24-h Creatinine Excretion Research Articles

Monitoring glucose levels in urine using FTIR spectroscopy combined with univariate and multivariate statistical methods

The development of novel platforms for non-invasive continuous glucose monitoring applied in the screening and monitoring of diabetes is crucial to improve diabetes surveillance systems. Attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy of urine can be an alternative as a sustainable, label-free, fast, non-invasive, and highly sensitive analysis to detect changes in urine promoted by diabetes and insulin treatment. In this study, we used ATR-FTIR to evaluate the urinary components of non-diabetic (ND), diabetic (D), and diabetic insulin-treated (D + I) rats. As expected, insulin treatment was capable to revert changes in glycemia, 24-h urine collection volume, urine creatinine, urea, and glucose excretion promoted by diabetes. Several differences in the urine spectra of ND, D, and D + I were observed, with urea, creatinine, and glucose analytes being related to these changes. Principal components analysis (PCA) scores plots allowed for the discrimination of ND and D + I from D with an accuracy of ∼ 99 %. The PCA loadings associated with PC1 confirmed the importance of urea and glucose vibrational modes for this discrimination. Univariate analysis of second derivative spectra showed a high correlation (r: 0.865, p < 0.0001) between the height of 1074 cm-1 vibrational mode with urinary glucose concentration. In order to estimate the amount of glucose present in the infrared spectra from urine, multivariate curve resolution-alternating least square (MCR-ALS) was applied and a higher predicted concentration of glucose in the urine was observed with a correlation of 78.9 % compared to urinary glucose concentration assessed using enzyme assays. In summary, ATR-FTIR combined with univariate and multivariate chemometric analyses provides an innovative, non-invasive, and sustainable approach to diabetes surveillance.

The effects of synbiotic supplementation on enteral feeding tolerance, protein homeostasis, and muscle wasting of critically ill adult patients: a randomized controlled trial

BackgroundEnteral feeding intolerance, energy-protein malnutrition, and muscle wasting are common conditions in the critical care setting. The primary aim of this study was to investigate the effect of synbiotic supplementation on enteral feed volume, energy and protein homeostasis, and muscle mass maintenance in critically ill adult patients.MethodsA consecutive of 42 patients admitted to the Edalatian Medical ICU, requiring enteral nutrition (EN), were prospectively randomized to receive the synbiotic capsule (containing a combination of Lactobacillus, Bifidobacterium, Streptococcus, and fructooligosaccharides) or placebo (21 patients in each group) for a maximum of 14 days. Enteral intolerance and energy homeostasis were evaluated on a daily basis. Nitrogen balance and 24-h urine creatinine excretion were recorded on days 1 and 14. Mid-arm circumference was recorded every 3 days.ResultsMean EN volume, energy, and protein intake per day were 962.5 ± 533.82 ml, 770 ± 427.05 kcal, and 38.5 ± 21.35 g (fourth day) vs. 590 ± 321.1 ml, 472 ± 256.81 kcal, and 23.6 ± 12.84 g (first day) in the synbiotic group (p < 0.05). Changes in the placebo group were not statistically significant. On day 1, nitrogen balance (NB) was − 19.84 ± 8.03 in the synbiotic vs. − 10.99 ± 9.12 in the placebo group (p = 0.003). On day 14, NB was − 14.18 ± 13.05 in the synbiotic and − 9.59 ± 7.71 in the placebo group (p = 0.41). Mid-arm circumference (MAC), 24-h urine creatinine, and creatinine-height index were almost steady in the synbiotic group, while they decreased in the placebo group.ConclusionOverall, it can be concluded that enteral nutrition supplemented with synbiotics has no statistically significant effect on energy and protein homeostasis and muscle mass maintenance of critically ill patients on day 14, but it can increase enteral feed volume and energy and protein intake during the first 4 days of ICU admission.Trial registrationThe trial protocol has been approved in Iranian Registry of Clinical Trials on March 17, 2019. The registration reference is IRCT20190227042857N1.

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

BackgroundMuscle 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.MethodsIn 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.ResultsA 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.ConclusionsThe 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.

Iodine intake in healthy Japanese aged from 6 to 70 years residing in the same district

Iodine is an essential component of thyroid hormones and a dietary micronutrient for humans, and adequate iodine intake is necessary to maintain thyroid function. A population's iodine intake and nutritional status are assessed based on urinary iodine excretion. There are few studies on iodine nutritional status for all age groups residing in the same area in Japan. Between 2010 and 2017, a total of 769 healthy subjects aged 6.4-73 years in three sites in Yokohama City, were enrolled in the survey. The urinary iodine concentration (UIC), iodine to creatinine (Cr) ratio (UI/Cr) and estimated 24-h urinary iodine excretion (UIE) in single spot urine samples were measured, and habitual dietary iodine intake was assessed by food frequency questionnaires. The estimated 24-h UIE was calculated using individual predicted 24-h creatinine excretion by the validated equations developed for healthy Japanese children and adults which vary by age, gender and anthropometry. The median UIC for all participants was 219 μg/L, suggesting adequate iodine intake for this population. There was an increasing trend in median UI/Cr and estimated 24-h UIE by age. A significant correlation between UIC and UI/Cr (r = 0.6378), UIC and estimated 24-h UIE (r = 0.6804), and UI/Cr and estimated 24-h UIE (r = 0.5756) were observed. These estimates can be feasible, convenient and alternative methods to 24-h urine collection in order to assess iodine status in some populations such as ethnically or racially homogeneous and well-nourished people. Additional studies are required to validate these findings.

Iodine Status of Canadian Children, Adolescents, and Women of Childbearing Age

BackgroundAdequate iodine intake is important for children and women of childbearing age because iodine is vital for fetal brain development and early life. ObjectiveIodine status of children (n = 1875), adolescents (n = 557), and women of childbearing age (n = 567) was assessed using urinary iodine concentrations (UIC) from duplicate spot samples collected in the Canadian Health Measures Survey, cycle 5 (2016–2017). MethodsDaily iodine intakes were estimated from urinary iodine and creatinine concentrations using a formula based on iodine absorption and predicted 24-h creatinine excretion. Usual UIC and iodine intakes, adjusted for within-person variation, were estimated using the National Cancer Institute method. Iodine status was assessed by 1) comparing median UIC with WHO/UNICEF/ICCIDD reference ranges and 2) estimating the prevalence of inadequate and excessive intakes using the estimated average requirement (EAR) and tolerable upper intake level (UL) cut-point method, respectively. ResultsMedian UIC for males and females 6–11 or 12–19 y old were ≥100 μg/L, the lower cutoff for adequate intakes. For women 20–39 y old, the median UIC of an unadjusted sample was 81 μg/L (95% CI: 67, 95) and for the usual UIC was 108 μg/L (95% CI: 84, 131). The percentage of children 3 y old with iodine intake ≥EAR was 82% (95% CI: 75, 89). The corresponding estimates for males 4–8, 9–13, and 14–18 y old were 93% (95% CI: 88, 97), 91% (95% CI: 87, 96), and 84% (95% CI: 76, 91), respectively. Estimates for females 4–8, 9–13, 14–18, and 19–39 y old were 86% (95% CI: 83, 89), 87% (95% CI: 80, 95), 68% (95% CI: 55, 80), and 68% (95% CI: 59, 76), respectively. For all sex–age groups, 91–100% had iodine intakes ≤UL. ConclusionsIodine intakes may be insufficient for some women of childbearing age. Public health policies and programs should continue to recommend that all women who could become pregnant, or women who are pregnant or breastfeeding, take a daily multivitamin–mineral supplement containing iodine.

Estimating urine volume from the urine creatinine concentration.

Spot determinations of the urine creatinine concentration are widely used as a substitute for 24-h urine collections. Expressed as the amount excreted per gram of creatinine, urine concentrations in a single-voided sample are often used to estimate 24-h excretion rates of protein, sodium, potassium, calcium, magnesium, urea and uric acid. These estimates are predicated on the assumption that daily creatinine excretion equals 1 g (and that a urine creatinine concentration of 100mg/dL reflects a 1 L 24-h urine volume). Such estimates are invalid if the serum creatinine concentration is rising or falling. In addition, because creatinine excretion is determined by muscle mass, the assumption that 24-h urine creatinine excretion equals 1 g yields a misleading estimate at the extremes of age and body size. In this review, we evaluate seven equations for the accuracy of their estimates of urine volume based on urine creatinine concentrations in actual and idealized patients. None of the equations works well in patients who are morbidly obese or in patients with markedly decreased muscle mass. In other patients, estimates based on a reformulation of the Cockroft-Gault equation are reasonably accurate. A recent study based on this relationship found a high strength of correlation between estimated and measured urine output with chronic kidney disease (CKD) studied in the African American Study of Kidney Disease (AASK) trial and for the patients studied in the CKD Optimal Management with Binders and NictomidE (COMBINE) trial. However, the equation systematically underestimated urine output in the AASK trial. Hence, an intercept was added to account for the bias in the estimated output. A more rigorous equation derived from an ambulatory Swiss population, which includes body mass index and models the non-linear accelerated decline in creatinine excretion with age, could potentially be more accurate in overweight and elderly patients. In addition to extremes of body weight and muscle mass, decreased dietary intake or reduced hepatic synthesis of creatine, a precursor of creatinine or ingestion of creatine supplements will also result in inaccurate estimates. These limitations must be appreciated to rationally use predictive equations to estimate urine volume. If the baseline urine creatinine concentration is determined in a sample of known volume, subsequent urine creatinine concentrations will reveal actual urine output as well as the change in urine output. Given the constraints of the various estimating equations, a single baseline timed collection may be a more useful strategy for monitoring urine volume than entering anthropomorphic data into a calculator.

Low Creatininuria due to Hyponatremia Is Reversible in Many Patients

Background: Chronic hyponatremia has been reported to be associated with low solute intake and low creatinine excretion (reflecting likely sarcopenia). We wanted to study the effect, on the long term, of correction of hyponatremia on solute and creatinine excretion in chronic SIADH. Methods: We made a retrospective review of clinical and biochemical data of patients with euvolemic hyponatremia. We analyzed 24-h urine solute and creatinine excretion in volunteers with hyponatremia induced by dDAVP over 4 days, in 12 patients with chronic SIADH (>1 month) before and after a few days of SNa correction and in 12 patients (6 women and 6 men) before and after 3 months of SNa correction by a vaptan or urea. Results: We confirm a low urine creatinine and solute excretion only in patients with chronic hyponatremia (>1 month). Correction of SNa (from 127 ± 2.3 mEq/L to 139 ± 2.8 mEq/L) for >3 months, in the 12 patients (mean age 58 ± 18), was associated with an increase in 24-h creatinine excretion (from 986 ± 239 to 1,238 ± 220 mg; p < 0.02) and in patients treated with a vaptan (n = 5) solute excretion increased from 656 ± 207 mmol/24 h to 960 ± 193 mmol/24 h (p < 0.02). Sodium excretion increased also in the 12 patients (from 100 ± 53 mEq/24 h to 169 ± 38 mEq/24 h; p < 0.01). Conclusion: Chronic hyponatremia (>1 month) is associated with a decrease in solute output (or intake) and in creatinine excretion. In many patients, these abnormalities are reversible in the long term.

ACCURATE ESTIMATION OF INDIVIDUAL SODIUM INTAKE WITH REPEATED SPOT URINE SAMPLING

Objective: In clinical practice, individual sodium (Na+) intake is estimated by measuring Na+ excretion in one 24-h urine collection (UC), whereas long-term Na+ balance studies indicate that 7 consecutive 24-h UCs may be needed. In this study, we investigate whether the use of repeated spot UCs is an appropriate alternative for multiple 24-h UCs to estimate Na+ intake. Design and method: We performed a post-hoc analysis of a metabolic ward study in 8 healthy male adults who consumed a 7-d diet with a fixed amount of 200 mmol/d Na+. Urine was collected in 4 daily intervals (7–13 h, 13–19 h, 19–23 h and 23–7 h). After reaching steady state, we estimated Na+ intake by single and repeated 24-h UCs and repeated spot UCs, using the Kawasaki formula with measured 24-h urine creatinine excretion. Results: At day 5, mean 24-h Na+ excretion matched intake, indicating that steady state was achieved (Fig 1A). Mean absolute differences (δ) between measured Na+ intake and 3-d spot UC estimates were 18.8 (SD 14.6), 32.3 (SD 18.7), 74.6 (SD 30.0) and 28.2 (SD 19.8) mmol for interval 7–13 h, 13–19 h, 19–23 h and 23–7 h, respectively (Fig 1B). With the exception of samples collected between 19–23 h, Na+ intake estimates by 3-d spot UCs did not significantly differ from Na+ intake estimates by single (δ 29.8 mmol; SD 23.9) and three 24-h UCs (δ 22.9 mmol; SD 11.4). Figure 1. (A) Mean 24-h Na+ excretion during 7-d diet. (B) Comparison of the performance of three consecutive spot UCs (blue), single 24-h UC (green) and three consecutive 24-h UCs (red) for estimating Na+ intake (200 mmol/d). Absolute differences (δ) between estimated and measured Na+ intake. Data are mean and SD. Conclusions: In this 7-d Na+ balance study, repeated spot UCs performed similar to a single and repeated 24-h UCs in estimating Na+ intake. Adequately powered studies need to confirm whether repeated spot UCs are an accurate and low burden alternative to 24-h UCs.

Prevalence of sarcopenic obesity and sarcopenic overweight in the general population: The lifelines cohort study

Sarcopenic obesity (SO) is defined by a relatively low muscle mass in combination with obesity. Sarcopenic obesity was first noted as a health risk in geriatric populations but has recently been recognized as a scientific and clinical priority that may extend beyond geriatric settings. Obesity is generally preceded by overweight, so the prevalence and health risks of sarcopenia in those with overweight (SOW) is of interest for preventive purposes. The aim of this study, therefore, was to assess the prevalence and determinants of SO and SOW in a general population. Participants (n=119,494), aged 18-90 years were included from the Dutch Lifelines cohort study. Muscle mass was assessed by 24-h urine creatinine excretion and stratified for gender for analysis, and obesity was defined as a Body Mass Index (BMI) ≥30kg/m2 and overweight ≥25kg/m2. Multivariate logistic regression models were applied to assess the relevant determinants of SO and SOW. Respectively for men and women the prevalence of SO was 0.9% and 1.4%, and prevalence of SOW 6.5% and 6.0%. In subjects with sarcopenia, BMI was ≥25kg/m2 in 45.5% and ≥30kg/m2 in 6.1%. Overall females had a higher prevalence of SOW and SO in all age groups except for SOW in males between ages 40-59. Also, age was a significant determinant of SO and SOW, with a rise in prevalence as of age 50. Of all subjects with SO and SOW, respectively 82.5% and 80.4% were below the age of 70. Compared to those with no morbidities, the odds ratio of SO and SOW among participants with >3 comorbidities was 2.71 (95% CI: 1.62-4.54) and 1.33 (95% CI: 1.07-1.65) among males and 1.14 (95% CI: 0.79-1.65) and 1.28 (95% CI: 1.06-1.54) among females, independent of other determinants. Overall, an inverse association was found between SOW and SO and physical activity and macronutrient intake. The results support the need for more awareness of SO beyond the field of geriatrics, in particular in subjects with comorbidities. SOW is more prevalent than SO and may provide opportunities for preventive strategies for the general population.

Relationship between age-related decreases in serum 25-hydroxyvitamin D levels and skeletal muscle mass in Japanese women.

A clearer understanding of skeletal muscle mass (SMM) in middle-aged and elderly individuals is important for maintaining functionality. In the present study, age-related changes in SMM, the threshold of SMM with walking difficulty, intestinal nutrient absorption rate, and various serum factors were examined in Japanese populations of different ages. We used 24-h creatinine excretion as a measure of total body SMM. Age-related decreases in SMM, intestinal nutrient absorption rates, and serum 25-hydroxyvitamin D [25(OH)D] concentrations were significantly higher in women than in men. The cut-off values for SMM (kg), its percentage of total body weight (BW), the SMM index [SMMI] (Kg / m2), and creatinine height index (CHI) (%) in elderly individuals with walking difficulty were approximately 8-10 kg, 17-20% of BW, 3.9-4.6 kg / m2, and 44%, respectively. Serum 25(OH)D concentrations were closely associated with SMM (kg, % of BW, kg / m2) and CHI (%) as well as the intestinal absorption rates of nitrogen (%) and phosphorus (%) in women, but not in men. The present results demonstrate that vitamin D is an important metabolic factor in skeletal muscle, and contributes to the optimal management of skeletal muscle and the prevention of sarcopenia. J. Med. Invest. 67 : 151-157, February, 2020.

Impact of Daily Antiperspirant Use on the Systemic Aluminum Exposure: An Experimental Intervention Study

Background and Objectives: Adverse health effects such as neurotoxic and carcinogenic effects through aluminum from cosmetic products have been repeatedly discussed. The dermal uptake and impact on the systemic aluminum load is still poorly understood. Therefore, we investigated the effect of daily antiperspirant use on the systemic aluminum load under real-life conditions. Methods: 21 healthy subjects meeting certain selection criteria to ensure a low systemic aluminum background load were asked to use a commercial aluminum-containing antiperspirant for 14 days. A questionnaire enquired about shaving habits and other sources of aluminum. Aluminum levels were measured before and after the exposure in 24-h urine and plasma using atomic absorption spectroscopy. Urine samples (n = 6) with <700 mg/day creatinine excretion or more than 30% difference in 24-h creatinine excretion were excluded from further analysis. Results: No significant increase in plasma aluminum concentration or total excreted aluminum per day before and after exposure was measurable. No sample exceeded the reference values of the general population (maximum: 9.42 µg/g creatinine and 2.1 µg/L plasma). Shaving habits did not have a significant influence on the systemic aluminum load. Also, no correlation between the total amount of antiperspirant applied and the systemic aluminum level could be demonstrated. Conclusions: No measurable contribution to the overall systemically available aluminum load due to daily use of an antiperspirant for 14 days could be shown, but real-life data concerning long-term use or higher concentrations are still lacking. Considering toxicological occupational exposure data, adverse neurotoxic changes are unlikely in the case of urinary excretion of <50 µg aluminum/g creatinine (= no observed adverse effect level), even following long-term exposure.

Longitudinal progression trajectory of random urine creatinine as a novel predictor of ESRD among patients with CKD

BackgroundThe clinical importance of random urine creatinine concentration in CKD population remains undetermined. Earlier studies found that lower 24-h urine creatinine excretion was associated with the risk of ESRD and all-cause mortality among CKD patients. MethodsWe modeled the longitudinal trajectories of serial random urine creatinine among 4689 CKD patients enrolled in a national registry-based pre-ESRD program between 2003 and 2015 at a tertiary medical center. Other biochemical parameters including kidney function and serum albumin were regularly evaluated. Primary study outcomes were ESRD requiring maintenance dialysis and all-cause mortality. ResultsBy group-based trajectory modeling, the urine creatinine trajectories were characterized into three patterns: (1) stable low; (2) medium; and (3) high-declining. The adjusted hazard ratio of incident ESRD and all-cause mortality increased by 6% (95% CI: 1–12%) and 9% (95% CI: 2–17%), respectively, for each 20 mg/dL reduction in baseline random urine creatinine concentration. Consistently, there was a significant inverse linear dose-response relationship between baseline random urine creatinine and incident ESRD, but not all-cause mortality. Compared to patients with “medium” and “high-declining” urine creatinine trajectories combined, the adjusted hazard ratio for incidental ESRD among patients with a “stable-low” trajectory who had serial random urine creatinine concentrations stably below 100 mg/dL was 1.46 (95% CI: 1.00–2.12) after considering the competing risk of death. ConclusionsRandom urine creatinine not only serves as a common urinary concentration corrector but has its own clinical significance in risk stratification and outcome prediction in patients with advanced CKD.

PO403 Integration of Telemedicine and Echocardiography By Non-Physicians Into the Primary Healthcare System In Brazil

The clinical importance of random urine creatinine concentration in CKD population remains undetermined. Earlier studies found that lower 24-h urine creatinine excretion was associated with the risk of ESRD and all-cause mortality among CKD patients.We modeled the longitudinal trajectories of serial random urine creatinine among 4689 CKD patients enrolled in a national registry-based pre-ESRD program between 2003 and 2015 at a tertiary medical center. Other biochemical parameters including kidney function and serum albumin were regularly evaluated. Primary study outcomes were ESRD requiring maintenance dialysis and all-cause mortality.By group-based trajectory modeling, the urine creatinine trajectories were characterized into three patterns: (1) stable low; (2) medium; and (3) high-declining. The adjusted hazard ratio of incident ESRD and all-cause mortality increased by 6% (95% CI: 1–12%) and 9% (95% CI: 2–17%), respectively, for each 20 mg/dL reduction in baseline random urine creatinine concentration. Consistently, there was a significant inverse linear dose-response relationship between baseline random urine creatinine and incident ESRD, but not all-cause mortality. Compared to patients with “medium” and “high-declining” urine creatinine trajectories combined, the adjusted hazard ratio for incidental ESRD among patients with a “stable-low” trajectory who had serial random urine creatinine concentrations stably below 100 mg/dL was 1.46 (95% CI: 1.00–2.12) after considering the competing risk of death.Random urine creatinine not only serves as a common urinary concentration corrector but has its own clinical significance in risk stratification and outcome prediction in patients with advanced CKD.

Anthropometry-based 24-h urinary creatinine excretion reference for Chinese children.

To establish 24-h urinary creatinine excretion reference ranges based on anthropometry in healthy Chinese children, a cross-sectional survey was conducted using twice-sampled 24-h urine and anthropometric variables. Age- and sex-specific 24-h creatinine excretion reference ranges (crude and related to individual anthropometric variables) were derived. During October 2013 and May 2014, urine samples were collected. Anthropometric variables were measured in the first survey. Data of 710 children (377 boys and 333 girls) aged 8–13 years who completed the study were analyzed. No significant difference was observed in 24-h urine volumes between the two samples (median [interquartile range): 855.0 [600.0–1272.0) mL vs. 900.0 [660.0–1220.0) mL, P = 0.277). The mean 24-h urine creatinine excretion was regarded as representative of absolute daily creatinine excretion in children. Sex-specific, body-weight-adjusted creatinine excretion reference values were 15.3 mg/kg/day (0.1353 mmol/kg/day) for boys and 14.3 mg/kg/day (0.1264 mmol/kg/day) for girls. Differences were significant between boys and girls within the same age group but not across different age groups within the same sex. Ideal 24-h creatinine excretion values for height were derived for potential determination of the creatinine height index. These data can serve as reference ranges to calculate ratios of analyte to creatinine. The creatinine height index can be used to assess somatic protein status.

Urinary 24-h creatinine excretion in adults and its use as a simple tool for the estimation of daily urinary analyte excretion from analyte/creatinine ratios in populations.

The assessment of urinary excretion of specific nutrients (e.g. iodine, sodium) is frequently used to monitor a population's nutrient status. However, when only spot urines are available, always a risk of hydration-status-dependent dilution effects and related misinterpretations exists. The aim of the present study was to establish mean values of 24-h creatinine excretion widely applicable for an appropriate estimation of 24-h excretion rates of analytes from spot urines in adults. Twenty-four-hour creatinine excretion from the formerly representative cross-sectional German VERA Study (n=1463, 20-79 years old) was analysed. Linear regression analysis was performed to identify the most important influencing factors of creatinine excretion. In a subsample of the German DONALD Study (n=176, 20-29 years old), the applicability of the 24-h creatinine excretion values of VERA for the estimation of 24-h sodium and iodine excretion from urinary concentration measurements was tested. In the VERA Study, mean 24-h creatinine excretion was 15.4 mmol per day in men and 11.1 mmol per day in women, significantly dependent on sex, age, body weight and body mass index. Based on the established 24-h creatinine excretion values, mean 24-h iodine and sodium excretions could be estimated from respective analyte/creatinine concentrations, with average deviations <10% compared with the actual 24-h means. The present mean values of 24-h creatinine excretion are suggested as a useful tool to derive realistic hydration-status-independent average 24-h excretion rates from urinary analyte/creatinine ratios. We propose to apply these creatinine reference means routinely in biomarker-based studies aiming at characterizing the nutrient or metabolite status of adult populations by simply measuring metabolite/creatinine ratios in spot urines.

Underestimation of urinary albumin to creatinine ratio in morbidly obese subjects due to high urinary creatinine excretion

Albuminuria, a chronic kidney and/or cardiovascular disease biomarker, is currently measured as albumin-to-creatinine ratio (ACR). We hypothesize that in severely obese individuals ACR might be abnormally low in spite of relatively high levels of urinary albumin due to increased creatininuria. One-hundred-eighty-four subjects were divided into tertiles based on their BMI. Fat-free mass (FFM) and fat-mass were assessed by DEXA; 24-h creatinine and albumin excretion, ACR, lipid profile and blood pressure were measured. Twenty-four-hour creatinine highly correlated (R = 0.75) with FFM. Since both creatininuria and albuminuria increased with the BMI, being the increase in creatininuria preponderant in subjects with BMI>35, their ratio (AC-ratio) did not change significantly from that of subjects in the lower BMI tertile. ACR only correlated with the systolic blood pressure, while both albuminuria and cretininuria correlated (P = 0.01) with the absolute 10-year CHD risk. In subjects with BMI>35, 100 mg of albumin excreted with urine increased the CHD risk of 2%. Albumin-to-creatinine ratio is underestimated in severely obese individuals as a consequence of the large creatininuria, which is proportional to the increased FFM. Therefore, at least in this population 24-h albuminuria should be more reliable than ACR.

Estimation of 24-h Sodium Excretion From a Spot Urine Sample Using Chloride and Creatinine Dipsticks

Despite its clinical relevance, sodium intake is seldom monitored by physicians, largely because of shortcomings of the 24-h urine collection for sodium excretion. In a prior study, sodium excretion was shown to be accurately estimated from a late afternoon/early evening spot urine sodium/creatinine ratio, adjusted for 24-h creatinine excretion. In this study, we assessed a more convenient and inexpensive method, using chloride and creatinine dipsticks. Subjects submitted 24-h urine collections along with an "AM sample," collected at the beginning, a "PM sample" collected in the late afternoon/early evening before dinner, at roughly the midpoint, and a "random sample," collected after completion, of the 24-h collection. Predicted 24-h sodium excretion was then determined from the spot urine dipstick chloride/creatinine ratio, measured by two independent observers, and from the spot urine laboratory sodium/creatinine ratio. Both ratios were adjusted for 24-h creatinine excretion. For PM samples, predicted sodium excretion correlated strongly with actual 24-h sodium excretion, both for the dipstick method (r = 0.71; observer 1 and r = 0.65; observer 2; both P < 0.001), and the laboratory method (r = 0.86, P < 0.001). PM samples also differentiated subjects with sodium excretion <100 mEq/day vs. > or =100 mEq/day (sensitivity and specificity: dipstick method: 83 and 82%, respectively for observer 1, 89 and 77%, respectively, for observer 2; laboratory method: 100 and 82%, respectively). AM samples and random samples correlated less strongly. The dipstick method appears promising as a convenient and inexpensive means to serially assess sodium excretion.

Hypophosphatemic Osteomalacia after Low-Dose Adefovir Dipivoxil Therapy for Hepatitis B

A 40-yr-old male presented with a 5-month history of bone pain involving both knees, ankles, and several ribs with no antecedent trauma. He had an antalgic gait, tenderness involving the bony margins of both knees, but no synovitis. He had a history of chronic hepatitis B infection, receiving lamivudine at a daily dose of 100 mg for 43 months and adefovir dipivoxil (adefovir) at a daily dose of 10 mg for the past 29 months. He had been receiving tramadol hydrochloride intermittently for pain relief. Investigations revealed a reduced serum phosphate level of 2.0 mg/dl (0.64 mmol/liter), normal serum corrected calcium of 8.8 mg/dl (2.20 mmol/liter), PTH of 39 pg/ml (4.1 pmol/liter), 25-hydroxyvitamin D3 level of 24.4 ng/ml (61 nmol/liter), and 1,25-hydroxyvitamin D level of 57 pmol/liter. Bone-specific alkaline phosphatase was elevated at 85.4 g/liter (normal, 3.7–20 g/liter). The urine deoxypyridinoline/creatinine ratio was elevated at 11 nmol/mmol (normal, 2.3–5.4 nmol/ mmol) with an estimated glomerular filtration rate of 60.1 ml/min. A 24-h urinalysis demonstrated hyperphosphaturia at 1.054 g/d (34 mmol/d) [normal, 0.465– 0.93 g/d (15–30 mmol/d)], hypercalciuria at 580 mg/d (14.5 mmol/d) [normal, 100 –300 mg/d (2.5–7.5 mmol/d)], glycosuria, and massive aminoaciduria. The 24-h creatinine excretion was normal at 1.41 g/d (12.5 mmol/d) [normal, 1.02–2.03 g/d (9 –18 mmol/d)]. Calculated maximal tubular phosphate reabsorption was reduced at 0.3% (normal, 0.8 –1.3%). Magnetic resonance imaging of both knees revealed microfractures across the femoral and tibial metaphyses (Fig. 1). A whole body bone scan showed intense uptake at the subchondral bone of both knees and several bilateral ribs (Fig. 2A). The diagnosis of hypophosphatemic osteomalacia in the context of Fanconi’s syndrome secondary to adefovir therapy was made. Fanconi’s syndrome is a recognized complication of high-dose adefovir therapy when used in the treatment of HIV (1). However, at the time of writing, there were only two other published reports of hypophosphatemic osteomalacia after low-dose adefovir therapy (2, 3). Fifteen weeks after cessation of adefovir and after regular phosphate supplementation, the patient reported significant improvement in his knee and other bony pain. ISSN Print 0021-972X ISSN Online 1945-7197 Printed in U.S.A. Copyright © 2010 by The Endocrine Society doi: 10.1210/jc.2009-2051 Received September 23, 2009. Accepted October 27, 2009. * T.W. and C.M.G. are joint first authors. FIG. 1. Left knee coronal proton-density weighted magnetic resonance image. There are incomplete undisplaced fractures across the femoral and tibial metaphyses, consistent with recent insufficiency fractures. S P E C I A L F E A T U R E

Body mass index (BMI), body composition and mortality of nursing home elderly residents

The body mass index (BMI) is a key marker of nutritional status among older patients, but does not reflect changes in body composition, The aim of the present study was to investigate BMI levels and body composition in a sample of disabled nursing home residents, and to study possible interrelations between BMI, fat-free body mass (FFM), body fat mass (BFM), skeletal muscle mass (SMM) and 1-year mortality rates. FFM and SMM were assessed by 24-h urine creatinine excretion and BFM as the difference between BMI and FFM. We calculated relative risk (RR) and odds ratio (OR) of 1-year mortality, associated with different levels of BMI, FFM index (where index = value/height 2), SMM index and BFM index in 82 disabled institutionalized elderly patients. One-year mortality rate was 29.3%. Adjusted relative risk of mortality of low BMI patients was 1.45 (95% CI = 0.73–2.89; OR = 1.73) and 0.63 (95% CI = 0.33–1.60; OR = 0.72) in high BMI. Risk of mortality was higher in those having low FMM index or SMM index (RR = 2.42, 95% CI = 0.36–16.18; OR = 2.55 and RR = 3.22, 95% CI = 0.78–13.32; OR = 3.67, respectively). It is concluded that low FFM and SMM indexes among disabled nursing home residents are far better predictors than BMI for 1-year mortality estimation.

Serial Changes in Urinary Proteome Profile of Membranous Nephropathy: Implications for Pathophysiology and Biomarker Discovery

Membranous nephropathy is one of the most common causes of primary glomerular diseases worldwide. The present study adopted a gel-based proteomics approach to better understand the pathophysiology and define biomarker candidates of human membranous nephropathy using an animal model of passive Heymann nephritis (PHN). Clinical characteristics of Sprague-Dawley rats injected with rabbit anti-Fx1A antiserum mimicked those of human membranous nephropathy. Serial urine samples were collected at Days 0, 10, 20, 30, 40, and 50 after the injection with anti-Fx1A (number of rats = 6; total number of gels = 36). Urinary proteome profiles were examined using 2D-PAGE and SYPRO Ruby staining. Quantitative intensity analysis and ANOVA with Tukey post-hoc multiple comparisons revealed 37 differentially expressed proteins among 6 different time-points. These altered proteins were successfully identified by MALDI-TOF MS and classified into 6 categories: (i) proteins with decreased urinary excretion during PHN; (ii) proteins with increased urinary excretion during PHN; (iii) proteins with increased urinary excretion during PHN, but which finally returned to basal levels; (iv) proteins with increased urinary excretion during PHN, but which finally declined below basal levels; (v) proteins with undetectable levels in the urine during PHN; and (vi) proteins that were detectable in the urine only during PHN. Most of these altered proteins have functional significance in signaling pathways, glomerular trafficking, and controlling the glomerular permeability. The ones in categories (v) and (vi) may serve as biomarkers for detecting or monitoring membranous nephropathy. After normalization of the data with 24-h urine creatinine excretion, changes in 34 of initially 37 differentially expressed proteins remained statistically significant. These data underscore the significant impact of urinary proteomics in unraveling disease pathophysiology and biomarker discovery.