Glomerular Lesions and Urinary Albumin Excretion in Type I Diabetes without Overt Proteinuria

Abstract

Since several studies have suggested that a slight increase in urinary albumin excretion (microalbuminuria) is predictive of nephropathy in patients with diabetes mellitus, we studied the relation of albumin excretion to renal structure in patients with insulin-dependent (Type I) diabetes. Renal biopsy specimens were evaluated with light- and electron-microscopical morphometric techniques in 48 patients who had had diabetes for 5 to 40 years and who excreted less than 200 mg of urinary albumin per 24 hours. Patients in Group I (n = 26) had normal urinary albumin excretion, creatinine clearance, and blood pressure; those in Group II (n = 10) had increased urinary albumin excretion but normal creatinine clearance and blood pressure; those in Group III (n = 12) had increased urinary albumin excretion and hypertension, decreased creatinine clearance, or both. Glomerular structure varied similarly, ranging from normal to abnormal in Groups I and II, but was consistently abnormal in Group III. The thickness of the glomerular basement membrane, the fractional volume of the mesangium, and the mesangial volume per glomerulus in Group III exceeded the corresponding values in the other groups significantly. Thus, microalbuminuria, when present with hypertension, decreased creatinine clearance, or both, indicates established abnormalities of glomerular structure. Normal albumin excretion, or microalbuminuria without these other functional abnormalities, does not accurately predict the severity of the underlying glomerular lesions in patients with Type I diabetes.

Are glomerular volume differences between type 1 and type 2 diabetic patients pathologically significant?

“…Despite being normotensive, our type 1 diabetic patients demonstrated the characteristic lesions of diabetic glomerulopathy, some to quite an extensive degree; other studies have also reported patients with normotension and classical glomerular lesions [30,31].Thus we believe that although this group may not be entirely typical, they are representative.…”

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

“…These problems are also found in early human diabetic nephropathy. 6,7 In this study, we investigated the hyperfiltration stage, which is separated from the late progression stage. We speculate that this argument might come from the difference of the stage in the development of diabetic nephropathy.…”

“…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.…”

Amiloride-sensitive Na + /H + exchange in erythrocytes of patients with NIDDM: a prospective study

“…Aggressive treatment modalities, such as combined therapy with antihyperglycaemic drugs and insulin, appear to decrease the extent of microvascular damage, but are associated with increased incidence of hypoglycaemic events and weight gain [1]. Their risk-to-benefit ratio is high also because less than one third of diabetic patients develop nephropathy [2].Attempts have been made to find a marker that can predict micro-angiopathy in diabetes, and identify a group of patients for whom aggressive treatment is indicated despite its possible adverse effects. Urinary excretion of very small amounts of albumin (microalbuminuria) and elevation of arterial pressure [3] have been proposed for this purpose, but both appear when renal damage is already impending [4].…”

“…Aggressive treatment modalities, such as combined therapy with antihyperglycaemic drugs and insulin, appear to decrease the extent of microvascular damage, but are associated with increased incidence of hypoglycaemic events and weight gain [1]. Their risk-to-benefit ratio is high also because less than one third of diabetic patients develop nephropathy [2].…”