Isolate diffuse thickening of glomerular capillary basement membrane: a renal lesion in prediabetes?

Abstract

A total of 23 patients with proteinuria and isolated ultrastructural diffuse thickening of the glomerular capillary basement membrane were studied, focusing on the possibility of diabetes mellitus, morphometry of the capillary basement membrane, and the comparison with three other groups of patients. These included 14 patients with minimal change nephropathy (MCN), 45 patients with type II diabetes arbitrarily divided into 11 early and 34 late diabetic patients, defined, respectively, as less than 3 and over 5 years history, and 13 patients biopsied for transient mild proteinuria or hematuria, with no evidence of renal disease on follow-up were used as controls. The level of proteinuria and prevalence of hematuria were similar in patients with isolated thick basement membrane and with diabetes. Diabetic retinopathy was present in 10% of early diabetes, 69% of late diabetes, but not in isolated thick basement membrane. Kimmelstiel-Wilson nodules were seen in late diabetes, and not in other patients. Hyaline arteriosclerosis was more common in late diabetes than in early diabetes or isolated thick basement membrane. The basement membrane thickness was similar between controls (371717 nm) and MCN (345716 nm), between patients with isolated thick basement membrane (482769 nm) and early diabetes (457764 nm), but significantly thicker in isolated thick basement membrane as compared to controls and MCN. In patients with isolated thick basement membrane, the basement membrane thickness was not correlated with age, smoking, body weight, hyaline arteriosclerosis, and hypertension. However, blood tests for diabetes were positive in 20% of patients at biopsy, in 44% at 6 months and 70% at 24 months followup, while seven patients showed no evidence of diabetes on follow-up. Patients with proteinuria and isolated thick glomerular basement membrane must be differentiated from MCN for therapeutic implications, and specifically managed for its strong association with prediabetes or early diabetes.

Normoglycemic Diabetic Nephropathy: The Role of Insulin Resistance

“…Many showed frankly abnormal glucose metabolism [30, 33, 34], and others had evidence of MS, especially obesity [35]. Nevertheless, DN is pathologically distinct from obesity-related glomerulopathy, a lesion that is primarily characterized by glomerulomegaly and features of focal segmental glomerulosclerosis.…”

Astragaloside IV ameliorates renal injury in db/db mice

“…GBM and TBM (10–13 photographs in each sample, n = 3 per group) were measured using the grid intersect method41. The average podocyte FPW = (π/4) × (∑GBM length/∑number of foot process)42 was measured; and the FPW (6 photographs in each sample, n = 3 per group) was presented as nanometer (nm).…”

Pathologic Classification of Diabetic Nephropathy

“…20,21 GBM thickening has even been described as a "prediabetic" lesion: In patients with proteinuria and isolated GBM thickening but without overt diabetes, 20% were positive on a blood test for diabetes at the time of biopsy, whereas 44% were diagnosed with diabetes at 6 months, and 70% at 2 years after the biopsy was taken. 24 Long-term glucose control and urinary albumin excretion (UAE) correlate strongly with basement membrane thickness. 25 In 1979, Jensen et al 26 were among the first to measure GBM thickness using the orthogonal intercept method.…”