Low Glomerular Filtration Rate in Normoalbuminuric Type 1 Diabetic Patients

Abstract

Increased urinary albumin excretion rate is widely accepted as the first clinical sign of diabetic nephropathy. However, it is possible that some diabetic patients could first manifest reduced glomerular filtration rate (GFR) or hypertension. Relatively advanced diabetic renal lesions can be present in some diabetic patients with long-standing normoalbuminuria, and this might indicate increased risk of progression to microalbuminuria and then to overt diabetic nephropathy. The aim of this study was to identify a group of normoalbuminuric type 1 diabetic patients with low GFR and compare them with normoalbuminuric patients with normal GFR. Altogether, 105 normoalbuminuric type 1 diabetic patients with at least 10 years of diabetes duration that had a renal biopsy performed for research purposes were studied. Patients were divided according to GFR into groups with normal (>90 ml ⅐ min -1 ⅐ 1.73 m -2 ) or reduced (<90 ml ⅐ min -1 ⅐ 1.73 m -2 ) GFR. Clinical and renal structural parameters were compared between these two groups. Glomerular structural parameters were estimated by electron microscopic morphometry. The 23 patients with reduced GFR had more advanced diabetic glomerular lesions. The finding of reduced GFR was much more common among female patients, particularly if retinopathy and/or hypertension were also present. This report confirms that reduced GFR occurs among long-standing normoalbuminuric type 1 diabetic patients and is associated with more advanced diabetic glomerular lesions and, probably, with increased risk of progression. For these reasons, we suggest that regular measurements of GFR be performed in long-standing normoalbuminuric type 1 diabetic female diabetic patients, especially in those with retinopathy or hypertension. Diabetes 52

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

“…Studies in patients with type 1 diabetes have yielded conflicting results. Some studies have not found a reduced GFR at all in patients with normal AER [17], while others have [10,18].…”

“…In general, an increase in AER is paralleled by a decrease in GFR, although some patients with normal AER may already have a decreased GFR together with more advanced diabetic glomerular lesions [10]. So far data on the association between early changes in GFR and lipid disturbances in patients with type 1 diabetes are limited.…”

Expression of Smad1 is directly associated with mesangial matrix expansion in rat diabetic nephropathy

“…4 It is reported that albuminuria does not reflect the severity of glomerular structural changes of diabetic nephropathy. 5 It is generally accepted that albuminuria predicts the late development of diabetic nephropathy. However, in our study, albuminuria was not correlated with mesangial matrix expansion, which is a predictor for declining of GFR in the late stage.…”

“…Recent study suggests that the percentage of microalbuminuric patients progressing to proteinuria over B10 years is only 30-45%. 5 Furthermore, extensive studies of the glomerular structure in diabetic patients with or without microalbuminuria failed to find a significant difference in the glomerular structural changes such as mesangial matrix expansion between the two groups in the absence of a raised blood pressure or reduced creatinine (Cre) clearance. 6,7 These reports show that albuminuria might not be a definite marker for mesangial matrix expansion in the early phase of diabetic nephropathy, although albuminuria correlates with and predicts the late development of diabetic nephropathy with decreased GFR and glomerulosclerosis.…”

Therapeutic Modalities in Diabetic Nephropathy: Standard and Emerging Approaches

“…5,6 Perhaps more worrisome is the realization that some diabetic patients develop DN in the absence of microalbuminuria. 7 In newly diagnosed diabetics, Zerbini et al 8 found that GFR began to decrease prior to the appearance of microalbuminuria. Thus, urinary albumin lacks both sensitivity and specificity to detect early DN.…”