No abstract

Macroalbuminuria, erythrocyturia, and impaired renal function are strong predictors of poor renal outcome in patients with known renal disease. However, the yield of mass screening for these variables to identify individuals who are at risk for GFR loss is yet unknown in a Western population. With the use of data from the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study, a prospective, population-based cohort study, the cardiovascular and renal prognosis was investigated in patients with classical renal risk markers: Macroalbuminuria (>300 mg albumin/24 h urine), erythrocyturia (>250 erythrocytes/L, without leukocyturia), and impaired renal function (both 24-h creatinine clearance and Modification of Diet in Renal Disease clearance below the fifth percentile of age-and gender-matched control subjects). The 8592 patients who were included in this study were followed for a 4-yr period. We identified 134 patients with macroalbuminuria, 128 with erythrocyturia, and 103 with impaired renal function. There was only a little overlap among the three groups. The prevalence of macroalbuminuria, erythrocyturia, and impaired renal function was calculated to be in the general population 0.6, 1.3, and 0.9%, respectively. In all three groups, fewer than 30% of patients were known to have this laboratory abnormality before screening. The incidence of cardiovascular disease was high in the macroalbuminuria group (e.g., the age-and gender-adjusted hazard ratio for mortality as a result of cardiovascular disease is 2.6 [1.1 to 6.0]) and for the impaired renal function group (3.4 [1.5 to 8.0]). After a mean follow-up of 4.2 yr, the macroalbuminuria group showed a ؊7.2 ml/min per 1.73 m 2 estimated GFR (eGFR) loss, compared with ؊2.3 ml/min per 1.73 m 2 in the control group (difference P < 0.001), whereas the rate of eGFR loss in the impaired renal function group (؊0.2 ml/min per 1.73 m 2 ; P ‫؍‬ 0.18) and the erythrocyturia group (؊2.6 ml/min per 1.73 m 2 ) was not different from the control group. Macroalbuminuria and impaired renal function both predict a worse prognosis with respect to cardiovascular morbidity and mortality. However, macroalbuminuria is a better risk marker than low eGFR or erythrocyturia to identify in population screening of individuals who are at risk for accelerated GFR loss.

We sought to identify predictors of the decline in renal function, especially those that are modifiable, in the 5488 participants of the prospective, community-based cohort study PREVEND who completed three visits during a mean follow-up of 6.5 years. The change in renal function was used as the outcome and this was calculated as the linear regression of three estimated GFR measurements obtained during follow-up. Risk factors, known to influence renal outcome in patients with primary renal diseases, were used as potential predictors in multivariate regression analyses. High systolic blood pressure and plasma glucose were found to be independent predictors for an accelerated decline in function for both genders. In males, albuminuria was the strongest independent predictor for renal function decline, whereas in females albuminuria was univariately associated only after adjustment for age. The direction of the association between cholesterol/HDL ratio and decline of renal function differed by gender. Surprisingly, in males, waist circumference was an independent predictor and positively associated with renal function outcome. These studies show that there are gender differences in the standard predictors of the decline in renal function.

Urinary albumin excretion is a powerful predictor of progressive cardiovascular and renal disease. In rats and humans, administration of a synthetic vasopressin analogue, 1-desamino-8-D-arginine-vasopressin, increases urinary albumin excretion; however, it is unknown if endogenous vasopressin levels influence albumin excretion. To determine this we measured copeptin, a marker of endogenous vasopressin levels, and its association with urinary albumin excretion in 7593 patients in the PREVEND study, a prospective population based, observational cohort. Urinary albumin excretion was measured in two consecutive 24-h urine samples by nephelometry while copeptin was measured by an immunoassay. Median copeptin concentrations were significantly higher in males than females and high levels were associated with significantly lower 24-h urine volumes of high osmolarity. With increasing quintiles of copeptin levels, the percentage of microalbuminuric subjects increased from 13 to 25 for males and from 8 to15 for females. This association was independent of age and other potential confounders; however, we found an interaction between age and copeptin in their association with urinary albumin excretion. Our study shows that plasma copeptin levels are associated with microalbuminuria, consistent with the hypothesis that vasopressin is involved in urinary albumin excretion. If future studies show that this association is causal, then drinking more water or pharmacological intervention to decrease plasma vasopressin may have beneficial effects on the kidney, especially in the elderly.