AIM:To study intestinal permeability(IP) and its relationship to the disease activity in patients with inflammatory bowel diseases(IBD)-Crohn's disease(CD) and ulcerative colitis(UC).METHODS:Fifty-eight patients w...AIM:To study intestinal permeability(IP) and its relationship to the disease activity in patients with inflammatory bowel diseases(IBD)-Crohn's disease(CD) and ulcerative colitis(UC).METHODS:Fifty-eight patients with active IBD(32 with CD and 26 with UC) and 25 healthy controls consented to participate in the study.The clinical activity of CD was estimated using the Crohn's Disease Activity Index(CDAI),and the endoscopic activity of UC using the Mayo scoring system.IP was assessed by the rise in levels of iohexol,which was administered orally(25 mL,350 mg/mL) 2 h after breakfast.Three and six hours later serum(SIC mg/L) and urine(UIC g/mol) iohexol concentrations were determined by a validated HPLC-UV technique.RESULTS:In the CD group,SIC values at 3 h(2.95 ± 2.11 mg/L) and at 6 h after ingestion(2.63 ± 2.18 mg/L) were significantly higher compared to those of healthy subjects(1.25 ± 1.40 mg/L and 1.11 ± 1.10 mg/L,respectively,P < 0.05).UIC(g/mol) values were also higher in patients,but the differences were significant only for UIC at 6 h.Significant positive correlation(P < 0.05) was found between the CDAI and IP,assessed by SIC at 3 h(r = 0.60) and 6 h(r = 0.74) after the ingestion.In comparison to controls,SIC and UIC of UC patients were higher in the two studied periods,but the differences were significant at 6 h only.Significantly higher values of SIC(P < 0.05) were found in patients with severe endoscopic activity of UC compared to those of patients with mild and moderate activity(3.68 ± 3.18 vs 0.92 ± 0.69 mg/L).CONCLUSION:Serum levels of iohexol at 3 h and 6 h after its ingestion reflect increased IP,which is related to the disease activity in patients with IBD.展开更多
One of the most important tools used to evaluate kidney function in the context of chronic kidney disease or other renal function related pathologies is the exploration of glomerular filtration rate (GFR). Iohexol is ...One of the most important tools used to evaluate kidney function in the context of chronic kidney disease or other renal function related pathologies is the exploration of glomerular filtration rate (GFR). Iohexol is up to this moment a good candidate molecule for the GFR assessment since it exhibits minimum protein binding rates and minimum extra-renal clearance, being neither secreted nor reabsorbed at the tubular level. This study proposes and evaluates a new LC-MS/MS method for the iohexol determination from capillary blood, prelevated using volumetric absorbative microsampling (VAMS) systems. As an alternative to VAMS, a brand new HemaPEN■ device for micro-prelevation was also tested. A new high throughput sample preparation protocol adapted for iohexol quantification from whole blood VAMS samples was developed. The medium term stability study of iohexol in dried whole blood VAMS samples that was conducted showed a good stability of this molecule for up to 12 days. By collecting only 10 mL of blood, iohexol can be analyzed from dried whole blood VAMS samples for concentration ranges between 1 and 250 mg/mL. Due to the analyte stability in VAMS for up to 12 days, this approach might be successfully applied for GFR assessment for clinical cases allowing minimum invasiveness and even delayed analysis.展开更多
BACKGROUND Renal failure is an independent prognostic factor for survival in patients with cirrhosis.Equations to calculate serum creatinine significantly overestimate the glomerular filtration rate(GFR).Plasma cleara...BACKGROUND Renal failure is an independent prognostic factor for survival in patients with cirrhosis.Equations to calculate serum creatinine significantly overestimate the glomerular filtration rate(GFR).Plasma clearance of direct biomarkers has been used to improve the accuracy of evaluations of GFR in this population,but no study has simultaneously measured plasma and urinary clearance,which is the gold standard.AIM To study calculated plasma and urinary concentrations of iohexol,based on the kinetics of samples collected over 24 h from cirrhotic patients with three different grades of ascites.METHODS One dose of iohexol(5 mL)was injected intravenously and plasma concentrations were measured 11 times over 24 h in nine cirrhotic patients.The urinary concentration of iohexol was also measured,in urine collected at 4,8,12 and 24 h.RESULTS The plasma and urinary curves of iohexol were similar;however,incomplete urinary excretion was detected at 24 h.Within the estimated GFR limits of our population(>30 and<120 mL/min/1.73 m^(2)),the median measured GFR(m GFR)was 63.7 mL/min/1.73 m^(2)(range:41.3–111.3 mL/min/1.73 m^(2)),which was an accurate reflection of the actual GFR.Creatinine-based formulas for estimatingGFR showed significant bias and imprecision,while the Brochner–Mortensen(BM)equation accurately estimated the m GFR(r=0.93).CONCLUSION Plasma clearance of iohexol seems useful for determining GFR regardless of the ascites grade.We will secondly devise a pharmacokinetics model requiring fewer samples andvalidate the BM equation.展开更多
BACKGROUND Equations for estimation glomerular filtration rate(eGFR)have been associated with poor clinical performance and their clinical accuracy and reliability have been called into question.AIM To assess the long...BACKGROUND Equations for estimation glomerular filtration rate(eGFR)have been associated with poor clinical performance and their clinical accuracy and reliability have been called into question.AIM To assess the longitudinal changes in measured glomerular filtration rate(mGFR)in patients with autosomal dominant polycystic kidney disease(ADPKD).METHODS Analysis of an ambispective data base conducted on consecutive patients diagnosed with ADPKD.The mGFR was assessed by iohexol clearance;while eGFR was calculated by three different formulas:(1)The chronic kidney disease epidemiology collaboration(CKD-EPI);(2)Modification of diet in renal disease(MDRD);and(3)The 24-hour urine creatinine clearance(CrCl).The primary end-points were the mean change in mGFR between the baseline and final visit,as well as the comparison of the mean change in mGFR with the change estimated by the different formulas.RESULTS Thirty-seven patients were included in the study.As compared to baseline,month-6 mGFR was significantly decrease by-4.4 mL/minute±10.3 mL/minute(P=0.0132).However,the CKD-EPI,MDRD,and CrCl formulas underestimated this change by 48.3%,89.0%,and 45.8%respectively,though none of these differences reached statistical significance(P=0.3647;P=0.0505;and P=0.736,respectively).The discrepancies between measured and estimated glomerular filtration rate values,as evaluated by CKD-EPI(r=0.29,P=0.086);MDRD(r=0.19,P=0.272);and CrCl(r=0.09,P=0.683),were not correlated with baseline mGFR values.CONCLUSION This study indicated that eGFR inaccurately reflects the decline in mGFR and cannot reliably track changes over time.This poses significant challenges for clinical decision-making,particularly in treatment strategies.展开更多
文摘AIM:To study intestinal permeability(IP) and its relationship to the disease activity in patients with inflammatory bowel diseases(IBD)-Crohn's disease(CD) and ulcerative colitis(UC).METHODS:Fifty-eight patients with active IBD(32 with CD and 26 with UC) and 25 healthy controls consented to participate in the study.The clinical activity of CD was estimated using the Crohn's Disease Activity Index(CDAI),and the endoscopic activity of UC using the Mayo scoring system.IP was assessed by the rise in levels of iohexol,which was administered orally(25 mL,350 mg/mL) 2 h after breakfast.Three and six hours later serum(SIC mg/L) and urine(UIC g/mol) iohexol concentrations were determined by a validated HPLC-UV technique.RESULTS:In the CD group,SIC values at 3 h(2.95 ± 2.11 mg/L) and at 6 h after ingestion(2.63 ± 2.18 mg/L) were significantly higher compared to those of healthy subjects(1.25 ± 1.40 mg/L and 1.11 ± 1.10 mg/L,respectively,P < 0.05).UIC(g/mol) values were also higher in patients,but the differences were significant only for UIC at 6 h.Significant positive correlation(P < 0.05) was found between the CDAI and IP,assessed by SIC at 3 h(r = 0.60) and 6 h(r = 0.74) after the ingestion.In comparison to controls,SIC and UIC of UC patients were higher in the two studied periods,but the differences were significant at 6 h only.Significantly higher values of SIC(P < 0.05) were found in patients with severe endoscopic activity of UC compared to those of patients with mild and moderate activity(3.68 ± 3.18 vs 0.92 ± 0.69 mg/L).CONCLUSION:Serum levels of iohexol at 3 h and 6 h after its ingestion reflect increased IP,which is related to the disease activity in patients with IBD.
文摘One of the most important tools used to evaluate kidney function in the context of chronic kidney disease or other renal function related pathologies is the exploration of glomerular filtration rate (GFR). Iohexol is up to this moment a good candidate molecule for the GFR assessment since it exhibits minimum protein binding rates and minimum extra-renal clearance, being neither secreted nor reabsorbed at the tubular level. This study proposes and evaluates a new LC-MS/MS method for the iohexol determination from capillary blood, prelevated using volumetric absorbative microsampling (VAMS) systems. As an alternative to VAMS, a brand new HemaPEN■ device for micro-prelevation was also tested. A new high throughput sample preparation protocol adapted for iohexol quantification from whole blood VAMS samples was developed. The medium term stability study of iohexol in dried whole blood VAMS samples that was conducted showed a good stability of this molecule for up to 12 days. By collecting only 10 mL of blood, iohexol can be analyzed from dried whole blood VAMS samples for concentration ranges between 1 and 250 mg/mL. Due to the analyte stability in VAMS for up to 12 days, this approach might be successfully applied for GFR assessment for clinical cases allowing minimum invasiveness and even delayed analysis.
文摘BACKGROUND Renal failure is an independent prognostic factor for survival in patients with cirrhosis.Equations to calculate serum creatinine significantly overestimate the glomerular filtration rate(GFR).Plasma clearance of direct biomarkers has been used to improve the accuracy of evaluations of GFR in this population,but no study has simultaneously measured plasma and urinary clearance,which is the gold standard.AIM To study calculated plasma and urinary concentrations of iohexol,based on the kinetics of samples collected over 24 h from cirrhotic patients with three different grades of ascites.METHODS One dose of iohexol(5 mL)was injected intravenously and plasma concentrations were measured 11 times over 24 h in nine cirrhotic patients.The urinary concentration of iohexol was also measured,in urine collected at 4,8,12 and 24 h.RESULTS The plasma and urinary curves of iohexol were similar;however,incomplete urinary excretion was detected at 24 h.Within the estimated GFR limits of our population(>30 and<120 mL/min/1.73 m^(2)),the median measured GFR(m GFR)was 63.7 mL/min/1.73 m^(2)(range:41.3–111.3 mL/min/1.73 m^(2)),which was an accurate reflection of the actual GFR.Creatinine-based formulas for estimatingGFR showed significant bias and imprecision,while the Brochner–Mortensen(BM)equation accurately estimated the m GFR(r=0.93).CONCLUSION Plasma clearance of iohexol seems useful for determining GFR regardless of the ascites grade.We will secondly devise a pharmacokinetics model requiring fewer samples andvalidate the BM equation.
文摘BACKGROUND Equations for estimation glomerular filtration rate(eGFR)have been associated with poor clinical performance and their clinical accuracy and reliability have been called into question.AIM To assess the longitudinal changes in measured glomerular filtration rate(mGFR)in patients with autosomal dominant polycystic kidney disease(ADPKD).METHODS Analysis of an ambispective data base conducted on consecutive patients diagnosed with ADPKD.The mGFR was assessed by iohexol clearance;while eGFR was calculated by three different formulas:(1)The chronic kidney disease epidemiology collaboration(CKD-EPI);(2)Modification of diet in renal disease(MDRD);and(3)The 24-hour urine creatinine clearance(CrCl).The primary end-points were the mean change in mGFR between the baseline and final visit,as well as the comparison of the mean change in mGFR with the change estimated by the different formulas.RESULTS Thirty-seven patients were included in the study.As compared to baseline,month-6 mGFR was significantly decrease by-4.4 mL/minute±10.3 mL/minute(P=0.0132).However,the CKD-EPI,MDRD,and CrCl formulas underestimated this change by 48.3%,89.0%,and 45.8%respectively,though none of these differences reached statistical significance(P=0.3647;P=0.0505;and P=0.736,respectively).The discrepancies between measured and estimated glomerular filtration rate values,as evaluated by CKD-EPI(r=0.29,P=0.086);MDRD(r=0.19,P=0.272);and CrCl(r=0.09,P=0.683),were not correlated with baseline mGFR values.CONCLUSION This study indicated that eGFR inaccurately reflects the decline in mGFR and cannot reliably track changes over time.This poses significant challenges for clinical decision-making,particularly in treatment strategies.
