Urinary Albumin as an Indicator of Diabetic Nephropathy Lesions in Japanese Type 2 Diabetic Patients

Abstract

Caucasian type 2 diabetic patients with microalbuminuria (MA) or overt nephropathy (ON) show greater heterogeneity of renal lesions than type 1 diabetic patients. We examined whether a similar situation exists in 30 Japanese type 2 diabetic patients [21 male, age 48 ± (SD) 8 years, known duration 11 ± (SD) 8 years] without definable renal disease other than diabetic nephropathy. Six patients were normoalbuminuric (NA), 11 MA, and 13 had ON. Normal controls were 9 age-matched Japanese living-related renal transplant donors. Electron microscopic morphometry was performed on renal biopsy specimens and related to renal function. Glomerular basement membrane width and mesangial fractional volume [Vv(Mes/glom)] were increased in all type 2 diabetic patients groups (NA, MA, ON) as compared with normal controls. The Vv(Mes/glom) correlated directly with urinary albumin/creatinine. However, Vv(Mes/glom) as well as glomerular basement membrane width overlapped among the three functional categories (NA, MA, ON) and normal controls. In conclusion: (1) similar to Caucasian type 2 diabetic patients, Japanese type 2 diabetic patients have greater heterogeneity of renal structure than Caucasian type 1 diabetic patients, and (2) urinary albumin is not a reliable indicator of underlying renal structure in Japanese type 2 diabetic patients.

Urinary IgG4 and Smad1 Are Specific Biomarkers for Renal Structural and Functional Changes in Early Stages of Diabetic Nephropathy

“…As shown in Supplementary (16,17). The normal renal structural reference was obtained from light microscopy of normal-appearing renal tissue from nephrectomy specimens from 10 patients with renal cell carcinoma (three women, seven men; mean age 66.8 6 13.1 years).…”

Arteriolar Hyalinosis Predicts Increase in Albuminuria and GFR Decline in Normo- and Microalbuminuric Japanese Patients With Type 2 Diabetes

“…The biopsies showed no evidence of nondiabetic renal glomerular or tubular/interstitial changes. Some of the patient data have been included in previous studies (6,8,14), but we excluded patients whose biopsies were performed for clinical indications. There were 7 women and 22 men (mean 6 SD age 49 6 10 years) with a known diabetes duration of mean 6 SD 12 6 7 years.…”

“…Routine stereological techniques, previously described (1,6,20,21), were used to measure the GBM width, mesangial volume fraction [Vv(Mes/glom)], and the surface density of the peripheral GBM [Sv(PGBM/ glom)]. Briefly, the GBM width was measured using the orthogonal intercept method (21), Vv(Mes/glom) by point counting, and Sv(PGBM/glom) by using the line-intercept method (1,6,20).…”

“…In Japanese patients with type 2 diabetes, GBM thickening and mesangial expansion also predicted an increase in UAE after 6 years' follow-up (5). However, the severity of the lesions also showed considerable overlap between normo-and microalbuminuria in a cross-sectional study (6). Nosadini et al (7) showed that GBM thickening and mesangial expansion predicted GFR decline in 108 patients with type 2 diabetes who underwent research renal biopsies.…”

Improvement of Renal Function in Type 2 Diabetic Nephropathy

“…[2] However, it has recently been noted that structural as well as functional aberrations are illustrated even in the normoalbuminuric stage of a diabetic patient. [3,4] Pagtalunan et al demonstrated a structural change such as increased glomerular basement membrane width and mesangial fractional volume in normoalbuminuric type 2 diabetes mellitus. In this regard, tubulointerstitial disease or fibrosis appears to be the most acceptable marker for the determinant of kidney involvement as well as its disease severity.…”