Search

Serum creatinine (CR) is regarded as one of the most sought out prognostic biomarkers in medical evaluation of chronic kidney disease (CKD). In light of the diagnostic significance of CR, the utility of a fluorescence biosensor for its detection in human urine specimens has been explored based on Förster resonance energy transfer (FRET) across nitrogen-doped carbon dots (N-CDs) and gold nanoparticles (GNPs). A straightforward microwave-assisted synthesis procedure has been adopted to prepare N-CDs (λ excitation  = 400 nm, λ emission  = 540 ± 5 nm) with bright green emissions. On addition of pre-synthesized GNPs, the radiative emanation of the N-CDs is completely suppressed on account of FRET across the N-CDs and the GNPs. About 77 % of their fluorescence intensity is recovered after adding CR to GNPs@N-CDs nanocomposite. The limit of detection for CR sensing is estimated as 0.02 µg•mL -1 . This biosensor is selective enough to recognize CR in the existence of potential interfering substances (e.g., ascorbic acid, glucose, glutathione, urea, and electrolytes). Its practical utility for CR detection has been validated further on the basis of satisfactory correlation with the benchmark Jaffe method, as observed in artificial/human urine specimens. Consequently, this manuscript marks a pioneering report on employing CDs and GNPs-based FRET for identifying CR in urine specimens of CKD patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: This study aimed to examine the relationship between measures of kidney function and impaired lung function in individuals with diabetes and to assess all-cause mortality risk associated with having chronic kidney disease (CKD) and or impaired lung function., Design: Cross-sectional and retrospective cohort study., Setting: The National Health and Nutrition Examination Survey 2007-2012., Participants: A total of 10 809 participants aged over 20 years were included in this study: 9503 with normal spirometry, 951 with preserved ratio impaired spirometry (PRISm) and 355 with variable obstruction (VO)., Exposure and Outcome Measures: Kidney function measures, including estimated glomerular filtration rate (eGFR) and urinary albumin to creatinine ratio (UACR), were considered exposure variables. PRISm and VO were outcome variables. PRISm was defined as a forced expiratory volume in 1 s (FEV1)<80% predicted and an FEV1/forced vital capacity (FVC) ratio≥0.7, while VO was defined as an FEV1/FVC ratio <0.7 prebronchodilator and ≥0.7 postbronchodilator. In the cross-sectional analysis, multivariate logistic regression models were used to assess the relationship between kidney function measures and spirometry findings. In the retrospective cohort analysis, Cox proportional hazards models were employed to evaluate the impact of having PRISm or VO, combined with CKD, on all-cause mortality., Results: An increase in UACR was significantly associated with higher odds of PRISm (OR (95% CI)=1.10 (1.01, 1.21), p=0.03). Additionally, eGFR <60 was associated with the odds of variable obstructive lung function (OR (95% CI)=1.72 (1.07, 2.74), p=0.03) compared with eGFR >60. After adjustments, an increase in UACR was associated with higher odds of PRISm in individuals with diabetes (OR (95% CI)=1.21 (1.08, 1.36), p=0.002), and UACR ≥300 mg/g significantly increased odds of having PRISm in idividuals with diabetes (OR (95% CI)=2.34 (1.23, 4.47), p=0.01). During a mean follow-up of 12.3 years, 10 500 deaths occurred. In the diabetic group, compared with normal spirometry without CKD, those with both PRISm and CKD had a significantly increased risk of all-cause mortality (HR (95% CI)=3.46 (1.94, 6.16), p<0.0001)., Conclusion: An elevated UACR and albuminuria were linked to a higher risk of PRISm. Our study emphasises that kidney and lung function are correlated. Further research is necessary to confirm our findings., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Chihuahua represents an increasingly widespread breed predisposed to cardiac disease. N-terminal pro-B-type natriuretic peptide (NT-proBNP) might be a useful point-of-care biomarker for dogs suspected of having heart disease, but breed differences have been reported. The urinary aldosterone-to-creatinine ratio (UAldo: C) appears to be a good indicator of renin-angiotensin-aldosterone system activity in dogs, but Chihuahuas showed significantly higher UAldo: C than other breeds. The objective of this study was to assess preliminary breed-specific reference intervals for NT-proBNP and UAldo: C in healthy Chihuahuas and evaluate sex differences in these parameters., Results: Forty-three healthy Chihuahuas dogs were enrolled. The median NT-proBNP was 347 (125-515) pmol/L, and the median UAldo: C was 2.59 (1.57-4.61) µg/g. The NT-proBNP reference interval was 125 (90% CI 125-125) - 2121.4 (90% CI 941.6-2248) pmol/L. 91% of the Chihuahuas were below the nonbreed-specific cut-off (900 pmol/L). The UAldo: C reference interval was 0.6 (90% CI 0.5-0.9) - 16.8 (90% CI 10.9-27.4) µg/g. No significant sex differences in NT-proBNP or UAldo: C were found., Conclusions: The median value, interindividual coefficient of variation and reference interval of NT-proBNP were in line with those reported for other small breeds. In contrast to previous studies, no sex differences in NT-proBNP were detected. As previously suggested, Chihuahuas seem to be characterized by higher values of UAldo: C than other breeds., (© 2024. The Author(s).)

Demonstrating drug efficacy in slowing kidney disease progression requires large clinical trials when targeting participants with an early stage of chronic kidney disease (CKD). In this randomized, parallel-group, open-labeled trial (CANPIONE study), we assessed the effect of the sodium-glucose cotransporter 2 (SGLT2) inhibitor canagliflozin using the individual's change in estimated glomerular filtration rate (eGFR) slope before (pre-intervention slope) and during treatment (chronic slope). We randomly assigned (1:1) participants with type 2 diabetes, urinary albumin-to-creatinine ratio (UACR) of 50 to under 300 mg/g, and an eGFR of at least 45 ml/min/1.73m 2 to receive canagliflozin or guideline-recommended treatment except for SGLT2 inhibitors (control). The first and second primary outcomes were the geometric mean percentage change from baseline in UACR and the change in eGFR slope, respectively. Of 98 randomized participants, 96 received at least one study treatment. The least-squares mean change from baseline in log-transformed geometric mean UACR was significantly greater in the canagliflozin group than the control group (between group-difference, -30.8% (95% confidence interval -42.6 to -16.8). The between-group difference (canagliflozin group - control group) of change in eGFR slope (chronic - pre-intervention) was 4.4 (1.6 to 7.3) ml/min/1.73 m 2 per year, which was more pronounced in participants with faster eGFR decline. In summary, canagliflozin reduced albuminuria and the participant-specific natural course of eGFR decline in participants with type 2 diabetes and microalbuminuria. Thus, the CANPIONE study suggests that the within-individual change in eGFR slope may be a novel approach to determine the kidney protective potential of new therapies in early stages of CKD., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: Intrauterine fetal growth restriction (IUGR) affects up to 10% of all pregnancies. Severe IUGR is associated with impaired kidney development, reduced nephron endowment, and chronic kidney disease later in life. Currently, no early predictive biomarker exists for detecting altered kidney function in neonates with IUGR. Because nephrons produce key enzymes for the metabolism of arginine and methylarginine components, we quantified and compared the concentrations of arginine and methylarginine metabolites between IUGR and non-IUGR neonates to identify potential biomarkers for the early detection of altered kidney function in IUGR neonates., Methods: Seventy-one IUGR and 123 non IUGR neonates were examined. Serum and Urine samples were obtained between 30 h and 5 days of life and between 5 and 70 days of life. Serum concentrations of creatinine, urea, symmetric and asymmetric-dimethylarginine metabolites (SDGV, SDMA, ADGV, and ADMA), guanidino-2-oxo-caproic acid (GOCA), citrulline, homocitrulline, arginine, and homoarginine were quantified using LC-MS/MS and standard clinical laboratory methods. Datasets were compared by Mann-Whitney--Wilcoxon or Chi-square tests for continuous and discrete parameters. P values were corrected for multiple comparisons using the Bonferroni method., Results: After Bonferroni correction, we found that serum creatinine, urea, SDGV, ADGV, and GOCA levels were significantly lower in neonates with IUGR. Consequently, the ratios of SDGV/SDMA, ADGV/ADMA, and GOCA/homoarginine were significantly lower in IUGR neonates., Conclusion: Our study suggests that arginine and methylarginine are possible early biomarkers for detecting altered kidney function in IUGR neonates., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: To investigate the clinical features, kidney pathology, treatment regimens, and clinical outcomes of IgA vasculitis nephritis (IgAVN) with nephrotic-range proteinuria in children., Methods: A retrospective review of children diagnosed with IgAVN between January 2019 and December 2022 was conducted. Participants were divided into two groups based on their urine protein/creatinine (UPCR) levels. Biodata, clinical characteristics, laboratory findings, pathologic features, treatment regimens, and outcomes were abstracted from case records and analyzed., Results: A total of 255 children were identified, 94 with nephrotic-range proteinuria (UPCR ≥ 200 mg/mmol) and 161 with non-nephrotic proteinuria (UPCR < 200 mg/mmol). Patients in the nephrotic-range proteinuria group were significantly younger and had worse grades of glomerular and acute tubulointerstitial injury compared to those in the non-nephrotic proteinuria group. Higher levels of blood urea nitrogen (BUN), D-dimer (DD), and fibrin degradation products (FDP), and lower levels of total protein (TP), albumin (ALB), urine creatinine (Cr), prothrombin time (PT), activated partial thromboplastin time (APTT), IgG, CD3 + cells, and CD4 + cells were found in patients in the nephrotic-range proteinuria group. Clinical outcome of patients with nephrotic-range proteinuria was significantly associated with ISKDC grading, proportion of glomerular crescents and severity of acute tubulointerstitial injury., Conclusions: Children with nephrotic-range proteinuria exhibit more severe disordered immunologic function, hypercoagulability, glomerular and tubulointerstitial pathological damage, and have worse outcomes than those with lower proteinuria levels. Clinicians should pay great attention to the kidney injury and more extensive studies are required to identify optimal treatment regimens to improve outcomes in patients., (© 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Background: Accurate estimation of glomerular filtration rate (GFR) is crucial in living kidney donation. While most estimated GFR (eGFR) equations are based on plasma creatinine, its levels are strongly influenced by muscle mass. Application of cystatin C (cysC)-based estimates before donation may improve both estimation of current GFR and prediction of post-donation GFR., Methods: We assessed the performance of Chronic Kidney Disease Epidemiology Collaboration equations based on creatinine (eGFRcreat-2009, eGFRcreat-2021), cysC (eGFRCysC-2012) or both (eGFRcombined-2012, eGFRcombined-2021) for estimating pre- and post-donation (mGFR) GFR in 486 living kidney donors. We subsequently focused on a subgroup of individuals with high/low muscle mass (25% highest/lowest 24-hour urinary creatinine excretion, sex stratified and height indexed)., Results: Pre-donation eGFRcombined-2012 and eGFRcombined-2021 showed the strongest associations with pre- and post-donation mGFR. Pre-donation eGFRcombined-2021 was most accurate for estimating both pre-donation (bias 0.01 ± 11.9 ml/min/1.73 m2) and post-donation mGFR (bias 1.3 ± 8.5 ml/min/1.73 m2). In donors with high/low muscle mass, cysC-based equations (with or without creatinine) performed better compared with equations based on only creatinine., Conclusions: Combined eGFR equations yielded a better estimate of pre- and post-donation mGFR compared with estimates based on creatinine or cysC only. The added value of cysC seems particularly pronounced in donors with high or low muscle mass., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Whereas urinary creatinine excretion (UCE) is an established marker of muscle mass, both in critically ill and non-critically ill patients, analysis of urinary urea excretion (UUE) may allow estimation of proteolysis that is associated with critical illness. We evaluated the time courses of plasma urea and creatinine as well UUE and UCE in critically ill patients with a prolonged ICU stay. Our goal was to evaluate changes in plasma urea and creatinine in conjunction with their urinary excretion, to get a better understanding of urea handling in ICU patients. From 2002 to 2021, plasma urea and creatinine, UUE and UCE were determined in routinely obtained 24 h urine samples between ICU admission and day 30, in adult patients with an ICU-stay ≥ 28d. Urea-to-creatinine ratios in plasma and urine were calculated. Patients with stage 3 acute kidney injury (AKI) were excluded. Analyses were performed separately for females and males and for patients with and without acute renal failure to account for respectively differences in muscle mass and impaired renal function. Of 47,120 patients, who were admitted to the ICU between 2002 and 2021, 638 patients met the inclusion criteria. During the first 10 days mean ± SD plasma urea increased from 9.7 ± 6.0 mmol/L at ICU admission to 12.4 ± 7.9 mmol/L (P < 0.001) on day 11 and decreased afterwards with a rate of 0.1 mmol/l/d. UUE peaked at 590 ± 317 mmol/day on day 13 whereas UCE peaked already on day 4. Males had higher plasma urea, plasma creatinine, UUE and UCE than females. Plasma and urinary urea-to-creatinine ratio (UCR) stabilized after day 7, with a gradual increase in plasma UCR and urinary UCR between day 7 and day 30. Similar courses, although less pronounced, were seen in patients without AKI. The course of urea in critically ill patients is characterized by an initial rise of both plasma urea and urinary urea excretion, presumably due to increased catabolism of endogenous and exogenous protein in the first week of ICU admission. Subsequently, UUE and UCE declined steadily in a rate that was comparable to the known loss of muscle mass during ICU admission of approximately 1%/day., (© 2024. The Author(s).)

Introduction: To explore PTEN-induced putative kinase 1 (PINK1) expression and its clinical value in diabetic nephropathy., Methods: Ninety patients with diabetic nephropathy were recruited and divided into metformin hydrochloride monotherapy group, telmisartan monotherapy group and combination therapy (metformin and telmisartan) group. Renal function indices and PINK1 expression, inflammatory factors, reactive oxygen species (ROS), mitochondrial membrane potential (MMP) levels were detected. The correlation between PINK1 and inflammatory factors, renal function indicators including estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (UACR) and serum creatinine (SCr)] were analyzed by Pearson correlation., Results: Following treatments, the combination therapy group exhibited increased PINK1 expression levels and decreased ROS levels compared to the groups receiving metformin hydrochloride or telmisartan monotherapy. The combination therapy group showed significant improvements in renal function indices and inflammatory markers. Additionally, the MMP ratio in the combination therapy group was higher compared to the two monotherapy groups. Furthermore, PINK1 was negatively correlated with UACR, SCr, tumor necrosis factor (TNF-α) and interleukin-6 (IL-6), while positively correlated with eGFR and interleukin-2 (IL-2)., Conclusion: PINK1 exhibits low expression levels in patients with diabetic nephropathy and its expression is strongly associated with the inhibition of disease progression, thereby offering significant clinical diagnostic value. Additionally, it may serve as a potential biological marker for clinical diagnosis and treatment of diabetic nephropathy.

Alkaptonuria is characterized by the accumulation of homogentisic acid which causes dark coloration of urine upon standing, ochronosis, and arthritis. A 4-year old child was referred to our pediatric nephrologist with hyperoxaluria and a history of unexplained pink-to-brown discolouration of his diapers associated with a brown-staining of clothes and skin since he was six months old. He had no other symptoms and his past medical history only included minor child illnesses. His 11-month-old brother had the same dark discoloration of his diapers. Laboratory testing on a spot urine sample showed hyperoxaluria and nephrotic range proteinuria with low creatinine and normal albumin concentrations. Considered causes were hyperoxaluria, alkaptonuria, interfering substance, adulteration. The further diagnostic work-up revealed increased homogentisic acid in urine, compatible with alkaptonuria. Urinary creatinine and total protein measurements on Roche Cobas were, respectively, falsely decreased and increased in the presence of homogentisic acid. The false-low creatinine resulted in an elevated oxalate/creatinine ratio. Alkaptonuria can cause a false increase of results expressed per creatinine and should be excluded in case of an unexplained marked increase of urine total protein without a concomitant increase of albumin., Competing Interests: Potential conflict of interest None declared., (Croatian Society of Medical Biochemistry and Laboratory Medicine.)

Few studies have investigated the associations between phthalate exposure and kidney function indicators in adults by simultaneously performing covariate-adjusted creatinine standardization, cumulative risk assessment, and mixture analysis. Thus, we applied these methods simultaneously to investigate the aforementioned associations in an adult population. This cross-sectional study analyzed data (N = 839) from a community-based arm of the Taiwan Biobank. The levels of 10 urinary phthalate metabolites were measured and calculated as the sum of the molar concentrations of the dibutyl phthalate metabolite (ΣDBPm) and di(2-ethylhexyl) phthalate (DEHP) metabolite (ΣDEHPm). The hazard index (HI) and daily intake (DI) were estimated by measuring the urinary levels of the phthalate metabolite. Kidney function biomarkers were assessed by measuring the following: blood urea nitrogen (BUN), uric acid, the albumin-to-creatinine ratio (ACR), and the estimated glomerular filtration rate (eGFR). Generalized linear models were implemented to examine the associations between exposure to individual phthalates, HI scores, and kidney function biomarkers. We also employed Bayesian kernel machine regression (BKMR) to analyze the relationships between exposure to various combinations of phthalates and kidney function. ΣDEHPm levels were significantly and positively associated with BUN and ACR levels, and ΣDBPm levels were positively associated with ACR levels. In addition, eGFR was negatively associated with ΣDBPm and ΣDEHPm levels. In the BKMR model, a mixture of 10 phthalate metabolites was significantly associated with BUN, uric acid, ACR, and eGFR results. Higher DI DEHP and higher DI DnBP values were significantly associated with lower eGFRs and higher ACRs, respectively. Higher DI DiBP and DI DEP values were significantly associated with higher uric acid levels. A higher HI was significantly associated with lower eGFRs and higher ACRs. Our results suggest that exposure to environmental phthalates is associated with impaired kidney function in Taiwanese adults., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Previous research introduced V-PFCRC as an effective spot urinary dilution adjustment method for various metal analytes, including the major environmental toxin arsenic. V-PFCRC normalizes analytes to 1 g/L creatinine (CRN) by adopting more advanced power-functional corrective equations accounting for variation in exposure level. This study expands on previous work by examining the impacts of age and sex on corrective functions., Methods: Literature review of the effects of sex and age on urinary dilution and the excretion of CRN and arsenic. Data analysis included a Data Set 1 of 5,752 urine samples and a partly overlapping Data Set 2 of 1,154 combined EDTA blood and urine samples. Both sets were classified into age bands, and the means, medians, and interquartile ranges for CRN and TWuAs in uncorrected (UC), conventionally CRN-corrected (CCRC), simple power-functional (S-PFCRC), sex-aggregated (V-PFCRC SA), and sex-differentiated V-PFCRC SD modes were compared. Correlation analyses assessed residual relationships between CRN, TWuAs, and age. V-PFCRC functions were compared across three numerically similar age groups and both sexes. The efficacy of systemic dilution adjustment error compensation was evaluated through power-functional regression analysis of residual CRN and the association between arsenic in blood and all tested urinary result modes., Results: Significant sex differences in UC and blood were neutralized by CCRC and reduced by V-PFCRC. Age showed a positive association with blood arsenic and TWuAs in all result modes, indicating factual increments in exposure. Sex-differentiated V-PFCRC best matched the sex-age kinetics of blood arsenic. V-PFCRC formulas varied by sex and age and appeared to reflect urinary osmolality sex-age-kinetics reported in previous research. V-PFCRC minimized residual biases of CRN on TWuAs across all age groups and sexes, demonstrating improved standardization efficacy compared to UC and CCRC arsenic., Interpretation: Sex differences in UC and CCRC arsenic are primarily attributable to urinary dilution and are effectively compensated by V-PFCRC. While the sex and age influence on V-PFCRC formulas align with sex- and age-specific urinary osmolality and assumed baseline vasopressor activities, their impact on correction validity for entire collectives is minimal., Conclusion: The V-PFCRC method offers a robust correction for urinary arsenic dilution, significantly reducing systemic dilution adjustment errors. Its application in various demographic contexts enhances the accuracy of urinary biomarker assessments, benefiting clinical and epidemiological research. V-PFCRC effectively compensates for sex differences in urinary arsenic. Age-related increases in TWuAs are exposure-related and should be additionally accounted for by algebraic normalization, covariate models, or standard range adjustments., (© 2024. The Author(s).)

Urine analysis represents a crucial diagnostic technique employed in clinical laboratories. Creatinine and uric acid in urine are essential biomarkers in the human body and are widely utilized in clinical analysis. Research has demonstrated a correlation between the normal physiological concentrations of creatinine and uric acid in urine and an increased risk of hypertension, cardiovascular diseases, and kidney disease. Furthermore, the pH of urine indicates the body's metabolic processes and homeostatic balance. In this study, an integrated multi-channel electrochemical sensing system was developed, combining electrochemical analysis techniques, microelectronic design, and nanomaterials. The architecture of an intelligent medical detection system and the production of an interactive interface for smartphones were accomplished. Initially, multi-channel selective electrodes were designed for creatinine, uric acid, and pH detection. The detection range was 10 nM to 100 μM for creatinine, 100 μM to 500 μM for uric acid, and 4 to 9 for pH. Furthermore, interference experiments were also conducted to verify the specificity of the sensors. Subsequently, multi-channel double-sided sensing electrodes and function-integrated hardware were designed, with the standard equations of target analytes stored in the system's read-only memory. Moreover, a WeChat mini-program platform was developed for smartphone interaction, enabling off-body detection and real-time display of target analytes through smartphones. Finally, the aforementioned electrochemical detection electrodes were integrated with the smart sensing system and wirelessly interfaced with smartphones, allowing for intelligent real-time detection in primary healthcare and individual household settings.

Introduction: In patients admitted to the intensive care unit (ICU), muscle mass is inversely associated with mortality. Although muscle mass can be estimated with 24-h urinary creatinine excretion (UCE), its use for risk prediction in individual patients is limited because age-, sex-, weight- and length-specific reference values for UCE are lacking. The ratio between measured creatinine clearance (mCC) and estimated glomerular filtration rate (eGFR) might circumvent this constraint. The main goal was to assess the association of the mCC/eGFR ratio in ICU patients with all-cause hospital and long-term mortality., Methods: The mCC/eGFR ratio was determined in patients admitted to our ICU between 2005 and 2021 with KDIGO acute kidney injury (AKI) stage 0-2 and an ICU stay ≥ 24 h. mCC was calculated from UCE and plasma creatinine and indexed to 1.73 m 2 . mCC/eGFR was analyzed by categorizing patients in mCC/eGFR quartiles and as continuous variable., Results: Seven thousand five hundred nine patients (mean age 61 ± 15 years; 38% female) were included. In-hospital mortality was 27% in the lowest mCC/eGFR quartile compared to 11% in the highest quartile (P < 0.001). Five-year post-hospital discharge actuarial mortality was 37% in the lowest mCC/eGFR quartile compared to 19% in the highest quartile (P < 0.001). mCC/eGFR ratio as continuous variable was independently associated with in-hospital mortality in multivariable logistic regression (odds ratio: 0.578 (95% CI: 0.465-0.719); P < 0.001). mCC/eGFR ratio as continuous variable was also significantly associated with 5-year post-hospital discharge mortality in Cox regression (hazard ratio: 0.27 (95% CI: 0.22-0.32); P < 0.001)., Conclusions: The mCC/eGFR ratio is associated with both in-hospital and long-term mortality and may be an easily available index of muscle mass in ICU patients., (© 2024. The Author(s).)

Objective: Chronic kidney disease (CKD) is increasingly recognized as a risk factor for alterations in brain function. However, detecting early-stage symptoms and structural changes remains challenging, potentially leading to delayed treatment. In our study, we aimed to investigate spontaneous brain activity changes in CKD patients using resting-state functional magnetic resonance imaging (fMRI). Additionally, we explored the correlation between common biomarkers reflecting CKD severity and brain activity., Methods: We recruited a cohort of 22 non-dialysis-dependent CKD patients and 22 controls for resting-state fMRI scans. Amplitude of low-frequency fluctuations (ALFFs) and regional homogeneity (ReHo) were calculated to evaluate brain activity. Regression analysis was conducted to explore the correlations between biomarkers reflecting the severity of CKD and brain activity., Results: CKD patients exhibited reduced z-scored ALFF (zALFF) and mean ALFF (mALFF) in the bilateral putamen, right caudate nucleus, left anterior cingulate, and right precuneus. Changes in bilateral putamen were also found in smCohe-ReHo and szCohe-ReHo analyses. Urine albumin-to-creatinine ratio (UACR), urine protein-to-creatinine ratio (UPCR), and serum albumin levels were associated with attenuated putamen activity., Conclusion: Non-dialysis-dependent CKD patients had changes in zALFF, mALFF, smCohe-ReHo, and szCohe-ReHo values in specific brain regions, especially bilateral putamen. UACR, UPCR, and serum albumin levels are associated with putamen activity attenuation in rs-fMRI., (© 2024 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.)

Background: Solar greenhouse workers, a unique farmer group, have been reported to have a higher risk of chronic kidney disease (CKD) compared to the general population, possible due to exposure to multiple metals., Objective: This study aimed to investigate the associations between exposure to multiple metals and the estimated glomerular filtration rate (eGFR)., Methods: A cross-sectional study was conducted in the Northwest China. Urine samples were tested for concentration of 14 metals, including chromium, manganese, iron et al. Blood creatinine was measured to calculate eGFR, which was to evaluate the kidney function. Linear model and the Bayesian Kernel Machine Regression (BKMR) models were used to evaluate the associations between metals exposure and eGFR., Result: The study included 281 solar greenhouse workers, with 128 (45.6%) males and 153 (54.4%) females. The highest median concentrations of metals were zinc (418.55 μg/L), strontium (368.77 μg/L), and iron (55.73 μg/L), respectively. The linear model analysis showed that urinary levels of copper and zinc were negatively associated with eGFR [β = -0.021, 95% CI (-0.048, -0.007); β = -0.018, 95% CI (-0.068, -0.005)] considering a false discovery rate. BKMR results indicated a significant overall negative effect of 14 metals exposure on the eGFR when all metal levels were above the 50th percentile compared to the median value., Conclusions: The decrease in eGFR among solar greenhouse workers was related to mixed metal exposure. Reducing exposure to the metals of copper, zinc, and lead could effectively protects kidney function. Further prospective studies are needed to resolve concerns about reverse causality., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This cross-sectional study was conducted in Department of Paediatrics, Mymensingh Medical College Hospital (MMCH), Bangladesh from February 2016 to December 2016 to detect massive proteinuria by spot urinary protein creatinine ratio as an alternative diagnostic test to 24 hrs urinary total protein in nephrotic syndrome. Fifty one (51) children aged 2 to 12 years admitted with 1st episode of nephrotic syndrome in the pediatric department of MMCH were included in this by purposive sampling technique. All the patients were asked to give a 24 hours urine sample. After this collection the next spot urine samples were collected for protein and creatinine estimation. Among 51 patients 33 were male and 18 were female. The mean age was 5.5+2.3 years. The entire patient had normal renal function. The mean 24 hours urinary protein level was 3.8±1.7 gm/m²/24 hours, the mean spot urinary protein-creatinine ratio was 5.4±2.5. Mean serum albumin was 1.8±0.6 gm/dl and the mean serum cholesterol was 357.6±74.7 mg/dl. The spot urinary protein creatinine ratio was increased with the increase in the amount of 24 hours urinary total protein and a strong positive Pearson correlation (r=0.805) was found. In all the cases of nephrotic syndrome spot urinary protein creatinine ratio were found more than 2. Based on this study, it can be concluded that the determination of the spot urinary protein-creatinine ratio can replace the 24 hours urine collection in the quantitation of proteinuria in nephrotic syndrome.

The urinary normetanephrine to creatinine ratio (uNMN/Cr) and urinary metanephrine to creatinine ratio (uMN/Cr) are commonly evaluated for the diagnosis of pheochromocytomas (PCC) in dogs. This study aimed to establish reference intervals for uNMN/Cr and uMN/Cr in 56 healthy dogs in Japan and to investigate the effect of urine collection methods on these measurements in 15 non-PCC dogs. The upper limits of reference intervals for uNMN/Cr and uMN/Cr were 124.4 nmol/mmol (90% confidence interval [CI] 107.7-137.0) and 121.1 nmol/mmol (90% CI 102.8-145.1), respectively. Both uNMN/Cr and uMN/Cr were significantly higher when urine was collected in the hospital compared to at home. Several factors, including the method of urine collection, should be considered when utilizing these reference intervals.

Purpose: There is no consensus on how to estimate kidney function for the assessment of eligibility in clinical cancer trials., Patients and Methods: We recalculated the creatinine clearance (CrCl)/glomerular filtration rate (GFR) at baseline in a total of 1768 patients enrolled in twelve clinical trials using the Cockcroft-Gault (CG), Modification of Diet in Renal Disease (MDRD), 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI 2021) and European Kidney Function Consortium (EKFC) formulas. Patients were classified as having renal impairment (RI; CrCl/GFR <60 mL/min) or no renal impairment (NRI; CrCl/GFR ≥60 mL/min) with each of the four formulas, respectively. Furthermore, we analyzed the number of adverse events (AE) per month under study treatment using measures of central tendency, variability and regression models., Results: Using CG, EKFC, MDRD and CKD-EPI 2021, 152 (8 %), 140 (8 %), 110 (6 %), and 61 (4 %) patients had RI respectively. Indeed, 47 (3 %) patients had RI using all 4 formulas, while 158 (9 %) had RI by at least one but not all four methods. CG showed the broadest variability and inconsistencies with other methods. All calculation methods performed similarly for excluding patients at risk of severe AE. EKFC demonstrated superior predictive ability for excluding patients at risk of renal and urinary tract AE., Conclusion: This post hoc analysis highlights the importance of choosing accurate and representative methods for kidney function estimation in clinical cancer trials. CG should be replaced by newer methods. While CKD-EPI 2021 may maximize trial accrual, EKFC should be considered for treatment affecting kidney function., Competing Interests: Declaration of Competing Interest HCP has received travel support from Eli Lilly, MSD, Novartis, Pfizer, Pierre Fabre and Roche and received lecture honoraria from Eli Lilly. MP has received honoraria for lectures, consultation or advisory board participation from the following for-profit companies: Bayer, Bristol-Myers Squibb, Novartis, Gerson Lehrman Group (GLG), CMC Contrast, GlaxoSmithKline, Mundipharma, Roche, BMJ Journals, MedMedia, Astra Zeneca, AbbVie, Lilly, Medahead, Daiichi Sankyo, Sanofi, Merck Sharp & Dome, Tocagen, Adastra, Gan & Lee Pharmaceuticals, Janssen, Servier, Miltenyi, Böhringer-Ingelheim, Telix, Medscape., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Duchenne muscular dystrophy (DMD) results in a progressive loss of functional skeletal muscle mass (MM) and replacement with fibrofatty tissue. Accurate evaluation of MM in DMD patients has not previously been available. Our objective was to measure MM using the D 3 creatine (D 3 Cr) dilution method and determine its relationship with strength and functional capacity in patients with DMD over a wide range of ages. Subjects were recruited for participation in a 12 month, longitudinal, observational study. Here, we report the baseline data. A 20 mg dose of D 3 Cr dissolved in water was ingested by 92 patients with DMD (ages 4-25 years) followed later with a fasting urine sample. Enrichment of D 3 creatinine was determined by liquid chromatography-mass spectrometry analysis. The North Star Ambulatory Assessment (NSAA) total score was determined for ambulatory participants, and the Performance of Upper Limb (PUL 2.0) total score and grip strength for all participants. We observed a significant age-associated increase in body weight along with a substantial decrease in MM/body weight (%MM). MM and %MM were associated with PUL score (r = 0.517, P < 0.0001 and r = 0.764, P < 0.0001 respectively). The age-associated decrease in MM and %MM was strongly associated with ambulatory status. We observed very little overlap in %MM between ambulant and non-ambulant subjects, suggesting a threshold of 18-22% associated with loss of ambulation. MM is substantially diminished with advancing age and is highly related to clinically meaningful functional status. The D 3 Cr dilution method may provide a biomarker of disease progression and therapeutic efficacy in patients with DMD or other neuromuscular disorders. KEY POINTS: The non-invasive D 3 creatine dilution method provides novel data on whole body functional muscle mass (MM) in a wide range of ages in patients with DMD and reveals profoundly low functional MM in older non-ambulant patients. The difference in %MM between ambulant and non-ambulant subjects suggests a threshold for loss of ambulatory ability between 18 and 22% MM. The data suggest that as functional MM declines with age, maintaining a lower body weight may help to conserve ambulatory ability., (© 2024 The Author(s). The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Canine leishmaniosis (CanL), caused by Leishmania sp., presents a wide array of symptoms; renal dysfunction is frequently observed in these dogs and is associated with a poor prognosis and increased mortality. The traditional biomarkers namely urea and creatinine can detect renal damage but only in advanced stages of the disease. However, it has been shown that the symmetric dimethylarginine assay (SDMA) or the protein/creatinine ratio (UPC) and are early biomarkers of renal dysfunction. Their elevation occurs earlier than that of creatinine, but other novel biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL) are currently under investigation. Our objective was to determine whether the urine NGAL-creatinine ratio (uNGAL/c) can provide very early diagnosis of kidney disease in CanL. In total, 68 dogs were included in the study: 15 healthy dogs and 53 dogs with CanL who were classified according to International Renal Interest Society (IRIS) classification: IRIS 1 (N= 34), IRIS 2 (N= 9) and IRIS 3/4 (N= 10). IRIS 1 was subdivided according to proteinuria in IRIS 1 NP (13 dogs with UPC < 0.2), IRIS 1 BL (8 dogs with UPC = 0.2-0.5) and IRIS 1 P (13 dogs with UPC > 0.5). Blood samples were collected for complete hematological and biochemistry analysis including plasma NGAL. Urinalysis included specific gravity, UPC, CysC and NGAL expressed as a ratio with creatinine. The mean concentrations of pCysC and SDMA in CanL, show a statistically significant increase from IRIS 1 NP , not being statistically significant for pCysC in the IRIS 1 BL group. The UPC show a statistically significant increase from IRIS 1 NP. In all groups with CanL for uCysC/c and uNGAL/c was observed a statistically significant increase. The uNGAL/c in the group proteinuric animals, presents a positive correlation with all renal biomarkers studied. In the group of non-proteinuric animals, the uNGAL/c presents a positive correlation with SDMA and UPC. The uNGAL/c can be considered a reliable indicator of renal disease in dogs diagnosed with CanL who are non-azotemic and non-proteinuric., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Brown Swiss (BS) cows have greater urea concentrations in milk and blood compared with Holstein (HO) cows. We tested the hypothesis that BS and HO cows differ in kidney function and nitrogen excretion. Blood, saliva, urine, and feces were sampled in 31 multiparous BS and 46 HO cows kept under identical feeding and management conditions. Samples were collected at different lactational stages after the monthly DHIA control test-day. To test the glomerular filtration rate (GFR) and urea excretion, concentrations of creatinine and urea were measured in serum, urine, and saliva. As an additional marker to estimate GFR, we determined symmetric dimethylarginine (SDMA) in serum. Feces were analyzed for DM content and nitrogen concentration. Data on milk urea and protein concentrations and daily milk yield were obtained from the monthly DHIA test-day records. The effects of breed, time, and parity number on blood, saliva, urine, feces, and milk parameters were evaluated with the GLM procedure of SAS, with breed, time, and parity number as fixed effects. Differences between BS and HO were assessed by the Tukey-corrected t-test. Concentrations of urea, creatinine, and SDMA in serum, were greater in BS than in HO cows: 5.46 ± 0.19 versus 4.72 ± 0.13 mmol/L (urea), 105.96 ± 2.23 versus 93.07 ± 1.50 mmol/L (creatinine), and 16.78 ± 0.69 versus 13.39 ± 0.44 µg/dL (SDMA). We observed a greater urea concentration in BS cows (25.8 ± 0.7 vs. 21.8 ± 0.7 mg/dL) and protein content in milk (3.70% ± 0.08% vs. 3.45% ± 0.07%) than in HO cows. Urea and creatinine concentrations in urine and saliva did not differ between breeds. No differences between BS and HO were observed for milk yield, fecal DM, and fecal nitrogen content. Dry matter intake and BW were similar in BS and HO cows. Despite greater urea, creatinine, and SDMA concentrations in blood, as well as a higher milk urea content in BS compared with HO, respective concentrations in urine did not differ between breeds. In conclusion, our results demonstrate a lower renal GFR in BS compared with HO cows, thereby contributing to the greater plasma urea concentration in BS cows. However, estimation of nitrogen excretion via milk, urine, and feces does not entirely reflect nitrogen turnover within the animal., (The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Purpose: Proteinuria can cause interindividual variability in the pharmacokinetics of therapeutic antibodies and may affect therapeutic efficacy. Here, we measured the serum and urinary concentrations of bevacizumab (BV) and nivolumab (NIVO) in patients with proteinuria and reported a case series of these patients., Methods: Thirty-two cancer patients who received BV every 3 weeks or NIVO every 2 weeks between November 2020 and September 2021 at Kyoto University Hospital were enrolled in this study. The serum and urinary concentrations of BV and NIVO were measured using liquid chromatography-tandem mass spectrometry., Results: We divided the BV-treated patients and the NIVO-treated patients into two groups based on the urine protein-creatinine ratio (UPCR): UPCR 1 g/g or higher (BV, n = 9; NIVO, n = 3) and UPCR less than 1 g/g (BV, n = 14; NIVO, n = 6). Serum concentrations of the therapeutic antibodies adjusted by their doses were significantly lower in both BV- and NIVO-treated patients with UPCR 1 g/g or higher compared to those with less than 1 g/g. In patients with UPCR 1 g/g or higher, urinary concentrations of the therapeutic antibodies adjusted by their serum concentrations and urinary creatinine concentrations tended to increase., Conclusion: This case-series study suggests a possibility of reduction in serum concentrations of BV and NIVO in patients with proteinuria by urinary excretion of these drugs., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aim: To examine the associations of tea consumption (both frequency and type) with (1) prediabetes and diabetes and (2) urinary glucose and sodium excretion in Chinese community-dwelling adults., Materials and Methods: In 1923 participants (457 with diabetes, 720 with prediabetes, and 746 with normoglycaemia), the frequency (occasional, frequent, daily, or nil) and type (green, black, dark, or other) of tea consumption were assessed using a standardized questionnaire. Morning spot urinary glucose and urine glucose-to-creatinine ratios (UGCRs) were assessed as markers of urinary glucose excretion. Tanaka's equation was used to estimate 24-h urinary sodium excretion. Logistic and multivariate linear regression analyses were performed., Results: Compared with non-tea drinkers, the corresponding multivariable-adjusted odds ratios (ORs) for prediabetes and diabetes were 0.63 (95% confidence interval [CI] 0.48, 0.83) and 0.58 (95% CI 0.41, 0.82) in participants drinking tea daily. However, only drinking dark tea was associated with reduced ORs for prediabetes (0.49, 95% CI 0.36, 0.66) and diabetes (0.41, 95% CI 0.28, 0.62). Dark tea consumption was associated with increased morning spot urinary glucose (0.22 mmol/L, 95% CI 0.11, 0.34 mmol/L), UGCR (0.15 mmol/mmol, 95% CI 0.05, 0.25 mmol/L) and estimated 24-h urinary sodium (7.78 mEq/day, 95% CI 2.27, 13.28 mEq/day)., Conclusions: Regular tea consumption, especially dark tea, is associated with a reduced risk of dysglycaemia and increased urinary glucose and sodium excretion in Chinese community-dwelling adults., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aims: We aim to identify the most accurate marker for early prediction of poor diuretic response in acute heart failure (AHF) patients with signs of congestion requiring intravenous diuretic treatment., Methods: In this single-centre, prospective observational study, AHF patients with signs of congestion received a standardized intravenous furosemide dose (1 mg/kg of body weight; 40 mg in bolus and remaining dose in 2 h continuous infusion). Subsequently, we assessed spot urine composition at 2 h post-administration, comparing it with total urine output at 6 h. Various potential urine markers were analysed for predicting urine output using receiver operating characteristic (ROC) curves and logistic regression models. We investigated guideline-recommended markers, including spot urine sodium (UNa + ) and its cut-off, and introduced the UNa + /UCr (urine creatinine concentration) ratio adjusting UNa + for urine dilution., Results: Out of 111 patients (85% males, 66.4 ± 13.9 years old, NTproBNP 7290 [4493-14 582] pg/ml), there were 18 (16%) with a poor diuretic response (cumulative urine output <600 ml during the first 6 h). The mean 6 h cumulative diuresis in patients with poor and good diuretic response was 406 ± 142 and 2114 ± 1164 ml, respectively, P < 0.005. After an initial evaluation of several potential biomarkers, only UNa + , UCr and UNa + /UCr were selected as candidates with the highest predictive value. The cut-off for UNa + adjusted for urine dilution: UNa + /UCr ratio <0.167 mmol/mg × 10 -1 was determined by ROC analysis with the highest area under the curve (95% confidence interval): 0.956 (0.915-0.997), P < 0.001. When compared with the guideline-recommended cut-off (UNa + <50 mmol/L as a reference, specificity-0.97; sensitivity-0.83), the odds ratio (OR) for UNa + /UCreat to identify a poor diuretic response was 2.5 times greater, regardless of kidney function (OR for estimated glomerular filtration rate in the logistic regression model was 0.978 [0.945-1.013, P = 0.222])., Conclusions: The UNa + /UCr ratio in a spot urine sample 2 h after intravenous diuretic administration is a simple, highly predictive marker for the identification of AHF patients with poor diuretic response, surpassing guidelines-recommended markers like UNa + ., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Fractional excretion of magnesium (FE Mg ) is commonly used to diagnose of renal magnesium (Mg) wasting, but it can be affected by serum Mg (SMg) and serum creatinine concentration (SCr). We investigated the sensitivity and specificity of FE Mg to diagnose Mg wasting in subgroups with different SMg and eGFR (estimated glomerular filtration rate) in pediatric nephrology practice., Methods: One hundred and nineteen patients (59 males and 60 females, median 15 years) seen in our pediatric clinic were investigated for FE Mg , SMg, eGFR, and urine Mg-to-creatinine ratio (Mg/Cr). Normal eGFR was defined as ≥ 90 ml/min/1.73 m 2 or for infants SCr < chronic kidney disease stage 2. Urine Mg/Cr was compared with age-specific reference values., Results: Sixteen of all patients (13 %) had hypomagnesemia. All had FE Mg greater than the cut-off value of 2 %. Only 4 patients had elevated urine Mg/Cr. Of 65 patients with normal SMg and eGFR, 19 had FE Mg above the cut-off value of 4 %. Of these, 13 patients had elevated urine Mg/Cr i.e. Mg wasting (sensitivity and specificity of FE Mg , 93 % and 88 %, respectively). Among 38 patients with normal SMg and low eGFR, 30 had FE Mg  > 4 %, but only 6 had elevated urine Mg/Cr (sensitivity 100 % and specificity 25 %). Overall, hypomagnesemic patients and normomagnesemic patients with elevated urine Mg/Cr were diagnosed with Mg wasting (36/119, 30 %)., Conclusions: FE Mg has variable sensitivity and specificity depending on SMg and eGFR in the diagnosis of Mg wasting. Mg wasting is not uncommon in pediatric nephrology practice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

This study evaluates distal tubular damage in early stages of renal disease in dogs with naturally acquired leishmaniosis. Pherograms of urinary proteins separated in vertical electrophoresis system (SDS-PAGE) were evaluated. Peptide fingerprint and fragmentation (MALDI-TOF TOF) identified bands located at 100 and 60 kDa as Tamm-Horsfall protein (THP) and albumin, respectively. The variables examined were: urine protein to creatinine ratio (UPC), total number of bands, quantification of THP urinary excretion through the optical density (OD %) of bands located at 100 kDa, blood creatinine, and urine specific gravity (USG). Positive correlation was found between UPC and the number of bands (ρ = 0.75849, P = <0.0001). Negative correlation was identified between UPC and OD % of 100 kDa bands (ρ = -0.85332, P = <0.0001), and the number of bands and OD % of 100 kDa bands (ρ = -0.74479, P = <0.0001). The area under the ROC curve was 0.991 (95 % CI, 0.976-1). The optimal cut-off UPC that better discriminated between urines with high or low OD% of THP was 0.46 with 92.6 % sensitivity and 96.2 % specificity. Our findings indicate that non azotemic dogs with borderline proteinuria might excrete low amount of THP, which could suggest tubular damage in early stages of chronic kidney disease., Competing Interests: Declaration of Competing Interest The assessment of proteinuria and SDS-PAGE electrophoresis was funded by Novartis Animal Health., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aim: To assess the association between urinary albumin-to-creatinine ratio (UACR) categories within the normal range with mortality and adverse cardiovascular outcomes., Materials and Methods: PubMed and Embase were systematically searched for real-world evidence studies. Studies were manually evaluated according to predefined eligibility criteria. We included prospective and retrospective cohort studies of the association between UACR categories <30 mg/g and cardiovascular outcomes or mortality. Published information regarding study design, participants, UACR categorization, statistical methods, and results was manually collected. Two UACR categorization approaches were defined: a two-category (UACR <10 mg/g vs. 10-30 mg/g) and a three-category division (UACR <5 mg/g vs. 5-10 and 10-30 mg/g). A random effects meta-analysis was performed on studies eligible for the meta-analysis., Results: In total, 22 manuscripts were identified for the systematic review, 15 of which were eligible for the meta-analysis. The results suggest an association between elevated UACR within the normal to mildly increased range and higher risks of all-cause mortality, cardiovascular death, and coronary heart disease, particularly in the range of 10-30 mg/g. Compared with UACR <10 mg/g, the hazard ratio [HR (95% confidence interval, CI)] for UACR between 10 and 30 mg/g was 1.41 (1.15, 1.74) for all-cause mortality and 1.56 (1.23, 1.98) for coronary heart disease. Compared with UACR <5 mg/g, the risk of cardiovascular mortality for UACR between 10 and 30 mg/g was more than twofold [HR (95% CI): 2.12 (1.61, 2.80)]. Intermediate UACR (5-10 mg/g) was also associated with a higher risk of all-cause mortality [HR (95% CI): 1.14 (1.05, 1.24)] and cardiovascular mortality [HR (95% CI): 1.50 (1.14, 1.99)]., Conclusions: We propose considering higher UACR within the normoalbuminuric range as a prognostic factor for cardiovascular morbidity and mortality. Our findings underscore the clinical significance of even mild increases in albuminuria., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Current kidney perfusion protocols are not optimized for addressing the ex vivo physiological and metabolic needs of the kidney. Ex vivo normothermic perfusion may be utilized to distinguish high-risk kidneys to determine suitability for transplantation. Here, we assessed the association of tissue metabolic changes with changes in a kidney injury biomarker and functional parameters in eight deceased donor kidneys deemed unsuitable for transplantation during a 12-hour ex vivo normothermic perfusion. The kidneys were grouped into good and poor performers based on blood flow and urine output. The mean age of the deceased kidney donors was 43 years with an average cold ischemia time of 37 hours. Urine output and creatinine clearance progressively increased and peaked at six hours post-perfusion among good performers. Poor performers had 71 ng/ml greater (95% confidence interval 1.5, 140) urinary neutrophil gelatinase-associated lipocalin at six hours compared to good performers corresponding to peak functional differences. Organ performance was distinguished by tissue metabolic differences in branched chain amino acid metabolism and that their tissue levels negatively correlated with urine output among all kidneys at six hours. Tissue lipid profiling showed poor performers were highlighted by the accumulation of membrane structure components including glycerolipids and sphingolipids at early perfusion time points. Thus, we showed that six hours is needed for kidney function recovery during ex vivo normothermic perfusion and that branched chain amino acid metabolism may be a major determinant of organ function and resilience., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

The urine albumin (Alb)-to-creatinine (Crn) ratio (UACR) is a sensitive and early indicator of chronic kidney disease (CKD) and cardiorenal syndrome. This study developed a portable and wireless electrochemical-sensing platform for the sensitive and accurate determination of UACR. The developed platform consists of a carbon nanotube (CNT)-2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)(ABTS)-based modified UACR sensor, a miniaturised potentiostat, a cup holder embedded with a magnetic stirrer and a smartphone app. The UACR sensing electrode is composed of two screen-printed carbon working electrodes, one screen-printed carbon counter electrode and a screen-printed AgCl reference electrode. The miniaturised potentiostat, which is controlled by the developed app, performs cyclic voltammetry and amperometry to detect Alb and Crn, respectively. Clinical trials of the proposed system by using spot urine samples from 30 diabetic patients indicate that it can accurately classify all three CKD risk statuses within 30 min. The high accuracy of our proposed sensing system exhibits satisfactory agreement with the commercial biochemical analyser TBA-25FR (Y = 0.999X, R 2 = 0.995). The proposed UACR sensing system offers a convenient, reliable and affordable solution for personal mobile health monitoring and point-of-care urinalysis.

Background: Previous studies with several limitations have comparatively analyzed the relationship between ambulatory blood pressure (BP) and self-measured BP and biomarkers of organ damage. This study extends this line of research by examining the relationship between ambulatory and self-measured BP and cardiac, renal, and atherosclerotic biomarkers in outpatients at cardiovascular risk., Methods: In 1,440 practice outpatients who underwent office, ambulatory, and self-measured BP monitoring, we assessed the relationships of each BP with organ damage biomarkers including b-type natriuretic peptide (BNP), echocardiographic left ventricular mass index (LVMI), urine albumin-creatinine ratio (UACR), and brachial-ankle pulse wave velocity (baPWV)., Results: In the comparison of correlation, self-measured systolic BP (SBP) was more strongly correlated to log-transformed (Ln) BNP (n = 1,435; r = 0.123 vs. r = -0.093, P < 0.001), LVMI (n = 1,278; r = 0.223 vs. r = 0.094, P < 0.001), Ln-UACR (n = 1,435; r = 0.244 vs. r = 0.154, P = 0.010), and baPWV (n = 1,360; r = 0.327 vs. r = 0.115, P < 0.001) than daytime ambulatory SBP. In the linear regression models including office, ambulatory, and self-measured SBP, only self-measured SBP was significantly related to Ln-BNP (P = 0.016) and LVMI (P < 0.001). In the logistic regression models for the top quartile of LVMI, adding self-measured SBP improved the model predictability (P = 0.027), but adding daytime ambulatory SBP did not. However, adding daytime ambulatory SBP improved the model predictability in the logistic model for the top quartile of baPWV including office and self-measured SBP (P = 0.030)., Conclusions: Our study findings suggested that self-measured BP was associated with cardiac biomarkers independent of ambulatory BP., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Lead (Pb) poisoning is estimated to account for 1 % of the global disease burden. The gold standard for diagnosing lead poisoning in human body relies on blood lead level (BLL), which is always performed in hospitals using expensive instruments. However, there are still many countries and regions with a lack of medical resources (without enough professional medical staff and analytical instruments). To achieve a facile diagnosis of lead poisoning by ordinary residents (without any expertise), this study conducted a research study on 810 participants to discover and validate a new lead poisoning indicator (creatinine-corrected urinary lead level, cULL) beyond BLL in non-invasive samples. A point-of-care testing (POCT) device to measure cULL was developed, equipped with liquid-phase microextraction and electromembrane extraction on a paper-based analytical device for on-site separation of lead and creatinine in the urine, using a smartphone for the quantification of analytes. The cULL as a novel indicator and the POCT device developed could be effective in reducing the risk of damage from lead contamination., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Renal cell carcinoma (RCC) is the sixth most common cancer in men and is often asymptomatic, leading to incidental detection in advanced disease stages that are associated with aggressive histology and poorer outcomes. Various cancer biomarkers are found in urine samples from patients with RCC. In this study, we propose to investigate the use of Attenuated Total Reflection-Fourier Transform Infrared Spectroscopy (ATR-FTIR) on dried urine samples for distinguishing RCC. We analyzed dried urine samples from 49 patients with RCC, confirmed by histopathology, and 39 healthy donors using ATR-FTIR spectroscopy. The vibrational bands of the dried urine were identified by comparing them with spectra from dried artificial urine, individual urine components, and dried artificial urine spiked with urine components. Urea dominated all spectra, but smaller intensity peaks, corresponding to creatinine, phosphate, and uric acid, were also identified. Statistically significant differences between the FTIR spectra of the two groups were obtained only for creatinine, with lower intensities for RCC cases. The discrimination of RCC was performed through Principal Component Analysis combined with Linear Discriminant Analysis (PCA-LDA) and Support Vector Machine (SVM). Using PCA-LDA, we achieved a higher discrimination accuracy (82%) (using only six Principal Components to avoid overfitting), as compared to SVM (76%). Our results demonstrate the potential of urine ATR-FTIR combined with machine learning techniques for RCC discrimination. However, further studies, especially of other urological diseases, must validate this approach.

Objectives: We aim to evaluate estimated glomerular filtration rate (eGFR) patterns of progression in a multiethnic cohort of people with type I diabetes mellitus and with baseline eGFR ≥45 mL/min/1.73 m 2 ., Design: Observational cohort., Setting: People with a clinical diagnosis of type 1 diabetes, attending two university hospital-based outpatient diabetes clinics, in South London between 2004 and 2018., Participants: We studied 1495 participants (52% females, 81% white, 12% African-Caribbean and 7% others)., Primary and Secondary Outcome Measures: Clinical measures including weight and height, systolic blood pressure, diastolic blood pressure and laboratory results (such as serum creatinine, urine albumin to creatinine ratio (ACR), HbA1c were collected from electronic health records (EHRs) and eGFR was estimated by the Chronic Kidney Disease-Epidemiology Collaboration. Ethnicity was self-reported., Results: Five predominantly linear patterns/groups of eGFR trajectories were identified. Group I (8.5%) had a fast eGFR decline (>3 mL/min/1.73 m 2 year). Group II (23%) stable eGFR, group III (29.8%), groups IV (26.3%) and V (12.4%) have preserved eGFR with no significant fall. Group I had the highest proportion (27.6%) of African-Caribbeans. Significant differences between group I and the other groups were observed in age, gender, HbA1C, systolic and diastolic blood pressure, body mass index, cholesterol and urine ACR, p<0.05 for all. At 10 years of follow-up, 33% of group I had eGFR <30 and 16.5%<15 (mL/min/1.73 m 2 )., Conclusions: Distinct trajectories of eGFR were observed in people with type 1 diabetes. The group with the highest risk of eGFR decline had a greater proportion of African-Caribbeans compared with others and has higher prevalence of traditional modifiable risk factors for kidney disease., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Estimating glomerular filtration (eGFR) after Continuous Renal Replacement Therapy (CRRT) is important to guide drug dosing and to assess the need to re-initiate CRRT. Standard eGFR equations cannot be applied as these patients neither have steady-state serum creatinine concentration nor average muscle mass. In this study we evaluate the combination of dynamic renal function with CT-scan based correction for aberrant muscle mass to estimate renal function immediately after CRRT cessation. We prospectively included 31 patients admitted to an academic intensive care unit (ICU) with a total of 37 CRRT cessations and measured serum creatinine before cessation (T1), directly (T2) and 5 h (T3) after cessation and the following two days when eGFR stabilized (T4, T5). We used the dynamic creatinine clearance calculation (D3C) equation to calculate eGFR (D3C GFR ) and creatinine clearance (D3C creat ) between T2-T3. D3C creat was corrected for aberrant muscle mass when a CT-scan was available using the CRAFT equation. We compared D3C GFR to stabilized CKD-EPI at T5 and D3C Creat to 4-h urinary creatinine clearance (4-h uCrCl) between T2-T3. We retrospectively validated these results in a larger retrospective cohort (NICE database; 1856 patients, 2064 cessations). The D3C GFR was comparable to observed stabilized CKD-EPI at T5 in the prospective cohort (MPE = - 1.6 ml/min/1.73 m 2 , p30 = 76%) and in the retrospective NICE-database (MPE = 3.2 ml/min/1.73 m 2 , p30 = 80%). In the prospective cohort, the D3C Creat had poor accuracy compared to 4-h uCrCl (MPE = 17 ml/min/1.73 m 2 , p30 = 24%). In a subset of patients (n = 13) where CT-scans were available, combination of CRAFT and D3C Creat improved bias and accuracy (MPE = 8 ml/min/1.73 m 2 , RMSE = 18 ml/min/1.73 m 2 ) versus D3C Creat alone (MPE = 18 ml/min/1.73 m 2 , RMSE = 32 ml/min/1.73 m 2 ). The D3C GFR improves assessment of eGFR in ICU patients immediately after CRRT cessation. Although the D3C Creat had poor association with underlying creatinine clearance, inclusion of CT derived biometric parameters in the dynamic renal function algorithm further improved the performance, stressing the role of muscle mass integration into renal function equations in critically ill patients., (© 2024. The Author(s).)

Objective: This study investigated the correlation between thyroid function and urinary iodine/creatinine ratio (UI/Cr) in pregnant women during different trimesters and explored potential influencing factors., Methods: In this cross-sectional study, serum levels of thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), and UI/Cr were measured in 450 pregnant women. Correlations were analyzed using Pearson's correlation coefficient and multiple linear regression. Subgroup analyses were performed based on age, body mass index (BMI), parity, gestational age, education, occupation, and family history of thyroid disorders., Results: UI/Cr was positively correlated with FT4 levels in the first and second trimesters, particularly in women with older age, higher BMI, multiparity, higher education, and employment. No significant correlations were found between UI/Cr and TSH or FT3 levels., Conclusion: UI/Cr is positively correlated with FT4 levels in early pregnancy, especially in women with certain risk factors. Regular monitoring of iodine status and thyroid function is recommended for pregnant women to ensure optimal maternal and fetal health., (© 2024. The Author(s).)

Objective: This study aimed to assess the reliability of the spot urine protein/creatinine (sP/Cr) ratio for evaluating proteinuria across different ranges and renal functions., Methods: In this retrospective study, we analyzed 24-hour urine protein excretion (24 h UP) and sP/Cr measurements in 216 patients with renal disease. Pearson correlation and Bland-Altman analyses were performed to evaluate the correlation and agreement between 24 h UP and the sP/Cr., Results: The patients were categorized into the following three 24 h UP groups: 150 to 299 mg/24 hours, 300 to 3499 mg/24 hours, and >3500 mg/24 hours. Significant positive correlations were found between the sP/Cr and the first two 24 h UP groups (r = 0.9104 and r = 0.9721, respectively) but not between the third group (r = 0.3110). Bland-Altman analysis confirmed good agreement in the group with <3500 mg/day proteinuria. Estimated glomerular filtration rates ≥60 mL/minute and <60 mL/minute were significantly correlated with the sP/Cr (r = 0.8714 and r = 0.4516, respectively)., Conclusion: The sP/Cr ratio is a reliable indicator for non-nephrotic proteinuria, irrespective of renal function, but is unreliable for nephrotic-range proteinuria., Competing Interests: Declaration of conflicting interestThe authors declare that there is no conflict of interest.

As a result of excessive salt loss, cystic fibrosis patients are at risk of dehydration, especially in hot weather. The urinary sodium/creatinine ratio is an easy and noninvasive tool for assessing whether dietary salt intake is adequate, whatever the patient's age. Recently, new reference values have been established, adapted to the patient's age. The objectives of this study are to investigate the impact of these new standards on the diagnosis of inadequate sodium intake and the variation in this ratio as a function of body mass index (BMI), outdoor temperature and the use of modulator therapy of CFTR protein. The present study included 40 patients and 335 urine samples. Adapting the urinary sodium/creatinine ratio with the new reference values reduced the number of patients with sodium deficiency by 11.8%. However, there were no significant differences in BMI, lung function or outdoor temperature between the sodium deficient and non-deficient groups. The CFTR modulator-treated group had a better mean urinary sodium/creatinine ratio compared with the group without modulators (p = 0.01), However, larger-scale studies are needed to provide a definitive answer to this question.

Background: Exogenous iodine interferes with the uptake of radioactive iodine ( 131 I) by the thyroid gland. This has potential implications for the treatment of cats with hyperthyroidism that have recently undergone computed tomography (CT) with IV administration of iodinated contrast medium (ICM)., Hypothesis: To determine the time to normalize urinary iodine clearance after administration of ICM. We hypothesized that it would require 4 weeks for urinary iodine concentration (UIC) to decrease to baseline after IV administration of ICM., Animals: Ten healthy adult neutered male cats., Methods: All cats were sedated and received Iopamidol at a dose of 2 mL/kg (600 mg/kg). Urinary iodine and creatinine concentrations were measured before administration of Iopamidol and on days 1, 2, 3, 7, 10 and weeks 2 to 6 after administration. The urinary iodine-to-creatinine ratio (UICR) was calculated. Outcome variables were modeled using a linear mixed-effects model., Results: Urinary iodine concentration increased 37- to 884-fold on Day 1 after ICM injection and returned to baseline during Week 2. Compared with baseline, UIC was significantly increased for Days 1 to 7 (all P < .001); UC was significantly lower for Days 1 to 10 (all P < .03); and UICR was significantly increased from Days 1 to 10 (all P < .001, except Day 10 P = .05)., Conclusions: Urinary clearance of iodine after IV administration of ICM requires 10 days to return to baseline in healthy cats. A 2-week interval between the iodinated contrast study and 131 I treatment could be appropriate but needs to be confirmed in hyperthyroid cats., (© 2024 The Author(s). Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Purpose: The primary goal was to estimate reference values of parathyroid hormone (PTH) in very low birth weight infants without severe neonatal morbidity. A secondary objective was to assess the relationship between PTH serum levels and selected laboratory markers of bone metabolism., Methods: Ninety two infants with birth weight less than 1500 g met the inclusion criteria of the study. Serum levels of PTH, 25-hydroxyvitamin-D [25(OH)D], C3-epi-25(OH)D, total calcium, phosphorus, and alkaline phosphatase, and urinary levels of calcium, phosphorus, and creatinine were examined on day 14 and subsequently every 2 weeks until discharge., Results: Of the total 167 serum samples examined for PTH levels in infants without 25(OH)D deficiency the estimated range was 0.9-11.9 pmol/l (8.5-112.3 pg/mL). During the first month, no statistically significant correlation was observed between PTH level and that of 25(OH)D, C3-epimers of 25(OH)D, S-Ca, S-P, or ALP, nor with urinary excretion of calcium and phosphorus. From the second month of life, there was a moderately significant correlation between PTH and 25(OH)D (Rho = -0.40, P =< .001), between PTH and calcium/creatinine ratio (Rho = -0.56, P = < .001), and between PTH and phosphorus/creatinine ratio (Rho = 0.51, P = < .001)., Conclusions: The physiological range for PTH levels for preterm neonates without 25(OH)D deficiency was estimated as 0.9-11.9 pmol/l (8.5-112.3 pg/mL). It seems that elevation of serum PTH above this range can be considered as hyperparathyroidism in very low birth weight infants., 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: Iron deficiency (ID) is the most common nutritional deficiency affecting young children. Serum ferritin concentration is the preferred biomarker for measuring iron status because it reflects iron stores; however, blood collection can be distressing for young children and can be logistically difficult. A noninvasive means to measure iron status would be attractive to either diagnose or screen for ID in young children., Objectives: This study aimed to determine the correlation between urinary and serum ferritin concentrations in young children; to determine whether correcting urinary ferritin for creatinine and specific gravity improves the correlation; and to determine a urine ferritin cut point to predict ID., Methods: Validation study was conducted using paired serum and urine collected from 3-y-old children (n = 142) participating in a longitudinal birth cohort study: the ORIGINS project in Perth, Western Australia. We calculated the sensitivity, specificity, positive, and negative predictive values of urinary ferritin amount in identifying those with ID at the clinical cut point used by the World Health Organization (serum ferritin concentration of <12 ng/mL)., Results: Urine ferritin, corrected for creatinine, correlated moderately with serum ferritin [r = 0.53 (0.40-0.64)] and performed well in predicting those with ID (area under the curve: 0.85; 95% confidence interval: 0.75, 0.94). Urine ferritin <2.28 ng/mg creatinine was sensitive (86%) and specific (77%) in predicting ID and had a high negative predictive value of 97%; however, the positive predictive value was low (40%) owing to the low prevalence of ID in the sample (16%)., Conclusions: Urine ferritin shows good diagnostic performance for ID. This noninvasive biomarker maybe a useful screening tool to exclude ID in healthy young children; however, further research is needed in other populations., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Urine output and urinary urea-N excretion (UUN e ) excretion are critical measures to accurately evaluate N metabolism in lactating dairy cows and environmental concerns related to manure N. The objectives of this study were: (1) to compare estimates of UUN e , urine output, and related variables from 3 pre-established measurement protocols (bladder catheterization, external collection cup, and spot sampling) and from dietary salt supplementation, (2) to study temporal variation in UUN e , urine output, and related variables as affected by measurement protocol, and (3) to evaluate urine specific gravity as a predictor of urine output. Twelve multiparous Holstein cows were used in a split-plot, Latin square design. Cows were randomly assigned to a diet (main plot) containing either 0.7% or 1.6% NaCl (DM basis) and then assigned to a sequence of 3 protocols (subplot) in a balanced 3 × 3 Latin square with 14-d period. For each protocol, measurements were conducted every 4 h for 3 consecutive days. Urine output was determined gravimetrically for bladder catheterization and external collection cup or based on measured cow BW, measured urinary creatinine concentration, and the assumed creatinine excretion of 29 mg/kg BW per day for spot sampling. Urine specific gravity was measured by refractometry. When averaged over a 3-d measurement period and compared with bladder catheterization, spot sampling underestimated urine output (6.8 kg/d; 20%) and UUN e (26 g/d; 13%) but exhibited greater concentration of urinary urea-N (+58 mg/dL; 10%). There were no differences in any measurements determined via bladder catheterization or external cup device protocols, except for urine output that tended to be 3.7 kg/d lower for collection cup compared with bladder catheterization. The 2 gravimetric protocols yielded lower urinary creatinine concentration than spot sampling (64.7 vs. 88.1 mg/dL) and lower creatinine excretion (25.3 mg/kg BW per day) than the value of 29 mg/kg BW per day generally assumed in the spot sampling protocol. Salt supplementation tended to increase urine output (+5.2 kg/d) and decrease urinary urea-N concentration (-93 mg/dL), urinary creatinine concentration (-9.5 mg/dL), milk protein concentration (-0.19 percentage unit) and milk protein yield (-70 g/d). There was greater temporal variation of urine output when measured via the collection cup compared with bladder catheterization in the first 2 d but not the third day of sampling, suggesting that an extended period of adaptation might have improved data quality of the collection cup protocol. The R 2 of the linear regression to predict urine output with urine specific gravity was 67%, 73%, and 32% for bladder catheterization, collection cup, and spot sampling, respectively. In this study, spot sampling underestimated both urine output and UUN e , but UUN e determination did not differ between external collection cup and bladder catheterization. However, our data suggested the need to investigate the adaptation protocol, required days of measurements and the conversion of urine mass to urine volume to improve accuracy and precision of urine collection protocols., (The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

The possible relationship between dietary magnesium status and proteinuria has been suggested by a number of previous studies. However, human studies on this association are limited. Therefore, the present study aimed to investigate the independent relationship between dietary magnesium intake and urinary protein excretion. The present study was a post hoc analysis of the previous randomized clinical trial that evaluated the effect of dietary phosphorus restriction on proteinuria. The baseline data of 90 participants with proteinuria and chronic kidney disease was used to measure the association between dietary magnesium intake and proteinuria. Participants were asked to record their 24-h food intake for three days a week in a questionnaire. Urinary protein to creatinine ratio (UPCR) in a random urine sample was measured to be a marker for proteinuria. Out of 90 patients included in the study, 47 were men and 43 were women. The mean ± standard deviation of age and body mass index were 59.05 ± 14.16 years and 29.02 ± 5.54 kg/m 2 , respectively. The patients' average daily dietary intake of energy and magnesium were 2183 kcal and 169.44 mg, respectively. A significant inverse correlation was found between the dietary intake of magnesium and UPCR (r =  - 0.219, p = 0.042). This association remained significant even after adjusting for confounding variables (β =  - 0.222, p = 0.028). The findings of the present study showed a significant inverse relationship between the magnesium intake and proteinuria. Although, the design of the current research was cross-sectional, it has provided a basis for conducting future longitudinal studies and trials to better elucidate such a relationship., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Carnitine is essential for fatty acid metabolism. Free carnitine (FCA) is excreted in the urine in the glomerulus, but is partly reabsorbed by a carnitine transporter. The mechanism underlying the decrease in serum carnitine level during pregnancy is unclear., Objective: To investigate whether low carnitine level is associated with increased renal excretion in pregnant women., Methods: We recruited 43 healthy pregnant and 25 non-pregnant women. Total carnitine (TCA) and FCA levels were measured using the enzymatic cycling method, and the acylcarnitine (ACA) level was calculated. Fractional excretion (FE) was calculated as carnitine clearance divided by creatinine clearance., Results: The mean TCA, FCA, and ACA levels were lower at 12 weeks of gestation in pregnant than non-pregnant women ( P < .001); the levels decreased further at 36 weeks, reaching 39%, 36%, and 52% of those in non-pregnant women, respectively ( P < .001). The FEs were 3-4-fold higher in pregnant women than non-pregnant women. Pregnant women had a lower serum FCA/TCA ratio than non-pregnant women (0.788 ± 0.098 vs 0.830 ± 0.074, respectively; P < .05), whereas the urine FCA/TCA ratio was similar between the groups., Conclusion: Low carnitine level is associated with increased renal excretion during late pregnancy., 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.

Creatinine is the end product of the catabolism of creatine and creatine phosphate. Creatine phosphate serves as a reservoir of high-energy phosphate, especially in skeletal and cardiac muscle. Besides typical known changes in serum and urinary creatinine concentrations, rare cases associated with changes in serum and urinary creatine levels have been described in the literature in humans. These cases are mostly linked to an excessive intake of creatine ethyl ester or creatine monohydrate, often resulting in increased urine creatinine concentrations. In addition, it is known that at such elevated creatinine concentrations, creatinine crystallisation may occur in the urine. Analysis of crystals and urinary concrements, often of heterogenous chemical composition, may provide diagnostic and therapeutic hints to the benefit of the patient. The aim of the present work was to analyze urine crystals of unclear composition with microscopic and spectroscopic techniques. On routine microscopic analysis of urine, a preliminary suspicion of uric acid or creatinine crystals was expressed. The crystals were of a cuboid shape and showed polarization effects in microscopy. The dried urine sample was whitish-orange in colour, odourless and dissolved well in water. Protein concentration in dry weight (DW) urine was about 0.3 mg/mg. The measured zinc content in the studied sample was approximately 660 µg/g DW sample and copper content was approximately 64 µg/g DW sample. A lead signal of around 10 µg/g DW sample was also observed. UV-Vis analysis showed a maximum creatine peak around 220 nm, compatible with the spectrum of creatinine with a maximum peak of 230 nm. Using HPLC technique, an extreme high ratio of creatine to creatinine of about 38 was measured, which led to the conclusion of the occurrence of rare creatine crystals in urine., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The burgeoning recognition of the nexus between renal functionality and the prevalence of dementia has precipitated a surge in research endeavors. This study aims to substantiate the causal relationship between kidney functionality and dementia., Methods: We utilized clinical renal function metrics from the Chronic Kidney Disease Genetics (CKDGen) Consortium and diverse dementia types (Alzheimer's disease [AD] and vascular dementia) from the FinnGen Biobank by using Mendelian randomization analysis. At the stratum of genetic susceptibility, we tested the causal relationship between variations index in renal function and the occurrence of dementia. Inverse-variance weighted (IVW) method was the main analysis, and several supplementary analyses and sensitivity analyses were performed to test the causal estimates., Results: The findings indicate a significant correlation between each unit increase in cystatin C-based estimated glomerular filtration rate (eGFR-cys) levels was significantly associated with a reduction in the incidence of late-onset Alzheimer's disease (LOAD) (IVW: OR = 0.35, 95% CI: 0.13-0.91, p  = 0.031). After adjusting for creatinine-based eGFR (eGFR-cre) and urinary albumin-to-creatinine ratio (UACR), a causal relationship was still identified between elevated levels of eGFR-cys and decreased risk of LOAD (IVW: OR: 0.08; 95% CI: 0.01-0.97, p  = 0.047). Sensitivity tests demonstrated the reliability of causal estimates., Conclusions: The association between renal function based on cystatin C and the augmented risk of developing AD lends support to the perspective that regular monitoring of cystatin C may be a valuable investigative biomarker.

Aims: Finerenone has been approved for treating diabetic kidney disease (DKD) with reducing cardiorenal risk. Real-world data on finerenone treatment for the management of DKD are presently lacking. This study aimed to investigate the effect of finerenone on the renal parameters of the Chinese DKD population in the real-world medical setting for the first time, especially in combination with renin-angiotensin system inhibitors (RASi) and sodium-glucose cotransporter 2 inhibitors (SGLT2i)., Methods: Forty-two DKD patients were selected and completed a 6-month finerenone treatment. Renal parameters and adverse effects were collected at every visit., Results: The median urine albumin-to-creatinine ratio (UACR) was 1426.11 (755.42, 3638.23) mg/g. Among them, the proportion of patients with a UACR of 300-5000 mg/g was 76.2%, and the proportion of patients with a UACR of >5000 mg/g was 14.3%. The median estimated glomerular filtration rate (eGFR) was 54.50 (34.16, 81.73) mL/min/1.73 m 2 . Finerenone decreased the UACR significantly throughout the study period ( p  < .05). The maximal decline of UACR at month 6 was 73%. Moreover, the proportion of patients with a 30% or greater reduction in UACR was 68.42% in month 6. There was a smaller decline (9-11%) in the eGFR after initiating finerenone ( p  > .05). One patient each discontinued finerenone due to hyperkalemia (2.4%) and acute kidney injury (2.4%). No patient reported hypotension, breast pain, and gynecomastia., Conclusions: This study from China first demonstrated finerenone decreased UACR with manageable safety in real-world DKD treatment. A triple regimen of RASi, SGLT2i, and finerenone may be a promising treatment strategy for lowering albuminuria and reducing hyperkalemia risk in advanced DKD patients.

Background: Chronic kidney disease (CKD), which has become a global public health issue, is associated with mitochondrial dysfunction. Niacin is a necessary coenzyme for mitochondrial energy metabolism. However, the association between dietary niacin intake and CKD remains uncertain. This study aimed to investigate the association between dietary niacin intake and CKD in American adults., Methods: This is a cross-sectional study. 25,608 individuals aged ≥20 years from the National Health and Nutrition Examination Survey from 2007 to 2018 were involved.Dietary niacin intake was estimated based on 24-hour dietary recalls conducted by trained personnel. CKD was determined by an estimated glomerular filtration rate (eGFR) (<60 ml/min/1.73 m 2 ) or a urinary albumin-to-creatinine ratio (ACR) (≥30mg/g). The association between dietary niacin intake and CKD was investigated using multivariable logistic regression analysis., Results: Of 25,608 participants, 17.14% (4388/25,608) had CKD. Compared to individuals with lower niacin intake (quartile [Q]1, ≤15.30 mg/day), those with higher niacin intake in Q2 (15.31-22.07 mg/day), Q3 (22.08-31.09 mg/day), and Q4 (≥31.10 mg/day) exhibited adjusted odds ratios for CKD of 0.89 (95% confidence interval [CI]:0.81-0.99, p  = 0.024), 0.83 (95% CI:0.75-0 .92, p  < 0 .001), and 0.83 (95% CI:0.75-0.93, p  = 0.001) respectively. The relationship between dietary niacin intake and CKD among U.S. adults follows an L-shaped pattern, with an inflection point at approximately 28.04 mg/day., Conclusions: These results suggest an L-shaped association between dietary niacin intake and CKD. Individuals with low dietary niacin intake levels should be alert to the risk of CKD.

Background: Cardiopulmonary bypass (CPB) is associated with hemolysis and acute kidney injury (AKI). The study aim was to determine if urine dipstick blood in infants after CPB was associated with AKI and urine neutrophil gelatinase-associated lipocalin (NGAL)., Methods: Infants who underwent CPB at a single center were enrolled prospectively between October 2017 and June 2019. Urine samples prior to CPB and 6 h after CPB cessation were analyzed in batch for NGAL and dipstick blood. AKI was defined using creatinine-based KDIGO criteria within 72 h of CPB. Spearman correlation examined associations between urine dipstick blood and NGAL at each time point. Linear regression estimated the associations between urine dipstick blood and log-transformed NGAL 6 h after CPB. Logistic regression estimated associations and compared discrimination between urine dipstick blood and NGAL for predicting AKI., Results: At baseline, 7/63 samples (11%) had > trace blood. Six hours after CPB, 62/98 samples (63%) had > trace blood and 26% had 3 + (large) blood. In total, 18/98 (18%) with a 6-h post-CPB sample had postoperative AKI. Urine dipstick blood values correlated with urine NGAL 6 h after CPB (r = 0.52, p < 0.01), but not at baseline (r = 0.06, p = 0.66). Those with 3 + (large) blood on urine dipstick had 6 times higher mean NGAL values compared to those with negative/trace blood (mean ratio 6.6, 95%CI 3.1-14.4, p < 0.01). Those with 3 + (large) blood had 8 times higher odds of AKI (OR 7.99, 95%CI 1.5-41.9, p = 0.01)., Conclusions: Urine dipstick blood post CPB may be a simple and inexpensive tool to help predict AKI in infants., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)