Area under the curve of methotrexate and creatinine clearance are outcome - determining factors in primary CNS lymphomas

Although high-dose methotrexate(HD-MTX)is the most effective drug against primary CNS lymphomas(PCNSL),outcome-de-termining variables related to its administration schedule have not been defined.The impact on toxicity and outcome of the area under thecurve(AUC(MTX)),dose intensity(DI(MTX))and infusion rate(IR(MTX))of MTX and plsamatic creatinine clearance(CL(crea))was investigated in a retrospective series of 45 PCNSL patients treated with three different HD-MTX-basedcombinations.Anticon-vulsants were administered in 31 pts(69%).Age>60 years,anticonvulsant therapy,slow IR(MTX)(

Potential effect of Silybum marianum L. and Cistus ladaniferus L.extracts on urine volume, creatinine clearance and renal function

Objective:To investigate the diuretic and renal effects of Silybum marianum L.and Cistus ladaniferus L.in normal rats.Methods:Four groups of rats were used in each experiment.The first group received water,the second group received Cistus ladaniferus L.extract(100 mg/kg b.wt),the third group received Silybum marianum L.extract(100 mg/kg b.wt),and the fourth group received furosemide(10 mg/kg b.wt).Variables including urine volume,plasma and urine sodium,potassium and creatinine,and creatinine clearance were measured.Two experiments were conducted.A single dose of each intervention was used and the variables were measured during 24 h,and the interventions were given daily for a total of 8 d and the variables were measured during various intervals.Results:The single dose of each plant extract increased urine volume at all-time intervals and increased urine sodium and potassium excretion without affecting plasma sodium and potassium(P<0.05).On the day 8 after daily administration,the plant extracts induced a significant diuresis and natriuresis without affecting serum electrolytes(P<0.05),while furosemide caused hypokalemia.Both plant extracts significantly increased creatinine clearance(P<0.05).Conclusions:Silybum marianum L.and Cistus ladaniferus L Increase creatinine clearance and have a significant diuretic effect without affecting serum electrolytes.Silybum marianum L.is more potent than furosemide or Cistus ladaniferus L.

Two-Hour Creatinine Clearance and Glomerular Filtration Rate Estimated from Serum Cystatin C and Creatinine in the Elderly to Preoperative Period

Introduction: The utility of estimates of glomerular filtration rate based on creatinine and cystatin C serum levels to assess renal function in older surgical patients remains to be determined. Objective: To determine whether 2h-creatinine clearance (CrCl-2h) can be an adequate substitute for glomerular filtration rate estimates obtained by measuring serum cystatin C and creatinine in the elderly at preoperation. Methods: A total of 102 consecutive elder patients undergoing pre-anesthesia evaluation for routine surgeries were included. Study subjects were allocated into three groups: Group 1 (G1)—hypertensive diabetic patients, Group 2 (G2)—hypertensive patients, and Group 3 (G3)—non-hypertensive and non-diabetic patients. Two-hour urine collection was performed and CrCl-2h adjusted for ultrasonic residual bladder volume was estimated. GFR was estimated based on creatinine and cystatin C serum levels. Bland-Altman analysis was used to compare methods. Results: The mean difference between the evaluated methods and CrCl-2h was &middotmin-1&middot1.73 m-2 for Cys-GFR, and >20 mL&middotmin-1&middot1.73 m-2 for Cr-GFR in all groups. CrCl-2h adjusted for ultrasonic residual bladder volume did not differ from non-adjusted CrCl-2h in none of the groups. Conclusion: Two-hour creatinine clearance was not an adequate substitute for GFR estimates based on creatinine and cystatin C serum levels in older patients at preoperation. The ultrasonic assessment of residual bladder volume had no significant influence on the calculation of two-hour creatinine clearance.

Volume-to-creatinine clearance ratio:a predictor for contrast-induced nephropathy in chronic kidney disease after primary percutaneous coronary intervention

The volume of contrast media to the creatinine clearance （V/CrCl） ratio correlate with the contrast-induced nephropathy （CIN）. The chronic kidney disease （CKD） more likely to develop CIN after primary percutaneous coronary intervention （PCI）. Objectiv has been shown to patients would be e To determine a relatively safe V/CrCl cutoff value to avoid CIN in CKD patients undergoing primary PCI. Methods We enrolled a total of 114 patients with CKD and calculated V/CrCl. Receiver-operator characteristic methods were used to identify the optimal sensitivity and specificity for the observed range of V/CrCl for CIN. We used multivariable logistic regression to assess the predictive value of V/CrCl for the risk of CIN in CKD patients. Results Overall, there were 24 cases （21%） of CIN. The baseline mean and median V/CrCl values were significantly greater among patients with CIN （mean 5.08 ±2.01, median 4.81, and interquartile range 3.53-6.33） than among those without CIN （mean 3.35 ±1.48, median 3.12, and interquartile range 2.27-4.14, P 〈 0.001）. The receiveroperator characteristic curve analysis indicated that a V/CrCl ratio of 3.62 was a fair discriminator for CIN （Cstatistic of 0.75） in CKD patients. After adjusting for other known predictors of CIN,a V/CrCl ratio 〉3.62 remained significantly associated with CIN in CKD patients（odds ratio 8.46,95% confidence interval 2.37-30.19, P 〈 0.001）. medium dose Conclusions based on the AV/CrCl ratio〉3.62 is a simple,useful indicator for determining the safe contrast pre-PCI CrCl values in CKDs.

Establishing the presence or absence of chronic kidney disease:Uses and limitations of formulas estimating the glomerular filtration rate

The development of formulas estimating glomerular filtration rate(eG FR) from serum creatinine and cystatin C and accounting for certain variables affecting the production rate of these biomarkers, including ethnicity, gender and age, has led to the current scheme of diagnosing and staging chronic kidney disease(CKD),which is based on e GFR values and albuminuria.This scheme has been applied extensively in various populations and has led to the current estimates of prevalence of CKD. In addition, this scheme is applied in clinical studies evaluating the risks of CKD and the efficacy of various interventions directed towards improving its course. Disagreements between creatinine-based and cystatin-based e GFR values and between e GFR values and measured GFR have been reported in various cohorts. These disagreements are the consequence of variations in the rate of production and in factors, other than GFR, affecting the rate of removal of creatinine and cystatin C. The disagreements create limitations for all e GFR formulas developed so far. The main limitations are low sensitivity in detecting early CKD in several subjects, e.g., those with hyperfiltration, and poor prediction of the course of CKD. Research efforts in CKD are currently directed towards identification of biomarkers that are better indices of GFR than the current biomarkers and,particularly, biomarkers of early renal tissue injury.

eGFR is a reliable preoperative renal function parameter in patients with gastric cancer

AIM: To evaluate the validity of the estimated glomerular filtration rate (eGFR) as a preoperative renal function parameter in patients with gastric cancer. METHODS: A retrospective study was conducted in 147 patients with gastric cancer. Preoperative creatinine clearance (Ccr), eGFR, and preand postoperative serum creatinine (sCr) data were examined. Preoperative Ccr and eGFR were then compared for their reliability in predicting postoperative renal dysfunction. RESULTS: Among 110 patients with normal preoperative Ccr values, 7 (6.3%) had abnormal postoperative sCr values, and among 112 patients with normal preoperative eGFR values, postoperative sCr was abnormal in 5 (4.5%) (P = 0.53). Among 37 patients with abnormal preoperative Ccr values, 30 (81.1%) had normal postoperative sCr values, and of 35 patients with abnormal preoperative eGFR values, postoperative sCr was normal in 25 (71.4%) (P = 0.34). PreoperativeCcr was signifi cantly correlated with eGFR (r = 0.514), and postoperative sCr was significantly correlated with preoperative Ccr (r = -0.334) and eGFR (r = -0.02). CONCLUSION: Preoperative eGFR is as effective as Ccr for predicting postoperative renal dysfunction. eGFR should therefore be used as an indicator of preoperative renal function in place of Ccr since it is a cheaper and easier to perform test.

Quantitative Assessment of Protective Effects of Antioxidant Agents against Drug-Induced Nephrotoxicity Using Dynamic Contrast-Enhanced Computed Tomography

Purpose: The purpose of this study was to develop a method for quantifying the extent of renal dysfunction due to drug-induced nephrotoxicity using dynamic contrast-enhanced computed tomography (DCE-CT) and to investigate the protective effects of various antioxidant agents against cis-dichlorodiammineplatinum (cisplatin)-induced nephrotoxicity in rats using this method. Materials and Methods: The DCE-CT studies were performed in 8-week-old male Sprague-Dawley rats. The CT scanning started 4 s before a bolus intravenous injection of iodinated contrast agent (CA) (150 mgI/kg) from the tail vein using an automatic injector and lasted 90 s at 1-s intervals. The contrast clearance per unit renal volume (K1) was estimated from the DCE-CT data using the Patlak model. The renal volume (V) was calculated by manually delineating the kidney on the CT image. The contrast clearance of the entire kid-ney (K) was obtained by . First, to investigate the effect of CA itself, the DCE-CT studies were performed without injecting cisplatin 2, 4, and 7 days after the first DCE-CT study on day 0. Second, to investigate the effect of injected dose of cisplatin, the DCE-CT study was performed after the intraperitoneal (i.p.) injection of cisplatin (1.8 mg/kg) and was repeated every other day for one week. Finally, to investigate the protective effects of antioxidant agents [L-arginine (300 mg/kg), N-acetylcysteine (500 or 1000 mg/kg), methimazole (40 mg/kg), captopril (60 mg/kg), and taurine (750 mg/kg)], the DCE-CT studies were performed on days 0, 2, 4, and 7 after the i.p. injection of cisplatin (3.6 mg/kg). For comparison, the DCE-CT data were also acquired without injecting the antioxidant agents (CDDP group). Results: When cisplatin was not injected, there were no significant changes in the K value as compared to that on day 0 within the studied period. The K valuesignificantly (p < 0.05) decreased with increasing dose of cisplatin. Although some differences were observed in the extent of change in the K value normalized by that on day 0, depending on the antioxidant agents and their injected dose and schedule, the normalized K values on day 7 in the groups injected with the antioxidant agents were significantly higher than those in the CDDP group, suggesting that the antioxidant agents studied here had protective effects against cisplatin-induced nephrotoxicity in varying degrees. Conclusion: Our method appears useful for quantitatively evaluating the protective effects of antioxidant agents against cisplatin-induced nephrotoxicity and for investigating the optimal injected dose and schedule of the agents, because it allows repeated measurements of split renal function in a single animal.

Effects of Oenethera Oil on Plasma Lipid，Thromboxane A2 and Angiotensin Ⅱ of Chronic Renal Insufficiency

Oenethera biennis oil was administered (6 g per day) in 23 chronic renal insufficiency pa-tients over a 4 week period. Changes of serum creatinine, creatinine clearance, plasma lipid, renin activity,and angiatensin , urinary thromboxane B2 and 6-keto-prostaglandin F1 were observed before and after thetreatment. Results showed that after treatment. the creatinine clearance increased, serum total cholesterol,triglyceride and low density lipoprotein decreased, high density lipoprotein increased, plasma renin activity,angiotensin and urinary thromboxane B2 decreased significantly. The conclusion was that Oenethera bien-nis oil could improve the pathological process of renal diseases, and has benoficial effects on plasma lipiddisorder and glomerular hemodynamics .