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

INTRODUCTION: In patients admitted to the intensive care unit (ICU), muscle mass is inversely associated with mortality. Although muscle mass can be estimated with 24-h urinary creatinine excretion (UCE), its use for risk prediction in individual patients is limited because age-, sex-, weight- and length-specific reference values for UCE are lacking. The ratio between measured creatinine clearance (mCC) and estimated glomerular filtration rate (eGFR) might circumvent this constraint. The main goal was to assess the association of the mCC/eGFR ratio in ICU patients with all-cause hospital and long-term mortality. METHODS: The mCC/eGFR ratio was determined in patients admitted to our ICU between 2005 and 2021 with KDIGO acute kidney injury (AKI) stage 0-2 and an ICU stay ≥ 24 h. mCC was calculated from UCE and plasma creatinine and indexed to 1.73 m2. mCC/eGFR was analyzed by categorizing patients in mCC/eGFR quartiles and as continuous variable. RESULTS: Seven thousand five hundred nine patients (mean age 61 ± 15 years; 38% female) were included. In-hospital mortality was 27% in the lowest mCC/eGFR quartile compared to 11% in the highest quartile (P < 0.001). Five-year post-hospital discharge actuarial mortality was 37% in the lowest mCC/eGFR quartile compared to 19% in the highest quartile (P < 0.001). mCC/eGFR ratio as continuous variable was independently associated with in-hospital mortality in multivariable logistic regression (odds ratio: 0.578 (95% CI: 0.465-0.719); P < 0.001). mCC/eGFR ratio as continuous variable was also significantly associated with 5-year post-hospital discharge mortality in Cox regression (hazard ratio: 0.27 (95% CI: 0.22-0.32); P < 0.001). CONCLUSIONS: The mCC/eGFR ratio is associated with both in-hospital and long-term mortality and may be an easily available index of muscle mass in ICU patients.

Effect of age, sex, and chronic kidney disease on urinary creatinine excretion in Japanese patients.

BACKGROUND: Urinary creatinine levels are used to estimate the excretion rates of certain analytes from the respective analyte-to-creatinine ratios. We clarified the influence of age and sex on estimated daily urinary creatinine excretion (eUCrE) based on the urinary creatinine level and daily urine volume. METHODS: All inpatients aged ≥ 18 years who attended the Kochi Medical School Hospital with serum and urinary creatinine measurement results were enrolled. Serum and urinary creatinine concentrations were extracted from the database and fluctuations with sex and age were investigated. The eUCrE was calculated for patients with early morning spot urine protein excretion (UPE), and daily urine volume was measured on the same day. RESULTS: Overall, 643 participants (322 men, 321 women) were enrolled. The eUCrE levels of men and women aged 18 - 64 and 18 - 44 years, respectively, significantly exceeded 1 g/day. Those of women aged 65-74 and ≥ 75 years were significantly lower than 1 g/day. Each age group was further categorised into Groups A (patients with eGFR ≥ 30 mL/min/1.73 m2 and UPE < 0.5 g/gCr), B (eGFR ≥ 30 mL/min/1.73 m2 and UPE ≥ 0.5 g/gCr), and C (eGFR < 30 mL/min/1.73 m2 and UPE ≥ 0.5 g/gCr). The eUCrE levels were the highest in Group A, followed by Groups B and C. CONCLUSION: This study revealed age-, sex-, and renal function-related biases in adjusted values using urinary biomarkers, including proteinuria and creatinine ratio.

Sarcopenia augments the risk of excess weight on COVID-19 hospitalization: A prospective study using the Lifelines COVID-19 cohort.

OBJECTIVE: We investigated the associations of sarcopenia alone, overweight or obesity, and sarcopenic overweight or obesity with COVID-19 hospitalization. METHODS: Participants from the Lifelines COVID-19 cohort who were infected with COVID-19 were included in this study. Sarcopenia was defined as a relative deviation of muscle mass of ≤ -1.0 SD from the sex-specific mean 24-h urinary creatinine excretion. Overweight or obesity was defined as a body mass index ≥ 25 kg/m2. Sarcopenic overweight or obesity was defined as the presence of overweight or obesity and low muscle mass. COVID-19 hospitalization was self-reported. Logistic regression models were used to analyze the associations of sarcopenia alone, overweight or obesity, and sarcopenic overweight or obesity with COVID-19 hospitalization. RESULTS: Of the 3594 participants infected with COVID-19 and recruited in this study, 173 had been admitted to the hospital. Compared with the reference group, individuals with overweight or obesity and sarcopenic overweight or obesity were 1.78-times and 2.09-times more likely to have been hospitalized for COVID-19, respectively, whereas sarcopenia alone did not increase the risk of COVID-19 hospitalization. CONCLUSIONS: In this middle-aged population, sarcopenic overweight or obesity elevated the risk of hospitalization for COVID-19 in those infected with COVID-19 more than overweight or obesity alone. These data support the relevance of sarcopenic overweight or obesity as a risk factor beyond the geriatric setting and should be considered in risk stratification in future public health and vaccination campaigns.

Estimation of 24-hour urinary creatinine excretion from patient variables: A novel approach to identify patients with low muscle mass and malnutrition and relationship to outcomes.

BACKGROUND: Low muscle mass has been correlated with adverse outcomes in patients who are critically ill. Methods to identify low muscularity such as computed tomography scans or bioelectrical impedance analyses are impractical for admission screening. Urinary creatinine excretion (UCE) and creatinine height index (CHI) are associated with muscularity and outcomes but require a 24-h urine collection. The estimation of UCE from patient variables avoids the need for a 24-h urine collection and may be clinically useful. METHODS: Variables of age, height, weight, sex, plasma creatinine, blood urea nitrogen (BUN), glucose, sodium, potassium, chloride, and carbon dioxide from a deidentified data set of 967 patients who had UCE measured were used to develop models to predict UCE. The model identified with the best predictive ability was validated and then retrospectively applied to a separate sample of 120 veterans who were critically ill to examine if UCE and CHI predicted malnutrition or were associated with outcomes. RESULTS: A model was identified that included variables of plasma creatinine, BUN, age, and weight and was found to be highly correlated, moderately predictive of UCE, and statistically significant. Patients with model-estimated CHI ≤ 60% had significantly lower body weight, body mass index, plasma creatinine, and sera albumin and prealbumin levels; were 8.0 times more likely to be diagnosed with malnutrition; and were 2.6 times more likely to be readmitted in 6 months. CONCLUSION: A model that predicts UCE offers a novel method to identify patients with low muscularity and malnutrition on admission without the use of invasive tests.

Handgrip Strength Is Positively Associated with 24-hour Urine Creatine Concentration.

BACKGROUND: Muscle mass evaluation methods are often expensive and therefore limited in their daily use in clinical practice. In this study, we investigated the relationship between hand grip strength (HGS) and other parameters of body measurements with urine creatinine, especially to investigate whether HGS measurement is an indicator of muscle metabolism. METHODS: In total, 310 relatively healthy people (mean age 47.8 + 9.6; 161 people or 51.9% of the total population were men) who were undergoing preventive examinations were included in this study and given a container to collect 24-h urine, and the amount of creatinine in the urine was determined by a kinetic test without deproteinization according to the Jaffe method. A digital dynamometer (Takei Hand Grip Dynamometer, Japan) was used in the measurement of HGS. RESULTS: There was a significant difference in 24-h urine creatinine (24 hCER) between the sexes, with a mean of 1382.9 mg/24 h in men and 960.3 mg/24 h in women. According to the correlation analysis, the amount of urine creatinine was related to age (r = -0.307, p < 0.001 in men, r = -0.309, p < 0.001 in women), and HGS (r = 0.207, p = 0.011 in men, r = 0.273, p = 0.002 in women) was significant for either sex. However, other parameters of body measurements, such as girth, forearm circumference, and muscle mass measured by bioelectrical impedance, were not related to urine 24 hCER. A correlation between HGS and 24 hCER was observed in age groups. CONCLUSIONS: We found that HGS is a potential marker in muscle metabolism assessment that is proven through 24 hCER. In addition, therefore, we suggest using the HGS measure in clinical practice to evaluate muscle function and well-being.

Association between Urinary Creatinine Excretion and Hypothyroidism in Patients with Chronic Kidney Disease.

While hypothyroidism increases serum creatinine (Cr) levels, it is uncertain whether the elevation is mediated via a decline in the glomerular filtration rate (GFR) or the reflection of enhanced Cr production from the muscles or both. In the present study, we explored an association between urinary Cr excretion rate (CER) and hypothyroidism. A total of 553 patients with chronic kidney disease were enrolled in a cross-sectional study. Multiple linear regression analysis was performed to explore the association between hypothyroidism and urinary CER. The mean urinary CER was 1.01 ± 0.38 g/day and 121 patients (22%) had hypothyroidism. The multiple linear regression analysis revealed explanatory variables with urinary CER, including age, sex, body mass index, 24 h Cr clearance (24hrCcr), and albumin while hypothyroidism was not considered an independent explanatory variable. In addition, scatter plot analysis with regression fit line representing the association between estimated GFR calculated using s-Cr (eGFRcre) and 24hrCcr revealed that eGFRcre and 24hrCcr had strong correlations with each other in hypothyroid patients as well as euthyroid patients. Collectively, hypothyroidism was not considered an independent explanatory variable for urinary CER in the present study and eGFRcre is a useful marker to evaluate kidney function regardless of the presence of hypothyroidism.

Health Risk in a Geographic Area of Thailand with Endemic Cadmium Contamination: Focus on Albuminuria.

An increased level of cadmium (Cd) in food crops, especially rice is concerning because rice is a staple food for over half of the world's population. In some regions, rice contributes to more than 50% of the total Cd intake. Low environmental exposure to Cd has been linked to an increase in albumin excretion to 30 mg/g creatinine, termed albuminuria, and a progressive reduction in the estimated glomerular filtration rate (eGFR) to below 60 mL/min/1.73 m2, termed reduced eGFR. However, research into albuminuria in high exposure conditions is limited. Here, we applied benchmark dose (BMD) analysis to the relevant data recorded for the residents of a Cd contamination area and a low-exposure control area. We normalized the excretion rates of Cd (ECd) and albumin (Ealb) to creatinine clearance (Ccr) as ECd/Ccr and Ealb/Ccr to correct for differences among subjects in the number of surviving nephrons. For the first time, we defined the excretion levels of Cd associated with clinically relevant adverse kidney health outcomes. Ealb/Ccr varied directly with ECd/Ccr (ß = 0.239, p < 0.001), and age (ß = 0.203, p < 0.001), while normotension was associated with lower Ealb/Ccr (ß = −0.106, p = 0.009). ECd/Ccr values between 16.5 and 35.5 ng/L of the filtrate were associated with a 10% prevalence of albuminuria, while the ECd/Ccr value of 59 ng/L of the filtrate was associated with a 10% prevalence of reduced eGFR. Thus, increased albumin excretion and eGFR reduction appeared to occur at low body burdens, and they should form toxicity endpoints suitable for the calculation of health risk due to the Cd contamination of food chains.

Dose-Response Analysis of the Tubular and Glomerular Effects of Chronic Exposure to Environmental Cadmium.

We retrospectively analyzed data on the excretion of cadmium (ECd), ß2-microglobulin (Eß2M) and N-acetyl-ß-D-glucosaminidase (ENAG), which were recorded for 734 participants in a study conducted in low- and high-exposure areas of Thailand. Increased Eß2M and ENAG were used to assess tubular integrity, while a reduction in the estimated glomerular filtration rate (eGFR) was a criterion for glomerular dysfunction. ECd, Eß2M and ENAG were normalized to creatinine clearance (Ccr) as ECd/Ccr, Eß2M/Ccr and ENAG/Ccr to correct for interindividual variation in the number of surviving nephrons and to eliminate the variation in the excretion of creatinine (Ecr). For a comparison, these parameters were also normalized to Ecr as ECd/Ecr, Eß2M/Ecr and ENAG/Ecr. According to the covariance analysis, a Cd-dose-dependent reduction in eGFR was statistically significant only when Ecd was normalized to Ccr as ECd/Ccr (F = 11.2, p < 0.001). There was a 23-fold increase in the risk of eGFR ≤ 60 mL/min/1.73 m2 in those with the highest ECd/Ccr range (p = 0.002). In addition, doubling of ECd/Ccr was associated with lower eGFR (ß = -0.300, p < 0.001), and higher ENAG/Ccr (ß = 0.455, p < 0.001) and Eß2M/Ccr (ß = 0.540, p < 0.001). In contrast, a covariance analysis showed a non-statistically significant relationship between ECd/Ecr and eGFR (F = 1.08, p = 0.165), while the risk of low eGFR was increased by 6.9-fold only among those with the highest ECd/Ecr range. Doubling of ECd/Ecr was associated with lower eGFR and higher ENAG/Ecr and Eß2M/Ecr, with the ß coefficients being smaller than in the Ccr-normalized dataset. Thus, normalization of Cd excretion to Ccr unravels the adverse effect of Cd on GFR and provides a more accurate evaluation of the severity of the tubulo-glomerular effect of Cd.

Decreased haemoglobin levels are associated with lower muscle mass and strength in kidney transplant recipients.

BACKGROUND: Post-transplant anaemia and reduced muscle mass and strength are highly prevalent in kidney transplant recipients (KTRs). Decreased haemoglobin levels, a marker of anaemia, could adversely affect muscle mass and strength through multiple mechanisms, among others, through diminished tissue oxygenation. We aimed to investigate the association between haemoglobin levels with muscle mass and strength in KTRs. METHODS: We included stable KTRs from the TransplantLines Biobank and Cohort study with a functional graft ≥1 year post-transplantation. Muscle mass was assessed using 24 h urinary creatinine excretion rate (CER) and bioelectrical impedance analysis (BIA). Muscle strength was assessed with a handgrip strength test using a dynamometer and, in a subgroup (n = 290), with the five-times sit-to-stand (FTSTS) test. We used multivariable linear and logistic regression analyses to investigate the associations of haemoglobin levels with muscle mass and strength. RESULTS: In 871 included KTRs [median age 58 (interquartile range (IQR), 48-66)] years; 60% men; eGFR 51 ± 18 mL/min/1.73 m2 ) who were 3.5 (1.0-10.2) years post-transplantation, the mean serum haemoglobin level was 13.9 ± 1.8 g/dL in men and 12.8 ± 1.5 g/dL in women. Lower haemoglobin levels were independently associated with a lower CER (std. ß = 0.07, P = 0.01), BIA-derived skeletal muscle mass (std. ß = 0.22, P < 0.001), handgrip strength (std. ß = 0.15, P < 0.001), and worse FTSTS test scores (std. ß = -0.17, P = 0.02). KTRs in the lowest age-specific and sex-specific quartile of haemoglobin levels had an increased risk of being in the worst age-specific and sex-specific quartile of CER (fully adjusted OR, 2.09; 95% CI 1.15-3.77; P = 0.02), handgrip strength (fully adjusted OR, 3.30; 95% CI 1.95-5.59; P < 0.001), and FTSTS test score (fully adjusted OR, 7.21; 95% CI 2.59-20.05; P < 0.001). CONCLUSIONS: Low haemoglobin levels are strongly associated with decreased muscle mass and strength in KTRs. Future investigation will need to investigate whether maintaining higher haemoglobin levels may improve muscle mass and strength in KTRs.

Paradoxical mortality of high estimated glomerular filtration rate reversed by 24-h urine creatinine excretion rate adjustment: sarcopenia matters.

BACKGROUND: Muscle wasting may explain the paradoxical mortality of patients with high estimated glomerular filtration rates (eGFRs) derived from equation methods. However, empirical evidence and solutions remain insufficient. METHODS: In this retrospective cohort study, we compared the performance of equation methods for predicting all-cause mortality; we used 24-h creatinine clearance (24-h CrCl), equation-based eGFRs, and a new eGFR estimating equation weighting for population 24-h urine creatinine excretion rate (U-CER). From 2003 to 2018, we identified 4986 patients whose data constituted the first 24-h CrCl measurement data in the Clinical Research Data Repository of China Medical University Hospital and were followed up for at least 5 years after careful exclusion. Three GFR estimation equations [the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Modification of Diet in Renal Disease (MDRD) Study, and Taiwanese MDRD], 24-h CrCl, and 24-h U-CER-adjusted eGFR were used. RESULTS: A high correlation was observed among the eGFR levels derived from the equation methods (0.995-1.000); however, the correlation decreased to 0.895-0.914 when equation methods were compared with the 24-h CrCl or 24-h U-CER-adjusted equation-based eGFR. In the Bland-Altman plots, the average discrepancy between the equation methods and the 24-h CrCl method was close to zero (maximal bias range: 5.12 for the Taiwanese MDRD equation vs. 24-h CrCl), but the range in limit of agreement was wide, from ±43.7 mL/min/1.73 m2 for the CKD-EPI equation to ±54.3 mL/min/1.73 m2 for the Taiwanese MDRD equation. A J-shaped dose-response relationship was observed between all equation-based eGFRs and all-cause mortality. Only 24-h CrCl exhibited a non-linear negative dose-response relationship with all-cause mortality. After adjustment for 24-h U-CER in the statistical model, the paradoxical increase in mortality risk for an eGFR of >90 mL/min/1.73 m2 returned to null. When 24-h U-CER was used directly to correct eGFR, the monotonic non-linear negative relationship with all-cause mortality was almost identical to that of 24-h CrCl. CONCLUSIONS: The 24-h U-CER-adjusted eGFR and 24-h CrCl are viable options for informing mortality risk. The 24-h U-CER adjustment method can be practically implemented to eGFR-based care and effectively mitigate the inherent confounding biases from individual's muscle mass amount due to both sex and racial differences.

Improving the urine spot protein/creatinine ratio by the estimated creatinine excretion to predict proteinuria in pediatric kidney transplant recipients.

BACKGROUND: Since the daily creatinine excretion rate (CER) is directly affected by muscle mass, which varies with age, gender, and body weight, using the spot protein/creatinine ratio (Spot P/Cr) follow-up of proteinuria may not always be accurate. Estimated creatinine excretion rate (eCER) can be calculated from spot urine samples with formulas derived from anthropometric factors. Multiplying Spot P/Cr by eCER gives the estimated protein excretion rate (ePER). We aimed to determine the most applicable equation for predicting daily CER and examine whether ePER values acquired from different equations can anticipate measured 24 h urine protein (m24 h UP) better than Spot P/Cr in pediatric kidney transplant recipients. METHODS: This study enrolled 23 children with kidney transplantation. To estimate m24 h UP, we calculated eCER and ePER values with three formulas adapted to children (Cockcroft-Gault, Ghazali-Barratt, and Hellerstein). To evaluate the accuracy of the methods, Passing-Bablok and Bland-Altman analysis were used. RESULTS: A statistically significant correlation was found between m24 h UP and Spot P/Cr (p < .001, r = 0.850), and the correlation was enhanced by multiplying the Spot P/Cr by the eCER equations. The average bias of the ePER formulas adjusted by the Cockcroft-Gault, Ghazali-Barratt, and Hellerstein equations were -0.067, 0.031, and 0.064 g/day, respectively, whereas the average bias of Spot P/Cr was -0.270 g/day obtained by the Bland-Altman graphics. CONCLUSION: Using equations to estimate eCER may improve the accuracy and reduce the spot urine samples' bias in pediatric kidney transplantation recipients. Further studies in larger populations are needed for ePER reporting to be ready for clinical practice.

Time courses of urinary creatinine excretion, measured creatinine clearance and estimated glomerular filtration rate over 30 days of ICU admission.

PURPOSE: Baseline urinary creatinine excretion (UCE) is associated with ICU outcome, but its time course is not known. MATERIALS AND METHODS: We determined changes in UCE, plasma creatinine, measured creatinine clearance (mCC) and estimated glomerular filtration (eGFR) in patients with an ICU-stay ≥30d without acute kidney injury stage 3. The Cockcroft-Gault, MDRD (modification of diet in renal disease) and CKD-EPI (chronic kidney disease epidemiology collaboration) equations were used. RESULTS: In 248 patients with 5143 UCEs hospital mortality was 24%. Over 30d, UCE absolutely decreased in male survivors and non-survivors and female survivors and nonsurvivors by 0.19, 0.16, 0.10 and 0.05 mmol/d/d (all P < 0.001). Relative decreases in UCE were similar in all four groups: 1.3, 1.4, 1.2 and 0.9%/d respectively. Over 30d, mCC remained unchanged, but eGFR rose by 31% (CKD-EPI) and 73% (MDRD) and creatinine clearance estimated by Cockcroft-Gault by 59% (all P < 0.001). CONCLUSIONS: Over 1 month of ICU stay, UCE declined by ≥1%/d which may correspond to an equivalent decline in muscle mass. These rates of UCE decrease were similar in survivors, non-survivors, males and females underscoring the intransigent nature of this process. In contrast to measured creatinine clearance, estimates of eGFR progressively rose during ICU stay.

Estimation of glomerular filtration rate from skeletal muscle mass. A new equation independent from age, weight, gender, and ethnicity.

BACKGROUND AND AIMS: The most used indicator for the renal function is the glomerular filtration rate (GFR). Current used predictive GFR equations were calibrated on patients with chronic kidney disease. Thus, they are not very precise in healthy individuals. The estimation of skeletal muscle mass (SMM) allows the prediction of the daily urinary creatinine excretion (24hUCrE). This study proposes an equation for the estimation of GFR based on SMM (eGFRMuscle) and serum creatinine (SCr). METHODS AND RESULTS: Four hundred sixty-six free-living men underwent a bioelectrical impedance analysis for the evaluation of SMM (kg), a blood withdrawal for the measurement of SCr (mg/dL), and a 24-h urinary collection for the assessment of 24hUCrE (g/24 h). The linear regression analysis between SMM and 24hUCrE and the measurement of SCr allowed developing a predictive equation of eGFRMuscle. The equation predicting eGFRMuscle (ml/min/1.73 m2) was SMM (kg) × 3.06/SCr (mg/dL). eGFRMuscle was statistically different from eGFR predicted by Cockroft-Gault, MDRD Study, and CKD-EPI equations (p = 0.017, p < 0.001, and p < 0.001, respectively). Pairwise comparison of standard error of the area under the ROC curve (AUC) of eGFRMuscle with all the other AUCs of ROC curves highlighted significant differences. CONCLUSIONS: The equation presented in this study results in age, weight, gender, and ethnicity independent because it arises directly from SMM estimation. Therefore, the proposed equation could allow evaluating the GFR also in healthy people with low, average, or high weight, and in older people, regardless of GFR and SCr levels.

Evaluation of methodologies of urine collection to estimate microbial synthesis in bovines diets containing lipids or not / Avaliação de metodologias de coleta de urina para estimar a síntese microbiana em dietas de bovinos contendo ou não lipídios

This study investigated the effectiveness of the urine sample collection method in predicting the volume urinary and synthesis of microbial nitrogen. Eight fistulated steers were used with accessible rumens and kept in individual stalls. Their diets consisted of corn silage; corn silage + concentrate; corn silage + concentrate with addition of lipids in the form of soybean oil; and corn silage + concentrate with addition of lipids in the form of soybean grains. Estimates of microbial protein synthesis were obtained based on the urinary excretion of purine derivatives. There was no effect of diets on daily creatinine excretion (P>0.05). There were differences (P<0.05) between the urinary volume and microbial synthesis values determined by the total urine collection and those estimated from the urine spot samples and equations proposed by different authors. The estimation of microbial synthesis based on the urine excretion of purine derivatives should be performed from the total collection of the urine for a period of 24 hours.

Este estudo investigou a eficácia do método de coleta de amostras de urina sobre a predição do volume urinário e síntese de nitrogênio microbiano. Oito novilhos fistulados foram utilizados com rúmen acessível e mantidos em baias individuais. Suas dietas consistiram de silagem de milho; silagem de milho + concentrado; silagem de milho + concentrado com adição de lipídios na forma de óleo de soja; e silagem de milho + concentrado com adição de lipídios na forma de grãos de soja. Estimativas de síntese de proteína microbiana foram obtidas com base na excreção urinária de derivados de purina. Não houve efeito de dietas na excreção diária de creatinina (P> 0,05). Houve diferenças (P <0,05) entre o volume urinário e os valores de síntese microbiana determinados pela coleta total de urina e os estimados a partir das amostras de manchas de urina e equações propostas por diferentes autores. A estimativa da síntese microbiana baseada na excreção de urina dos derivados de purina deve ser realizada a partir da coleta total da urina por um período de 24 horas.

Effect of the Creatinine Excretion Rate Index, a Marker of Sarcopenia, on Prediction of Intracranial Hemorrhage in Patients With Advanced Heart Failure and a Continuous-Flow Left Ventricular Assist Device.

BACKGROUND: Sarcopenia is characterized by progressive loss of skeletal muscle and has frequently been associated with poor clinical outcomes in patients with advanced heart failure (HF). The urinary creatinine excretion rate (CER) index is an easily measured marker of muscle mass, but its predictive capacity for mortality and cerebrovascular events has not been investigated in patients with a continuous-flow implantable left ventricular assist device (CF-iLVAD).Methods and Results:We retrospectively reviewed 147 patients (mean [±SD] age 43.7±12.5 years, 106 male) who underwent CF-iLVAD implantation between April 2011 and June 2019. CER indices in 24-h urine samples before CF-iLVAD implantation were determined. Over a median follow-up of 2.3 years, there were 10 (6.8%) deaths and 43 (29.3%) cerebrovascular events. Patients were divided into 2 groups (low and high CER index) according to the median CER index in men and women (i.e., 13.71 and 12.06 mg·kg-1·day-1, respectively). Mortality and intracranial hemorrhage rates after CF-iLVAD implantation were significantly higher in the low than high CER index group (mortality 12.3% vs. 1.4% [P<0.01]; intracranial hemorrhage 23.3% vs. 8.1% [P=0.01]). Multivariate Cox proportional hazard models revealed that a low CER index was an independent predictor of intracranial hemorrhage in patients receiving a CF-iLVAD (hazard ratio 3.63; 95% confidence interval 1.43-9.24; P<0.01). CONCLUSIONS: A low preoperative CER index is an independent, non-invasive predictor of intracranial hemorrhage after CF-iLVAD implantation.

A Comparison of the Nephrotoxicity of Low Doses of Cadmium and Lead.

Environmental exposure to moderate-to-high levels of cadmium (Cd) and lead (Pb) is associated with nephrotoxicity. In comparison, the health impacts of chronic low-level exposure to Cd and Pb remain controversial. The aim of this study was to therefore evaluate kidney dysfunction associated with chronic low-level exposure to Cd and Pb in a population of residents in Bangkok, Thailand. The mean age and the estimated glomerular filtration rate (eGFR) for 392 participants (195 men and 197 women) were 34.9 years and 104 mL/min/1.73 m2, respectively, while the geometric mean concentrations of urinary Cd and Pb were 0.25 µg/L (0.45 µg/g of creatinine) and 0.89 µg/L (1.52 µg/g of creatinine), respectively. In a multivariable regression analysis, the eGFR varied inversely with blood urea nitrogen in both men (ß = -0.125, p = 0.044) and women (ß = -0.170, p = 0.008), while inverse associations of the eGFR with urinary Cd (ß = -0.132, p = 0.043) and urinary Pb (ß = -0.130, p = 0.044) were seen only in women. An increased urinary level of Cd to the median level of 0.38 µg/L (0.44 µg/g of creatinine) was associated with a decrease in the eGFR by 4.94 mL/min/1.73 m2 (p = 0.011). The prevalence odds of a reduced eGFR rose 2.5-, 2.9- and 2.3-fold in the urinary Cd quartile 3 (p = 0.013), the urinary Cd quartile 4 (p = 0.008), and the urinary Pb quartile 4 (p = 0.039), respectively. This study suggests that chronic exposure to low-level Cd is associated with a decline in kidney function and that women may be more susceptible than men to nephrotoxicity due to an elevated intake of Cd and Pb.

Muscle mass determined from urinary creatinine excretion rate, and muscle performance in renal transplant recipients.

BACKGROUND: Muscle mass, as determined from 24-h urinary creatinine excretion rate (CER), is an independent predictor for mortality and graft failure in renal transplant recipients (RTR). It is currently unknown whether CER is comparable with healthy controls after transplantation and whether it reflects muscle performance besides muscle mass. We aimed to compare urinary CER and muscle performance between RTR and healthy controls and to investigate whether urinary CER is associated with muscle performance in RTR. METHODS: We included RTR, transplanted between 1975 and 2016 in the University Medical Center Groningen. Healthy controls were subjects screened for kidney donation. CER was calculated from a 24-h urine collection. Muscle performance was assessed by handgrip strength, sit-to-stand test, and 2-min walk test. Statistical analyses were performed using linear regression analyses. RESULTS: We included 184 RTR (mean age 56.9 ± 11.9 years, 54% male recipient) and 78 healthy controls (age 57.9 ± 9.9, 47% male recipient). RTR were at a median time of 4.0 (1.1-8.8) years after transplantation. Mean CER was lower in RTR compared to healthy controls (11.7 ± 4.0 vs. 13.1 ± 5.2 mmol/24 h; P = 0.04). Significantly poorer results in muscle performance were found in RTR compared to controls for the handgrip strength (30.5 [23.7-41.1] N vs. 38.3 [29.3-46.0] N, P < 0.001) and the 2-min walk test (151.5 ± 49.2 m vs. 172.3 ± 12.2 m, P < 0.001) but not for the sit-to-stand (12.2 ± 3.3 m vs. 11.9 ± 2.8 m, P = 0.46). In RTR, CER was significantly associated with handgrip strength (std. ß 0.33; P < 0.001), independent of adjustment for potential confounders. In RTR, CER was neither associated with the time used for the sit-to-stand test (std. ß -0.09; P = 0.27) nor with the distance covered during the 2-min walk test (std. ß 0.07; P = 0.40). CONCLUSIONS: Muscle mass as measured by CER in RTR is lower compared to controls. CER is positively associated with muscle performance in RTR. The results demonstrate that CER does not only reflect muscle mass but also muscle performance in this patient setting. Determination of CER could be an interesting addition to the imaging technique armamentarium available and applied for evaluation of muscle mass in clinical intervention studies and observational studies.

Factors affecting urinary creatinine in heifers and cows.

A series of total urine collections were conducted to evaluate the effects of age, diet, gestation, and body condition score (BCS) on urinary creatinine (UC) and purine derivative (PD) excretion in heifers and cows. For each collection, urine was collected over a 5-d period and composited by animal within day. Daily samples were analyzed for UC and PD concentration and averaged over the 5-d period. All animals were fed in individual stanchions at 2.0% of body weight (BW). To evaluate the relationship between age and UC excretion, 21 animals ranging from 5 to 80 months of age were fed a forage-based diet supplemented with dried distillers grains (DDG). Creatinine excretion (mg/kg BW) was not correlated with age (P = 0.37). To determine if diet alters UC, 11 heifers were sampled for two urine collection periods. In period 1, heifers were fed a forage-based diet supplemented with DDG. In period 2, heifers were fed a finishing diet (90% concentrate, 10% forage). Creatinine excretion (mg/kg BW) and PD:creatinine (PD:C) was greater (P = 0.01) for heifers when fed the forage-based diet than when fed the concentrate-based diet. Eleven cows fed a forage-based diet supplemented with DDG were sampled to determine the effect of gestation on urinary metabolites. Gestation did not affect UC (P = 0.42) or PD:C (P = 0.30). To evaluate the relationship between 12th rib fat thickness and metabolite excretion, 40 heifers were fed a common finishing diet. There was no relationship between UC (mg/kg BW; P = 0.28) or PD:UC (P = 0.47) and 12th rib fat thickness. To evaluate the relationship between BCS and UC, 11 cows were fed a forage diet supplemented with DDG. There was no relationship between BCS and UC (mg/kg BW; P = 0.99) or PD:C (P = 0.84). To evaluate daily and diurnal variation in UC, nine heifers were fed a forage diet supplemented with DDG. Seven of the heifers were fed a finishing diet (90% concentrate, 10% forage) in a second period. Urine was collected every 2 h from 0600 to 1800 hours. When expressed as mg/kg BW, UC excretion was not different across animals fed the forage-based (P = 0.40) or concentrate-based diet (P = 0.18). Stepwise regression indicated that at least 3 d of collection were required to estimate UC. Time within day and day within period effects were observed (P < 0.01) for UC from 2-h interval samples. The UC varies with type of diet and diurnal variation is present. Variation among animals is relatively small.