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Background: This cross-sectional study aimed to explore the variation trend of renal function for healthy pregnant women at different gestational ages and aimed to establish RIs for renal function set tests according to the trimester of pregnancy., Methods: A total of 120 healthy pregnant women and 40 healthy non-pregnant women were enrolled in this study and divided into early trimester (1 - 13 weeks of gestation, n = 40), second trimester (14 - 27 weeks of gestation, n = 40), third trimester (≥ 28 weeks of gestation, n = 40), and a non-pregnant women group (n = 40). Analytes of UA, BUN, Cr, β2-MG, Cys-C, RBP, NAG, CO2, HCY, C1q, and NGAL were measured by using the analytical systems of the Second Xiangya Hospital. The RIs were defined by using non-parametric 95% intervals., Results: The RIs for UA, Cr, β2-MG, NAG, CO2, Hcy, and C1q were established for the first and second trimester group and the third trimester group. There were huge differences after pregnancy. The RIs for BUN were different for the 1 - 13 weeks group and the after 14 weeks group. There were significant differences for NGAL in pregnant and non-pregnant women, but not for Cys-C and RBP., Conclusions: The RIs for renal function tests in pregnant women were established, thus providing clinical reference intervals for the clinicians.

Creatinine-based estimated glomerular filtration rate (eGFR) is imprecise at individual level, due to non-GFR-related serum creatinine determinants, including atypical muscle mass. Cystatin C has the advantage of being independent of muscle mass, a feature that led to the development of race- and sex-free equations. Yet, cystatin C-based equations do not perform better than creatinine-based equations for estimating GFR unless both variables are included together. The new race-free Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation had slight opposite biases between Black and non-Black subjects in the USA, but has poorer performance than that the previous version in European populations. The European Kidney Function Consortium (EKFC) equation developed in 2021 can be used in both children and adults, is more accurate in young and old adults, and is applicable to non-white European populations, by rescaling the Q factor, i.e. population median creatinine, in a potentially universal way. A sex- and race-free cystatin C-based EKFC, with the same mathematical design, has also be defined. New developments in the field of GFR estimation would be standardization of cystatin C assays, development of creatinine-based eGFR equations that incorporate muscle mass data, implementation of new endogenous biomarkers and the use of artificial intelligence. Standardization of different GFR measurement methods would also be a future challenge, as well as new technologies for measuring GFR. Future research is also needed into discrepancies between cystatin C and creatinine, which is associated with high risk of adverse events: we need to standardize the definition of discrepancy and understand its determinants., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Measurement of glomerular filtration rate (GFR) is crucial in assessing kidney function status. Estimating GFR using clearance methodologies is cumbersome, as plasma and urinary concentrations and timed urine collections are required. Recently, a transcutaneous sensor has been developed whereby the rate of renal washout of a fluorescent marker administered intravenously allows calculation of GFR. The challenge is to ensure that the values of GFR obtained using the washout approach are in accord with those obtained conventionally., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: It is essential to have an accurate assessment of the renal function of patients with chronic kidney disease to monitor, treat, and predict further development of the condition. Measurement of renal function in terms of glomerular filtration rate (GFR) requires either urine or blood sampling, but especially in children, more simple methods of measurement are preferable. The main objective of this study was to examine if the estimated GFR (eGFR) calculated with different cystatin-C-based equations was comparable to the GFR measured by a radiotracer (mGFR) in pediatric patients., Methods: In this retrospective study, 28 pediatric patients contributed with 73 pairs of measurements collected within 5 years. Bland-Altman Limits of Agreement were used to evaluate the performance and accuracy of two different cystatin-C-based estimates, the CKiD Crea-CysC and the CKiD U25 respectively, compared to an mGFR based on plasma clearance of technetium-99m-diethylenetriaminepentaacetic acid or chromium-51-ethylenediaminetetraacetic acid., Results: Using the CKiD Crea-CysC equation, 58.9% of the datasets were within P10 and 87.7% were within P30. The mean difference was 4.8 mL/min/1.73m 2 (standard deviation: 8.5 mL/min/1.73m 2 ) and tended to overestimate GFR and thereby overrate the kidney function within the entire GFR range. Using the CKiD U25 equation, 53.4% were within P10 and 93.2% within P30. The mean difference was -2.9 mL/min/1.73m 2 (standard deviation: 8.4 mL/min/1.73m 2 ), but the difference varied with the GFR value., Conclusions: A cystatin-C-based eGFR provides a viable substitute for monitoring renal function in pediatric patients with chronic kidney disease. However, it has a lower accuracy than mGFR and can therefore not replace mGFR in clinical use., (© 2024 The Authors. Pediatric Transplantation published by Wiley Periodicals LLC.)

Objectives: Accurate glomerular filtration rate (GFR) assessment is essential in critically ill patients. GFR is often estimated using creatinine-based equations, which require surrogates for muscle mass such as age and sex. Race has also been included in GFR equations, based on the assumption that Black individuals have genetically determined higher muscle mass. However, race-based GFR estimation has been questioned with the recognition that race is a poor surrogate for genetic ancestry, and racial health disparities are driven largely by socioeconomic factors. The American Society of Nephrology and the National Kidney Foundation (ASN/NKF) recommend widespread adoption of new "race-free" creatinine equations, and increased use of cystatin C as a race-agnostic GFR biomarker., Data Sources: Literature review and expert consensus., Study Selection: English language publications evaluating GFR assessment and racial disparities., Data Extraction: We provide an overview of the ASN/NKF recommendations. We then apply an Implementation science methodology to identify facilitators and barriers to implementation of the ASN/NKF recommendations into critical care settings and identify evidence-based implementation strategies. Last, we highlight research priorities for advancing GFR estimation in critically ill patients., Data Synthesis: Implementation of the new creatinine-based GFR equation is facilitated by low cost and relative ease of incorporation into electronic health records. The key barrier to implementation is a lack of direct evidence in critically ill patients. Additional barriers to implementing cystatin C-based GFR estimation include higher cost and lack of test availability in most laboratories. Further, cystatin C concentrations are influenced by inflammation, which complicates interpretation., Conclusions: The lack of direct evidence in critically ill patients is a key barrier to broad implementation of newly developed "race-free" GFR equations. Additional research evaluating GFR equations in critically ill patients and novel approaches to dynamic kidney function estimation is required to advance equitable GFR assessment in this vulnerable population., Competing Interests: Drs. Miano, Sakhuja, and Barreto received funding from the National Institutes of Health (NIH) (K08DK124658 to Dr. Miano); (K08KD 131286 to Dr. Sakhuja); and (K23AI143882 to Dr. Barreto). Dr. Barreto received funding from Wolters Kluwer. Dr. Martin received funding from Astra Zeneca, Nestle, and FloBio. Dr. Sakhuja’s institution received funding from the National Institute of Diabetes and Digestive and Kidney Diseases (1K08DK131286-01A1). Dr. Basu received funding from BioPorto Diagnostics, Biomerieux, Potrero, and Seastar Therapeutics; he received support for article research from NIH. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background: The CELTIC ranges project aims to deliver a comprehensive range of reference intervals for commonly ordered laboratory investigations suitable for use in an Irish population as well as enabling comparison with relevant international studies. In this paper, we describe our methodology used throughout the entire project and present paediatric reference intervals for renal profile tests in plasma (sodium, potassium, urea and creatinine)., Methods: 1023 children aged up to 17 years were recruited from our hospital's general practitioner paediatric phlebotomy clinic. Clinical chemistry analyses were performed on the Roche modular system and statistical analysis was completed in line with CLSI guideline EP28-A3c., Results: The plasma reference interval for sodium for ages 0.45-16.99 years was 137-143 mmol/L in 1000 subjects (combined genders). For plasma potassium, the corresponding ranges between 1 and 16.99 years (combined genders) were 3.6-4.8 mmol/L. Apart from neonates and in keeping with other studies, age partitioning for electrolytes was not required. Data for plasma creatinine (enzymatic methodology) and urea is also presented and, as anticipated, required partitioning for both age and gender., Conclusions: Our renal profile findings are broadly consistent with those of international studies, for example, CALIPER, HAPPI, NORDIC, PRINCE and KiGGs. Moreover, the CELTIC ranges study is also based on over 1000 subjects whose samples were analysed on the widely used Roche modular analytics system. We also expect the findings will improve knowledge of children's metabolic health in Ireland., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background and Objectives : The European Kidney Function Consortium (EKFC) equation has been newly proposed for estimating glomerular filtration rate (eGFR) across the spectrum of age. We compared the EKFC equation with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations in a large-scale Korean population. Materials and Methods : Using the representative Korean health examination data, the Korea National Health and Nutrition Examination Survey (KNHANES 2008-2021), the records of 91,928 subjects (including 9917 children) were analyzed. We compared the EKFC equation with CKiD, CKD-EPI 2009, and CKD-EPI 2021 equations and investigated their agreement across GFR categories. Results : In the total population, the CKD-EPI 2021 equation yielded the highest eGFR value, followed by the CKD-EPI 2009 and EKFC equations. In children, the distribution of eGFR differed significantly between the EKFC and CKiD equations ( p < 0.001), with a wider range of eGFR values found with the CKiD equation. Each equation showed weak or moderate agreement on the frequency of the GFR category (κ = 0.54 between EKFC and CKD-EPI 2021; κ = 0.77 between EKFC and CKD-EPI 2009). The eGFR values found by the EKFC equation showed high or very high correlations with those by the CKiD, CKD-EPI 2009, and CKD-EPI 2021 equations (r = 0.85, 0.97, and 0.97, respectively). As eGFR values increased, bigger differences were observed between equations. Conclusions : This large-scale study demonstrates that the EKFC equation would be applicable across the entire age spectrum in Asian populations. It also underscores that national kidney health would be highly affected by an eGFR equation being implemented. Additional investigation and more caution would be warranted for the transition of eGFR equations.

Objectives: The European Kidney Function Consortium (EKFC) developed two novel equations in 2023 for estimating glomerular filtration rate (GFR): one sex-free cystatin C-based equation (EKFC Cys ) and one creatinine-cystatin C combined equation (EKFC Cr-Cys ). This study compared their performance with the previous creatinine-based EKFC equation (EKFC Cr ) and commonly used Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Berlin Initiative Study (BIS) equations in Chinese adults., Methods: A total of 2,438 Chinese adults (mean age=53.04 years) who underwent the 99mTc-DTPA renal dynamic imaging for reference GFR (rGFR) were included. Diagnostic value was evaluated using correlation coefficients, sensitivity, specificity, and area under the receiver operating characteristic curve (ROC AUC ). Performance was assessed in terms of bias, precision (interquartile range of the median difference [IQR]), accuracy (percentage of estimates ±30 % of rGFR [P30], and root-mean-square error [RMSE]) across age, sex, and rGFR subgroups. Gender differences in bias and P30 were also analyzed., Results: Average rGFR was 73.37 mL/min/1.73 m 2 . EKFC equations showed stronger correlations and larger AUCs compared to the parallel CKD-EPI equations, with EKFC Cr-Cys demonstrating the greatest improvement (R=0.771, ROC AUC =0.913). Concerning bias, precision, and accuracy, EKFC equations consistently outperformed CKD-EPI equations. EKFC Cr-Cys and EKFC Cr performed acceptably well in the entire population and were equivalent to BIS equations in the elderly. All equations, including EKFC Cys , showed similar P30 accuracy across sexes., Conclusions: EKFC equations provided a reasonable alternative for estimating GFR in the Chinese adult population. While EKFC Cys did not outperform EKFC Cr , EKFC Cr-Cys improved the accuracy of single-marker equations., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Background and Aims: Patients with inflammatory bowel diseases (IBD) are exposed to drug-related nephrotoxicity and kidney-related extra-intestinal manifestations (EIMs). Patients should be monitored but guidance is lacking in current international recommendations. The objective of the Kidney Function Monitoring in Inflammatory Bowel Disease (MONITORED) initiative was to achieve an expert consensus about monitoring kidney function in IBD., Methods: A literature review was first conducted. Then, an expert consensus meeting, involving 28 attendees representing French-speaking gastroenterologists and nephrologists, was held as part of an academic initiative on May 28, 2021. An anonymous Delphi process was used to discuss and vote on statements. Agreement was defined as at least 75% of participants voting for any one statement., Results: Experts reached consensus on 11 criteria for referral to the nephrologist. Concerning kidney function monitoring, participants unanimously validated the use of serum creatinine with estimation of the glomerular filtration rate via the MDRD or CKD-EPI equations. A blood ionogram and a urine sample with measurement of a protein-to-creatinine ratio were also broadly agreed validated. Experts recommended performing this monitoring at IBD diagnosis, prior introducing a new treatment, and annually for EIMs screening and evaluation of treatment tolerance. An evaluation 3 months after starting mesalamine and then every 6 months was felt necessary, while for biologics an annually monitoring was deemed sufficient., Conclusion: The MONITORED consensus proposed guidelines on how to monitor kidney function in IBD. These recommendations should be considered in clinical practice to preserve kidney function and ensure the best approach to our patients., Competing Interests: Conflict of interest L Guillo declares consulting fees for Abbvie. A Amiot declares counseling, boards, lecture, transports or fees from Abbvie, Hospira, Takeda, Gilead, Biocodex, Janssen, Ferring and MSD. B Caron has received lecture and/or consulting fees from Abbvie, Amgen, Celltrion, Janssen, Takeda. G Boschetti has served as a speaker and advisory board member for Abbvie, Janssen, Ferring, Norgine, Tillotts, Pfizer, Celltrion, Takeda, Amgen, Sandoz. G Bouguen has received lecture fees from Abbvie, Ferring, MSD, Takeda, Otsuka, Amgen, Biogen, Celtrion, Janssen, Tillots and Pfizer and consultant fees from Takeda, Janssen, Mylan, Vifor Pharma and Gilead. JM Gornet has received personal fees from Amgen, Janssen Cilag, Sanofi, Takeda, Roche and Tillots Pharma. J Bonnet has received consulting fees for Amgen. L Vuitton has received lecture fees from Abbvie, MSD, Takeda, Ferring, Janssen and Pfizer, and research grants from MSD, Takeda and Pfizer. M Nachury received board membership, consultancy, or lecture fees from Abbvie, Adacyte, Amgen, Arena, CTMA, Celltrion, Ferring, Fresenius-Kabi, Janssen, Mayoli-Spindler, MSD, Pfizer, Takeda. M Uzzan has served as a speaker for Janssen and Abbvie. M Serrero declares lecture and consulting fees for Abbvie, Celltrion, Ferring, Janssen, MSD, Takeda and Tillotts. L Peyrin-Biroulet has served as a speaker, consultant and advisory board member for Merck, Abbvie, Janssen, Genentech, Mitsubishi, Ferring, Norgine, Tillotts, Vifor, Hospira/Pfizer, Celltrion, Takeda, Biogaran, Boerhinger-Ingelheim, Lilly, HAC- Pharma, Index Pharmaceuticals, Amgen, Sandoz, For- ward Pharma GmbH, Celgene, Biogen, Lycera, Samsung Bioepis, Theravance. The remaining authors declare no conflict of interest., (Copyright © 2021 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

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: Reference intervals (RIs) for clinical chemistry test parameters are specific to the method of measurement and population under service. However, there has been no locally available dry chemistry based RIs for the Nepalese population. Thus, the present study aimed to establish dry chemistry based RIs for sodium, potassium, urea, and creatinine specific to adult populations of Kaski districts, Nepal METHODS: This was a cross-sectional study conducted at the Manipal Teaching Hospital, Pokhara, Kaski, Nepal on 360 healthy adult participants aged 18-65 years. The test parameters under study were analyzed using a fully automated OCD Vitros 350 dry chemistry analyzer following the protocols provided by the reagent kit manufacturer. The RIs were estimated using reference limits at 2.5th and 97.5th percentiles. The normal distribution of the data was tested by Kolmogorov-Smirnov, and Shapiro-Wilk tests. The differences between males and females RIs were compared by the Mann-Whitney test while age-specific RIs for each sex was compared by One-Way-ANOVA and Dunnett's Multiple Comparisons Tests. All the data were managed and analyzed using MS Excel and SPSS version 20., Results: The RIs of urea, creatinine, sodium, and potassium specific to the adult population of Kaski district, Nepal are as follows: urea: 4.20-13.70 mmol/L (males: 4.70-13.99; females: 4.20-13.23); creatinine: 44.20-106.10 μmol/L (males: 48.82-106.10; females: 35.40-83.78); sodium 135-146 mmol/L (males: 135-146; females: 135-146) and potassium 3.60-5.10 mmol/L (males: 3.54-5.0; females: 3.60-5.10). These RIs were found to be different from currently used RIs provided by the reagent manufacturer. RIs of all the test parameters were significantly influenced by the age of the study participants. However, only the RIs of urea, creatinine, and potassium were significantly influenced by sex., Conclusions: The present study has for the first time established dry chemistry based RIs for selected renal function test parameters specific to the adult population of Kaski district, Nepal. This result will aid the clinician in minimizing the errors in result interpretation and making a precise clinical decision., (© 2021. The Author(s).)

Acute kidney injury (AKI) is common in the intensive care unit, where it is associated with increased mortality. AKI is often defined using creatinine and urine output criteria. The creatinine-based definition is more reliable but less expedient, whereas the urine output based definition is rapid but less reliable. Our goal is to examine the urine output criterion and augment it with physiological features for better agreement with creatinine-based definitions of AKI. The objectives are threefold: (1) to characterize the baseline agreement of urine output and creatinine definitions of AKI; (2) to refine the urine output criteria to identify the thresholds that best agree with the creatinine-based definition; and (3) to build generalized estimating equation (GEE) and generalized linear mixed-effects (GLME) models with static and time-varying features to improve the accuracy of a near-real-time marker for AKI. We performed a retrospective observational study using data from two independent critical care databases, MIMIC-III and eICU, for critically ill patients who developed AKI in intensive care units. We found that the conventional urine output criterion (6 hr, 0.5 ml/kg/h) has specificity and sensitivity of 0.49 and 0.54 for MIMIC-III database; and specificity and sensitivity of 0.38 and 0.56 for eICU. Secondly, urine output thresholds of 12 hours and 0.6 ml/kg/h have specificity and sensitivity of 0.58 and 0.48 for MIMIC-III; and urine output thresholds of 10 hours and 0.6 ml/kg/h have specificity and sensitivity of 0.49 and 0.48 for eICU. Thirdly, the GEE model of four hours duration augmented with static and time-varying features can achieve a specificity and sensitivity of 0.66 and 0.61 for MIMIC-III; and specificity and sensitivity of 0.66 and 0.64 for eICU. The GLME model of four hours duration augmented with static and time-varying features can achieve a specificity and sensitivity of 0.71 and 0.55 for MIMIC-III; and specificity and sensitivity of 0.66 and 0.60 for eICU. The GEE model has greater performance than the GLME model, however, the GLME model is more reflective of the variables as fixed effects or random effects. The significant improvement in performance, relative to current definitions, when augmenting with patient features, suggest the need of incorporating these features when detecting disease onset and modeling at window-level rather than patient-level., (© 2021. The Author(s).)

Background: Accurate estimating glomerular filtration rate (GFR) is crucial both in clinical practice and epidemiological survey. We incorporated semi-supervised learning technology to improve GFR estimation performance., Methods: AASK [African American Study of Kidney Disease and Hypertension], CRIC [Chronic Renal Insufficiency Cohort] and DCCT [Diabetes Control and Complications Trial] studies were pooled together for model development, whereas MDRD [Modification of Diet in Renal Disease] and CRISP [Consortium for Radiological Imaging Studies of Polycystic Kidney Disease] studies for model external validation. A total of seven variables (Serum creatinine, Age, Sex, Black race, Diabetes status, Hypertension and Body Mass Index) were included as independent variables, while the outcome variable GFR was measured as the urinary clearance of 125 I-iothalamate. The revised CKD-EPI [Chronic Kidney Disease Epidemiology Collaboration] creatinine equations was selected as benchmark for performance comparisons. Head-to-head performance comparisons from four-variable to seven-variable combination were conducted between revised CKD-EPI equations and semi-supervised models., Results: In each independent variables combination, the semi-supervised models consistently achieved superior results in all three performance indicators compared with corresponding revised CKD-EPI equations in the external validation data set. Furthermore, compared with revised four-variable CKD-EPI equation, the seven-variable semi-supervised model performed less biased (mean of difference: 0.03 [- 0.28, 0.34] vs 1.53 [1.28, 1.85], P < 0.001), more precise (interquartile range of difference: 7.94 [7.37, 8.50] vs 8.28 [7.76, 8.83], P = 0.1) and accurate (P30: 88.9% [87.4%, 90.2%] vs 86.0% [84.4%, 87.4%], P < 0.001., Conclusions: The superior performance of the semi-supervised models during head-to-head comparisons supported the hypothesis that semi-supervised learning technology could improve GFR estimation performance., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Context: As the number of transgender (trans) people (including those who are binary and/or nonbinary identified) seeking gender-affirming hormone therapy rises, endocrinologists are increasingly asked to assist with interpretation of laboratory tests. Many common laboratory tests such as hemoglobin, iron studies, cardiac troponin, and creatinine are affected by sex steroids or body size. We seek to provide a summary of the impact of feminizing and masculinizing hormone therapy on common laboratory tests and an approach to interpretation., Cases: Case scenarios discussed include 1) hemoglobin and hematocrit in a nonbinary person undergoing masculinizing hormone therapy; 2) estimation of glomerular filtration rate in a trans woman at risk of contrast-induced nephropathy; 3) prostate-specific antigen (PSA) in a trans woman; and 4) chest pain in a trans man with a cardiac troponin concentration between the reported male and female reference ranges., Conclusions: The influence of exogenous gender-affirming hormone therapy on fat and muscle distribution and other physiological changes determines interpretation of laboratory tests that have sex-specific differences. In addition to affirmative practice to ensure a patient's name, gender, and pronoun are used appropriately, we propose that once individuals have commenced gender-affirming hormone therapy, the reference range of the affirmed gender be reported (and specified by treating clinicians) except for PSA or cardiac troponin, which are dependent on organ size. While suggestions may be challenging to implement, they also represent an opportunity to lead best practice to improve the quality of care and experiences of healthcare for all trans people., (© Endocrine Society 2020.)

We report the case of a 43-year-old man, suffering from ankylosing spondylitis and treated with Infliximab 5 mg/kg every 2 months, with an excellent disease control. During a follow-up consultation, an incipient renal insufficiency is detected. A urine analysis showed haematuria and proteinuria and a renal puncture-biopsy revealed an image of IgA nephropathy.Several cases of IgA nephropathy have been reported in the literature associated with ankylosing spondylitis. Some of them occur in patients treated with antitumour necrosis factor, but it is unclear whether this pathology is caused by the treatment or whether treatment failed to prevent its occurrence.Our clinical case highlights the importance of regular monitoring of renal function in patients with ankylosing spondylitis, as well as urinary spotting.The question of whether the disease itself, the treatment or other factors such as immune dysregulation could be held responsible for kidney disease will be addressed in the discussion., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Calcitonin (CT) is a marker for both initial diagnosis and monitoring of patients with residual or recurrent medullary thyroid carcinoma (MTC). In Japan, serum CT had been measured by radioimmunoassay (RIA) until recently. Electrochemiluminescence immunoassay (ECLIA) became commercially available in 2014, and this technique is now the only method used to examine CT concentration. The purposes of this study were to investigate the correlations between the CT concentration measured with ECLIA (ECLIA-CT) and RIA (RIA-CT) and to explore the clinical characteristics of patients with elevated ECLIA-CT. CT concentrations of 348 sera samples from 334 patients with various thyroid disorders including nine MTC were measured using both assays. The correlation analysis revealed an excellent correlation between ECLIA-CT and RIA-CT among the cases with CT level >150 pg/mL by both assays (r s = 0.991, p < 0.001). However, 63% of all samples exhibited undetectable ECLIA-CT, while their RIA-CTs were measured between 15 and 152 pg/mL. The ECLIA-CTs in all patients who underwent total thyroidectomy for non-MTC showed low concentrations. High ECLIA-CT was observed in patients with MTC or pancreas neuroendocrine tumor. ECLIA-CT was also increased in 14 other male patients with non-MTC, including four with renal failure. Multivariate logistic regression analysis showed that male sex, negative TgAb, and lower estimated glomerular filtration rate were independent factors to predict detectable ECLIA-CT (≥0.500 pg/mL). These results indicate that ECLIA-CT correlates well with RIA-CT in higher range and is affected by sex, TgAb, and renal function.

Background: Obesity is an established risk factor for renal disease and for disease progression. Therefore, an accurate determination of renal function is necessary in this population. Renal function is currently evaluated by estimated glomerular filtration rate (GFR) by formulas, a procedure with a proven high variability. Moreover, the adjustment of GFR by body surface area (BSA) confounds the evaluation of renal function. However, the error of using estimated GFR adjusted by BSA has not been properly evaluated in overweight and obese subjects., Methods: We evaluated the error of 56 creatinine- and/or cystatin-C-based equations and the adjustment of GFR by BSA in 944 subjects with overweight or obesity with or without chronic kidney disease (CKD). The error between estimated (eGFR) and measured GFR (mGFR) was evaluated with statistics of agreement: the total deviation index (TDI), the concordance correlation coefficient (CCC) and the coverage probability (cp)., Results: The error of eGFR by any equation was common and wide: TDI averaged 55%, meaning that 90% of estimations ranged from -55 to 55% of mGFR. CCC and cp averaged 0.8 and 26, respectively. This error was comparable between creatinine and cystatin-C-based formulas both in obese or overweight subjects. The error of eGFR was larger in formulas that included weight or height. The adjustment of mGFR or eGFR led to a relevant underestimation of renal function, reaching at least 10 mL/min in 25% of the cases., Conclusions: In overweight and obese patients, formulas failed in reflecting real renal function. In addition, the adjustment for BSA led to a relevant underestimation of GFR. Both errors may have important clinical consequences. Thus, whenever possible, the use of a gold standard method to measure renal function is recommended. Moreover, the sense of indexing for BSA should be re-considered and probably abandoned.

Background: Prior papers have been inconsistent regarding how much creatinine clearance (CrCl) overestimates glomerular filtration rate (GFR). A recent cross-sectional study suggested that measurement error alone could entirely account for the longstanding observation that CrCl/GFR ratio is larger when GFR is lower among patients with chronic kidney disease (CKD); but there have been no validation of this in other cohorts., Methods: To fill these gaps in knowledge regarding the relation between CrCl and GFR, we conducted cross-sectional and longitudinal analysis of the Modification of Diet in Renal Disease study (MDRD) and African American Study of Kidney Disease and Hypertension (AASK); and cross-sectional analysis of a clinical dataset from the Mayo Clinic of four different patient populations (CKD patients, kidney transplant recipients, post kidney donation subgroup and potential kidney donors). In the cross-sectional analyses (MDRD, AASK and Mayo Clinic cohort), we examined the relation between the CrCl/iothalamate GFR (iGFR) ratio at different categories of iGFR or different levels of CrCl. In the MDRD and AASK longitudinal analyses, we studied how the CrCl/iGFR ratio changed with those who had improvement in iGFR (CrCl) over time versus those who had worsening of iGFR (CrCl) over time., Results: Observed CrCl/iGFR ratios were generally on the lower end of the range reported in the literature for CKD (median 1.24 in MDRD, 1.13 in AASK and 1.25 in Mayo Clinic cohort). Among CKD patients in whom CrCl and iGFR were measured using different timed urine collections, CrCl/iGFR ratio were higher with lower iGFR categories but lower with lower CrCl categories. However, among CKD patients in whom CrCl and iGFR were measured using the same timed urine collections (which reduces dis-concordant measurement error), CrCl/iGFR ratio were higher with both lower iGFR categories and lower CrCl categories., Conclusions: These data refute the recent suggestion that measurement error alone could entirely account for the longstanding observation that CrCl/GFR ratio increases as GFR decreases in CKD patients. They also highlight the lack of certainty in our knowledge with regard to how much CrCl actually overestimates GFR.

Background: It is unclear whether discharging patients from renal clinic to primary care is safe., Aim: To determine the characteristics, primary care monitoring and renal outcomes of patients discharged from renal clinic., Design and Setting: A retrospective study of 2236 adults discharged from a tertiary renal clinic between 2013-2018., Method: Patient demographics, primary renal disease, laboratory results and timeline dates were collected from the renal IT system. Timing of blood tests, renal progression, needing dialysis and patient survival were analysed. Reasons for discharge and cause of disease progression were reviewed in patients developing new estimated glomerular filtration rate <20 ml/min/1.73 m2., Results: Patients were older (median age 75; interquartile range 63-84) with non-progressive, seemingly non-proteinuric renal disease. Median time to repeat blood test post-discharge was 75 days with 90% tested within 12 months. Sixty-six percent saw an improvement in kidney function post-discharge and only 13% had a decline of >10 ml/min/1.73 m2. Only 132 patients (6%) developed new advanced chronic kidney disease (estimated glomerular filtration rate < 20 ml/min/1.73 m2) of whom 40% were palliative, 36% had developed acute kidney injury and 23% discharged for failing to attend clinic. One hundred and thirty-four patients (6%) were referred back to nephrology and eight started dialysis of whom six were discharged for failure to attend clinic., Conclusion: Most discharged patients are low risk of progressive renal disease and need infrequent monitoring. Non-adherent patients discharged for failing to attend appear to be at risk of poor outcomes and new strategies are needed to better support this population., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved.For permissions, please e-mail: journals.permissions@oup.com.)

Background: Pediatric acute kidney injury (AKI) is associated with long-term morbidity and mortality; however, outcomes improve when AKI is detected earlier. Current definitions of AKI use baseline creatinine; community-acquired AKI (CA-AKI) is difficult to define and detect in the pediatric emergency department (ED) when no baseline creatinine is available. Our objective was to compare age- and gender-based creatinine norms to the traditional baseline (lowest creatinine in previous 3 months) to diagnose CA-AKI., Methods: This was a retrospective cross-sectional study conducted in children 1 month-18 years of age seen in the pediatric ED in whom a creatinine was obtained., Results: Per the Kidney Disease Improving Global Outcomes AKI definition in encounters with baseline creatinine available, 343/2338 (14.7%) had CA-AKI. When the upper limit of the age- and gender-based creatinine norm was applied as a surrogate baseline creatinine, CA-AKI was diagnosed in 1.5% of encounters (239/15,486). Additionally, CA-AKI was diagnosed in 178 cases using the upper limit of age- and gender-based creatinine norms only, as these cases did not have a baseline creatinine., Conclusions: Age- and gender-based creatinine norms can be applied as a surrogate baseline to detect CA-AKI in all children regardless of whether baseline creatinine is available, potentially detecting it earlier.

Background: Dynamic renal scintigraphy remains the recognized method for evaluation of kidney function and perfusion. Although there is an extensive body of knowledge about the use of technetium-99m-mercaptoacetyltriglycine (99mTc-MAG3), much less has been written about renal technetium-99m-ethylenedicysteine (99mTc-EC) scintigraphy. The aim of this study was to determine the normal value of renal function parameters in 99mTc-EC dynamic renal scintigraphy: Tmax and T1/2. The effects of age, left or right side in the retroperitoneal space, and sex on those parameters were examined., Material and Methods: The research was conducted on 123 patients (F/M: 70/53; aged 2-71; averaging 14.8 years of age) with at least one normal kidney. A total of 194 healthy kidneys were examined, including pediatric kidneys., Results: According to this study, the normal value of Tmax is 2.85 min (± 1.16) and T1/2 is 8.7 min (± 3.61). Values calculated for pediatric studies are Tmax is 2.81 (± 1.16) and T1/2 is 8.63 (± 3.71)., Conclusions: The normal value of secretory and excretory renal function parameters was calculated. Although the value is slightly lower for children, this is not statistically significant, as globally there are no differences between the kidney-location sides and sexes for any parameter.

Introduction: Thyroid function is evaluated by thyroid stimulating hormone (TSH) and free thyroxine (fT4). Although many studies have indicated an intimate relationship between thyroid hormones and kidney functions, reports about the simultaneous evaluation of TSH and fT4 are rare., Objective: We aimed to analyze the association between TSH and kidney function, with emphasis on a potential nonlinear relationship, and identify an independent relationship between fT4 and kidney function., Methods: We reviewed the data of 7,061 subjects in the Korea National Health and Nutrition Examination Surveys who were randomly subsampled for thyroid function evaluation between 2013 and 2015. A total of 5,578 subjects were included in the final analysis, after excluding people <18 years old, and those with a short fasting time, abnormal fT4 levels, and thyroid disease or related medications. Creatinine-based estimated glomerular filtration rate (eGFR) was used to define kidney function., Results: A 1 mmol/L increase of logarithmic TSH was associated with decreased eGFR (β: -1.8; 95% CI -2.3 to -1.2; p < 0.001), according to multivariate linear regression analysis. On the multivariate generalized additive model plot, TSH demonstrated an L-shaped relationship with eGFR, showing a steeper slope for 0-4 mIU/L of TSH. A 1 µg/dL increase of fT4 was also associated with decreased eGFR (β: -7.0; 95% CI -0.94 to -4.7; p < 0.001) on the multivariate linear regression analysis; this association was reversed after adjusting for age. On the mediation analysis, the indirect effect via age and direct effect per 1 µg/dL increase of fT4 on eGFR was 9.9 (8.1 to 11.7, p < 0.001) and -7.1 (-9.3 to -4.8, p < 0.001), respectively., Conclusions: Increased TSH was associated with decreased eGFR, particularly in the reference range. The direct effect of increased fT4 was decreased eGFR, which may be affected indirectly by age., (© 2020 The Author(s) Published by S. Karger AG, Basel.)

Background: Patients with chronic kidney disease (CKD) are at high risk of end-stage kidney disease (ESKD). The Kidney Failure Risk Equation (KFRE), which predicts ESKD risk among patients with CKD, has not been validated in primary care clinics in Southeast Asia (SEA). Therefore, we aimed to (1) evaluate the performance of existing KFRE equations, (2) recalibrate KFRE for better predictive precision, and (3) identify optimally feasible KFRE thresholds for nephrologist referral and dialysis planning in SEA., Methods: All patients with CKD visiting nine primary care clinics from 2010 to 2013 in Singapore were included and applied 4-variable KFRE equations incorporating age, sex, estimated glomerular filtration rate (eGFR), and albumin-to-creatinine ratio (ACR). ESKD onset within two and five years were acquired via linkage to the Singapore Renal Registry. A weighted Brier score (the squared difference between observed vs predicted ESKD risks), bias (the median difference between observed vs predicted ESKD risks) and precision (the interquartile range of the bias) were used to select the best-calibrated KFRE equation., Results: The recalibrated KFRE (named Recalibrated Pooled KFRE SEA) performed better than existing and other recalibrated KFRE equations in terms of having a smaller Brier score (square root: 2.8% vs. 4.0-9.3% at 5 years; 2.0% vs. 6.1-9.1% at 2 years), less bias (2.5% vs. 3.3-5.2% at 5 years; 1.8% vs. 3.2-3.6% at 2 years), and improved precision (0.5% vs. 1.7-5.2% at 5 years; 0.5% vs. 3.8-4.2% at 2 years). Area under ROC curve for the Recalibrated Pooled KFRE SEA equations were 0.94 (95% confidence interval [CI]: 0.93 to 0.95) at 5 years and 0.96 (95% CI: 0.95 to 0.97) at 2 years. The optimally feasible KFRE thresholds were > 10-16% for 5-year nephrologist referral and > 45% for 2-year dialysis planning. Using the Recalibrated Pooled KFRE SEA, an estimated 82 and 89% ESKD events were included among 10% of subjects at highest estimated risk of ESKD at 5-year and 2-year, respectively., Conclusions: The Recalibrated Pooled KFRE SEA performs better than existing KFREs and warrants implementation in primary care settings in SEA.

Of the glomerular, tubular and endocrine functions of the kidney, nephrologists have mostly focused their attention on the glomerular functions-albuminuria and glomerular filtration rate (GFR)-to grade the severity of chronic kidney disease (CKD). Although both albuminuria and GFR are associated with renal and cardiovascular morbidity and mortality, the utility of measured GFR (mGFR) has been questioned. GFR when measured adequately is the most precise measure of glomerular function and can be useful to individualize therapy among patients with CKD. In situations where estimated GFR is known to provide imprecise estimates of glomerular function, for example, sarcopenia and advanced cirrhosis, the measurement of GFR may be especially important. We discuss several clinical situations where mGFR can potentially influence the quality of life or complications of therapy because of interventions based on imperfect knowledge of GFR. We reason that although large databases may not detect the benefits of mGFR at the population level, precision medicine requires that therapy be individualized based on the best estimate of GFR that can be obtained particularly when the risk of harm is increased. The recent standardization of mGFRs is a step in the right direction and may help in treating the individual patient with CKD with a lower risk of complications and a better quality of life. We call for research in these subgroups of patients where it is clinically felt that mGFR is useful for clinical decision-making., (Published by Oxford University Press on behalf of ERA-EDTA 2018. This work is written by US Government employees and is in the public domain in the US.)

Direct measurement methods of glomerular filtration rate (GFR) are considered as the gold standard to assess kidney function. Following the withdrawal of the Proinuline Serb® specialty by the French National Health Surveillance Agency, iohexol remains the most suitable marker to replace inulin as the marker for GFR in France. The assay is performed by high performance liquid chromatography (HPLC) coupled with ultraviolet (UV) detection or by mass spectrometry. Plasma clearance measurement is the protocol of choice: single-sample protocols dominate, but multiple-sample protocols may be more accurate in specific situations to improve accuracy. In some cases, urinary clearance protocols may be proposed. National and international recommendations suggest using a GFR measurement as a confirmatory test in cases where the creatinine-based estimated GFR is inappropriate, ie clinical situations characterized by a significant alteration of muscle mass or volume distribution. The indications retained by the working group were graded according to the level of recommendations. The essential indications are the evaluation of living kidney donor, the monitoring of kidney allograft function at one year post-transplantation, drugs with narrow therapeutic range (anticoagulant, chemotherapy) in patients with inadequate estimation of GFR by creatinine and clinical research.

Blood concentration of cystatin C is independent of muscle mass and tubular secretion. It can be used, in the absence of a reference method, as an alternative marker to creatinine for the evaluation of renal function and the estimation of glomerular filtration rate (GFR). Both particle-enhanced immunonephelemetry (PENIA) or immunoturbidimetry (PETIA) methods are available to determine cystatin C. From an analytical point of view, it is recommended to use methods whose calibration is traceable to the reference material (ERM-DA471/IFCC) and to report an estimated GFR based on cystatin C. The main equations used are those developed in 2012 by the group "Chronic kidney disease epidemiology collaboration (CKD-EPI)" for adults and those published by Schwartz in 2012 for children. National and international recommendations suggest using a cystatin C-based GFR estimate as a confirmatory test in the clinical settings where the relationship between creatinine production and muscular mass impairs the clinical performance of creatinine. The indications retained by the working group were graded according to the level of recommendations. The essential indications are the estimation and/or the monitoring of renal function in children and adolescents due to rapid changes in muscle mass; in patients with impaired muscle mass and in patients with an alteration of tubular secretion of creatinine (essentially iatrogenic effects).

Background: Most validations of paediatric glomerular filtration rate (GFR) estimating equations using standardized creatinine (CR) and cystatin C (CYS) assays have comprised relatively small cohorts, which makes accuracy across subgroups of GFR, age, body mass index (BMI) and gender uncertain. To overcome this, a large cohort of children referred for GFR determination has been established from several European medical centres., Methods: Three thousand four hundred eight measurements of GFR (mGFR) using plasma clearance of exogenous substances were performed in 2218 children aged 2-17 years. Validated equations included Schwartz-2009 CR /2012 CR/CYS/CR+CYS , FAS CR/CYS/CR+CYS , LMR CR , Schwartz-Lyon CR , Berg CYS , CAPA CYS , CKD-EPI CYS , Andersen CR+CYS and arithmetic means of the best single-marker equations in explorative analysis. Five metrics were used to compare the performance of the GFR equations: bias, precision and three accuracy measures including the percentage of GFR estimates (eGFR) within ± 10% (P 10 ) and ± 30% (P 30 ) of mGFR., Results: Three of the cystatin C equations, Berg CYS , CAPA CYS and CKD-EPI CYS , exhibited low bias and generally satisfactory accuracy across all levels of mGFR; CKD-EPI CYS had more stable performance across gender than the two other equations. Among creatinine equations, Schwartz-Lyon CR had the best performance but was inaccurate at mGFR < 30 mL/min/1.73 m 2 and in underweight patients. Arithmetic means of the best creatinine and cystatin C equations above improved bias compared to the existing composite creatinine+cystatin C equations., Conclusions: The present study strongly suggests that cystatin C should be the primary biomarker of choice when estimating GFR in children with decreased GFR. Arithmetic means of well-performing single-marker equations improve accuracy further at most mGFR levels and have practical advantages compared to composite equations.

Aim: To understand the agreement, precision, and accuracy between other estimated glomerular filtration rate (eGFR) equations and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine-cystatin C equation (EPI&#95;Cr&#95;CysC)., Materials and Methods: We conducted a cross-sectional study of 1,913 CKD patients. The eGFRs were calculated separately by creatinine clearance rate and Cockcroft-Gault equation corrected for standard body surface area (Ccr&#95;BSA and eCcr&#95;BSA); CKD-EPI creatinine equation (EPI&#95;Cr); CKD-EPI cystatin C equation (EPI&#95;CysC); EPI&#95;Cr&#95;CysC equation; Modification of Diet in Renal Disease (MDRD) Study equation with standardized serum creatinine; and full-age spectrum creatinine equation (FAS). The EPI&#95;Cr&#95;CysC equation was used as the reference., Results: When compared with the EPI&#95;Cr&#95;CysC equation, the EPI&#95;Cr equation achieved the highest agreement in eGFRs (Lin's concordance correlation coefficient = 0.936, 95% confidence interval (CI) = 0.930, 0.941). eCcr&#95;BSA and EPI&#95;Cr equations achieved the first and second highest percentage agreement in the accurate classification of CKD stage (72.55 vs. 71.25%). The MDRD equation had minimal bias and was closely followed by the EPI&#95;Cr equation (median difference = -1.3, 95% CI = -2.0, -0.8 vs. median difference = 2.5, 95% CI = 1.7, 3.3 mL/min/1.73m 2 ). The EPI&#95;CysC and EPI&#95;Cr equations achieved the first and second highest precision (interquartile range (IQR) of the difference = 12.2, 95% CI = 11.6, 12.9 vs. IQR of the difference = 15.5, 95% CI = 14.7, 16.3 mL/min/1.73m 2 ). The EPI&#95;Cr and MDRD equations performed similarly and both had the highest accuracy at 30% (1 - P 30 = 18.6, 95% CI = 16.9, 20.4 vs. 1 - P 30 = 18.6, 95% CI = 16.8, 20.3%)., Conclusion: For assessment of renal function, the EPI&#95;Cr equation performed the best and remained an acceptable alternative to the EPI&#95;Cr&#95;CysC equation in the absence of cystatin C.
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Kidney diseases are among the most frequently reported diseases with a poor prognosis that are diagnosed too late. According to current Kidney Disease Improving Global Outcomes (KDIGO) guidelines, diagnosis and risk stratification are mainly based on functional markers (creatinine and cystatin C), which are used to determine the estimated glomerular filtration rate (eGFR) and the analysis of urinary albumin excretion as a marker of kidney damage. These methods have limitations that can complicate the interpretation of the results and can lead to a delay of the diagnosis as well as to a misinterpretation of the prognosis. Therefore, new damage markers are required that sensitively and specifically detect kidney damage and enable targeted treatment. Urinalysis complements the laboratory diagnostic spectrum of diseases of the kidneys and urinary tract. It is mainly used for screening and provides important information on localization (renal/postrenal) and differentiation of kidney diseases (glomerular/tubulointerstitial).

Objective: To investigate the utility of estimated glomerular filtration rate for assessing kidney function in living kidney donors before and after nephrectomy., Methods: A total of 101 donors underwent inulin clearance measurements before and 1 year after nephrectomy. The mean of three inulin clearance values was used as the measured glomerular filtration rate. Estimated glomerular filtration rate based on serum creatinine and cystatin C levels was calculated using the Japanese estimated glomerular filtration rate equation, Chronic Kidney Disease Epidemiology Collaboration formula and new full age spectrum equation. Age-adjusted chronic kidney disease was defined as glomerular filtration rate <75 mL/min/1.73m 2 for donors aged <40 years, <60 mL/min/1.73m 2 for donors aged 40-65 years and <45 mL/min/1.73m 2 for donors aged >65 years., Results: The postoperative measured glomerular filtration rate <60 mL/min/1.73m 2 and age-adjusted chronic kidney disease rate were 36.0% and 27.0%, respectively. In younger donors (aged <50 years), postoperative measured glomerular filtration rate <60 mL/min/1.73m 2 and age-adjusted chronic kidney disease rates were 5.3% and 26.3%, respectively. In older donors (aged >70 years), postoperative measured glomerular filtration rate <60 mL/min/1.73m 2 and age-adjusted chronic kidney disease rates were 75.0% and 33.3%, respectively. Donor age and measured glomerular filtration rate were significant predictors of postoperative measured glomerular filtration rate. The Japanese estimated glomerular filtration rate equation based on creatinine and cystatin C showed the strongest correlation with measured glomerular filtration rate. However, the Japanese estimated glomerular filtration rate equation based on creatinine overestimated the prevalence of measured glomerular filtration rate <60 mL/min/1.73m 2 , whereas the Japanese estimated glomerular filtration rate based on cystatin C underestimated it., Conclusions: Aged donors might have an increased risk of lower glomerular filtration rate after donor nephrectomy; post-surgery, long-term monitoring of renal function is recommended. Measurement of glomerular filtration rate should be carried out for donors, especially pre-surgery. A more precise glomerular filtration rate equation is required in the future., (© 2019 The Japanese Urological Association.)

Objectives: The aim of the study was to identify a threshold value of the estimated glomerular filtration rate (eGFR) that would predict a measured glomerular filtration rate (mGFR) of ≤25 ml/min/1.73 m. This is to guide use of the new British Nuclear Medicine Society guidelines, which specifies a 24 h sample for patients with a GFR of ≤25 ml/min/1.73 m, when using the single-sample (SS) method., Patients and Methods: Data from 1956 patient studies were used to calculate values for the GFR using the slope intercept (SI) method and SS , which was taken 210 min after injection. A sub-data set of 241 patients was taken with patients having an mGFR of ≤80 ml/min/1.73 m by the SS or SI method and an eGFR value within 28 days of the mGFR. The Modification of Diet in Renal Disease equation was used to calculate the eGFR. Receiver operator characteristic curves comparing the sensitivity and specificity of using the eGFR to predict values of the mGFR were used to find a threshold value for the eGFR., Results: There is a large variation in the accuracy of using the eGFR to predict the mGFR value. The mean difference for the SI method is -2%, with an absolute percentage difference of 22% and a range of -121 to 63%. The SS method has a mean percentage difference of -1%, absolute percentage difference of 23% and a range of -153 to 86%.From the receiver operator characteristic graphs, an eGFR value of 40 ml/min/1.73 m was chosen to maximise the sensitivity of the eGFR threshold value used to predict an mGFR value of ≤25 ml/min/1.73 m., Conclusion: The eGFR value has a high error when used for predicting the mGFR. Therefore, the study recommends that an eGFR threshold value of ≤40 ml/min/1.73 m is used to predict mGFRs of ≤25 ml/min/1.73 m in order to optimise the likelihood of identifying all such patients.

Background: The growth and development of children and adolescents influence values of liver and renal function tests. The purpose of this study was to determine age- and gender-specific reference intervals for liver and renal function tests in apparently healthy Chinese children and adolescents., Methods: A total of 63,086 apparently healthy children and adolescents (0-15 y) were chosen as reference individuals in this study. The 15 biochemical analytes relating to liver and renal function were measured using an Olympus AU5400 analyzer. Reference intervals were partitioned according to age and/or gender subgroups using the Harris and Boyd's method and established using non-parametric methods., Results: Our results showed that all analytes except for cholinesterase (ChE) and α1-microglobulin (α1-MG) required partitioning by age. Gender partitions were also required for alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), creatinine (Cre), and uric acid (UA). Age- and gender-appropriate reference intervals for liver and renal function tests were established for apparently healthy Chinese children and adolescents., Conclusions: When establishing pediatric reference intervals, partitioning by age and/or gender is essential. Those reference intervals can be adopted in other clinical laboratories after appropriate validation., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: There is a growing interest in the relationship between obesity and renal damage. The effect of obesity on renal function in children and adolescents has not been adequately investigated. In addition, there is no complete consensus on the reliability of various renal function parameters. The primary goal of this study was to evaluate renal function in obese children and adolescents using glomerular filtration rate (GFR), cystatin C, and creatinine (Cr)-derived formulas. We also compared classical GFR measurement methods with methods based on bioimpedance analysis-derived body cell mass (BCM)., Methods: We enrolled 108 obese and 46 healthy subjects aged 6-18 years. Serum cystatin C, serum Cr, 24-hour proteinuria, Cr clearance, and GFR were evaluated in both groups. Estimated GFR was measured with Cr-based, cystatin C-based, combined (cystatin C and Cr) and BCM-based formulae. Both actual and fat-free mass body surface areas (BSA) were used when required. Metabolic parameters (blood glucose, insulin, and lipids) were analyzed in the obese subjects. International Diabetes Federation criteria were used to identify metabolic syndrome (MetS)., Results: We did not detect statistically significant differences between the obese and control groups for mean Cr (p=0.658) and mean cystatin C (p=0.126). Mean cystatin C levels of MetS patients were significantly higher than those of non-MetS obese participants (p<0.001). Cr-based GFR measurements, BCM-based measurements and a combined Cr and cystatin C measurement showed a statistically significant increase in the GFR of obese subjects compared to controls (p=0.002 and p<0.001). This increase was negatively correlated with duration of obesity. Estimations based on actual or fat-free mass BSA did not differ either. Only the Filler equation showed a statistically significant decrease in eGFR in MetS patients. There were no statistically significant differences between the obese and control groups for proteinuria (p=0.994) and fat-free mass proteinuria (p=0.476)., Conclusion: We conclude that cystatin C could be used as an earlier biomarker than Cr in the detection of impaired renal function in obese children, especially those with MetS. Cr-based formulae reveal hyperfiltration as the first change in renal function. Decreasing eGFR seen in MetS patients with cystatin C-based formulae, but not Cr-based formulae, may represent the early stages of renal damage. Using fat-free mass or BCM for eGFR formulae in obese children seems to provide no additional information.

Objective: Aimed to evaluate the validity of five published equations that estimate 24-h urinary sodium excretion (24-h USE) by timed spot urine specimens., Methods: All of the spot urines within 24 h were collected from 99 healthy volunteers aged 21-57 years. The spot urinary sodium and 24-h USE were measured. The 24-h USE was estimated by INTERSALT equation and Tanaka equation with casual spot urine and four timed spot urines (i.e. overnight, second morning, post meridiem, and evening urine), by Kawasaki equation and SunSMU equation with second morning urine, and by SunPM equation with post meridiem urine, respectively. At last, the agreement between measured and estimated 24-h USE was evaluated., Results: The average of the measured 24-h USE was 4558.25 ± 1908.75 mg/day. The proportion of participants with more than ±40% of relative difference between measured 24-h USE and estimated 24-h USE by five equations varied from 21.18 to 42.35%. The absolute differences of 24-h USE among approximately half of the participants were more than ±1170.00 mg/day estimated by Kawasaki equation, INTERSALT equation, and SunPM equation, respectively. In addition, misclassification rates of individual salt intake for five equations were more than 60%. It was found that overestimation occurred at low levels of sodium excretion whereas underestimation occurred at high levels of sodium excretion except Kawasaki equation. The 24-h USE estimated using Tanaka equation with four timed spot urine specimens varied substantially, although Tanaka equation with casual spot urine specimen provided the highest correlation coefficient and the least mean difference., Conclusion: There is still no evidence to support that 24-h USE could be estimated accurately using the current equations, especially for the equations developed by casual spot urine specimens.

Aging causes significant changes in the kidneys. One of the most important manifestations of an aging kidney is a reduction in glomerular filtration rate (GFR). Unfortunately, there is no generally accepted, adequate method for evaluating GFR in the elderly. The perspectivies of the relatively new approaches (BIS1, BIS2, FAS) are not clear and doubtful. The feasibility of standardization of GFR values by body surface area among of the older persons has not been determined. Possible that the diagnosis setting «chronic kidney disease» in elderly solely on the base of GFR decline may be an inadequate approach and promote a kind of «nephrological ageism».

Background: The evaluation of chronic kidney disease (CKD) in cancer patients seems to rely mostly on the Cockcroft-Gault (CG) formula or the creatinine levels to adjust treatment dosages which is a practice refuted by internists., Aims: We evaluate the overall agreement of the CG, modification of diet in renal disease (MDRD) and CKD-epidemiology collaboration equations (CKD-EPI) equation with the newly devised Janowitz and Williams' (JW) equation., Methods: The renal function was estimated in 235 cancer patients according to the CG, MDRD, body surface area (BSA)-adjusted MDRD, CKD-EPI, BSA-adjusted CKD-EPI and JW formulae., Results: JW equation was more in agreement with CG and CKD-EPI estimations than the other equations. Taking JW equation as reference, receiver operating characteristic curve analysis showed that CG eGFR had the higher area under the curve when compared with other equations. Hierarchical cluster analysis showed more proximity between CG and JW equations than the other equations., Conclusion: The newly proposed JW eGFR estimation was more in agreement with CG equation than the other equations., (© 2018 Royal Australasian College of Physicians.)

Acute kidney injury (AKI) is characterized clinically as an abrupt decline in renal function marked by reduced excretion of waste products, disordered electrolytes, and disrupted fluid homeostasis. The recent development of a standardized AKI definition has transformed our understanding of AKI epidemiology and outcomes. We now know that in the short term, children with AKI experience greater morbidity and mortality; additionally, observational studies have established that chronic renal sequelae are far more common after AKI events than previously realized. Many of these studies suggest that patients who develop AKI are at greater risk for the subsequent development of chronic kidney disease (CKD). The goal of this review is to critically evaluate the data regarding the association between AKI and CKD in children. Additionally, we describe best practice approaches for future studies, including the use of consensus AKI criteria, the application of rigorous definitions for CKD and renal sequelae, and the inclusion of non-AKI comparator groups. Finally, based upon existing data, we suggest an archetypal approach to follow-up care for the AKI survivors who may be at greater CKD risk, including children with more severe AKI, those who endure repeated AKI episodes, patients who do not experience full recovery, and those with pre-existing CKD.

Background: Renal injury is a common perioperative complication. The adoption of renal endpoints, standardised and valid for use in perioperative clinical trials, would enhance the quality of perioperative clinical research. The Standardised Endpoints in Perioperative Medicine (StEP) initiative was established to derive standardised endpoints for use in perioperative clinical trials., Methods: A systematic review was conducted to identify renal endpoints currently reported in perioperative clinical trials. In parallel, an initial list of candidate endpoints was developed based on renal theme group expertise. A multi-round Delphi consensus process was used to refine this list and produce a suite of recommended perioperative renal outcome measures., Results: Based on our systematic review, 63 studies were included for analysis. Marked heterogeneity and imprecision of endpoint definitions were observed. Our initial list of candidate endpoints included 10 endpoints for consideration. The response rates for Delphi rounds 1, 2, and 3 were 89% (n=16), 90% (n=75), and 100% (n=6), respectively. A final list of four renal endpoints was identified: acute kidney injury defined by the Kidney Disease: Improving Global Outcomes (KDIGO) consensus criteria, acute kidney disease defined by ≥30% decline in estimated glomerular filtration rate from baseline at 30 days after operation in patients meeting the acute-kidney-injury criteria within 7 days of surgery, the composite of death or renal replacement therapy, and the Major Adverse Kidney Events (MAKE) composite., Conclusions: We identified four key renal outcome measures that should be considered for use in perioperative clinical trials. Using standardised definitions to capture and report these endpoints will facilitate improved benchmarking and meta-analysis of future trials., (Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background The use of serum creatinine equations for estimating glomerular filtration rate is well known in adults and children. We evaluated the revised Schwartz creatinine-based estimated glomerular filtration rate prediction equation in Black African children in KwaZulu-Natal, South Africa. Methods Review of medical records of all Black African patients aged 2-18 years old who have had glomerular filtration rate determined by intravenous Technetium-99 m-diethylene-triamine-pentaacetate, for the period 1 January 2010 to 31 December 2014 at the Inkosi Albert Luthuli Central Hospital, Durban, South Africa was performed. Estimated glomerular filtration rate result obtained using the revised Schwartz equation was compared to Technetium-99 m-diethylene-triamine-pentaacetate plasma clearance measured glomerular filtration rate. Accuracy of the estimated glomerular filtration rate equations within 10% (P 10 ) and 30% (P 30 ) of the measured glomerular filtration rate, sensitivity and specificity for predicting glomerular filtration rate < 60 mL/min/1.73 m 2 and < 30 mL/min/1.73 m 2 was determined. Results Results from 148 African children between 2 and 18 years old were analysed. P 10 and P 30 values were 16 and 49%, respectively. Sensitivity of 92.9% (95% CI: 80.5-85), specificity of 95.3 (95% CI: 89.3-98.5) and AUC of 0.96 (95% CI 0.92-0.99) were obtained for measured estimated glomerular filtration rate < 60 mL/min/1.73 m 2 . Sensitivity of 88.2% (95% CI: 63.6-98.5), specificity of 90.8 (95% CI: 84.5-95.2) and area under the curve of 0.93 (95% CI 0.88-0.96) were obtained for measured estimated glomerular filtration rate < 30 mL/min/1.73 m 2 . Conclusions The revised Schwartz equation did not meet the National Kidney Foundation Kidney Disease Outcomes Quality Initiative guidelines of 90% of estimated glomerular filtration rate results within 30% of measured glomerular filtration rate.

Aims Physiological changes that occur during pregnancy can influence biochemical parameters. Therefore, using reference intervals based on specimens from non-pregnant women to interpret laboratory results during pregnancy may be inappropriate. This study aimed to establish the essential reference intervals for a range of analytes during pregnancy. Methods A cross-sectional study was performed in 13,656 healthy pregnant and 2634 non-pregnant women. Fifteen biochemical measurands relating to renal and hepatic function were analysed using an Olympus AU5400 analyzer (Olympus, Tokyo, Japan). All the laboratory results were checked for outliers using Dixon's test. Reference intervals were established using a non-parametric method. Results Alanine aminotransferase, aspartate aminotransferase, albumin, cholinesterase, creatinine, direct bilirubin, gamma-glutamyl transpeptidase, total bilirubin, total bile acid and total protein showed a decrease during the whole gestational period, while alkaline phosphatase and uric acid increased. Urea nitrogen, β 2 -microglobulin and cystatin-C fell significantly during the first trimester and then remained relatively stable until third trimester. Reference intervals of all the measurands during normal pregnancy have been established. Conclusions The reference intervals established here can be adopted in other clinical laboratories after appropriate validation. We verified the importance, for some measurands, of partitioning by gestational age when establishing reference intervals during pregnancy.

There is no simple method to measure glomerular filtration rate (GFR) in swine, an established model for studying renal disease. We developed a protocol to measure GFR in conscious swine by using the plasma clearance of iohexol. We used two groups, test and validation, with eight animals each. Ten milliliters of iohexol (6.47 g) was injected into the marginal auricular vein and blood samples (3 mL) were collected from the orbital sinus at different points after injection. GFR was determined using two models: two-compartment (CL2: all samples) and one-compartment (CL1: the last six samples). In the test group, CL1 overestimated CL2 by ~30%: CL2 = 245 ± 93 and CL1 = 308 ± 123 mL/min. This error was corrected by a first-order polynomial quadratic equation to CL1, which was considered the simplified method: SM = -47.909 + (1.176xCL1) - (0.00063968xCL1²). The SM showed narrow limits of agreement with CL2, a concordance correlation of 0.97, and a total deviation index of 14.73%. Similar results were obtained for the validation group. This protocol is reliable, reproducible, can be performed in conscious animals, uses a single dose of the marker, and requires a reduced number of samples, and avoids urine collection. Finally, it presents a significant improvement in animal welfare conditions and handling necessities in experimental trials., Competing Interests: The authors declare no conflict of interest.

Background: Dynamic renal scintigraphy provides effective diagnosis of obstructive uropathy and nephropathy. However, in case of a bilateral outflow impairment, relative differential renal function (DRF), which is a primary quantitative criterion for diagnosis of unilateral obstructive nephropathy (when its value is below 45%, according to EANM guidelines from 2011), becomes unreliable. In case of bilateral nephropathy with similar severity, this parameter may even be within the normal range (45-55%) for both kidneys. The aim of this study was therefore to assess diagnostic usefulness of the original, normalized, absolute parameter proportional to the value of renal clearance function (K) in the evaluation of obstructive nephropathy in a group of patients with bilateral uropathy., Material and Methods: 16 healthy volunteers (32 kidneys) without history of kidney diseases were examined to determine normative value of K index. Then, 8 patients (16 kidneys) with bilateral obstructive uropathy found in standard dynamic renal scintigraphy performed using 111 MBq of 99mTc-EC (cumulative renographic curve that continued rising or dropped by less than 50% after i.v. administration of Furosemide) were examined. For each of the subjects 60 sequential 20s images were obtained, which were then assessed using an original method of post-processing scintigraphic data. It included normalization of renographic curves to the area under the heart curve. Subsequently, these normalized values from the uptake phase (between 2nd and 3rd minute) were inserted into the linear regression equation, from which K index was obtained., Results: In healthy volunteers the average value of K index was 0.23 ± 0.05. The value of 0.13 (mean -2 SD) was taken as the lower limit of the norm. Values below that limit suggest obstructive nephropathy. In patients with bilateral obstructive uropathy, 5 kidneys met the conventional criteria of nephropathy (DRF < 45%), while 11 kidneys had DRF within normal range. K index was below the norm in 9 kidneys (including 4 kidneys with low and 5 with normal DRF), while its value was normal in 7, including one kidney with reduced DRF (37%). K index changed the diagnosis in 6 kidneys out of 16 (38%)., Conclusions: Preliminary results indicate usefulness of K index in diagnosis of obstructive nephropathy in patients with bilateral obstructive uropathy. For further evaluation of clinical value of this method, it is planned to examine a larger group of patients with varying degrees of renal parenchymal function impairments.

Background: Measurements of GFR may be performed with a slope/intercept method (S/I), using only two blood samples taken in strictly defined time points. The aim of the study was to modify this method in order to extend time intervals suitable for blood sampling. Modification was based on a variation of a Russel et al. model parameter, selection of time intervals suitable for blood sampling and assessment of uncertainty of calculated results., Material and Methods: Archived values of GFR measurements of 169 patients with different renal function, from 5.5 to 179 mL/min, calculated with a multiple blood sample method were used. Concentrations of a radiopharmaceutical in consecutive minutes, from 60th to 190th after injection, were calculated theoretically, using archived parameters of biexponential functions describing a decrease in 99mTc-DTPA concentration in blood plasma with time. These values, together with injected activities, were treated as measurements and used for S/I clearance calculations. Next, values of S/I clearance were compared with the multiple blood sample method in order to calculate suitable values of exponent present in a Russel's model, for every combination of two blood sampling time points. A model was considered accurately fitted to measured values when SEE ≤ 3.6 mL/min. Assessments of uncertainty of obtained results were based on law of error superposition, taking into account mean square prediction error and also errors introduced by pipetting, time measurement and stochastic radioactive decay., Results: The accepted criteria resulted in extension of time intervals suitable for blood sampling to: between 60 and 90 minutes after injection for the first sample and between 150 and 180 minutes for the second sample. Uncertainty of results was assessed as between 4 mL/min for GFR = 5-10 mL/min and 8 mL/min for GFR = 180 mL/min., Conclusions: Time intervals accepted for blood sampling fully satisfy nuclear medicine staff and ensure proper determination of GFR. Uncertainty of results is entirely acceptable and for high GFR values even comparable with uncertainty of multi-sample measurements.

Electrolyte disorders due to tubular disorders are rare, and knowledge about validated clinical diagnostic tools such as tubular function tests is sparse. Reference values for tubular function tests are based on studies with small sample size in young healthy volunteers. Patients with tubular disorders, however, frequently are older and can have a compromised renal function. We therefore evaluated four tubular function tests in individuals with different ages and renal function. We performed furosemide, thiazide, furosemide-fludrocortisone, and desmopressin tests in healthy individuals aged 18-50 years, healthy individuals aged more than 50 years and individuals with compromised renal function. For each tubular function test we included 10 individuals per group. The responses in young healthy individuals were in line with previously reported values in literature. The maximal increase in fractional chloride excretion after furosemide was below the lower limit of young healthy individuals in 5/10 older subjects and in 2/10 patients with compromised renal function. The maximal increase in fractional chloride excretion after thiazide was below the lower limit of young healthy individuals in 6/10 older subjects and in 7/10 patients with compromised renal function. Median maximal urine osmolality after desmopressin was 1002 mosmol/kg H 2 O in young healthy individuals, 820 mosmol/kg H 2 O in older subjects and 624 mosmol/kg H 2 O in patients with compromised renal function. Reference values for tubular function tests obtained in young healthy adults thus cannot simply be extrapolated to older patients or patients with compromised kidney function. Larger validation studies are needed to define true reference values in these patient categories., (© 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)