Glomerular Filtration Rate Changes in Normoalbuminuric and Microalbuminuric Type 2 Diabetic Patients and Normal Individuals. A 10-year Follow-up

Marussi M, Gross JL, Silveiro SP. J Diabetes Complications. 2006;20:210-215.

The National Kidney Foundation (NKF) classifies chronic kidney disease (CKD) in stages 1 to 5. Stages are defined by glomerular filtration rate (GFR), with the most severe stage (stage 5) having the lowest filtration rate (>15 mL/min/1.73m²). The rate of GFR decline is variable among type 2 diabetes patients with microalbuminuria or proteinuria. In addition, previous studies have reported a notable decline in GFR levels in normal individuals or type 2 diabetic patients with normoalbuminuria after age 40. It is thus important to formulate a better understanding of the relationship between GFR decline, renal status, and age to better evaluate new therapeutic methodologies. The aim of this study was to prospectively analyze GFR changes in both normal individuals and normoalbuminuric type 2 diabetes patients and to identify factors associated with GFR decline.

At baseline, this 10-year prospective study included 65 patients with type 2 diabetes and normoalbuminuria (urinary albumin excretion rate [UAER] <20 μg/min) and 44 nondiabetic patients serving as the control group. All individuals underwent clinical evaluation at baseline consisting of height and weight measurement, blood pressure (BP), race (white or nonwhite), smoking status, presence of diabetic retinopathy, and cardiovascular disease (CVD); the procedure was repeated during the follow-up evaluation. Fifty normoalbuminuric type 2 diabetes patients and 32 control subjects were available for follow-up.

GFR was measured by the 51Cr-EDTA single-injection method. Glomerular hyperfiltration was defined as GFR >137 mL/min/1.73 m². Change in GFR was calculated as follows: (Final GFR - baseline GFR)/number of months of follow-up. CKD was staged according to the classifications established by the NKF. The stage of diabetic nephropathy was precisely determined by repeated 24-hour UAER measurements; 2 of 3 urine collections were used to confirm the presence of microalbuminuria or macroalbuminuria. UAER values for microalbuminuria and macroalbuminuria were defined as 20-199 μg/min and ≥200 μg/min, respectively. Fasting plasma glucose (FPG) and A1C levels were also measured at baseline and during the subsequent follow-up period. Multiple linear regression analysis was used to determine the association between change in GFR and possible reasons for its decline.

Participants were followed for a mean of 10 years. At baseline, study patients with type 2 diabetes were characterized as having a higher baseline GFR, systolic blood pressure, and a higher number of hypertensive patients. However, no difference was seen between diabetes patients and nondiabetic individuals with regard to BMI, age, or diastolic blood pressure. Twenty-eight percent of participants with diabetes developed microalbuminuria (progressors). The progressors demonstrated a higher baseline UAER and FPG than diabetes patients with normoalbuminuria (nonprogressors). Interestingly, the number of patients with stage 2 CKD was the same for progressors and nonprogressors; however, stage 3 CKD was not noted in any of the normoalbuminuric patients. Progressor and nonprogressor groups were the same in terms of gender proportion, ethnicity, systolic and diastolic BP, GFR values, number of hyperfiltering patients, number of hypertensive patients, and number of patients taking angiotensin-converting enzyme (ACE) inhibitors.

At the end of the study, UAER values for progressors and nonprogressors were 65.4 μg/min and 5.5 μg/min, respectively. There was no difference between the progressor group and the nonprogressor group regarding presence of hypertension, use of antihypertensive medication and ACE inhibitors, final BMI, smoking status, FPG, A1C, or insulin use. However, systolic and diastolic BP, total cholesterol, and LDL cholesterol were higher among progressors than nonprogressors. Progressors were also distinguished by a higher prevalence of diabetic retinopathy, CVD, and mortality compared to nonprogressors.

Change in GFR was analyzed in 3 groups: diabetes patients with persistent normoalbuminuria (nonprogressors; n=36), diabetes patients with new onset of microalbuminuria (progressors; n=14), and nondiabetic control participants (n=32). Results show a higher rate of GFR decline in patients who developed microalbuminuria compared to those with normoalbuminuria and/or control group. Nonprogressors and control participants had similar rates of GFR decline (-0.16 ± 0.16 mL/min/month and -0.13 ± 0.14 mL/min/month, respectively). From the multiple linear regression analysis, factors related to decline in GFR in type 2 diabetes were revealed. Data manifests a significantly strong association with GFR reduction and baseline FPG and the presence of microalbuminuria at the end of the study. Age, blood pressure, and UAER were notably not significant factors in the relationship.

The study was potentially limited by a lack of intermediate GFR measurements for some patients. However, analysis of data from patients with only baseline and follow-up measurements confirmed overall findings. The pronounced GFR decline in type 2 diabetes patients with diabetes was related mainly to poor baseline glycemic control.