Is Nonalbuminuric Renal Insufficiency in Type 2 Diabetes Related to an Increase in Intrarenal Vascular Disease?

Abstract

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...

Postprandial hyperglycemia and hyperinsulinemia associated with renal arterio-arteriolosclerosis in chronic kidney disease

“…30 Recently, it has been noted that a substantial proportion of type 2 diabetes mellitus patients have renal insufficiency without albuminuria. 33,34 MacIsaac et al 34 showed that in type 2 diabetes mellitus patients with renal insufficiency, intra-renal resistive index obtained by Doppler ultrasound, which reflects intra-renal vascular injury, 35 was high regardless of the amount of albuminuria. Considering the results obtained in our studies, abnormal glucose metabolism/insulin resistance may induce tubulointerstitial injury and renal arterio-arteriolosclerosis even before the development of diabetes.…”

Relationship between lipid profiles and kidney function in patients with type 1 diabetes

“…Importantly, a third of our patients with normal AER had mildly impaired renal function and 2% had impaired renal function. It has previously been shown that patients with type 2 diabetes and a reduced eGFR (calculated by MDRD6 formula) have a similar degree of intrarenal vascular damage irrespective of their AER status [23]. Likewise, a decline in renal function has been reported to be associated with an increase in carotid intimalmedial thickness and an increase in intrarenal arterial resistance index [24].…”

A metabolomic study of low estimated GFR in non-proteinuric type 2 diabetes mellitus

“…It has been variously reported that some diabetic patients have low renal function (typically expressed as estimated GFR [eGFR]) even in the absence of proteinuria [1][2][3][4][5]. However, little else is known about the risk factors or mechanisms associated with low eGFR in patients with either type 1 [5] or type 2 diabetes [1][2][3][4].…”