Macroalbuminuria Is a Better Risk Marker than Low Estimated GFR to Identify Individuals at Risk for Accelerated GFR Loss in Population Screening

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.

Progression of Kidney Disease in Indigenous Australians: The eGFR Follow-up Study

“…These findings are consistent with previous work of Hoy et al in a remote Australian community (4), studies among Pima Indians (6), and more broadly among high-risk population cohorts (where ACR and low GFR were the key factors) (17). Our findings of the important role of albuminuria are consistent with those of the Prevention of Renal and Vascular End-stage Disease study among Europeans (7,8) and those of international CKD cohorts (9).…”

“…Macroalbuminuria was an identified risk factor for renal and all-cause death in this study; however, prospective cohort studies recruiting participants across multiple communities and geographic regions have not been reported. The important association of albuminuria with accelerated GFR loss is consistent with findings among Pima Indians with diabetes (6), the Prevention of Renal and Vascular End-stage Disease study among Europeans (7,8), a recent metaanalysis of available CKD cohorts (9), and recent changes in CKD classification to incorporate level of albuminuria (9).…”

Masked Hypertension Determined by Self-Measured Blood Pressure at Home and Chronic Kidney Disease in the Japanese General Population: The Ohasama Study

“…GFR decline is closely related to poor volume control and is linked with an elevation of oxidative stress, a non-traditional CVD risk (19). On the other hand, proteinuria, which is a risk of GFR decline (20) and cardiovascular events (21), is a marker of endothelial cell dysfunction or systemic vasculopathy (22). Based on this medical background information, it has been speculated that decreased GFR with proteinuria may exaggerate the risk of CVD events and poor patient outcomes.…”

Proteinuria and Rate of Change in Kidney Function in a Community-Based Population

“…Although previous studies have examined progression of kidney function, these reports were predominantly based on selected patient populations (older adults) or involved a relatively small number of participants. [3][4][5][6] The presence of proteinuria, a marker of kidney damage, identifies patients at increased risk of adverse clinical outcomes, including progression to ESRD. [7][8][9][10][11][12] However, whether the effects of proteinuria on earlier signs of kidney damage, namely the rate of change in estimated GFR (eGFR), vary by baseline level of kidney function is less clear.…”