The correlation of urea and creatinine concentrations in sweat and saliva with plasma during hemodialysis: an observational cohort study.

OBJECTIVES: Urea and creatinine concentrations in plasma are used to guide hemodialysis (HD) in patients with end-stage renal disease (ESRD). To support individualized HD treatment in a home situation, there is a clinical need for a non-invasive and continuous alternative to plasma for biomarker monitoring during and between cycles of HD. In this observational study, we therefore established the correlation of urea and creatinine concentrations between sweat, saliva and plasma in a cohort of ESRD patients on HD. METHODS: Forty HD patients were recruited at the Dialysis Department of the Catharina Hospital Eindhoven. Sweat and salivary urea and creatinine concentrations were analyzed at the start and at the end of one HD cycle and compared to the corresponding plasma concentrations. RESULTS: A decrease of urea concentrations during HD was observed in sweat, from 27.86 mmol/L to 12.60 mmol/L, and saliva, from 24.70 mmol/L to 5.64 mmol/L. Urea concentrations in sweat and saliva strongly correlated with the concentrations in plasma (ρ 0.92 [p<0.001] and 0.94 [p<0.001], respectively). Creatinine concentrations also decreased in sweat from 43.39 µmol/L to 19.69 µmol/L, and saliva, from 59.00 µmol/L to 13.70 µmol/L. However, for creatinine, correlation coefficients were lower than for urea for both sweat and saliva compared to plasma (ρ: 0.58 [p<0.001] and 0.77 [p<0.001], respectively). CONCLUSIONS: The results illustrate a proof of principle of urea measurements in sweat and saliva to monitor HD adequacy in a non-invasive and continuous manner. Biosensors enabling urea monitoring in sweat or saliva could fill in a clinical need to enable at-home HD for more patients and thereby decrease patient burden.

Redefining urine output thresholds for acute kidney injury criteria in critically Ill patients: a derivation and validation study.

INTRODUCTION: The current definition of acute kidney injury (AKI) includes increased serum creatinine (sCr) concentration and decreased urinary output (UO). Recent studies suggest that the standard UO threshold of 0.5 ml/kg/h may be suboptimal. This study aimed to develop and validate a novel UO-based AKI classification system that improves mortality prediction and patient stratification. METHODS: Data were obtained from the MIMIC-IV and eICU databases. The development process included (1) evaluating UO as a continuous variable over 3-, 6-, 12-, and 24-h periods; (2) identifying 3 optimal UO cutoff points for each time window (stages 1, 2, and 3); (3) comparing sensitivity and specificity to develop a unified staging system; (4) assessing average versus persistent reduced UO hourly; (5) comparing the new UO-AKI system to the KDIGO UO-AKI system; (6) integrating sCr criteria with both systems and comparing them; and (7) validating the new classification with an independent cohort. In all these steps, the outcome was hospital mortality. Another analyzed outcome was 90-day mortality. The analyses included ROC curve analysis, net reclassification improvement (NRI), integrated discrimination improvement (IDI), and logistic and Cox regression analyses. RESULTS: From the MIMIC-IV database, 35,845 patients were included in the development cohort. After comparing the sensitivity and specificity of 12 different lowest UO thresholds across four time frames, 3 cutoff points were selected to compose the proposed UO-AKI classification: stage 1 (0.2-0.3 mL/kg/h), stage 2 (0.1-0.2 mL/kg/h), and stage 3 (< 0.1 mL/kg/h) over 6 h. The proposed classification had better discrimination when the average was used than when the persistent method was used. The adjusted odds ratio demonstrated a significant stepwise increase in hospital mortality with advancing UO-AKI stage. The proposed classification combined or not with the sCr criterion outperformed the KDIGO criteria in terms of predictive accuracy-AUC-ROC 0.75 (0.74-0.76) vs. 0.69 (0.68-0.70); NRI: 25.4% (95% CI: 23.3-27.6); and IDI: 4.0% (95% CI: 3.6-4.5). External validation with the eICU database confirmed the superior performance of the new classification system. CONCLUSION: The proposed UO-AKI classification enhances mortality prediction and patient stratification in critically ill patients, offering a more accurate and practical approach than the current KDIGO criteria.

Machine learning derived serum creatinine trajectories in acute kidney injury in critically ill patients with sepsis.

BACKGROUND: Current classification for acute kidney injury (AKI) in critically ill patients with sepsis relies only on its severity-measured by maximum creatinine which overlooks inherent complexities and longitudinal evaluation of this heterogenous syndrome. The role of classification of AKI based on early creatinine trajectories is unclear. METHODS: This retrospective study identified patients with Sepsis-3 who developed AKI within 48-h of intensive care unit admission using Medical Information Mart for Intensive Care-IV database. We used latent class mixed modelling to identify early creatinine trajectory-based classes of AKI in critically ill patients with sepsis. Our primary outcome was development of acute kidney disease (AKD). Secondary outcomes were composite of AKD or all-cause in-hospital mortality by day 7, and AKD or all-cause in-hospital mortality by hospital discharge. We used multivariable regression to assess impact of creatinine trajectory-based classification on outcomes, and eICU database for external validation. RESULTS: Among 4197 patients with AKI in critically ill patients with sepsis, we identified eight creatinine trajectory-based classes with distinct characteristics. Compared to the class with transient AKI, the class that showed severe AKI with mild improvement but persistence had highest adjusted risks for developing AKD (OR 5.16; 95% CI 2.87-9.24) and composite 7-day outcome (HR 4.51; 95% CI 2.69-7.56). The class that demonstrated late mild AKI with persistence and worsening had highest risks for developing composite hospital discharge outcome (HR 2.04; 95% CI 1.41-2.94). These associations were similar on external validation. CONCLUSIONS: These 8 classes of AKI in critically ill patients with sepsis, stratified by early creatinine trajectories, were good predictors for key outcomes in patients with AKI in critically ill patients with sepsis independent of their AKI staging.

A low BUN/creatinine ratio predicts histologically confirmed acute interstitial nephritis.

INTRODUCTION: In hospitalized patients with acute renal injury (AKI), acute tubulointerstitial nephritis (AIN) constitutes one of the leading etiologies. The objective of this study was to identify clinical and biochemical variables in patients with AKI associated with kidney biopsy-confirmed AIN. METHODS: For our prospective study, we recruited hospitalized patients aged 18 years and older who were diagnosed with AKI based on biochemical criteria. Prior to enrollment, each patient was assessed with a complete metabolic panel and a kidney biopsy. RESULTS: The study consisted of 42 patients (with a mean age of 45 years) and equal numbers of male and female patients. Diabetes and hypertension were the main comorbidities. Nineteen patients had histological findings consistent with AIN. There was a correlation between histology and the BUN/creatinine ratio (BCR) (r = -0.57, p = 0.001). The optimal Youden point for classifying AIN via a receiver operating characteristic (ROC) curve analysis was a BCR ≤ 12 (AUC = 0.73, p = 0.024). Additionally, in diagnosing AIN, BCR had a sensitivity of 76%, a specificity of 81%, a positive predictive value of 81%, a negative predictive value of 76%, and OR of 14 (95% CI = 2.6 to 75.7, p = 0.021). In the multivariable analysis, BCR was the sole variable associated with AIN. CONCLUSION: A BCR ≤ 12 identifies AIN in patients with AKI. This study is the first to prospectively assess the relationship between renal biopsy results and BCR.

Comparative analysis of biochemical, hormonal, and mineral compositions of preovulatory and cystic ovarian follicles in buffalo during the non-breeding season.

This study is a comparative analysis of the biochemical, hormonal, and mineral compositions of follicular fluid in preovulatory and cystic follicles of water buffalo (Bubalus bubalis). In total, reproductive tracts from 215 buffalo along with intact ovaries were collected randomly from an abattoir. The incidence of cystic conditions found in this study was 3.72% (8/215), involving the right ovary in 62.5% of instances and the left ovary in 37.5% of instances during the non-breeding season. Follicular fluid was aspirated from preovulatory follicles (12-15 mm diameter, oestrogen-active, follicular phase or stage IV corpus luteum on one of the two ovaries, n = 10) and cystic follicles (at least 20 mm diameter, no corpus luteum on any one of the two ovaries, n = 8). The follicular fluid samples were assayed for biochemical components (uric acid, creatinine, blood urea nitrogen, cholesterol, total protein, glucose, ascorbic acid, and alkaline phosphatase), hormones (progesterone, estradiol, and insulin), and minerals (calcium, magnesium, phosphorus, copper, zinc, and cobalt). Cystic follicles had greater (P < 0.05) concentrations of creatinine, blood urea nitrogen, cholesterol, progesterone, copper, zinc, and cobalt, and lesser (P < 0.05) concentrations of uric acid, glucose, ascorbic acid, estradiol, insulin, calcium, magnesium, and phosphorus compared with preovulatory follicles. These results indicated the marked differences in follicular fluid composition between preovulatory and cystic follicles in buffalo. Some of the changes were indicative of oxidative stress and disturbed steroidogenesis, two important mechanisms shown to be associated with cystic ovarian disease in various species. Further studies are warranted to investigate whether these differences are directly or indirectly involved in the formation of cystic follicles or are mere manifestations of the condition.

Estimated Glomerular Filtration Rate, Albuminuria, and Adverse Outcomes: An Individual-Participant Data Meta-Analysis.

Importance: Chronic kidney disease (low estimated glomerular filtration rate [eGFR] or albuminuria) affects approximately 14% of adults in the US. Objective: To evaluate associations of lower eGFR based on creatinine alone, lower eGFR based on creatinine combined with cystatin C, and more severe albuminuria with adverse kidney outcomes, cardiovascular outcomes, and other health outcomes. Design, Setting, and Participants: Individual-participant data meta-analysis of 27 503 140 individuals from 114 global cohorts (eGFR based on creatinine alone) and 720 736 individuals from 20 cohorts (eGFR based on creatinine and cystatin C) and 9 067 753 individuals from 114 cohorts (albuminuria) from 1980 to 2021. Exposures: The Chronic Kidney Disease Epidemiology Collaboration 2021 equations for eGFR based on creatinine alone and eGFR based on creatinine and cystatin C; and albuminuria estimated as urine albumin to creatinine ratio (UACR). Main Outcomes and Measures: The risk of kidney failure requiring replacement therapy, all-cause mortality, cardiovascular mortality, acute kidney injury, any hospitalization, coronary heart disease, stroke, heart failure, atrial fibrillation, and peripheral artery disease. The analyses were performed within each cohort and summarized with random-effects meta-analyses. Results: Within the population using eGFR based on creatinine alone (mean age, 54 years [SD, 17 years]; 51% were women; mean follow-up time, 4.8 years [SD, 3.3 years]), the mean eGFR was 90 mL/min/1.73 m2 (SD, 22 mL/min/1.73 m2) and the median UACR was 11 mg/g (IQR, 8-16 mg/g). Within the population using eGFR based on creatinine and cystatin C (mean age, 59 years [SD, 12 years]; 53% were women; mean follow-up time, 10.8 years [SD, 4.1 years]), the mean eGFR was 88 mL/min/1.73 m2 (SD, 22 mL/min/1.73 m2) and the median UACR was 9 mg/g (IQR, 6-18 mg/g). Lower eGFR (whether based on creatinine alone or based on creatinine and cystatin C) and higher UACR were each significantly associated with higher risk for each of the 10 adverse outcomes, including those in the mildest categories of chronic kidney disease. For example, among people with a UACR less than 10 mg/g, an eGFR of 45 to 59 mL/min/1.73 m2 based on creatinine alone was associated with significantly higher hospitalization rates compared with an eGFR of 90 to 104 mL/min/1.73 m2 (adjusted hazard ratio, 1.3 [95% CI, 1.2-1.3]; 161 vs 79 events per 1000 person-years; excess absolute risk, 22 events per 1000 person-years [95% CI, 19-25 events per 1000 person-years]). Conclusions and Relevance: In this retrospective analysis of 114 cohorts, lower eGFR based on creatinine alone, lower eGFR based on creatinine and cystatin C, and more severe UACR were each associated with increased rates of 10 adverse outcomes, including adverse kidney outcomes, cardiovascular diseases, and hospitalizations.

Presence of galectin-3 in peritoneal dialysate. Does it have a role in the peritoneal membrane inflammatory process?

Peritoneal dialysis (PD) causes structural and functional changes in the peritoneal membrane, which are attributed to local inflammatory process. This study assessed the presence of galectin-3 (Gal-3), a known inflammatory modulator, in dialysate effluent and correlated its levels with markers of inflammatory process. Gal-3 levels in serum and dialysate effluent were measured in prevalent PD patients on morning visits (n = 27) or during peritoneal equilibration tests (PET, n = 16), it association with clinical and laboratory parameters, including dialysate/plasma creatinine (D/P creatinine) and interleukin-6 (IL-6) levels was analysed. Gal-3 levels in dialysate effluent correlated with D/P creatinine (0.663, p = 0.005) and dialysate effluent IL-6 levels (0.674, p = 0.002), but not with serum Gal-3 levels or dialysis vintage. Patients who were high transporters had higher Gal-3 levels in dialysate effluent, as compared to lower transporters. In multivariate regression analysis, dialysate IL-6 level was the strongest predictor of dialysate Gal-3 levels. This study found Gal-3 in dialysate effluent correlated with D/P creatinine and dialysate IL-6 levels. These findings may imply that Gal-3 has a role in the intraperitoneal inflammatory process. However, this needs to be investigated further.

A genome-wide association study implicates multiple mechanisms influencing raised urinary albumin-creatinine ratio.

Raised albumin-creatinine ratio (ACR) is an indicator of microvascular damage and renal disease. We aimed to identify genetic variants associated with raised ACR and study the implications of carrying multiple ACR-raising alleles with metabolic and vascular-related disease. We performed a genome-wide association study of ACR using 437 027 individuals from the UK Biobank in the discovery phase, 54 527 more than previous studies, and followed up our findings in independent studies. We identified 62 independent associations with ACR across 56 loci (P < 5 × 10-8), of which 20 were not previously reported. Pathway analyses and the identification of 20 of the 62 variants (at r2 > 0.8) coinciding with signals for at least 16 related metabolic and vascular traits, suggested multiple pathways leading to raised ACR levels. After excluding variants at the CUBN locus, known to alter ACR via effects on renal absorption, an ACR genetic risk score was associated with a higher risk of hypertension, and less strongly, type 2 diabetes and stroke. For some rare genotype combinations at the CUBN locus, most individuals had ACR levels above the microalbuminuria clinical threshold. Contrary to our hypothesis, individuals carrying more CUBN ACR-raising alleles, and above the clinical threshold, had a higher frequency of vascular disease. The CUBN allele effects on ACR were twice as strong in people with diabetes-a result robust to an optimization-algorithm approach to simulating interactions, validating previously reported gene-diabetes interactions (P ≤ 4 × 10-5). In conclusion, a variety of genetic mechanisms and traits contribute to variation in ACR.

2D material assisted SMF-MCF-MMF-SMF based LSPR sensor for creatinine detection.

The purpose of this work is to propose a simple, portable, and sensitive biosensor structure based on singlemode fiber-multicore fiber-multimode fiber-singlemode fiber (SMF-MCF-MMF-SMF) for the detection of creatinine in the human body. Chemical etching has been used to modify the diameter of the sensing probe to approximately 90 µm in order to generate strong evanescent waves (EWs). The sensor probe is functionalized with graphene oxide (GO), gold nanoparticles (AuNPs), molybdenum disulfide nanoparticles (MoS2-NPs), and creatininase (CA) enzyme. The concentration of creatinine is determined using fiber optic localized surface plasmon resonance (LSPR). While EWs are used to enhance the LSPR effect of AuNPs, two-dimensional (2D) materials (GO and MoS2-NPs) are used to increase biocompatibility, and CA is used to increase probe specificity. Additionally, HR-TEM and UV-visible spectroscopy are used to characterize and measure the nanoparticle (NP) morphology and absorption spectrum, respectively. SEM is used to characterize the NPs immobilized on the surface of the fiber probe. The sensor probe's reusability, reproducibility, stability, selectivity, and pH test results are also tested to verify the sensor performance. The sensitivity of proposed sensor is 0.0025 nm/µM, has a standard deviation of 0.107, and has a limit of detection of 128.4 µM over a linear detection range of 0 - 2000 µM.

Magnetic resonance Spectrum simulator (MARSS), a novel software package for fast and computationally efficient basis set simulation.

The aim of this study was to develop a novel software platform for the simulation of magnetic resonance spin systems, capable of simulating a large number of spatial points (1283 ) for large in vivo spin systems (up to seven coupled spins) in a time frame of the order of a few minutes. The quantum mechanical density-matrix formalism is applied, a coherence pathway filter is utilized for handling unwanted coherence pathways, and the 1D projection method, which provides a substantial reduction in computation time for a large number of spatial points, is extended to include sequences of an arbitrary number of RF pulses. The novel software package, written in MATLAB, computes a basis set of 23 different metabolites (including the two anomers of glucose, seven coupled spins) with 1283 spatial points in 26 min for a three-pulse experiment on a personal desktop computer. The simulated spectra are experimentally verified with data from both phantom and in vivo MEGA-sLASER experiments. Recommendations are provided regarding the various assumptions made when computing a basis set for in vivo MRS with respect to the number of spatial points simulated and the consideration of relaxation.

Evaluation of the diagnostic performance of the creatinine-based Chronic Kidney Disease Epidemiology Collaboration equation in people with diabetes: A systematic review.

AIMS: GFR estimated with the creatinine-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPICr ) equation is used to screen for diabetic kidney disease and assess its severity. We systematically reviewed the process and outcome of evaluating CKD-EPICr in estimating point GFR or GFR decline over time in adults with type 1 or type 2 diabetes. METHODS: In this systematic review, MEDLINE, Embase and Cochrane Central Register of Controlled Trials were searched up to August 2019. Observational studies comparing CKD-EPICr with measured GFR (mGFR) in adults with diabetes were included. Studies on people with kidney transplant, non-diabetes related kidney disease, pregnancy, potential kidney donors, and those with critical or other systematic illnesses were excluded. Two independent reviewers extracted data from published papers and disagreements were resolved by consensus. Risk-of-bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. (PROSPERO registration number: CRD42018108776). RESULTS: From the 2820 records identified, 29 studies (14 704 participants) were included. All studies were at risk of bias. Bias (eight different forms) ranged from -26 to 35 ml min-1  1.73 m-2 ; precision (five different forms) ranged between 9 and 63 ml min-1  1.73 m-2 ; accuracy (five different forms) ranged between 16% and 96%; the correlation coefficient between CKD-EPICr and mGFR (four different forms) ranged between 0.38 and 0.86; and the reduced major axis regression slope ranged between 0.8 and 1.8. CONCLUSIONS: Qualitative synthesis of data suggested CKD-EPICr was inaccurate in estimating point GFR or GFR decline over time. Furthermore, a lack of consistency in the methods and processes of evaluating the diagnostic performance of CKD-EPICr limits reliable quantitative assessment. The equation needs to be improved in adults with diabetes.

Creatinine filtration kinetics in critically Ill neonates.

BACKGROUND: Creatinine values are unreliable within the first weeks of life; however, creatinine is used most commonly to assess kidney function. Controversy remains surrounding the time required for neonates to clear maternal creatinine. METHODS: Eligible infants had multiple creatinine lab values and were admitted to the neonatal intensive care unit (NICU). A mathematical model was fit to the lab data to estimate the filtration onset delay, creatinine filtration half-life, and steady-state creatinine concentration for each subject. Infants were grouped by gestational age (GA) [(1) 22-27, (2) >27-32, (3) >32-37, and (4) >37-42 weeks]. RESULTS: A total of 4808 neonates with a mean GA of 34.4 ± 5 weeks and birth weight of 2.34 ± 1.1 kg were enrolled. Median (95% confidence interval) filtration onset delay for Group 1 was 4.3 (3.71, 4.89) days and was significantly different than all other groups (p < 0.001). Creatinine filtration half-life of Groups 1, 2, and 3 were significantly different from each other (p < 0.001). There was no difference in steady-state creatinine concentration among the groups. CONCLUSIONS: We quantified the observed kidney behavior in a large NICU population as a function of day of life and GA using creatinine lab results. These results can be used to interpret individual creatinine labs for infants to detect those most at risk for acute kidney injury. IMPACT: One of the largest cohorts of premature infants to describe the evolution of kidney development and function over their entire hospitalization. New concept introduced of the kidney filtration onset delay, the time needed for the kidney to begin clearance of creatinine, and that it can be used as an early indicator of kidney function. The smallest premature infants from 22 to 27 weeks gestation took the longest time to begin and complete maternal creatinine clearance. Clinicians can easily compare the creatinine level of their patient to the normative curves to improve understanding of kidney function at the bedside.

Low expression of estrogen receptor ß in renal tubular epithelial cells may cause hyperuricemia in premenopausal patients with systemic lupus erythematosus.

We investigated the impact of estrogen receptor (ER) expression in renal tubular epithelial cells on serum uric acid (UA) levels in premenopausal patients with systemic lupus erythematosus (SLE). Thirty patients underwent renal biopsy: 18 with SLE (LN group) and 12 with IgA nephritis (IgAN group). ERs (ERα and ERß) in renal tubular epithelial cells were measured using immunohistochemistry. The ER expression levels of the two groups were compared, and the relationship between the expression of ERs and serum UA levels was analyzed. Mean serum UA levels in the LN group were significantly higher than those of the IgA nephropathy group, while the mean creatinine levels and GFRs of the two groups were similar. Pathological changes in the LN group were significantly more severe than those in the IgAN group. ERß was expressed in renal tubular epithelial cells in both groups, but not in the glomeruli. ERß expression in the LN group was significantly lower than that in the IgAN group. ERß expression scores significantly negatively correlated with serum UA levels. These findings suggest that the expression of ERß in premenopausal female SLE patients may cause hyperuricemia, and may subsequently promote glomerular damage, suggesting that ERß may be involved in UA excretion.

Simultaneous quantification of trimethylamine N-oxide, trimethylamine, choline, betaine, creatinine, and propionyl-, acetyl-, and L-carnitine in clinical and food samples using HILIC-LC-MS.

Trimethylamine-N-oxide (TMAO), a microbiome-derived metabolite from the metabolism of choline, betaine, and carnitines, is associated to adverse cardiovascular outcomes. A method suitable for routine quantification of TMAO and its precursors (trimethylamine (TMA), choline, betaine, creatinine, and propionyl-, acetyl-, and L-carnitine) in clinical and food samples has been developed based on LC-MS. TMA was successfully derivatized using iodoacetonitrile, and no cross-reactions with TMAO or the other methylamines were detected. Extraction from clinical samples (plasma and urine) was performed after protein precipitation using acetonitrile:methanol. For food samples (meatballs and eggs), water extraction was shown to be sufficient, but acid hydrolysis was required to release bound choline before extraction. Baseline separation of the methylamines was achieved using a neutral HILIC column and a mobile phase consisting of 25 mmol/L ammonium formate in water:ACN (30:70). Quantification was performed by MS using external calibration and isotopic labelled internal standards. The assay proved suitable for both clinical and food samples and was linear from ≈ 0.1 up to 200 µmol/L for all methylamines except for TMA and TMAO, which were linear up to 100 µmol/L. Recoveries were 91-107% in clinical samples and 76-98% in food samples. The interday (n=8, four duplicate analysis) CVs were below 9% for all metabolites in clinical and food samples. The method was applied successfully to determine the methylamine concentrations in plasma and urine from the subjects participating in an intervention trial (n=10) to determine the effect of animal food ingestion on methylamine concentrations.

Galectin-3 in septic acute kidney injury: a translational study.

BACKGROUND: Galectin-3 (Gal-3) is a pleiotropic glycan-binding protein shown to be involved in sepsis and acute kidney injury (AKI). However, its role has never been elucidated in sepsis-associated AKI (S-AKI). We aimed to explore Gal-3's role and its potential utility as a therapeutic target in S-AKI. METHODS: In 57 patients admitted to the intensive care unit (ICU) with sepsis, serum Gal-3 was examined as a predictor of ICU mortality and development of AKI. In a rat model of S-AKI induced by cecal ligation and puncture (CLP), 7-day mortality and serum Gal-3, Interleukin-6 (IL-6), and creatinine were examined at 2, 8, and 24 hours (h) post-CLP. Two experimental groups received the Gal-3 inhibitor modified citrus pectin (P-MCP) at 400 mg/kg/day and 1200 mg/kg/day, while the control group received water only (n = 18 in each group). RESULTS: Among 57 patients, 27 developed AKI and 8 died in the ICU. Serum Gal-3 was an independent predictor of AKI (OR = 1.2 [95% CI 1.1-1.4], p = 0.01) and ICU mortality (OR = 1.4 [95% CI 1.1-2.2], p = 0.04) before and after controlling for age, AKI, and acute physiology and chronic health evaluation (APACHE II) score. In the CLP rat experiment, serum Gal-3 peaked earlier than IL-6. Serum Gal-3 was significantly lower in both P-MCP groups compared to control at 2 h post-CLP (400 mg: p = 0.003; 1200 mg: p = 0.002), and IL-6 was significantly lower in both P-MCP groups at all time points with a maximum difference at 24 h post-CLP (400 mg: p = 0.015; 1200 mg: p = 0.02). In the Gal-3 inhibitor groups, 7-day mortality was significantly reduced from 61% in the control group to 28% (400 mg P-MCP: p = 0.03) and 22% (1200 mg P-MCP: p = 0.001). Rates of AKI per RIFLE criteria were significantly reduced from 89% in the control group to 44% in both P-MCP groups (400 mg: p = 0.007; 1200 mg: p = 0.007). CONCLUSIONS: This translational study demonstrates the importance of Gal-3 in the pathogenesis of S-AKI, and its potential utility as a therapeutic target.

A prediction model of delayed graft function in deceased donor for renal transplant: a multi-center study from China.

BACKGROUND: Kidneys obtained from deceased donors increase the incidence of delayed graft function (DGF) after renal transplantation. Here we investigated the influence of the risk factors of donors with DGF, and developed a donor risk scoring system for DGF prediction. METHODS: This retrospective study was conducted in 1807 deceased kidney donors and 3599 recipients who received donor kidneys via transplants in 29 centers in China. We quantified DGF associations with donor clinical characteristics. A donor risk scoring system was developed and validated using an independent sample set. RESULTS: The incidence of DGF from donors was 19.0%. Six of the donor characteristics analyzed, i.e., age, cause of death, history of hypertension, terminal serum creatinine, persistence of hypotension, and cardiopulmonary resuscitation (CPR) time were risk factors for DGF. A 49-point scoring system of donor risk was established for DGF prediction and exhibited a superior degree of discrimination. External validation of DGF prediction revealed area under the receiver-operating characteristic (AUC) curves of 0.7552. CONCLUSIONS: Our study determined the deceased donor risk factors related to DGF after renal transplantation pertinent to the Chinese cohort. The scoring system developed here had superior diagnostic significance and consistency and can be used by clinicians to make evidence-based decisions on the quality of kidneys from deceased donors and guide renal transplantation therapy.

Effects of hemodialysis treatment on saliva flow rate and saliva composition during in-center maintenance dialysis: a cross-sectional study.

AIM: To analyze changes in saliva flow rate and clinical measures from unstimulated whole saliva (UWS) among patients undergoing hemodialysis for end-stage kidney disease (ESKD). BACKGROUND: Chronic hemodialysis causes changes in blood chemistry as well as dry mouth, due to removal of excess fluids. UWS is used to examine saliva flow rate as an indicator of mouth dryness. Whether UWS can be used to measure changes in clinical variables following hemodialysis has not been explored. DESIGN: A cross-sectional quantitative study. METHODS: Patients with ESKD were recruited by purposive sampling (n = 100) between 1 January and 30 June 2015 from a hospital in northern Taiwan. UWS was collected 1-hour pre-dialysis (T1), mid-dialysis (T2), and 1-hour post-dialysis (T3). Saliva flow rate and clinical variables were analyzed. RESULTS: Saliva flow rate increased significantly from T1 to T3 (Wald χ2 = 10.40, p < .01). Changes in saliva from T1 to T3 included decreases in blood urea nitrogen and creatinine (Wald χ2 = 97.12, p < .001 and Wald χ2 = 36.98, p < .001, respectively). The pH and osmolality also decreased (p < .001 and p < .01, respectively). Changes in electrolytes included decreases in potassium and calcium (Wald χ2 = 6.71, p < .05 and Wald χ2 = 17.64, p < .01, respectively) and increases in chloride (Wald χ2 = 17.64, p < .001). CONCLUSION: Our findings demonstrated saliva flow rate and several saliva components were altered during hemodialysis. The total volume of saliva secretion increased following dialysis, which can reduce xerostomia. Therefore, medical personnel could provide interventions of relieving dry mouth symptoms and increasing saliva flow rate before hemodialysis treatment.

In Vivo and In Vitro Evaluation of Urinary Biomarkers in Ischemia/Reperfusion-Induced Kidney Injury.

Oxidative stress plays an important role in the pathophysiology of acute kidney injury (AKI). Previously, we reported that vanin-1, which is involved in oxidative stress, is associated with renal tubular injury. This study was aimed to determine whether urinary vanin-1 is a biomarker for the early diagnosis of AKI in two experimental models: in vivo and in vitro. In a rat model of AKI, ischemic AKI was induced in uninephrectomized rats by clamping the left renal artery for 45 min and then reperfusing the kidney. On Day 1 after renal ischemia/reperfusion (I/R), serum creatinine (SCr) in I/R rats was higher than in sham-operated rats, but this did not reach significance. Urinary N-acetyl-ß-D-glucosaminidase (NAG) exhibited a significant increase but decreased on Day 2 in I/R rats. In contrast, urinary vanin-1 significantly increased on Day 1 and remained at a significant high level on Day 2 in I/R rats. Renal vanin-1 protein decreased on Days 1 and 3. In line with these findings, immunofluorescence staining demonstrated that vanin-1 was attenuated in the renal proximal tubules of I/R rats. Our in vitro results confirmed that the supernatant from HK-2 cells under hypoxia/reoxygenation included significantly higher levels of vanin-1 as well as KIM-1 and NGAL. In conclusion, our results suggest that urinary vanin-1 might be a potential novel biomarker of AKI induced by I/R.

Comparison of serum and urinary biomarker panels with albumin/creatinine ratio in the prediction of renal function decline in type 1 diabetes.

AIMS/HYPOTHESIS: We examined whether candidate biomarkers in serum or urine can improve the prediction of renal disease progression in type 1 diabetes beyond prior eGFR, comparing their performance with urinary albumin/creatinine ratio (ACR). METHODS: From the population-representative Scottish Diabetes Research Network Type 1 Bioresource (SDRNT1BIO) we sampled 50% and 25% of those with starting eGFR below and above 75 ml min-1 [1.73 m]-2, respectively (N = 1629), and with median 5.1 years of follow-up. Multiplexed ELISAs and single molecule array technology were used to measure nine serum biomarkers and 13 urine biomarkers based on our and others' prior work using large discovery and candidate studies. Associations with final eGFR and with progression to <30 ml min-1 [1.73] m-2, both adjusted for baseline eGFR, were tested using linear and logistic regression models. Parsimonious biomarker panels were identified using a penalised Bayesian approach, and their performance was evaluated through tenfold cross-validation and compared with using urinary ACR and other clinical record data. RESULTS: Seven serum and seven urine biomarkers were strongly associated with either final eGFR or progression to <30 ml min-1 [1.73 m]-2, adjusting for baseline eGFR and other covariates (all at p<2.3 × 10-3). Of these, associations of four serum biomarkers were independent of ACR for both outcomes. The strongest associations with both final eGFR and progression to <30 ml min-1 [1.73 m]-2 were for serum TNF receptor 1, kidney injury molecule 1, CD27 antigen, α-1-microglobulin and syndecan-1. These serum associations were also significant in normoalbuminuric participants for both outcomes. On top of baseline covariates, the r2 for prediction of final eGFR increased from 0.702 to 0.743 for serum biomarkers, and from 0.702 to 0.721 for ACR alone. The area under the receiver operating characteristic curve for progression to <30 ml min-1 [1.73 m]-2 increased from 0.876 to 0.953 for serum biomarkers, and to 0.911 for ACR alone. Other urinary biomarkers did not outperform ACR. CONCLUSIONS/INTERPRETATION: A parsimonious panel of serum biomarkers easily measurable along with serum creatinine may outperform ACR for predicting renal disease progression in type 1 diabetes, potentially obviating the need for urine testing.

Diagnostic utility of protein to creatinine ratio (P/C ratio) in spot urine sample within routine clinical practice.

The spot (random) urine protein to creatinine ratio (P/C ratio) is an alternative, fast and simple method of detecting and estimating the quantitative assessment of proteinuria. The aim of the work was to review the literature concerning the usefulness of spot urine P/C ratio evaluation in the diagnosis of proteinuria in the course of kidney disease, hypertension, gestational hypertension, preeclampsia, immunological diseases, diabetes mellitus, and multiple myeloma, and in the diagnosis of proteinuria in children. We searched the PubMed and Google Scholar databases using the following keywords: proteinuria, spot urine protein to creatinine ratio, spot urine P/C ratio, protein creatinine index, PCR (protein to creatinine ratio), P/C ratio and methods, Jaffe versus enzymatic creatinine methods, urine protein methods, spot urine protein to creatinine ratio versus ACR (albumin to creatinine ratio), proteinuria versus albuminuria, limitations of the P/C ratio. More weight was given to the articles published in the last 10-20 years. A spot urine P/C ratio >20 mg/mmol (0.2 mg/mg) is the most commonly reported cutoff value for detecting proteinuria, while a P/C ratio value >350 mg/mmol (3.5 mg/mg) confirms nephrotic proteinuria. The International Society for the Study of Hypertension in Pregnancy recommends a P/C ratio of 30 mg/mmol (0.3 mg/mg) for the classification of proteinuria in pregnant women at risk of preeclampsia. A high degree of correlation was observed between P/C ratio values and the protein concentration in 24-h urine collections. The spot urine P/C ratio is a quick and reliable test that can eliminate the need for a daily 24-h urine collection. However, in doubtful situations, it is still recommended to assess proteinuria in a 24-h urine collection. The literature review indicates the usefulness of the spot P/C ratio in various disease states; therefore, this test should be available in every laboratory. However, the challenge for the primary care physician is to know the limitations of the methods used to determine the protein and creatinine concentrations that are used to calculate the P/C ratio. Moreover, the P/C ratio cutoff used should be determined in individual laboratories because it depends on the patient population and the laboratory methodologies.