Measuring Serum Creatinine Concentrations Research Articles

Interference of metamizole in the measurement of serum creatinine concentration.

There is little literature on the interference of metamizole in measurement creatinine concentration by the enzymatic method. Some studies have postulated that the dipyrone molecule is responsible for interfering in the last reaction of the enzymatic method sequence, due to its similarity with the 4-aminophenazone molecule. The aim of this study is to examine the interference of the presence of metamizole in the measurement of serum creatinine concentration by the enzymatic method. An interference study of the measurement of creatinine concentration was carried out with two measurement procedures (enzymatic and Jaffe), by adding different concentrations of metamizole to pool from 30 serum samples of patients. The interference study indicates that the results of serum creatinine concentrations in patients, as measured by the enzymatic method, decrease with the addition of increasing concentrations of metamizole. There is interference with metamizole in the measurement of serum creatinine concentration by the enzymatic method that it is have not seen in the Jaffe method.

Renal function in patients with chronic hepatitis B during antiviral therapy

<p><strong>Aim</strong> <br />To analyse the impact of the length of antiviral therapy with tenofovir disoproxil fumarate (TDF) on the renal function in patients with chronic hepatitis B (CHB).<br /><strong>Methods<br /></strong> A cross-sectional study included 75 patients with CHB treated with tenofovir, who had a normal renal function at the beginning of the treatment. Renal function was determined based on glomerular filtration rate (eGFR) value using the Modification of Diet in Renal Disease formula (MDRD). Measurement of serum creatinine concentration and urinary protein excretion were performed using standard laboratory analyses. Viral load quantification (HBV-DNA) was determined by polymerase chain reaction (PCR). The degree of liver fibrosis was determined using fibrosis4 (FIB-4) and aspartate transaminase to platelet ratio index (APRI) fibrosis score.<br /><strong>Results</strong><br />Out of 75 CHB patients, 37 were on antiviral treatment for up to 2 years (group 1) and 38 patients on antiviral treatment<br />longer than two years (group 2). Mean age of patients was not significantly different between the groups (p=0.076), nor was the gender distribution. There was no statistically significant difference between the mean values of the eGFR in the two groups (91.89±9.24 vs. 88.42±7.84 mL/min/1.73m2 ; p=0.42), as well as between the mean values of serum creatinine (p=0.360) and 24-hour urine protein excretion (p=0.380). There was no statistically significant correlation between renal parameters and viral load, APRI and FIB-4 fibrosis score.<br /><strong>Conclusion</strong> <br />Results of our study did not show significant changes in the measured parameters of renal function in group 1 and group<br />2 of patients, regardless of the length of antiviral treatment, indicating a good renal safety profile of TDF.</p>

Comparability and Stability of Serum Creatinine Concentration in Capillary and Venous Blood.

Background: The use of self-collected capillary blood has several advantages over phlebotomy, as such finger-prick testing is rapidly becoming accepted as a routine sample type for adults. However, there is limited evidence that venous and capillary serum is comparable for many analytes. This study aimed to determine whether capillary samples could offer an alternative sampling method to venous samples for the assessment of serum creatinine using the enzymatic method and if this analyte was stable in unspun capillary blood for 3days. Methods: Matched capillary and venous blood samples were collected from 48 patients for the determination of serum creatinine, one set being processed on day zero, the other set being stored at ambient temperature and then processed on day three. Self-collected capillary blood was compared with phlebotomist-collected venous samples. Results: Serum creatinine concentrations from venous and capillary blood samples taken on day zero were compared to concentrations in capillary blood from day three. Data produced showed serum creatinine concentrations from capillary and venous serum to be comparable. Conclusion: It is believed that this is the first published study to determine if self-collected capillary blood sampling is an acceptable alternative to venous sampling for the measurement of serum creatinine concentration; our data indicates that there is no significant difference in results from unspun venous and capillary blood stored at room temperature for at least 3days compared to venous blood tested on the same day of collection.

Assessment of Measurement of Salivary Urea by ATR-FTIR Spectroscopy to Screen for CKD.

Stages of CKD are currently defined by eGFR and require measurement of serum creatinine concentrations. Previous studies have shown a good correlation between salivary and serum urea levels and the stage of CKD. However, quantitative salivary urea assays in current clinical use require costly and labor-intensive commercial kits, which restricts the advantage of using saliva and limits wider applicability as a quick and easy means of assessing renal function. Attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy has been shown to provide a potentially straightforward, reagent-free method for the identification of a range of disease-related biomarkers and is in current clinical use for analyses of the chemical composition of kidney stones. We assessed the feasibility of ATR-FTIR spectroscopy as an alternative method to measure salivary urea in patients with different stages of CKD. The ATR-FTIR spectra of dried saliva samples from six healthy controls and 20 patients with CKD (stages 1-5) were analyzed to provide their urea concentrations. The lower limit of detection of salivary urea by the ATR-FTIR spectroscopy method was 1-2 mM, at the lower end of the clinically relevant range. Statistically significant differences in salivary urea concentrations were demonstrated between healthy subjects (4.1±0.5 mM) and patients with CKD stages 3-5 (CKD stage 3, 6.8±0.7 mM; CKD stage 4, 9.1±1 mM; CKD stage 5, 14.8±1.6 mM). These salivary urea concentrations correlated well with serum urea levels in the same patients measured by an automated analyzer (Spearman rank correlation coefficient of 0.71; P<0.001). The ability of the method to detect and stage CKD was assessed from the sensitivity and specificity parameters of a receiver operating characteristics (ROC) curve analysis. This proof-of-concept study demonstrates that quantitation of salivary urea by ATR-FTIR spectroscopy could provide a viable tool for rapid and cost-effective diagnosis of stages 3-5 CKD.

Nano-molecularly imprinted polymers for serum creatinine sensing using the heat transfer method

Serum creatinine concentration is an important clinical measure of kidney function. However, standard methods of detection, such as the Jaffe method or enzymatic assays, suffer several disadvantages, including non-specificity and procedural complexity, or high cost, respectively. In this work, we propose the use of nano-molecularly imprinted polymers (nMIPs) in conjunction with the novel Heat Transfer Method (HTM) as a promising alternative sensing platform to these existing methods for measuring serum creatinine concentration. More specifically, it is shown that creatinine-imprinted nMIPs can be produced using a solid-phase templating method, and that simple drop-casting onto a cheap, disposable substrate can be used in conjunction with HTM to detect creatinine with a limit-of-detection of (7.0 ± 0.5) μM in buffer solutions. Furthermore, the nMIPs are shown to selectively bind creatinine in comparison to several similar molecules, and the sensing platform is demonstrated to be able to detect changes in creatinine concentration in complex blood plasma samples.

Characteristics of runners meeting acute kidney injury criteria following a 161‐km ultramarathon

The incidence of acute kidney injury (AKI) associated with ultramarathon running is varied partially because onsite measurement of serum creatinine concentration (Cr) is rarely performed at races due to logistical challenges. We conducted a prospective observational study using blood samples from volunteer athletes before and immediately after the Leadville Trail 100 Run in August 2014. The goals of our study were to determine the incidence of those meeting the AKI criteria immediately following the ultramarathon race and to evaluate the utility of using medical equations to back-calculate creatinine levels for runners without known baseline creatinine levels and to identify possible risk factors for developing AKI. We were able to collect pre-race and post-race blood samples on 64 and 84 volunteers, respectively. AKI was defined as a Cr increase (≥1.5 times or ≥0.3 mg/dl from baseline). Of the 37 runners for whom we had both pre- and post-race blood samples, 18 (49%) met the criteria for AKI. Using two different methods of back-calculating baseline estimated creatinine (a fixed eGFR [estimated glomerular filtration rate] and an aged-based eGFR), 6 (16%) and 22 (59%) of 37 runners met the criteria for AKI, respectively. We found that there is no accurate way to estimate baseline Cr in this population.

Rapid Simultaneous Determination of Paraquat and Creatinine in Human Serum Using a Piece of Paper.

Paraquat intoxication is characterized by acute kidney injury and multi-organ failure, causing substantial mortality and morbidity. This study aims to develop a 2-in-1 paper-based analytical device to detect the concentrations of paraquat and creatinine in human serum, which can help clinicians diagnose patients with paraquat poisoning in a more rapid and geographically unrestricted manner. The procedure involves fabrication of a paper-based analytical device, i.e., printing of design on a filter paper, heating of wax-printed micro zone plates so as molten wax diffusing into and completely through the paper to the other side, forming hydrophobic boundaries that could act as detection zones for the paraquat colorimetric assay, and finally analysis using ImageJ software. The paper employed a colorimetric sodium dithionite assay to indicate the paraquat level in a buffer or human serum system in less than 10 min. In this study, colorimetric changes into blue color could be observed by the naked eye. By curve fitting models of sodium dithionite in normal human serum, we evaluated the serum paraquat levels for five paraquat patients. In the sodium dithionate assay, the measured serum paraquat concentrations in patients 1–5 were 22.59, 5.99, 26.52, 35.19 and 25.00 ppm, respectively. On the other hand, by curve fitting models of the creatinine assay in normal human serum, the measured serum creatinine concentrations were 16.10, 12.92, 13.82, 13.58 and 12.20 ppm, respectively. We found that the analytical performance of this device can compete with the standard of Clinical Laboratory of Chang Gung Memorial Hospital, with a less complicated sample preparation process and more rapid results. In conclusion, this 2-in-1 paper-based analytical device has the advantage of being simple and cheap, enabling rapid detection of paraquat intoxication as well as assessment of renal prognosis.

Serum Creatinine in Pregnancy: A Systematic Review

IntroductionStandard assessment of renal function in pregnancy is by measurement of serum creatinine concentration yet normal gestational ranges have not been established. The aim of this systematic review was to define the difference in serum creatinine in a healthy pregnancy compared with concentrations in nonpregnant women to facilitate identification of abnormal kidney function in pregnancy.MethodsMedline, PubMed, Embase, Web of Science, theses, key obstetric texts, and conference proceedings were searched to July 2017. Eligible studies included quantification of serum creatinine concentration in a pregnant cohort, with either a reported local laboratory reference range or matched quantification in a nonpregnant cohort. The outcomes of interest were the mean and upper reference limits for creatinine in pregnancy, measured as a ratio of pregnant:nonpregnant values. Study heterogeneity was examined by meta-regression analysis.ResultsForty-nine studies were identified. Data synthesis included 4421 serum creatinine values in pregnancy, weighted according to cohort size. Mean values for serum creatinine in pregnancy were 84%, 77%, and 80% of nonpregnant mean values during the first, second, and third trimesters, respectively. The 97.5th centile (upper limit of the 95% reference range) for serum creatinine in pregnancy was 85%, 80%, and 86% of the nonpregnant upper limit in sequential trimesters.ConclusionBased on a nonpregnant reference interval of 45–90 μmol/l (0.51–1.02 mg/dl), a serum creatinine of >77 μmol/l (0.87 mg/dl) should be considered outside the normal range for pregnancy. Future work can use this value to explore correlation of adverse pregnancy outcomes with serum creatinine concentration. PROSPERO registration: CRD42017068446

Laboratory diagnosis of chronic kidney disease in adults: an overview of hospitals inserted in the Portuguese National Health System

ABSTRACT Introduction: The laboratory diagnosis of chronic kidney disease (CKD) is a simple and cost-effective procedure that allows the detection of early stages of the disease, which is essential to avoid kidney damage and a life threateaning event. It consists of measuring serum creatinine concentration, urinary albumin concentration and calculating the estimated glomerular filtration rate (eGFR). In 2012, the guidelines for laboratory evaluation of the CKD were published by the Kidney Disease: Improving Global Outcomes (KDIGO). Objectives: This study aimed to evaluate whether the laboratories in hospitals of the Portuguese National Health System follow these guidelines and provide a correct diagnosis of CKD. Material and method: A questionnaire composed of 32 questions was sent to the Clinical Pathology Services of all hospitals inserted in the System. Results: All 49 labs responded that measure serum creatinine, 18 reported measurering eGFR. Ten reported measuring eGFR only if specifically ordered. Forty-four measure total protein and albumin in the urine, three only protein, one albumin alone, and one measure none of them. The type of samples, methods, reagents, equipment, expression units of results and reference intervals varied. Conclusion: There is great variability among laboratories in relation to the methodology of measuring serum creatinine, albumin and total protein in the urine. There are wide variations in the release of results. Most laboratories do not follow the guidelines recommended by the KDIGO 2012. This work indicates that there is a need to develop education and alignment processes in the laboratory diagnosis of CKD in the laboratories installed in hospitals inserted in the Portuguese National Health System.

Methods for Measuring Serum Creatinine Concentrations in Dogs and Cats Given Squid in Their Diet

Methods for Measuring Serum Creatinine Concentrations in Dogs and Cats Given Squid in Their Diet

Subclinical Bacteriuria in Older Cats and its Association with Survival.

BackgroundBacterial urinary tract infections are uncommon in cats in general but the prevalence increases to 29% in older cats with comorbidities (Veterinary Clinical Pathology 2008, 37, 317; Journal of Feline Medicine & Surgery 2007, 9, 124; Veterinary Microbiology 2009, 136, 130). Frequently, the infections are subclinical. The clinical relevance of subclinical bacteriuria (SB) is uncertain, and the optimal treatment requires clarification.ObjectiveProspective, observational study to: (i) identify the prevalence and incidence count of SB in older (≥7 years), nonazotemic cats, (ii) evaluate specific risk factors for SB, and (iii) investigate the potential relationship between untreated SB and survival.AnimalsSixty‐seven, nonazotemic cats were tested on 5 occasions over 3 years.MethodsUrine samples were obtained by cystocentesis for quantitative urine culture and blood samples for measurement of serum creatinine concentration. Episodes of SB were not treated. Serum creatinine concentration, body weight, urine specific gravity, sex, and age were evaluated as potential risk factors for a positive urine culture. The association between urine culture results and survival was evaluated with Cox's proportional hazard model.ResultsA total of 256 urine samples was obtained. The prevalence of SB varied between 10 and 13%, and incident infections were uncommon. Female cats were 21 times more likely to have a positive urine culture than were male cats (odds ratio [OR], 21.2; confidence interval [CI], 4.1–110; P = .00028). Subclinical bacteriuria was not significantly associated with survival.Conclusion and clinical importanceSubclinical bacteriuria is common in nonazotemic, older cats. Although antimicrobial treatment was withheld, the presence of SB was not adversely associated with survival.

Sodium bicarbonate does not prevent postoperative acute kidney injury after off-pump coronary revascularization: a double-blinded randomized controlled trial

BackgroundAcute kidney injury (AKI) is a common morbidity after off-pump coronary revascularization. We investigated whether perioperative administration of sodium bicarbonate, which might reduce renal injury by alleviating oxidative stress in renal tubules, prevents postoperative AKI in off-pump coronary revascularization patients having renal risk factors. MethodsPatients (n=162) having at least one of the following AKI risk factors were enrolled: (i) age >70 yr; (ii) diabetes mellitus; (iii) chronic renal disease; (iv) congestive heart failure or left ventricular ejection fraction <35%; and (v) reoperation or emergency. Patients were evenly randomized to receive either sodium bicarbonate (0.5 mmol kg−1 for 1 h upon induction of anaesthesia followed by 0.15 mmol kg−1 h−1 for 23 h) or 0.9% saline. Acute kidney injury within 48 h after surgery was assessed using the Acute Kidney Injury Network criteria. ResultsThe incidences of AKI were 21 and 26% in the bicarbonate and control groups, respectively (P=0.458). Serially measured serum creatinine concentrations and perioperative fluid balance were also comparable between the groups. The length of postoperative hospitalization and incidence of morbidity end points were similar between the groups, whereas significantly more patients in the bicarbonate group required prolonged mechanical ventilation (>24 h) relative to the control group (20 vs 6, P=0.003). ConclusionsPerioperative sodium bicarbonate administration did not decrease the incidence of AKI after off-pump coronary revascularization in high-risk patients and might even be associated with a need for prolonged ventilatory care. Clinical trial registrationNCT01840241.

The role of the uncertainty of measurement of serum creatinine concentrations in the diagnosis of acute kidney injury

Uncertainty of measurement is the numeric expression of the errors associated with all measurements taken in clinical laboratories. Serum creatinine concentration is the most common diagnostic marker for acute kidney injury. The goal of this study was to determine the effect of the uncertainty of measurement of serum creatinine concentrations on the diagnosis of acute kidney injury. We calculated the uncertainty of measurement of serum creatinine according to the Nordtest Guide. Retrospectively, we identified 289 patients who were evaluated for acute kidney injury. Of the total patient pool, 233 were diagnosed with acute kidney injury using the AKIN classification scheme and then were compared using statistical analysis. We determined nine probabilities of the uncertainty of measurement of serum creatinine concentrations. There was a statistically significant difference in the number of patients diagnosed with acute kidney injury when uncertainty of measurement was taken into consideration (first probability compared to the fifth p = 0.023 and first probability compared to the ninth p = 0.012). We found that the uncertainty of measurement for serum creatinine concentrations was an important factor for correctly diagnosing acute kidney injury. In addition, based on the AKIN classification scheme, minimizing the total allowable error levels for serum creatinine concentrations is necessary for the accurate diagnosis of acute kidney injury by clinicians.

Single point measurement of cystatin C has similar performance as serum creatinine for assessment of kidney function in critically ill patients

The gold standard for routine evaluation of kidney function is measurement of serum creatinine concentration (Scr). In ICU patients, muscle loss and dilution leads to decreased Scr. Scr is distributed in total body water, resulting in delay of Scr changes when the glomerular filtration rate (GFR) changes (lag time). Cystatin C (CysC) is a protein produced by all cells with a nucleus and therefore less affected by muscle mass. Also, the lag time may be shorter as the volume of distribution is only extracellular fluid. The objective of this study was to evaluate whether single point measurement of CysC is more adequate than Scr for monitoring of kidney function in ICU patients.

Analysis of oncological outcomes and renal function after laparoendoscopic single‐site (LESS) partial nephrectomy: a multi‐institutional outcome analysis

To report on a large multi-institutional series of laparoendoscopic single-site (LESS) partial nephrectomy (PN) and analyse renal function and short-term oncological outcomes. We conducted a retrospective analysis of consecutive cases of LESS-PN performed between November 2007 and March 2012 at 11 participating institutions. Demographic data and data on the main peri-operative outcomes and complications were gathered and analysed. Kidney function was evaluated by measuring serum creatinine concentration and estimated glomerular filtration rate (eGFR). Chronic kidney disease was defined in stages for each patient according to the National Kidney Foundation, Kidney Disease Outcomes Quality Initiative. A total of 190 cases were included in this analysis. The mean renal tumour size was 2.6 cm, and the mean PADUA score was 7.2. The median operating time was 170 min with a median estimated blood loss of 150 mL. A clampless technique was used in 70 cases (36.8%) and the median warm ischaemia time (WIT) was 16.5 min. PADUA score independently predicted the length of WIT (low vs high score: odds ratio 5.11, CI 1.50-17.41, P = 0.009; intermediate vs high score: odds ratio 5.13, CI 1.56-16.88, P = 0.007). The overall postoperative complication rate was 14.7%. Where a clamping technique was used, a significant increase in serum creatinine concentration and a significant decrease in eGFR were observed postoperatively and at 6 months. On multivariate analysis PADUA score was the only predicting factor. Overall survival rates were 99, 97 and 88% at 12-, 24- and 36-month follow-up, respectively, while disease-free survival rates were 98% at 12-month and 97% at 24- and 36-month follow-up. The study showed that LESS-PN is effective in terms of renal function preservation and oncological control at short- and intermediate-term follow-up.

Evaluation of glomerular filtration rate in cats with reduced renal mass and administered meloxicam and acetylsalicylic acid

To determine whether administration of meloxicam or acetylsalicylic acid alters glomerular filtration rate (GFR) in cats with renal azotemia. 6 young adult cats. 3 sexually intact male cats and 3 sexually intact female cats had surgically reduced renal mass and azotemia comparable to International Renal Interest Society chronic kidney disease stages 2 and 3. Renal function was evaluated by measurement of serum creatinine concentration, urinary clearance of exogenously administered creatinine, and the urine protein-to-creatinine concentration ratio (UP:C). Measurements taken in cats receiving placebo at the beginning and end of the study were compared with results obtained at the end of 7 days of treatment with either meloxicam (0.2 mg/kg, SC, on day 1; 0.1 mg/kg, SC, on days 2 to 7) or acetylsalicylic acid (20 mg/kg, PO, on days 1, 4, and 7). No significant treatment effects on urinary clearance of exogenously administered creatinine, serum creatinine concentration, or UP:C were detected. Mean ± SEM serum creatinine concentration and urinary clearance of exogenously administered creatinine measurements following 7 days of treatment with meloxicam (serum creatinine concentration, 2.67 ± 0.17 mg/dL; urinary clearance of exogenously administered creatinine, 1.34 ± 0.08 mL/min/kg) and acetylsalicylic acid (serum creatinine concentration, 2.62 ± 0.12 mg/dL; urinary clearance of exogenously administered creatinine, 1.35 ± 0.07 mL/min/kg) were not significantly different from the mean baseline values for these variables (serum creatinine concentration, 2.77 ± 0.14 mg/dL; urinary clearance of exogenously administered creatinine, 1.36 ± 0.07 mL/min/kg). Neither meloxicam nor acetylsalicylic acid had a measurable effect on urinary clearance of exogenously administered creatinine, serum creatinine concentration, or UP:C. These results are consistent with the hypothesis that GFR of euvolemic cats with normal or reduced renal function is not dependent on cyclooxygenase function.

Clampless laparoendoscopic single‐site partial nephrectomy for renal cancer with low PADUA score: technique and surgical outcomes

WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Laparoendoscopic single-site (LESS) surgery has proved to be immediately applicable in the clinical field, being safe and feasible in the hands of experienced laparoscopic surgeons in well-selected patients. All extirpative and reconstructive urological procedures have been described in the literature, but LESS partial nephrectomy (PN) is one of the most complex procedures and few studies have been published on this subject. The study describes a clampless technique for LESS PN, by reducing the blood pressure and increasing the intra-abdominal pressure of the pneumoperitoneum to 20 mmHg, timed to precisely coincide with excision of the tumour. This technique was found to be safe and feasible in the treatment of low-risk T1a RCC. To describe the technique and report the surgical outcomes of clampless laparoendoscopic single-site (LESS) partial nephrectomy (PN) in the treatment of renal cell carcinoma (RCC) with low PADUA score. Clampless LESS PN was performed in 14 patients with cT1a renal tumours. Indications to perform a clampless LESS PN were low-risk, laterally based renal tumours, located away from the renal hilum, with a PADUA score ≤7. Demographic data and peri-operative and postoperative variables were recorded and analysed. Kidney function was evaluated by measuring serum creatinine concentration and estimated glomerular filtration rate (eGFR) pre- and postoperatively and at 6-month follow-up. The median operating time was 120 min and warm ischaemia time was zero in all cases. Only one early complication (Clavien grade 1) was recorded: one patient developed a flank haematoma which it was possible to treat by conservative therapy. Serum creatinine and modification of diet renal disease eGFR were not found to be significantly different pre- and postoperatively and at 6-month follow-up. Definitive pathological results showed 12 pT1a RCCs and two pT1a-chromophobe RCCs. All tumours were removed with negative surgical margins. All patients were satisfied with the cosmetic results. At a median (range) follow-up period of 12 (8-15) months, all patients were alive without evidence of tumour recurrence or port-site metastasis. Clampless LESS PN is a safe and feasible surgical procedure in the treatment of low-risk T1a RCC, with excellent cosmetic results.

Effects of Targeting Higher Vancomycin Trough Levels on Clinical Outcomes and Costs in a Matched Patient Cohort

To compare clinical outcomes and costs in patients treated with the new vancomycin guidelines recommending goal serum trough concentrations of 15-20 mg/L versus patients treated with vancomycin doses targeting trough concentrations 5-20 mg/L prior to the new guidelines. Retrospective quasi-experimental study. Urban level I trauma center. A total of 200 patients treated with vancomycin for at least 72 hours for confirmed, complicated methicillin-resistant Staphylococcus aureus (MRSA) bacteremia during one of two study phases relative to the implementation of the vancomycin dosing guidelines targeting serum trough concentrations of 15-20 mg/L: 2005-2007 (preperiod phase) and 2008-2010 (postperiod phase). One hundred patients in each phase were matched in a 1:1 ratio according to diagnosis, any concomitant nephrotoxic agents (e.g., aminoglycosides, colistin, acyclovir), and age ± 5 years. Patients in the preperiod had significantly lower success rates with vancomycin than those in the postperiod (45% vs 60%, p=0.034). Median length of stay (LOS) was not significantly higher in patients in the preperiod versus postperiod (15 days vs 13.5 days; p=0.28), and patients in the preperiod received a longer median duration of vancomycin versus those in the postperiod (13 days vs 8.5 days; p<0.001). No statistically significant difference was noted in total hospital costs for patients treated with vancomycin during the preperiod versus the postperiod ($32,754 vs $27,709, p=0.147). However, total drug and monitoring costs of vancomycin were significantly higher for patients in the postperiod. Initial vancomycin trough levels were significantly lower in patients in the preperiod versus postperiod (12.3 mg/L vs 15.8 mg/L, p=0.02). Patients in the preperiod had lower rates of nephrotoxicity than those in the postperiod, although this difference was not statistically significant (15% vs 18%; p=0.85). Median (interquartile range) LOS was significantly longer in patients who developed nephrotoxicity compared with patients who did not develop nephrotoxicity (17 days [11.5-36.5 days] vs 14 days [9-24 days], p=0.017). Costs associated with measurement of serum creatinine concentrations and vancomycin trough levels as well as labor were significantly higher in patients who developed nephrotoxicity. Higher vancomycin trough concentrations improved outcomes in patients with complicated MRSA bacteremia. In addition, more aggressive dosing was shown to significantly decrease overall duration of vancomycin therapy, which may affect total hospital LOS and cost. Patients who experienced nephrotoxicity had a significantly longer hospital LOS. Additional studies evaluating optimal therapy for MRSA bacteremia in a larger cohort of matched patients are warranted.

Highlights of This Issue

Deletion of the PTEN tumor suppressor gene, which occurs in a large proportion of prostate cancers, has been linked to reduced homologous recombination–mediated DNA repair, reduced RAD51 expression, and increased sensitivity to PARP inhibitors. Using preclinical prostate cancer models and primary prostate cancer tissues, Fraser and colleagues show that PTEN loss does not alter homologous recombination function or RAD51 expression as the basis for differential sensitivity to experimental radiotherapy, chemotherapy, or PARP inhibition. Instead, other DNA damage response genes, such as MRE11, can confer PARP inhibitor sensitivity. PTEN status is not a direct biomarker of RAD51 function and is unlikely to predict therapeutic response in prostate cancer clinical trials on its own.HER3 receptor tyrosine kinase has been shown to play a crucial role in mediating various human tumors. Beji and colleagues designed a strategy to explore the significance of this pseudokinase in colon cancer. HER3 expression may represent a putative prognostic marker because it correlates with reduced patient survival. Reduction in HER3 expression by either siRNA or monoclonal antibodies abrogated a wide range of cellular processes, including proliferation, migration, and invasion; interfered with progression of the cell cycle; and induced a shift in cell morphology. HER3 may therefore represent a promising target for novel targeted therapy.Circulating tumor cells (CTC) can be detected in peripheral blood of breast cancer patients by antibodies against epithelial-specific keratin proteins. However, during epithelial–mesenchymal transition, keratin expression may be downregulated and these CTCs remain undetected. Joosse and colleagues have shown that the keratins currently targeted for CTC detection are downregulated in particular in breast cancer patients with unfavorable outcome. By targeting more keratins, detection of clinically relevant CTCs can be improved, and this information can be used in the future for better assessment of prognosis and monitoring therapeutic efficacy.Assessment of kidney function in cancer patients receiving chemotherapeutic agents is usually accomplished by measuring serum creatinine concentration and creatinine clearance. Using an array of technologies, including transfected cell models, transporter-deficient mice, genetic-association analyses, and drug-creatinine interaction studies in patients, Ciarimboli and colleagues found that the organic cation transporter 2 (OCT2) plays a decisive role in the renal secretion of creatinine. This process can be inhibited by OCT2 substrates such as the chemotherapeutic drug cisplatin. Therefore, treatment with such agents may compromise the usefulness of creatinine as a marker of renal function in cancer patients.

新規腎機能マーカーシスタチンCを応用した抗MRSA薬の投与設計

An accurate estimate of the renal function is necessary for the precise therapeutic drug monitoring of anti-MRSA drugs such as vancomycin, arbekacin and teicoplanin, which are eliminated by the kidneys. In clinical practice, the measurement of endogenous serum substances in order to estimate the glomerular filtration rate (GFR) is commonly performed, and the serum creatinine concentration has become the most commonly used serum marker of renal function. However, the serum creatinine concentration is affected by age and gender. As a result, the measurement of serum creatinine concentration can lead to an overestimation of GFR, especially in the elderly. In recent years, it has been reported that the serum cystatin C concentration is not influenced by gender or age, so serum cystatin C concentration is a better marker of renal function than serum creatinine concentration. A recent meta-analysis demonstrated that the serum cystatin C concentration was a better renal function marker for detecting the GFR than the conventional measurement of the serum creatinine concentration, and several formula using the cystatin C concentration have also recently been reported to accurately estimate GFR. Recent studies have reported that the serum cystatin C concentration is a better marker of the clearance of drugs eliminated by the kidneys than the serum creatinine concentration. In this article, we review the application of cystatin C in the drug administration plan of anti-MRSA drugs.