Early detection of endothelial injury and dysfunction in conjunction with correction of hemodynamic maladjustment can effectively restore renal function in type 2 diabetic nephropathy.

This paper was aimed to investigate (1) the early marker of endothelial injury in type 2 diabetes, (2) the intrarenal hemodynamics and renal function, and (3) the therapeutic strategy aiming to restore renal function. Fifty patients (35 normoalbuminuric and 15 albuminuric type 2 diabetes) were examined. Blood was collected for determination of circulating vascular endothelial cells (CEC) and the serum was prepared for determination of transforming growth factor beta (TGFbeta), ratio of CEC/TGFbeta, and soluble vascular cell adhesion molecule. Intrarenal hemodynamics and renal function were also assessed. The results showed that increased number of circulating EC, elevated TGFbeta and depleted ratio of CEC/TGFbeta were significantly observed. Intrarenal hemodynamic study revealed a hemodynamic maladjustment characterized by preferential constriction of the efferent arteriole, intraglomerular hypertension and reduction in peritubular capillary flow. It was concluded that early marker of endothelial injury is reflected by increasing number of CEC. Such markers correlate with the glomerular endothelial dysfunction associated with hemodynamic maladjustment. Early detection of endothelial injury and appropriate correction of hemodynamic maladjustment by multidrug vasodilators can effectively restore renal function in type 2 diabetic nephropathy.

Tubular dysfunction and hemodynamic alteration in normoalbuminuric type 2 diabetes.

Altered renal function has been encountered in normoalbuminuric patient with type 2 diabetes. A search for alternative index that is more sensitive than microalbuminuria for early detection of diabetic nephropathy has been performed. In the present paper, compartmental functions of nephron namely creatinine clearance (CCr) reflecting glomerular function, fractional excretion of magnesium (FE Mg) reflecting tubular function and intrarenal hemodynamics reflecting vascular function were assessed in 40 type 2 diabetic patients with normoalbuminuria and in 10 type 2 diabetic patients with albuminuria. In normoalbuminuric patients, glomerular function showed a low, normal or high CCr due to hyperfiltration. Tubular function revealed a significantly elevated FE Mg. Vascular function was altered with preferential constriction of the efferent arteriole, intraglomerular hypertension and profound reduction in peritubular capillary flow. A greater degree of functional defect was observed in albuminuric patients. Defective functions of the nephron implies that renal tissue injury has already been present in normoalbuminuric state. FE Mg appears to be a sensitive marker for early detection of diabetic nephropathy. Significant reduction in peritubular capillary flow correlates inversely with the altered FE Mg. Such correlation favors the chronic ischemic concept of tubulointerstitial injury and therefore supports the tubular functional defect observed in type 2 diabetes.

Altered renal function in normoalbuminuric type 2 diabetes.

Altered renal function namely enhanced FE Mg and impaired hemodynamics is observed in normoalbuminuric type 2 diabetes. Since FE Mg correlates directly with tubulointerstitial fibrosis, enhanced FE Mg reflects tubulointerstitial disease even in normoalbuminuric type 2 diabetes. This implies that microalbuminuria is not sensitive to early detect diabetic nephropathy.