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 m 2 were 6.7, 18.8, and 65.7, respectively (P Ͻ 0.001 for all), and for micro-and macroalbuminuria were 13.0 and 47.2 (P Ͻ 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 m 2 ) 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.

Background:The cardiovascular risk implications of a combined assessment of reduced kidney function and microalbuminuria are unknown. In elderly persons, traditional cardiovascular risk factors are less predictive, and measures of end organ damage, such as kidney disease, may be needed for improved cardiovascular mortality risk stratification.Methods: The glomerular filtration rate was estimated from calibrated serum creatinine, and the urine albumincreatinine ratio (ACR) was measured in 3 urine samples in 9709 participants of the second Nord-Trøndelag Health Study (HUNT II), a Norwegian community-based health study, followed for 8.3 years with a 71% participation rate.Results: An estimated glomerular filtration rate (EGFR) at levels of less than 75 mL/min/1.73 m 2 was associated with higher cardiovascular mortality risk, whereas a higher ACR was associated with higher risk with no lower limit. Low EGFR and albuminuria were synergistic cardiovascular mortality risk factors. Compared with subjects with an EGFR greater than 75 mL/min/1.73 m 2 and ACR below the sex-specific median who were at the lowest risk, subjects with an EGFR of less than 45 mL/min/1.73 m 2 and microalbuminuria had an adjusted incidence rate ratio of 6.7 (95% confidence interval, 3.0-15.1; P Ͻ.001). The addition of ACR and EGFR improved traditional risk models: 39% of subjects with intermediate risk were reclassified to low-or high-risk categories with corresponding observed risks that were 3-fold different than the original category. Age-stratified analyses showed that EGFR and ACR were particularly strong risk factors for persons 70 years or older.Conclusions: Reduced kidney function and microalbuminuria are risk factors for cardiovascular death, independent of each other and traditional risk factors. The combined variable improved cardiovascular risk stratification at all age levels, but particularly in elderly persons where the predictive power of traditional risk factors is attenuated.

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Abstract. Romundstad S, Holmen J, Hallan H, Kvenild K, Krü ger Ø, Midthjell K (HUNT Research Centre, Verdal, Norway; Levanger Hospital, Levanger, Norway; and Naerøy Health Centre, Naerøy, Norway). Microalbuminuria, cardiovascular disease and risk factors in a nondiabetic/nonhypertensive population. The Nord-Trøndelag Health Study (HUNT, 1995-97) Objective. Microalbuminuria (MA) as an independent marker of cardiovascular morbidity and mortality in nondiabetic/nonhypertensive individuals is under international debate. The aim of this study was to investigate the associations between MA and known cardiovascular risk factors/markers and disease in a randomly selected nondiabetic/nonhypertensive sample. Design. Cross-sectional study. Setting. Participants in the population-based NordTrøndelag Health Study (HUNT), Norway (n ¼ 65 258). Subjects. A total of 2113 individuals ( ‡20 years), randomly selected without diabetes and treated hypertension, delivered three morning urine samples for MA analysis. Main outcome measures. MA expressed as albuminto-creatinine ratio (ACR), cardiovascular risk factors and disease.Results. Increasing age, pulse pressure, systolic (SBP) and diastolic blood pressure (DBP) and coronary heart disease (CHD) significantly predicted MA in men and increasing pulse pressure, SBP and DBP were associated with MA in women, adjusted for other cardiovascular risk factors/markers. After excluding individuals with known CHD and untreated hypertension (SBP ‡ 140 mmHg, DBP ‡ 90 mmHg) and hence a high total risk of cardiovascular disease (CVD), only increasing age was associated with ACR in men and increasing SBP and pulse pressure in women. Smoking, elevated lipid and glucose levels were strongly associated with MA in individuals with a high total risk of CVD than in individuals with a low total risk. Conclusion. MA was associated with increasing blood pressure in both genders, age and CHD in men. Other cardiovascular risk factors/markers might be more influential in predicting ACR variation in nondiabetic/nonhypertensive individuals with a high total risk of CVD than in individuals with a low total risk.