Structural-functional correlations of diabetic nephropathy

Abstract

Patient 1. A 30-year-old woman had had type-I (insulin-dependent) diabetes mellitus (IDDM) for 27 years. At the time of evaluation, she weighed 50 kg, was 157 cm tall, and had a blood pressure of 114/80 mm Hg. She had background retinopathy and no clinical neuropathy. Her urine was positive for protein by dipstick and the albumin excretion rate was 2500 /tg/min. Her hemoglobin A1 was 8.9%; serum creatinine, 1.2 mg/dl; and creatinine clearance, 79 mI/mm/i .73 m2. As part of the study of renal structure and function in siblings concordant for IDDM, she underwent a percutaneous renal biopsy. Light microscopy revealed that 30% of the glomeruli were globally sclerosed. The others all had moderately severe diffuse mesangial expansion. Many afferent and efferent glomerular arterioles showed varying amounts of hyalinosis, with some vessel walls completely replaced by the waxy, homogeneous, pink hyaline material. Mild diffuse interstitial expansion was evident, and patchy areas of more marked interstitial fibrosis were found, mainly in association with atrophic tubules or sclerotic glomeruli. Electron microscopic morphometric analysis showed the mesangial volume fraction (that is, fraction of glomerular volume occupied by mesangium [VvMesJ) to be 0.40 (upper limit of normal, 0.22). The VvMes cells measured 0.11 and VvMes matrix 0.26; the ratio of mesangial matrix to total mesangium was 0.65 (normal ratio 0.5). The surface density of the peripheral glomerular basement membrane (that is, the filtration surface per unit of tuft area {SvPGBM]) was 0.087 (lower limit of normal, 0.095) and the GBM width was 661 nm (upper limit of normal, 450 nm). Patient 2. The 28-year-old sister of Patient 1 developed IDDM at age 5. She had no retinopathy or neuropathy. She weighed 60 kg, was 164 cm tall, and had a blood pressure of 102/64 mm Hg. The urine was negative for protein by dipstick; urine albumin excretion rate was 75 g/min. Her hemoglobin A1 was 14%; serum creatinine, 0.9 mg/dl; and creatinine clearance, 71 ml/min/l .73 m2. Light microscopic evaluation of her renal biopsy specimen was similar to that of her sister. Morphometric analysis revealed a VvMes of 0.45, a ratio of mesangial matrix to total mesangium of 0.63, an SvPGBM of 0.83, and a GBM width of 712 nm.