Adjustment For Creatinine Research Articles

Organophosphate insecticide exposure and respiratory symptoms among school children in Northern Thailand: Interaction by biomass burning, dampness and season

The aim was to study associations between dialkylphosphates (DAPs), organophosphate (OP) metabolites in urine, biomarkers of OP insecticide exposure, and respiratory symptoms among children in upper northern Thailand. We recruited junior high school children in randomly selected schools in four cities (N = 337), with repeated data collection in wet and dry seasons. Urine was collected and analyzed for six OP metabolites, with creatinine adjustment. Total DAP was expressed as sum of DAPs. Data on respiratory symptoms was collected by a standardized questionnaire. Associations were analyzed by multiple logistic regression. Totally 11.3 % lived in farm families. Total DAPs concentration was higher in dry season (p = 0.002) but did not differ between farm and non-farm children. Total DAPs in wet season was associated with current wheeze (p = 0.019), current asthma attacks (p = 0.012) and attacks of breathlessness in last 12 months (p = 0.021). Total DAPs in dry season was associated with current wheeze (p = 0.042), and associations between DAPs and respiratory symptoms were stronger for dimethylphosphate metabolites (DMPs) than for diethylphosphate metabolites (DEPs). DMPs are produced by certain OP pesticides. Biomass burning inside or outside the home, and dampness or mold at home, enhanced the association between total DAPs and attacks of breathlessness.In conclusion, OP pesticide exposure, measured as urinary DAPs, was higher in dry season and similar in farm and non-farm children. OPs exposure, especially to DMP related pesticides, can increase asthmatic symptoms, especially in wet season. Combined exposure to OP and smoke from biomass burning, or dampness and mold, can further increase the prevalence of attacks of breathlessness. There is a need to reduce OP insecticide and biomass smoke exposure among Thai children. Since different pesticides can be used in different seasons, studies on respiratory health effects of OPs pesticide exposure should be done in different seasons.

PATIENTS WITH CKD SECONDARY TO GLOMERULAR DISORDERS HAVE DECREASED ARTERIAL STIFFNESS, AS COMPARED TO HYPERTENSIVE AND DIABETIC CKD

Objective: To compare pulse wave velocity (PWV), a marker of arterial stiffness, between CKD patients of different etiologies: hypertensive and diabetic nephrosclerosis. vs. CKD secondary to glomerular disorders. Design and method: Clinical data were collected on 56 patients followed at the Nephrology and Hypertension Institute in Samson Assuta Ashdod University Hospital. All patients had at least one visit at our Nephrology clinics prior to recruitment. All patients with a glomerular disorder had a clinical-pathological diagnosis based on a recent kidney biopsy. Pulse wave velocity (PWV) was measured using a validated Sphygmocor XCEL® device. Univariate and multivariate analyses were performed to compare PWV between hypertensive/diabetic CKD and CKD secondary to glomerular disorders. Results: PWV was significantly higher in the hypertensive/diabetic CKD group, compared to the CKD-GN group, with an average of. 12.2 m/s vs 8.3 m/s, respectively. In a multivariate linear regression model, having CKD secondary to glomerulonephritis was associated with a significantly lower PWV, compared with CKD secondary to hypertension and diabetes, with adjustment of age, creatinine, and comorbidities. Conclusions: CKD Patients secondary to glomerulonephritis, have lower PWV when compared to CKD patients with diabetes and/or hypertension, even after adjusting for age, renal function, and the presence of comorbidities. It is intriguing to further study the possible protective role of immunosuppression on the arterial properties of CKD patients.

Inorganic nitrate benefits contrast-induced nephropathy after coronary angiography for acute coronary syndromes: the NITRATE-CIN trial.

Contrast-induced nephropathy (CIN), also known as contrast-associated acute kidney injury (CA-AKI) underlies a significant proportion of the morbidity and mortality following coronary angiographic procedures in high-risk patients and remains a significant unmet need. In pre-clinical studies inorganic nitrate, which is chemically reduced in vivo to nitric oxide, is renoprotective but this observation is yet to be translated clinically. In this study, the efficacy of inorganic nitrate in the prevention of CIN in high-risk patients presenting with acute coronary syndromes (ACS) is reported. NITRATE-CIN is a double-blind, randomized, single-centre, placebo-controlled trial assessing efficacy of inorganic nitrate in CIN prevention in at-risk patients presenting with ACS. Patients were randomized 1:1 to once daily potassium nitrate (12 mmol) or placebo (potassium chloride) capsules for 5 days. The primary endpoint was CIN (KDIGO criteria). Secondary outcomes included kidney function [estimated glomerular filtration rate (eGFR)] at 3 months, rates of procedural myocardial infarction, and major adverse cardiac events (MACE) at 12 months. This study is registered with ClinicalTrials.gov: NCT03627130. Over 3 years, 640 patients were randomized with a median follow-up of 1.0 years, 319 received inorganic nitrate with 321 received placebo. The mean age of trial participants was 71.0 years, with 73.3% male and 75.2% Caucasian; 45.9% had diabetes, 56.0% had chronic kidney disease (eGFR <60 mL/min) and the mean Mehran score of the population was 10. Inorganic nitrate treatment significantly reduced CIN rates (9.1%) vs. placebo (30.5%, P < .001). This difference persisted after adjustment for baseline creatinine and diabetes status (odds ratio 0.21, 95% confidence interval 0.13-0.34). Secondary outcomes were improved with inorganic nitrate, with lower rates of procedural myocardial infarction (2.7% vs. 12.5%, P = .003), improved 3-month renal function (between-group change in eGFR 5.17, 95% CI 2.94-7.39) and reduced 1-year MACE (9.1% vs. 18.1%, P = .001) vs. placebo. In patients at risk of renal injury undergoing coronary angiography for ACS, a short (5 day) course of once-daily inorganic nitrate reduced CIN, improved kidney outcomes at 3 months, and MACE events at 1 year compared to placebo.

An anti-inflammatory response of an organic food intervention by reducing pesticide exposures in children of Cyprus: A cluster-randomized crossover trial

Organic food consumption in children has been shown to reduce the body burden of chemical pesticides. However, there is little evidence of human health benefits associated with the consumption of organic foods. The objectives were to i) determine the effectiveness of an organic food intervention treatment in reducing the magnitude of an inflammation biomarker (C-reactive protein, CRP) in children (10–12 years) and ii) assess the association between the urinary biomarkers of exposure to pesticides and CRP. This work was part of the ORGANIKO cluster-randomized cross-over trial entailing a 40-day organic food treatment in healthy children. Urinary biomarkers of exposure to pesticides and inflammation (CRP) were measured using tandem mass spectrometry and ELISA immunoassay, respectively. Linear mixed-effect regression models of CRP were used to account for the effect and duration of organic food treatment. Multiple comparisons were handled using Benjamini-Hochberg correction. Results supported an anti-inflammatory effect of organic food treatment in children, albeit with mixed results, depending on the creatinine adjustment method; biomarker levels were divided by urinary creatinine (method a1), or urinary creatinine was used as a fixed effect variable (a2). In the a1 method, a time-dependent reduction for creatinine-adjusted CRP (β = −0.019; 95% CI: −0.031, −0.006; q = 0.045) was observed during the organic food intervention period. A statistically significant association (β = 0.104; 95% CI: 0.035, 0.173; q = 0.045) was found between the biomarker of pyrethroids exposure (3-PBA) and CRP inflammatory biomarker, but not for 6-CN. In the a2 method, similar trend of time-dependent reduction for creatinine-adjusted CRP (β = −0.008; 95% CI: −0.021, 0.004; p = 0.197) was observed during the organic food intervention period, but did not reach statistical significance (q > 0.05); the associations of pyrethroid and neonicotinoid biomarkers with CRP were not statistically significant (q > 0.05). More studies are warranted to sufficiently understand the potential anti-inflammatory response of an organic food treatment.

Associations of concentrations of eight urinary phthalate metabolites with the frequency of use of common adult consumer and personal-care products

This study analyzed the relationship between urine concentrations of phthalate metabolites (UCOM) and personal care products (PCPs) used in adults and examined the change in UCOM according to the usage frequency of PCPs based on raw data from the 3rd Korean National Environmental Health Survey conducted between 2015 and 2017. The relationship between PCP use frequency and UCOM was analyzed using multiple regression analysis, adjusting for baseline factors. The regression model consisted of a Crude Model with log-transformed UCOM before and after adjustment for urine creatinine concentrations. Model 1 was additionally adjusted for age, sex, and obesity, while Model 2 was additionally adjusted for smoking, alcohol consumption, pregnancy history, average monthly income of the household, and PCP exposure within the past 2 days. PCP usage frequency was significantly associated with the UCOM without adjustment for urine creatinine and correlated with demographic characteristics, urine creatinine concentration, and PCP exposure within the past 2 days. This study on exposure to urinary phthalates will play a crucial role in Korean public health by aligning with the fundamentals of research priorities and providing representative data on phthalate exposure for conducting population-level studies.

Exploring the Utility of Urinary Creatinine Adjustment for KIM-1, NGAL, and Cystatin C for the Assessment of Kidney Function: Insights from the C-KidnEES Cohort.

Normalization of urinary biomarkers of kidney injury is a common practice in clinical and research settings to account for variations in urine concentration, and urinary creatinine is often used as a reference. However, to date, there is no consensus on the adjustment of urinary biomarkers with creatinine, and both absolute and creatinine-adjusted biomarker levels are adopted for making interpretations of kidney health. Hence, the present study aimed to investigate the associations of urinary creatinine with three widely used kidney injury biomarkers, KIM-1, NGAL, and cystatin C, to validate the applicability of urinary creatinine as a reference for normalization. A cross-sectional study was performed with 2100 students, 10-18 years of age in the Children's Kidney Environmental Exposure Study (C-KidnEES) cohort established in Sri Lanka. As identified in linear regression analyses, normalization of urinary KIM-1, NGAL, and Cys-C to urinary creatinine did not result in significant under-adjustment or over-adjustment to the absolute urinary concentrations, giving no specific rationale for creatinine adjustment. Hence, absolute urinary concentrations of the above biomarkers can be adopted for the characterization of subclinical kidney injury in adolescents in community studies where early morning urine sampling is practiced. However, for spot urine samples, consideration of both absolute and creatinine-adjusted biomarker levels would be a better approach.

Variation in presepsin and thrombomodulin levels for predicting COVID-19 mortality

Coronavirus disease (COVID-19) has caused extensive mortality globally; therefore, biomarkers predicting the severity and prognosis of COVID-19 are essential. This study aimed to evaluate the application of presepsin (P-SEP) and thrombomodulin (TM), which are biomarkers of sepsis and endothelial dysfunction, respectively, in the prognosis of COVID-19. Serum P-SEP and TM levels from COVID-19 patients (n = 183) were measured. Disease severity was classified as mild, moderate I, moderate II, or severe based on hemoglobin oxygen saturation and the history of intensive care unit transfer or use of ventilation at admission. Patients in the severe group were further divided into survivors and non-survivors. P-SEP and TM levels were significantly higher in the severe group than those in the mild group, even after adjusting for creatinine values. In addition, TM levels were significantly higher in non-survivors than in survivors. Changes in the P-SEP levels at two time points with an interval of 4.1 ± 2.2 days were significantly different between the survivors and non-survivors. In conclusion, TM and continuous P-SEP measurements may be useful for predicting mortality in patients with COVID-19. Moreover, our data indicate that P-SEP and TM values after creatinine adjustment could be independent predictive markers, apart from renal function.

Cardiogenic shock complicating acute myocardial infarction; mechanical circulatory support use in the Netherlands

Abstract Introduction Mortality rates in cardiogenic shock complicating acute myocardial infarction (AMICS) linger around 40-50%. Despite the lack of evidence, the use of mechanical circulatory support (MCS) in this population is increasing rapidly worldwide. Purpose This study aimed to give insights in MCS use in the Netherlands and to assess how the use of MCS is associated with mortality. Methods Data from all patients undergoing percutaneous coronary intervention (PCI) in the Netherlands is prospectively registered in the Netherlands Heart Registration (NHR) database. On top of the obligatory registration, additional data were retrieved for all patients with cardiogenic shock undergoing PCI between 2017 and 2021 in 14 Dutch hospitals. The additional variables included the use of different types of MCS. Multivariate logistic regression was used to test the association between MCS and mortality in adjustment for confounders. Results In total, we included 2328 patients, with a mean age of 66.4 ± 12.3 years and of whom 72.9% were male. Of all patients, 23.6% received a form of MCS (11.5% an IABP, 4.5% an Impella, 3.1% VA-ECMO, 4.2% a combination of devices and 0.3% other). Compared to patients who did not receive MCS, MCS supported patients were younger (64.2 vs. 67.1 years, p &amp;lt;0.001), presented after an out-of-hospital cardiac arrest (OHCA) less often (33.3% vs. 39.9%, p = 0.008), had complaints for over three hours more often (50.3% vs. 38.8%, p = 0.001) and had a lower mean arterial pressure (MAP) (74.9 vs. 78.6 mmHg, p &amp;lt;0.005) and higher heartrate (88.2 vs 81.8 beats per minute, p &amp;lt;0.001) at admission. Also, mean admission lactate (6.4 vs. 5.2, p &amp;lt;0.001), glucose (13.4 vs. 11.8, p &amp;lt;0.001) and creatinine levels (104 vs. 99, p &amp;lt;0.001) were higher in MCS-receiving patients. Additionally, patients who received MCS support more often suffered from multivessel disease (68.7% vs. 58.4%, p &amp;lt;0.001) and chronic total occlusions (CTO) (3.5% vs. 1.9%, p = 0.027) and were treated with inotropes prior to PCI more often (54.9% vs. 46.2%, p &amp;lt;0.001). The overall 30-day mortality was higher in the MCS cohort than in the no-MCS cohort, namely 54.4% vs. 34.3% (OR = 2.28, 95%CI = 1.88-2.78). In adjustment for age, OHCA, complaints duration, admission MAP, heartrate, lactate, glucose and creatinine, the presence of multivessel disease and CTO and inotrope use before PCI, MCS was independently associated with 30-day mortality (adjusted OR = 2.23, 95% CI = 1.54-3.23). Conclusion MCS was deployed in 23.6% of the patients in this cohort. Despite the results of the IABP-SHOCK II trial, IABP was the most frequently used device. In this cohort, MCS was independently associated with 30-day mortality. However, residual confounding is probably present. Besides randomised controlled trials guiding clinical decision making regarding MCS use and timing, future research should also focus on investigating barriers to implement the results of previous trials.KM-curve of unadjusted survival

Troponin level at presentation as a prognostic factor among patients presenting with non-ST-segment elevation myocardial infarction.

Timely reperfusion within 120 min is strongly recommended in patients presenting with non-ST-segment myocardial infarction (NSTEMI) with very high-risk features. Evidence regarding the use of high-sensitivity cardiac troponin (hs-cTn) concentration upon admission for the risk-stratification of patients presenting with NSTEMI to expedite percutaneous coronary intervention (PCI) and thus potentially improve outcomes is limited. All patients admitted to a tertiary care center ICCU between July 2019 and July 2022 were included. Hs-cTnI levels on presentaion were recorded, dividing patients into quartiles based on baseline hs-cTnI. Association between initial hs-cTnI and all-cause mortality during up to 3 years of follow-up was studied. A total of 544 NSTEMI patients with a median age of 67 were included. Hs-cTnI levels in each quartile were: (a) ≤122, (b) 123-680, (c) 681-2877, and (d) ≥2878 ng/L. There was no difference between the initial hs-cTnI level groups regarding age and comorbidities. A higher mortality rate was observed in the highest hs-cTnI quartile as compared with the lowest hs-cTnI quartile (16.2% vs. 7.35%, p = .03) with hazard ratio (HR) for mortality of 2.6 (95% confidence interval [CI]: 1.23-5.4; p = .012) in the unadjusted model, and HR of 2.06 (95% CI: 1.01-4.79; p = .047) with adjustment for age, gender, serum creatinine, and significant comorbidities. Patients with NSTEMI and higher hs-cTnI levels upon admission faced elevated mortality risk. This underscores the need for further prospective investigations into early reperfusion strategies' impact on NSTEMI patients' mortality, based on admission troponin elevation.

A-136 Usefulness of Presepsin and Thrombomodulin Measurements for Predicting COVID-19 Mortality

Abstract Background Coronavirus disease (COVID-19) is a novel infectious disease developed into a pandemic since early 2020, resulting in extensive morbidity and mortality globally. Therefore, it is important to identify biomarkers for predicting the severity and mortality of COVID-19. We focused on presepsin (P-SEP) and thrombomodulin (TM), which are biomarkers of sepsis and endothelial dysfunction, respectively. Some reports have already suggested that these biomarkers can be associated with COVID-19, however, most of them assessed blood P-SEP and TM levels using only a single day measurement. In addition, since both P-SEP and TM are excreted by the kidney, renal dysfunction should be considered when evaluating these levels. In this study, to evaluate the usefulness of P-SEP and TM for the prognosis and prediction of COVID-19 severity, we investigated the changes in these levels after admission with or without adjustment for creatinine (CRE) level in COVID-19 patients. Methods Samples were residual sera obtained from COVID-19 patients (n = 674) admitted to the TMDU Hospital. Serum P-SEP and TM levels were measured using the STACIA clinical assay system. Disease severity was classified as mild, moderate, or severe based on hemoglobin oxygen saturation and the history of intensive care unit transfer or use of ventilation at admission. Patients in the severe group were further classified into survivors and non-survivors. This study was approved by the institutional research ethics committee (No. M2020-110). Results Since patients who received recombinant human TM treatment had abnormally high TM levels (&amp;gt; 1000 U/mL), data after administration were excluded from the analysis. P-SEP and TM levels during hospitalization were significantly correlated with CRE levels. In the correlation between P-SEP and CRE, the slope of the severe group was different from that of the non-severe group. When compared the data extracted within 5 days after admission (n = 183) among the three severity groups, CRE levels showed no significant difference among them. On the other hand, P-SEP and TM levels at admission were significantly higher in the severe group than those in the mild group, even after adjusting for CRE levels. In addition, there was no significant difference in the P-SEP levels between survivors and non-survivors, whereas TM levels were significantly higher in non-survivors than in survivors. Changes in the P-SEP levels at two time points (interval: 4.1 ± 2.2 days) were significantly different between survivors and non-survivors. The second measurement of TM levels were elevated in both groups from the first measurement at admission. Conclusion This study suggested that the elevation of P-SEP and TM levels in severe COVID-19 patients might not only fluctuate with renal dysfunction, but might reflect severity. TM and continuous P-SEP measurements are available for predicting mortality in patients with COVID-19. Moreover, P-SEP and TM values after CRE adjustment would be independent predictive markers, apart from renal function.

Thigh muscle fat fraction is independently associated with impaired glucose metabolism in individuals with obesity.

The aim of this study was to address the intramuscular adipose tissue (IMAT) accumulation in the lower extremities and further detect the relationship between adipose tissue (AT) distribution in the muscle and glucose metabolism in subjects with obesity. We conducted a cross-sectional study in 120 Chinese obese adults (80 male and 40 female) with BMI ≥ 28 kg/m2. MRI was applied to access the IMAT content in lower extremities. The oral glucose tolerance test was used to evaluate the glucose metabolism and insulin secretion in all individuals. The correlations between glucose metabolism and the fat content of the lower extremities were further assessed. Among 120 included subjects, 54 were classified as subjects with normal glucose tolerance (NGT) and 66 with impaired glucose regulation (IGR). We presented that those with IGR had higher fat accumulation in semitendinosus, adductor magnus, gracilis and sartorius than those with NGT (all P < 0.05). In sex-specific analyses, females have higher IMAT in adductor magnus than males (P < 0.001). Males with IGR had higher fat fraction of semitendinosus and sartorius than those with NGT (P = 0.020, P = 0.014, respectively). Logistic regression analyses revealed that IMAT content in semitendinosus was the independent factor of IGR in individuals with obesity after adjustment for age, gender, triglycerides, creatinine and albumin (odds ratio: 1.13, 95% CI: 1.02-1.26, P = 0.024). Increased adipose tissue accumulation in thigh muscles was associated with glucose dysregulation in patients with obesity. IMAT content in semitendinosus may serve as a possible risk factor for impaired glucose metabolism.

Impact of weight and creatinine adjustments on the accuracy of Cockcroft-gault equation in hematopoietic cell transplant patients.

Hematopoietic cell transplant (HCT) patients undergo pre- transplant renal function evaluation to confirm transplant eligibility and tailor pharmacotherapy. There is limited evidence regarding the most accurate method of estimating creatinine clearance (CrCl) within this patient population and no studies exist that evaluate the weight utilized within the Cockcroft-Gault (CG) equation in HCT patients. This study evaluates different weight and serum creatinine (SCr) adjustments utilized within the CG equation estimating for renal clearance in patients undergoing HCT. This is a retrospective, single center analysis of adult HCT patients who underwent pre-transplant evaluation with a measured CrCl using a 24-h urine creatinine collection. The primary outcome was to evaluate the correlation of various weights used in estimation of CrCl compared to measured CrCl. Key secondary outcomes include evaluation of the impact of various weights on estimated CrCl in subpopulations, evaluation of adjusting SCr to pre-determined limits, and determination of an appropriate obesity threshold to utilize body weight adjustments. Seven-hundred and forty-two patients were included in the study. In the primary analysis, CG utilizing adjusted body weight (ADjBW0.4 ) had a greater correlation (r=.812) to measured CrCl when compared to total or ideal body weight (r=.801 and r=.790 respectively). The threshold of 120% of ideal body weight (IBW) produced less bias and greater accuracy in comparison to the threshold of 140% IBW. In patients 60 years or older, rounding low SCr values up .8 or 1mg/dL resulted in decreased correlation and a greater mean difference in comparison to not rounding SCr. In HCT patients who are overweight or obese, ADjBW .4 is the most accurate weight for the CG equation. In HCT patients who have a total body weight<120% IBW, total body weight is the most accurate weight to utilize. Rounding up low SCr to .8 or 1mg/dL does not improve the accuracy or led to less bias of the CG equation.

Adjustment of creatinine clearance for carboplatin dosing in Calvert's formula and clinical efficacy for lung cancer.

The Cockcroft-Gault formula is commonly used as a substitute for glomerular filtration rate (GFR) in Calvert's formula for carboplatin dosing, where adjusting serum creatinine measured using the enzymatic method with 0.2 mg/dL has been suggested in Japan. However, the effects of these adjustments on efficacy in patients with non-small-cell lung cancer remain unknown. We conducted a post hoc analysis of the PREDICT1 study (CJLSG1201), a multicenter prospective observational trial of carboplatin-pemetrexed. Glomerular filtration rate values in Calvert's formula were back-calculated from the administered dosages of carboplatin and the reported value of the target area under the curve. We estimated the serum creatinine adjustments and divided the patients into crude and adjusted groups. Patients in the crude group (N = 169) demonstrated similar efficacy to those in the adjusted group (N = 104) in progression-free survival (PFS) and overall survival (OS) (hazard ratio [HR], 1.02; 95% confidence interval [CI], 0.76-1.35; p = 0.916 vs. HR, 0.87; 95% CI, 0.65-1.17; p = 0.363), with higher grade 3-4 hematologic toxicity. Among patients aged ≥75 years, the crude group (N = 47) showed superior efficacy compared with the adjusted group (N = 17) in PFS and OS (HR, 0.37; 95% CI, 0.20-0.69; p = 0.002 vs. HR, 0.43; 95% CI, 0.23-0.82; p = 0.010). Serum creatinine adjustment may be associated with similar efficacy compared to the crude serum creatinine value. In older patients, the adjustment should be cautiously applied owing to the potential for reduced efficacy.

Environmental exposure to perchlorate, nitrate, and thiocyanate in relation to chronic kidney disease in the general US population, NHANES 2005-2016.

Few studies have explored the impact of perchlorate, nitrate, and thiocyanate (PNT) on kidney function. This study aimed to evaluate the association of urinary levels of PNT with renal function as well as the prevalence of chronic kidney disease (CKD) among the general population in the United States. This analysis included data from 13,373 adults (≥20 years) from the National Health and Nutrition Examination Survey 2005 to 2016. We used multivariable linear and logistic regression, to explore the associations of urinary PNT with kidney function. Restricted cubic splines were used to assess the potentially non-linear relationships between PNT exposure and outcomes. After traditional creatinine adjustment, perchlorate (P-traditional) was positively associated with estimated glomerular filtration rate (eGFR) (adjusted β: 2.75; 95% confidence interval [CI]: 2.25 to 3.26; P < 0.001), and negatively associated with urinary albumin-to-creatinine ratio (ACR) (adjusted β: -0.05; 95% CI: -0.07 to -0.02; P = 0.001) in adjusted models. After both traditional and covariate-adjusted creatinine adjustment, urinary nitrate and thiocyanate were positively associated with eGFR (all P values <0.05), and negatively associated with ACR (all P values <0.05); higher nitrate or thiocyanate was associated with a lower risk of CKD (all P values <0.001). Moreover, there were L-shaped non-linear associations between nitrate, thiocyanate, and outcomes. In the adjusted models, for quartiles of PNT, statistically significant dose-response associations were observed in most relationships. Most results were consistent in the stratified and sensitivity analyses. Exposures to PNT might be associated with kidney function, indicating a potential beneficial effect of environmental PNT exposure (especially nitrate and thiocyanate) on the human kidney.

Proteinuria and hematuria after remission induction are associated with outcome in ANCA-associated vasculitis

In anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), hematuria and proteinuria are biomarkers reflecting kidney involvement at diagnosis. Yet, the prognostic value of their persistence after immunosuppressive induction therapy, reflecting kidney damage or persistent disease, remains uncertain. To study this, our post-hoc analysis included participants of five European randomized clinical trials on AAV (MAINRITSAN, MAINRITSAN2, RITUXVAS, MYCYC, IMPROVE). Urine protein-creatinine ratio (UPCR) and hematuria of spot urine samples collected at the end of induction therapy (four-six months after treatment initiation) were correlated with the occurrence of a combined endpoint of death and/or kidney failure, or relapses during follow-up. Among 571 patients (59% men, median age 60), 60% had anti-proteinase 3-ANCA and 35% had anti-myeloperoxidase-ANCA, while 77% had kidney involvement. After induction therapy, 157/526 (29.8%) had persistent hematuria and 165/481 (34.3%) had UPCR of 0.05 g/mmol or more. After a median follow-up of 28 months (inter quartile range 18-42), and adjustment for age, ANCA type, maintenance therapy, serum creatinine and persistent hematuria after induction, a UPCR of 0.05 g/mmol or more after induction was associated with significant risk of death/kidney failure (adjusted Hazard Ratio (HR) 3.06, 95% confidence interval (1.09-8.59) and kidney relapse (adjusted subdistribution HR 2.22, 1.16-4.24). Persistent hematuria was associated with significant kidney relapse (adjusted subdistribution HR 2.16, (1.13-4.11) but not with relapse affecting any organ nor with death/kidney failure. Thus, in this large cohort of patients with AAV, persistent proteinuria after induction therapy was associated with death/kidney failure and kidney relapse, whereas persistent hematuria was an independent predictor of kidney relapse. Hence, these parameters must be considered to assess long-term kidney prognosis of patients with AAV.

Urinary L-Type Fatty Acid-Binding Protein Predicts Oxygen Demand of COVID-19 in Initially Mild Cases.

To predict COVID-19 disease severity within 10 days, distinguishing cases that will progress to moderate or severe versus mild, patient urinary L-type fatty acid-binding protein (L-FABP) was assayed within 4 days of receiving a diagnosis. The study also examined whether L-FABP point of care (POC) test is helpful in risk screening. Symptomatic subjects who tested positive for SARS-CoV-2 and were hospitalized were prospectively enrolled at the National Center for Global Health and Medicine (NCGM), Yamanashi Prefectural Central Hospital (YPCH), and Sinai Hospital in Maryland. The outcome of each case was evaluated 7 days after admission and the diagnostic performance of L-FABP was assessed. Subjects were treated for COVID-19 at public healthcare centers in Japan from January 31, 2020, to January 31, 2021, to NCGM, YPCH, and at Sinai Hospital in Baltimore, MD, during the same period. The primary outcome was to determine whether urinary L-FABP within 48 hours of admission can predict the patient's severity of COVID-19 1 week later. We obtained demographic data, information on clinical symptoms, radiographic images, and laboratory data. Diagnostic performance was assessed using receiver operating characteristic analysis. Of the 224 participants in the study, 173 initially had a mild form of COVID-19. The area under the curve (AUC) for a severe outcome was 93.5%. L-FABP POC risk prediction of a severe outcome had an AUC of 88.9%. Urinary L-FABP can predict patient risk of COVID-19 illness severity. L-FABP POC is implementable for patient management. (ClinicalTrials.gov number, NCT04681040).

Exposure to polycyclic aromatic hydrocarbons assessed by biomonitoring of firefighters during fire operations in Germany.

Firefighters are exposed to a variety of hazardous substances including carcinogens such as polycyclic aromatic hydrocarbons (PAH) during firefighting. In order to minimize the uptake of such substances into the body, firefighters wear personal protective equipment. Only few data exist from real-life firefighting missions and under common although highly variable exposure scenarios such as fighting fires in residential buildings, outdoor, and vehicle fires. The aim of this study is to assess the levels of 1-Hydroxypyrene (1-OHP) as marker for incorporated PAH during firefighting operations in Germany using biomonitoring methods. We analyzed urine samples for 1-OHP from 77 firefighters who reported firefighting operations (with and without creatinine adjustment). Urine samples were collected before (baseline) and, where applicable, after firefighting operations at three time points subsequent (2-4, 6-8, and 12h). Compared to the baseline measurements, mean 1-OHP concentrations after firefighting missions were doubled (0.14 vs. 0.31μg/L urine, 0.13μg/g vs. 0.27μg/g creatinine) and this increase was observed 2-4h after firefighting. Firefighting in residential buildings (N=54) and of outdoor and vehicle fires (N=17) occurred most frequently, whereas blazes, vegetation fires, and fires in underground facilities (N=6) were rarely encountered. For residential building fires, a 3-fold increase in mean 1-OPH concentrations was observed, whereas no increase could be observed for outdoor and vehicle fires. The highest increase was observed for firefighters with interior attack missions (0.11μg/L vs. 0.48μg/L 1-OHP) despite the use of self-contained breathing apparatus (SCBA). During the suppression of outdoor or vehicle fires using SCBA, again, no increase was observed. Although PAH are taken up during certain firefighting missions, the 1-OHP levels almost entirely remained (in 64 of the 77 reported missions) within the normal range of the German general population, i.e., below the reference levels (95th percentiles) of smokers (0.73μg/g creatinine) and non-smokers (0.30μg/g creatine). Under study conditions, properly applied protective clothing and wearing of SCBA led to a significant reduction of PAH exposure levels. But there are individual situations in which PAH are increasingly incorporated since the incorporation depends on several factors and can be extremely variable. In contrast to many workplaces with high occupational exposure levels, firefighters are not exposed to PAH on a daily basis. Nevertheless, the possibility of an individual increased cancer risk for a particular firefighter cannot completely be ruled out.

Elevated serum uric acid is associated with renal arteriolopathy and predict poor outcome in patients with lupus nephritis.

Increased serum uric acid (SUA) levels are well known to be concomitant of cardiovascular and kidney diseases, and have been proposed to be implicated in the development of arteriolar damage. The aim of the present study was to assess the association between SUA levels, renal damage and its implication for outcome in patients with lupus nephritis (LN). This retrospective study included 194 cases with biopsy proven LN at the Affiliated Hospital of Qingdao University between January 2013 and June 2021. We reviewed clinical, laboratory and histologic data of patients and analysed the correlation between SUA levels, renal damage and the primary outcome (death or ESRD). Biopsy-proven arteriolar damage was defined by the presence of arteriolar hyalinosis and/or intimal thickening. Compared to LN patients without hyperuricemia, LN patients with hyperuricaemia presented with higher BP, hyperlipidaemia, lower eGFR, lower haemoglobin, lower serum albumin, worse renal arteriolar damage and proteinuria, and also higher SLEDAI score, activity index and chronicity index (p<0.05). At logistic regression analysis, SUA was independently related to the presence of arteriolar damage. For each 100 μmol/L increase in SUA levels the risk for arteriolar damage raised by 53.8% (hazard ratio [HR] =1.538; 95% CI: 1.147-2.063; p=0.004) after adjustment for haemoglobin, serum creatinine and erythrocyte sedimentation rate. Cox regression analysis showed that female (HR=3.180; 95% CI: 1.216-8.313; p=0.018), white blood cell count (HR=1.111; 95% CI: 1.027-1.202; p=0.009), SUA (HR=1.100; 95% CI: 1.023-1.253; p=0.035), serum creatinine (HR=1.800; 95% CI: 1.348-2.404; p<0.001), and renal arteriolar damage (HR=3.117; 95% CI: 1.022-9.511; p=0.046) was significantly associated with development of ESRD or death in patients with LN after adjustment for several potential confounding factors. Furthermore, for each 100 μmol/L increase in SUA levels, the risk of ESRD or death increased by 10%. SUA levels are directly associated with renal arteriolar damage and poor prognosis in LN patients. Hyperuricaemia is an important predictor for poor prognosis in patients with LN.

Urinary Creatinine Concentrations and Its Explanatory Variables in General Chinese Population: Implications for Creatinine Limits and Creatinine Adjustment

ObjectiveThe study aimed to analyze the applicability of the World Health Organization's exclusionary guidelines for Urinary creatinine (Ucr) in the general Chinese population, and to identify Ucr related factors. MethodsWe conduct a cross-sectional study using baseline data from 21,167 participants in the China National Human Biomonitoring Program. Mixed linear models and restricted cubic splines (RCS) were used to analyze the associations between explanatory variables and Ucr concentration. ResultsThe geometric mean and median concentrations of Ucr in the general Chinese population were 0.90 g/L and 1.01 g/L, respectively. And 9.36% samples were outside 0.3–3.0 g/L, including 7.83% below the lower limit and 1.53% above the upper limit. Middle age, male, obesity, smoking, higher frequency of red meat consumption and chronic kidney disease were associated significantly with higher concentrations of Ucr. Results of the RCS showed Ucr was positively and linearly associated with body mass index, inversely and linearly associated with systolic blood pressure, diastolic blood pressure, triglycerides level, and glomerular filtration rate, and were non-linearly associated with triiodothyronine. ConclusionThe age- and gender-specific cut-off values of Ucr that determine the validity of urine samples in the general Chinese population were recommended. To avoid introducing bias into epidemiologic associations, the potential predictors of Ucr observed in the current study should be considered when using Ucr to adjust for variations in urine dilution.

Confounding factors of Alzheimer's disease plasma biomarkers and their impact on clinical performance.

Plasma biomarkers will likely revolutionize the diagnostic work-up of Alzheimer's disease (AD) globally. Before widespread use, we need to determine if confounding factors affect the levels of these biomarkers, and their clinical utility. Participants with plasma and CSF biomarkers, creatinine, body mass index (BMI), and medical history data were included (BioFINDER-1: n=748, BioFINDER-2: n=421). We measured beta-amyloid (Aβ42, Aβ40), phosphorylated tau (p-tau217, p-tau181), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP). In both cohorts, creatinine and BMI were the main factors associated with NfL, GFAP, and to a lesser extent with p-tau. However, adjustment for BMI and creatinine had only minor effects in models predicting either the corresponding levels in CSF or subsequent development of dementia. Creatinine and BMI are related to certain plasma biomarkers levels, but they do not have clinically relevant confounding effects for the vast majority of individuals. Creatinine and body mass index (BMI) are related to certain plasma biomarker levels. Adjusting for creatinine and BMI has minor influence on plasma-cerebrospinal fluid (CSF) associations. Adjusting for creatinine and BMI has minor influence on prediction of dementia using plasma biomarkers.