Nonalbuminuric Renal Insufficiency in Type 2 Diabetes

Abstract

OBJECTIVE -To determine the prevalence and characteristics of patients with type 2 diabetes who have impaired renal function, defined as a glomerular filtration rate (GFR) Ͻ60 ml ⅐ min Ϫ1 ⅐ 1.73 m Ϫ2 , and normoalbuminuria. RESEARCH DESIGN AND METHODS-A cross-sectional survey of 301 outpatients attending a single tertiary referral center using the plasma disappearance of isotopic 99m Tcdiethylene-triamine-penta-acetic acid to measure GFR and at least two measurements of urinary albumin excretion rate (AER) over 24 h to determine albuminuria.RESULTS -A total of 109 patients (36%) had a GFR Ͻ60 ml ⅐ min Ϫ1 ⅐ 1.73 m Ϫ2 . The overall prevalence of normo-, micro-, and macroalbuminuria was 43 of 109 (39%), 38 of 109 (35%), and 28 of 109 (26%), respectively. Compared with patients with macroalbuminuria, those with normoalbuminuria were more likely to be older and female. After excluding patients whose normoalbuminuric status was possibly related to the initiation of a renin-angiotensin system (RAS) inhibitor before the start of the study, the prevalence of a GFR Ͻ60 ml ⅐ min Ϫ1 ⅐ 1.73 m Ϫ2and normoalbuminuria was 23%. Temporal changes in GFR in a subset of 34 of 109 (32%) unselected patients with impaired renal function were available for comparison over a 3-to 10-year period. The rates of decline in GFR (ml ⅐ min Ϫ1 ⅐ 1.73 m Ϫ2 ⅐ year Ϫ1 ) of Ϫ4.6 Ϯ 1.0, Ϫ2.8 Ϯ 1.0, and Ϫ3.0 Ϯ 07 were not significantly different for normo-(n ϭ 12), micro-(n ϭ 12), and macroalbuminuric (n ϭ 10) patients, respectively.CONCLUSIONS -These results suggest that patients with type 2 diabetes can commonly progress to a significant degree of renal impairment while remaining normoalbuminuric. Diabetes Care 27:195-200, 2004A reduced glomerular filtration rate (GFR), mainly estimated from creatinine clearance measurements, has been reported to occur in some longstanding normoalbuminuric type 1 diabetic patients (1,2). Work from our group has suggested that this phenomenon can also occur in both type 1 or type 2 diabetes and that it may be more common in type 2 diabetes (3). Furthermore, in comparison to patients with type 1 diabetes, albuminuric patients with type 2 diabetes have a great deal of renal ultrastructural heterogeneity (4,5). This structural heterogeneity raises the possibility that different GFR and AER relationships are seen in patients with type 2 compared with those with type 1 diabetes. We have therefore further investigated the association between GFR and AER in patients with type 2 diabetes. In particular, we determined the prevalence and characteristics of patients with impaired renal function, defined as a GFR Ͻ60 ml ⅐ min Ϫ1 ⅐ 1.73 m Ϫ2 , and an AER within the normoalbuminuric range. RESEARCH DESIGN ANDMETHODS -A total of 625 patients attending the diabetes clinic at Austin Health, a tertiary referral center and teaching hospital of The University of Melbourne, Victoria, Australia, were studied between 1990 and 2001 as part of an ongoing project investigating the pathogenesis of diabetic renal disease. Isotopic estimations o...

Dynamic evaluation of renal resistive index in normoalbuminuric patients with newly diagnosed hypertension or type 2 diabetes

“…However, microalbuminuria identifies an already established glomerular damage, which is likely to be preceded by earlier structural and functional alterations undetectable to date, unless by kidney biopsy [7][8][9]. Moreover, a variable percentage of type 2 diabetic patients show an impairment of GFR even in the presence of normal albumin excretion [10]. Thus, new reliable markers of early renal dysfunction, specifically linked to vascular renal impairment, are needed in order to better identify the mechanisms responsible and the ideal timing of treatment, aiming to delay the onset and/ or slow the progression of renal damage.…”

Correlation of Microalbuminuria with Estimated GFR (eGFR) by Cockcroft–Gault and MDRD Formula in Type 2 Diabetics and Hypertensives

“…In general, the proportion of intact albumin increases as renal disease progresses from normoalbuminuria to microalbuminuria to macroalbuminuria. It is possible that in people who follow the normoalbuminuric pathway to renal insufficiency, there is an exaggerated rate of urinary albumin fragmentation [16].…”

Androgenic correlates of genetic variation in the gene encoding 5α-reductase type 1

“…Sixty-two males diagnosed with type 2 diabetes were drawn from a larger study of diabetes and its complications as published previously (MacIsaac et al 2004). All subjects gave informed consent, and the studies were sanctioned by the Human Experimentation Ethics Committee of Austin Health.…”

“…Urine was collected for measurement of urinary albumin excretion rates (AER). Serum albumin was measured by automated Bromo Cresol Purple (BCP) method (Hitachi 911/747), and urinary AER was measured by immunoturbidimetry (Dade-Behring; MacIsaac et al 2004). HbA1c was measured by automated HPLC (Biorad Diamat).…”