Risks for glomerular filtration rate decline in association with progression of albuminuria in type 2 diabetes.

BACKGROUND: The aim of this study was to investigate the annual rate of glomerular filtration rate (GFR) decline and risks for this decline in association with albuminuria progression in type 2 diabetes. METHODS: An observational 4-year cohort study was performed on 1002 subjects with preserved GFR (699 normoalbuminuric), and the predictive value of baseline variables on the GFR slope was investigated. GFR decliner and albuminuria progressor were defined as a GFR slope <-4.0%/year and changes in the geometric mean of urinary albumin from baseline to follow-up >150%, respectively. RESULTS: Annual rates of GFR decline (percent per year, median and interquartile range) were -2.58 (-4.70 to -0.48) in normoalbuminuria, -3.49 (-5.93 to -1.11) in microalbuminuria and -6.58 (-10.64 to -3.53) in macroalbuminuria. Subjects cross-classified according to GFR decliner/albuminuria progressor consisted of 51% (-/-), 13% (-/+), 28% (+/-) and 8% (+/+). Common risks for GFR decline and albuminuria progression were retinopathy, neuropathy, hemoglobin A(1C) (HbA(1C)) and urinary albumin. Independent significant risks for GFR decline were baseline GFR, systolic blood pressure (SBP), total protein (TP) and hypertension. Proportions with progression to albuminuria were similar between GFR decliners and non-decliners. Multiple linear regression analysis indicated that GFR slope was predicted by baseline variables of urinary albumin, GFR, HbA(1C), SBP, plasma TP and retinopathy. These risks appeared variable according to high or low levels of urinary albumin and GFR. CONCLUSIONS: Urinary albumin excretion is only one risk factor for albuminuria progression and GFR decline, and other important factors were implicated as important for prevention of end-stage renal disease.

Determinants of decline in glomerular filtration rate in nonproteinuric subjects with or without diabetes and hypertension.

BACKGROUND AND OBJECTIVES: This study investigated whether the slope of estimated GFR is different between nonproteinuric subjects with and without diabetes, and what clinical factors are associated with the GFR slope. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: An observational cohort study was performed in 923 subjects, and the predictive value of baseline variables on the GFR slope was investigated. RESULTS: On the basis of the median 3-yr follow-up and 7 measurements of GFR, GFR slope (%/yr, median and interquartile range) was significantly larger in subjects with diabetes (-2.39 (-4.86 to 0.15), n=729) than in those without diabetes (-1.02 (-4.28 to 1.37), n=194), and this difference remained significant with or without presence of hypertension. After adjustments for confounding factors, predictors of GFR decline were found to be baseline high values of glycosylated hemoglobin A1C(HbA1C), GFR, systolic blood pressure, and low plasma total protein in subjects with diabetes, whereas only the latter two were significant in subjects without diabetes. In subjects with diabetes, the high GFR was accounted for by high HbA1C at baseline, and the predictors of GFR decline differed between those with and without hypertension, or with high and low baseline GFR. Any combination of the predictors showed increased risk for GFR decline. CONCLUSIONS: GFR slope is substantially affected by multiple factors at various stages. The degree of chronic hyperglycemia is likely to play a crucial role in elevating GFR and accelerating the decline in patients with type 2 diabetes even from the normoalbuminuric stage.