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Background: Accurate assessment of kidney function is clinically important, but estimates of glomerular filtration rate (GFR) by regression are imprecise., Methods: We hypothesized that ensemble learning could improve precision. A total of 1419 participants were enrolled, with 1002 in the development dataset and 417 in the external validation dataset. GFR was independently estimated from age, sex and serum creatinine using an artificial neural network (ANN), support vector machine (SVM), regression, and ensemble learning. GFR was measured by 99mTc-DTPA renal dynamic imaging calibrated with dual plasma sample 99mTc-DTPA GFR., Results: Mean measured GFRs were 70.0 ml/min/1.73 m 2 in the developmental and 53.4 ml/min/1.73 m 2 in the external validation cohorts. In the external validation cohort, precision was better in the ensemble model of the ANN, SVM and regression equation (IQR = 13.5 ml/min/1.73 m 2 ) than in the new regression model (IQR = 14.0 ml/min/1.73 m 2 , P < 0.001). The precision of ensemble learning was the best of the three models, but the models had similar bias and accuracy. The median difference ranged from 2.3 to 3.7 ml/min/1.73 m 2 , 30% accuracy ranged from 73.1 to 76.0%, and P was > 0.05 for all comparisons of the new regression equation and the other new models., Conclusions: An ensemble learning model including three variables, the average ANN, SVM, and regression equation values, was more precise than the new regression model. A more complex ensemble learning strategy may further improve GFR estimates.

Pediatric AKI has become a significant health concern due to its rising incidence and association with adverse outcomes. Because of the limitations of serum creatinine, ongoing research has evaluated multiple novel biomarkers for the early detection of AKI. Identifying biomarkers that precede changes in serum creatinine is vital, because these biomarkers provide opportunities to improve outcomes through early diagnosis and timely disease management. In this review, we discuss salient findings on 16 candidate biomarkers and their association with AKI. We explore the differences in biomarker distribution by age and discuss why adult biomarker research findings cannot be directly extrapolated to children. With future research, more consideration needs to be given to how the maturing kidney affects biomarker levels and how we interpret biomarker performance in children. A comprehensive approach using age-specific biomarker reference ranges is required to develop pediatric biomarkers and improve outcomes for children with kidney disease., (Copyright © 2017 by the American Society of Nephrology.)

Background: In 2012, the international nephrology organization Kidney Disease Improving Global Outcomes (KDIGO) released recommendations for nephrology referral for chronic kidney disease (CKD) patients. The feasibility of adhering to these recommendations is unknown., Methods: We conducted a retrospective analysis of the primary care population at Brigham and Women's Hospital (BWH). We translated referral recommendations based upon serum creatinine, estimated glomerular filtration rate (eGFR), and albuminuria into a set of computable criteria in order to project referral volume if the KDIGO referral recommendations were to be implemented. Using electronic health record data, we evaluated each patient using the computable criteria at the times that the patient made clinic visits in 2013. We then compared the projected referral volume with baseline nephrology clinic volume., Results: Out of 56,461 primary care patients at BWH, we identified 5593 (9.9%) who had CKD based on albuminuria or estimated GFR. Referring patients identified by the computable criteria would have resulted in 2240 additional referrals to nephrology. In 2013, this would represent a 38.0% (2240/5892) increase in total nephrology patient volume and 67.3% (2240/3326) increase in new referral volume., Conclusions: This is the first study to examine the projected impact of implementing the 2012 KDIGO referral recommendations. Given the large increase in the number of referrals, this study is suggestive that implementing the KDIGO referral guidelines may not be feasible under current practice models due to a supply-demand mismatch. We need to consider new strategies on how to deliver optimal care to CKD patients using the available workforce in the U.S. health care system.

Determination of the protein composition of urine is a non-invasive method helping to diagnose renal lesions and evaluate therapeutic interventions. We present here five observations that highlight the performance and relevance of urine protein analysis combining selected glomerular and tubular protein measurements. Total urine protein level and measurements of urinary IgG, albumin, transferrin alpha-1 microglobulin and retinol binding protein were performed on a urine sample by immunonephelometry. The results were normalized for urine creatinine concentration and integrated in the MDI interpretation software that provides a "urine protein profile" (UPP). Sequential UPP were performed in two patients with drug-induced tubular toxicity. One resolved after drug withdrawal. The second concomitantly developped glomerular lesions and repeated UPP was warranted to follow evaluation of the distinct renal lesions. Two cases illustrate two distinct clinical situations in patients with multiple myeloma, respectively myeloma cast nephropathy and toxic acute tubular necrosis. Those differential diagnoses were early anticipated by UPP. In one case, UPP was in favour of the presence of large amount of urinary monoclonal light chain excretion before performing urine electrophoresis analysis and renal biopsy while this was not in the other case. In the last case, we compared sequential UPP, renal function and kidney biopsies in a patient with a diagnosis of membranous nephropathy, and demonstrated a good correlation between urine glomerular and tubular protein excretion and progression of the renal lesions. The use of the UPP in clinical practice, particularly through the accurate quantification of tubular markers, is a more efficient tool for the diagnosis and follow-up of renal diseases than the less sensitive semi-quantitative urine electrophoresis or combined assays of both total proteinuria and albuminuria.

The purpose of the present research was to establish reference intervals for renal function indexes (Cystatin C, Blood Urea Nitrogen Creatinine and Uric Acid) in pregnant women in China. Blood samples were collected from 203 healthy non-pregnant women and 623 healthy pregnant women in different trimesters. Samples from 23 healthy consecutive pregnant women were collected to validate. Serum Cystatin C was measured by latex particle enhanced immune turbidity assay (Dade Behring, Germany) using Centaur 2400 (Siemens, New York, USA). Creatinine, Blood Urea Nitrogen and Uric Acid were measured by conventional enzymatic assay using a Centaur 2400 (Siemens, New York, USA). The calculated reference intervals for serum cystatin C were (0.76±0.12) mg/L, (0.70±0.14) mg/L, (0.75±0.16) mg/L, (1.19±0.23) mg/L in control group, 1st trimester, 2nd trimester and 3rd trimester, respectively. Creatinine were (54.21±7.49) µmol/L, (45.90±8.55) µmol/L, (44.56±8.65) µmol/L, (52.78±11.76) µmol/L in each group. Blood Urea Nitrogen were (4.74±1.24) mmol/L, (3.52±1.44) mmol/L, (3.81±2.32) mmol/L, (3.95±1.54) mmol/L. And Uric Acid were (281.35±63.61) µmol/L, (226.93±25.20) µmol/L, (252.39±62.32) µmol/L, (350.86±93.31) µmol/L. In addition, all the data of consecutive pr egnant women were in the central 95% intervals. The results show the necessity to establish the special reference intervals for pregnancy, even each trimester. Different areas show the different intervals, indicating we need own ones in our region, and we provided. And Cystatin C is the most stable between these indexes. But we also should cautiously treat it in the 3st trimester.

Background: C-terminal agrin fragment (CAF) has been shown to be a promising new biomarker for kidney function. The aim of this study was to verify the reference intervals for CAF in Chinese healthy adults and to assess the efficiency of CAF for monitoring renal function after transplantation., Methods: Serum samples were collected from 200 healthy adult subjects and 60 living donor kidney recipients before and on day 1, day 2 and at 6 months after transplantation. We measured serum CAF, creatinine, cystatin C and NGAL concentrations at each time. Estimated glomerular filtration rate (eGFR) was evaluated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Reference intervals for CAF were determined at 2.5th and 97.5th percentiles., Results: Serum CAF concentrations were observed to be higher in females of old age groups while no significant differences were discovered in males between age groups. There were significant gender-related differences in CAF in old age groups (50-64 and ≥65 years). Serum CAF correlated positively with serum creatinine, cystatin C and negatively with eGFR on day 1, day 2 and at 6 months after kidney transplantation. CAF and NGAL fell rapidly into the normal range on the second postoperative day, prior to creatinine and cystatin C., Conclusions: This study verified the reference intervals for serum CAF. CAF could be a potential new biomarker for kidney function monitoring., (© 2016 Wiley Periodicals, Inc.)

Evaluation of GFR, required in the evaluation of living kidney donor candidates, is now receiving increasing emphasis because recent data demonstrate increased risk of kidney disease after donation, including a small increase in the risk of kidney failure. The international guideline development group, Kidney Disease Improving Global Outcomes, recently published a comprehensive set of recommendations for living donor evaluation, with three recommendations regarding GFR. ( 1 ) Donor candidacy is evaluated in light of long-term risk, in which GFR is one of many factors. ESRD is considered a central outcome, and a method for estimating long-term risk of ESRD in donor candidates is described. ( 2 ) Two GFR thresholds are used for decision-making: a high threshold (≥90 ml/min per 1.73 m 2 ) to accept and a low threshold (<60 ml/min per 1.73 m 2 ) to decline, with 60-89 ml/min per 1.73 m 2 as an intermediate range in which the decision to accept or decline is made on the basis of factors in addition to GFR. ( 3 ) GFR is evaluated using several methods available at the transplant center, including estimating equations and clearance measurements. We review the rationale for the guideline recommendations, principles of GFR measurement and estimation, and our suggestions for implementation., (Copyright © 2017 by the American Society of Nephrology.)

To develop an equation for the evaluation of renal function in rats using three dilutions of plasma samples and to validate this method by comparison with a reference method. The investigation was conducted in Sprague-Dawley (SD) rats after delivery of three doses of iohexol, with blood samples collected before and after dosage using a quantitative blood collection method. Plasma iohexol concentrations were detected by high performance liquid chromatography (HPLC). The extraction recovery of iohexol from plasma was >97.30% and the calibration curve was linear (r 2  = 0.9997) over iohexol concentrations ranging from 10 to 1000 µg/mL. The method had an RE of <9.310 and intra- and inter-day RSD of <5.137% and <3.693%, respectively. The plasma clearance values obtained from the equation correlated closely (r = 0.763) with those obtained using the reference method. The relatively correlation in the results obtained using the method under investigation and the reference method indicate that this new equation can be used for preliminary assessment of renal function in rats., (© 2016 Asian Pacific Society of Nephrology.)

Direct oral anticoagulants (DOACs) may require dose reduction or avoidance when glomerular filtration rate is low. However, glomerular filtration rate is not usually measured in routine clinical practice. Rather, equations that incorporate different variables use serum creatinine to estimate either creatinine clearance in mL/min or glomerular filtration rate in mL/min/1.73 m 2 . The Cockcroft-Gault equation estimates creatinine clearance and incorporates weight into the equation. By contrast, the Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations estimate glomerular filtration rate and incorporate ethnicity but not weight. As a result, an individual patient may have very different renal function estimates, depending on the equation used. We now highlight these differences and discuss the impact on routine clinical care for anticoagulation to prevent embolization in atrial fibrillation. Pivotal DOAC clinical trials used creatinine clearance as a criterion for patient enrollment, and dose adjustment and Federal Drug Administration recommendations are based on creatinine clearance. However, clinical biochemistry laboratories provide CKD-EPI glomerular filtration rate estimations, resulting in discrepancies between clinical trial and routine use of the drugs., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: We evaluated the effect of kidney glomerular function on serum concentrations of human epididymis protein 4 (HE4) using creatinine (Cr), cystatin C (CysC) and related chronic kidney disease epidemiology collaboration (CKD-EPI) equations., Methods: We enrolled 101 women aged ≤56 years with a glomerular filtration rate (GFR) (estimated by CKD-EPI eGFRCr) ranging from 60 to 120 mL/min/1.73 m2, free of any disease and biological and life-style factors known to influence serum HE4 concentrations, and we measured serum Cr, CysC and HE4 concentrations. Cr and CysC values were included in the three CKD-EPI equations to obtain GFR estimates., Results: A statistically significant increase in HE4 median concentrations was detected in subjects with an eGFRCr between 60 and 74 mL/min/1.73 m2 when compared with those with an eGFR >90 mL/min/1.73 m2 (54.2 vs. 42.2 pmol/L, p=0.003). Regression models showed that CysC measurement per se and eGFRCysC were the most sensitive markers to catch HE4 increases due to a mild decrease in renal function [adjusted r2, 0.38 (p=0.00003) and 0.37 (p=0.0004), respectively]. By assuming baseline CysC and eGFRCysC at 0.80 mg/L and 101.5 mL/min/1.73 m2, an increase of 0.10 mg/L in CysC concentrations and a decrease of 10 mL/min of eGFRCysC implied an average (±SE) increase in serum HE4 concentrations of 9.2 (±1.2) and 8.8 (±1.1) pmol/L, respectively., Conclusions: Our study shows that a better estimate of the effect of GFR on serum HE4 is obtained by measuring CysC in serum or using CKD-EPI eGFRCysC equation.

Competing Interests: Conflicts of Interest: None declared

Purpose: We aimed to identify the most accurate single-sample glomerular filtration rate (SS-GFR) technique for all patient ages., Materials and Methods: We performed a systematic review of all published SS-GFR measurement techniques and compared the results from each test with a gold-standard nine-point 'area-under-curve' measurement of GFR as well as slope-intercept (SI-GFR) methods for 412 GFR tests., Results: We have shown that for patients of all ages the SS-GFR technique developed by Fleming and colleagues delivers the best accuracy and precision, with results equivalent to those calculated by SI-GFR. The median percentage difference from the gold-standard GFR for the Fleming technique is 4.8% (95% confidence interval 3.9-5.7%) and that for the three-point SI-GFR is 5.6% (95% confidence interval 4.9-6.3%). The interquartile range of the distribution of percentage difference from the gold standard is -0.23 to 11% for the Fleming method and 1.6-11% for the three-point SI-GFR., Conclusion: The Fleming technique outperforms the method currently recommended by the international guidelines, and is simpler as only one equation is required for all patients instead of separate equations for adults and children. We propose that the SS-GFR technique of Fleming replace the methods currently recommended by the international and BNMS guidelines for routine measurement of GFR for expected results greater than 30 ml/min/1.73 m. A thorough system of measurement checks should be implemented for all methods of GFR assessment; the perceived lack of opportunity for quality control checks to be performed on the result of a single-sample measurement is addressed in the companion paper of this study.

Purpose: In this work, we aimed to identify the types of errors encountered in glomerular filtration rate (GFR) measurement and test the effectiveness of all published quality control (QC) methods for detection of clinically significant errors., Methods: A total of 412 GFR tests were carried out on adults and children. The three-point slope-intercept glomerular filtration rate (SI-GFR) was compared with the nine-point 'area under curve' calculation as a gold standard to determine the error in SI-GFR. The Durbin-Watson test was used to characterize the nature of the errors. The sensitivity, specificity and positive predictive value (PPV) of QC methods for detecting clinically significant errors were calculated and receiver operating characteristic curves were constructed. The QC methods were also applied to a dataset of 100 four-point GFR tests from different institutions., Results: Model failure is the dominant cause of clinically significant error in this dataset, with individual point measurement errors only giving rise to clinically significant errors in a small number of cases. No QC test had an acceptable combination of sensitivity, PPV and specificity. The correlation coefficient QC test had the largest area under the receiver operating characteristic curve (0.73). No other QC test had an area greater than 0.57., Conclusion: All the QC methods have poor sensitivity and PPV for detecting clinically significant errors and so cannot be relied on to ensure a robust measurement of GFR, underlining the need for careful working practices and a thorough system of measurement checks. We found no evidence for the value of multiple sampling with respect to QC; until such evidence is published, their clinical utility is unproven.

Background: The Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score is a prognostic model to identify heart failure (HF) patients at risk for cardiovascular mortality (CVM) and urgent heart transplantation (uHT) based on 6 routine clinical parameters: hemoglobin, sodium, kidney function by the Modification of Diet in Renal Disease (MDRD) equation, left ventricle ejection fraction (LVEF), percentage of predicted peak oxygen consumption (VO2) and VE/VCO2 slope., Objectives: MECKI score must be generalizable to be considered useful: therefore, its performance was validated in a new sequence of HF patients., Methods: Both the development (MECKI-D) and the validation (MECKI-V) cohorts were composed of consecutive HF patients with LVEF <40% able to perform a symptom-limited cardiopulmonary exercise testing. The CVM or uHT rates were analyzed at one, two and three years in both cohorts: all patients with a censoring time shorter than the scheduled follow-up were excluded, while those with events occurring after 1, 2 and 3 years were considered as censored., Results: MECKI-D and MECKI-V consisted of 2009 and 992 patients, respectively. MECKI-V patients had a higher LVEF, higher peak VO2 and lower VE/VCO2 slope, higher prescription of beta-blockers and device therapy: after the 3-year follow-up, CVM or uHT occurred in 206 (18%) MECKI-D and 44 (13%) MECKI-V patients (p<0.000), respectively. MECKI-V AUC values at one, two and three years were 0.81 ± 0.04, 0.76 ± 0.04, and 0.80 ± 0.03, respectively, not significantly different from MECKI-D., Conclusions: MECKI score preserves its predictive ability in a HF population at a lower risk., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: We evaluated the accuracy and precision of creatinine- and cystatin C-based prediction equations for estimating glomerular filtration rate compared to measured glomerular filtration rate in an antiretroviral-naive human immunodeficiency virus population., Methods: The study population consisted of 100 treatment-naive HIV patients. Glomerular filtration rate was estimated using the Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, as well as cystatin C-based equations (CKD-EPIcystatin C, cystatin Cvan Deventer and CKD-EPIcombined)) compared to (51)Cr-EDTA plasma clearance-measured glomerular filtration rate. We calculated percentage bias, standard deviation of the differences, accuracy within 15 and 30% of measured glomerular filtration rate and sensitivity and specificity for predicting measured glomerular filtration rate <60 mL/min/1.73 m(2)., Results: Bias for all estimating glomerular filtration rate equations ranged from -9.4% to 38.4%. The CKD-EPIcombined without ethnicity correction factor equation had the least bias, 2.9% (-2.9 to 8.8). Bias was higher for the Modification of Diet in Renal Disease and CKD-EPI equation with the African-American ethnicity factor (38.4 and 33.7%) than without (14.2 and 15.3%). Standard deviation of the differences ranged from 29.2% (CKD-EPIcombined without ethnicity factor) to 54.0% (Modification of Diet in Renal Disease with ethnicity factor). Accuracy within 30% of measured glomerular filtration rate ranged from 78% for CKD-EPIcombined without ethnicity factor to 56.7% for the Cockcroft-Gault equation. Sensitivity for creatinine-based equations was less than 50% and for the CKD-EPIcystatin C equation was 75%., Conclusion: Sensitivity of creatinine-based equations for predicting glomerular filtration rate was poor in this group of patients. The CKD-EPIcombined equation performed better than creatinine-based equations., (© The Author(s) 2015.)

Background/aims: We have reported that the eGFR overestimates renal function when glycemic control is poor. It has been reported that eGFR calculated by serum creatinine underestimates GFR in living kidney donors. We compared the utility of the eGFR in diabetic patients, non-diabetic patients and living kidney donors. Forty diabetic patients, 40 non-diabetic patients, and 40 living kidney donors were enrolled., Methods: GFR was measured by inulin clearance (C(in)). eGFR was calculated based on serum creatinine (eGFR(cr)) or serum cystatin C (eGFR(cys)). We compared the agreements between each of the eGFR and C(in) in each group., Results: There were significant and positive correlations between each eGFR and C(in) in diabetic patients and non-diabetic patients. However, the intraclass correlation coefficients (ICC) between each eGFR and C(in) in diabetic patients (ICC: eGFR(cr) 0.699, eGFR(cys) 0.604) were weaker than those in non-diabetic patients (ICC: eGFR(cr) 0.865, eGFR(cys) 0.803). The correlation coefficients between each eGFR and C(in) (eGFR(cr); r = 0.422, p = 0.0067 and eGFR(cys); r = 0.358, p = 0.0522) in living kidney donors were significantly weaker than those in non-diabetic patients. The ICCs between each eGFR and C(in) (ICC: eGFR(cr) 0.340, eGFR(cys) 0.345) in living kidney donors were significantly weaker than those in non-diabetic patients., Conclusions: Based on C(in), eGFR was accurate in non-diabetic patients. However, eGFR was inaccurate in living kidney donors and relatively inaccurate in diabetic patients., (© 2016 The Author(s) Published by S. Karger AG, Basel.)

Background: The Jaffe and enzymatic methods are the two most common methods for measuring serum creatinine. The Jaffe method is less expensive than the enzymatic method but is also more susceptible to interferences. Interferences can lead to misdiagnosis but interferences may vary by patient population. The overall risk associated with the Jaffe method depends on the probability of misclassification and the consequences of misclassification. This study assessed the risk associated with the Jaffe method in an outpatient population. We analyzed the discordance rate in the estimated glomerular filtration rate based on serum creatinine measurements obtained by the Jaffe and enzymatic method., Methods: Method comparison and risk analysis. Five hundred twenty-nine eGFRs obtained by the Jaffe and enzymatic method were compared at four clinical decision limits. We determined the probability of discordance and the consequence of misclassification at each decision limit to evaluate the overall risk., Results: We obtained 529 paired observations. Of these, 29 (5.5%) were discordant with respect to one of the decision limits (i.e. 15, 30, 45 or 60 ml/min/1.73m2). The magnitude of the differences (Jaffe result minus enzymatic result) were significant relative to analytical variation in 21 of the 29 (72%) of the discordant results. The magnitude of the differences were not significant relative to biological variation. The risk associated with misclassification was greatest at the 60 ml/min/1.73m2 decision limit because the probability of misclassification and the potential for adverse outcomes were greatest at that decision limit., Conclusion: The Jaffe method is subject to bias due to interfering substances (loss of analytical specificity). The risk of misclassification is greatest at the 60 ml/min/1.73m2 decision limit; however, the risk of misclassification due to bias is much less than the risk of misclassification due to biological variation. The Jaffe method may pose low risk in selected populations if eGFR results near the 60 ml/min/1.73m2 decision limit are interpreted with caution.

Background: Guidelines exist for chronic kidney disease (CKD) but are not well implemented in clinical practice. We evaluated the impact of a guideline-based clinical decision support system (CDSS) on laboratory monitoring and achievement of laboratory targets in stage 3-4 CKD patients., Methods: We performed a matched cohort study of 12,353 stage 3-4 CKD patients whose physicians opted to receive an automated guideline-based CDSS with CKD-related lab results, and 42,996 matched controls whose physicians did not receive the CDSS. Physicians were from US community-based physician practices utilizing a large, commercial laboratory (LabCorp®). We compared the percentage of laboratory tests obtained within guideline-recommended intervals and the percentage of results within guideline target ranges between CDSS and non-CDSS patients. Laboratory tests analyzed included estimated glomerular filtration rate, plasma parathyroid hormone, serum calcium, phosphorus, 25-hydroxy vitamin D (25-D), total carbon dioxide, transferrin saturation (TSAT), LDL cholesterol (LDL-C), blood hemoglobin, and urine protein measurements., Results: Physicians who used the CDSS ordered all CKD-relevant testing more in accord with guidelines than those who did not use the system. Odds ratios favoring CDSS ranged from 1.29 (TSAT) to 1.88 (serum phosphorus) [CI, 1.20 to 2.01], p < 0.001 for all tests. The CDSS impact was greater for primary care physicians versus nephrologists. CDSS physicians met guideline targets for LDL-C and 25-D more often, but hemoglobin targets less often, than non-CDSS physicians. Use of CDSS did not impact guideline target achievement for the remaining tests., Conclusions: Use of an automated laboratory-based CDSS may improve physician adherence to guidelines with respect to timely monitoring of CKD.

Background: The prevalence of chronic kidney disease (CKD) is high in general populations around the world. Targeted testing and screening for CKD are often conducted to help identify individuals that may benefit from treatment to ameliorate or prevent their disease progression., Aims: This systematic review examines the methods used in economic evaluations of testing and screening in CKD, with a particular focus on whether test accuracy has been considered, and how analysis has incorporated issues that may be important to the patient, such as the impact of testing on quality of life and the costs they incur., Methods: Articles that described model-based economic evaluations of patient testing interventions focused on CKD were identified through the searching of electronic databases and the hand searching of the bibliographies of the included studies., Results: The initial electronic searches identified 2,671 papers of which 21 were included in the final review. Eighteen studies focused on proteinuria, three evaluated glomerular filtration rate testing and one included both tests. The full impact of inaccurate test results was frequently not considered in economic evaluations in this setting as a societal perspective was rarely adopted. The impact of false positive tests on patients in terms of the costs incurred in re-attending for repeat testing, and the anxiety associated with a positive test was almost always overlooked. In one study where the impact of a false positive test on patient quality of life was examined in sensitivity analysis, it had a significant impact on the conclusions drawn from the model., Conclusion: Future economic evaluations of kidney function testing should examine testing and monitoring pathways from the perspective of patients, to ensure that issues that are important to patients, such as the possibility of inaccurate test results, are properly considered in the analysis.

Background: This study compares glomerular filtration rate (GFR) equations in children based on standardized cystatin C (CYSC) and creatinine (CREA) and their combinations with renal clearance of inulin (C-inulin)., Methods: A total of 220 children with different renal disorders were referred for C-inulin (median 84 ml/min/1.73 m(2)). Bias, precision (interquartile range, IQR), and accuracy (percentage of estimates ±30 % of C-inulin; P30) were evaluated for two cystatin C equations, CAPACYSC and BergCYSC, for creatinine equations, SchwartzCREA and GaoCREA, the arithmetic mean of CAPACYSC and SchwartzCREA (MEANCAPA+Schwartz), BergCYSC and SchwartzCREA (MEANBERG+SCHWARTZ) and the composite equation ChehadeCYSC+CREA., Results: Overall results of CAPACYSC, BergCYSC, SchwartzCREA, GaoCREA, MEANCAPA+Schwartz, MEANBERG+SCHWARTZ and ChehadeCYSC+CREA were: median bias -7.6/-4.9/-3.7/-2.3/-4.6/-4.0/-10.1 %, IQR 20.0/19.9/21.7/22.4/21.0/20.9/23.3 ml/min/1.73 m(2) and P30 86/86/80/83/89/91/83 %. The cystatin C equations, MEANCAPA+Schwartz and MEANBERG+SCHWARTZ had a more stable performance across subgroups compared with SchwartzCREA, GaoCREA and ChehadeCYSC+CREA., Conclusions: Cystatin C was the preferred filtration marker for GFR estimation in children, while the benefit of combining cystatin C and creatinine deserves further investigations.

Background: Chronic kidney disease is an important concern in preventive medicine, but the rate of decline in renal function in healthy population is not well defined. The purpose of this study was to determine reference values for the estimated glomerular filtration rate (eGFR) and rate of decline of eGFR in healthy subjects and to evaluate factors associated with this decline using a large cohort in Japan., Methods: Retrospective cross-sectional and longitudinal studies were performed with healthy subjects aged ≥18 years old who received a medical checkup. Reference values for eGFR were obtained using a nonparametric method and those for decline of eGFR were calculated by mixed model analysis. Relationships of eGFR decline rate with baseline variables were examined using a linear least-squares method., Results: In the cross-sectional study, reference values for eGFR were obtained by gender and age in 72,521 healthy subjects. The mean (±SD) eGFR was 83.7±14.7 ml/min/1.73 m2. In the longitudinal study, reference values for eGFR decline rate were obtained by gender, age, and renal stage in 45,586 healthy subjects. In the same renal stage, there was little difference in the rate of decline regardless of age. The decline in eGFR depended on the renal stage and was strongly related to baseline eGFR, with a faster decline with a higher baseline eGFR and a slower decline with a lower baseline eGFR. The mean (±SD) eGFR decline rate was ‒1.07±0.42 ml/min/1.73 m2/year (‒1.29±0.41%/year) in subjects with a mean eGFR of 81.5±11.6 ml/min/1.73 m2., Conclusions: The present study clarified for the first time the reference values for the rate of eGFR decline stratified by gender, age, and renal stage in healthy subjects. The rate of eGFR decline depended mainly on baseline eGFR, but not on age, with a slower decline with a lower baseline eGFR.

Background: Pregnancy during dialysis is increasingly being reported and represents a debated point in Nephrology. The small number of cases available in the literature makes evidence-based counselling difficult, also given the cultural sensitivity of this issue. Hence, the need for position statements to highlight the state of the art and propose the unresolved issues for general discussion., Methods: A systematic analysis of the literature (MESH, Emtree and free terms on pregnancy and dialysis) was conducted and expert opinions examined (Study Group on Kidney and Pregnancy; experts involved in the management of pregnancy in dialysis in Italy 2000-2013). Questions regarded: timing of dialysis start in pregnancy; mode of treatment, i.e. peritoneal dialysis (PD) versus haemodialysis (HD); treatment schedules (for both modes); obstetric surveillance; main support therapies (anaemia, calcium-phosphate parathormone; acidosis); counselling tips., Main Results: Timing of dialysis start is not clear, considering also the different support therapies; successful pregnancy is possible in both PD and HD; high efficiency and strict integration with residual kidney function are pivotal in both treatments, the blood urea nitrogen test being perhaps a useful marker in this context. To date, long-hour HD has provided the best results. Strict, personalized obstetric surveillance is warranted; therapies should be aimed at avoiding vitamin B12, folate and iron deficits, and at correcting anaemia; vitamin D and calcium administration is safe and recommended. Women on dialysis should be advised that pregnancy is possible, albeit rare, with both types of dialysis treatment, and that a success rate of over 75% may be achieved. High dialysis efficiency and frequent controls are needed to optimize outcomes.

Objectives: This study screened current GFR evaluation equations that showed high accuracy for elderly populations and evaluated the applicability of these equations for an elderly Chinese population., Measurements: A standard dual plasma sampling method (DPSM) of estimating 99mTc-diethylene triamine penta-acetic acid clearance was used to determine measured GFR (mGFR)., Results: Comprehensive information was received for a total of 151 elderly individuals, with a mean mGFR of 65.39 ± 24.19 ml/min/1.73 m2. For the overall samples, the accuracy (P30), bias, absolute bias and interquartile ranges (IQRs) of the CKD2 (cystatin C(CysC)-serum creatinine(SCr)), CKD-EPI(CysC-SCr), Cockcroft-Gault(CG), CKD2(CysC), CKD-EPI(CysC), and Hoek equations were superior to c-aGFR3, c-aGFR4 and Grubb equation, Bland-Altman analysis also demonstrated a consistent result. Among elderly subjects with mGFR≥60 ml/min/1.73 m2, the CKD2 (CysC-SCr) and CKD-EPI (CysC-SCr) equations showed significantly higher correlations and accuracy than the other examined equations. Among elderly subjects with mGFR<60 ml/min/1.73 m2, only the CG equation showed an accuracy (P30) of greater than 70% and demonstrated higher precision than the other examined equations., Conclusion: For the elderly population, the CG, CKD2, CKD-EPI, and Hoek equations exhibited good accuracy. The CKD2(CysC-SCr) equation and CKD-EPI(CysC-SCr) equation demonstrated relatively high accuracy for evaluating elderly subjects with mGFR≥60 ml/min/1.73 m2, whereas the CG equation was more suitable for evaluating elderly subjects with mGFR<60 ml/min/1.73 m2.

Background: The calibration to isotope dilution mass spectrometry-traceable creatinine is essential for valid use of the new Chronic Kidney Disease Epidemiology Collaboration equation to estimate the glomerular filtration rate., Methods: For 5,210 participants in the Jackson Heart Study (JHS), serum creatinine was measured with a multipoint enzymatic spectrophotometric assay at the baseline visit (2000-2004) and remeasured using the Roche enzymatic method, traceable to isotope dilution mass spectrometry in a subset of 206 subjects. The 200 eligible samples (6 were excluded, 1 for failure of the remeasurement and 5 for outliers) were divided into 3 disjoint sets-training, validation and test-to select a calibration model, estimate true errors and assess performance of the final calibration equation. The calibration equation was applied to serum creatinine measurements of 5,210 participants to estimate glomerular filtration rate and the prevalence of chronic kidney disease (CKD)., Results: The selected Deming regression model provided a slope of 0.968 (95% confidence interval [CI], 0.904-1.053) and intercept of -0.0248 (95% CI, -0.0862 to 0.0366) with R value of 0.9527. Calibrated serum creatinine showed high agreement with actual measurements when applying to the unused test set (concordance correlation coefficient 0.934, 95% CI, 0.894-0.960). The baseline prevalence of CKD in the JHS (2000-2004) was 6.30% using calibrated values compared with 8.29% using noncalibrated serum creatinine with the Chronic Kidney Disease Epidemiology Collaboration equation (P < 0.001)., Conclusions: A Deming regression model was chosen to optimally calibrate baseline serum creatinine measurements in the JHS, and the calibrated values provide a lower CKD prevalence estimate.

Importance: Because early-stage kidney disease is asymptomatic and is associated with both morbidity and mortality, laboratory measurements are required for its detection., Objective: To summarize evidence supporting the use of laboratory tests for glomerular filtration rate (GFR) and albuminuria to detect and stage acute kidney injury, acute kidney diseases and disorders, and chronic kidney disease in adults., Evidence Review: We reviewed recent guidelines from various professional groups identified via the National Guideline Clearing House and author knowledge, and systematically searched MEDLINE for other sources of evidence for selected topics., Findings: The KDIGO (Kidney Disease Improving Global Outcomes) guidelines define and stage acute and chronic kidney diseases by GFR and albuminuria. For initial assessment of GFR, measuring serum creatinine and reporting estimated GFR based on serum creatinine (eGFRcr) using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2009 equation is recommended. If confirmation of GFR is required because of conditions that affect serum creatinine independent of GFR (eg, extremes of muscle mass or diet), or interference with the assay, cystatin C should be measured and estimated GFR should be calculated and reported using cystatin C (eGFRcys) and serum creatinine (eGFRcr-cys) or GFR should be measured directly using a clearance procedure. Initial assessment of albuminuria includes measuring urine albumin and creatinine in an untimed spot urine collection and reporting albumin-to-creatinine ratio. If confirmation of albuminuria is required because of diurnal variation or conditions affecting creatinine excretion, such as extremes of muscle mass or diet, the albumin excretion rate should be measured from a timed urine collection., Conclusions and Relevance: Detection and staging of acute and chronic kidney diseases can be relatively simple. Because of the morbidity and mortality associated with kidney disease, early diagnosis is important and should be pursued in at-risk populations.

Background/aims: Estimated glomerular filtration rate (eGFR) is used extensively in epidemiological research. Validations of eGFR have demonstrated acceptable performance, but the dependence of creatinine and cystatin C on non-GFR factors could confound associations with disease. Few studies have investigated this issue in direct comparison with measured GFR (mGFR). We compared the associations between eGFR and mGFR and retinal vasculopathy, a marker of systemic microvasculopathy., Methods: Iohexol clearance and retinal photography were examined in the Renal Iohexol Clearance Survey in Tromsø 6, which consists of a representative sample of middle-aged persons from the general population. A total of 1,553 persons without self-reported kidney disease, cardiovascular disease or diabetes were investigated. Three eGFR equations based on creatinine and/or cystatin C from the Chronic Kidney Disease Epidemiology Collaboration were studied. Differences between eGFR and mGFR were analyzed with seemingly unrelated regression methods., Results: mGFR in the lowest quartile was associated with an increased multivariable-adjusted odds ratio of retinopathy (OR 1.86, 95% CI 1.16-2.97), but not with retinal artery or vein diameters. eGFR based on cystatin C (eGFRcys) was consistently biased relative to mGFR in its associations with retinal vessel diameters across different models. eGFR based on creatinine (eGFRcrea) and eGFR based on both creatinine and cystatin C were also biased in several of these models (p < 0.05). For retinopathy, the differences between the 3 eGFR and mGFR measurements were not statistically significant., Conclusions: Low mGFR is associated with retinopathy in the general population. eGFR based on creatinine and/or cystatin C are not valid substitutes for mGFR in studies of the relationship between the retina and kidney function in healthy persons., (© 2015 S. Karger AG, Basel.)

Objective: Neonatologists still commonly use creatinine as a proxy for renal clearance, despite issues related to neonatal (patho)physiology and methodology (assay variability). Cystatin C (CysC) has been suggested to be a more reliable biomarker, but assay related differences have also been reported in children and adults. We are unaware of any review on the assay related impact on CysC reference values in newborns., Methods: A structured literature search was performed on published CysC values in (pre)term neonates., Results: The extensive range (>5-fold) in serum CysC observations in neonates in part relates to the fact that CysC concentrations are higher at birth with subsequent decrease and that CysC concentrations are higher in preterm compared to term neonates. The CysC assay matters while disease characteristics also affect CysC values, but not always in the predicted direction., Conclusions: Similar to creatinine, the extensive CysC range in neonates is only in part explained by renal (patho)physiology. Its applicability in neonatal medicine can be further improved by use of assay specific reference values, adapted to neonatal renal physiology (e.g. weight, age) and should be compared to a gold standard such as inulin clearance.

Background: Guidelines for measuring glomerular filtration rate (GFR) using Cr-EDTA require normalizing of GFR for body surface area (BSA) before applying the Bröchner-Mortensen (BM) correction. The guideline explicitly mentions the importance of performing BSA normalization before BM correction and that this is particularly important in children in whom the effects of BSA normalization are largest., Materials and Methods: We theoretically showed that the order of applying BM correction and BSA indexing is indeed important for patient populations having a low BSA and a high slow GFR. We then compared the exact GFR, obtained from the double-exponential concentration-time curve in Duchenne muscular dystrophy (DMD) patients, with the GFR obtained from the slow compartment method using the BM correction., Results: The median GFR for the 20 DMD patients obtained from the BSA-BM order deviates 5.40% from the exact GFR (P=0.0006), whereas the median GFR obtained from the BM-BSA order deviates only -0.05% (P>0.05) from the exact GFR, resulting in a median of differences of 5.50% between the two methods (P<0.0001)., Conclusion: The correct order of application in this DMD population should be BM correction first, followed by BSA indexing, and not vice versa. In general, the order of applying the BM correction and BSA normalization becomes more important with increasing slow GFR and extreme low BSA. The order of application is of less importance for people with normal BSA and/or normal GFR.

Serum creatinine (SCr) is the main variable for estimating glomerular filtration rate (GFR). Due to inter-assay differences, the prevalence of chronic kidney disease (CKD) varies according to the assay used, and calibration standardization is necessary. For SCr, isotope dilution mass spectrometry (IDMS) is the gold standard. Systematic differences are observed between Jaffe and enzymatic methods. Manufacturers subtract 0.30 mg/dl from Jaffe results to match enzymatic results ('compensated Jaffe method'). The analytical performance of enzymatic methods is superior to that of Jaffe methods. In the original Modification of Diet in Renal Disease (MDRD) equation, SCr was measured by a Jaffe Beckman assay, which was later recalibrated. A limitation of this equation was an underestimation of GFR in the high range. The Chronic Kidney Disease Epidemiology (CKD-EPI) consortium proposed an equation using calibrated and IDMS traceable SCr. The gain in performance was due to improving the bias whereas the precision was comparable. The CKD-EPI equation performs better at high GFR levels (GFR >60 ml/min/1.73 m(2)). Analytical limitations have led to the recommendation to give a grade (>60 ml/min/1.73 m(2)) rather than an absolute value with the MDRD equation. By using both enzymatic and calibrated methods, this cutoff-grade could be increased to 90 ml/min/1.73 m(2) (with MDRD) and 120 ml/min/1.73 m(2) (with CKD-EPI). The superiority of the CKD-EPI equation over MDRD is analytical, but the precision gain is limited. IDMS traceable enzymatic methods have been used in the development of the Lund-Malmö (in CKD populations) and Berlin Initiative Study equations (in the elderly). The analytical errors for cystatin C are grossly comparable to issues found with SCr. Standardization is available since 2011. A reference method for cystatin C is still lacking. Equations based on standardized cystatin C or cystatin C and creatinine have been proposed. The better performance of these equations (especially the combined CKD-EPI equation) has been demonstrated.

Background: Vancomycin dose selection is challenging in the spinal cord injury (SCI) population because of the difficulty in accurately estimating the renal function. Creatinine-based equations have been shown to be unreliable in this patient population. Adjusted equations designed for patients with SCI have not been well studied. Cystatin C is an alternative marker of renal function that is less affected by muscle mass and may offer improvement in estimating renal function leading to improved initial dose selection., Objective: To compare the accuracy of serum creatinine- and serum cystatin C-based equations used in a pharmacokinetic (PK) model to predict steady-state serum vancomycin concentration in an SCI population. The rationale for this study is the need for an improved predictive model to guide initial vancomycin dose design before the availability of a measured steady-state serum concentration., Methods: Patients with SCI receiving vancomycin with measured serum creatinine, cystatin C, and steady-state serum vancomycin concentration were identified. Serum creatinine- and cystatin C-based equations to estimate renal function were substituted into a population-based PK model to predict steady state-serum vancomycin concentration. Predictions using each equation in the model were compared with the measured steady-state serum vancomycin concentration. Predictive performances using each equation in the PK model were compared., Results: The final study population included 37 patients with SCI. The Chronic Kidney Disease Epidemiology Collaboration cystatin C equation provided significantly less bias, greater precision, and superior accuracy when used in the PK model., Conclusions: In the SCI population, the use of Chronic Kidney Disease Epidemiology Collaboration cystatin C equation may improve initial vancomycin dosing. Further study into this potential is encouraged.

Aims: Assessment of renal function is important for bleeding risk stratification in acute coronary syndrome (ACS). There are three formulas routinely used to assess renal function: the Cockroft-Gault (C-G) formula, the MDRD-4 formula and the new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Our aim was to compare the ability of these formulas to predict the risk of in-hospital bleeding in patients with ACS., Methods: The study included 3270 patients with ACS. The performance of each formula with respect to in-hospital TIMI (Thrombolysis In Myocardial Infarction) major or TIMI minor bleeding were assessed using continuous data and by dividing patients into four subgroups according to the estimated glomerular filtration rate (eGFR): ≥90, 89-60, 30-59 and <30 ml/min/1.73 m(2)., Results: Bleeding predictive ability was significantly higher for the C-G formula than for MDRD-4 and CKD-EPI formulas, as evaluated by the area under the curve (AUC); continuous eGFR AUCs: 0.73, 0.69 and 0.71, respectively; categorical eGFR AUCs: 0.71, 0.66 and 0.68, respectively. Net reclassification improvement based on the eGFR categories was significantly positively favored C-G: 9.5% (95% confidence interval (CI) 1.8-17.2%) and 19.1% (95% CI 11.3-26.9%) compared with CKD-EPI and MDRD-4, respectively. After multivariable adjustment, the C-G formula predicted in-hospital bleeding better than MDRD-4 formula (severe renal dysfunction vs. normal renal function: odds ratio 7.98, 95% CI 2.61-24.38 with C-G; odds ratio 3.76, 95% CI 1.63-8.69 with MDRD-4; and odds ratio 5.77, 95% CI 2.18-15.24 with CKD-EPI., Conclusions: Our findings suggest that the C-G eGFR may improve risk prediction of in-hospital bleeding more than the MDRD-4 equation and the new CKD-EPI equation in patients with ACS., (© The European Society of Cardiology 2014.)

Background: Men commence dialysis with a higher estimated glomerular filtration rate (eGFR) than women and are more likely to transition from chronic kidney disease (CKD) to end-stage renal disease. We hypothesized that for a given estimated body surface area (BSA) men have a greater metabolic burden, and that consequently, the practice of indexing GFR to BSA results in gender differences in the degree of biochemical uraemia., Methods: Metabolic burden was assessed as estimated dietary protein, calorie, phosphorus, sodium and potassium intakes and urinary urea nitrogen excretion in the Chronic Renal Insufficiency Cohort, Modification of Diet in Renal Disease study, and National Health and Nutrition Examinations Surveys (NHANES) 1999-2010. Uraemia was characterized by serum biochemistry., Results: Per m(2) BSA, men had greater urea nitrogen excretion and intakes of all dietary parameters (P < 0.001 for all). For a given BSA-indexed iothalamate GFR or eGFR, male gender was associated with a 10-15% greater serum urea nitrogen (P < 0.001), giving men with a BSA-indexed GFR of 70-75 mL/min/1.73 m(2) the same serum urea nitrogen concentration as women with a GFR of 60 mL/min/1.73 m(2). However, indexing metabolic burden and GFR to alternative body size measures (estimated total body water, lean body mass or resting energy expenditure) abolished/reversed the gender associations. In NHANES, BSA-indexed eGFR distribution was very similar for men and women, so that adjusting for eGFR had little effect on the gender difference in serum urea., Conclusions: Indexing GFR to BSA across genders may approximate nature's indexing approach, but gives men a greater ingested burden of protein, calories, sodium, phosphorus and potassium per mL/min GFR. This has implications for gender differences in CKD outcomes., (© The Author 2013. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: Glomerular filtration rate (GFR) estimating equations using the combination of creatinine and cystatin C (eGFRcr-cys) are more accurate than equations using either alone (eGFRcr or eGFRcys). New guidelines suggest measuring cystatin C as a confirmatory test when eGFRcr may be inaccurate, but do not specify demographic or clinical conditions in which eGFRcys or eGFRcr-cys are more accurate than eGFRcr nor which estimate to use in such circumstances., Methods: We compared the performance of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations in 1119 subjects in the CKD-EPI cystatin C external validation dataset. Subgroups were defined by eGFRcr, age, sex, diabetes status and body mass index (BMI). The reference test was GFR measured using urinary or plasma clearance of exogenous filtration markers. Cystatin C and creatinine assays were traceable to primary reference materials. Accuracy was defined as the absolute difference in eGFR compared with mGFR., Results: The mean mGFR was 70 ± 41 (SD) mL/min/1.73 m(2). eGFRcys was more accurate than eGFRcr at lower BMI and less accurate at higher BMI, especially at higher levels of eGFRcr. There were small differences in accuracy in people according to the diabetes status. eGFRcr-cys was as accurate or more accurate than eGFRcr or eGFRcys in these and all other subgroups., Conclusions: eGFRcr-cys, but not eGFRcys, is more accurate than eGFRcr in most subgroups we studied, suggesting preferential use of eGFRcr-cys when serum cystatin C is measured as a confirmatory test to obtain more accurate eGFR. Further studies are necessary to evaluate diagnostic strategies for using eGFRcys and eGFRcr-cys., (© The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

The appearance of the K/DOQI guidelines in 2002 on the definition, evaluation and staging of chronic kidney disease (CKD) have led to a major change in how to assess renal function in adults and children. These guidelines, recently updated, recommended that the study of renal function is based, not only on measuring the serum creatinine concentration, but this must be accompanied by the estimation of glomerular filtration rate (GFR) obtained by an equation. However, the implementation of this recommendation in the clinical laboratory reports in the paediatric population has been negligible. Numerous studies have appeared in recent years on the importance of screening and monitoring of patients with CKD, the emergence of new equations for estimating GFR, and advances in clinical laboratories regarding the methods for measuring plasma creatinine and cystatin C, determined by the collaboration between the departments of paediatrics and clinical laboratories to establish recommendations based on the best scientific evidence on the use of equations to estimate GFR in this population. The purpose of this document is to provide recommendations on the evaluation of renal function and the use of equations to estimate GFR in children from birth to 18 years of age. The recipients of these recommendations are paediatricians, nephrologists, clinical biochemistry, clinical analysts, and all health professionals involved in the study and evaluation of renal function in this group of patients., (Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.)

Background: Urinary creatinine can be quantified by Jaffe or enzymatic assays and is commonly used as denominator of urinary excretion of electrolytes or protein. Paired analysis in pediatric and adult samples documented inter-assay differences (up to 80%). We verified the interchangeability of two IDMS-traceable assays (Jaffe and enzymatic) for neonatal urine and report on neonatal urinary creatinine values using these IDMS-traceable methods., Methods: Creatinine was measured in 84 neonatal urine samples from 46 neonates by an IDMS traceable Jaffe and enzymatic assay (Roche Diagnostics, Cobas c702 module). Creatinine values, differences in urinary creatinine and clinical characteristics were described and covariates of between assay difference were explored (Wilcoxon, Bland-Altman, correlation, multiple regression)., Results: Median Jaffe and enzymatic urinary creatinine concentrations were 9.25 (range 3.7-42.2) and 9.15 (range 3.8-42.9) mg/dL respectively, resulting in a median difference of 0.08 (SD 0.6, range -2.4 to 0.96) mg/dL. In a multiple regression model, urinary enzymatic creatinine concentration (r = 0.45) and postnatal age (r = -0.59) remained independent variables of the difference between both assays (r2 adj = 0.45)., Conclusions: The tested IDMS-traceable assays showed interchangeable in heterogeneous neonatal urine samples. Using these assays, neonatal urinary creatinine showed 5-20 fold lower values than those observed in children or adults with a significant negative correlation with postnatal age.

Introduction: There is great interest in the use of animal models in the study of renal pathophysiology requires standardization of parameters., Objective: Standardize assessment of renal function in rats from in the Center for Reproductive Biology of Federal University of Juiz de Fora's colony., Methods: Thirty Wistar rats were used and performed measurements of creatinine (serum and urine), serum urea and proteinuria. Were evaluated: the urine collection interval in metabolic cages (24 hours or 12 hours), the need for 12-hour fast, the need of urine and serum deproteinization for creatinine measurement, need of serum deproteinization in animals with acute kidney injury to a spectrophotometer and ELISA, and the comparison of 24-hour proteinuria (PT 24 hours) with the protein/creatinine ratio (rP/C). Means were compared by the Student's t test, Pearson correlation, Bland-Altman plot for agreement and linear regression model to estimate PT 24 hours from rP/C., Results: The 24 hours urine output was greater than 12 hours, interfering with the creatinine clearance calculation. In the fasting group showed less water intake and lower urinary creatinine. There was great variability for the deproteinized whey and readings performed in the two devices were similar. There was a strong correlation between PT 24 hours and rP/C and the equation was generated: PT 24 hours = (8.6113 x rP/C) + 1.0869., Conclusion: Was standardized: 24-hour urine collection without fasting. The deproteinization showed no benefit. The measurements were performed with spectrophotometer reliability. It generated a practical formula for estimating PT 24 hours through rP/C.

Aims: To investigate how urologists generally perform the follow-up of adult spina bifida (SB) patients and to see to which extent recommendations from guidelines on neurogenic lower urinary tract dysfunction are followed., Methods: A self-designed electronic multiple choice questionnaire was sent to all 365 urologists in the Netherlands., Results: Overall 100 urologists (27.4%) responded, of which 96 (26.3%) responses were usable. Of 95 urologists, 18 (18.9%) saw no adult SB patients, 47 (49.5%) saw 1-5 patients/year, 15 (15.8%) saw 6-10, and 15 urologists (15.8%) saw >10 adult SB patients/year. Of 96 urologists, a specialized clinic for adult SB patients was present in only 11 (11.5%) cases. Ultrasonography was performed regularly (at least once every 1-5 years) by 68/74 (91.9%) urologists. Glomerular filtration rate (GFR) was determined at least every 5 years by 66/74 (89.1%) urologists. For determination of GFR, serum creatinine was most often used (94.5%). Renography and video-urodynamic investigations (UDS) were performed on a regular basis by 8.1% and 24.3%, respectively., Conclusions: In adult SB patients, the responding Dutch urologists regularly evaluate bladder and kidney function using GFR and ultrasonography, although less frequently than recommended by the guidelines. UDS is performed on indication only, which is not in accordance with the guidelines. Regular UDS might be valuable to detect risk factors for insidious renal damage. The role of renography, as well as the desirability of multidisciplinary teams, has yet to be determined., (© 2013 Wiley Periodicals, Inc.)

Background: A number of recent reports have suggested that the cystatin C/creatinine (CysC/Cr) ratio might be a useful biomarker of renal function in pediatric patients. In this study we investigated the reference intervals of the serum CysC/Cr ratio for neonates including very low birth weight infants., Case-Diagnosis/treatment: A total of 883 blood samples were collected from 246 neonates during the first 30 days of life for the concurrent measurement of serum CysC and Cr levels. Infants with symptoms or signs of acute kidney injury, systemic illness, congenital anomaly, or renal pathology were excluded. The association between serum CysC/Cr ratio and the subgroups of patients was also analyzed. Reference intervals of serum CysC/Cr ratio were determined according to the postnatal age and post-conceptional age (PCA). CysC/Cr ratio level increased according to PCA, except in the first three postnatal days. The serum CysC/Cr ratio correlated positively with gestational age at birth, birth weight, postnatal age, and PCA, and negatively with serum CysC and Cr (P < 0.001)., Conclusions: Reference levels of serum CysC/Cr ratio were determined according to postnatal age and PCA. As the serum CysC/Cr ratio is dependent on several clinical parameters, these should be considered when assessing the serum CysC/Cr ratio in neonates.

The clinical implementation of urinary and plasma renal injury biomarkers has been hampered by the variability associated with nonstandardized commercially available biomarker assays, uncertainty and variations in patient selection criteria, and the absence of context-specific cutoffs for biomarker concentrations. These limitations are increased by comparison with serum creatinine to define acute kidney injury. The critical problem affecting biomarker performance is patient heterogeneity involving the cause, context (including comorbidity and baseline renal function), and timing of the injury. We suggest strategies for stratifying subjects to provide appropriate context, and illustrate a creatinine-independent method for defining thresholds for biomarker concentrations in these contexts which utilizes the same sensitivity for the clinical outcomes of dialysis or death. Large multicenter cohort studies are needed to validate the proposed cutoffs., (2014 S. Karger AG, Basel.)

Strategies for obtaining reliable results are increasingly implemented in order to reduce errors in the analysis of human and veterinary samples; however, further data are required for murine samples. Here, we determined an average factor from the murine body surface area for the calculation of biochemical renal parameters, assessed the effects of storage and freeze-thawing of C57BL/6 mouse samples on plasmatic and urinary urea, and evaluated the effects of using two different urea-measurement techniques. After obtaining 24 h urine samples, blood was collected, and body weight and length were established. The samples were evaluated after collection or stored at -20°C and -70°C. At different time points (0, 4, and 90 days), these samples were thawed, the creatinine and/or urea concentrations were analyzed, and samples were restored at these temperatures for further measurements. We show that creatinine clearance measurements should be adjusted according to the body surface area, which was calculated based on the weight and length of the animal. Repeated freeze-thawing cycles negatively affected the urea concentration; the urea concentration was more reproducible when using the modified Berthelot reaction rather than the ultraviolet method. Our findings will facilitate standardization and optimization of methodology as well as understanding of renal and other biochemical data obtained from mice.

Background: Kidney transplants from living donors with an estimated glomerular filtration rate (eGFR) < 80 mL/min per 1.73 m(2) may be at risk for increased graft loss compared with a recipient who receives a kidney from a living donor with a higher eGFR., Methods: This retrospective cohort study considered 2057 living kidney donors and their recipients from July 1993 to March 2010 at five centres in Ontario, Canada, and linked them to population-based, universal healthcare databases. Recipients were divided into five groups based on their donor's baseline eGFR. The median (inter-quartile range) for the lowest eGFR group was 73 (68-77) mL/min per 1.73 m(2). Subjects were followed for a median of 6 years (IQR: 3-10 years)., Results: There was no significant difference in the adjusted hazard ratio (HR) for graft loss when comparing recipients in each eGFR category to the referent group (≥110 mL/min per 1.73 m(2)). The adjusted HRs (95% CI) from the lowest (<80 mL/min per 1.73 m(2)) to highest (100-109.9 mL/min per 1.73 m(2)) eGFR categories were 1.27 (0.84-1.92), 1.43 (0.96-2.14), 1.23 (0.86-1.77) and 1.23 (0.85-1.77), respectively. Similar results were observed when dichotomizing the baseline donor eGFR using a cut-point of 80 mL/min per 1.73 m(2)-adjusted HR 1.01 [95% confidence interval (95% CI) (0.76-1.44)]., Conclusions: Further research in this setting should clarify whether additional tests (i.e. measured GFR) should be performed in potential donors whose eGFR is considered borderline, whether eGFR values should be standardized to body surface area, and the outcomes for donors after nephrectomy.

Unlabelled: Testing the rate of creatinine clearance by measuring the level of creatinine in the blood and in a 24-h urine collection is a common method of evaluating renal function. The result is routinely normalized for body surface area (BSA). Alternatively, renal clearance can be measured by (99m)Tc-mercaptoacetyltriglycine (MAG3) renal imaging without the need for urine collection. Frequently, the (99m)Tc-MAG3 camera-based result is also normalized for BSA., Methods: I evaluated the need for BSA normalization of renal clearance measurements in (99m)Tc-MAG3 imaging studies from both a conceptual and a mathematic point of view. Both approaches involved analyzing the effect of patient size, that is, BSA, on the factors blood volume, renal blood flow, and amount of test substance present in the blood in the creatinine clearance method compared with the (99m)Tc-MAG3 camera-based method., Results: Both the conceptual and the mathematic analyses were consistent with a significant difference between the creatinine and (99m)Tc-MAG3 approaches to measuring renal clearance. Larger patients have larger kidneys, greater renal blood flow, higher renal clearances, larger blood volumes, more muscle mass, and higher BSAs than smaller patients. However, the concentration of creatinine in the blood of patients of any size with normal renal function is similar because the amount of creatinine released into the blood varies with patient muscle mass, which varies with blood volume. Because normalization for BSA is needed for creatinine clearance, a single reference range can be used for all patients. In the case of measurement of renal clearance with (99m)Tc-MAG3 imaging (assuming a constant dose), the concentration of tracer in the blood will vary inversely with patient size because blood volume varies with patient size. Thus, as patient size increases, the blood concentration of tracer will go down and compensate for the increase in renal blood flow and renal clearance, and conversely. Consequently, the (99m)Tc-MAG3 renal imaging study is self-correcting for BSA and no additional correction is needed., Conclusion: A conceptual and mathematic analysis suggests that, although normalization for BSA is necessary in the measurement of renal clearance by the standard creatinine clearance test, such normalization is inappropriate in the (99m)Tc-MAG3 camera-based imaging study because the (99m)Tc-MAG3 method is inherently self-normalizing for BSA.