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Objective: To study the adverse maternal and perinatal outcomes in women with severe pre-eclampsia (SPE) among different ranges of proteinuria., Methods: This prospective cohort study was conducted in Jawaharlal Institute of Postgraduate Medical Education and Research, India. After obtaining informed written consent, the 202 singleton women fulfilling the criteria of severe features of pre-eclampsia were stratified based on the value of urine protein-creatinine ratio (UPCR) as mild, moderate, severe, and massive proteinuria during pregnancy. Clinical outcomes were assessed and patients were followed up until 12 weeks postpartum to identify persistent proteinuria and hypertension., Results: Of the 202 women with SPE, adverse maternal outcomes were seen in 34.65% (n = 70) and adverse perinatal outcomes in 75.74% (n = 153). The demographic and clinical factors were similar among women with increasing severity of proteinuria, except for mean systolic blood pressure, serum creatinine and total serum protein. UPCR was found to have a significant correlation with composite adverse perinatal outcome (P < 0.001) and individual outcomes of neonatal intensive care unit admission for >48 h (P = 0.01) and neonatal sepsis (P = 0.02) but not adverse maternal outcomes (P = 0.201). The optimum UPCR cutoff for adverse perinatal outcomes was 1.6 (sensitivity, 73.2%; specificity, 52.7%). In addition, 14.85% of the women had a persistently elevated UPCR and 3.96% had hypertension at 3 months postpartum., Conclusion: In women with SPE, severe and massive proteinuria were related to composite adverse perinatal outcome but not composite adverse maternal outcome. Moreover, antenatal 24-h proteinuria was significantly associated with persistent proteinuria. Significant proteinuria in women with SPE poses a risk for chronic renal dysfunction, requiring follow-up., (© 2023 International Federation of Gynecology and Obstetrics.)

Background: Low muscle mass has been correlated with adverse outcomes in patients who are critically ill. Methods to identify low muscularity such as computed tomography scans or bioelectrical impedance analyses are impractical for admission screening. Urinary creatinine excretion (UCE) and creatinine height index (CHI) are associated with muscularity and outcomes but require a 24-h urine collection. The estimation of UCE from patient variables avoids the need for a 24-h urine collection and may be clinically useful., Methods: Variables of age, height, weight, sex, plasma creatinine, blood urea nitrogen (BUN), glucose, sodium, potassium, chloride, and carbon dioxide from a deidentified data set of 967 patients who had UCE measured were used to develop models to predict UCE. The model identified with the best predictive ability was validated and then retrospectively applied to a separate sample of 120 veterans who were critically ill to examine if UCE and CHI predicted malnutrition or were associated with outcomes., Results: A model was identified that included variables of plasma creatinine, BUN, age, and weight and was found to be highly correlated, moderately predictive of UCE, and statistically significant. Patients with model-estimated CHI  ≤  60% had significantly lower body weight, body mass index, plasma creatinine, and sera albumin and prealbumin levels; were 8.0 times more likely to be diagnosed with malnutrition; and were 2.6 times more likely to be readmitted in 6 months., Conclusion: A model that predicts UCE offers a novel method to identify patients with low muscularity and malnutrition on admission without the use of invasive tests., (© 2023 American Society for Parenteral and Enteral Nutrition. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Although sodium-glucose cotransporter 2 (SGLT2) inhibitors lower serum uric acid, their long-term effect on uric acid metabolism is not well understood. We analyzed pooled data from studies wherein patients with type 2 diabetes mellitus received luseogliflozin, an SGLT2 inhibitor. Upon stratifying patients by baseline glycated hemoglobin (HbA 1c ) or serum uric acid, lower HbA 1c or higher serum uric acid level was associated with a greater reduction in serum uric acid after treatment. At week 12 of treatment, significant increases in urinary glucose/creatinine (Cr) ratio and urinary uric acid clearance/Cr clearance ratio (C UA /C Cr ratio) and a significant reduction in serum uric acid were observed. Comparison of the subgroups of patients with a reduction or an increase in serum uric acid showed that the increase subgroup had a higher estimated glomerular filtration rate (eGFR) at baseline, and the eGFR was significantly reduced, associated with a significant reduction in the C UA /C Cr ratio. Multiple regression analysis showed that the reduction in serum uric acid in the luseogliflozin group was strongly associated with baseline high serum uric acid, low HbA 1c levels, and an increase in eGFR. Luseogliflozin was shown to reduce serum uric acid by enhancing urinary uric acid excretion in association with increased urinary glucose. Treatment with luseogliflozin resulted in increased serum uric acid in some patients, which may be due to reduced glomerular filtration of uric acid via the tubuloglomerular feedback. SGLT2 inhibitors reduced serum uric acid desirably in patients with type 2 diabetes mellitus with low HbA 1c and high serum uric acid., (© 2021 The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)

Background: The urine protein/creatinine ratio (UPCR) is commonly used in current clinical practice. However, there are only few published clinical data on UPCR from large cohorts of Chinese adults. This study aimed to determine the overall and age- and sex-specific UPCR reference values for healthy Dalian adults., Methods: According to the Clinical & Laboratory Standards Institute EP28-A3c guidelines, 1321 healthy Dalian adults (646 men and 675 women) aged 20-69 years were enrolled. Urine protein and creatinine levels were analyzed in the random morning spot urine samples, and UPCR was calculated. The 95th percentile of the UPCR was used as the normal upper limit. The Mann-Whitney U test was used to test differences among groups., Results: The UPCR reference value was 141.7 mg/g for the entire cohort, 128.7 mg/g for men, and 150.8 mg/g for women. In addition, women had relatively higher UPCR values than men in the same age group. We also compared the UPCR reference values between different estimated glomerular filtration rate (eGFR) groups and found that women had significantly higher UPCR values than men in the normal eGFR groups., Conclusions: This study provides the overall and age- and sex-specific UPCR reference values for healthy Dalian adults., (© 2021 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Background: Urinary oxalate can provide important clues for the screening and monitoring of children with primary hyperoxaluria (PH), which is a potentially life-threatening condition. However, little effort has been devoted to improve the oxalate assay in recent years. We have proposed a reliable and cost-effective high-performance liquid chromatography (HPLC) method for urinary oxalate determination., Methods: Urine specimens were centrifuged after one-step derivatization, and the supernatants were subjected to HPLC analysis., Results: The method was validated with consistent linearity from 0.0625 to 2.0 mmol/L with coefficients of variation ≤7.73%, good recovery, low carryover, satisfactory sample stability, and analytical specificity. The lower limit of quantification and the limit of detection were 0.03130 and 0.0156 mmol/L, respectively. Imprecision values were ≤2.92% and ≤16.6% for externally and internally produced controls, respectively. The pediatric reference interval of spot urinary oxalate to creatinine ratios was established together with its application in screening of PH in patients with renal diseases, revealing its successful deployment in our laboratory., Conclusions: This reliable HPLC method could serve as a significant tool to determine urinary oxalate levels for screening and monitoring of children with PH in routine clinical laboratories., (© 2021 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Objective: To assess the changes of spot urinary sodium and potassium and blood pressure (BP) throughout pregnancy and their correlations in southern Thailand., Methods: A longitudinal study was conducted in southern Thailand from March 2018 to November 2019. Spot urinary excretion of sodium per creatinine (U[Na + ]/[Cr]), potassium per creatinine (U[K + ]/[Cr]) and U[Na + ]/[K + ] ratios, and BP were measured at four time points throughout pregnancy. A one-way analysis of variance with repeated measures and Bonferroni correction with post hoc analysis was used to identify significant differences between time points. The correlations were measured using Pearson's correlation coefficients., Results: A total of 327 pregnant women were included. Both systolic and diastolic BPs decreased gradually from up to 14 weeks of pregnancy to 18-22 weeks and then increased until 30-34 weeks. Mean spot U[Na + ]/[Cr] ratios did not significantly change during the study period. Mean spot U[K + ]/[Cr] ratios gradually increased, and spot U[Na + ]/[K + ] ratios gradually decreased. The correlation of spot U[Na + ]/[Cr] and U[K + ]/[Cr] ratios with BPs was weakly negative at all four time points., Conclusions: Spot U[Na + ]/[Cr] and U[K + ]/[Cr] ratios are inversely correlated with BPs; weak correlations are found among pregnant women in southern Thailand. Further research in different populations is required to confirm its correlation and broader use., (© 2020 International Federation of Gynecology and Obstetrics.)

Creatinine is an important diagnostic marker and is also used as a standardization tool for the quantitative evaluation of exogenous/endogenous substances in urine. This study aimed at evaluating and comparing three analytical approaches, based on hyphenations of different separation [two-dimensional capillary isotachophoresis (CITP-CITP), capillary zone electrophoresis (CZE), ultra-high-performance liquid chromatography (UHPLC)] and detection [conductivity (CD), ultraviolet (UV), tandem mass spectrometry (MS/MS)] techniques, for their ability to provide reliable clinical data along with their suitability for the routine clinical use (cost, simplicity, sample throughput). The developed UHPLC-MS/MS, CITP-CITP-CD, and CZE-UV methods were characterized by favorable performance parameters, such as linearity (r ˃ 0.99), precision (relative standard deviation, 0.22-2.97% for the creatinine position in analytical profiles), and recovery (87.1-115.1%). Clinical data, obtained from the analysis of 24 human urine samples by a reference enzymatic method, were comparable with those obtained by the tested methods (Passing-Bablok regression and Bland-Altman analysis), approving their usefulness for the routine clinical use. In this context, the UHPLC-MS/MS method provides benefits of enhanced orthogonality/accuracy and high sample throughput (threefold shorter total analysis times than the CE methods), whereas advantages of the CE methods for routine labs are simplicity and low cost of both the instrumentation and measurements., (© 2020 John Wiley & Sons, Ltd.)

Purpose: In this study, we evaluated the renal protective effects of montelukast (MLK) against ionizing radiation (IR) induced nephrotoxicity in mice., Materials and Methods: Radioprotective effects of MLK were assessed by biochemical analysis including measurements of kidney malondialdehyde (MDA), reduced glutathione (GSH), and serum creatinine and urea levels. Besides, for further evaluation of protective effects of MLK on renal system, 99m Tc-dimercaptosuccinic acid (DMSA) has been applied. The total antioxidant capacity of MLK was measured by using 1,1-diphenyl-2-picryl hydrazyl radical reagents and compared with butylated hydroxyl toluene standard antioxidant., Results: The biochemical evaluation revealed that better results have been achieved for the groups administered with MLK than the only radiation group. Besides only IR-treated mice group, those treated with MLK demonstrated a significant decrease in urea and creatinine levels. Statistically, significant differences of MDA and SHG levels (P < .05) were found between the radiation group and MLK plus IR-treated group. Also, 99m Tc-DMSA kidney uptake value (%ID/g) was observed lower for MLK plus IR-treated mice group than only radiation-treated mice group., Conclusions: According to our findings, MLK has a potential role to be used as a renal protective agent against gamma radiation in radiotherapy., (© 2020 Wiley Periodicals, Inc.)

Oxidative stress induced by long-term cyclosporine A (CsA) administration is a major cause of chronic nephrotoxicity, which is characterized by tubular atrophy, tubular cell apoptosis, and interstitial fibrosis in the progression of organ transplantation. Although hydrogen-rich water (HRW) has been used to prevent various oxidative stress-related diseases, its underlying mechanisms remain unclear. This study investigated the effects of HRW on CsA-induced nephrotoxicity and its potential mechanisms. After administration of CsA (25 mg/kg/day), rats were treated with or without HRW (12 mL/kg) for 4 weeks. Renal function and vascular activity were investigated. Histological changes in kidney tissues were analyzed using Masson's trichrome and terminal deoxynucleotidyl transferase dUTP nick-end labeling stains. Oxidative stress markers and the activation of the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway were also measured. We found that CsA increased the levels of reactive oxygen species (ROS) and malonaldehyde (MDA), but it reduced glutathione (GSH) and superoxide dismutase (SOD) levels. Such alterations induced vascular dysfunction, tubular atrophy, interstitial fibrosis, and tubular apoptosis. This was evident secondary to an increase in urinary protein, serum creatinine, and blood urea nitrogen, ultimately leading to renal dysfunction. Conversely, HRW decreased levels of ROS and MDA while increasing the activity of GSH and SOD. This was accompanied by an improvement in vascular and renal function. Moreover, HRW significantly decreased the level of Keap1 and increased the expression of Nrf2, NADPH dehydrogenase quinone 1, and heme oxygenase 1. In conclusion, HRW restored the balance of redox status, suppressed oxidative stress damage, and improved kidney function induced by CsA via activation of the Keap1/Nrf2 signaling pathway., (© 2020 Wiley Periodicals, Inc.)

Objective: To determine the diagnostic accuracy and optimal threshold of the spot protein-to-creatinine ratio (PCR) compared to the gold standard, 24-hour proteinuria (24HP) in patients with suspected pre-eclampsia., Methods: A prospective observational study was performed from June 2015 to May 2017 consisting of patients hospitalized for suspected pre-eclampsia in a tertiary care referral center. To compare the two diagnostic tests, a spot urine sample was obtained to perform the PCR before starting the collection of the 24HP. Only patients who had both tests were analyzed., Results: In total, 148 patients (216 samples) were included. The two tests were highly correlated (r=0.80, P<0.001). The receiver operating characteristic curve analysis and the area under the curve (AUC=0.92) highlighted the accuracy of PCR in diagnosing significant proteinuria and thus pre-eclampsia. The optimal cut-off using the Liu method was 56.9 mg/mmol (sensitivity=79.3%, specificity=91.5%)., Conclusion: The results suggest that PCR could replace 24HP when diagnosing proteinuria in pre-eclampsia. Moreover, it is a simple test, easy to realize and standardize, and cheap with no need for systematic hospitalization. The best cut-off should be chosen by thinking about the risks for adverse maternal and/or fetal outcomes. The test may help to optimize medical care in pre-eclampsia worldwide., (© 2019 International Federation of Gynecology and Obstetrics.)

Objectives: The aim of the study was to assess the effect of tenofovir alafenamide (TAF) on kidney and bone biomarkers in patients who developed proximal renal tubulopathy (PRT) while receiving tenofovir disoproxil fumarate (TDF)., Methods: Individuals with a history of TDF-associated PRT and currently suppressed HIV infection on a tenofovir-sparing regimen were randomized 1:1 to continue current antiretroviral therapy or initiate emtricitabine (F)/TAF with discontinuation of nucleoside reverse transcriptase inhibitors (NRTIs) as appropriate. Renal and bone biomarkers were analysed at baseline, week 4 and week 12. The primary outcome was the mean difference between study arms in urine retinol-binding protein:creatinine ratio (RBPCR) change from baseline to week 12. Data were analysed using linear regression, with robust standard errors (primary outcome), and repeated measures mixed effects models (secondary outcomes). The trial was registered under European Union Drug Regulating Authorities Clinical Trials Database 2016-003345-29., Results: We randomized 31 individuals [mean age 52.4 (standard deviation 0.3) years; 97% male; 90% white); all completed the study. At 12 weeks, there was no difference in change in RBPCR (β 19.6; 95% confidence interval -35.3, 74.5; P = 0.47), and no difference in change in estimated glomerular filtration rate (eGFR) (based on creatinine or cystatin C), albuminuria, proteinuria, renal phosphate or urea handling, (fasting) urine osmolality, parathyroid hormone and bone turnover markers in the control versus the F/TAF exposed groups. No cases of PRT were observed., Conclusions: In people with a history of proximal renal tubulopathy while on TDF, 12-week exposure to TAF did not adversely affect renal tubular function. These data support continued evaluation of the long-term safety of TAF in this group of patients., (© 2019 British HIV Association.)

Relebactam is a small-molecule β-lactamase inhibitor developed as a fixed-dose combination with imipenem/cilastatin. The pharmacokinetics of relebactam and imipenem across 10 clinical studies were analyzed using data from adult healthy volunteers and patients with bacterial infections. Renal function estimated by creatinine clearance significantly affected the clearance of both compounds, whereas weight and health status were of less clinical significance. Simulations were used to calculate probability of joint target attainment (ratio of free drug area under the curve from 0 to 24 hours to minimum inhibitory concentration (MIC) for relebactam and percentage of time the free drug concentration exceeded the MIC for imipenem) for the proposed imipenem/relebactam dose of 500/250 mg, with adjustments for patients with renal impairment, administered as a 30-minute intravenous infusion four times daily. These dosing regimens provide sufficient antibacterial coverage (MIC ≤ 4 μg/mL) for all renal groups., (© 2019 Merck Sharp & Dohme Corp. a subsidiary of Merck & Co. Inc. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics.)

Mammalian targets of rapamycin inhibitors (mTORIs), including sirolimus and everolimus, are used for minimizing calcineurin inhibitors after liver transplantation. However, head-to-head randomized comparisons of these 2 mTORIs are lacking. We assessed the differences in renoprotection and possible mechanisms between sirolimus and everolimus in liver transplant recipients. For this prospective cohort study, we recruited liver transplant recipients whose regimens were switched from tacrolimus to sirolimus or everolimus at a Taiwan medical center. Serial changes in estimated glomerular filtration rate (eGFR), urinary N-acetyl-β-D-glucosaminidase, neutrophil gelatinase-associated lipocalin, 8-hydroxy-2'-deoxyguanosine, and transforming growth factor-β1 during 1 year after mTORI conversion were compared within and between groups. In the 61 patients analyzed, no significant change in eGFR occurred within 12 months after conversion in both mTORI groups. Among patients with baseline eGFR <60 mL/min/1.73 m 2 , eGFR improved at 6 months and 1 year after conversion (+12.3 and +12.0 mL/min/1.73 m 2 , both P < .05). Urinary N-acetyl-β-D-glucosaminidase decreased in both sirolimus and everolimus groups at 6 months (-68.7 ± 137.6 and -62.0 ± 92.4 U/g creatinine, both P < .05), and the reduction of urinary neutrophil gelatinase-associated lipocalin was significant in the sirolimus group (-4345.1 ± 7763.5 ng/g creatinine; P < .05). Neither transforming growth factor-β1 nor 8-hydroxy-2´-deoxyguanosine changed significantly. In conclusion, the renoprotective effect of mTORI conversion was significant in liver transplant recipients with renal insufficiency, which was similar for sirolimus and everolimus, in the first year and may be associated with ameliorated tubular injury. Available evidence remains insufficient to determine which mTORI conversion therapy is more effective in renoprotection in the long run., (© 2018, The American College of Clinical Pharmacology.)

Background: Preterm infants are at risk of oxidative stress from neonatal intensive care interventions. 8-Oxo-2'-deoxyguanosine (8-oxodG), generated by oxygen radical attack on DNA, is a potential marker of oxidative stress. The aim of the present study was to investigate the impact of quality and source of enteral nutrition (EN) on renal excretion of 8-oxodG in preterm infants., Methods: Spontaneous urine samples were collected on postnatal days 26-31 in 33 preterm infants. Infants were fed either breast milk (BM), formula (FM), or BM/FM mixtures. Daily iron (Fe) supplementation was started day 28 ± 1 postnatally. 8-oxodG was determined by highperformance liquid chromatography-electrochemical detection (HPLC-EC)., Results: The 8-oxodG/creatinine ratio was significantly higher in infants fed FM vs FM/BM (38.7 ± 28.7 vs 16.7 ± 12.2 nmol 8-oxodG/mmol creatinine, P < 0.0001) or BM (11.6 ± 10.4 nmol 8-oxodG/mmol creatinine, P < 0.0001). There was no significant effect of Fe supplementation (P = 0.547). 8-OxodG excretion showed significant interindividual variation but was similar within pairs of twins., Conclusion: Quality and source of EN seem to influence oxidative stress in preterm infants. The underlying pathophysiological mechanism is unclear and needs further investigation. It may be speculated that other mechanisms than Fe supplementation contribute to oxidative stress, such as cow's milk protein-mediated up-regulation of the intestinal inflammatory cascade., (© 2018 American Society for Parenteral and Enteral Nutrition.)

Background: IgA nephropathy (IgAN) is the most frequent primary glomerular disease and the leading cause of end-stage renal disease. We investigated clinicopathologic predictors of renal survival in patients with IgAN with a focus on glomerular filtration rate (GFR) decline slope., Materials and Methods: We screened all patients with primary IgAN between 1995 and 2012. Renal progression was defined as doubling of serum creatinine. Using serial serum creatinine levels during the first-year, we calculated the GFR decline slopes. Further, we defined patients in the steepest GFR slope quartile as rapid decliners and those in the second steepest GFR slope quartile as slow decliners. Others were defined as nondecliners., Results: Of 214 participants, baseline GFR was 81 (62, 100) mL/min/1.73 m 2 , which was not different among the 3 groups. Rapid decliners and slow decliners had higher levels of urinary protein/creatinine ratio (0.88, 0.89 and 0.58 g/gCr, respectively, P < .001). Five-year renal survival was 76% in rapid decliners, 91% in slow decliners and 100% in nondecliners (P < .001, rapid or slow decliners vs nondecliners). After adjustment for clinicopathologic variables, slow decliners were associated with an 8.8-fold higher risk of progression (P = .011), and rapid decliners were associated with a 10.2-fold increased risk of progression (P = .007) compared with nondecliners., Conclusions: First-year GFR slope was associated with increased risk of renal progression, independent of proteinuria and histologic findings. Further studies are needed to investigate whether early GFR change can identify high-risk patients who benefit from immunosuppressive treatment in IgAN., (© 2018 Stichting European Society for Clinical Investigation Journal Foundation.)

A population pharmacokinetic (PopPK) model of lenalidomide was developed using data pooled from 13 clinical studies (dose range, 5-400 mg) in participants who were considered to have adequate capability for renal excretion of lenalidomide (creatinine clearance [CrCl] > 50 mL/min). The analysis population included 305 healthy volunteers and 83 patients with multiple myeloma or myelodysplastic syndromes. A 1-compartment model with linear absorption and elimination described well the observed data for both healthy volunteers and patients. Covariate analysis suggested lenalidomide apparent clearance was positively correlated with CrCl, and lenalidomide volume of distribution was positively correlated with body weight. Both pharmacokinetic parameters were reduced by 29% in patients, independent of the effect of CrCl or body weight. Despite their statistical significance, effects of study population and body weight are considered clinically unimportant in adult patients with CrCl > 50 mL. After accounting for the above effects, body weight had no significant effect on CL/F, whereas age, sex, race, and mild hepatic impairment had no significant effect on either lenalidomide parameter. The PopPK model should be useful for future modeling of lenalidomide pharmacokinetics in the pediatric population and for further comparison of pharmacokinetic properties among structurally similar immunomodulatory drugs., (© 2017, The American College of Clinical Pharmacology.)

Introduction: The replacement of 24-h urine collection by protein-creatinine ratio (PCR) for the diagnosis of preeclampsia has been recently recommended. However, the literature is conflicting and there are concerns about the impact of demographic characteristics on the performance of PCR., Material and Methods: This was an implementation audit of the introduction of PCR in a London Tertiary obstetric unit. The performance of PCR in the prediction of proteinuria ≥300 mg/day was assessed in 476 women with suspected preeclampsia who completed a 24-h urine collection and an untimed urine sample for PCR calculation. Multivariate logistic regression was used to assess the independent predictors of significant proteinuria., Results: In a pregnant population, ethnicity and PCR are the main predictors of ≥300 mg proteinuria in a 24-h urine collection. A PCR cut-off of 30 mg/mmol would have incorrectly classified as non-proteinuric, 41.4% and 22.9% of black and non-black women, respectively. Sensitivity of 100% is achieved at cut-offs of 8.67 and 20.56 mg/mmol for black and non-black women, respectively. Applying these levels as a screening tool to inform the need to perform a 24-h urine collection in 1000 women, would lead to a financial saving of €2911 in non-black women and to an additional cost of €3269 in black women., Conclusions: Our data suggest that a move from screening for proteinuria with a 24-h urine collection to screening with urine PCR is not appropriate for black populations. However, the move may lead to cost-saving if used in the white population with a PCR cut-off of 20.5., (© 2018 Nordic Federation of Societies of Obstetrics and Gynecology.)

Objective: The prevalence of nonalcoholic fatty liver disease (NAFLD) has been rapidly increased, becoming a public health problem worldwide. Our objective was to investigate the association between urine retinol-binding protein (RBP) and NAFLD in a Chinese population and develop a multivariate logistic regression model for NAFLD prediction., Methods: A total of 317 NAFLD patients and 391 healthy controls were enrolled in this cross-sectional study based on inclusion and exclusion criteria, from whom fasting urine and blood were collected for further study. Urine RBP level and other parameters were measured and compared between NAFLD subjects and controls., Results: Urine RBP levels (expressed by RBP/creatinine ratio) in NAFLD patients were significantly higher than controls (median 133.1 mg/g vs 110.7 mg/g; P < .001). Urine RBP/creatinine ratio was verified as an independent factor for NAFLD prediction after adjustment in multivariate logistic regression. The area under curve (AUC) of receiver operating characteristic (ROC) was 0.889 with the 95% confidence interval from 0.867 to 0.912.With a cutoff point of 0.215, the sensitivity and specificity of urine RBP/creatinine ratio in NAFLD prediction were 81.1% and 84.5%, respectively., Conclusion: Our results demonstrated that urine RBP/creatinine ratio was an independent risk factor for NAFLD while the predictive model for NAFLD diagnosis is noninvasive with high sensitivity and specificity., (© 2017 Wiley Periodicals, Inc.)

Background: The urine albumin/creatinine ratio (ACR) test is used to screen patients with chronic diseases, such as diabetes, hypertension and cardiovascular diseases that put them at an increased risk of developing kidney disease. Here, we evaluated the performance of the URiSCAN 2 ACR Strip (URiSCAN; YD diagnostics, Yongin, Korea), a semiquantitative point-of-care testing (POCT) assay, and we compared to an existing POCT assay and a quantitative assay., Materials and Methods: A total of 1,020 random urine specimens were analyzed using the semiquantitative URiSCAN 2 ACR Strip and semiquantitative CLINITEK Microalbumin 2 Strip (CLINITEK; Siemens, New York, USA). We evaluated the precision of the URiSCAN 2 ACR Strip and compared the results of the ACR obtained from URiSCAN to those of CLINITEK with the quantitative results of a quantitative assay as a reference., Results: The precision evaluation of the URiSCAN revealed a range between the cutoff (C 50 )-20% and C 50 +20% bounds, the C 5 -C 95 interval, with 85.8% confidence. URiSCAN and CLINITEK showed sensitivity and specificity of 87.7% and 72.2%, and 90.2% and 83.0%, respectively. The concordance rates of URiSCAN with CLINITEK and the quantitative assay were 75.6% and 79.1%, respectively. The concordance rate in the abnormal range (≥30 mg/g) between URiSCAN and the quantitative assay were higher than that between CLINITEK and the quantitative assay (78.8% vs 75.4%)., Conclusions: URiSCAN showed good precision and comparable sensitivity with lower specificity than those of CLINITEK., (© 2017 Wiley Periodicals, Inc.)

Objective: The aim of this study was to explore the possible influences of age and gender on urinary Alpha 1-Microglobulin (α1-MG) concentrations and establish specific reference values of urinary α1-MG in a group of healthy adults., Methods: Two hundred and ninety-nine adults (141 males and 158 females) aged 20-60 were selected and grouped by gender and age. Urinary levels of α1-MG were detected in morning spot-urine samples, and statistical analysis was performed to explore the association between urinary α1-MG and clinical parameters, and the differences between groups were compared. The 95th percentile of distribution was used as the normal upper limit., Results: The value of urinary α1-MG was sex-dependent (P<0.001), the 95th percentile of urinary α1-MG of males was 26.4 mg/L, whereas females was 8.6 mg/L. Whereas urinary α1-microglobulin-to-creatinine ratio (α1-MG/Cr) was both gender-and age-dependent (both P<0.001), and age 30 may be the cut-off point in this study. The 95th percentile of males and females aged 20-30 was 16.9 mg/g, of males aged 31-60 was 19.8 mg/g, of females aged 31-60 was 28.5 mg/g., Discussions: The relationship between urinary α1-MG concentrations and gender, age is different from previous studies. It is recommended that hospitals and laboratories should develop their own α1-MG reference intervals based on their experimental conditions., (© 2017 Wiley Periodicals, Inc.)

Background: We used the 15 N glycine urinary end-product enrichment technique to quantify whole body protein turnover following thoracic surgery., Materials and Methods: A single dose of 15 N glycine (2 mg/kg) was administered orally on postoperative day 1 to children (1-18 years) following thoracic surgery. 15 N enrichment of ammonia and urea was measured in mixed urine after 12 and 24 hours, respectively, and protein synthesis, breakdown, and net balance determined. Nitrogen balance (dietary intake minus urinary excretion) was calculated. Urinary 3-methylhistidine:creatinine ratio was measured as a marker of skeletal muscle protein breakdown., Results: We enrolled 19 subjects-median (interquartile range): age, 13.8 years (12.2-15.1); weight, 49.2 kg (38.4-60.8)-who underwent thoracotomy (n = 12) or thoracoscopic (n = 7) surgery. Protein synthesis and breakdown by 15 N enrichment were 7.1 (5.5-9) and 7.1 (5.6-9) g·kg -1 ·d -1 with ammonia (12 hours) as the end product, and 5.8 (3.8-6.7) and 6.7 (4.5-7.6) with urea (24 hours), respectively. Net protein balance by the 15 N glycine and urinary urea nitrogen methods were -0.34 (-0.47, -0.3) and -0.48 (-0.65, -0.28) g·kg -1 ·d -1 , respectively (r s = 0.828, P < .001). Postoperative change in 3-methylhistidine:creatinine ratio did not correlate significantly with protein breakdown or balance., Conclusion: The single-dose oral administration of 15 N glycine stable isotope with measurement of urinary end-product enrichment is a feasible and noninvasive method to investigate whole body protein turnover in children. After major surgery, children manifest increased protein turnover and net negative balance due to increased protein breakdown., (© 2016 American Society for Parenteral and Enteral Nutrition.)

Background: The aim of this study is to evaluate and compare the analytical performance characteristics of the two creatinine methods based on the Jaffe and enzymatic methods., Methods: Two original creatinine methods, Jaffe and enzymatic, were evaluated on Architect c16000 automated analyzer via limit of detection (LOD) and limit of quantitation (LOQ), linearity, intra-assay and inter-assay precision, and comparability in serum and urine samples. The method comparison and bias estimation using patient samples according to CLSI guideline were performed on 230 serum and 141 urine samples by analyzing on the same auto-analyzer., Results: The LODs were determined as 0.1 mg/dL for both serum methods and as 0.25 and 0.07 mg/dL for the Jaffe and the enzymatic urine method respectively. The LOQs were similar with 0.05 mg/dL value for both serum methods, and enzymatic urine method had a lower LOQ than Jaffe urine method, values at 0.5 and 2 mg/dL respectively. Both methods were linear up to 65 mg/dL for serum and 260 mg/dL for urine. The intra-assay and inter-assay precision data were under desirable levels in both methods. The higher correlations were determined between two methods in serum and urine (r=.9994, r=.9998 respectively). On the other hand, Jaffe method gave the higher creatinine results than enzymatic method, especially at the low concentrations in both serum and urine., Conclusions: Both Jaffe and enzymatic methods were found to meet the analytical performance requirements in routine use. However, enzymatic method was found to have better performance in low creatinine levels., (© 2017 Wiley Periodicals, Inc.)

Lead (Pb) is an environmental pollutant associated with several diseases, such as nephrotoxicity. Methylglyoxal (MG) is a reactive dicarbonyl compound formed during glycolysis and reported to increase in kidney damage. Metformin is used as an MG scavenger in the clinic. In this study, we investigated the mechanism of Pb-induced renal injury and the effect of metformin on Pb-induced nephrotoxicity. Eighteen Wistar rats were randomly divided into three groups: control, Pb, and Pb + metformin groups. Pb (250 ppm) was administered in drinking water, and 50 mg/kg of metformin was co-administered orally. After 28 days, the levels of MG and its metabolite d-lactate in urine, serum and renal tissues were examined. The elevation of renal MG (56.86 ± 17.47 vs 36.40 ± 5.69, p < 0.01) and urinary d-lactate (0.68 ± 0.28 vs 0.32 ± 0.13, p < 0.01) was observed in Pb-exposed rats compared with those in control rats. After co-treatment with metformin, these phenomena were attenuated. In the present study, it was demonstrated for the first time that urinary d-lactate might serve as the candidate marker for Pb-induced nephrotoxicity in the clinic, and metformin might be a new therapeutic candidate for Pb poisoning., (Copyright © 2016 John Wiley & Sons, Ltd.)

Introduction: The aim of this study was to determine the prognostic value of the first urinary albumin/creatinine ratio (ACR) for adverse maternal and neonatal outcomes and how it relates to other prognostic factors., Material and Methods: We performed a retrospective cohort study from December 2009 to February 2012 with analysis of demographic, clinical and biochemical data from two obstetric day assessment units in hospitals in Southeast Scotland. We included 717 pregnant women, with singleton pregnancies after 20 weeks' gestation, referred for evaluation of suspected preeclampsia and having their first ACR performed. The ability of ACR to predict future outcomes was assessed in both univariable and multivariable logistic regression models. The latter assessed its prognostic value independent of (adjusting for) existing prognostic factors. Primary outcome measures were maternal and neonatal composite adverse outcomes, and a secondary outcome was gestation at delivery., Results: In all, 204 women (28.5%) experienced a composite adverse maternal outcome and 146 women (20.4%) experienced a composite adverse neonatal outcome. Multivariate analysis of log-transformed ACR demonstrated that a 1-unit increase in log ACR is associated with an increased odds of adverse maternal [odds ratio 1.60, 95% confidence interval (CI) 1.45-1.80] and adverse neonatal (odds ratio 1.15, 95% CI 1.02-1.29) composite outcomes, and with reduced gestational age at delivery (coefficient: -0.46, 95% CI -0.54 to -0.38)., Conclusions: ACR is an independent prognostic factor for maternal and neonatal adverse outcomes in suspected preeclampsia. ACR may be useful to inform risk predictions within a prognostic model., (© 2017 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Background: A persistent hypermetabolic state delays anabolism and growth in burned children. However, our own clinical experience has been that resting energy expenditure (REE) is not increased during the rehabilitative phase, suggesting other contributing factors. We measured total energy expenditure (TEE) and its components in rehabilitating pediatric burn patients to identify the basis for accelerated energy metabolism in this population., Materials and Methods: Children admitted with initial burns of 20% of their total body surface area (TBSA) or greater were enrolled into this prospective, descriptive study. TEE was measured using the doubly labeled water method over a 7-day period. During that period, REE was measured on 2 days by indirect calorimetry. Activity energy expenditure (AEE) was assessed using a physical activity monitoring device for a 24-hour period. TEE and REE were compared with sex-specific, age-matched, and weight-matched norms using the Dietary Reference Intakes (DRI) standards., Results: Ten children with an average burn size of 53.7% ± 20% (range, 27%-82%) of TBSA completed this study. Their mean age and weight were 10.4 ± 5.5 years and 35.8 ± 16.4 kg, respectively. Daily TEE averaged 66 kcal/kg and was 1.08% of reference DRI. REE was 92% ± 25% of predicted basal metabolic rate, not exceeding 120% as a maximum value in any child., Conclusions: TEE and REE in rehabilitating burn children are comparable to reference standards. Increased REE was not typical in our population, but measures of AEE were commonly high.

Background: Netrin-1 is a diagnostic biomarker that has been identified recently for chronic renal failure (CRF) in animal experiments. Netrin-1 levels in urine have been shown to have increased significantly at the acute kidney damage. Human studies on the relation between the CRF and plasma netrin-1 levels have not been found in the literature. This study aimed to investigate whether plasma netrin-1 levels increased in the early stages of the CRF in diabetic patients., Methods: Plasma samples from healthy volunteers and diabetic patients with and without microalbuminuria were collected after receiving consent. Netrin-1 in plasma was quantified by enzyme-linked immunosorbent assay and the data were analyzed to determine whether plasma netrin-1 correlates significantly with disease progression., Result: Plasma netrin-1 level in microalbuminuric diabetic patients was significantly higher than in normoalbuminuric diabetic patients and the control group. However, no significant difference between normoalbuminuric patients and control group was determined. Plasma netrin-1 level was significantly associated with albuminuria and estimated glomerular filtration rate, independently of age and sex., Conclusion: This study supports that plasma netrin-1 level increases significantly when glomerular damage occurs in diabetic nephropathy., (© 2016 Wiley Periodicals, Inc.)

Introduction: Some pregnant women develop significant proteinuria in the absence of hypertension. However, clinical significance of isolated gestational proteinuria (IGP) is not well understood. This study aimed to determine the prevalence of IGP in singleton pregnancies and the proportion of women with IGP who subsequently developed preeclampsia (IGP-PE) among all PE cases., Material and Methods: This was an observational study of 6819 women with singleton pregnancies at 12 centers, including 938 women with at least once determination of protein-to-creatinine ratio (P/Cr). Significant proteinuria in pregnancy (SPIP) was defined as P/Cr (mg/mg) level >0.27. IGP was defined as SPIP in the absence of hypertension. Gestational hypertension (GH) preceding preeclampsia (GH-PE) was defined as preeclampsia (PE) in which GH preceded SPIP. Simultaneous PE (S-PE) was defined as PE in which both SPIP and hypertension occurred simultaneously., Results: IGP and PE were diagnosed in 130 (1.9%) and 158 (2.3%) of 6819 women, respectively. Of 130 women with IGP, 32 (25%) progressed to PE and accounted for 20% of all women with PE. Hence, women with IGP had a relative risk of 13.1 (95% CI; 9.2-18.5) for developing PE compared with those without IGP [25% (32/130) vs. 1.9% (126/6689)]. At diagnosis of SPIP, P/Cr levels already exceeded 1.0 more often in women with S-PE than in those with IGP-PE [67% (33/49) vs. 44% (14/32), respectively, p = 0.031]., Conclusions: IGP is a risk factor for PE, and IGP-PE accounts for a considerable proportion (20%) of all PE., (© 2016 Nordic Federation of Societies of Obstetrics and Gynecology.)

Background: Prolidase is a cytosolic exopeptidase that plays a pivotal role in collagen turnover. Diabetic nephropathy (DN) is associated with structural changes in glomerular basement membrane accompanied with increased amounts of collagen. Prolidase is known to be abundant in kidney and collagen accumulation is increased in DN, so we aimed to determine the value of serum prolidase activity (SPA) in predicting the progression of nephropathy in type 2 diabetes mellitus (DM)., Methods: Thirty type 2 DM patients having microalbuminuria (microalbuminuric group), 30 type 2 DM patients without albuminuria (normoalbuminuric group), and 28 healthy controls (control group) were enrolled. Study groups had similar age, sex distribution, and body mass index (BMI)., Results: Metabolic parameters, SPA and urinary microalbumin were determined. SPA was significantly higher in microalbuminuric group when compared with normoalbuminuric and control groups (P = 0.05 and P < 0.001, respectively). Triglyceride levels were significantly higher and high density lipoprotein cholesterol (HDL-C) levels were significantly lower in microalbuminuric group compared to control group (Both P < 0.05). SPA showed a negative correlation with HDL-C level and a positive correlation with urinary albumin excretion (r = -0.219, P < 0.05 and r = 0.39, P < 0.001 respectively). In regression analysis, albumin excretion was the sole parameter influencing SPA., Conclusion: SPA appears to be higher in type 2 DM patients having microalbuminuria compared to patients without microalbuminuria and healthy controls. The pathophysiological role and the significance of SPA in predicting DN need to be further evaluated., (© 2015 Wiley Periodicals, Inc.)

Objective: To evaluate the accuracy of protein measurement and protein-to-creatinine ratio (PCR) in 4-, 8-, and 12-h urine samples as compared with 24-h urine samples as the gold standard method for suspected pre-eclampsia., Methods: In a prospective study, 120 women at more than 20weeks of pregnancy with high blood pressure and no history of hypertension were enrolled between April 2010 and December 2012. Net protein excretion and PCR were evaluated in urine samples collected over 4h, 8h, 12h (day), and 12h (night) and compared with 24-h protein excretion as the gold standard test., Results: A significant positive correlation was found between the values of the 4-h, 8-h, 12-h (day), and 12-h (night) samples and the 24-h samples. The best cutoff point of the PCR to detect significant urine protein excretion was 0.28, 0.24, 0.25, and 0.23 for the 4-h, 8-h, 12-h (day), and 12-h (night) samples, respectively., Conclusion: Measurement of protein and PCR in 4-h, 8-h, and 12-h urine samples might provide an alternative test for detecting proteinuria among pregnant women with suspected pre-eclampsia when there is insufficient time to collect 24-h urine samples., (Copyright © 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.)

Background: Albumin/creatinine ratio (ACR) from a first morning urine is recommended as a early indicator for diabetic nephropathy. However, it is not always feasible to collect the first morning urine for outpatients. We aimed to explore whether ACR from a second morning urine had a good consistency with that from a first morning urine to predict albuminuria in Chinese elderly citizens., Method: One hundred and ninety-one elderly citizens (≧60 years old) from Junliangcheng community, Dongli district, Tianjin, China were included. A first and second morning urine was collected from each participants, successfully and detected the urinary albumin and creatinine of each urine sample. Albumin to creatinine ratio from a first morning urine (ACR1) was compared with that from a second morning urine (ACR2), and the ability of ACR1 and ACR2 to predict albuminuria was assessed., Result: ACR1 and ACR2 were highly correlated (r = 0.901), especially in male and hypertension group (r = 0.938 and 0.904). The slope and intercept were 0.93 and 0.11 after log-transformed. And there was no statistical difference between values of ACR1 and ACR2 (P = 0.271). Overall, 26.2% participants were detected with albuminuria when judged by ACR1 and 28.3% by ACR2. A good concordance of ACR category (normal or albuminuria) was found between ACR1 and ACR2 (Kappa value = 0.815 in overall; in male and hypertension group were 0.900 and 0.850)., Conclusion: A second morning urine ACR could be the alternative to a first morning urine ACR for albuminuria detection in elderly population., (© 2015 Wiley Periodicals, Inc.)

Continuous infusion of meropenem is a candidate strategy for optimization of its pharmacokinetic/pharmacodynamic profile. However, plasma concentrations are difficult to predict in critically ill patients. Steady-state concentrations of meropenem were determined prospectively during continuous infusion in 32 surgical ICU patients (aged 21-85 years, body weight 55-125 kg, APACHE II 5-29, measured creatinine clearance 22.7-297 mL/min). Urine was collected for the quantification of renal clearance of meropenem and creatinine. Cystatin C was measured as an additional marker of renal function. Population pharmacokinetic models were developed using NONMEM(®) , which described total meropenem clearance and its relationship with several estimates of renal function (measured creatinine clearance CLCR , Cockcroft-Gault formula CLCG , Hoek formula, 1/plasma creatinine, 1/plasma cystatin C) and other patient characteristics. Any estimate of renal function improved the model performance. The strongest association of clearance was found with CLCR (typical clearance = 11.3 L/h × [1 + 0.00932 × (CLCR  - 80 mL/min)]), followed by 1/plasma cystatin C; CLCG was the least predictive covariate. Neither age, weight, nor sex was found to be significant. These models can be used to predict dosing requirements or meropenem concentrations during continuous infusion. The covariate CLCR offers the best predictive performance; if not available, cystatin C may provide a promising alternative to plasma creatinine., (© 2015, The American College of Clinical Pharmacology.)

Despite several introduced preventive modalities, cisplatin nephrotoxicity remains a clinical problem. Some in vitro and in vivo studies have addressed the protective effects of silymarin against cisplatin nephrotoxicity. This study evaluated the effects of silymarin administration on cisplatin nephrotoxicity as the first human study. During this pilot, randomized, double-blinded, placebo-controlled clinical trial, the effect of oral silymarin 420 mg daily in three divided doses starting 24-48 h before the initiation of cisplatin infusion and continuing to the end of three 21-day cisplatin-containing chemotherapy courses on cisplatin-induced renal electrolytes wasting and kidney function were assessed. Cisplatin-associated acute kidney injury (AKI) occurred in 8% of the patients. Urine neutrophil gelatinase-associated lipocalin to urine creatinine ratio (NGAL/Cr) and urinary magnesium and potassium wasting increased significantly after cisplatin infusion in both groups. Significant positive correlation was found between cumulative dose of cisplatin and urine NGAL/Cr after three courses of cisplatin infusion. Incidence of AKI and the magnitude of urinary magnesium and potassium wasting did not differ between silymarin and placebo groups. No adverse reaction was reported by silymarin administration. Prophylactic administration of conventional form of silymarin tablets could not prevent cisplatin-induced urine electrolyte wasting or renal function impairment., (Copyright © 2015 John Wiley & Sons, Ltd.)

Background: Inflammation is implicated in many adverse health conditions, and recent interest has focused on the effects of chronic low-grade inflammation in generally healthy populations. Cytokines measured in plasma or serum are commonly used as biomarkers of systemic levels of inflammation. Measurement of cytokines in urine may offer a simpler and less invasive alternative, although the degree to which levels of cytokines correlate in plasma and urine among healthy individuals is unknown., Materials and Methods: We assessed the correlation of blood and urine levels of 13 cytokines, including interleukin (IL)-1b, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12(p70) and IL-13, granulocyte macrophage colony-stimulating factor, interferon gamma and tumour necrosis factor alpha in 61 healthy women aged 18-30. Cytokine concentrations were considered with and without correction for creatinine., Results: Plasma and urine levels of the 13 cytokines were not significantly correlated using measured urinary cytokine concentrations and after adjustment for creatinine. Correlation coefficients for log-transformed cytokine concentrations in paired plasma and urine specimens ranged from -0.28 to 0.087., Conclusions: These results suggest that urine has limited utility as a proxy for plasma for the measurement of inflammatory factors in a healthy population with low levels of inflammation., (© 2015 Stichting European Society for Clinical Investigation Journal Foundation.)

To explore the correlation between urinary protein:creatinine ratio and 24-h excretion of protein, we studied 149 women referred to a day assessment unit for investigations for suspected preeclampsia. Paired samples were obtained for measurement of urinary protein:creatinine ratio and 24-h protein excretion. Collection of a 24-h urine sample was validated by the daily creatinine excretion. The outcome measure was proteinuria of 300 mg/day or more. Inaccurate 24-h collection was observed in 17% of women. All women (n = 56) with a protein:creatinine ratio >60 mg/mM had significant proteinuria. No woman with protein:creatinine ratio <18 mg/mM (n = 20) had significant proteinuria. We recommend that a dual cut-off should be used for excluding and "ruling in" the diagnosis of significant proteinuria. A 24-h urine collection should be used only for urinary protein:creatinine ratio values between 18 and 60 mg/mM in the detection of significant proteinuria., (© 2015 Nordic Federation of Societies of Obstetrics and Gynecology.)

Serelaxin, a recombinant form of the human relaxin-2 hormone, is currently under clinical investigation for treatment of acute heart failure. This double-blind, placebo-controlled, dose-ranging study investigated the effect of Japanese ethnicity on the pharmacokinetics (PK), pharmacodynamics (PD), and safety and tolerability of serelaxin. Japanese healthy subjects (n = 32) received 10, 30, or 100 µg/kg/day of serelaxin, or placebo, administered as a 48-hour intravenous infusion. A Caucasian cohort (n = 8) receiving 30 µg/kg/day open-label serelaxin was included for comparison. In all subjects, serum serelaxin concentrations increased rapidly after the start of infusion, approached steady state as early as 4 hours, and declined rapidly upon treatment cessation. Serum exposure to serelaxin increased with increasing doses. Statistical dose proportionality was shown for AUC(inf) over the entire dose range. A significant increase in estimated glomerular filtration rate from baseline to Day 2 (30 and 100 µg/kg/day) and to Day 3 (10 and 100 µg/kg/day) was observed compared with placebo. Serelaxin was well tolerated by all subjects. In conclusion, PK, PD, and safety profiles of serelaxin were generally comparable between Japanese and Caucasian subjects, suggesting that no dose adjustment will be required in Japanese subjects during routine clinical use of this agent., (© 2015, The American College of Clinical Pharmacology.)

Background: Measurement of serum creatinine (SCr) and urine creatinine (UCr) is regularly used in clinical and research settings. For small animal experiments and for studies in which sample collection is spare (i.e. neonatal cohorts), measuring SCr and UCr using tiny amounts of sample (as low as 10 mcl) would maximize exploration and minimize iatrogenic blood loss., Methods: We performed an evaluation in six healthy adults to determine differences between SCr and UCr values in different methodologies and storage environments and time. Study was conducted using 20 mcl of sample. Analyses were done using two-way repeated measures of ANOVA., Results: Scr values showed no significant differences between LC/MS vs. Jaffe. However, the SCr using LC/MS method was lowest when measured immediately compared to other time points (F = 7.2; P< 0.001). Similarly, Jaffe measurements showed changes in the mean differences over time; however, these were not significant. UCr values were consistently higher using LC/MS than Jaffe (F = 19; P< 0.01), and UCr changed over time (F = 8.7; P < 0.02). In addition, the interaction term for method and time was also significant (F = 5.8; P < 0.04) which reflects the stability of the Jaffe measurements over time whereas the LC/MS measurements declined; especially after being frozen for 1 year (P < 0.001)., Conclusion: UCr measured by Jaffe is lower than samples measured by LC/MS. UCr measurements by LC/MS vary more over time, mostly due to the sample measured after 1 year; therefore, storage of urine for more than 90 days measured by LC/MS may provide altered results., (© 2014 Wiley Periodicals, Inc.)