Measurement of serum cystatin C,creatinine clearance and urea micro-albumin as renal function evaluation indicators in cancer patients during chemotherapy with platinum

Objective:Chemotherapy drugs such as platinum may cause damage to the renal function,creatinine clearance(Ccr),as a "golden standard" indicator in clinical evaluation of renal function,was limited in application due to complicated detection steps.By detecting the expression of serum Cystatin C(Cys C),Ccr and urinary micro-albumin(UMA),this study was designed to analyze and discuss their roles and status in renal function evaluation for cancer patients before and after chemotherapy with platinum.Methods:We retrospectively reviewed 110 patients who receiving platinum-containing protocols or non-platinum-containing ones,and got the expression of Cys C,Ccr(was calculated by Cockcroft-Gault equation) and UMA,then analyzed whether there were differences for Cys C,Ccr and UMA in those patients;for patients with mildly impaired renal function(Ccr between 50-75 mL/min),whether there were differences for Cys C and UMA before and after chemotherapy with platinum.Results:There was statistical significance for Ccr,Cys C and UMA in patients who receiving platinum-containing protocols(85.01 ± 28.40) vs(76.79 ± 26.63) mL/min,(1.49 ± 0.50) vs(1.80 ± 0.84) mg/L and(14.30 ± 9.15) vs(16.90 ± 10.95) mg/L,P = 0.00,0.00 and 0.01),and no statistical significance for those receiving non-platinum-containing ones(89.45 ± 29.69) vs(86.78 ± 27.96) mL/min,(1.51 ± 0.78) vs(1.63 ± 0.73)mg/L and(17.31 ± 10.46) vs(16.59 ± 8.33) mg/L,P = 0.45,0.07 and 0.57);and there were also significant differences for Cys C for patients with mildly impaired renal function before and after chemotherapy(1.68 ± 0.55) vs(2.04 ± 0.68) mg/L,P = 0.03),while no statistical significance for UMA for the same ones(21.11 ± 10.06) vs(21.22 ± 8.81) mg/L,P = 0.93).There were statistical significance both for Cys C and UMA before and after chemotherapy in platinum-containing group,but the AUC for Ccr and Cys C is greater than that for UMA(P < 0.02).Conclusion:Cys C and UMA can both access renal dysfunction early after chemotherapy,but Cys C is more sensitive than UMA in reflecting early renal dysfunction,so Cys C can replace Ccr and become a reliable indicator in the assessment of renal function for cancer patients before and after chemotherapy especially with platinum.

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.

Comparison of GFR by Creatinine Clearance with Estimated GFR by Various Prediction Equations in a Bangladeshi Population

Glomerular filtration rate （GFR） is considered as the best marker of kidney function. Evaluation of various prediction equations to estimate GFR is rare in our population. The aim of this study was to compare GFR estimated by various prediction equations with GFR by creatinine clearance （GFRer） in Bangladeshi population. Serum creatinine and 24 hours urinary creatinine concentrations were measured in 216 adult Bangladeshi subjects （100 males and 116 females）. Creatinine clearance rate was calculated and adjusted for body surface area to obtain GFRcr. GFR was also calculated by CKD-EPI, MDRD4, Cockcroft-Gault, Jelliffe, Mawer, Bjornsson, Gates, Apollo-Chennai and Mayo Clinic prediction equations and compared with GFRcr. Results were expressed as mean ＋ SD and compared by two-tailed paired t-test, precision （r2） and receiver-operating characteristic curve. Mean ± SD of age of the total subjects was 57.15 ±10.96 years. The mean GFILzr was 42.41 ± 22.95 mL/min/1.73m2. Estimated GFR （eGFR） by CKD-EPI, MDRD4, Cockcroft-Gault, Jelliffc 1, Jelliffe 2, Mawer, Bjornsson, Gates, Apollo-Chennai and Mayo Clinic prediction equations were 8.19 ± 13.80, 5.30 ±13.61, 11.54 ± 16.86, 8.66± 18.64, 17.25 ± 19.98, 10.86 ± 22.48, 14.60 ± 17.92, 12.18 ± 16.42, 39.86 ± 21.96 and 20.47 ± 20.49 mL/min/1.73m2 higher than GFR, （P 〈 0.001）. The precision （r2） of eGFRs were 0.7114, 0.6924, 0.6431, 0.4802, 0.5048, 0.5921, 0.6286, 0.6158, 0.1635, and 0.5586 for CKD-EPI, MDRD4, Cockcroft-Gault, Jelliffe 1, Jelliffe 2, Mawer, Bjornsson, Gates, Apollo-Chennai and Mayo Clinic prediction equations, respectively. The area under receiver-operating characteristic curve was the lowest for MDRD4 equation. This study revealed that GFR estimated by standardized MDRD4 variables equation is closer to creatinine clearance rate in the study population.

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.

Cockcroft-gault revisited: New de-liver-ance on recommendations for use in cirrhosis

The Cockcroft-Gault(CG) equation has become perhaps the most popular practical approach for estimating renal function among health care professionals. Despite its widespread use, clinicians often overlook not only the limitations of the original serum creatinine(SCr) based equation, but also may not appreciate the validity of the many variations used to compensate for these limitations. For cirrhotic patients in particular, the underlying pathophysiology of the disease contributes to a falsely low SCr, thereby overestimating renal function with use of the CG equation in this population. We reviewed the original CG trial from 1976 along with data surrounding clinician specific alterations to the CG equation that followed through time. These alterations included different formulas for body weight in obese patients and the "rounding up" approach in patients with low SCr. Additionally, we described the pathophysiology and hemodynamic changes that occur in cirrhosis; and reviewed several studies that attempted to estimate renal function in this population. The evidence we reviewed regarding the most accurate manipulation of the original CG equation to estimate creatinine clearance(Cr Cl) was inconclusive. Unfortunately, the homogeneity of the patient population in the original CG trial limited its external validity. Elimination of body weight in the CG equation actually produced the estimate closest to the measure Cr Cl. Furthermore, "rounding up" of SCr values often underestimated Cr Cl. This approach could lead to suboptimal dosing of drug therapies in patients with low SCr. In cirrhotic patients, utilization of SCr based methods overestimated true renal function by about 50% in the literature we reviewed.

When to initiate renal replacement therapy: The trend of dialysis initiation

The timing of renal replacement therapy for patients with end-stage renal disease has been subject to considerable variation. The United States Renal Data System shows an ascending trend of early dialysis initiation until 2010, at which point it decreased slightly for the following 2 years. In the 1990s, nephrologists believed that early initiation of dialysis could improve patient survival. Based on the Canadian-United States Peritoneal Dialysis study, the National Kidney Foundation Dialysis Outcomes Quality Initiative recommended that dialysis should be initiated early. Since 2001, several observational studies and 1 randomized controlled trial have found no beneficial effect when patients were placed on dialysis early. In contrast, they found that an increase in mortality was associated with early dialysis initiation. The most recent dialysis initiation guidelines recommend that dialysis should be initiated at an estimated glomerular filtration rate （eGFR） of greater than or equal to 6 mL/min per 1.73 m2. Nevertheless, the decision to start dialysis is mainly based on a predefned eGFR value, and no convincing evidence has demonstrated that patients would benefit from early dialysis initiation as indicated by the eGFR. Even today, the optimal dialysis initiation time remains unknown. The decision of when to start dialysis should be based on careful clinical evaluation.

Estimating glomerular filtration rate preoperatively for patients undergoing hepatectomy

AIM:To compare creatinine clearance(Ccr) with estimated glomerular filtration rate(eGFR) in preoperative renal function tests in patients undergoing hepatectomy.METHODS:The records of 197 patients undergoing hepatectomy between August 2006 and August 2008 were studied,and preoperative Ccr,a three-variable equation for eGFR(eGFR3) and a five-variable equation for eGFR(eGFR5) were calculated.Abnormal values were defined as Ccr < 50 mL/min,eGFR3 and eGFR5 < 60 mL/min per 1.73 m2.The maximum increases in the postoperative serum creatinine(post Cr) level and postoperative rate of increase in the serum Cr level(post Cr rate) were compared.RESULTS:There were 37 patients(18.8%) with abnormal Ccr,31(15.7%) with abnormal eGFR3,and 40(20.3%) with abnormal eGFR5.Although there were no significant differences in the post Cr rate between patients with normal and abnormal Ccr,eGFR3 and eGFR5 values,the post Cr level was significantly higher in patients with eGFR3 and eGFR5 abnormality than in normal patients(P < 0.0001).Post Cr level tended to be higher in patients with Ccr abnormality(P = 0.0936 and P = 0.0875,respectively).CONCLUSION:eGFR5 and the simpler eGFR3,rather than Ccr,are recommended as a preoperative renal function test in patients undergoing hepatectomy.

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 AngiotensinⅡof 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 .