Renal Function Decline Often Precedes Macroalbuminuria in Type 2 Diabetes

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Decreases in glomerular filtration rate (GFR) frequently occur before the onset of macroalbuminuria in patients with type 2 diabetes, according to a study. A GFR decline that predicts development of end-stage renal disease (ESRD), however, strongly depends on progression to macroalbuminuria.

Meda E. Pavkov, MD, of the Centers for Disease Control and Prevention in Atlanta, and collaborators measured GFR serially over about four years in 195 Pima Indians with type 2 diabetes. The researchers measured GFR using urinary clearance of iothalamate. They defined renal function decline (RFD) during this initial period by an average GFR loss of 3.3% or more per year. They subsequently followed patients for up to 17.8 years until ESRD onset, death, or December 31, 2010, whichever came first.

The RFD prevalence during the initial period was 32% in 68 subjects with normal baseline albuminuria (albumin/creatinine ratio [ACR] below 30 mg/g), 42% in 88 subjects with microalbuminuria (ACR of at least 30 but less than 300 mg/g), and 74% in 39 participants with macroalbuminuria (ACR of 300 mg/g or greater), according to findings published in the Clinical Journal of the American Society of Nephrology (2012;7:78-84). The cumulative incidence of ESRD 10 years after the initial period was significant greater in subjects with than without RFD (41% vs. 15%).

ESRD developed in 36 subjects with RFD and 13 without. Of these 49 ESRD cases, 41 (83.7%) developed in subjects who had or developed macroalbuminuria during the initial period.  

After adjusting for age, gender, diabetes duration, and hemoglobin A1c level, the risk of ESRD was about 4.8 times greater in those with than without RFD. After additional adjustment for albuminuria, however, the association between RFD and ESRD was no longer significant.

“The appearance of RFD often preceded the appearance of macroalbuminuria or even microalbuminuria, confirming observations in type 1 diabetes that RFD may be an early event,” the authors concluded.

“Nevertheless, years of observation are required to firmly establish the presence of RFD, and a decline predictive of ESRD is strongly dependent on progression to macroalbuminuria. Given these considerations, the clinical value of ascertaining GFR slopes in patients with normal urinary albumin excretion or microalbuminuria to identify progressive kidney disease is limited.”

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