Serial renal biopsies in normo- and microalbuminuric patients with type 2 diabetes demonstrate that loss of renal function is associated with a reduction in glomerular filtration surface secondary to mesangial expansion

Abstract

Aims: The aim of the present study was to explore the relationship between changes in renal structure in patients with type 2 diabetes at an early stage of diabetic nephropathy using serial renal biopsies, and change in renal function.

Methods: The study population comprised 10 patients with type 2 diabetes with normo- or microalbuminuria at baseline. Light and electron microscopy-based morphometric analyses were performed to quantitatively evaluate glomerular and interstitial structural changes. Urinary albumin excretion (UAE) and glomerular filtration rate (GFR) were measured annually. A second renal biopsy was performed after a mean of 6.1 ± 2.4 years of follow-up.

Results: UAE, GFR, blood pressure and severity of diabetic retinopathy (DR) did not change between the baseline and follow-up. The annual decrease in the surface density of the peripheral glomerular basement membrane (GBM) (Sv[PGBM/glom]) was correlated with the rate of loss of GFR during the six-year follow-up period. The annual change in the Sv(PGBM/glom) was negatively correlated with the change in mesangial volume fraction.

Conclusions: Decreases in the GFR in patients with type 2 diabetes with normo- or microalbuminuria at baseline were associated with a decreased glomerular filtration surface, as a result of mesangial expansion during a mean six years of observation. These findings confirm ongoing pathological progression of glomerulopathy despite no significant change in albuminuria or retinopathy status.

Keywords: Albuminuria; Diabetic nephropathy; GFR; Renal biopsy; Type 2 diabetes.