Treatments of hemodynamic maladjustment and oxidative stress prevent renal disease progression in chronically severe glomerulonephritides

Hemodynamic maladjustment is a unique observation in chronically severe glomerulonephritides. It is characterized by a markedly elevated efferent arteriolar resistance (RE), an elevated intraglomerular hydrostatic pressure (PG) and a markedly decreased renal plasma flow (RPF), and peritubular capillary flow (PTCF). A correction of such hemodynamic maladjustment can be accomplished by administering a combination of vasodilators (angiotensin receptor antagonist, angiotensin converting enzyme inhibitor, and calcium channel blocker) in 14 chronic glomerulonephritides with severe renal function impairment (mean serum creatinine 3.6 + 1.3 mg/dL). Doses titration aim for maximal renal perfusion effect (increased RPF, PTCF) or maximal renal function improvement (increased CCr, reduced FE Mg) usually higher than needed for maximal blood pressure reduction. Evidence of oxidative stress is also corrected with high doses of vitamins C and E. After a mean period of treatment for 13.5 months, improvements in CCr (pre R-x 22 +/- 10 vs. post R-x 32 +/- 13 mL/min/1.73 m(2)), and FE Mg (pre R-x 11.9 +/- 4% vs. post R-x 10 +/- 3%) were observed in conjunction with the improvement in intrarenal hemodynamics namely RPF (pre R-x 201 +/- 71 vs. post R-x 288 +/- 99 mL/min/1.73 m(2)), PTCF (pre R-x 161 +/- 57 vs. post R-x 242 +/- 90 mL/min/1.73 m(2)), PG (pre R-x 56.7 +/- 0.5 vs. post R-x 51 +/- 0.1 mm Hg), and RE (pre R-x 12085 +/- 6503 vs. post R-x 6550 +/- 1872 dyne.s.cm(-5)).