role of nitric oxide in type-1 diabetic nephropathy: relation to persistent microalbuminuria and glomerular hyperfiltration

ABSTRACT

Hyperglycemia has been causally linked to vascular and glomerular dysfunction by a variety of biochemical mechanisms, including a glucose-dependent abnormality in nitric oxide [NO] production and action. Nitric oxide is a candidate for mediating hyper filtration and the increased vascular permeability induced by diabetes. Serum nitric oxide concentrations were assessed in 30 children and young adolescent with type 1 diabetes, 15 with and 15 without microalbuminuria compared with a well-balanced group of healthy control subjects. In all subjects, glomerular filtration rate [GFR] was determined using Cockcroft formula. Our study showed that serum nitric oxide values were significantly higher in microalbuminuria diabetic patients than in the other 2 groups [group I versus group II; 46.7 + 7.9 versus. 32.2 +/- 6.1 [micro]mol/l, P < 0.05; while group I versus group III, 46.7 +/- 7.9 versus 25.4 +/- 4.2 [micro]mol/11 P < 0.02]. GFR was significantly and positively related to albumin excretion rate [AER] levels [r[2] = 0.75, P < 0.0001], whereas Serum nitric oxide was independently associated with both AER and GFR values [B = 2.086, P < 0.05, B = 1.273, P < 0.0085, respectively]. These findings suggest a strong link between circulating nitric oxide, glomerular hyper filtration, and microalbuminuria in type 1 diabetic patients with early nephropathy. Mean HbA[1c] serum concentration was significantly higher in microalbuminuric than in normoalbuminuric diabetic subjects [P < 0.05] and was independently associated with AER values, suggesting a role for chronic hyperglycemia in the genesis of diabetic nephropathy. HbA[1c] serum concentration was significantly and positively related to serum nitric oxide [r[2] = 0.45, P = 0.0063] and GFR values [r[2] = 0.57, P = 0.0011], suggesting that chronic hyperglycemia may act through a mechanism that involves increased nitric oxide generation and/or action