Glomerular Structure in Nonproteinuric IDDM Patients With Various Levels of Albuminuria

Abstract

Although microalbuminuria is known to foretell the later development of overt proteinuria in patients with insulindependent diabetes mellitus (IDDM), different investigators have reported different levels of albuminuria as being predictive. However, whether different levels of albuminuria reflect differences in glomerular structure is not well known. In this study, we divided a cohort of 66 nonproteinuric long-standing (duration 20 ± 7 years) IDDM patients, who had both renal functional and structural studies performed, into four groups according to their urinary albumin excretion rate (AER). The several different levels of microalbuminuria previously reported to be predictive served to demarcate these groups: group I, AER ≤22 mg/24 h (upper limit for normal in our laboratory) (33 patients); group II, AER 23–45 mg/24 h (11 patients); group HI, AER 46–100 mg/24 h (13 patients); and group IV, AER 101–220 mg/24 h (9 patients). Creatinine clearance was similar in groups I, II, and III but was lower in group IV. Systemic hypertension was present in five patients in group I, one in group II, seven in group III, and five in group IV. Mean values for glomerular basement membrane (GBM) width and volume fraction of the mesangium [Vv(mes/glom)] were greater in all groups than in a group of 52 age-matched normal kidney donors (P < 0.0001). Also, filtration surface density [Sv(PGBM)], inversely related to Vv(mes/glom) (r = 0.61, P < 0.0001), was reduced in all diabetic groups compared with the normal group (P < 0.0001). Structural measures were identical in group I and II. GBM width, Vv(mes/ glom), and Sv(PGBM) were more abnormal in groups III and IV than either group I or II (P < 0.05). Hypertension was unrelated to the values for any of these structural measures. However, AER and blood pressure had an interactive effect on Vv(mes/glom) (P = 0.002); in patients with AER <45 mg/24 h and hypertension, Vv(mes/ glom) was higher than in normotensive patients in the same AER category (P < 0.03). Thus, morphometric measures characteristic of diabetic glomerulopathy are present in normoalbuminuric IDDM patients, albeit in some of these patients renal structure is in the normal range. Lesions, on average, are more advanced when albuminuria exceeds 45 mg/24 h. In patients with AER >45 but <220 mg/24 h, a further division based on AER (< and >100) does not discriminate groups with different glomerular lesions. Therefore, albuminuria >45 mg/24 h indicates more advanced diabetic glomerulopathy and is frequently associated with other functional abnormalities such as reduced glomerular filtration rate and increasing blood pressure. These results are consistent with the majority of studies that have found the higher ranges of microalbuminuria to predict progression to overt nephropathy with greater specificity.