Uric acid is the end product of purine catabolism and its plasma levels are maintained below its maximum solubility in water(6–7 mg/dl).The plasma levels are tightly regulated as the balance between the rate of produ...Uric acid is the end product of purine catabolism and its plasma levels are maintained below its maximum solubility in water(6–7 mg/dl).The plasma levels are tightly regulated as the balance between the rate of production and the rate of excretion,the latter occurring in urine(kidney),bile(liver)and feces(intestinal tract).Reabsorption in kidney is also an important component of this process.Both excretion and reabsorption are mediated by specific transporters.Disruption of the balance between production and excretion leads to hyperuricemia,which increases the risk of uric acid crystallization as monosodium urate with subsequent deposition of the crystals in joints causing gouty arthritis.Loss-of-function mutations in the transporters that mediate uric acid excretion are associated with gout.The ATP-Binding Cassette exporter ABCG2 is important in uric acid excretion at all three sites:kidney(urine),liver(bile),and intestine(feces).Mutations in this transporter cause gout and these mutations occur at significant prevalence in general population.However,mutations that are most prevalent result only in partial loss of transport function.Therefore,if the expression of these partially defective transporters could be induced,the increased number of the transporter molecules would compensate for the mutation-associated decrease in transport function and hence increase uric acid excretion.As such,pharmacologic agents with ability to induce the expression of ABCG2 represent potentially a novel class of drugs for treatment of gouty arthritis.展开更多
Objective:To study the correlation of urinary albumin excretion rate with renal function, inflammatory response and oxidative stress response in patients with diabetic nephropathy (DN).Methods: A total of 78 patients ...Objective:To study the correlation of urinary albumin excretion rate with renal function, inflammatory response and oxidative stress response in patients with diabetic nephropathy (DN).Methods: A total of 78 patients with DN treated in our hospital December 2012 and March 2016 were collected and divided into early diabetic nephropathy group (n=51) and middle-advanced diabetic nephropathy group (n=27) according to the DN grading standard;60 subjects with normal renal function who receiving physical examination in our hospital during the same period were selected as normal control group. Immediately after admission, the urinary albumin excretion rate (UAER) of all groups were determined;automatic biochemical analyzer was used to determine renal function index levels, ELISA method was used to determine inflammatory factor levels, and RIA method was used to determine the oxidative stress index levels;Pearson test was used to analyze the correlation of UAER value with renal function, inflammatory response and oxidative stress response in patients with DN.Results:Differences in UAER value as well as renal function index, inflammatory response index and oxidative stress index levels were statistically significant among three groups of subjects. UAER value as well as BUN, Scr, CysC,β2-MG, IL-6, hs-CRP, TNF- , MDA and AOPP levels of early DN group and middle-advanced DN group were higher than those of normal control group while T-AOC and SOD levels were lower than those of normal control group;UAER value as well as BUN, Scr, CysC,β2-MG, IL-6, hs-CRP, TNF- , MDA and AOPP levels of middle-advanced DN group was higher than those of early DN group while T-AOC and SOD levels were lower than those of early DN group;UAER value in patients with DN was correlated with renal function, inflammatory response and oxidative stress.Conclusion:UAER value can directly reflect the renal injury, inflammation and oxidative stress in patients with DN, and be the reliable means for early disease diagnosis and treatment guidance.展开更多
Under common practice, the conventional diagnostic marker such as microalbuminuria determination does not recognized early stage of diabetic kidney disease （normoalbuminuria, chronic kidney disease stage 1, 2）; due ...Under common practice, the conventional diagnostic marker such as microalbuminuria determination does not recognized early stage of diabetic kidney disease （normoalbuminuria, chronic kidney disease stage 1, 2）; due to the insensitiveness of the available marker. Treat-ment at later stage （microalbuminuria） simply slows the renal disease progression, but is rather diffcult to restore the renal perfusion. Intrarenal hemodynamic study in these patients revealed an impaired renal per-fusion and abnormally elevated renal arteriolar resis-tances. Treatment with vasodilators such as angiotensin converting enzyme inhibitor and angiotensin receptor blocker fails to correct the renal ischemia. Recent study on vascular homeostasis revealed a defective mecha-nism associated with an impaired nitric oxide production which would explain the therapeutic resistance to va-sodilator treatment in microalbuminuric diabetic kidney disease. This study implies that the appropriate thera-peutic strategy should be implemented at earlier stage before the appearance of microalbuminuria.展开更多
基金This work was supported by the National Institutes of Health grant R41 AR074854the Welch Endowed Chair in Biochemistry,Grant No.BI-0028,at Texas Tech University Health Sciences Center.
文摘Uric acid is the end product of purine catabolism and its plasma levels are maintained below its maximum solubility in water(6–7 mg/dl).The plasma levels are tightly regulated as the balance between the rate of production and the rate of excretion,the latter occurring in urine(kidney),bile(liver)and feces(intestinal tract).Reabsorption in kidney is also an important component of this process.Both excretion and reabsorption are mediated by specific transporters.Disruption of the balance between production and excretion leads to hyperuricemia,which increases the risk of uric acid crystallization as monosodium urate with subsequent deposition of the crystals in joints causing gouty arthritis.Loss-of-function mutations in the transporters that mediate uric acid excretion are associated with gout.The ATP-Binding Cassette exporter ABCG2 is important in uric acid excretion at all three sites:kidney(urine),liver(bile),and intestine(feces).Mutations in this transporter cause gout and these mutations occur at significant prevalence in general population.However,mutations that are most prevalent result only in partial loss of transport function.Therefore,if the expression of these partially defective transporters could be induced,the increased number of the transporter molecules would compensate for the mutation-associated decrease in transport function and hence increase uric acid excretion.As such,pharmacologic agents with ability to induce the expression of ABCG2 represent potentially a novel class of drugs for treatment of gouty arthritis.
文摘Objective:To study the correlation of urinary albumin excretion rate with renal function, inflammatory response and oxidative stress response in patients with diabetic nephropathy (DN).Methods: A total of 78 patients with DN treated in our hospital December 2012 and March 2016 were collected and divided into early diabetic nephropathy group (n=51) and middle-advanced diabetic nephropathy group (n=27) according to the DN grading standard;60 subjects with normal renal function who receiving physical examination in our hospital during the same period were selected as normal control group. Immediately after admission, the urinary albumin excretion rate (UAER) of all groups were determined;automatic biochemical analyzer was used to determine renal function index levels, ELISA method was used to determine inflammatory factor levels, and RIA method was used to determine the oxidative stress index levels;Pearson test was used to analyze the correlation of UAER value with renal function, inflammatory response and oxidative stress response in patients with DN.Results:Differences in UAER value as well as renal function index, inflammatory response index and oxidative stress index levels were statistically significant among three groups of subjects. UAER value as well as BUN, Scr, CysC,β2-MG, IL-6, hs-CRP, TNF- , MDA and AOPP levels of early DN group and middle-advanced DN group were higher than those of normal control group while T-AOC and SOD levels were lower than those of normal control group;UAER value as well as BUN, Scr, CysC,β2-MG, IL-6, hs-CRP, TNF- , MDA and AOPP levels of middle-advanced DN group was higher than those of early DN group while T-AOC and SOD levels were lower than those of early DN group;UAER value in patients with DN was correlated with renal function, inflammatory response and oxidative stress.Conclusion:UAER value can directly reflect the renal injury, inflammation and oxidative stress in patients with DN, and be the reliable means for early disease diagnosis and treatment guidance.
基金Supported by Thailand Research-Fund,Bhumirajanagarindra Kidney Institute and National Research Council Fund of Thailand
文摘Under common practice, the conventional diagnostic marker such as microalbuminuria determination does not recognized early stage of diabetic kidney disease （normoalbuminuria, chronic kidney disease stage 1, 2）; due to the insensitiveness of the available marker. Treat-ment at later stage （microalbuminuria） simply slows the renal disease progression, but is rather diffcult to restore the renal perfusion. Intrarenal hemodynamic study in these patients revealed an impaired renal per-fusion and abnormally elevated renal arteriolar resis-tances. Treatment with vasodilators such as angiotensin converting enzyme inhibitor and angiotensin receptor blocker fails to correct the renal ischemia. Recent study on vascular homeostasis revealed a defective mecha-nism associated with an impaired nitric oxide production which would explain the therapeutic resistance to va-sodilator treatment in microalbuminuric diabetic kidney disease. This study implies that the appropriate thera-peutic strategy should be implemented at earlier stage before the appearance of microalbuminuria.
