Renal hypertrophy is the primary dysfunction that leads to diabetic nephropathy, findings suggest
Gianpaolo Zerbini, MD, of the Istituto Scientifico San Raffaele in Milan, and his colleagues studied 146 patients with type 1 diabetes and normal renal function. They determined baseline kidney volume and glomerular filtration rate (GFR). These patients were compared with a control group of 30 nondiabetics.
After a mean follow-up of 8.1 years, microalbuminuria developed in 27 patients (18.5%), the investigators reported in Diabetes (2006;55:2620-2625). The mean albumin excretion rate rose from 7.9 to 110.4 µg/min. In the other 119 patients, the mean albumin excretion rate remained with-in the normal range (from 6.3 to 7.4 µg/min) after a mean follow-up of 9.8 years (normoalbuminuria group).
At baseline, kidney volume was higher in the diabetics than the controls (287.2 vs. 236.8 mL/1.73 m2). The microalbuminuria group had significantly higher kidney volumes than the normoalbuminuria group and controls (312.8 vs. 281.4 vs. 236.8 mL/1.73 m2, respectively). In the diabetes patients, microalbuminuria developed in 15 of 110 patients (13.6%) with normal kidney volume and 12 of 36 patients (33.3%) with type 1 diabetes and increased kidney volume.
Baseline GFR in the microalbuminuria group was similar to that of the normoalbuminuria group (121.7 and 117.6 mL/min per 1.73 m2, respectively), but higher than the GFR in the controls (110.7 mL/min per 1.73 m2), the study found.
The researchers also examined a subset of 68 patients who underwent a second evaluation of kidney volume and GFR four years after the baseline evaluation. This analysis also showed that the risk of progression to microalbuminuria was significantly higher in patients with a greater increase in kidney volume. During the four years, kidney volume increased to a greater extent in the microalbuminuria group (from 311.0 to 328.2 mL/1.73 m2) than in the normoalbuminuria group (279.7 to 283.0 mL/1.73 m2). GFR decreased significantly in both groups, but the decline was greater in the microalbuminuria group (from 126.1 to 102.9 mL/min per 1.73 m2 vs. a decline from 124.4 to 115.3 mL/min per 1.73 m2 in the normoalbuminuria subjects).
The investigators concluded that their findings “support the hypothesis that renal hypertrophy is the primary dysfunction in the development of diabetic nephropathy.