disease in 2002,¹ several studies based on this classification system have shown very high prevalence estimates of chronic kidney disease (CKD) in the general population (10 to 13%).^2,3 Screening for CKD is therefore increasingly suggested^1,4; however, only a small proportion of patients with stage 3 to 4 CKD progress to ESRD.⁵ There is an ongoing discussion on whether the current CKD criteria are appropriate.^6–8 Developing a risk score to identify better the patients who are at increased risk for ESRD would be of major importance for the current efforts to establish clinical guidelines and public health plans for CKD.^4,9,10Several predictors of progression to ESRD have been identified,⁹ but their independent predictive power has not been well studied either in the general population or in high-risk subgroups. Intuitively, a low estimated GFR (eGFR) is an important risk factor for ESRD, and eGFR is the backbone of the current CKD classification. High urine albumin is a well-established major risk factor for progression.⁹ Only a few studies have examined the renal risk as a function of the combination of eGFR and albuminuria.^11–14 These studies are of restricted value, however, because of exclusion of patients with diabetes¹⁴; inclusion of men only¹²; inclusion of only patients with diabetes¹³; or absence of information on potentially important risk factors, such as smoking, obesity, dyslipidemia, and cardiovascular disease.^11,14CKD screening beyond patients with known hypertension or diabetes has been proposed,^1,4 but such screening programs have remained unsatisfactory because of their limited predictive power. We used the data of the Second Nord-Trøndelag Health Study (HUNT 2), Norway, to improve such prediction. HUNT 2 is a large population-based study with a high participation rate.¹⁵ Our aim was to examine how accurately subsequent progression to ESRD could be predicted by a combined variable of baseline eGFR and urine albumin. We also tested whether further potential renal risk factors provided additional independent prediction.