PubMed Health⌕ Search

Biomedical subjects

Prasit Futrakul

Publications and source records attributed to Prasit Futrakul.

At least 19 recordsLinked to original sources
PubMed2006

Microvascular disease and endothelial dysfunction in chronic kidney diseases: therapeutic implication.

This paper was aimed to study biomarkers of endothelial injury in chronic kidney diseases. Fifty chronic kidney disease patients were subject to the following determinations: (i) circulating endothelial cells, (ii) soluble VCAM-1, (iii) transforming growth factor beta (TGFB), and (iv) intrarenal hemodynamics. Increased number of circulating endothelial cells was significantly observed. A significant depletion of vascular endothelial growth factor (VEGF) or a depleted VEGF/TGFB ratio was also documented. Results showed that sVCAM was not significantly different from normal control. Intrarenal hemodynamic alteration demonstrated a characteristic of hemodynamic maladjustment. Since increased number of circulating endothelial cells is a sensitive biomarker for endothelial cell injury in chronic kidney diseases, such injury is supported by the depletion of VEGF. The endothelial cell loss correlates with the glomerular endothelial dysfunction characterized by hemodynamic maladjustment at the efferent arteriole and reduction in peritubular capillary flow. In conclusion, correction of such hemodynamic maladjustment with multidrug vasodilators can effectively restore renal function in chronic kidney diseases.

Biomarkers↗
PubMed2006

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.

Adult↗
PubMed2005

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.

Adult↗
PubMed2005

Biomarkers of endothelial injury in focal segmental glomerulosclerotic nephrosis.

Enhanced circulating endothelial cells, elevated transforming growth factor beta, and depleted vascular endothelial growth factor were observed in nephrosis associated with focal segmental glomerulosclerosis (FSGS). Increased endothelial cell loss may be due to the elevated transforming growth factor beta, which can induce apoptosis of podocyte as well as tubular epithelium. Such injury may explain the depletion of vascular endothelial growth factor and increased endothelial cell loss in these patients. There biomarkers may have relevance to the altered intrarenal hemodynamics commonly observed in FSGS nephrosis.

Biomarkers↗
PubMed2004

Renal tubular cell damage and oxidative stress in renal stone patients and the effect of potassium citrate treatment.

Our objective was to evaluate the oxidative stress and renal tubular cell damage in patients who have renal stones compared to normal subjects. The patients were re-evaluated after 1-months supplementation with potassium citrate. We recruited 30 patients (11 males and 19 females) diagnosed with kidney stones and scheduled for surgical stone removal the following month, and 30 healthy non-stone formers (14 males and 16 females). Two 24-h urine samples and one heparinized blood sample were collected from each subject. Plasma was separated from the erythrocytes and assayed for creatinine, potassium, sodium, calcium, magnesium, phosphate, malondialdehyde (MDA, a lipid peroxidation product) (P-MDA), protein thiol as an indicator of protein oxidation, and vitamin E. Erythrocytes were analysed for MDA (E-MDA), reduced glutathione (GSH) and cellular glutathione peroxidase (cGPx) activity. The urine was analyzed for pH, creatinine, potassium, sodium, calcium, magnesium, phosphate, oxalate, citrate, MDA (U-MDA), total protein (U-protein) and N-acetyl-beta-glucosaminidase (NAG) activity. For the stone patients, urine and blood samples were re-evaluated after supplementation with potassium citrate (60 mEq/day) for 1 month. Renal stone patients had higher plasma creatinine and lower plasma potassium, urinary pH, potassium, magnesium, phosphate and citrate than the controls. The patients had higher P-MDA, E-MDA, U-MDA, U-protein and NAG activity, but lower GSH, cGPx activity, protein thiol and vitamin E, when compared with controls. After potassium citrate supplementation, P-MDA and E-MDA decreased while plasma vitamin E, urinary NAG activity and citrate increased. Renal stone disease is associated with high oxidative stress and damage to renal tubular cells. These abnormalities are coincident with an increase in blood lipid peroxidation products and a decrease in antioxidant status. Although supplementation with potassium citrate improved urinary citrate levels and oxidative stress, it neither reduced urinary lipid peroxidation products nor remedied the damage to renal tubular cells, probably due to the existence of kidney stones.

Adult↗
PubMed2004

Hemodynamic maladjustment and disease progression in nephrosis with FSGS.

Idiopathic nephrotic syndrome (NS) associated with focal segmental glomerulosclerosis (FSGS) and severe renal function impairment is usually refractory to the conventional treatment and progresses to end-stage renal disease. Herein, we reported 10 patients with NS-FSGS who had initially had CCr 34 +/- 12 mL/min/1.73 m2 (normal 120 mL/min/1.73 m2), FE Mg 7.8 +/- 2.6% (normal 2.2%), 24-h urinary protein 3.1 g (normal <200 mg) and been followed up for over 10 years. The initial intrarenal hemodynamic study revealed a marked elevation of efferent arteriolar resistance (RE 17289 +/- 8636 dyne x s x cm(-5); normal 3000 dyne x s x cm(-5)), intraglomerular hypertension (PG 57 +/- 1 mm Hg; normal 52 mm Hg), hyperfiltration (FF 0.24; normal 0.2), marked reductions in GFR 35 +/- 17 mL/min/1.73 m2, renal plasma flow (RPF 159 +/- 61 mL/min/1.73 m2; normal 600 mL/min/1.73 m2) and peritubular capillary flow (PTCF 123 +/- 57 mL/min/1.73 m2; normal 480 mL/min/1.73 m2). Such a hemodynamic alteration indicated a hemodynamic maladjustment with a preferential constriction at RE. Treatment consists of multidrugs, namely angiotensin converting enzyme inhibitor, calcium channel blocker, antiplatelet and anticoagulant, with or without angiotensin II receptor antagonist. Following the treatment, correction of hemodynamic maladjustment has been achieved which is characterized by reductions in RE 6046 +/- 2191 dyne x s x cm(-5), PG 52 +/- mm Hg, FF 0.19 +/- 0.1 and increments in RPF 341 +/- 118 mL/min/1.73 m2, PTCF 280 +/- 106 mL/min/1.73 m2 and GFR 64 +/- 17 mL/min/1.73 m2. Coinciding with hemodynamic improvement, there has been a steadily increased creatinine clearance and improvement in FE Mg 4.3 +/- 2.6% and suppression of proteinuria 0.29 +/- 0.4 g/24 h after the period of follow-up of greater than 10 years.

Disease Progression↗
PubMed2004

Glomerular endothelial dysfunction in chronic kidney disease.

A dysfunctioning glomerular endothelium was demonstrated in chronic kidney disease (CKD) patients by means of in vitro endothelial cell cytotoxicity test and of in vivo intrarenal hemodynamic study. An enhanced endothelial cell cytotoxicity in CKD patients was 26.5 +/- 12% as compared to 0.4 +/- 1% of control. An altered intrarenal hemodynamics revealed 1) a reduction in renal plasma flow, 190 +/- 67 mL/min/1.73 m2 versus control 595 +/- 45 mL/min/1.73 m2, and in peritubular capillary flow, 149 +/- 55 mL/min/1.73 m2 versus control 479 +/- 46 mL/min/1.73 m2, 2) an elevated intraglomerular hydrostatic pressure, 55 +/- 2 mmHg versus control 51 mmHg, elevated afferent arteriolar resistance, 13184 dyne x s x cm(-5) versus control 2443 +/- 154 dyne x s x cm(5), and elevated efferent arteriolar resistance, 13591 +/- 7591 dyne x s x cm(-5) versus control 3062 +/- 177 dyne x s x cm(-5). Both enhanced endothelial cell cytotoxicity and altered intrarenal hemodynamics reflect glomerular endothelial dysfunction which is likely responsible for the renal disease progression in CKD.

Case-Control Studies↗
PubMed2004

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.

Albuminuria↗
PubMed2004

Correction of peritubular capillary flow reduction with vasodilators restores function in focal segmental glomerulosclerotic nephrosis.

Due to the previously therapeutic failure in treating eleven focal segmental glomerulosis (FSGS) nephrotic patients (group I) with prednisolone, cyclophosphamide and antihypertensive agents (reserpine, hydralazine or prazosin) who all entered end-stage renal disease, we prospectively evaluate 18 FSGS nephrotic patients who have been treated with combined formula consisting of ACEI, AIIRA, CCB, antiplatelet+/-heparin; group II. All the patients were subject to renal function studies namely creatinine clearance, fractional excretion of magnesium (FE Mg) and intrarenal hemodynamics. Treatment outcome of patients in group II was comparatively assessed before and after therapy. Clinical profiles were comparatively matched between groups I and II. The intrarenal hemodynamic study in all nephrotic patients revealed hemodynamic maladjustment characterized by preferential constriction at the efferent arteriole. Such constriction induced intraglomerular hypertension and exaggeratedly reduced peritubular capillary flow (PTCF). Following treatment with combined formula (group II), reductions in efferent arteriolar resistance and intraglomerular hydrostatic pressure were observed in conjunction with the increases in PTCF and glomerular filtration rate in all 18 patients. Correction of hemodynamic maladjustment with combined formula effectively restores renal function and thereby prevents the renal disease progression in FSGS nephrosis.

Adolescent↗
PubMed2004

Ganoderma lucidum suppresses endothelial cell cytotoxicity and proteinuria in persistent proteinuric focal segmental glomerulosclerosis (FSGS) nephrosis.

A persistent proteinuria is commonly observed in nephrotic patient with focal segmental glomerulosclerosis (FSGS) under treatment with prednisolone+/-cyclophosphamide or with vasodilators (ACEI+AII receptor antagonist, calcium channel blocker and antiplatelet agent). Fourteen such patients with persistent proteinuria were subject to be treated with Ganoderma lucidum. Initial study revealed an enhanced endothelial cell cytotoxicity induced by patient's serum, and an altered immunocirculatory balance with predominant proinflammatory cytokine TNF alpha activity in the presence of defective anti-inflammatory cytokine interleukin-10. Treatment with Ganoderma lucidum suppressed endothelial cell cytotoxicity, restored immunocirculatory balance and successfully suppressed proteinuria in all of these 14 patients.

Anti-Inflammatory Agents↗
PubMed2003

Glomerular endothelial dysfunction and hemodynamic maladjustment in vesicoureteric reflux.

A structural defect of the non-vascular component of a nephron namely vesicoureteric reflex (VUR) can induce injury to the vascular component, which is reflected by the alteration in intrarenal hemodynamics. A mild alteration in intrarenal hemodynamics was observed in grades I-II VUR which revealed (a) mild reductions in renal plasma flow (RPF) 543 +/- 104 mL/min/1.73 m2; in peritubular capillary flow (PTCF) 438 +/- 103mL/min/1.73 m2; in glomerular filtration rate (GFR) 105 +/- 19 mL/min/1.73 m2 and in ultrafiltration coefficient (KFG) 0.04 +/- 0.01 mL/s/mmHg; (b) normal values of filtration fraction (FF) 0.2 +/- 0.04, of intraglomerular hydrostatic pressure (PG) 50 +/- 0.3 mmHg, and of afferent arteriolar resistance (RA) 2261 +/- 718 dyne s cm(-5); and (c) a slight elevation of efferent arteriolar resistance (RE) 3914 +/- 962 dyne s cm(-5). In contrast, a moderately severe alteration in intrarenal hemodynamics was observed in severe VUR (grades III up) which revealed greater reductions in RPF 267 +/- 114 mL/min/1.73 m2, in PTCF 195 +/- 90 mL/min/1.73 m2, in GFR 72 +/- 34 mL/min/1.73 m2 and in KFG 0.03 +/- 0.01 mL/s/mmHg; and elevation of PG 53 +/- 2 mmHg, of filtration fraction 0.27 +/- 0.07, of RA 4557 +/- 2340 dyne s cm(-5) and of RE 9417 +/- 4163 dyne s cm(-5). Such an alteration in intrarenal hemodynamics observed in severe VUR induces both intraglomerular hypertension (elevated PG) and an exaggeratedly reduced PTCF. This intrarenal hemodynamic defect is due to the glomerular endothelial dysfunction and its hemodynamic maladjustment. In accordance with the preceding information, treatment to correct the hemodynamic maladjustment is likely to improve renal function and prevent renal disease progression.

Capillaries↗
PubMed2003

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 m2), 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 m2), PTCF (pre R(x) 161 +/- 57 vs. post R(x) 242 +/- 90 mL/ min/1.73 m2), 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)).

Adult↗
PubMed2003

A hemodynamically mediated mechanism of renal disease progression in severe glomerulonephritides or nephrosis.

Glomerular endothelial cell (GEC) dysfunction due to oxidative stress and enhanced proinflammatory cytokines plays an important role in inducing proteinuria and procoagulant activity, namely blood hypercoagulability, hyperviscosity and local intravascular coagulation and altered hemorheology in NS. A dysfunctioning GEC releases fewer endothelium-dependent vasodilators but produces more vasoconstrictors. Severe intrarenal hemodynamic alteration associated with hemodynamic maladjustment with preferential constriction at the efferent arteriole has been uniquely implicated in severe GN and NS-FSGS. Such a constriction exerts three significant hemodynamic impacts. Proximal to the efferent arteriolar constriction, it induces (i) an overestimated GFR due to hyperfiltration and (ii) an elevated intraglomerular hydrostatic pressure. Distal to the efferent arteriolar constriction, it (iii) exaggeratedly reduces PTCF which correlates with the TIF.

Disease Progression↗