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Background: A key restriction of label-free surface-enhanced Raman spectroscopy (SERS) in analysis of objects with complex composition (including with several target analytes) is the competition of mixture components for interaction with SERS-active surface. This leads to poor selectivity of the analysis of such mixtures (e.g., body fluids) and the need to use advanced sample pretreatment procedures such as HPLC or TLC. Therefore, this work aims to develop a set of simple and fast pretreatment steps (dilution, pH correction, etc.) to increase the sorption of the target analyte, reduce the sorption of admixtures, and prevent suppression of the target analyte SERS signal., Results: We have developed label-free SERS assay suitable for the determination of three analytes (methotrexate, cephalosporin antibiotic, and creatinine) in one real urine sample as a model matrix with complex and deviating composition. The choice of drugs is justified by the need to monitor their concentration in urine during joint drug treatment of cancer patients with concomitant bacterial infection, while monitoring creatinine concentration helps to evaluate kidney function of the patients. Additionally, three cephalosporin representatives were used in the study to maximize versatility of the assay. As a results, the optimized pretreatment steps enable to eliminate the negative influence of excess of interferences (including other analytes) and achieve precise (≤12 % RSD) and accurate (88-111 % recovery) determination of several analytes in the therapeutically relevant ranges: 300-3000 μg mL -1 for creatinine, 20-200 μg mL -1 for methotrexate and cephalosporins., Significance: Therefore, in addition to reporting a new SERS assay for the analysis of body fluids, this study clearly demonstrates the importance of taking into account competitive adsorption processes on the SERS substrate surface. We suggest making this practice mandatory when developing any label-free SERS assay because it enables to maximize the selectivity and accuracy of the analysis as well as to simplify the analysis procedure., 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.)

Chronic kidney disease (CKD) poses a significant global public health challenge, with environmental toxins potentially contributing to its prevalence. In Taiwan, where arsenic (As) contamination is endemic in certain areas, assessing its impact on renal health is crucial due to the country's high rates of unexplained CKD. This cross-sectional study assessed associations between urinary As species and early renal impairment biomarkers-the microalbumin-to-creatinine ratio (ACR) and β2-microglobulin (B2MG)-in 248 young Taiwanese adults (aged 20-29 years). We measured urinary As species (including arsenite [As 3+ ], arsenate [As 5+ ], monomethylarsonic acid [MMA], and dimethylarsinic acid [DMA]) and early renal impairment biomarkers (urinary microalbumin and B2MG levels). Median concentrations of urinary As 3+ , As 5+ , MMA, DMA, inorganic As (iAs), and the sum of inorganic and methylated As species (iSumAs) were 1.43, 1.02, 3.79, 31.53, 2.82, and 39.22 μg/g creatinine (Cre.), respectively. We also evaluated the first methylation ratio (FMR) and the second methylation ratio (SMR). After adjusting for potential confounding factors, a multivariate linear regression showed significant associations between B2MG and urinary As 5+ (β = 0.299, 95% confidence interval [CI]: 0.113-0.485) and iAs (β = 0.281, 95% CI: 0.061-0.502) concentrations. A generalized additive model revealed non-linear relationships among As 5+ , iAs, and B2MG concentrations. Moreover, there were elevated risks associated with the highest tertile of B2MG concentrations compared to the highest tertile of urinary As 5+ (odds ratio [OR] = 2.366, 95% CI: 1.196-4.682), MMA (OR = 1.917, 95% CI: 1.002-3.666), DMA (OR = 1.952, 95% CI: 1.015-3.753), and iSumAs (OR = 2.302, 95% CI: 1.182-4.483). These results indicated that exposure to As was associated with early renal impairment, particularly evidenced by increased urinary B2MG concentrations., 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.)

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.)

Objective: To analyze the clinical features of creatine transporter(CRTR) deficiency associated with SLC6A8 gene variants. Methods: The clinical data (clinical presentation, brain imaging, creatine metabolism test and gene variants) of 5 patients admitted to Beijing Children's Hospital, Capital Medical University and diagnosed with CRTR deficiency associated with SLC6A8 gene variants from January 2016 to June 2024 were retrospectively analyzed. Results: A total of 5 patients, all male, presented with the onset of the disease at 1 year and 1 month old to 1 year and 10 months old, and diagnosis at 1 year and 3 months to 9 years old. All patients exhibited varying degrees of intellectual and physical developmental deficits, with autistic-like behaviors present in 2 patients and convulsive episodes present in 4 patients. The brain magnetic resonance imaging, of all 5 patients showed either poor or slightly delayed myelination. Additionally, the brain magnetic resonance spectroscopy (MRS) imaging of 5 patients all showed decreased creatine peaks, and 4 patients had elevated urinary creatine levels indicated by blood and (or) urine creatine metabolism tests. There were 3 patients completed blood creatinine tests, all indicating reduction. Whole-exome sequencing was conducted on all 5 patients, and 4 unreported novel variants were identified: c.371G>C, c.1017-1G>A, c.912+1G>T and c.1016+2T>A. Following treatment with creatine, arginine, and glycine supplementation, no significant advancement was observed in motor and language development. Conclusions: CRTR deficiency associated with SLC6A8 gene variants manifests as developmental delay with or without seizures, with atypical clinical features, the presence of decreased blood creatinine levels and elevated urinary creatine levels. Combined with brain MRS and genetic testing results, patients can be diagnosed.

Introduction: In outpatient settings, it is challenging to exclude acute kidney disease (AKD) based on a single serum creatinine (SCr) measurement. This retrospective study aimed to explore the usefulness of urinary biomarkers and a novel functional biomarker, a spot urine creatinine-to-osmolality ratio (sUCr/Osm), for inferring the absence of AKD., Methods: The cohort was from the ASSESS-AKI Study. 'No AKD' was defined as the absence of a SCr increase ≥ 26.5 μmol/L between the preceding visit and the index visit, with a three-month interval. Urinary neutrophil gelatinase-associated lipocalin (UNGAL) was selected as the representative biomarker out of six known candidates. UNGAL levels < 100 ng/mL indicated a positive test. sUCr/Osm values ≥ 7.07 indicated a positive test., Results: Of the 1,570 participants, 38.0% were female. The mean age (mean ± SD) was 64.6 ± 13.0 years, and the mean SCr level was 102.5 ± 51.4 μmol/L. The area under the receiver operating characteristic curve for UNGAL in identifying 'No AKD' for all participants was 0.548 (95% confidence interval: 0.495-0.600), whereas that for sUCr/Osm was 0.578 (0.525-0.630). The sensitivity of UNGAL was 0.867 (0.849-0.884), with a positive predictive value of 0.917 (0.902-0.932) and an accuracy of 0.808 (0.788-0.827). The corresponding values of sUCr/Osm were 0.926 (0.912-0.939), 0.906 (0.891-0.921), and 0.845 (0.827-0.863). In individuals whose SCr-derived estimated glomerular filtration rate was < 60 mL/min/1.73 m 2 , sUCr/Osm performed comparably to UNGAL., Conclusion: Using sUCr/Osm to infer the absence of AKD in outpatients with a single SCr measurement may be as effective as using UNGAL.

IgA nephropathy (IgAN) is the most common type of primary glomerulonephritis worldwide and leads to end-stage kidney disease. The proteinuria selectivity index (PSI) has been used to assess the prognosis in nephrotic syndrome, but its predictive value in patients with IgAN remains unclear. This single-center retrospective cohort study included patients who diagnosed with IgAN between March 2012 and March 2020. The PSI was calculated at the time of kidney biopsy. Patients were followed up from the time of kidney biopsy to kidney replacement therapy, death, transfer to another facility, or study completion. Ninety-four patients with a median age of 51 years were enrolled and divided according to the cutoff value of PSI determined by the receiver operating characteristic curve analysis into low-PSI (PSI <0.243, n  = 39) and high-PSI groups (PSI ≥0.243, n  = 55). The median follow-up duration was 70 months. Rates of remission of proteinuria and survival without a two-fold increase in serum creatinine were significantly better in the low-PSI group (both p  < 0.01, log-rank test). Cox regression analysis showed that a low PSI was significantly associated with an increased likelihood of remission of proteinuria and hematuria (hazard ratio [HR] 1.96; 95% confidence interval [CI] 1.02-3.85 and HR 1.75; 95% CI 1.01-3.13, respectively), and a decreased risk of a two-fold increase in serum creatinine (HR 0.10; 95% CI 0.01-0.81). In conclusion, The PSI could have the potential to support the assessment of the prognosis of IgAN, in addition to established prognostic markers, by reflecting the overall glomerular permeability.

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.

Introduction: Increased albuminuria is associated with elevated mortality. Urine albumin (U-ALB) above 20 mg/L or albumin-to-creatinine ratio (U-ACR) of 3 g/mol are indicative of moderately increased albuminuria. Due to limited standardization among U-ALB methods, diagnosis of increased albuminuria might prove difficult., Materials and Methods: Data from Equalis's external quality assessment scheme for low U-ALB levels during 2005-2023 were categorized according to manufacturer and divided into central laboratory (CLAB) and point-of-care testing (POCT) methods. Manufacturer median values were compared to total group mean consensus values and manufacturer CV% was compared at different U-ALB levels., Results: CLAB was generally closer to consensus values and had lower CV% than POCT at U-ALB levels around 20 mg/L. For CLAB, Roche methods were approximately equal to consensus U-ALB, Abbott 4 % above, and Siemens 5 % below. For POCT, HemoCue was 1 % below, Siemens 7 % above, and Abbott 8 % below. For U-Creatinine, all manufacturers generally had a good agreement differing on average by 1-4 % from consensus., Conclusions: Although U-ALB methods generally meet The National Kidney Disease Education Program (NKDEP) recommendations of method bias less than 13 % and imprecision less than 30 %, differences among manufacturers have increased over the last years, with 2023 showing the largest differences between methods. This highlights the need for guidelines for albuminuria and ACR to take method differences into consideration, but also for implementation of suitable urine reference materials., 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 Author(s). Published by Elsevier Inc. All rights reserved.)

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.

Cotadutide is a glucagon-like peptide-1 (GLP-1) and glucagon receptor agonist that may improve kidney function in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). In this phase 2b study, patients with T2D and CKD (estimated glomerular filtration rate [eGFR] of 20 or more and under 90 mL/min per 1.73 m 2 and urinary albumin-to-creatinine ratio [UACR] over 50 mg/g) were randomized 1:1:1:1:1 to 26 weeks' treatment with standard of care plus subcutaneous cotadutide uptitrated to 100, 300, or 600 μg, or placebo daily (double-blind), or the GLP-1 agonist semaglutide 1 mg once weekly (open-label).The co-primary endpoints were absolute and percentage change versus placebo in UACR from baseline to the end of week 14. Among 248 randomized patients, mean age 67.1 years, 19% were female, mean eGFR was 55.3 mL/min per 1.73 m 2 , geometric mean was UACR 205.5 mg/g (coefficient of variation 270.0), and 46.8% were receiving concomitant sodium-glucose co-transporter 2 inhibitors. Cotadutide dose-dependently reduced UACR from baseline to the end of week 14, reaching significance at 300 μg (-43.9% [95% confidence interval -54.7 to -30.6]) and 600 μg (-49.9% [-59.3 to -38.4]) versus placebo; with effects sustained at week 26. Serious adverse events were balanced across arms. Safety and tolerability of cotadutide 600 μg were comparable to semaglutide. Thus, our study shows that in patients with T2D and CKD, cotadutide significantly reduced UACR on top of standard of care with an acceptable tolerability profile, suggesting kidney protective benefits that need confirmation in a larger study., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Rationale & Objective: Patients treated with kidney replacement therapy experience a 1.5- to 2-fold increased risk of cancer and cancer mortality compared with the general population. Whether this excess risk extends to people with earlier stage chronic kidney disease and whether reduced kidney function is causally related to cancer is unclear., Study Design: Two-sample Mendelian randomization (MR)., Setting & Participants: Genome-wide association study (GWAS) summary statistics for estimated glomerular filtration rate (eGFR) (n=567,460) and urinary albumin-creatine ratio (UACR) (n=127,865) from the CKDGen consortium and cancer outcomes from the UK Biobank (n = 407,329)., Exposure: eGFR and UACR., Outcome: Overall cancer incidence, cancer-related mortality and site-specific colorectal, lung, and urinary tract cancer incidence., Analytical Approach: Univariable and multivariable MR conducted for all outcomes., Results: The mean eGFR and median UACR were 91.4mL/min/1.73m 2 and 9.32mg/g, respectively, in the CKDGen, and 90.4mL/min/1.73m 2 and 9.29mg/g, respectively, in the UK Biobank. There were 98,093 cases of cancer, 15,850 cases of cancer-related death, 6,664 colorectal, 3584 lung, and 3,271 urinary tract cancer cases, respectively. The genetic instruments for eGFR and UACR comprised 34 and 38 variants, respectively. Genetically predicted kidney function (eGFR and UACR) was not associated with overall cancer risk or cancer death. The association between genetically predicted eGFR and UACR and overall cancer incidence had an odds ratio of 0.88 ([95% CI, 0.40-1.97], P=0.8) and 0.90 ([95% CI, 0.78-1.04], P=0.2) respectively, using the inverse-variance weighted method. An adjusted generalized additive model for eGFR and cancer demonstrated evidence of nonlinearity. However, there was no evidence of a causal association between eGFR and cancer in a stratified MR., Limitations: To avoid overlapping samples a smaller GWAS for UACR was used, which reduced the strength of the instrument and may introduce population stratification., Conclusions: Our study did not show a causal association between kidney function, overall cancer incidence, and cancer-related death., Plain-Language Summary: Does reduced kidney function cause cancer? Patients with chronic kidney disease have been shown to have an increased risk of cancer and cancer-related death. However, it is not clear whether kidney disease is causally related to cancer or the association is due to other factors such as immune suppression and inflammation or a result of distortion of the analyses from unidentified variables (confounding). We used large, published genetic studies as well a database including 407,329 people in the United Kingdom in a series of Mendelian randomization analysis. Mendelian randomization uses the random assignment of genetic variants at birth to investigate causal relationships without confounding from measured and unmeasured confounders. We found that there is no evidence of a causal relationship between reduced kidney function and cancer., (Copyright © 2024 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

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.)

Background: Daily serum creatinine monitoring protocols for acute kidney injury (AKI) are invasive and may lead to surveillance resistance. We aimed to understand if use of urine neutrophil gelatinase-associated lipocalin (uNGAL) could increase high-risk nephrotoxic medication (NTMx) associated AKI screening adherence in neonates., Methods: Statistical process control methods prior to and post implementation were trended. The primary outcome, screening adherence, was defined as either daily serum creatinine or uNGAL assessment through 2 days post high-risk NTMx exposure., Results: 1291 monitoring days from the pre-implementation era (4/2020-6/2021) were compared to1377 monitoring days from the post-era (6/2021-10/2022). AKI screening adherence increased (81 to 92%) following implementation of optional uNGAL screening. Urine NGAL accounted for 35% of screening obtained. Use of uNGAL resulted in a 40% reduction in blood sampling for serum creatinine., Conclusions: Incorporation of uNGAL as a complementary screening tool to serum creatinine demonstrated sustained increased AKI surveillance in our Baby NINJA monitoring program., Competing Interests: Competing interests: Cara Slagle, MD is a consultant for AM Pharma and Medtronic and has received honorariums from Medtronic, the University of Alabama, and the AKI Critical Care Foundation, all unrelated to the work above. Stuart Goldstein, MD and Cincinnati Children’s Hospital receive royalties from Vigilanz Corporation (Minneapolis, MN) for the NINJA application licensed to Vigilanz from Cincinnati Children’s Hospital Medical Center. Dr. Goldstein consults and receives research funding from BioPorto Diagnostics, Inc, which markets The ProNephroAKI NGAL Test™., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: The successful treatment and improvement of acute kidney injury (AKI) depend on early-stage diagnosis. However, no study has differentiated between the three stages of AKI and non-AKI patients following heart surgery. This study will fill this gap in the literature and help to improve kidney disease management in the future., Methods: In this study, we applied Raman spectroscopy (RS) to uncover unique urine biomarkers distinguishing heart surgery patients with and without AKI. Given the amplified risk of renal complications post-cardiac surgery, this approach is of paramount importance. Further, we employed the partial least squares-support vector machine (PLS-SVM) model to distinguish between all three stages of AKI and non-AKI patients., Results: We noted significant metabolic disparities among the groups. Each AKI stage presented a distinct metabolic profile: stage 1 had elevated uric acid and reduced creatinine levels; stage 2 demonstrated increased tryptophan and nitrogenous compounds with diminished uric acid; stage 3 displayed the highest neopterin and the lowest creatinine levels. We utilized the PLS-SVM model for discriminant analysis, achieving over 90% identification rate in distinguishing AKI patients, encompassing all stages, from non-AKI subjects., Conclusions: This study characterizes the incidence and risk factors for AKI after cardiac surgery. The unique spectral information garnered from this study can also pave the way for developing an in vivo RS method to detect and monitor AKI effectively.

Background: Systemic Immune-Inflammation Index (SII) is a novel inflammatory biomarker closely associated with the inflammatory response and chronic kidney disease. Klotho is implicated as a pathogenic factor in the progression of kidney disease, and supplementation of Klotho may delay the progression of chronic kidney disease by inhibiting the inflammatory response. Our aim is to investigate the potential relationship between SII and Klotho in adult patients in the United States and explore the differences in the populations with and without albuminuria., Methods: We conducted a cross-sectional study recruiting adult participants with complete data on SII, Klotho, and urine albumin-to-creatinine ratio (ACR) from the National Health and Nutrition Examination Survey from 2007 to 2016. SII was calculated as platelet count × neutrophil count/lymphocyte count, with abnormal elevation defined as values exceeding 330 × 10^9/L. Albuminuria was defined as ACR >30 mg/g. Weighted multivariable regression analysis and subgroup analysis were employed to explore the independent relationship between SII and Klotho., Results: Our study included a total of 10,592 individuals. In all populations, non-albuminuria population, and proteinuria population with ACR ≥ 30, participants with abnormally elevated SII levels, as compared to those with SII less than 330 × 10^9/L, showed a negative correlation between elevated SII levels and increased Klotho, which persisted after adjusting for covariates., Conclusions: There is a negative correlation between SII and Klotho in adult patients in the United States. This finding complements previous research but requires further analysis through large prospective studies.

Introduction: This study focuses on investigating the relationship between serum neurofilament light chain (sNfL) and urinary albumin-to-creatinine ratio (uACR) among American adults aged 25-75., Methods: An analysis was conducted on information gathered from 1741 individuals aged between 25 and 75 who participated in the National Health and Nutrition Examination Survey (NHANES) during the years 2013-2014. Generalized linear models were utilized, and restricted cubic spline (RCS) analysis was conducted to assess a non-linear relationship., Results: Upon adjusting for multiple variables, a non-linear inverse J-shaped relationship was observed between sNfL and uACR. Compared with individuals in quartile 1 (Q1) of sNfL (2.8-8.3), those with quartile 4 (Q4) (≥19.1) had an adjusted β for uACR of 51.57., Conclusions: The study found a J-shaped curve linking sNfL and uACR in American adults, with a turning point around log(sNfL) 2.928 pg/mL.

Purpose: It is unknown whether febuxostat can delay the progression of kidney dysfunction and reduce kidney endpoint events. The aim was to evaluate the renoprotective effect of febuxostat in patients with hyperuricemia or gout by performing a meta-analysis of randomized controlled trials (RCTs)., Methods: MEDLINE, Web of science, EMBASE, ClinicalTrials.gov, and the Cochrane Central Register for Randomized Controlled Trials were searched. The main outcomes included kidney events (serum creatinine doubling or progression to end-stage kidney disease or dialysis). The secondary outcomes were the rate of change in the estimated glomerular filtration rate (eGFR) and changes in the urine protein or urine albumin to creatinine ratio from baseline to the end of follow-up. We used random-effects models to calculate the pooled risk estimates and 95% CIs., Results: A total of 16 RCTs were included in the meta-analysis. In comparison with the control group, the patients who received febuxostat showed a reduced risk of kidney events (RR = 0.56, 95% CI 0.37-0.84, p  = 0.006) and a slower decline in eGFR (WMD = 0.90 mL/min/1.73 m 2 , 95% CI 0.31-1.48, p  = 0.003). The pooled results also revealed that febuxostat use reduced the urine albumin to creatinine ratio (SMD = -0.21, 95% CI -0.41 to -0.01, p  = 0.042)., Conclusion: Febuxostat use is associated with a reduced risk of kidney events and a slow decline in eGFR. In addition, the urine albumin to creatinine ratio decreased in febuxostat users. Accordingly, it is an effective drug for delaying the progression of kidney function deterioration in patients with gout. Systematic review registration: PROSPERO CRD42021272591.

Background: House dust endotoxin is thought to be associated with systemic inflammatory responses and respiratory diseases. Previous studies have indicated that lung injury and systemic inflammation could lead to kidney damage. However, the potential link between house dust endotoxin and the increased risk of kidney injury remains unexplored., Objectives: This cross-sectional study and retrospective study aim to investigate the relationship between house dust endotoxin levels and renal markers, specifically the urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR), utilizing data from the NHANES 2005-2006 survey cycle., Results: Proteinuria was assessed using the UACR, with values categorized into negative (UACR ≤ 30 mg/g) and positive (UACR > 30 mg/g) groups. Significant differences in house dust endotoxin levels were observed between these groups (p value = 0.003). Weighted logistic regression analysis indicated that higher levels of house dust endotoxin were associated with an increased rate of positive UACR (OR [95% CI]: 1.57 [1.20, 2.05]; p value = 0.003). This association remained significant after adjusting for covariates such as age, gender, race, poverty income ratio (PIR), Type 2 Diabetes Mellitus (T2DM), and hypertension (OR [95% CI]: 1.46 [1.08, 1.97]; p-Value = 0.021). However, no significant correlation was found between house dust endotoxin levels and eGFR (Estimate [95% CI]: 1.19 [-1.28, 3.66]; p value = 0.32)., Conclusions: Our findings suggest a significant association between house dust endotoxin levels and proteinuria, based on data from the NHANES 2005-2006 survey cycle. This association indicates that elevated levels of house dust endotoxin may be linked to kidney damage. Further research is necessary to elucidate the specific relationship between exposure to house dust endotoxin and the risk of developing kidney disease., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Cardiovascular disease (CVD) is the leading cause of mortality in type 2 diabetes mellitus (T2DM) patients. Shrunken pore syndrome (SPS) is defined as eGFR cystatin C /eGFR creatinine ratio <0.70 and predicts high CVD mortality. The Framingham Risk Score (FRS) is used to estimate an individual's 10-year CVD risk. This study investigated the association between FRS and eGFR cystatin C /eGFR creatinine ratio in T2DM patients., Methods: Patients aged 18-80 years who were newly diagnosed with T2DM were included in this retrospective study. Ordinal logistic regression analysis was used to investigate the association between risk factors of T2DM and FRS. A Generalized Linear Model was used to calculate odds ratios (OR) and 95% confidence intervals (CI)., Results: There were 270 patients included in the study. Only 27 patients (10%) met the diagnostic criteria of SPS. Ordinal logistic regression analysis showed that SPS was not correlated with FRS risk (OR = 1.99, 95%CI = 0.94-4.23, p  = 0.07), whereas eGFR cystatin C /eGFR creatinine (OR = 0.86, 95%CI = 0.77-0.97, p  = 0.01) showed a significant negative association with FRS risk. Compared with eGFR cystatin C /eGFR creatinine >0.85, eGFR cystatin C /eGFR creatinine ≤0.85 increased FRS risk (OR = 1.95, 95%CI = 1.18-3.21, p  < 0.01). After adjustment for confounding factors, increased eGFR cystatin C /eGFR creatinine ratio was associated with decreased FRS risk when considered as a continuous variable (OR = 0.87, 95%CI = 0.77-0.99, p  = 0.03). The FRS risk in patients with eGFR cystatin C /eGFR creatinine ≤0.85 is 1.86 times higher than that in patients with eGFR cystatin C /eGFR creatinine >0.85 (OR = 1.86, 95%CI = 1.08-3.21, p  = 0.03)., Conclusions: In the current study, no significant association between SPS and FRS was identified. However, lower eGFR cystatin C /eGFR creatinine and eGFR cystatin C /eGFR creatinine ≤0.85 were associated with a significantly increased CVD risk in T2DM.

Background: Chronic liver disease is a common and important clinical problem.Hepatorenal syndrome (HRS) is a life threatening complication. Serum creatinine (Cr) remains the only conventional indicator of renal function. However, the interpretation of serum Cr level can be confounded by malnutrition and reduced muscle mass often observed in patients with severe liver disease. Here, we present a cross-sectional study to explore the sensitivity and specificity of other markers as urinary KIM-1 and NGAL for cases of HRS., Methods: Cross-sectional study was conducted on 88 patients who were admitted to Alexandria main university hospital. Enrolled patients were divided in two groups; group 1: patients with advanced liver cirrhosis (child B and C) who have normal kidney functions while group 2: patients who developed HRS. Stata© version 14.2 software package was used for analysis., Results: Group 1 included 18 males and 26 females compared to 25 males and 19 females in group 2 ( p  = 0.135). Only the urinary KIM-1 showed a statistically significant difference between both groups in the multivariate logistic regression analysis adjusted for gender, serum bilirubin, serum albumin, INR, serum K, AST and ALT levels., Conclusion: In conclusion, our study aligns with prior research, as seen in the consistent findings regarding Urinary NGAL elevation in cirrhotic patients with AKI. Urinary KIM-1, independent of Urinary NGAL, may have a role in precisely distinguishing between advanced liver cirrhosis and HRS and merits further exploration.

Objective: To evaluate modified versions of the Belimumab International Study in Lupus Nephritis (BLISS-LN) belimumab study primary efficacy renal response (mPERR) and complete renal response (mCRR) criteria (excluding mandatory corticosteroid tapering) as predictors of real-world, long-term renal outcomes among patients with lupus nephritis (LN)., Methods: This retrospective, observational study (GSK Study 212866) used deidentified data between 1970 and 2015 from the University of Toronto Lupus Cohort from adults diagnosed with systemic lupus erythematosus and biopsy-proven Class III±V, IV±V or V LN. At 24 months postbiopsy, patients were retrospectively indexed as responders/non-responders based on mPERR (estimated glomerular filtration rate (eGFR) ≤20% below biopsy value/≥60 mL/min/1.73 m 2 and urine protein:creatinine ratio (uPCR) ≤0.7 g/day) or mCRR (eGFR ≤10% below biopsy value/≥90 mL/min/1.73 m 2 and uPCR ≤0.5 g/day) criteria. The association between index mPERR (primary outcome) or mCRR (secondary outcome) status and long-term (up to 25 years, until censoring or death) renal survival (no progression to end-stage kidney disease (eGFR <30 mL/min/1.73 m 2 , dialysis or transplant) or death) was assessed., Results: Overall, 179 patients were included in the analysis (mPERR responders, n=128; non-mPERR responders, n=51). Most patients were female (87.2%); the mean (SD) age was 34.1 (11.3) years.Long-term renal survival was attained for 78.9% of mPERR responders and 60.8% of non-mPERR responders; achieving mPERR was associated with an increased likelihood of long-term renal survival versus not achieving mPERR (log-rank p=0.0119). Overall, 102 patients were mCRR responders, and 77 were non-mCRR responders. Long-term renal survival was attained for 80.4% of mCRR responders and 64.9% of non-mCRR responders; achieving mCRR was associated with an increased likelihood of long-term renal survival than not achieving mCRR (log-rank p=0.0259)., Conclusions: Achieving mPERR or mCRR was associated with improved long-term renal survival, highlighting that these statuses are suitable predictors of long-term renal outcomes in patients with LN., Competing Interests: Competing interests: MU has received grant/research support from GSK and consulting fees from GSK, UCB, Lilly and AstraZeneca, and has been a speaker for GSK, UCB, Lilly and AstraZeneca. ZT has received grant/research support from GSK and AZ and consulting fees from GSK, AbbVie, UCB and AstraZeneca, and has been a speaker for GSK, UCB and AstraZeneca. He has salary support from the Department of Medicine and holds the Dr MU Chair in Lupus Research at UHN. MEG, QF and RAL are employees of GSK and hold stock/shares in the company. PCJ was an employee of GSK at the time of the study and holds stock/shares in the company and is a current employee of RTI Health Solutions. KG was an employee of GSK at the time of the study and holds stocks and shares in GSK, and a current employee of AstraZeneca. JS, NA, JPDM and AM have nothing to disclose., (© 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: The 24-h urine protein (24-hUP) excretion is the gold standard for evaluating proteinuria. This study aimed to evaluate the diagnostic efficacy of protein/creatinine ratio (PCR) for estimating 24-hUP at various levels of renal function and proteinuria levels., Methods: A cross-sectional study was conducted between December 2021 and December 2023 in Salvador, Bahia-Brazil, as an extension of previously published data from the TUNARI study. The study included 217 samples from 152 patients with various levels of renal function and proteinuria. PCR in isolated samples and 24-hUP were determined conventionally within a 24-h timeframe. Patients were classified into three groups according to the level of renal function (Group 1 = 10 to < 30 mL/min, Group 2 = 30-60 mL/min, and Group 3 = > 60 mL/min) and level of proteinuria (< 0.3 g/day, 0.3-3.5 g/day, and > 3.5 g/day). The data were analyzed using the Spearman correlation (r s ), coefficient of determination (r 2 ), Bland-Altman plots and receiver operating characteristic (ROC) curve. Likelihood ratios, positive (LR +), and negative (LR-) were derived from the sensitivity and specificity of PCR., Results: Mean age was 41.5 ± 15.7 years, 61.8% were women, 36.8% Black and 52% Mixed-race. Glomerulopathies constituted 80.3%; 46.1% with lupus nephritis. Of the total urine samples, we observed a high correlation between PCR in the total sample of 24-hUP sample (r s  = 0.86, p < 0.001) across different levels of renal function. However, agreement between PCR and 24-hUP was reduced at higher levels of proteinuria. The ROC analysis showed an AUC of 0.95 (95% CI = 0.92, 0.98), sensitivity of 91% and specificity of 86.5% (LR + 6.7; LR- 0.1), with an optimal cut-off of 0.77. These results were similar across renal function levels. Proteinuria ≤ 0.3 g/day showed a high sensitivity of 83.3% and specificity of 90%, with an area under (AUC) of 0.85 (95% CI = 0.71; 0.94). In the 24-hUP range > 0.3-3.5 g/day, the sensitivity was 64.1%, the specificity was 84.6%, and the AUC was 0.76 (95% CI = 0.67; 0.84), PCR detected all cases > 3.5 g/day., Conclusions: PCR is a suitable measure to be used as an indicator of 24-hUP at different levels of renal function, but may have limitations at higher levels of proteinuria. Analysis of PCR by proteinuria level found that agreement as well as sensitivity decreases at higher levels, but it maintains good specificity and is able to identify nephrotic range proteinuria., Competing Interests: Declarations. Ethics approval and consent to participate: The Research Ethics Committee of HUPES at the Federal University of Bahia approved the study protocol, with Certificate of Presentation of Ethical Appreciation (CAAE): 64362522.7.0000.0049 and case number 5.909.208. All patients gave their informed consent to participate. The present investigation was carried out in accordance with the Declaration of Helsinki of the World Medical Association. Consent for publication: This study has the informed consent form duly applied and signed by the participants in accordance with the ethical standards for the publication of their clinical and/or imaging data. This study included obtaining and signing informed consent from participants, in compliance with ethical standards for the publication of their clinical data and images. The anonymity and confidentiality of the information provided was strictly guaranteed. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Objective: We evaluated the interaction of urinary protein-to-creatinine ratio (UPCR) with diabetes on the risk of cardiovascular events in a cohort study., Methods: The study population consisted of 639 participants with chronic kidney disease (CKD) stages 2-5, enrolled between 2010 and 2011 in Japan. Cox proportional hazards models were used to evaluate the independent and combined effects of the UPCR and diabetes on cardiovascular events., Results: During a median follow-up of 3 years, 59 participants developed cardiovascular events during follow-up. A notably higher risk of cardiovascular events was found in participants with proteinuria [hazards ratio (HR): 2.16, 95% confidence interval (95% CI): 1.17-3.97] compared to those without proteinuria at UPCR levels. In addition, the participants with diabetes had a higher risk of cardiovascular events (HR: 2.53, 95% CI: 1.49-4.30) than those without diabetes. Moreover, an interaction was found between UPCR and diabetes on cardiovascular events (P for interaction = 0.04). Participants with both proteinuria (UPCR ≥ 0.5 g/gCr) and diabetes had a 4.09 times higher risk of cardiovascular events (HR: 4.09, 95% CI: 1.97-8.47) compared with those without proteinuria (UPCR < 0.5 g/gCr) and diabetes., Conclusions: In summary, among participants with CKD stages 2-5, proteinuria and diabetes were found to independently and jointly affect the risk of cardiovascular events. Participants with proteinuria and diabetes had the highest risk of cardiovascular events compared with other groups., Competing Interests: Declarations Ethics approval and consent to participate In the previously published article, Iimori S et al. [12] has clearly stated that: This study was approved by the ethical committees of Tokyo Medical and Dental University, School of Medicine (No. 883) and all institutions participating in the study and was conducted in accordance with the ethical principles of the Declaration of Helsinki. All patients provided informed consent. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

A fluorescence (FL)-based nanosensor has been devised for creatinine (CR) detection in human urine specimens. The proposed nanosensor utilized a nanocomposite (NC) of carbon dots (CDs) and graphene oxide (GO). The formation of CDs/GO NC reduced the CD FL emission (λ excitation  = 390 nm, λ emission  = 461 nm) by ~ 75%. With the introduction of CR to the NC, the CD emission intensity was reinstated by approximately 70%. The linear detection range for CR was 10 -5 to 0.1 mg dL -1 (R 2  = 0.998), with a limit of detection of 4.3 × 10 -2  mg dL -1 . Additionally, CDs/GO NC exhibited outstanding consistency and specificity in recognizing CR within urine specimens from both healthy individuals and patients suffering from chronic kidney disease (CKD). The Bland-Altman assessment (utilizing 25 human urine specimens) displayed remarkable consensus (R 2  = 0.995) among the FL approach and the benchmark Jaffe technique. This observation indicates the hands-on usefulness of the nanosensor for identifying CR in biological specimens., Competing Interests: Declarations Ethical approval Ethical approval for collecting patient urine samples was obtained by the Institutional ethical committee and due consent was obtained from the subjects prior to sample collection. Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

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.)

Background and Aims: Diabetic peripheral neuropathy (DPN) and diabetic nephropathy (DN) both have microcirculation dysfunction. Urinary albumin-to-creatinine ratio (UACR) is a biomarker for DN. We aimed to explore the links between DPN and UACR in patients with type 2 diabetes mellitus (T2DM)., Methods: A total of 195 T2DM patients were defined as Control or DPN group. Clinical parameters were compared, and the association between HbA1c (or UACR) and DPN was analyzed. Risk factors for DPN were observed, and the diagnostic values of HbA1c and UACR were assessed., Results: Compared with 104 participants without DPN, 91 individuals with DPN exhibited higher HbA1c and UACR levels. In all patients, increased HbA1c and UACR were identified as risk factors for DPN in individuals with T2DM. Moreover, increased HbA1c was a risk factor for DPN in volunteers without DN, whereas elevated UACR was determined as a risk factor for DPN in participants with DN. The cut-off point for HbA1c (7.65%) in patients without DN had a sensitivity of 86.0% and specificity of 44.6%, while the cut-off point for UACR (196.081 mg/g) in patients with DN had a sensitivity of 52.9% and specificity of 76.2%., Conclusion: Elevated HbA1c and UACR levels are risk factors for DPN and may serve as potential biomarkers for DPN in T2DM patients., (© 2024. The Author(s).)

Importance: This paper highlights the urine albumin-to-creatinine ratio (UAC) as a valuable biomarker for the early detection of chronic kidney disease (CKD) in dogs. The UAC effectively distinguishes between healthy dogs and those with CKD, particularly in the early stages, and enhances diagnostic accuracy when used alongside other renal biomarkers., Objective: To evaluate the utility of the UAC as a biomarker for early CKD diagnosis in dogs and examine its correlation with other renal biomarkers in a large-scale clinical study., Methods: This study included 99 healthy dogs and 122 dogs with CKD. The UAC and other renal biomarkers were measured and evaluated in healthy dogs and those with CKD and categorized according to the staging criteria of the International Renal Interest Society (IRIS)., Results: Dogs with CKD had significantly higher UACs than healthy dogs ( p < 0.05). The UAC correlated with the IRIS stages and other renal biomarkers ( p < 0.05). Receiver operating characteristic curve analysis yielded an area under the curve of 0.817 ( p < 0.05) for the UAC, with a cut-off value of 19.20 mg/g, showing 72% sensitivity and 71% specificity. A "grey zone" diagnostic window for early-stage CKD was introduced., Conclusions and Relevance: The UAC is effective for the early diagnosis of renal disease in dogs. The UAC can differentiate between healthy dogs and those with CKD at IRIS stage 1. The diagnostic value is enhanced when used alongside other renal biomarkers, allowing for more specific guidelines for pet owners and veterinarians. This large-scale study addresses the limitations of previous research conducted on small clinical samples., Competing Interests: The authors declare that the research was funded by by i-SENS Inc (Seoul, Republic of Korea). The funding source had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript., (© 2024 The Korean Society of Veterinary Science.)

This prospective case-control study explored the association between urinary magnesium levels and acute urinary retention (AUR) in individuals presenting to the emergency department. Forty-six participants, comprising 23 cases and 23 age- and sex-matched controls, underwent urine analysis for magnesium, calcium, and creatinine concentrations. The exclusion criteria mitigated potential confounding factors. AUR cases exhibited significantly lower magnesium (5.97 vs.3.87, p = 0.031), calcium (11.04 vs. 5.3, p = 0.022), and creatinine (149.9 vs. 66.0, p = 0.005) levels (mg/dL) compared to controls. After adjusting for creatinine levels, no intergroup differences were observed. An inverse linear correlation was noted between the International Prostate Symptom Score and magnesium level (R2 = 0.15, p = 0.009). A magnesium cut-off of 3.57 mg/dL demonstrated 82.6 % sensitivity, 56.5 % specificity, and an AUC of 0.70. Patients with magnesium levels below 3.57 mg/dL had an 80 % higher risk of AUR (OR: 1.80, 95 % CI: 1.08-3.01, p = 0.016). This study highlights urinary magnesium as a potential marker for risk of AUR, paving the way for larger prospective studies in this intriguing domain. Future interventions that manipulate magnesium levels may offer innovative avenues for managing lower urinary tract disorders.

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).)

Background: Oxidative stress is a potential contributor to chronic kidney disease (CKD) progression but has not been evaluated in dogs and cats with CKD., Hypothesis: Oxidative stress is higher in animals with CKD compared with healthy controls and decreases with the advancing CKD stage. The aim of this study was to determine the presence and intensity of oxidative stress in dogs and cats at different CKD stages., Animals: Sixty dogs and 30 cats with naturally acquired CKD; 10 dogs and 14 cats, healthy controls., Methods: Analytical cross-sectional study. Oxidative stress was evaluated by measuring the urinary concentration of F2-isoprostane (uF2-IsoPs) normalized to urinary creatinine., Results: Urinary F2-isoprostanes normalized to urinary creatinine of healthy dogs and of dogs with CKD Stages 1 to 4 was 3.3 ng/mg, 4.7 ng/mg (range, 1.0-73.4), 2.4 ng/mg (range, 0.4-7.8), 0.52 ng/mg (range, 0.01-2.9), and 0.37 ng/mg (range, 0.01-0.6), respectively. Urinary F2-isoprostanes differed among CKD stages (P < .001), but not compared with controls. uF2-IsoPs of healthy cats and cats with CKD Stages 1 to 4 was 0.68 ng/mg (range, 0.2-1.4), 0.97 ng/mg (range, 0.4-1.8), 0.6 ng/mg (range, 0.002-2.0), 0.94 ng/mg (range, 0.3-2.3), and 0.2 ng/mg (range, 0.01-0.4). Urinary F2-isoprostanes differed among stages (P = .05) but not compared with healthy controls., Conclusion and Clinical Importance: Oxidative stress might be present in dogs and cats with CKD. Its magnitude declines as the disease progresses, therefore, it should be considered a potential therapeutic target mostly at the early stages of the disease., (© 2024 The Author(s). Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: Exposure to brominated flame retardants (BFRs) may contribute the advancement of chronic kidney disease (CKD). The objective is to evaluate the renal effects of BFRs in patients with CKD., Methods: Totally 7235 US participants of whom 1187 (16.41 %) were diagnosed with CKD were screened for this investigation from the National Health and Nutrition Examination Survey (NHANES) database spanning from 2005 to 2016. The isotope dilution gas chromatography high-resolution mass spectrometry (GC/IDHRMS) was employed for identification of 11 polybrominated diphenyl ethers (PBDEs) and PBB153 serving as the exposure factor. A set of covariates concerning basic characteristics, renal function indicators and suffering from diseases of these participants was considered as potential confounding factors. Subgroup analyses to examine the impact of age and gender on the relationship between serum BFRs and CKD, estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (UACR), serum creatinine (Scr), and blood urea nitrogen (BUN). Weighted Quantile Sum (WQS) regression and Quantile G-computation (QGC) analyses were applied to identify relationship of individual BFRs and other anthropometric indicators in CKD., Results: After adjusting for available confounding factors, PBDE100, PBDE28, PBDE85, PBDE47, PBDE99, and PBDE154 were positively correlated with CKD. PBDE28, PBDE66, PBDE47, PBDE183, PBDE100, PBDE99, PBDE85, PBDE154, and PBB153 were significantly negatively correlated with eGFR. PBDE66 and PBDE183 were positively correlated with UACR. PBDE28, PBDE17, PBDE66, PBDE100, PBDE47, PBDE85, PBDE154, PBDE99, PBDE183 and PBB153 were positively correlated with Scr. PBDE17, PBDE28, PBDE154, PBDE66, PBDE47, PBDE99, and PBDE209 were negatively associated with BUN. PBB153 was positively correlated with BUN. The subgroup results gender and age are key factors affecting the relationship of PBDEs and renal function indicators. Both WQS and QGS analyses revealed that exposure to mixed BFR was negatively correlated with eGFR and BUN, of which PBB153 and PBDE66 contributed the most, respectively, as well as positively correlated with Scr, in which PBDE66 contributed the most., Conclusion: Specific BFRs exposure was significantly correlated with renal function indicators, enhancing the potential risk of CKD. This pioneer investigation shed light on an overlooked impact of BFR exposure on CKD in US., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Biomarkers of kidney function, including glomerular, tubular, and fibrotic markers, have been associated with blood pressure in elderly populations and individuals with kidney and cardiovascular diseases. However, limited information is available in young adults. In this study, we compared levels of several kidney function biomarkers between normotensive and hypertensive young adults and explored the associations of these biomarkers with blood pressure within these groups. In this cross-sectional assessment, twenty-four-hour (24-h) blood pressure measurements of 1055 participants (mean age = 24.6 years) were used to classify hypertension as per the 2018 ESC/ESH guidelines. Biomarkers of kidney function included estimated glomerular filtration rate, urinary albumin, alpha-1 microglobulin (uA1M), neutrophil gelatinase-associated lipocalin (uNGAL), uromodulin (uUMOD), and the CKD273 classifier. All urinary biomarkers, except for the CKD273 classifier, were standardized for urinary creatinine (Cr). In the hypertensive group (61.0% White; 73.2% men), urinary albumin-to-creatinine ratio (uACR), uNGAL/Cr and uUMOD/Cr were lower than the normotensive group. In multiple regression analyses, 24-h systolic blood pressure (SBP) (β = 0.14; p = 0.042), 24-h diastolic blood pressure (DBP) (β = 0.14; p = 0.040), and 24-h mean arterial pressure (MAP) (β = 0.16; p = 0.020) associated positively with uA1M/Cr in the hypertensive group, while 24-h MAP positively associated with uACR (β = 0.17; p = 0.017). In exploratory factor analysis, positive associations of 24-h DBP and 24-h MAP with a factor pattern including tubular biomarkers were observed in the hypertensive group (24-h DBP: β = 0.18; p = 0.026, 24-h MAP: β = 0.17; p = 0.032). In the setting of hypertension, high perfusion pressure in the kidneys may play a role in the development of proximal tubule damage and promote early deterioration in kidney function in young adults. Trial Registration: ClinicalTrials.gov identifier: NCT03292094., (© 2024 The Author(s). The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Routinely used kidney biomarkers of injury and function such as serum creatinine and urine albumin to creatinine ratio, are neither sensitive nor specific. Future biomarkers are being developed for clinical use and have already been included in guidance from groups such as the U.S. Food and Drug Administration and the Predictive Safety Testing Consortium. These biomarkers have important implications for early identification of kidney injury and more accurate measurement of kidney function. Many antibiotics are either eliminated by the kidney or can cause clinically significant nephrotoxicity. As a result, clinicians should be familiar with new biomarkers of kidney function and injury, their place in clinical practice, and applications for antibiotic dosing., (Copyright © 2024 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

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.)

Objective: Loss of muscle mass and sarcopenia are common in chronic kidney disease (CKD) and end-stage renal disease (ESRD), and sarcopenia can worsen insidiously in patients with advancing CKD. The temporal dynamics of sarcopenia in patients with progressive loss of kidney function, and its association with future outcomes, is unclear., Methods: In a contemporary national cohort of incident ESRD US veterans, we selected 661 patients who had at least 2 24-hour urine creatinine (24hrUC) measurements, a surrogate of muscle mass, performed during the 3-year prelude period prior to ESRD transition. We estimated 24hrUC slopes in mixed effects models. To assess the temporal dynamics of pre-ESRD changes in 24hrUC and its association with changing eGFR, we separately fitted in mixed effects models a penalized spline regression of 24hrUC on time and on eGFR. We examined the association of 24hrUC slopes with postdialysis all-cause mortality using Cox models adjusted for confounders., Results: The mean slope of 24hrUC versus time was -78 mg/year (95% confidence interval: -102 to -54), with a steeper decline noted in the last year prior to ESRD. More severe decreases in 24hrUC were associated with higher all-cause mortality: a 100 mg/year decrease in 24hrUC was associated with a multivariable adjusted death hazard ratio of 1.41 (95% confidence interval: 1.00-1.98, P = .05)., Conclusion: Patients with advanced CKD lose a substantial proportion of their muscle mass each year during pre-ESRD prelude. Loss of muscle mass accelerates near ESRD transition, and more loss of muscle mass is associated with higher mortality after ESRD transition., (Published by Elsevier Inc.)

Objectives: Reportedly, patients with LN and low-level proteinuria have favourable short-term renal outcomes. We aimed to clarify the long-term renal outcomes and overall survival of these patients, and the significance of renal biopsy in the early phase with low-level proteinuria., Methods: We included 144 Japanese patients with biopsy-proven LN from 10 hospitals. Low-level proteinuria was defined by a urine protein:creatinine ratio (UPCR) of ≤1 g/gCr based on previous reports. The outcomes were end-stage renal disease (ESRD) and death., Results: Compared with patients with high-level proteinuria (UPCR >1 g/gCr), those with low-level proteinuria [n = 67 (46.5%)] had significantly improved renal function at the time of renal biopsy, and low activity index and chronicity index while the frequency of class III/IV was similar (79.1% vs 84.4%, P = 0.409). In patients with low-level proteinuria, CYC usage was less, and the incidences of ESRD (3.0% vs 13.0%, P = 0.036) and death (3.0% vs 16.9%, P = 0.006) during the total observation period (median, 72 months) were low. Kaplan-Meier analysis showed significant differences in the incidence of ESRD and death between the groups. Multivariate Cox regression analysis revealed that the significant risk factors for ESRD were high chronicity index and hypertension, whereas those for death were increased age and high-level proteinuria., Conclusion: Patients with LN and low-level proteinuria had favourable long-term renal and life outcomes. As these patients have substantial active pathological lesions, renal biopsy in the early phase with low-level proteinuria could enable early diagnosis and treatment and thus improve prognosis., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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).)

Objectives: After renal transplant, identification of early graft dysfunction is crucial for graft survival. We aimed to assess the perfusion of the transplanted kidney using near-infrared spectroscopy and to see any correlations between regional saturation and serum creatinine and urine output., Materials and Methods: We included male and female patients, aged 18 to 65 years, with end-stage renal disease and undergoing living related donor renal transplant in our study. Near-infrared spectroscopy was used for continuous monitoring of regional saturation. Urine output and serum creatinine were recorded at baseline and then every 24 hours until postoperative day 5., Results: Among 21 patients included in the study, mean age was 30.23 ± 4% at postoperative day 5. We found a significant negative correlation between regional saturation and serum creatinine at all time intervals (P < .05). A significant negative correlation between regional saturation and urine output was observed at baseline and at 24, 72, 96, and 120 hours (P < .05). Four patients developed postoperative complications. A significant change in regional saturation was detected at 40 hours, 1 hour, 2 hours, and 48 hours earlier by near-infrared saturation in 4 patients compared with other traditional indexes of renal function monitoring., Conclusions: Monitoring with near-infrared spectroscopy is feasible and safe in postoperative renal transplant patients. Near-infrared spectroscopy may be projected as a surrogate tool for real-time monitoring of renal perfusion in renal transplant recipients.

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.)