Improved vascular repair is relevant to enhanced renal function with vasodilators in early stage of chronic kidney disease

Background: Treatment with vasodilators can improve renal function in early stage of chronic kidney disease (CKD) patients. Objective: Study the mechanism of vascular repair in 20 CKD patients associated with actual creatinine clearance greater than 60 mL/min/1.73m2 (mean 84+24 mL/min/1.73m2) who had been under treatment with vasodilators. Results: Initial study on angiogenic factors revealed a low value of VEGF, no significant change in VEGF-R1, whereas antiangiogenic factors showed elevated angiopoietin-2 and no significant change in VEGF-R2. Initial actual creatinine clearance was significantly depleted and fractional excretion of magnesium (FE Mg) was elevated significantly. Follow-up study showed improved VEGF and a significant decline in angiopoietin-2. Such improved vascular repair coincided with enhanced creatinine clearance. Conclusion: Improved renal function can be achieved by vasodilators under environment favourable for adequate vascular repair.

Renal perfusion and disease progression.

The pathogenetic concept of renal hyperperfusion and hyperfiltration in inducing glomerular pathology and disease progression documented in the renal ablation model in experimental animals to mimic renal disease with reduced nephron mass has recently been challenged. In contrast to the above, the intrarenal hemodynamic study in a variety of chronic glomerulonephropathies reveals a unique characteristic of renal hypoperfusion rather than hyperperfusion. This is associated with an elevated renal arteriolar resistance and reductions in renal plasma flow and peritubular capillary blood flow. The magnitude of reduction in peritubular capillary blood flow is inversely proportional to the degree of tubulointerstitial disease and tubular dysfunction. A progressive reduction in the vascular space due to nonvascular expansion with disease progression supports the concept of hypoperfusion of a whole kidney as well as a single nephron. In accordance with the renal ablation model and early diabetes mellitus, a similar hypoperfusion pattern is also subsequently observed in the chronic stage of renal ablation model in animals and late diabetic nephropathy. The disparity between the hyperperfusion and hypoperfusion in inducing renal disease progression can be enlightened by the Noble Truth of Lord Buddha stating "The Middle Tract is The Balance of Nature". Further support of this conceptual view of renal hypoperfusion as a determinant of tubulointerstitial disease and disease progression is in accordance with the therapeutic benefit with an enhanced-renal-perfusion formula per se in a variety of chronic glomerulonephropathies.

Intrarenal hemodynamic abnormality in severe form of glomerulonephritis: therapeutic benefit with vasodilators.

Intrarenal hemodynamic and tubular function has been assessed in 16 patients who presented clinically with hypertension, hematuria and severe renal functional impairment. Twelve of these 16 patients had histopathologic classification as DPGN (3 cases), MPGN (3 cases) and FSGS (6 cases). The initial assessment of intrarenal hemodynamics in 11 patients revealed strikingly increased afferent (RA) and efferent arterioles (RE), filtration fraction (FF), intraglomerular capillary hydrostatic pressure (PG), whereas, there was marked reduction in renal plasma flow (RPF), in ultrafiltration coefficient (KFG) and in glomerular filtration rate (GFR). Tubular transporting defect as being reflected by enhanced fractional excretions of solutes was also observed. Both enhanced TXB2 production and diminished PGI2 may be in part responsible for the marked reduction of RPF and elevated intrarenal resistance. In light of the preceding intrarenal hemodynamics alteration, therapeutic intervention with vasodilators consisting of dipyridamole, calcium channel blocker and angiotensin convertase inhibitor has been accomplished with clinical improvement in glomerular and tubular functions following the improvement in intrarenal hemodynamics. Thus, this abnormal intrarenal hemodynamics renders a supportive view of the hemodynamically mediated glomerulo-tubulo-interstitial injury to be central to the pathogenetic mechanism.

Hemodynamic response to high-dose methyl prednisolone and mannitol in severe dengue-shock patients unresponsive to fluid replacement.

Nine children; 4 males and 5 females, aged ranging from 2 1/2 to 13 years presented with signs and symptoms of poor tissue perfusion associated with dengue shock syndrome. All these 9 patients were subjected to the therapeutic trial of high dose methyl prednisolone (MP; 9/9) and mannitol (M; 6/9) after their failure to the saline and plasma replacement. Following the high dose MP and M, a significant increment in the effective circulatory blood volume as reflected by the sustained increment in CVP, widening of PP and declining in PR as well as improvement in clinical tissue perfusion were established in 7 of these nine patients so treated.

Precipitating antibodies to non-treated dengue type 2 viral antigens in sera of Thai hemorrhagic fever patients by crossed immunoelectrophoresis.

Crossed immunoelectrophoresis of dengue type 2 virus revealed at least two precipitating antigens which shared some antigenic determinants. Glycoprotein components of both antigens were detected by binding to concanavalin A. Sera from dengue hemorrhagic fever patients showed precipitating antibodies to both antigens which could be quantitated according to the precipitate patterns formed in the intermediate gel of crossed immunoelectrophoresis. All secondary dengue hemorrhagic fever patients demonstrated an increase in precipitin titers in convalescence sera. Most patients with mild illness contained precipitating antibodies in acute phase sera whereas severe cases did not. Convalescent sera from severe cases showed only low titers. These precipitating antibodies may be associated with protection since they were produced early only in those with mild form of illness.