Methods For Creatinine Measurement Research Articles

Development of a simple HPLC method for the determination of urinary O-aminohippuric acid (OAH) and an establishment of OAH reference interval

Background: O-aminohippuric acid (OAH) is considered a low-abundance urinary fluorescent metabolite with the potential to be an innovative lung cancer biomarker. There is a lack of simple methods for measuring urinary OAH metabolite, and the measurement needs to be normalized by urinary creatinine, which is produced at a constant rate. Thus, the newly developed method must be able to determine urinary creatinine and OAH simultaneously in the same run. Objective: This work aimed to develop and validate a simple high-performance liquid chromatography (HPLC) method for measuring urinary OAH and to establish the reference intervals of OAH in healthy individuals. Materials and methods: We synthesized OAH standard in a simple route and optimized simple HPLC method for simultaneous measurement of creatinine and OAH in a single run. Analysis was performed on a RP-C18 column with a gradient elution system of acetonitrile - ammonium acetate buffer (pH 6.5, 100 mM). After implementing optimal conditions, the procedure was compiled according to the International Council for Harmonisation (ICH) validation parameters. The developed method was used for the establishment of reference intervals of a total of 120 random urine samples of healthy individuals. Results: The linear range of the calibration curve for creatinine and OAH were 1-1000 µg/mL and 0.1-100 µg/mL, respectively. The recoveries ranged for both metabolites were between 91.35 % and 109.12%. The relative standard deviations (RSDs) for the intra-day and inter-day results ranged from 0.11-0.66 % to 0.16-1.73 %, respectively. The limits of detection (LOD) and quantification (LOQ) were 0.258 µg/mL and 0.783 µg/mL for creatinine, while OAH was 0.045 µg/mL and 0.137 µg/mL, respectively. The method was successfully applied to establish reference intervals of OAH in healthy individuals and was defined as 0.420-2.287 mmol/mol creatinine. Conclusion: According to various validated parameters, the proposed method was proven to quantify urinary OAH and creatinine in a single run. It can also be analyzed noninvasively without additional sample processing. Reported herein is the first establishment of OAH reference intervals in healthy individuals, which may benefit the utilization of OAH as a noninvasive biomarker for lung cancer detection in the future.

Comparative Evaluation of Creatinine Interferences by Glucose in Various Dialysates Based on Creatinine Measurement Methods

Comparative Evaluation of Creatinine Interferences by Glucose in Various Dialysates Based on Creatinine Measurement Methods

Comparing Jaffe and Enzymatic Methods for Creatinine Measurement at Various Icterus Levels and Their Impacts on Liver Transplant Allocation.

The Model for End-Stage Liver Disease (MELD) scoring system is used to prioritize liver transplantations and assess disease severity. This includes the international normalized ratio (INR), creatinine, and total bilirubin. Since there are several ways to measure creatinine, MELD scores can produce inconsistent results. The objectives of this study were to define a valid cut-off for bilirubin interference in creatinine measurement and to assess the effects of various icteric levels on creatinine measurement and liver transplant allocation. A total of 400 serum samples were categorized into four groups based on their icteric indices and total bilirubin levels, including non-, mild, moderate, and severe icteric samples. Both chemical Jaffe and enzymatic techniques were used to determine the creatinine levels in all four groups, and the findings were compared. In parallel, serum samples from 83 liver transplant candidate patients were divided into three groups depending on their bilirubin levels and then similarly evaluated and interpreted. The MELD scores were then computed for each group and compared. In icteric samples, the enzymatic method produced higher results for the creatinine concentrations than the Jaffe method did, and the mean creatinine difference rose from 0.08 in nonicteric group to 1.95 in groups with severe icterus. In addition, the enzymatic approach yielded higher findings for creatinine and subsequently for MELD scores in patients who were liver transplant candidates. When the bilirubin concentration was above the 4 mg/dL threshold, there were differences between the approaches for both the creatinine and the MELD score (p values: 0.0001 and 0.027, respectively). The chemical Jaffe is a readily available and considerably cost-effective method for measuring creatinine. However, it is influenced by a variety of known and unknown interfering substances, and it should be applied cautiously when working with icteric samples. Alternate techniques such as the enzymatic method should be considered when the bilirubin level exceeds 4 mg/dL. Though this cut-off is instrument and kit-dependent, each laboratory is advised to have its cut-off for bilirubin interference.

Artificially raised creatinine concentrations due to analytical interference for samples contaminated with total parenteral nutrition fluid.

A sample received in the laboratory from a patient receiving total parenteral nutrition (TPN) indicated that the patient may have renal dysfunction, but the results were not considered to be reliable enough to report. Investigations using a reference method for measurement of creatinine confirmed positive interference in the creatinine assay and distribution of samples via an External Quality Assessment (EQA) Scheme showed that this positive interference was method dependent. Residual TPN fluid (Nutriflex Lipid Special) left in the bag after the patient had completed the infusion was collected and added to a patient serum pool in increasing amounts and distributed to different laboratories for analysis of creatinine and glucose through an EQA Scheme. Positive interference in a number of different creatinine assays was identified as a result of a component in the TPN fluid. Positive interference from high concentrations of glucose has been demonstrated to be a cause for falsely high results in Jaffe creatinine assays. The concern would be that a sample contaminated with TPN fluid would have both abnormal electrolytes and creatinine concentrations and give the impression that the patient was in renal failure due to analytical interference in the creatinine assay and laboratory staff need to be aware of this problem.

N-Acetylcysteine Interference With Creatinine Measurement: An In Vitro Analysis

N-Acetylcysteine Interference With Creatinine Measurement: An In Vitro Analysis

CamGFR v2: A New Model for Estimating the Glomerular Filtration Rate from Standardized or Non-standardized Creatinine in Patients with Cancer.

Management of patients with cancer, specifically carboplatin dosing, requires accurate knowledge of glomerular filtration rate (GFR). Direct measurement of GFR is resource limited. Available models for estimated GFR (eGFR) are optimized for patients without cancer and either isotope dilution mass spectrometry (IDMS)- or non-IDMS-standardized creatinine measurements. We present an eGFR model for patients with cancer compatible with both creatinine measurement methods. GFR measurements, biometrics, and IDMS- or non-IDMS-standardized creatinine values were collected for adult patients from three cancer centers. Using statistical modeling, an IDMS and non-IDMS creatinine-compatible eGFR model (CamGFR v2) was developed. Its performance was compared with that of the existing models Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Modification of Diet in Renal Disease (MDRD), Full Age Spectrum (FAS), Lund-Malmö revised, and CamGFR v1, using statistics for bias, precision, accuracy, and clinical robustness. A total of 3,083 IDMS- and 4,612 non-IDMS-standardized creatinine measurements were obtained from 7,240 patients. IDMS-standardized creatinine values were lower than non-IDMS-standardized values in within-center comparisons (13.8% lower in Cambridge; P < 0.0001 and 19.3% lower in Manchester; P < 0.0001), and more consistent between centers. CamGFR v2 was the most accurate [root-mean-squared error for IDMS, 14.97 mL/minute (95% confidence interval, 13.84-16.13) and non-IDMS, 15.74 mL/minute (14.86-16.63)], most clinically robust [proportion with >20% error of calculated carboplatin dose for IDMS, 0.12 (0.09-0.14) and non-IDMS, 0.17 (0.15-0.2)], and least biased [median residual for IDMS, 0.73 mL/minute (-0.68 to 2.2) and non-IDMS, -0.43 mL/minute (-1.48 to 0.91)] eGFR model, particularly when eGFR was larger than 60 ml/minute. CamGFR v2 can utilize IDMS- and non-IDMS-standardized creatinine measurements and outperforms previous models. CamGFR v2 should be examined prospectively as a practice-changing standard of care for eGFR-based carboplatin dosing.

Rapid Quantification of Plasma Creatinine Using a Novel Kinetic Enzymatic Assay.

Enzymatic assays are among the most common diagnostic tests performed in the clinical laboratory. Enzymatic substrate analysis is most commonly measured using endpoint methods; however, modulating the reaction kinetics allows fine control of the reaction rate, which can be adjusted based on specific monitoring technologies. We developed and optimized an enzymatic method for measurement of creatinine in plasma, using commonly paired enzymes of creatininase (Crtnnase), creatinase (Crtase), sarcosine oxidase (SOX), ascorbate oxidase (AOX), and horseradish peroxidase (HRP). The novel aspect of the assay is that it is fast and uses SOX as the limiting enzyme. The assay performance was assessed with respect to precision, accuracy, and interferences. The intrarun %CV (n = 12) was approximately 5% for each concentration tested, with biases ranging from -3 to -9%. The interrun %CV (n = 39) ranged from 5 to 8%, with biases ranging from -2 to -6%. During the accuracy assessment (n = 127), only 4 samples did not meet the minimum acceptability criteria. Minimal interference was observed, except at low creatinine concentrations with elevated creatine. Our novel and versatile enzymatic assay to measure plasma creatinine using kinetic analysis with SOX as the limiting enzyme is rapid (<2 mins), sensitive, and specific and demonstrates excellent concordance with the laboratory standard. We anticipate this rapid kinetic assay to be compatible with emerging technologies in the field of portable diagnostic devices, such as the usage of silicon photonics to monitor biochemical reactions.

Comparison of glomerular filtration rate estimation using Jaffé and enzymatic creatinine assays in diabetic patients.

Diabetic kidney disease (DKD) develops an end-stage renal failure and is a major cause of death in diabetic patients. A GFR below 60ml/min per 1.73m2 is one of the main markers of DKD. Therefore, the development of an accurate test for diagnosis and monitoring of the mentioned disease would be essential. Here, we examined the impacts of two different kits with different methods for creatinine measurement on the GFR values. Blood samples were collected from 80 diabetic patients referring to the clinical laboratory. The levels of serum creatinine were assessed using Jaffé and enzymatic assays by kits from two different manufacturers. Then to assess the eGFR levels, the MDRD equation was used. Further descriptive parameters of both methods and correlation of methods were also calculated. Descriptive analysis of the data demonstrates a slight increase in the serum creatinine measured by Jaffé assay which leads to a substantial decrease in the levels of eGFR compared to the eGFR calculated by the enzymatic assay. Moreover, eGFR over 60mL/min/1.73 m 2 in enzymatic assay was observed in 27.5% of participants while eGFR of the same participants was below 60mL/min/1.73m 2 when it was measured by Jaffé method. Consequently, 27.5% positive discordant cases were reported by Jaffé assay followed by misclassifying them as DKD patients compared with the enzymatic assay. While using Jaffé assay, a low level of eGFR is observed which generates more misclassification into the DKD group and demands to an inclusive consideration by physicians in order to diagnose and monitor the DKD patients.

Methods and reporting of kidney function: a systematic review of studies from sub-Saharan Africa.

Globally, chronic kidney disease (CKD) is an emerging public health challenge but accurate data on its true prevalence are scarce, particularly in poorly resourced regions such as sub-Saharan Africa (SSA). Limited funding for population-based studies, poor laboratory infrastructure and the absence of a validated estimating equation for kidney function in Africans are contributing factors. Consequently, most available studies used to estimate population prevalence are hospital-based, with small samples of participants who are at high risk for kidney disease. While serum creatinine is most commonly used to estimate glomerular filtration, there is considerable potential bias in the measurement of creatinine that might lead to inaccurate estimates of kidney disease at individual and population level. To address this, the Laboratory Working Group of the National Kidney Disease Education Program published recommendations in 2006 to standardize the laboratory measurement of creatinine. The primary objective of this review was to appraise implementation of these recommendations in studies conducted in SSA after 2006. Secondary objectives were to assess bias relating to choice of estimating equations for assessing glomerular function in Africans and to evaluate use of recommended diagnostic criteria for CKD. This study was registered with Prospero (CRD42017068151), and using PubMed, African Journals Online and Web of Science, 5845 abstracts were reviewed and 252 full-text articles included for narrative analysis. Overall, two-thirds of studies did not report laboratory methods for creatinine measurement and just over 80% did not report whether their creatinine measurement was isotope dilution mass spectroscopy (IDMS) traceable. For those reporting a method, Jaffe was the most common (93%). The four-variable Modification of Diet in Renal Disease (4-v MDRD) equation was most frequently used (42%), followed by the CKD Epidemiology Collaboration (CKD-EPI) equation for creatinine (26%). For the 4-v MDRD equation and CKD-EPI equations, respectively, one-third to one half of studies clarified use of the coefficient for African-American (AA) ethnicity. When reporting CKD prevalence, <15% of studies fulfilled Kidney Disease: Improving Global Outcomes criteria and even fewer used a population-based sample. Six studies compared performance of estimating equations to measured glomerular filtration rate (GFR) demonstrating that coefficients for AA ethnicity used in the 4-v MDRD and the CKD-EPI equations overestimated GFR in Africans. To improve on reporting in future studies, we propose an ‘easy to use’ checklist that will standardize reporting of kidney function and improve the quality of studies in the region. This research contributes some understanding of the factors requiring attention to ensure accurate assessment of the burden of kidney disease in SSA. Many of these factors are difficult to address and extend beyond individual researchers to health systems and governmental policy, but understanding the burden of kidney disease is a critical first step to informing an integrated public health response that would provide appropriate screening, prevention and management of kidney disease in countries from SSA. This is particularly relevant as CKD is a common pathway in both infectious and non-communicable diseases, and multimorbidity is now commonplace, and even more so when those living with severe kidney disease have limited or no access to renal replacement therapy.

A Reflex Protocol for Creatinine Testing Reduces Costs and Maintains Patient Safety.

The Jaffe and enzymatic methods are the 2 most common methods for creatinine measurement. The Jaffe method is less expensive but subject to interferences. Some laboratory scientists have called for the Jaffe method to be retired. To determine the most cost-effective and safe protocol for creatinine measurement. We performed a retrospective database review of all outpatient creatinine measurements for 1 year, testing the risk-based reflex testing protocol we had implemented for creatinine measurement. Samples were first measured using the Jaffe method and were reflexed to the enzymatic method if the estimated glomerular filtration rate (eGFR) was between 55 and 65 mL per min per 1.73 m2. There were 104,530 creatinine measurements, of which 11,420 (10.9%) were reflexed to the enzymatic method. The Jaffe method had a positive bias of 0.08 mg per dL (-6.14 mL/min/1.73 m2 eGFR). A total of 3.4% of the paired reflexed specimens were discordant. Also, 133 (1.2%) of the Jaffe results were classified as false negatives and 3411 (29.9%) were classified as false positives. None of the false-negative results and 5 of the false-positive results were considered clinically significant. Using the reflex protocol saved approximately $40,000 per year. The reflex protocol for creatinine measurement can reduce costs with acceptable risk.

Challenges in the measurement of plasma creatinine on the Roche cobas c702

The aim of this study was to document the differences between two Roche creatinine measurement methods, the CREP2 test on the cobas c702 and the CREA PLUS test on the Modular P. Samples with creatinine isotope dilution mass spectrometry (IDMS) values were analyzed on both instruments. Method comparison using the remaining plasma samples was performed twice, using two different lot numbers of reagents and two different lot numbers of calibrators on both instruments. Medians and percentiles of the plasma creatinine values produced on the Modular P and cobas c702 from 2012 to 2017 were compared. The recovery of samples with IDMS creatinine values (SRM 967a level 1, SRM 967a level 2, serum X and five serum pools from Roche) was 101.7%–110.2% on the cobas c702 and 98.9%–102.6% on the Modular P. Comparison of the two methods showed that the slope was close to 1.0 using linear, Deming and Passing Bablok regressions, but all equations showed a negative intercept, indicating that the cobas c702 overestimates plasma creatinine in relation to the Modular P by 4–6 µmol/L. The median value for routine plasma creatinine lies between 74 and 77 µmol/L for the Modular P and 81 µmol/L for the cobas c702. After the cobas c702 was factorized in September 2016, the median plasma creatinine value decreased to 75 µmol/L. In conclusion, the CREP2 method on the cobas c702 overestimates creatinine by 4–6 μmol/L, which has a significant influence on the estimated glomerular filtration rate (eGFR) in children.

A validated LC-MS/MS method for the quantitative measurement of creatinine as an endogenous biomarker in human plasma.

Creatinine is an endogenous compound generated from creatine by normal muscular metabolism. It is an important indicator of renal function and the serum level is routinely monitored in clinical labs. Results & methodology: Surrogate analyte (d3-creatinine) was used for calibration standard and quality control preparation and the relative instrument response ratio between creatinine and d3-creatinine was used to calculate the endogenous creatinine concentrations. A fit-for-purpose strategy of using a surrogate analyte and authentic matrix was adopted for this validation. The assay was the first human plasma assay using such strategy and was successfully applied to a clinical study to confirm a transient elevation of creatinine observed using an existing clinical assay.

40 years of paediatric chemical pathology – a personal view

My career in paediatric Chemical Pathology began in the early 1970s at the Royal Children's Hospital, Melbourne, and I retired from the Children's Hospital at Westmead in 2014. During that time, I have witnessed many advances in the field. Firstly, instrumentation has improved considerably, so that sample volumes have become much smaller. Centrifugal analysers were introduced in the 1970s, followed soon after in the 1980s by dry chemistry, which was particularly useful in paediatrics. In the 1990s, mass spectrometry became a powerful tool in paediatric biochemistry, especially in the diagnosis of inborn errors of metabolism. Specific methods have also improved, particularly with the almost universal use of enzymatic methods for creatinine measurement. Perhaps the greatest advances in paediatric biochemistry over the last 40 years have been in newborn screening, associated with the introduction of tandem mass spectrometry. Point of care testing has also shown great improvements, and more accurate paediatric reference intervals are now available. Blood collecting has shown advances over time, but the trauma of blood collection in babies remains. To maintain excellence in paediatric Chemical Pathology, pathologists in training should be encouraged to enter this field. My career in paediatric Chemical Pathology began in the early 1970s at the Royal Children's Hospital, Melbourne, and I retired from the Children's Hospital at Westmead in 2014. During that time, I have witnessed many advances in the field. Firstly, instrumentation has improved considerably, so that sample volumes have become much smaller. Centrifugal analysers were introduced in the 1970s, followed soon after in the 1980s by dry chemistry, which was particularly useful in paediatrics. In the 1990s, mass spectrometry became a powerful tool in paediatric biochemistry, especially in the diagnosis of inborn errors of metabolism. Specific methods have also improved, particularly with the almost universal use of enzymatic methods for creatinine measurement. Perhaps the greatest advances in paediatric biochemistry over the last 40 years have been in newborn screening, associated with the introduction of tandem mass spectrometry. Point of care testing has also shown great improvements, and more accurate paediatric reference intervals are now available. Blood collecting has shown advances over time, but the trauma of blood collection in babies remains. To maintain excellence in paediatric Chemical Pathology, pathologists in training should be encouraged to enter this field.

Impact of Different Creatinine Measurement Methods on Liver Transplant Allocation

IntroductionThe model for end-stage liver disease (MELD) score is used in many countries to prioritize organ allocation for the majority of patients who require orthotopic liver transplantation. This score is calculated based on the following laboratory parameters: creatinine, bilirubin and the international normalized ratio (INR). Consequently, high measurement accuracy is essential for equitable and fair organ allocation. For serum creatinine measurements, the Jaffé method and enzymatic detection are well-established routine diagnostic tests.MethodsA total of 1,013 samples from 445 patients on the waiting list or in evaluation for liver transplantation were measured using both creatinine methods from November 2012 to September 2013 at the university hospital Leipzig, Germany. The measurements were performed in parallel according to the manufacturer’s instructions after the samples arrived at the institute of laboratory medicine. Patients who had required renal replacement therapy twice in the previous week were excluded from analyses.ResultsDespite the good correlation between the results of both creatinine quantification methods, relevant differences were observed, which led to different MELD scores. The Jaffé measurement led to greater MELD score in 163/1,013 (16.1%) samples with differences of up to 4 points in one patient, whereas differences of up to 2 points were identified in 15/1,013 (1.5%) samples using the enzymatic assay. Overall, 50/152 (32.9%) patients with MELD scores >20 had higher scores when the Jaffé method was used.DiscussionUsing the Jaffé method to measure creatinine levels in samples from patients who require liver transplantation may lead to a systematic preference in organ allocation. In this study, the differences were particularly pronounced in samples with MELD scores >20, which has clinical relevance in the context of urgency of transplantation. These data suggest that official recommendations are needed to determine which laboratory diagnostic methods should be used when calculating MELD scores.

A regional survey of serum creatinine measurement methods and estimated glomerular filtration rate reporting

Only limited data are available on the diffusion of isotope dilution mass spectrometry (IDMS)-traceable methods used for serum creatinine measurement and on estimated glomerular filtration rate (eGFR) reporting. A questionnaire was addressed to accredited laboratories in Lombardy, Italy, including the following issues: method of creatinine measurement, instrument model, IDMS calibration traceability, reference intervals reported by sex and age, eGFR reporting, eGFR formula used and information about the eGFR value reported in patient records. A parallel questionnaire was addressed to nephrology centers and included the following: knowledge of methods for serum creatinine measurement in their center, usefulness of eGRF reporting and opinions on the need for educational initiatives. Seventy-two percent of 72 laboratories and 89% of 47 nephrology centers responded to the questionnaires. Among the methods used for serum creatinine measurement, 87% were IDMS traceable and 30% were enzymatic. Reference intervals were differentiated by sex and by age in 90% and 42%, respectively. Laboratories reported eGFR in 35% and only when requested in 13%. eGFR was calculated by the Modification of Diet in Renal Disease (MDRD) Study and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations in 88% and 12% of laboratories, respectively, and reporting was accompanied by information on the interpretation of values in 62%. Among nephrologists, 64% thought eGFR reporting useful, 29% were concerned with an excess of unnecessary requests for consultations and 95% expressed a favorable opinion of educational initiatives. Our survey highlights the need for further improvement in serum creatinine measurement and reporting, and for coordinated interventions involving all major stakeholders.

Limitations of compensated Jaffe creatinine assays in cirrhotic patients

This study aimed to evaluate the impact of two creatinine measurement methods on the Model for End Stage Liver Disease (MELD) score and glomerular filtration rate estimation (eGFR) in cirrhotic patients. We focused on ID-MS traceable method such as compensated Jaffe (cJafCreat) and enzymatic (EnzCreat) methods. Potential protein-related interferences in creatinine determination were evaluated using dialysates spiked with albumin. MELD score, CKD-EPI formula creatinine-based eGFR and cystatin C-based eGFR were evaluated in 100 cirrhotic patients. In vitro model demonstrated that low protein levels result in an underestimation of creatinine levels using cJafCreat. In patients, cJafCreat created a negative bias of -6.1 μmol/L that led to higher eGFR and lower MELD scores. cJafCreat contributes to an overestimation of renal function in cirrhotic patients and may alter cirrhosis-severity assessment. Compensated Jaffe assays should therefore be replaced by enzymatic methods.

Level of renal function in patients starting dialysis: an ERA-EDTA Registry study

The aims of this European study were (i) to compare the level of renal function at the start of dialysis between age groups, gender, primary renal disease, comorbid conditions, treatment modality, time periods and countries, and (ii) to determine which baseline characteristics are associated with the level of renal function at the start of dialysis. Renal registries participating in the European Renal Association-European Dialysis and Transplant Association Registry provided data on serum creatinine 0-4 weeks before the start of dialysis in incident dialysis patients in 1999 and 2003. Data were available in 11 472 patients from nine renal registries. Glomerular filtration rate (GFR) was estimated by the four-variable Modification of Diet in Renal Disease equation. The unadjusted median eGFR at the start of dialysis was 7.0 mL/min/1.73 m(2) in the 1999 data (median serum creatinine 7.5 mg/dL) and 7.7 mL/min/1.73 m(2) in the 2003 data (serum creatinine 7.0 mg/dL). Using linear regression with adjustment for the other covariates, older patients, males, patients with diabetes mellitus, hypertension/renal vascular disease (HT/RVD) as primary renal disease (vs glomerulonephritis), ischaemic heart disease or peripheral vascular disease and patients starting on peritoneal dialysis (PD) initiated dialysis at higher levels of eGFR (range Δ eGFR: 0.1-1.2 mL/min/1.73 m(2)). Using the same analyses, eGFR differed between countries (range: 6.5-8.6 mL/min/1.73 m(2)). During 2003, patients started dialysis at somewhat higher eGFR levels than those starting during 1999. There were also international differences in eGFR. Such differences may, at least in part, be explained by differences in creatinine measurement methods between countries and time periods. Finally, older patients, males, patients with HT/RVD or comorbidity and those starting on PD had slightly higher eGFR levels than younger patients, females, those with glomerulonephritis, without comorbidity and those starting on haemodialysis. Further research is needed into other, more clinically related factors affecting the decision to start dialysis.

The National Kidney Disease Education Program: Improving Understanding, Detection, and Management of CKD

The National Kidney Disease Education Program (NKDEP), an initiative of the National Institute of Diabetes and Digestive and Kidney Diseases, works to reduce the morbidity and mortality caused by chronic kidney disease (CKD) and its complications. Established in 2000, the NKDEP initially focused on increasing awareness in at-risk populations and helping the laboratory community recalibrate serum creatinine measurement methods and begin using a revised equation to estimate glomerular filtration rate. Expanding its focus in recent years, the NKDEP now works to improve provider practices by collaborating with health systems, community health centers, and professional associations to encourage testing and treatment of patients. Among its top priorities is to develop such resources as clinical encounter tools, patient education aids, and training programs that help primary care professionals better identify and care for patients with CKD. Other priorities include improving the coordination of federal responses to CKD and addressing the standardization of measurement and reporting of urine albumin. Improving CKD detection and management is an important challenge. To succeed, the NKDEP must work in close partnership with the renal community, public health agencies, professional associations, and voluntary organizations that serve at-risk and patient communities.

Plasma creatinine and creatine quantification by capillary electrophoresis diode array detector

Traditional clinical assays for nonprotein nitrogen compounds, such as creatine and creatinine, have focused on the use of enzymes or chemical reactions that allow measurement of each analyte separately. Most of these assays are mainly directed to urine quantification, so that their applicability on plasma samples is frequently hard to perform. This work describes a simple free zone capillary electrophoresis method for the simultaneous measurement of creatinine and creatine in human plasma. The effect of analytical parameters such as concentration and pH of Tris–phosphate running buffer and cartridge temperature on resolution, migration times, peak areas, and efficiency was investigated. Good separation was achieved using a 60.2-cm × 75-μm uncoated silica capillary, 75 mmol/L Tris–phosphate buffer, pH 2.25, at 15 °C, in less than 8 min. We compared the present method to a validated capillary electrophoresis assay, by measuring plasma creatinine in 120 normal subjects. The obtained data were compared by the Passing–Bablok regression and the Bland–Altman test. Moreover the performance of the developed method was assessed by measuring creatine and creatinine in 16 volunteers prior to and after a moderate physical exercise.

Automated enzymatic methods for creatinine measurement with special attention to bilirubin interference.

Four enzymatic methods for creatinine measurement were evaluated on a DuPont Dimension automatic analyzer. Biomed Creatinine-Duo-UV (BIO) and Raichem Creatinine Reagent Enzymatic (RAI) start creatinine breakdown with creatinine iminohydrolase (EC 3.5.4.21) resulting in the formation of NH4+. The Boehringer Mannheim Creatinine PAP (BM1) and SopaChem Creatinine (SOP) start the breakdown of creatinine with creatininase (EC 3.5.2.10) which yields creatine. In order to reduce bilirubin interference, the BM1 method was modified to contain K4Fe(CN)6. This substance was added with reagent 1 (BM2) or with reagent 2 (BM3). All the enzymatic creatinine methods tested displayed good linearity for concentrations up to at least 1000 mumol/l. The BIO, BM3, RAI and SOP methods showed good stability of test outcome for the tested period of a week. The outcome of the BM1 and BM2 method increased continually with time. Only the results of the RAI method were diminished by the presence of lipids. The BM1, BM2, BM3 and SOP methods showed no interference with haemoglobin, whereas this increased the outcome of the BIO method and slightly decreased the results of the RAI method. Using spiked human albumin solutions it was found that the BIO, BM2, BM3 and RAI methods displayed good resistance to interference by bilirubin or ditauro-bilirubin. The outcome of the BM1 and SOP method was strongly decreased by both bilirubin and ditauro-bilirubin. When creatinine was measured in a panel of sera originating from 100 patients with bilirubin concentrations higher than 50 mumol/l, the obtained results were in close agreement with those found for the spiked human albumin solutions.(ABSTRACT TRUNCATED AT 250 WORDS)