Improvement of renal function in type 2 diabetic nephropathy.
BACKGROUND
Therapeutic failure in preventing renal disease progression in type 2 diabetic nephropathy (DN) is due to a failure in the early detection of DN by microalbuminuria and the inappropriate correction of renal hemodynamic maladjustment secondary to glomerular endothelial dysfunction.


METHODS
Thirty patients associated with normoalbuminuric type 2 DN were subject to the following studies: tubular function by means of fractional excretion of magnesium (FE Mg), vascular function by means of determining the circulating endothelial cell, VEGF, VEGF/TGF B ratio, and intrarenal hemodynamic studies.


RESULTS
FE Mg, circulating endothelial cells, and TGF B were abnormally elevated, and VEGF/TGF B ratio was decreased in these normoalbuminuric patients. The intrarenal hemodynamic study revealed a hemodynamic maladjustment characterized by a preferential constriction at the efferent arteriole and a reduction in peritubular capillary flow. Following treatment with vasodilators, a decrease in efferent arteriolar resistance and increase in peritubular capillary flow as well as glomerular clearance were observed.


CONCLUSIONS
FE Mg appears to be a more sensitive marker than microalbuminuria for the early detection of DN. Increased endothelial cell injury is reflected by enhanced circulating endothelial cell loss in conjunction with the increased TGF B and the decreased ratio between VEGF and TGF B. This is further supported by the dysfunctioning glomerular endothelium, which is characterized by hemodynamic maladjustment and a reduction in the peritubular capillary flow. A correction of such hemodynamic maladjustment by multidrug vasodilators effectively improves renal perfusion and restores renal function in type 2 DN.
Futrakul
Narisa
N
Department of Physiology, King Chulalongkorn Memorial Hospital, Bangkok, Thailand. fmednft@med.chula.ac.th
Butthep
Punnee
P
Futrakul
Prasit
P
Sitprija
Visith
V
D000328:Adult; D001794:Blood Pressure / Q000502:physiology; D003404:Creatinine / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000097:blood / Q000503:physiopathology*; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007668:Kidney / Q000503:physiopathology*; D007677:Kidney Function Tests; D008875:Middle Aged; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*; D014665:Vasodilator Agents / Q000627:therapeutic use
D003404:Creatinine; D006442:Glycated Hemoglobin; D042461:Vascular Endothelial Growth Factor A; D014665:Vasodilator Agents