Urinary Creatinine Concentration Research Articles

Differences in urine creatinine and osmolality between black and white Americans after accounting for age, moisture intake, urine volume, and socioeconomic status.

Urine osmolality is used throughout research to determine hydration levels. Prior studies have found black individuals to have elevated urine creatinine and osmolality, but it remains unclear which factors explain these findings. This cross-sectional, observational study sought to understand the relationship of self-reported race to urine creatinine and urine osmolality after accounting for age, socioeconomic status, and fluid intake. Data from 1,386 participants of the 2009-2012 National Health and Nutrition Examination Survey were utilized. Age, poverty-to-income ratio (PIR), urine flow rate (UFR), fluid intake, estimated lean body mass (LBM), urine creatinine, and urine osmolality were measured. In a sex-specific manner, black and white participants were matched on age, dietary moisture, UFR, and PIR. Urine creatinine was greater in black men (171 mg/dL) than white men (150 mg/dL) and greater in black women (147 mg/dL) than white women (108 mg/dL) (p < .001). Similarly, urine osmolality was greater in black women than white women (723 vs. 656 mOsm/kg, p = .001), but no difference was observed between white and black men (737 vs. 731 mOsm/kg, p = .417). Estimated LBM was greater in black men (61.8 kg) and women (45.5 kg) than in white men (58.9 kg) and women (42.2 kg) (p≤.001). The strongest correlate of urine osmolality in all race-sex groups was urine creatinine (Spearman ρ = .68-.75). These results affirm that individuals identifying as black produce higher urine creatinine concentrations and, in women, higher urine osmolality after matching for age, fluid intake, and socioeconomic status. The findings suggest caution when comparing urine hydration markers between racial groups.

Water Intake and Hydration Status among Pregnant Women in the Second Trimester in China: A Three-Day Metabolic Trial.

Adequate water intake and optimal hydration status during pregnancy are crucial for maternal and infant health. However, research on water intake by pregnant women in China is very limited. This study mainly aimed to observe the daily total water intake (TWI) of pregnant women and its different sources and to investigate the relationship between their water intake and hydration biomarkers. From October to November 2020, a convenience sample of pregnant women in the second trimester (n = 21) was recruited. Under conditions close to daily life, they undertook a 3-day metabolic trial. Each participant was provided with sufficient bottled water, and the weight of what they drank each time was measured. The intake of other beverages and foods was measured using a combination of weighing and duplicate portion method. Fasting venous blood and 24 h urine samples were collected and analyzed for the hydration biomarkers, including the serum/urine osmolality, urine pH, urine specific gravity, and the concentrations of major electrolytes in urine and serum. The results showed that the mean daily TWI was 3151 mL, of which water from beverages and foods accounted for 60.1% and 39.9%, respectively. The mean total fluid intake (TFI) was 1970 mL, with plain water being the primary contributor (68.7%, r = 0.896). Among the participants, 66.7% (n = 14, Group 1) met the TWI recommendation set by the Chinese Nutrition Society. Further analysis revealed that the TFI, water from beverages and foods, plain water, and milk and milk derivatives (MMDs) were significantly higher in Group 1 than those who did not reach the adequate intake value (Group 2) (p < 0.05). The results of hydration biomarkers showed that the mean 24 h urine volume in Group 1 was significantly higher than that in Group 2 (p < 0.05), while the 24 h urine osmolality, sodium, magnesium, phosphorus, chloride, and creatinine concentrations in Group 1 were significantly lower than those in Group 2 (p < 0.05). However, no significant differences were observed in serum biomarkers. Partial correlation analysis showed that TWI was moderately positively correlated with 24 h urine volume (r = 0.675) and negatively correlated with urine osmolality, sodium, potassium, magnesium, calcium, phosphorus, and chloride concentrations (r = from-0.505 to -0.769), but it was not significantly correlated with serum biomarkers. Therefore, under free-living conditions, increasing the daily intake of plain water and MMDs is beneficial for pregnant women to maintain optimal hydration. The hydration biomarkers in urine are more accurate indicators of water intake and exhibit greater sensitivity compared to serum biomarkers. These findings provide a scientific basis for establishing appropriate water intake and hydration status for pregnant women in China.

Creating Creatinine: How to Pass a Urine Drug Test

Here we report on a patient that consumed recreational drugs, successfully passing a urine drug screen (UDS) by consuming a marketed detoxification product. After some exploration of the product consumed, there proved to be a viable mechanism by which the UDS outcome can be manipulated. The UDS relies on urine meeting specific concentration criteria to validate the sample. Dilute samples may mask the tested drugs as they fall below a concentration threshold for detection. Common UDS require a specific gravity with a reference range of 1.003-1.035 and a urine creatinine concentration above 20 mg/dL. Participants are told not to drink fluid for 4-5-hours pre-test to allow urine to concentrate above these thresholds. The 21-year-old female we describe along with each UDS had lab drawings on two separate occasions in which both measurements revealed elevated serum creatinines of 1.8 mg/dL. She had ingested QCarbo Maximum Strength Same-Day Cleansing Formula™, a marketed detoxification product, the day prior to the lab draws. The product recommended that the consumer ingest a large volume of water to “flush” the drugs from the body. This resulted in dilution of her urine to cause the drug levels to fall below the detectable range, while still exceeding the urine creatinine concentration to provide a valid test. Although she was unaware that this product increased both serum and urine creatinine, this proved successful. She passed the test and was awarded the position.

Iodine intake in the Swiss population 100years after the introduction of iodised salt: a cross-sectional national study in children and pregnant women.

The Swiss voluntary salt iodisation programme has successfully prevented iodine deficiency for 100years, but dietary habits are changing and todayonly one-third of processed foods contain iodised salt. We aimed to monitor the current iodine status in childrenand pregnant women. We conducted a nationwide cross-sectional study in children (6-12years) and pregnant women and measured the urinary iodine concentration (UIC) in spot urine samples. We estimated the iodine intake using UIC and urinary creatinine concentration (UCC) and determined the prevalence of intakes below the average requirement (AR) using the SPADE method. We measured dried blood spot (DBS) thyroglobulin (Tg), TSH and total T4 in pregnant women. The median UIC was 127μg/L (bootstrapped 95% CI 119, 140, n = 362) in children and 97μg/L (bootstrapped 95% CI 90, 106, n = 473) in pregnant women. The estimated prevalence of inadequate iodine intake (< 65μg/day) was 5.4% (bootstrapped 95% CI 0.0, 14.6) in children. Half (47%) of the women consumed iodine-containing multivitamin and mineral supplements (≥ 150μg/day). Compared to non-users, users had higher median UIC (129 vs. 81μg/L, P < 0.001), lower prevalence of inadequacy (< 160μg/day; 0.2 vs. 31%) and lower DBS-Tg (23 vs. 29μg/L, P < 0.001). All women were euthyroid. The Swiss diet and current salt fortification provides adequate iodine intake in children, but not in all pregnant women. Iodine supplements cover the dietary gap in pregnancy but are not universally consumed. Therefore, improved use of iodised salt in processed foods is desired to ensure adequate iodine intake in all population groups. This trial was registered at clinicaltrials.gov as NCT04524013.

An alkaline ferrocyanide non-enzymatic electrochemical sensor for creatinine detection

Creatinine is a useful metabolite for the evaluation of Chronic Kidney Disease (CKD). Creatinine concentrations in urine outside of the healthy range of 4 to 15 mM may indicate CKD and other kidney conditions. Early detection and monitoring can provide lifesaving intervention, and as such there is a need to develop rapid, cheap and selective electrochemical creatinine sensors. A simple non-enzymatic creatinine sensing platform enabled by the electrocatalytic response of the metabolite to ferricyanide in alkaline conditions is presented. Studies were made on unmodified glassy carbon (GCE) and screen printed carbon electrodes (SPCE), both giving sensitivity of 21 ± 5 µA mM−1 cm−2 and limit of detection of ca. 60 µM.

PSXIII-15 Use of Creatinine as a Marker to Estimate Urine Output in Beef Cattle Fed a Finishing Or Backgrounding Diet

Abstract Unlike for high forage diets, there has been limited validation of spot urine sampling and the use of urinary creatinine as a marker to estimate urine output in beef cattle fed high grain diets. Therefore, the objective of this study was to validate the use of creatinine as a marker for estimating urine output in cattle fed a finishing (FIN) compared with a backgrounding (BKGN) diet. Six heifers were randomly allocated to 2 treatments in a crossover design with 21 d periods. Dietary treatments were alfalfa silage at 12% (FIN) or 60% (backgrounding; BKGN) of dietary dry matter (DM), with the remainder of the diet consisting of corn grain (67.8 or 38.1% on a DM basis), corn dried distillers grains with solubles (DDGS; 0.75 or 19.0%) and a constant level (1.15%) of supplement. Total collection (TC) of urine was conducted during the last 3 d of each period. Twelve spot urine samples were also collected during TC to represent every 2-h sampling in a 24-h cycle. Data were analyzed using SAS. Creatinine excretion rate varied from 27.2 to 35.0 with an average of 31.3 mg/kg of body weight per day. The creatinine concentration of spot samples collected for each heifer were averaged to simulate urine samples obtained from various spot sampling frequencies [equally spaced 12, 6, 4, and 2 time points (TP) starting at feeding: 12TP, 6TP, 4TP, and 2TP, respectively]. There was diurnal variation in the urinary creatinine concentration on both diets. Although creatinine concentration did not differ (P = 0.82) between 12TP and TC, use of 12TP underestimated (P &amp;lt; 0.01) urine output (11.2 vs. 18.0 kg/d). However, there was no diet effect (P ≥ 0.32) on creatinine concentration and total urine output across methods (12TP vs. TC). When comparing spot sampling TP, there was no diet, method, or diet × method interaction (P ≥ 0.28) on urinary creatinine concentration and urine output. The regression between TC and 12TP had an intercept different from 0, and slope differed from 0 and 1. As for TC and 6TP, the intercept was not different from 0; however, slope was different from 0 and 1. As expected, increasing the frequency of spot sampling improved precision and accuracy of the regression between the estimated and measured urine output according to adjusted R2 (0.27, 0.24, 0.87 and 0.92 for 2TP, 4TP, 6TP, and 12TP, respectively) and root mean square prediction error (8.95, 9.09, 3.75, and 2.94). In summary, the use of the spot sampling technique and urinary creatinine as a marker to estimate urine output in beef cattle fed either FIN or BKGN diets might not be reliable due to the diurnal variation in creatinine excretion and variable creatinine coefficients.

Urinary IL-6 and IL-8 as predictive markers in bladder urothelial carcinoma: A pilot study.

Cytokines are known to be a key a factor in numerous malignancies and to exert an important regulatory role in the tumor microenvironment. Interest has grown in understanding how cytokines modulate the tumor microenvironment and which cytokines may serve as markers of the tumor process; however, a complete picture of the cytokine landscape in bladder cancer remains unclear. Fresh urine specimens with sufficient volume were collected at random intervals. The urine concentrations of IL-8 (CXCL8), CCL18, and CXCL9 were determined using the standard commercially available enzyme immunoassay. The urine concentrations of IL-6 were determined using the high sensitivity enzyme immunoassay kit. Urinary cytokine concentrations were normalized with urinary creatinine concentrations. Significantly elevated concentrations of IL-6 and IL-8 were detected in the urine from patients with urothelial carcinoma on follow-up compared to patients with benign follow-up. The presence of both IL-6 and IL-8 in the urine samples from the high grade urothelial carcinoma (HGUC) cohort revealed a clear discrimination when compared to samples from patients with benign follow-up. The presence of the combination of both IL-6 and IL-8 had a sensitivity of 90.0% and a specificity of 81.25%. Similar data were obtained when receiver operating characteristic analysis was performed on both IL-6 and IL-8 concentrations in the urine from patients with HGUC vs. the hematuria cohort. The presence of IL-6 and IL-8 in urine specimens may have predictive value for urothelial carcinoma. However, a large longitudinal study is required to statistically eliminate confounding factors and support this theory.

The effects of feeding sodium chloride pellets on the gastric mucosa, acid-base, and mineral status in exercising horses.

Electrolyte supplementation may be a risk factor for gastric mucosal lesions, but relevant evidence is limited in horses. Investigate the effects of PO sodium chloride (NaCl) supplementation on the gastric mucosa of exercising horses. We hypothesized that NaCl supplementation would neither cause nor exacerbate existing gastric mucosal damage. Fifteen 3-year-old healthy Warmblood stallions from a stud farm. Placebo-controlled study with a crossover design. Horses were fed either a NaCl pellet at a dosage adequate to replace the electrolyte losses in 10 L sweat or a placebo for 19 days with a washout period of 14 days between treatments. The gastric mucosa was evaluated by gastroscopy before and after treatment. Blood samples were collected for evaluation of acid-base status, packed cell volume (PCV), and total protein, creatinine and blood urea nitrogen concentrations. Urine was collected, and urine specific gravity, electrolyte, creatinine, and urea concentrations were measured. The initial prevalence of gastric mucosal lesions was 85%. Sodium chloride pellets did not adversely affect the gastric mucosa and treatment did not significantly alter the hematologic and serum biochemical variables. Urine creatinine concentrations significantly decreased and urinary sodium concentrations significantly increased after supplementation with NaCl pellets. Water intake did not significantly differ between treatments. Daily NaCl pellet supplementation is a palatable and safe way to replace electrolyte losses from sweating in exercising horses and has no negative effects on the gastric mucosa.

Urinary creatinine concentration and urine color as indicators of specimen validity test

In this study, the concentration of urinary creatinine (Cr) and urine color were analyzed, and a correlation obtained, to objectively verify normal urine samples prior to forensic drug testing. Cr was analyzed via a colorimetric method based on the Jaffé reaction using a Cobas C-311 analyzer (Roche SA, Basel, Switzerland; Hitachi, Tokyo, Japan). The Cr concentration for urine specimen validity testing was measured to screen urine samples submitted after dilution or upon the addition of a foreign substance that interferes with drug testing. Urine samples containing < 20 mg/dL of Cr were classified as abnormal. The Korea Standard Color Analysis program was used for urine color analysis and correlations with Cr concentration analyzed. The color and Cr concentration of 271 urine samples were analyzed according to age and sex. The mean ± standard deviation of Cr concentration in males and females was 136.4 ± 66.2 mg/dL and 109.5 ± 71.1 mg/dL, respectively, with a statistically insignificant difference (p = 0.4554). Furthermore, the participants were categorized into young (19–34 years), middle-aged (35–49 years), and elderly (≥ 50 years) groups to compare Cr concentration; however, no significant difference was found (p = 0.2143–0.983). Strong variable correlations were identified between Cr and the characteristics of urine color. Despite various factors such as water consumption, health problems, and vitamins, urine color was found applicable for urine specimen validity testing. Future plans include the development of a smartphone camera application for use in urine color analysis to identify abnormal urine samples.

Feeding spent hemp biomass to lactating dairy cows: Effects on performance, milk components and quality, blood parameters, and nitrogen metabolism

The legalization of industrial hemp by the 2018 Farm Bill in the United States has driven a sharp increase in its cultivation, including for cannabinoid extraction. Spent hemp biomass (SHB), produced from the extraction of cannabinoids, can potentially be used as feed for dairy cows; however, it is still illegal to do so in the United States, according to the US Food and Drug Administration Center for Veterinary Medicine, due to the presence of cannabinoids and the lack of data on the effect on animals. To assess the safety of this byproduct as feed for dairy cows, late-lactation Jersey cows (245 ± 37 d in milk; 483 ± 38 kg body weight; 10 multiparous and 8 primiparous) received a basal total mixed ration (TMR) diet plus 13% alfalfa pellet (CON) or 13% pelleted SHB for 4 wk (intervention period [IP]) followed by 4 wk of withdrawal period (WP), where all cows received only the basal TMR during WP. The dry matter intake (DMI), body weight, body condition score, milk yield, milk components, and fatty acid profile, blood parameters, N metabolism, methane emission, and activity were measured. Results indicated that feeding SHB decreased DMI mainly due to the low palatability of the SHB pellet, as the cows consumed only 7.4% of the total TMR with 13.0% SHB pellet offered in the ration. However, milk yield was not affected during the IP and was higher than CON during the WP, leading to higher milk yield/DMI. Milk components were not affected, except for a tendency in decreased fat percentage. Milk fat produced by cows fed SHB had a higher proportion of oleate and bacteria-derived fatty acids than CON. The activity of the cows was not affected, except for a shorter overall lying time in SHB versus CON cows during the IP. Blood parameters related to immune function were not affected. Compared with CON, cows fed SHB had a lower cholesterol concentration during the whole experiment and higher β-hydroxybutyric acid during the WP, while a likely low-grade inflammation during the IP was indicated by higher ceruloplasmin and reactive oxidative metabolites. Other parameters related to liver health and inflammatory response were unaffected, except for a tendency for higher activity of alkaline phosphatase during IP and a lower activity of gamma-glutamyl transferase during WP in the SHB group versus CON. The bilirubin concentration was increased in cows fed SHB, suggesting a possible decrease in the clearance ability of the liver. Digestibility of the dry matter and protein and methane emission were not affected by feeding SHB. The urea, purine derivatives, and creatinine concentration in urine was unaffected, but cows fed SHB had higher N use efficiency and lower urine volume. Altogether, our data revealed a relatively low palatability of SHB affecting DMI with minimal biological effects, except for a likely low-grade inflammation, a higher N use efficiency, and a possible decrease in liver clearance. Overall, the data support the use of SHB as a safe feed ingredient for lactating dairy cows.

Dynamics of urinary kim-1 as a biomarker of acute kidney injury in cancer patients undergoing cisplatin-based chemotherapy

Platinum is the main component of the most chemotherapy (CT) regimens, but their use may be limited because of nephrotoxicity. Kidney injury molecule 1 (KIM-1) is considered as an early marker of cisplatininduced acute kidney injury (AKI). The aim of our study was to evaluate the changes in the burinary levels of KIM-1 (uKIM-1) in cancer patients receiving nephrotoxic CT throughout the entire course of the treatment. Material and Methods. The level of uKIM-1 was determined by enzyme immunoassay in untreated 19 patients with solid malignancies before each CT cycle (regimens with cisplatin or oxaliplatin) and every next day after cytostatic drugs administration. uKIM-1 values were normalized to urinary creatinine concentration (uKIM-1). The kidneys function was assessed by the serum creatinine (sCr) and glomerular fltration rate (GFR) value. Results. According to laboratory parameters, renal function in patients before treatment corresponded to normal ranges. During CT, an increase in sCr by more than 50 % (decrease in GFR to 68 ml/min/1.73 m2 ), which corresponded to stage I AKI (KDIGO) was revealed in one patient (5.3 %) only. uKIM-1 levels before CT were above the upper limit of normal range (3.4 ng/mguCr) in 3 patients (15.8 %; median 2.1 ng/mguCr); at the beginning of the 2nd cycle of CT they were increased in 9 patients (47.4 %; median 3.2 ng/mguCr; p=0.0025, Mann-Whitney test); at the beginning of the 3rd cycle of CT uKIM-1 levels were increased in 12 patients (63.2 %; median 4.9 ng/mguCr; p=0.00007). During CT with cisplatin the average level of uKIM-1 increased with each subsequent cycle, in most cases it increased already the day after the administration of cytostatic drugs. No increase in uKIM-1 levels was observed during treatment with oxaliplatin-based regimens. The achievement of the threshold uKIM-1 level of 6.0 ng/mguCr at the beginning of the next cycle of CT was signifcantly associated with a high risk of its further increase (RR=18.8; p=0.0051). Conclusion. An increase in the level of uKIM-1 after cisplatin administration can be regarded as a marker of subclinical kidney damage. In the future, the increase in uKIM-1 level at the beginning of the cycle of CT may be a reason for enhanced preventive measures or the appointment of less nephrotoxic treatment regimens.

Spot Urinary Creatinine Concentration in Patients with Chronic Heart Failure Identifies a Distinct Muscle-Wasting Phenotype with a Strikingly Different Risk of Mortality.

There is a raising awareness that heart failure (HF) is a highly heterogeneous, multiorgan syndrome with an increasing global prevalence and still poor prognosis. The comorbidities of HF are one of the key reasons for presence of various phenotypes with different clinical profile and outcome. Heterogeneity of skeletal muscles (SMs) quantity and function may have an impact on patient's phenotype. We intended to compare clinical characteristics of phenotypes defined by a combination of various SM mass taken as a fat-free compartment from DEXA scans and different levels of SUCR (Spot Urinary Creatinine). All-cause mortality with mortality predicted by MAGGIC in such phenotypes were compared. In 720 HF patients with reduced ejection fraction (age: 52.3 ± 10 years, female: 14%, NYHA: 2.7 ± 0.7, LVEF: 24.3 ± 7.3%), admitted to the hospital for heart transplantation candidacy assessment, morning SUCR along with body composition scanning (DEXA) was performed. All study participants were dichotomized twice, first by low or normal appendicular muscle mass index (ASMI) and second by SUCR (Spot Urinary Creatinine) < and ≥of 1.34 g/L. Four study groups (phenotypes) were created as combinations of lower or higher SUCR and low or normal ASMI. Low ASMI was found in 242 (33.6%) patients, while the remaining 478 had normal muscle mass. In 446 patients (61.9%), SUCR was <1.34 g/L. During 3 years of follow-up, 223 (31.0%) patients died (all-cause). The phenotype of lower both ASMI and SUCR was associated with the highest mortality. The death rate in phenotype with both low ASMI and SUCR exceeded by 70% the risk estimated by MAGGIC. This difference was significant as judged by the 95% confidence interval for MAGGIC estimation. In Cox regression analysis adjusted for MAGGIC and parameters known to increase risk, the relative risk of patients with phenotype of low both ASMI and SUCR was elevated by 45-55% as compared to patients with all other phenotypes. The protective role of higher SUCR in patients with muscle wasting was, therefore, confirmed in Cox analysis. Measurement of SUCR in HF patients can identify clinical phenotypes with skeletal muscle wasting but strikingly different risk of death that is actually not captured by MAGGIC score. The higher level of SUCR was associated with similar risk independently of presence of muscle wasting. As the analysis of SUCR is cheap and easy to perform, it should be further tested as a potentially useful biomarker, which may precisely phenotype HF patients independently of their skeletal muscle status.

Urine and Plasma Complement Ba Levels During Disease Flares in Patients With Antineutrophil Cytoplasmic Autoantibody–Associated Vasculitis

Although the alternative complement pathway has been implicated in the pathogenesis of antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV), the specific nature of its involvement is unclear. This study measured levels of urine and plasma complement fragment Ba at multiple time points in a group of patients with AAV. The complement fragment Ba was measured by enzyme-linked immunosorbent assay in serial urine and plasma samples from 21 patients with AAV who developed a renal flare, 19 who developed a nonrenal flare, and 20 in long-term remission. Urine Ba levels were corrected for urine creatinine concentration. Changes in Ba levels were modeled using mixed linear-effect models. A logistic regression model was fit to predict a renal flare using Ba levels at the time of flare versus the nonrenal flare and long-term remission groups. Data from 60 patients with AAV were used for this analysis; 53% were male, 93% were White, and 74% had antiproteinase3-ANCA. Urine Ba levels increased at renal flare (P< 0.001) but remained stable during a nonrenal flare or long-term remission. Plasma Ba levels were stable over time in all groups. Urine Ba levels predicted a renal flare with an area under the curve of 0.76 (P< 0.001), with a cutoff of 12.53 ng/mg urine creatinine yielding a sensitivity of 76.2% and a specificity of 68.4%. Urine Ba levels, but not plasma Ba levels, are increased at the time of a renal flare in AAV, suggesting intrarenal complement activation and highlighting the potential use of this biomarker for surveillance of active renal vasculitis.

Concentrated urine, low urine flow, and postoperative elevation of plasma creatinine: A retrospective analysis of pooled data.

Elevations of plasma creatinine are common after major surgery, but their pathophysiology is poorly understood. To identify possible contributing mechanisms, we pooled data from eight prospective studies performed in four different countries to study circumstances during which elevation of plasma creatinine occurs. We included 642 patients undergoing mixed major surgeries, mostly open gastrointestinal. Plasma and urinary creatinine and a composite index for renal fluid conservation (Fluid Retention Index, FRI) were measured just before surgery and on the first postoperative morning. Urine flow was measured during the surgery. The results show that patients with a postoperative increase in plasma creatinine by >25% had a high urinary creatinine concentration (11.0±5.9 vs. 8.3±5.6 mmol/L; P< 0001) and higher FRI value (3.2±1.0 vs. 2.9±1.1; P< 0.04) already before surgery was initiated. Progressive increase of plasma creatinine was associated with a gradually lower urine flow and larger blood loss during the surgery (Kruskal-Wallis test, P< 0.001). The patients with an elevation > 25% also showed higher creatinine and a higher FRI value on the first postoperative morning (P< 0.001). Elevations to > 50% of baseline were associated with slightly lower mean arterial pressure (73 ± 10 vs. 80 ± 12 mmHg; P< 0.005). We conclude that elevation of plasma creatinine in the perioperative period was associated with low urine flow and greater blood loss during surgery and with concentrated urine both before and after the surgery. Renal water conservation-related mechanisms seem to contribute to the development of increased plasma creatinine after surgery.

The Urinary Concentration of Trefoil Factor 3 (TFF3) in the Term and Preterm Neonates.

Distinguishing between a pathologic state and renal development is important in neonatology. Because the assessment of serum creatinine in neonates is not reliable, better biomarkers are needed. Trefoil factor 3 (TFF3) is proposed as a biomarker of kidney injury. The study aimed to assess its urinary concentration in healthy term and stable preterm neonates. The study included 80 term and 20 preterm neonates born in the Department of Perinatology of the University Clinical Hospital in Bialystok. Urine was obtained from the term neonates on the 1st day of life and from the preterm neonates on the 1st, 8th, 15th and 22nd day of life. The urinary concentration of TFF3 was determined using a commercially available immunoassay and was normalized for the urinary creatinine concentration (cr.). The values of TFF3/cr. were higher in the preterm than in the term neonates (p < 0.05) (median (Q1-Q3): 1486.85 (614.92-3559.18) and 317.29 (68.07-671.40) ng/mg cr.). They did not differ in the subsequent days of the preterm neonates' lives. The ROC curve for TFF3/cr. in the preterm and term neonates showed AUC = 0.751 (cut-off value = 1684.25 ng/mg cr.). Prematurity is associated with higher urinary excretion of TFF3. Male gender is associated with an increased urinary TFF3 excretion in term neonates.

Urinary cadmium and endometriosis prevalence in a US nationally representative sample: results from NHANES 1999-2006.

Is exposure to toxic metal cadmium associated with increased endometriosis prevalence among a nationally representative sample of the US population? Concentrations of urinary cadmium, a long-term biomarker (10-30 years) of cadmium exposure, were associated with an increased prevalence of endometriosis. Cadmium exhibits estrogenic properties and may increase the risk of endometriosis, a gynecologic condition associated with substantial morbidity, for which estrogen has a central pathogenic role. Previous epidemiological studies of cadmium and endometriosis have yielded mixed results, with null, positive, and inverse associations being reported. We conducted a cross-sectional study using data from four cycles of the National Health and Nutrition Examination Survey (NHANES) 1999-2006. The study population comprised participants aged 20-54 years who had an endometriosis diagnosis, available data on urinary cadmium, and a glomerular filtration rate ≥60 ml/min/1.73 m2 (unweighted n = 1647). Urinary cadmium was measured by inductively coupled plasma-mass spectrometry, and we used urinary creatinine concentrations and covariate-adjusted standardization to account for urinary dilution. Self-reported diagnosis of endometriosis was ascertained by interview. We examined the association between quartiles of urinary cadmium and endometriosis using log-binomial regression to estimate adjusted prevalence ratios (aPRs) and 95% CIs. We observed twice the prevalence of endometriosis for participants with cadmium concentrations in the second quartile (versus the first quartile) (aPR 2.0, 95% CI: 1.1, 3.9) and the third quartile (versus the first quartile) (aPR 2.0, 95% CI: 1.1, 3.7). Our data also suggested a 60% increased prevalence of endometriosis with urinary cadmium concentrations in the fourth quartile (versus the first quartile) (aPR 1.6, 95% CI: 0.8, 3.2). In a sensitivity analysis, restricting the study population to premenopausal participants with an intact uterus and at least one ovary (unweighted n = 1298), stronger associations accompanied by wider CIs were observed. We were limited by the ascertainment of urinary cadmium and endometriosis diagnosis at a single time point, given the cross-sectional study design, and we relied on self-report of endometriosis diagnosis. However, urinary cadmium characterizes long-term exposure and findings from validation studies suggest that misclassification of self-reported endometriosis diagnosis may be minimal. This study suggests that cadmium is associated with an increased endometriosis prevalence. Given the substantial morbidity conferred by endometriosis and that the general population is ubiquitously exposed to cadmium, further research is warranted to confirm our findings. This work was supported by the National Institute of Nursing Research (grant R00NR017191 to K.U.) of the National Institutes of Health. The authors report no conflict of interest. N/A.

Polychlorinated Biphenyls (PCBs) Impact Prostatic Collagen Density and Bladder Volume in Young Adult Mice Exposed during in Utero and Lactational Development.

Polychlorinated biphenyls (PCBs) are persistent organic pollutants linked to deleterious health outcomes, including voiding dysfunction in developmentally exposed mice. Changes in prostate volume and/or extracellular matrix composition are associated with voiding dysfunction in men and animal models. Whether PCB-induced changes in voiding function in male mice occur in part via alterations to the prostate or an alternate mechanism is unclear. Therefore, we tested whether developmental exposure to the MARBLES PCB mixture altered prostate morphology in young adult offspring. C57Bl/6J female mice were dosed daily with the MARBLES PCB mixture at 0, 0.1, 1 or 6 mg/kg/d for two weeks prior to mating and through gestation and lactation, offspring were collected at 6 weeks of age. Ventral prostate mass was decreased in the 1 mg/kg/d PCB group compared to other PCB groups. There were no PCB-induced changes in prostate smooth muscle thickness, apoptosis, proliferation, or testes mass. PCBs impacted the prostate extracellular matrix; anterior prostate collagen density was decreased in the 1 mg/kg/d PCB group compared to all other groups. Normalized bladder volume was increased in male and female offspring in the 6 mg/kg/d PCB group compared to control. No change in water consumption, bladder mass or bladder smooth muscle thickness accompanied changes in bladder volume. Urine and serum creatinine concentrations were elevated but only in male mice. Together, these results suggest that developmental exposure to PCBs can influence prostate wet weight and prostate/bladder morphology, but PCBs do not promote prostate enlargement. Whether these changes persist throughout adult life and how they contribute to voiding function in animal models and humans is of future interest.

#3937 URINARY EXCRETION OF LIVER-TYPE FATTY ACID-BINDING PROTEIN DETECTS KIDNEY HISTOLOGICAL ALTERATIONS DURING PROGRESSIVE RENAL FIBROSIS

Abstract Background and Aims Subclinical sequelae of acute kidney injury (AKI) are commonly associated with the development of chronic kidney disease (CKD). Despite extensive investigation on AKI to CKD transition on different experimental models, the underlying mechanisms of this transition remain unclear, and there are no known biomarkers monitoring this transition to CKD. The liver-type fatty acid-binding protein (L-FABP) is expressed in the kidney under normal and pathological conditions, and seems to play an important role on kidney injury and repair. We evaluated the efficacy of urinary L-FABP excretion as a prognostic indicator of the progression of renal damage in our AKI to CKD experimental model. Method 8 week old male Wistar rats were divided in two experimental groups: “Control” group (n = 8): SHAM-operated rats, which received saline solution i.p; and Cpt-IR2 group (n = 8): 5 mg/kg cisplatin i.p and 2 weeks after renal function normalization, 60 min ischemia-reperfusion on the left kidney. Blood and urine samples were collected at day 0 (basal), day 4 (AKI development), day 8 (normalized renal function), day 24 (1 day after ischemia), and 2 (M2) and 3 (M3) months after first AKI induction. Renal function was estimated analysing by colorimetric methods plasma and urinary creatinine concentrations (pCr and uCr) and creatinine clearance. Animals were sacrificed at days 56 and 90. Tissue samples were stained with haematoxylin-Eeosin, periodic acid Schiff and Masson's Trichrome for histological analysis. Enzyme-linked immunosorbent assay was used to measure urinary L-FABP concentration. Results Cpt-IR2 rats showed a reduction in renal filtration with respect to control rats even though this decrease does not indicate a severe decline in renal function. This group also presented multiple histological alterations such as fibrosis, loss of brush border membrane, inflammatory infiltrates, basement membrane thickening, tubular dilatation, cellular debris and hyaline casts that worsen markedly from M2 to M3. uL-FABP was greater in Cpt-IR2 rats (52,299 ± 8,407 ng/g uCr M2 and 23,427 ± 4,778 ng/g uCr M3) than in control rats (16,657 ± 2,322 ng/g uCr M2 and 10,636 ± 1,395 ng/g uCr), but this urinary excretion does not correlate with the histological alterations in the last month of the study. Conclusion Urinary L-FABP may be a potential biomarker for the detection of the presence of histological damage although it is not correlated with the extent and degree of the damage in our AKI to CKD transition model. This research was funded by grants from Instituto de Salud Carlos III (ISCIII) PI21/00548 and PI21/01226 co-funded by the European Union and Red de Investigación Renal RICORS2040 (Kidney Disease), RD21/0005/0004 co-funded by the European Union – NextGenerationEU, Mecanismo para la Recuperación y la Resiliencia (MRR). Joana Mercado-Hernández is recipient of a predoctoral fellowship from the Junta de Castilla y Leon (Spain) and the European Social Fund from the European Commission.

Prenatal exposure to phthalates and gender-specific play behavior at seven years of age in the SELMA study

BackgroundA growing body of evidence shows that prenatal exposure to phthalates affects child development. Since many phthalates have been shown to alter endocrine signaling, they may influence reproductive development, neurodevelopment, and child behavior. Indeed, a few studies reported associations between prenatal phthalate exposure and gender-specific play behavior. However, evidence for this relationship is limited, and previous findings are based on single phthalates, while human exposure entails mixtures of chemicals. ObjectiveWe aimed to investigate the associations between prenatal exposure to single phthalates, as well as a phthalate mixture, and gender-specific play behavior. MethodsA total of 715 mother–child pairs from the Swedish Environmental Longitudinal, Mother and Child, Asthma and Allergy (SELMA) study were included. In the median week 10 of pregnancy, phthalate metabolites were measured in urine. Gender-specific play behavior was measured with Preschool Activities Inventory at the age of seven years. Linear and weighted quantile sum regressions were used; data was stratified by sex. Models were adjusted for child and maternal age, maternal education, parental attitudes toward play behavior, and urinary creatinine concentration. ResultsFor boys, single compound analyses revealed negative associations of prenatal exposure to di-isononyl phthalate (DINP) concentrations with masculine (β = −1.44; 95% CI = −2.72, −0.16) and composite (β = −1.43; 95% CI = −2.72, −0.13) scores. Suggestive associations were also observed with a mixture approach identifying DINP as the main contributor of the association of decreased masculine play. Among girls, higher urinary concentrations of 2,4-methyl-7-oxyooctyl-oxycarbonyl-cyclohexane carboxylic acid (MOiNCH) was associated with decreased feminine (β = −1.59; 95% CI = −2.62, −0.57) and masculine scores (β = −1.22; 95% CI = −2.14, −0.29), whereas the mixture analyses did not yield conclusive results for girls. ConclusionOur findings suggest associations of prenatal exposure to DINP with decreased masculine play behavior in boys while the results for girls were not fully conclusive.

Comparison of residual kidney function assessment between the hemodialysis two- and three-day interdialytic interval.

Background Residual kidney function (RKF) is a dynamic marker having been shown to demonstrate fluctuations over successive days of the interdialytic interval. This study compares measured RKF between the long (LIDP) and short interdialytic intervals (SIDP). Methods This was a prospective cohort study. Thirty-four clinically stable, ambulatory facility hemodialysis patients were recruited. Urine samples collected in the last twelve hours of each interdialytic interval were paired with a blood test at the conclusion of each twelve-hour interval to evaluate measured RKF through a mean of urinary urea and creatinine clearances. The paired Student's t-test and the Wilcoxon matched-pairs signed-ranks were used respectively to compare differences in assessed mean and median RKF. Results Although average serum creatinine (607 +/- 219 µmol/L vs. 547 +/- 192 µmol/L, p = <0.01) and serum urea concentrations (25 +/- 15 mmol/L vs. 19 +/- 5 mmol/L, p = 0.01) were higher in the LIDP compared to SIDP, there was no statistically significant difference in urine volume (630 +/- 460 mL vs. 520 +/- 470 mL, p = 0.06), urine urea (116 +/- 49mmol/L vs. 118 +/ 90, p = 0.87), or urine creatinine (7816 +/- 3943 µmol/L vs. 8926 +/- 5752 µmol/L, p = 0.06) concentrations. On the whole, there was no significant difference in assessed RKF between the long and short interdialytic intervals (mean 8 +/- 6 mL/min vs 6 +/- 4 mL/min, p = 0.24; median 6.3 [3.2 - 10.4] vs 5.8 [3.8 - 8.9], p = 0.13). Conclusions There was no statistically significant difference observed in assessed RKF between the LIDP and SIDP. Measured RKF through samples collected from the LDIP and SIDP are comparable.