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 m(2) 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 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.

Association of kidney function and albuminuria with cardiovascular mortality in older vs younger individuals: The HUNT II Study.

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 albumin-creatinine ratio (ACR) was measured in 3 urine samples in 9,709 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 < .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.

Microalbuminuria in treated hypertensives: only a mirror image of cardiovascular risk? The HUNT Study, Norway.

OBJECTIVES: Microalbuminuria as an independent marker of cardiovascular morbidity and mortality in hypertensive individuals is under debate. The aim of this study was to study the possible associations between microalbuminuria on one hand and known cardiovascular risk factors and cardiovascular disease on the other hand, in a large, unselected population of treated hypertensives without diabetes. DESIGN: Cross-sectional study. SETTING: Participants of the HUNT Study, Norway (n = 65,258). SUBJECTS: 5,369 individuals (> or =20 years) with treated hypertension delivered three morning urine samples for microalbuminuria analysis. MAIN OUTCOME MEASURES: Microalbuminuria expressed as albumin-to-creatinine ratio, cardiovascular risk factors and cardiovascular disease. RESULTS: Increasing age, pulse pressure (systolic blood pressure-diastolic blood pressure), s-creatinine, cigarette pack years, cardiovascular disease, antihypertensive medication group, and years with antihypertensive medication were significantly associated with microalbuminuria in men. Increasing pulse pressure, cigarette pack years, and antihypertensive medication group were associated with microalbuminuria in women, adjusted for other cardiovascular risk factors. When excluding individuals of both sexes with self-reported cardiovascular disease and blood pressure > 160/90 mm Hg, no variable associated with cardiovascular risk factors registered was statistically associated with microalbuminuria. CONCLUSION: The present study indicates that microalbuminuria mainly represents a mirror image of hypertension (BP > 160/90) and prior or present cardiovascular disease. We therefore question whether the treatment quality would improve if yet another risk factor, microalbuminuria, were introduced as a routine test in treated hypertensives.

Microalbuminuria and all-cause mortality in treated hypertensive individuals: does sex matter? The Nord-Trøndelag Health Study (HUNT), Norway.

BACKGROUND: In hypertensive individuals, few prospective studies are available in which the association between microalbuminuria (MA) and all-cause mortality in the 2 sexes have been studied within the same population. METHODS AND RESULTS: We conducted a 4.3-year follow-up of 2307 men and 3062 women (> or =20 years old) with self-reported treated hypertension, all identified in the Nord-Trøndelag Health Study (HUNT), Norway, 1995 to 1997 (n=65 258). The main outcome measures were relative risk (RR) of all-cause mortality according to increasing albuminuria, defined at different levels of albumin-to-creatinine ratio (ACR). There was a consistent positive association between increasing ACR and all-cause mortality in men. The adjusted RR for ACR in the fourth quartile (> or =1.70 mg/mmol) was 1.6 (95% CI, 1.0 to 2.6), compared with ACR in the first quartile (<0.55 mg/mmol). The corresponding RR in women was 1.5 (95% CI, 0.8 to 3.1). We found a positive association between mortality and increasing number of urine samples with ACR above different cutoff levels, especially in men. In 3 urine samples, the lowest ACR level associated with mortality in men was 0.86 mg/mmol, RR 1.6 (95% CI, 1.1 to 2.4). The sex differences persisted after exclusion of those who died during the first year of follow-up, those with hypertension not treated optimally, and those with known cardiovascular disease. CONCLUSIONS: The association between ACR and all-cause mortality was stronger in treated hypertensive men than in women. The persistent sex differences indicate that hypertensive women tolerate MA better than men and that MA in women should be interpreted differently than in men.

Microalbuminuria and all-cause mortality in 2,089 apparently healthy individuals: a 4.4-year follow-up study. The Nord-Trøndelag Health Study (HUNT), Norway.

BACKGROUND: To date, there are few large follow-up studies of apparently healthy subjects with microalbuminuria (MA). The aim of this study is to examine the association between MA and all-cause mortality in nondiabetic nonhypertensive individuals. METHODS: We conducted a 4.4-year mortality follow-up of 2,089 men and women (> or =20 years) without diabetes and treated hypertension, randomly selected from the population-based Nord-Trøndelag Health Study (1995 to 1997; n = 65,258). Main outcome measures were adjusted relative risk (RR) for all-cause mortality according to increasing albuminuria, defined at different albumin-creatinine ratio (ACR) levels and in 1/2 or 3 urine samples. The main analysis was performed after exclusion of those with cardiovascular disease. RESULTS: There was a positive association between all-cause mortality and MA. The lowest ACR level associated with increased RR for mortality was the 60th percentile (> or =6.7 microg/mg [0.76 mg/mmol]; RR, 2.4; 95% confidence interval, 1.1 to 5.2), applying 3 urine samples with an ACR greater than the cutoff level. We found a positive association between mortality and increasing numbers of urine samples with an ACR greater than different cutoff levels, in which 3 urine samples were superior. Results persisted after adjusting for several confounders and excluding individuals with untreated hypertension (systolic blood pressure > or = 140 mm Hg/diastolic blood pressure > or = 90 mm Hg) and those who died during the first year of follow-up. CONCLUSION: Although this study confirms the association of all-cause mortality and ACR level in apparently healthy individuals, intervention trials are necessary before clinical cutoff levels of ACR are established and before screening programs are recommended.

[Illness related to occupational factors encountered in a general practice setting]. / Arbeidsrelaterte sykdommer i allmennpraksis.

BACKGROUND: This study examines the extent of illnesses encountered in a general practice setting that are related to occupational factors and their distribution in relation to specific occupations and diagnostic groups. MATERIAL AND METHODS: From December 2000 until May 2001, all patients between 20 and 67 years of age who came in to our rural community medical centre on the coast of central Norway, were asked to fill in a questionnaire about their reason for seeing a doctor, their occupational status, and whether they saw their current illness as related to occupational factors. If they did, they were also asked about what factors they deemed the most important. RESULTS: Among the 412 occupationally active respondents, 40% of women and 54% of men saw a possible or definite relationship between occupational factors and their current illness. Repetitive work and physically hard work were the two factors most frequently mentioned. INTERPRETATION: Occupational factors as causes of or influencing factors for illness in general practice seem to be more frequent than anticipated. There also seems to be a potential for prevention of illness and disability through better collaboration between general practitioners, occupational health services hospital based departments of occupational medicine.

Microalbuminuria in diabetic and hypertensive patients and the general population--consequences of various diagnostic criteria--the Nord-Trøndelag Health Study (HUNT).

OBJECTIVE: The purpose of this paper was to study the prevalence of microalbuminuria (MA) in males and females of various ages by applying various diagnostic criteria. Three groups of subjects were studied: apparently healthy individuals; self-reported hypertensives; and diabetics. MATERIAL AND METHODS: A total of 9255 individuals (age > or =20 years), all of whom were identified from the large (n = 65 258) population-based Nord-Trøndelag Health Study (HUNT) performed in Norway between 1995 and 1997, delivered three morning urine samples for MA analysis. Of these individuals, 651 reported both diabetes and treated hypertension, 944 diabetes only and 5547 treated hypertension only. The remaining 2113 subjects without diabetes or treated hypertension were randomly selected. The albumin:creatinine ratio (ACR) was used as an expression of urine albumin excretion. RESULTS: Applying the classical definition of MA of ACR > or =2.5 mg/mmol in at least two out of three urine samples, the prevalence of MA in those with both diabetes and hypertension was 42.2% in males and 25.9% in females; corresponding values for those with diabetes only were 27.8% and 22.4%, for the hypertensives 19.3% and 11.5% and for the randomly selected sample 5.2% and 4.7%. The prevalence of MA increased strongly with increasing age for both genders in all subgroups. The prevalence of MA changed considerably when applying different cut-off values of ACR and at least one, two or three urine samples with ACRs above the cut-off value. CONCLUSIONS: This study, one of the largest cross-sectional screening studies of MA ever performed, clearly illustrates the consequences of applying different diagnostic criteria. The optimal cut-off levels of MA for the prediction of cardiovascular disease still remain to be properly defined, and more follow-up studies are therefore needed.