A case of alkaptonuria presenting with unexplained dark-stained diapers and spurious hyperoxaluria and proteinuria due to homogentisic acid interference.

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.

Study on PINK1 Expression and Its Clinical Value in Diabetic Nephropathy.

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.

Renal function and risk of dementia: a Mendelian randomization study.

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.

Difference in urinary protein-to-creatinine ratio using the benzethonium chloride and pyrogallol red methods in children.

BACKGROUND: The appropriate reference value of the urinary protein-to-creatinine ratio (PCR) for proteinuria may change when the urinary pyrogallol red (PR) protein assay method is changed to the benzethonium chloride method (BC). This study aimed to evaluate the difference between BC-based PCR (BC-PCR) and PR-based PCR (PR-PCR) values in children. METHODS: We compared the BC-PCR and PR-PCR values in the same first-morning urine samples without significant proteinuria in school urine screening settings. The upper limit of the reference values was set at the 97.5th percentile. RESULTS: Notably, 133 samples from 124 individuals (female: 62%, age: median 12.3 years, range 6.3-16.9 years) were collected between August 2020 and October 2022. The diagnoses included 34 normal individuals and 99 with asymptomatic hematuria. The urinary protein (UP) concentrations measured using the BC (BC-UP) and PR (PR-UP) methods were in a linear relationship; however, the BC-UP concentrations were higher than the PR-UP concentrations (mean of differences: 11.2, 95% confidence interval (CI): 11.0-13.4 mg/dL). Also, the BC-PCR values were higher than the PR-PCR values (mean of differences: 0.090, 95% CI: 0.082-0.098 g/gCr). The BC-PCR showed a body-size-related decrease, reflecting a body-size-related urinary creatinine increase. The suggested BC-PCR reference values for proteinuria were 0.25 and 0.17 g/gCr for elementary (6-12.4 years) and junior high school students (12.5-16 years), respectively. These values were higher than those of the PR-PCR and need further studies. CONCLUSIONS: When evaluating PCR results, the urinary protein assay should be stated.

The role of age and sex in non-linear dilution adjustment of spot urine arsenic.

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.

An Alternative Diagnostic Test rather than 24 hours Urinary Protein to Detect Massive Proteinuria in Nephrotic Syndrome in Mymensingh Medical College Hospital, Bangladesh.

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

Creatinine clearance/eGFR ratio: a simple index for muscle mass related to mortality in ICU patients.

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 m2. 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.

Time course of plasma urea and urinary urea excretion in patients with a prolonged ICU stay.

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.

Association between Regular Exercise and Urinary Uric Acid Excretion in Chinese Adults: A Cross-sectional Study.

ABSTRACT: Regular exercise decreases the risk of hyperuricemia, which is related to reduced urinary uric acid excretion (UUA/UAE). However, few studies have assessed the association between regular exercise and UAE. We conducted this study to investigate their associations in the general population. This was a cross-sectional study that involved a total of 5513 Chinese community-dwellers, who reported data on physical exercise. Fasting morning spot urine was used to measure UUA and creatinine. UAE was primarily assessed by UUA to creatinine ratio (UCr) and secondly by excretion of uric acid per volume of glomerular filtration (EurGF) and fractional excretion of uric acid (FEua). Linear regression analysis was used to assess their associations. Of the included participants, their mean age was 55.1 ± 13.0 years, and 1984 (36.0%) undertook regular exercise. Compared with participants with regular exercise, those with irregular exercise or no exercise had higher UUA/UCr (0.36 ± 0.15 vs. 0.39 ± 0.15, P < 0.001), EurGF (0.23 ± 0.10 vs. 0.24 ± 0.11 mg/dL, P < 0.001), and FEua (0.07 ± 0.04 vs. 0.08 ± 0.04, P = 0.006). These associations remained significant after controlling for multivariable including serum uric acid (SUA) or upon the exclusion of participants with renal dysfunction or urinary tract infection. In conclusion, regular exercise might be associated with decreased UAE, independent of SUA, in Chinese community-dwellers.

Urine Albumin-to-Creatinine Ratio as an Indicator of Brain Activity Changes in Chronic Kidney Disease: A Resting-State fMRI Study.

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.

Portable Electrochemical System and Platform with Point-of-Care Determination of Urine Albumin-to-Creatinine Ratio to Evaluate Chronic Kidney Disease and Cardiorenal Syndrome.

The urine albumin (Alb)-to-creatinine (Crn) ratio (UACR) is a sensitive and early indicator of chronic kidney disease (CKD) and cardiorenal syndrome. This study developed a portable and wireless electrochemical-sensing platform for the sensitive and accurate determination of UACR. The developed platform consists of a carbon nanotube (CNT)-2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)(ABTS)-based modified UACR sensor, a miniaturised potentiostat, a cup holder embedded with a magnetic stirrer and a smartphone app. The UACR sensing electrode is composed of two screen-printed carbon working electrodes, one screen-printed carbon counter electrode and a screen-printed AgCl reference electrode. The miniaturised potentiostat, which is controlled by the developed app, performs cyclic voltammetry and amperometry to detect Alb and Crn, respectively. Clinical trials of the proposed system by using spot urine samples from 30 diabetic patients indicate that it can accurately classify all three CKD risk statuses within 30 min. The high accuracy of our proposed sensing system exhibits satisfactory agreement with the commercial biochemical analyser TBA-25FR (Y = 0.999X, R2 = 0.995). The proposed UACR sensing system offers a convenient, reliable and affordable solution for personal mobile health monitoring and point-of-care urinalysis.

A Multi-Channel Urine Sensing Detection System Based on Creatinine, Uric Acid, and pH.

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.

Aminopeptidasic Enzymes as Early Biomarkers of Cardiac Surgery-Associated Acute Kidney Injury and Long-Term Events.

BACKGROUND: Diagnosis of acute kidney injury (AKI) relies on serum creatinine (SCr) changes. This study investigated if urinary aminopeptidases are early and predictive biomarkers of cardiac surgery-associated AKI (CSA-AKI). METHODS: Glutamyl aminopeptidase (GluAp), alanyl aminopeptidase (AlaAp), dipeptidyl peptidase-4 (DPP4), proteinuria, albuminuria, N-acetyl-ß-D-glucosaminidase (NAG), and neutrophile gelatinase-associated lipocalin (NGAL) were measured in urine samples from 44 patients at arrival in the intensive care unit (ICU) after cardiac surgery. Sensitivity, specificity, and positive and negative predictive value for diagnosis of stages 1, 2, and 3 of AKI were analyzed for the highest quartile of each marker. We also studied the relationship with SCr after surgery, 6- and 12-month glomerular filtration rates (GFRs), and other long-term events over the next 5 years. RESULTS: GluAp diagnosed the maximal number of patients that developed stage 2 or 3 of AKI, increasing diagnostic sensitivity from 0% to 75%. In addition, GluAp and DPP4 were related to the decrease in GFR at 6 or 12 months after surgery. CONCLUSIONS: Urinary aminopeptidases are a potential tool for the early diagnosis of CSA-AKI, with GluAp being the most effective marker for diagnosing stage 2 or 3 of AKI at ICU admission. GluAp and DPP4 serve as predictive biomarkers for a decrease in GFR.

Renal Cell Carcinoma Discrimination through Attenuated Total Reflection Fourier Transform Infrared Spectroscopy of Dried Human Urine and Machine Learning Techniques.

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

Urinary iodine clearance after iodinated contrast administration to healthy cats.

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

Ten years trajectories of estimated glomerular filtration rate (eGFR) in a multiethnic cohort of people with type 1 diabetes and preserved renal function.

OBJECTIVES: We aim to evaluate estimated glomerular filtration rate (eGFR) patterns of progression in a multiethnic cohort of people with type I diabetes mellitus and with baseline eGFR ≥45 mL/min/1.73 m2. DESIGN: Observational cohort. SETTING: People with a clinical diagnosis of type 1 diabetes, attending two university hospital-based outpatient diabetes clinics, in South London between 2004 and 2018. PARTICIPANTS: We studied 1495 participants (52% females, 81% white, 12% African-Caribbean and 7% others). PRIMARY AND SECONDARY OUTCOME MEASURES: Clinical measures including weight and height, systolic blood pressure, diastolic blood pressure and laboratory results (such as serum creatinine, urine albumin to creatinine ratio (ACR), HbA1c were collected from electronic health records (EHRs) and eGFR was estimated by the Chronic Kidney Disease-Epidemiology Collaboration. Ethnicity was self-reported. RESULTS: Five predominantly linear patterns/groups of eGFR trajectories were identified. Group I (8.5%) had a fast eGFR decline (>3 mL/min/1.73 m2 year). Group II (23%) stable eGFR, group III (29.8%), groups IV (26.3%) and V (12.4%) have preserved eGFR with no significant fall. Group I had the highest proportion (27.6%) of African-Caribbeans. Significant differences between group I and the other groups were observed in age, gender, HbA1C, systolic and diastolic blood pressure, body mass index, cholesterol and urine ACR, p<0.05 for all. At 10 years of follow-up, 33% of group I had eGFR <30 and 16.5%<15 (mL/min/1.73 m2). CONCLUSIONS: Distinct trajectories of eGFR were observed in people with type 1 diabetes. The group with the highest risk of eGFR decline had a greater proportion of African-Caribbeans compared with others and has higher prevalence of traditional modifiable risk factors for kidney disease.

Relationship between phthalate exposure and kidney function in Taiwanese adults as determined through covariate-adjusted standardization and cumulative risk assessment.

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 DIDEHP and higher DIDnBP values were significantly associated with lower eGFRs and higher ACRs, respectively. Higher DIDiBP and DIDEP 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.

Reference intervals for urinary metanephrines to creatinine ratios in dogs in Japan.

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

How to Assess the Glomerular Filtration Rate, and Which Method is Deemed Most Reliable?

The prevalence of chronic kidney disease (CKD) continues to rise globally, paralleled by an increase in associated morbidity and mortality, as well as significant implications for patient quality of life and national economies. Chronic kidney disease often progresses unrecognized by patients and physicians, despite diagnosis relying on two simple laboratory measures: estimated glomerular filtration rate (eGFR) and urine analysis. GFR measurement has been grounded in renal physiology, specifically the concept of clearance, with creatinine identified as a suitable endogenous marker for estimating creatinine clearance (CrCl). On this foundation, various equations have been developed to calculate CrCl or estimated GFR (eGFR) using four variables that incorporate creatinine and certain demographic information, such as sex and age. However, creatinine measurement requires standardization to minimize assay variability across laboratories. Moreover, the accuracy of these equations remains contentious in certain patient subgroups. For these reasons, additional mathematical models have been devised to enhance CrCl estimation, for example, when urine collection is impractical, in elderly or debilitated patients, and in individuals with trauma, diabetes, or obesity. Presently, eGFR in adults can be immediately measured and reported using creatinine-based equations traceable through isotope dilution mass spectrometry. In conclusion, leveraging insights from renal physiology, eGFR can be employed clinically for early diagnosis and treatment of CKD, as well as a public health tool to estimate its prevalence.

Predictive biomarkers of preeclampsia severity in a low resource setting: Role of red blood cell indices, NLR, and albumin-to-creatinine ratio.

Preeclampsia (PE), a serious medical condition with substantial maternal and perinatal implications, poses a significant challenge, particularly in high-incidence countries like Indonesia. Red blood cell (RBC) indices, neutrophil-to-lymphocyte ratio (NLR), and microalbuminuria (albumin-to-creatinine ratio (ACR)) may signal systemic inflammation and endothelial dysfunction, recently recognized as potential indicators for diagnosing and predicting disease severity. The aim of this study was to analyze RBC indices, NLR, and ACR changes in women with PE and their potential for predicting disease severity. A cross-sectional study was conducted at multi-center hospitals across Medan, Indonesia, from June 2022 to June 2023. The patients were grouped into PE cases with and without severe features. Demographic characteristics and complications were recorded while blood and urine were tested. The Chi-squared test, Fisher's exact test and Mann-Whitney test were used to determine biomarkers associated with severe PE. A total of 208 PE patients were included in the study (104 patients for each PE with and without severe features). Our data indicated that PE patients with severe features had higher red cell distribution width (18.5% vs 13.7%; p<0.001), NLR (5.66% vs 4.1%; p<0.001), and ACR (755.97 mg/dL vs 468.63 mg/dL; p<0.001) compared to those without severe features. In contrast, the platelet count was lower in severe features than those without (21.9 × 106/µL vs 27.0 × 106/µL; p=0.002). This study highlighted that PE patients with severe features predominantly had higher levels of RDW, NLR, and ACR and lower platelet counts compared to those without severe features. Therefore, basic tests such as complete blood count and urinalysis, which are inexpensive and feasible in primary care settings with limited resources, offer hope as valuable diagnostic biomarkers for pregnant women diagnosed with PE in a low resource setting.