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.

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.

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.

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.

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.

Validation of daily urinary creatinine excretion measurement by muscle-creatinine equivalence.

BACKGROUND: Twenty-four-hour urinary creatinine excretion (24hUCrE) is strongly correlated with skeletal muscle mass (SMM). This study suggests how to exploit the power of the SMM-24hUCrE correlation to assess the accuracy of 24hUCrE measurement. METHODS: Four hundred and sixty-six men, a subgroup of participants in the 2002-2004 follow-up examination of the Olivetti Heart Study, performed a 24-h urine collection to measure 24hUCrE and underwent bioelectrical impedance analysis to evaluate SMM. Linear regression analysis between 24hUCrE and SMM was used to calculate the muscle-creatinine equivalence and to develop an equation to predict the 24hUCrE depending on SMM. The accuracy of the 24hUCrE measurement was assessed using the change in the SMM-24hUCrE correlation coefficient upon variation in the percentage deviation (%D) between the measured and predicted 24hUCrE. RESULTS: The calculated muscle-creatinine equivalence was 1 g of 24hUCrE = 22.73 kg of SMM. The %Ds and the corresponding SMM-24hUCrE correlation coefficients were as follows: %D = 3.0, r = .997; %D = 4.7, r = .989; %D = 8.1, r = .963; %D = 10.5, r = .940; %D = 12.6, r = .909; %D = 18.9, r = .825; %D = 25.8, r = .707; %D = 33.5, r = .595; %D = 41.4, r = .453. CONCLUSION: The increase in %D corresponds to a reduced correlation between muscle mass and creatinine excretion, which indicated a poor performance in the measurement of the 24hUCrE. For studies on single individuals, where small variations in 24hUCrE could be significant, a %D up to 12.6% is suggested; on the other hand, a wider %D interval could be acceptable for population studies.

Estimation of Urinary Creatinine Excretion and Prediction of Renal Function in Morbidly Obese Patients: New Tools from Body Composition Analysis.

BACKGROUND/AIMS: In obese subjects the accuracy of prediction of renal function is quite low. The aim of this study was to obtain a more accurate estimate of urinary creatinine excretion (UCr), creatinine clearance (CCr), and GFR from body cell mass (BCM). METHODS: Seventy-three adult morbidly obese patients (BMI 35.2-64.5 kg/m2) were examined. BCM was calculated from body impedance analysis. CCr was measured (mCCr) and was predicted from BCM and antropometric data (MR-BCMCCr), with Cockcroft and Gault (C&GCCr) and Salazar and Corcoran (S&CCCr) formulas. GFR was predicted from BCM (BCM GFR) and with MDRD and CKD-EPI formulas. RESULTS: Multiple regression (MR) indicated a strict linear correlation between UCr, BCM and anthropometric data. UCr predicted from MR equation (MR-BCMUCr) was very similar to measured UCr. MR-BCMCCr (168±46 mL/min) and mCCr (167±51 mL/min) were also similar, while significant differences were found between mCCr, C&GCCr and S&CCCr. The correlation and the agreement between MR-BCMCCr and mCCr were closer and prediction error was lower than the other formulas. BCM GFR (125±32 mL/min) had close correlations and agreements with MDRD GFR and CKD EPI formulas. CONCLUSIONS: In morbidly obese patients the measurement of BCM meliorates the prediction of UCr and CCr, and allows the prediction of GFR.

Spot urine protein to creatinine ratio.

In a recent article in Pediatric Nephrology, EM Yang and colleagues (Pediatr Nephrol 2017: doi: 10.1007/s00467-016-3587-6 ) published a retrospective cross-sectional study involving a cohort of 442 children with an mean estimated glomerular filtration rate of >60 mL/min/1.73 m2. The authors measured 24-h urine protein excretion (24-h UProt) alongside the morning spot urine protein to creatinine ratio (Prot/Cr) in this group of patients. While the Prot/Cr may be the only feasible way to routinely estimate the daily protein excretion of a young child, inter-individual variability in childrens' urinary creatinine excretion (UCr) may heavily influence the result. The authors sought to determine which equation was the most accurate in predicting UCr. Not only did they discover that the adult Cockcroft-Gault equation worked best, they also found that multiplying the Prot/Cr by the estimated UCr significantly improved the accuracy of the 24-h UProt estimate. In this editorial we discuss both the strengths and limitations of the study by EM Yang and colleagues. We also highlight the importance of adhering to internationally agreed upon reporting guidelines such as the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) statement.

Clinical utility of spot urine protein-to-creatinine ratio modified by estimated daily creatinine excretion in children.

BACKGROUND: The spot urine protein-to-creatinine ratio (UPCR) is widely used to predict 24-h urine protein (24-h UP) excretion. In patients with low daily urine creatinine excretion (UCr), however, the UPCR may overestimate 24-h UP. The aim of this study was to predict 24-h UP using UPCR adjusted by estimated 24-h UCr in children. METHODS: This study included 442 children whose 24-h UP and spot UPCR were measured concomitantly. Estimated 24-h UCr was calculated using three previously existing equations. We estimated the 24-h UP excretion from UPCR by multiplying the estimated UCr. The results were compared with the measured 24-h UP. RESULTS: There was a strong correlation between UPCR and 24-h UP (r = 0.801, P < 0.001), and the correlation improved after multiplying the UPCR by the measured UCr (r = 0.847, P < 0.001). Using the estimated UCr rather than the measured UCr, there was high accuracy and strong correlation between the estimated UPCR weighted by the Cockcroft-Gault equation and 24-h UP. Improvement was also observed in the subgroup (proteinuria vs. non-proteinuria) analysis, particularly in the proteinuria group. CONCLUSIONS: The spot UPCR multiplied by the estimated UCr improved the accuracy of prediction of the 24-h UP in children.

Urinary creatinine excretion, measured glomerular filtration rate and CKD outcomes.

BACKGROUND: Muscle wasting predicts mortality in patients with end-stage renal disease (ESRD), but its role in the progression of chronic kidney disease (CKD) is uncertain. We studied CKD outcomes associated with low muscle mass, assessed by urinary creatinine excretion (UCr). METHODS: The NephroTest cohort included 1429 patients with CKD stages 1-4 and both measured glomerular filtration rate (mGFR) (by (51)Cr-EDTA) and estimated glomerular filtration rate (eGFR) (by CKD-Epidemiology Collaboration equation). We used cause-specific Cox models to estimate hazard ratios (HRs) for the competing risks of ESRD and death associated with gender-specific UCr quartiles. RESULTS: UCr was 13.6 ± 3.2 mmol/24 h (0.17 ± 0.05 mmol/kg/24 h) in men and 9.2 ± 2.1 (0.14 ± 0.05) in women. It was positively associated with mGFR, but not with eGFR. Over a median follow-up of 3.6 (2.1-5.8) years, 229 patients developed ESRD and 113 patients died before ESRD. Compared with patients in the highest UCr quartile, those in the lowest quartile had a higher crude HR (95% confidence interval) for pre-ESRD death: 4.3 (2.4-7.7), which was weakened, but remained statistically significant, independent of demographics, mGFR and several other factors: 2.1 (1.04-4.3). Their crude ESRD risk was not higher: HR: 0.95 (0.65-1.4), and even tended to be lower after adjusting for mGFR and log-proteinuria: HR: 0.70 (0.45-1.1). Adjustment for eGFR instead of mGFR reversed this relationship: HR: 1.7 (1.1-2.7). CONCLUSIONS: In early stage CKD, low UCr is associated with higher risk for mortality, but not for ESRD. Using creatinine-based equation to adjust for GFR may bias the relationship of UCr with ESRD risk.

Estimated albumin excretion rate versus urine albumin-creatinine ratio for the assessment of albuminuria: a diagnostic test study from the Prevention of Renal and Vascular Endstage Disease (PREVEND) Study.

BACKGROUND: Albumin-creatinine ratio (ACR) in spot urine samples is recommended for albuminuria screening instead of measured albumin excretion rate (mAER) in 24-hour urine collections. In patients with extremes of muscle mass, differences in spot urine creatinine values may lead to under- or overestimation of mAER by ACR. We hypothesized that calculating estimated AER (eAER) using spot ACR and estimated creatinine excretion rate (eCER) may improve albuminuria assessment. STUDY DESIGN: Diagnostic test study. SETTING & PARTICIPANTS: 2,711 community-living individuals from the general population of the Netherlands participating in the PREVEND (Prevention of Renal and Vascular Endstage Disease) Study. INDEX TEST: eAER was computed as the product of ACR and eCER. eCER was computed using 3 previously validated methods (Ix, Ellam, and Walser). REFERENCE TEST: mAER, based on two 24-hour urine collections. Accuracy of the eAER and ACR were defined as the percentage of participants falling within 30% (P30) of mAER. RESULTS: Mean age was 49 years, 46% were men, mean estimated glomerular filtration rate was 84 ± 15 mL/min/1.73 m(2), and median mAER was 7.2 (IQR, 5.4-11.0) mg/d. Mean measured CER was 1,381 mg/d, and median ACR was 4.9 mg/g. Using the Ix equation, median eAER was 6.4 mg/d. In the full cohort, eAER was more accurate and less biased compared to ACR (P30, 48.9% vs 33.6%; bias, -34.2% vs -14.1%, respectively). In subgroup analysis, improvement was most notable in the middle and highest weight tertiles and in men. Using the other methods for eCER produced similar results. LIMITATIONS: Little ethnic heterogeneity and a generally healthy cohort make extension of findings to other races and the chronically ill uncertain. CONCLUSIONS: In a large community-dwelling cohort, eAER was more accurate than ACR in assessing albuminuria.

Estimated albumin excretion rate versus urine albumin-creatinine ratio for the estimation of measured albumin excretion rate: derivation and validation of an estimated albumin excretion rate equation.

BACKGROUND: Glomerular filtration rate estimation equations use demographic variables to account for predicted differences in creatinine generation rate. In contrast, assessment of albuminuria from urine albumin-creatinine ratio (ACR) does not account for these demographic variables, potentially distorting albuminuria prevalence estimates and clinical decision making. STUDY DESIGN: Polynomial regression was used to derive an age-, sex-, and race-based equation for estimation of urine creatinine excretion rate, suitable for use in automated estimated albumin excretion rate (eAER) reporting. SETTING & PARTICIPANTS: The MDRD (Modification of Diet in Renal Disease) Study cohort (N=1,693) was used for equation derivation. Validation populations were the CRIC (Chronic Renal Insufficiency Cohort; N=3,645) and the DCCT (Diabetes Control and Complications Trial; N=1,179). INDEX TEST: eAER, calculated by multiplying ACR by estimated creatinine excretion rate, and ACR. REFERENCE TEST: Measured albumin excretion rate (mAER) from timed 24-hour urine collection. RESULTS: eAER estimated mAER more accurately than ACR; the percentages of CRIC participants with eAER within 15% and 30% of mAER were 33% and 60%, respectively, versus 24% and 39% for ACR. Equivalent proportions in DCCT were 52% and 86% versus 15% and 38%. The median bias of ACR was -20.1% and -37.5% in CRIC and DCCT, respectively, whereas that of eAER was +3.8% and -9.7%. Performance of eAER also was more consistent across age and sex categories than ACR. LIMITATIONS: Single timed urine specimens used for mAER, ACR, and eAER. CONCLUSIONS: Automated eAER reporting potentially is a useful approach to improve the accuracy and consistency of clinical albuminuria assessment.

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.

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.

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.

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.

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.

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.

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.