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...

OBJECTIVEThe structural basis of normoalbuminuric renal insufficiency in patients with type 2 diabetes remains to be elucidated. We compared renal biopsy findings in patients with type 2 diabetes and estimated glomerular filtration rate (eGFR) and measured GFR of <60 mL/min/1.73 m2, associated with either normo-, micro-, or macroalbuminuria.RESEARCH DESIGN AND METHODSIn patients with normo- (n = 8) or microalbuminuria (n = 6), renal biopsies were performed according to a research protocol. In patients with macroalbuminuria (n = 17), biopsies were performed according to clinical indication. Findings were categorized according to the Fioretto classification: category 1 (C1), normal/near normal; category 2 (C2), typical diabetic nephropathy (DN) with predominantly glomerular changes; and category 3 (C3), atypical with disproportionately severe interstitial/tubular/vascular damage and with no/mild diabetic glomerular changes.RESULTSIn our study population (mean eGFR 35 mL/min/1.73 m2), typical glomerular changes (C2) of DN were observed in 22 of 23 subjects with micro- or macroalbuminuria compared with 3 of 8 subjects with normoalbuminuria (P = 0.002). By contrast, predominantly interstitial or vascular changes (C3) were seen in only 1 of 23 subjects with micro- or macroalbuminuria compared with 3 of 8 normoalbuminuric subjects (P = 0.08). Mesangial area increased progressively from normal controls to patients with type 2 diabetes and normo-, micro-, and macroalbuminuria. Varying degrees of arteriosclerosis, although not necessarily the predominant pattern, were seen in seven of eight subjects with normoalbuminuria.CONCLUSIONSTypical renal structural changes of DN were observed in patients with type 2 diabetes and elevated albuminuria. By contrast, in normoalbuminuric renal insufficiency, these changes were seen less frequently, likely reflecting greater contributions from aging, hypertension, and arteriosclerosis.

OBJECTIVE -To investigate the role of intrarenal vascular disease in the pathogenesis of nonalbuminuric renal insufficiency in type 2 diabetes.RESEARCH DESIGN AND METHODS -We studied 325 unselected clinic patients who had sufficient clinical and biochemical information to calculate an estimated glomerular filtration rate (eGFR) using the Modified Diet in Renal Disease six-variable formula, at least two estimations of urinary albumin excretion rates (AER), and a renal duplex scan to estimate the resistance index of the interlobar renal arteries. The resistance index, measured as part of a complications surveillance program, was compared in patients with an eGFR Ͻ or Ն60 ml/min per 1.73 m 2 who were further stratified into normo-(AER Ͻ20), micro-(20 -200), or macroalbuminuria (Ͼ 200 g/min) categories.RESULTS -Patients with an eGFR Ͻ60 ml/min per 1.73 m 2 had a higher resistance index of the renal interlobar arteries compared with patients with an eGFR Ն60 ml/min per 1.73 m 2 . However, the resistance index was elevated to a similar extent in patients with an eGFR Ͻ60 ml/min per 1.73 m 2 regardless of albuminuric status (normo-0.74 Ϯ 0.01, micro-0.73 Ϯ 0.01, and macroalbuminuria resistance index 0.75 Ϯ 0.11). Multiple regression analysis revealed that increased age (P Ͻ 0.0001), elevated BMI (P ϭ 0.0001), decreased eGFR (P Ͻ 0.01), and decreased diastolic blood pressure (P Ͻ 0.01), but not an increased AER, were independently associated with an elevated resistance index in patients with impaired renal function.CONCLUSIONS -Subjects with type 2 diabetes and reduced glomerular filtration rate had similar degrees of intrarenal vascular disease, as measured by the intrarenal arterial resistance index, regardless of their AER status. The pathological mechanisms that determine the relationship between impaired renal function and AER status in subjects with type 2 diabetes remain to be elucidated. Diabetes Care 29:1560 -1566, 2006T raditionally, microvascular disease resulting in a glomerulopathy and an increase in albumin excretion rate (AER) is believed to be the only significant mechanism by which diabetic renal disease develops. However, recent results have challenged the concept that a decline in renal function in patients with diabetes is always accompanied by an increased AER. Results from our group (1,2) and from the Third National Health and Nutrition Survey (NHANES III) (3,4) have suggested that the finding of nonalbuminuric renal insufficiency is not an uncommon discovery for subjects with diabetes, especially those with type 2 diabetes.The structural basis of nonalbuminuric renal insufficiency in type 2 diabetes remains to be elucidated. However, the use of techniques such as duplex Doppler ultrasound allows for the rapid, noninvasive evaluation of the intrarenal vasculature (5). In particular, the presence of intrarenal vascular disease can be documented by the use of established methods such as the calculation of the resistance index (5,6). Intrarenal arteriosclerosis, as opposed to other forms of renal dama...