Association of Albuminuria With Chronic Kidney Disease Progression in Persons With Chronic Kidney Disease and Normoalbuminuria : A Cohort Study.

BACKGROUND: Albuminuria is a major risk factor for chronic kidney disease (CKD) progression, especially when categorized as moderate (30 to 300 mg/g) or severe (>300 mg/g). However, there are limited data on the prognostic value of albuminuria within the normoalbuminuric range (<30 mg/g) in persons with CKD. OBJECTIVE: To estimate the increase in the cumulative incidence of CKD progression with greater baseline levels of albuminuria among persons with CKD who had normoalbuminuria (<30 mg/g). DESIGN: Multicenter prospective cohort study. SETTING: 7 U.S. clinical centers. PARTICIPANTS: 1629 participants meeting criteria from the CRIC (Chronic Renal Insufficiency Cohort) study with CKD (estimated glomerular filtration rate [eGFR], 20 to 70 mL/min/1.73 m2) and urine albumin-creatinine ratio (UACR) less than 30 mg/g. MEASUREMENTS: Baseline spot urine albumin divided by spot urine creatinine to calculate UACR as the exposure variable. The 10-year adjusted cumulative incidences of CKD progression (composite of 50% eGFR decline or kidney failure [dialysis or kidney transplantation]) from confounder adjusted survival curves using the G-formula. RESULTS: Over a median follow-up of 9.8 years, 182 of 1629 participants experienced CKD progression. The 10-year adjusted cumulative incidences of CKD progression were 8.7% (95% CI, 5.9% to 11.6%), 11.5% (CI, 8.8% to 14.3%), and 19.5% (CI, 15.4% to 23.5%) for UACR levels of 0 to less than 5 mg/g, 5 to less than 15 mg/g, and 15 mg/g or more, respectively. Comparing persons with UACR 15 mg/g or more to those with UACR 5 to less than 15 mg/g and 0 to less than 5 mg/g, the absolute risk differences were 7.9% (CI, 3.0% to 12.7%) and 10.7% (CI, 5.8% to 15.6%), respectively. The 10-year adjusted cumulative incidence increased linearly based on baseline UACR levels. LIMITATION: UACR was measured once. CONCLUSION: Persons with CKD and normoalbuminuria (<30 mg/g) had excess risk for CKD progression, which increased in a linear fashion with higher levels of albuminuria. PRIMARY FUNDING SOURCE: None.

The relationship between low levels of albuminuria and mortality among adults without major cardiovascular risk factors.

AIMS: The determine if elevated levels of albuminuria within the low range (urinary albumin-to-creatinine ratio, UACR <30 mg/g) are linked to cardiovascular death in adults lacking major cardiovascular risk factors. METHODS: The association between UACR and cardiovascular mortality was investigated among 12,835 participants in the 1999-2014 National Health and Nutrition Examination Survey using Cox proportional hazard models and confounder-adjusted survival curves. We excluded participants with baseline cardiovascular disease, hypertension, diabetes, pre-diabetes, estimated glomerular filtration rate (eGFR) <60ml/min/1.73m2, currently pregnant, and those who had received dialysis in the last year. RESULTS: Over a median follow-up of 12.3 years, 110 and 621 participants experienced cardiovascular and all-cause mortality. In multivariable-adjusted models, each doubling of UACR was associated with a 36% higher risk of cardiovascular death [HR 1.36 (95% confidence interval (CI) 1.02-1.82)] and a 24% higher risk of all-cause mortality [HR 1.24 (95% CI 1.10-1.39)]. The 15-year adjusted cumulative incidences of cardiovascular mortality were 0.91%, 0.99%, and 2.1% for UACR levels of <4.18 mg/g, 4.18 to <6.91 mg/g, and ≥6.91 mg/g, respectively. The 15-year adjusted cumulative incidences of all-cause mortality were 5.1%, 6.1%, and 7.4% for UACR levels of <4.18 mg/g, 4.18 to <6.91 mg/g, and ≥6.91 mg/g, respectively. CONCLUSIONS: Adults with elevated levels of albuminuria within the low range (UACR <30 mg/g) and no major cardiovascular risk factors had elevated risks of cardiovascular and all-cause mortality. The risks increased linearly with higher albuminuria levels. This emphasizes a risk gradient across all albuminuria levels, even within the supposedly normal range, adding to the existing evidence.

In this study of 12,835 adults without major cardiovascular risk factors (such as hypertension, cardiovascular disease, diabetes, pre-diabetes, or chronic kidney disease), we investigated the association between higher albuminuria levels within the low range (urine albumin-to-creatinine ratio (UACR) <30 mg/g) and both cardiovascular and all-cause mortality. Our findings revealed a linear increase in excess risk for both outcomes with rising albuminuria among relatively healthy adults. Each doubling of albuminuria was associated with a 36% higher risk of cardiovascular death (HR 1.36, 95% CI 1.02-1.82) and a 24% higher risk of all-cause mortality (HR 1.24, 95% CI 1.10-1.39). Each 10 mg/g increase in albuminuria was associated with 66% higher risk of cardiovascular mortality (HR 1.66, 95% CI 1.20, 2.28) and 41% higher risk of all-cause mortality (HR 1.41, 95% CI 1.17-1.68). These results challenge the assumption that UACR values below 30 mg/g are non-prognostic in adults without major cardiovascular risk factors.

The relationship between low levels of albuminuria and cardiovascular mortality among apparently healthy adults.

Background: Albuminuria is associated with cardiovascular events among adults with underlying cardiovascular disease and diabetes, even at low levels of urinary albumin excretion. We hypothesized that low levels of albuminuria in the 'normal' range (urinary albumin-to-creatine ratio (UACR) <30 mg/g) are associated with cardiovascular death among apparently healthy adults. Methods: We studied adults who participated in the 1999-2014 National Health and Nutrition Examination Survey. We excluded participants with baseline cardiovascular disease, hypertension, diabetes, estimated glomerular filtration rate (eGFR) <60ml/min/1.73m2, those who were currently pregnant, and those who had received dialysis in the last year. After excluding these conditions, only 5.0% of the remaining population had UACR ≥30 mg/g (N=873) and were excluded. The final sample size was 16,247. We assessed the relationship between UACR and cardiovascular and all-cause mortality using multivariable-adjusted Cox proportional hazards models. Models were adjusted for age, sex, race or ethnicity, smoking status, systolic blood pressure, hemoglobin A1c, total cholesterol, health insurance, food insecurity, serum albumin, body mass index, use of statins, and eGFR. Results: Mean age was 38.9 years (SD 13.6) and 53.7% were women. The median length of follow-up was 12.2 years. In multivariable-adjusted models, each doubling of UACR (within the <30 mg/g range) was associated with a 36% higher risk of cardiovascular death [HR 1.36 (95% confidence interval (CI) 1.11-1.65)] and a 28% higher risk of all-cause mortality [HR 1.28 (95%CI 1.17-1.41)]. The highest tertile of UACR (7.1-29.9 mg/g) was associated with an 87% higher risk of cardiovascular death [HR 1.87 (95%CI 1.20-2.92)] and 59% higher risk of all-cause mortality [HR 1.59 (95%CI 1.28-1.96)], compared with the lowest tertile (< 4.3 mg/g). Conclusions: In a nationally representative sample of relatively healthy community-dwelling adults, higher levels of albuminuria in the conventionally "normal" range <30 mg/g in healthy individuals are associated with greater mortality. Overall, our findings contribute to the growing body of evidence on the existence of a risk gradient across all levels of albuminuria, even in the so-called normal range.