Creatinine Excretion Rate Research Articles

Laboratory issues in measuring and reporting urine albumin

Urine albumin is an important biomarker for kidney damage, and its measurement is recommended by clinical practice guidelines in many countries for identifying and managing patients with kidney disease. A recent publication reviewed current practices in measurement and reporting of urine albumin concentrations and made recommendations for improvement [1]. The paper reflected the work of the Laboratory Working Group of the National Kidney Disease Education Program (NKDEP, USA) and the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Joint Committee for Standardization of Albumin in Urine. Historically, the concentration of albumin excreted in 24 h was used to evaluate kidney function. The difficulty of collecting 24 h urine samples has lead to the common recommendation to use an untimed urine collection and to report the ratio of the albumin concentration to the creatinine concentration. This albumin:creatinine ratio (ACR) is widely viewed as an acceptable surrogate for the albumin excretion rate. The recommendations from various professional organizations, however, vary regarding the type of urine samples to collect for measurement of ACR (e.g. firstmorning void, random), the reporting units to use and the criteria for interpretation of the results. Most recommendations use a single decision threshold to identify patients with clinically significant albuminuria, despite the variation of both the albumin and creatinine excretion rates with time of day, exercise, gender, race and other factors. Further complicating the use of a single decision threshold is the increasing evidence that albumin excretion functions as a continuous variable in predicting a progressive increase in risk for complications related to decreased kidney function [2,3]. A number of urine collection issues need careful investigation before improved recommendations for practice can be developed. A wide range of estimates have been reported for the biologic variability of albumin and creatinine in urine samples collected at different times of the day. The evidence supports the conclusion that the ACR is less vari

Distribution of IgM and IgG antibodies to oxidized LDL in immune complexes isolated from patients with type 1 diabetes and its relationship with nephropathy

Modified lipoproteins are immunogenic and play a key pathogenic role in vascular disease. Antibodies to oxidized LDL (oxLDL) are mostly of the pro-inflammatory IgG 1 and IgG 3 isotypes. We measured IgG and IgM oxLDL antibodies in immune complexes (IC) isolated from 36 patients with type 1 diabetes using a nested case control design. IgG antibodies predominated over IgM antibodies by an 8:1 ratio. IgG antibody concentrations were higher in the nephropathy cases compared to controls ( p = 0.09), but no significant difference was observed because of two patients included in the study who had end-stage renal disease (creatinine > 5 mg/dL and glomerular filtration rate (GFR) less than 17 mL/min). After eliminating these patients from the analysis, significant positive associations of IgG antibody concentration with serum creatinine and albumin excretion rate were observed. Similarly, a negative correlation with estimated glomerular filtration rate was observed in this subsample of 34 patients. Differences in IgM antibody concentrations by nephropathy classification were not supported by the data. In conclusion, the predominance of pro-inflammatory IgG oxLDL antibodies is associated with existence of diabetic nephropathy, and a protective role of IgM antibodies could not be demonstrated.

Uric acid as a risk factor for progression of non-diabetic chronic kidney disease? The Mild to Moderate Kidney Disease (MMKD) Study

The kidney is one of the organs most prominently affected by aging. This can be seen by a loss of renal mass which is caused by a decrease in the number of nephrons resulting in hyperfiltration, hypertrophy and elevations in glomerular pressure. The factors influencing aging of the kidney are not fully elucidated. Epidemiological, experimental and interventional studies resulted in inconsistent results and have not firmly established whether uric acid levels affect progression of Chronic Kidney Disease (CKD). Therefore, we analyzed whether uric acid levels predict the progression of CKD in the Mild to Moderate Kidney Disease Study comprising at baseline 227 Caucasian patients aged 18–65 years with primary non-diabetic CKD of various degrees of renal impairment. Of them, 177 completed a prospective follow-up of 7 years. Primary endpoint was progression of CKD defined as doubling of baseline serum creatinine and/or terminal renal failure. Patients who reached a progression endpoint ( n = 65) were significantly older, had higher baseline serum creatinine and protein excretion rates as well as lower Glomerular Filtration Rate (GFR). Uric acid levels were only higher in patients with progression of disease when patients with uric acid-lowering drugs were excluded from the analysis. Cox regression analysis revealed that increasing uric acid levels predict disease progression only when the analysis was not adjusted for baseline kidney function parameters. As soon as we adjusted the analysis for GFR and proteinuria this association completely vanished. In summary, our prospective 7 year follow-up study in patients with non-diabetic primary CKD did not support uric acid as an independent predictor for CKD progression.

Indicators of lean body mass catabolism: emphasis on the creatinine excretion rate

The major stress response to critical illness leads to a catabolic state and loss of lean body mass. To test whether an increased rate of creatinine excretion might provide unique and timely information to monitor cell catabolism; to relate this information to balances of cell constituents (nitrogen, potassium, phosphate and magnesium); to evaluate the effectiveness of nutritional therapy to reverse this catabolic process. Prospective observational study. Children with severe traumatic brain injury admitted to the paediatric critical care units of The Hospital for Sick Children, Toronto, Canada and Hospital das Clínicas, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Brazil were studied. Complete 24 h urine collections were obtained for measurement of creatinine excretion rate and daily balances of nitrogen, potassium, phosphate and magnesium. Seventeen patients were studied for 3-10 days. On Day 1, all had negative balances for protein and phosphate. Balances for these intracellular constituents became positive when protein intake was >/=1 g/kg/day and energy intake was >/=50% of estimated energy expenditure (P < 0.0001). Creatinine excretion rate was positively correlated with the urea appearance rate (r = 0.60; P < 0.0001), and negatively with protein balance (r = -0.45; P < 0.0001). Sepsis developed in four patients; before its clinical detection, there were negative balances for all intracellular markers and an abrupt rise in the excretion of creatinine. Negative balances of intracellular components and an increase in rate of creatinine excretion heralded the onset of catabolism.

Renal disease in HIV-seropositive patients in Nigeria: an assessment of prevalence, clinical features and risk factors

In order to determine the pattern of renal disease and risk factors for renal disease in HIV-infected Nigerians, we studied 400 consecutive HIV/AIDS patients (210 males, 190 females) aged between 18 and 65 years (mean +/- SD; 34.6 +/- 9.4 years), and examined renal disease factors attributable to the infection. Diagnosis of renal disease was based on the consistent presence of at least 1+ albuminuria and/or elevated serum creatinine (>132 micromol/l) as well as the absence of other identifiable causes of chronic kidney disease (CKD). We determined socio-demography and clinical findings, as well as full laboratory work-ups including haemogram, CD4+ cell count, serum electrolytes, urea, creatinine, protein, cholesterol and urine analysis. Renal biopsies were taken in 10 patients who had moderate to massive proteinuria and had consented to the procedure. Finally, we compared HIV/AIDS cases with and without renal disease to determine the risk factors for nephropathy. We observed a high prevalence of renal disease (proteinuria and/or elevated serum creatinine), which was present in 152 (38%) of the patients. This subgroup included 74 males and 78 females with a M:F ratio of 1:1. The mean age (+/-SD) was 35.8 (+/-10.01) years. Systolic and/or diastolic hypertension was seen in 13.2% of these patients while the mean (+/- SD) body mass index (BMI) and packed cell volume (PCV) were 18.5 (+/-3.1) kg/m(2) and 25.26 (+/-6.81)%, respectively. The mean (+/-SD) CD4+ count was 246.49 (+/-192.8) cells/microl, while the mean (+/-SD) serum creatinine and 24-h urine protein excretion rates were 210.11 (+/-337.8) micromol/l and 2.57 (+/- 2.42) g/day, respectively. In subjects with and without nephropathy, there were significant differences in age, BMI, serum cholesterol, serum albumin and CD4+ counts, suggesting that these parameters may be risk factors for nephropathy. Histology revealed mainly focal glomerulosclerosis (FGS) with glomerular collapse. We conclude that the prevalence of proteinuria in HIV-seropositive patients is high in Nigeria. Such subjects show an equal male:female distribution, and glomerular histology revealed that a majority of biopsied patients had the collapsing FSGS variant. The risk factors for renal disease included severity of the HIV infection (inferred from the generally low CD4+ count), anaemia, malnutrition and increasing age.

Creatinine corrections for estimating children's and adult's pesticide intake doses in equilibrium with urinary pesticide and creatinine concentrations

A urine contaminant concentration per se has uncertain meaning for human health because of dilution by hydration. However, the estimation of the health-related daily intake dose of pollutant (mg/kg/day) that equilibrates with a spot urinary concentration of a pesticide residue or metabolite, or other analyte, can be made using creatinine-corrected toxicant levels (mg analyte/mg creatinine) multiplied by an estimate of the subjects' expected creatinine excretion rates (mg creatinine/kg/day). The objective was to develop a set of equations predicting a person's expected daily creatinine excretion (mg/kg) as a function of age, gender, race and morphometry, from birth to old age. We review the creatinine excretion literature where infants, children and adults provided 24 h total urine samples for creatinine analysis. Equations are developed for infants (<or=3 years), children (3-18 years) and adults (>or=18 years) that match at 3 and 18 years. A series of equations that estimate daily creatinine excretion (mg/day) are developed that are piecewise continuous from birth through infancy through adolescence and through adulthood for males and females, and Black and White races. Complicating factors such as diet, health status and obesity are discussed. We propose that these equations, with caveat, can now be used with measured urine concentrations to consistently estimate the corresponding equilibrium intake doses of toxicants at ages from birth to 92 years for the healthy non-obese. We recommend that this system of equations be considered for future development and reporting of applied doses in mg/kg/day of pollutants and toxicants that are measured in urine samples, as in the National Health and Nutrition Examination Survey.

Serum Cystatin C Predicts Progression of Subclinical Coronary Atherosclerosis in Individuals With Type 1 Diabetes

Renal function is an important determinant of coronary atherosclerosis, and serum cystatin C is a novel accurate measure of glomerular filtration rate (GFR) and a predictor of cardiovascular events and mortality. We hypothesized that in individuals with type 1 diabetes, cystatin C would 1) predict progression of subclinical coronary atherosclerosis (SCA) and 2) be a stronger predictor of SCA than serum creatinine, GFR (estimated by the Cockcroft-Gault [GFRCG] and Modification of Diet in Renal Disease [GFRMDRD] formulas), and albumin excretion rate. Coronary artery calcification was measured twice, using Imatron C-150 Ultrafast CT, over a 2.5 +/- 0.4-year interval in 509 adults with type 1 diabetes (42% male, age 36 +/- 9 years, duration 23 +/- 9 years). SCA progression (n = 131) was defined as a >2.5 increase in square root calcium volume score or development of clinical coronary artery disease. Predictors of SCA progression were examined in a model selected by stepwise logistic regression and an a priori-determined model. Next, each measure of renal function was inserted into the stepwise model, one at a time, and Akaike information criterion was used to compare the fit of the competing models. The stepwise model included cystatin C (odds ratio 1.44, 95% CI 1.00-2.18, P = 0.048), age, baseline coronary artery calcification, sex, diabetes duration, systolic blood pressure, and HDL. The stepwise model had a better fit than any of the competing models with serum creatinine, GFRCG, GFRMDRD, or albumin excretion rate replacing cystatin C. In individuals with type 1 diabetes, cystatin C modestly predicts SCA.

Suppression of mesangial cell proliferation and extracellular matrix production in streptozotocin‐induced diabetic rats by Sp1 decoy oligodeoxynucleotide in vitro and in vivo

Transcription factor Sp-1 is an important fibrogenic factor that is involved in the pathogenesis of diabetic nephropathy. In this study, we examined the effect of Sp1 decoy oligodeoxynucleotides (ODNs) on the extracellular matrix (ECM) gene expression in cultured rat mesangial cells (RMC) and streptozotocin (STZ)-induced diabetic rats. The ring-type Sp1 decoy ODNs significantly decreased ECM mRNA expression and Sp1 binding to the promoter region of these PDGF-induced genes in RMC. In addition, the decoy ODNs was introduced into the left renal artery of diabetic rat using the hemagglutinating virus of Japan (HVJ)-liposome mediated gene transfer method and effectively delivered to the kidney. On 14 days after ring-type Sp1 decoy ODNs injection, type IV collagen, fibronectin mRNA, and protein expression were markedly decreased, and the rate of urinary creatinine excretion was reduced in the ring-type Sp1 decoy ODNs-treated diabetic rats. These results indicated that the ring-type Sp1 decoy ODNs would be superior to P-Sp1 ODNs. Also, the R-Sp1 decoy ODN when introduced in vivo, effectively reduced ECM production during the progression of nephropathy. Therefore, ring-type Sp1 decoy is a promising tool for developing new therapeutic applications for progressive diabetic nephropathy.

Determination of creatinine excretion and evaluation of spot urine sampling in Holstein cattle

Four experiments were carried out to determine urinary creatinine excretion in Holstein growing bulls, lactating cows, and replacement heifers. In addition, we evaluated the use of spot sampling technique to estimate purine derivatives (PD) excretion. In Experiment I, 15 lactating cows were used in a randomized block design to compare creatinine excretion obtained in different time-spans of urine collection (during 6, 9, 12, 15, 18, 21, and 24 h). In Experiment II, four bulls were allocated in a 4 × 4 Latin square to evaluate the effect of diet (levels of cottonseed hulls of 0, 10, 20, and 30% of the DM) on excretion of creatinine. In Experiment III, 15 lactating cows were used to evaluate the effect of milk production (ranging from 3.9 to 36.7 kg/d) on daily creatinine and PD excretions. In Experiment IV, 22 replacement heifers were utilized to evaluate the effect of body weight (BW, ranging from 107 to 545 kg) on daily creatinine and PD excretions. For all experiments, total urine collections were made over 24 h and daily creatinine and PD excretions were determined. Different time-spans for total urine collection had no effect ( P = 0.70) on creatinine excretion compared to the 24-h collection period, indicating a constant excretion rate of creatinine. The roughage source did not influence ( P = 0.64) creatinine excretion by bulls, averaging 0.248 ± 0.008 mmol/kg BW. Similarly, milk production did not affect ( P = 0.82) creatinine excretion in cows, averaging 0.212 ± 0.004 mmol/kg BW. In contrast, the creatinine excretion (mmol/kg BW) decreased linearly ( P < 0.001) as BW of heifers increased, suggesting that creatinine excretion might vary with the degree of maturity of growing animals. There were no differences (P > 0.14) between the 24-h total collection and spot sampling technique in estimating daily PD excretion. The spot sampling technique may be used to estimate the daily excretion of urinary PD in Holstein cattle under practical conditions.

Albuminuria and Renal Function in Homozygous Sickle Cell Disease

The glomerular filtration rate (GFR) in homozygous sickle cell (SS) disease is supranormal in childhood but falls steeply with age, often culminating in renal failure. The risk factors underlying these observations are unclear. We therefore sought to investigate the relationships between blood pressure, renal hemodynamics, and urinary albumin excretion in subjects with SS disease and matched controls with a normal AA genotype (hereinafter, controls) as a prelude to intervention studies. Serum creatinine level, GFR, effective renal plasma flow, blood pressure, and urinary albumin and creatinine excretion rates were measured in Jamaican individuals with SS disease aged 18 to 23 years and in controls followed from birth in a cohort study. Compared with controls, subjects with SS disease showed lower blood pressure and normal or supranormal GFR and effective renal plasma flow. Urinary albumin excretion exceeded 20 microg/min in 26% of subjects with SS disease and correlated positively with GFR and systolic blood pressure and negatively with hematocrit. A higher GFR and increased tubular secretion of creatinine combined to lower serum creatinine levels in patients with SS disease, giving an upper limit of the reference range of 0.90 mg/dL (80 micromol/L) in men and 0.77 mg/dL (68 micromol/L) in women. In addition, creatinine clearance measurements were consistently greater than GFR in subjects with SS disease. The GFR remained within reference range or elevated in patients with SS disease aged 18 to 23 years. The higher GFR in patients with albuminuria was consistent with the hypothesis that high glomerular flows cause renal damage. Lower serum creatinine levels characterize patients with SS disease, and a revised clinical definition based on serum creatinine level alone is proposed.

Use of albumin creatinine ratio and urine albumin concentration as a screening test for albuminuria in an Indo-Asian population

Albuminuria (>30 mg/day) based on 24 h urine albumin excretion is one of the criteria for chronic kidney disease (CKD) and a predictor of cardiovascular disease (CVD). Differences in urine albumin concentration and creatinine excretion rates between Indo-Asians and other populations may require different threshold values for detection of albuminuria. We compared the use of spot urine albumin concentration and urine albumin to creatinine excretion ratio for detection of albuminuria in this population. A total of 577 subjects aged >or=40 years, 54% of whom were women, were recruited from the general population in Karachi, Pakistan. Albumin concentration (mg/l) and albumin to creatinine ratio (mg/g of creatinine) were determined in a spot morning urine sample, and albuminuria (30 mg/day or greater) measured in a 24 h urine collected on the subsequent day. The median (25-75 percentile) of urine albumin excretion was 4.8 (3.6-10.3) mg/day: 5.4 (3.7-12.5) mg/day in men and 4.5 (3.8-8.9) mg/day in women. The overall prevalence (95% CI) of albuminuria was 11.8% (7.2-12.0%): 14.8% in men and 9.2% in women (P = 0.04). The areas under the receiver operator characteristic (ROC) curves for urine albumin concentration were 0.86 (0.82-0.90) and 0.88 (0.84-0.92), respectively, in women and men. The areas under the ROC curves for albumin to creatinine ratio were 0.86 (0.82-0.89) and 0.90 (0.86-0.93), respectively, in women and men. For urine albumin concentration, the sensitivity and specificity were 37 and 97%, respectively, in women and 69 and 94%, respectively, in men at the conventionally recommended value of 2 mg/dl. The discriminator value of urine albumin concentration identified in the analysis was 0.5 mg/dl in women (sensitivity of 87% and specificity of 75%) and 1.7 mg/dl in men (sensitivity of 74% and specificity of 93%). For the albumin to creatinine ratio, the sensitivity and specificity were 46 and 95%, respectively, in women and 60 and 97%, respectively, in men at cut-off value of 30 mg/g. Both urine albumin concentration and albumin to creatinine ratio are acceptable tests for population screening for albuminuria in Indo-Asians. While sensitivities may be suboptimal, particularly in women, lowering the existing thresholds would compromise specificity. Those who screen positive need evaluation and management of CKD and prevention of CVD.

Reproducibility of Renal Function Measurements in Adult Men with Diabetic Nephropathy: Research and Clinical Implications

Background/Aim: Measurement of the renal function is critical to follow progression of kidney disease. Short-term and long-term variabilities in these measurements have significant impacts on clinical decision making and clinical trials. The goal of this study was to describe the variability in these measurements and to calculate minimum sample size estimates over varying time frames for clinical trials. Methods: We studied 44 elderly men with diabetic nephropathy who participated in a clinical trial. Glomerular filtration rate and renal plasma flow were measured by continuous infusion technique with five urine collection periods on two occasions 4 months apart. Protein and creatinine excretion rates were measured in the same specimens. In addition, two consecutive 24-hour specimens every month for 4 months were collected to analyze urine protein, creatinine, urea nitrogen, and electrolytes. A hierarchical random effects model was used to analyze the reproducibility from hour to hour, from day to day, and from month to month. Results: A total of 824 urine specimens were analyzed, of which 412 constituted specimens collected in the short term and 412 were 24-hour urine collections. Hour-to-hour variation accounted for 45% for urinary clearance of iothalamate, but for only 0.5% of the variability in plasma clearance of iothalamate. Day-to-day variability in 24-hour urinary excretion rates for creatinine was 46% and for protein 10%. Month-to-month variability in 24-hour excretion rates for creatinine was 11% and for protein 19%. The urine protein/creatinine ratio had a day-to-day variability of 2% and a month-to-month variability of 19%. Sample size requirements can be reduced by correcting for urine creatinine for some but not all urinary analytes. Conclusions: In nephrotic men with diabetic nephropathy, the coefficient of variation in the month-to-month protein excretion rate is 36%. Approximately 28 patients in each arm of two groups are needed to detect a difference in protein excretion rate of 28% (1 g/day in this study). The coefficient of variation in plasma iothalamate clearance over 4 months is 16%. To detect a 10% change in glomerular filtration rate between two groups, 44 patients per group are needed. To be deemed statistically significant, a change in daily protein excretion rate of at least 72% over month(s) is needed in individual patients.

Muscularity and adiposity in addition to net acid excretion as predictors of 24-h urinary pH in young adults and elderly

In patients with nephrolithiasis, an inverse relationship between 24-h urinary pH (24h-UpH) and body weight has been reported. Whether body composition indices and 24h-UpH are similarly associated in healthy subjects needs investigation. Cross-sectional, retrospective analysis. Dortmund, Germany and Gothenburg, Sweden. Healthy young adults (18-23 years; n=117) and elderly (55-75 years; n=85) having a mean body mass index (BMI) of 22.80+/-3.4 and 25.3+/-3.9 kg/m2, respectively. Anthropometric data, 24h-UpH, and 24-h urinary excretion rates of net acid (NAE), creatinine, and urea were determined. After adjusting for urea (reflecting protein intake), renal creatinine output was used as a biochemical marker for muscularity. The BMI served as a marker of adiposity. NAE, body weight, and BMI were significantly (P<0.05) higher, and height and creatinine significantly lower in the elderly, whereas body-surface area (BSA) was not different. Step-wise multiple regression analysis using BSA-corrected urinary variables revealed NAE as the primary predictor of 24h-UpH (with R2 values of 0.64 and 0.68 in young adults and elderly, respectively, P<0.0001), followed by urea (P<0.0001), creatinine (P<0.05), and BMI (P<0.05 for the young adults and P=0.12 for the elderly). These associations were negative for NAE and BMI, and positive for urea and creatinine. Muscularity (i.e. creatinine adjusted for urea) and particularly in the group of young adults, adiposity (i.e. BMI) proved to be modest, but significant predictors of 24h-UpH. Future research should focus on more obese subjects in whom insulin resistance and particular kidney functions should also be examined to further substantiate the role of obesity in low-urine pH-associated conditions, for example, nephrolithiasis.

Perchlorate exposure of the US Population, 2001-2002.

Perchlorate is commonly found in the environment and can impair thyroid function at pharmacological doses. As a result of the potential for widespread human exposure to this biologically active chemical, we assessed perchlorate exposure in a nationally representative population of 2,820 US residents, ages 6 years and older, during 2001 and 2002 as part of the National Health and Nutrition Examination Survey (NHANES). We found detectable levels of perchlorate (>0.05 microg/l) in all 2,820 urine samples tested, indicating widespread human exposure to perchlorate. Urinary perchlorate levels were distributed in a log normal fashion with a median of 3.6 microg/l (3.38 microg/g creatinine) and a 95th percentile of 14 microg/l (12.7 microg/g creatinine). When geometric means of urinary perchlorate levels were adjusted for age, fasting, sex and race-ethnicity, we found significantly higher levels of urinary perchlorate in children compared with adolescents and adults. We estimated total daily perchlorate dose for each adult (ages 20 years and older), based on urinary perchlorate, urinary creatinine concentration and physiological parameters predictive of creatinine excretion rate. The 95th percentile of the distribution of estimated daily perchlorate doses in the adult population was 0.234 microg/kg-day [CI 0.202-0.268 microg/kg-day] and is below the EPA reference dose (0.7 microg/kg-day), a dose estimated to be without appreciable risk of adverse effects during a lifetime of exposure. These data provide the first population-based assessment of the magnitude and prevalence of perchlorate exposure in the US.

Longitudinal examination of 24-h urinary iodine excretion in schoolchildren as a sensitive, hydration status–independent research tool for studying iodine status

Because worldwide iodine status (IS) depends on continuous fortification, the adequacy of IS needs to be regularly monitored. Our study aimed to evaluate IS in a longitudinal sample of healthy schoolchildren who regularly used table salt iodized with 20 microg I/g. Urine osmolality (Uosm) and 24-h urinary excretion rates of iodine (24-h UI), sodium, creatinine, and total urine volume (24-h Uvol) were measured in 1046 specimens that were collected at repeated intervals from 1996 to 2003 in a sample of 358 German children aged 6-12 y. Energy intake and food consumption were calculated from 3-d weighed dietary records that were collected in parallel to the urine samples. During the 4-y period from 1996 to 1999, the median 24-h UI increased from 87 to 93 microg I/d (P = 0.017), whereas urinary iodine concentration (UIC), Uosm, and 24-h Uvol did not change significantly. Thereafter (from 2000 to 2003), UIC stagnated and Uosm decreased (P = 0.004), whereas 24-h Uvol (P = 0.008) and 24-h UI (P = 0.002) increased. The final median 24-h UI reached 120 microg I/d. Milk, fish, egg, and meat intakes and 24-h sodium excretion were all significant predictors of IS, with an almost doubled contribution from milk intake during the second 4-y period. Our study shows a continuous improvement of IS in a longitudinal sample of German schoolchildren. This improvement was masked when UIC was used as an IS index, especially from 2000 to 2003 because of changes in hydration status. Thus, in research-oriented studies that focus on UIC measurements, hydration status can be a relevant confounder. Longitudinal analyses of 24-h UI in cohort studies may represent an alternative hydration status-independent tool to examine trends in IS and the contribution of relevant foods to IS.

Serum, urinary, and salivary nitric oxide in rheumatoid arthritis: complexities of interpreting nitric oxide measures

Nitric oxide (NO) may play important roles in rheumatoid arthritis (RA). RA is an inflammatory disease involving joints and other systems including salivary glands. To assess NO production in RA patients, we compared levels of serum, urine, and salivary nitrite and nitrate (NOx) in patients with RA and normal subjects, and we examined the relationships of these measures to disease activity. Serum, urine, and NOx levels as well as renal creatinine, NOx clearance and fractional excretion rates were compared in 25 RA patients and 20 age- and gender-matched healthy controls. Subjects were hospitalized for 3 days and placed on a NOxrestricted diet. NOx was assayed using nitrate reductase and the Griess reagent. RA activity was assessed using standard clinical and laboratory measures. While consuming a restricted diet for 3 days to eliminate the effects of oral intake of NOx, 24 hour urinary NOx excretion decreased in both RA patients and healthy controls. Urine NOx levels at all time points were not significantly different between RA patients and normal subjects. Serum NOx levels also decreased during the 3 days of NOx restriction, but RA patients had higher serum NOx levels at all time points compared with the control group. Likewise, serum NOx/creatinine ratios were higher in RA patients than in controls. Although basal salivary flow rate and tear flow were lower in RA patients, salivary NOx levels did not differ between normal and RA subjects. While renal creatinine clearance was not different between the two groups, we found that RA patients had lower renal NOx clearance and lower renal NOx fractional excretion. After correction of p values for multiple comparisons, there were no significant relationships for the RA group between measures of disease activity and the urinary NOx, serum NOx, or urinary NOx clearance. Despite interest in the use of NO as a marker of disease activity, alterations in renal NOx clearance and fractional excretion in RA make it difficult to assess in vivo NO production even with strict dietary restriction of NOx intake.

Urine urea-creatinine ratio of mammalian carnivores: a good nutritional index for the wrong reason?

Abstract Urine urea–creatinine ratio (U:C) often is used as an index of nutritional status of wild mammals, especially because urine can be collected from snow, providing a non-invasive index of nutrition. The rate of creatinine excretion has been assumed to be relatively stable; thus, creatinine concentration is used to normalize urea concentrations and control for dilution in snow. We present data from captive wolves (Canis lupus) to test how much variation in U:C is due to variation in urea vs. creatinine in relation to time since feeding. We found that U:C increases for ∼18 hours post-feeding but that this variation is primarily due to the 5-fold decrease in creatinine rather than the 2-fold increase in urea concentration. It is not clear what governs the variable creatinine concentrations in urine. Until a fuller understanding of this metabolite is achieved, ecological studies employing this nutritional index should report urea and creatinine values as well as the ratio. Physiological studies should ...

Timed-urine collections for renal clearance studies

The purpose of this study was to describe the reproducibility of timed-urine collections for renal clearance studies and the effect variations in urine collection has on measurement of glomerular filtration rate (GFR). Data from 222 cimetidine clearance studies (GFR-Cim) were obtained from 32 pediatric renal patients over a period of 8 years. There were three to 18 studies per child aged 4.8 years to 21 years at the time of a study. The urinary creatinine excretion rate is measured during supervised urine collection periods. The creatinine excretion rates in each child were compared to obtain data on the reproducibility of the urine collections. The coefficient of variation (CV) of the creatinine excretion rate is approximately 10% in both children and adults. The variation in GFR to be expected during repeated renal clearance studies in subjects with stable GFR, using voided urine collections, was similar in children and adults, with a CV of 12% to 14%.

Evaluation of the effect of governmental control of human exposure to two phthalates in Japan using a urinary biomarker approach

In Japan, the use of certain phthalates has been regulated. We analyzed the effectiveness of these measures using an analytical biomarker approach. We measured two phthalate metabolites, mono- n-butyl phthalate (MBP) and mono-2-ethylhexyl phthalate (MEHP) in urine samples from 36 participants using enzymatic deconjugation, offline solid phase extraction, and HPLC-ESI-MS/MS. From the levels measured and individual values of creatinine excretion rate the daily intake was determined and compared to each corresponding tolerable daily intake (TDI). The levels of urinary MBP and MEHP were <1.8–280 and 0.76–25 μg/l, respectively. The ranges of the estimated daily intake of di- n-butyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP) from 35 adult urine samples were 0.22–4.5 and 0.37–7.3 μg/kg/day, respectively. These values were lower than the corresponding TDIs. After comparing these values to previous exposure assessment data on DEHP in Japan, it could be seen that the DEHP intake dropped over the period from 1998 to 2001. Children were not covered in the present study, so the results may only be applicable to adults, not to the Japanese population at large. Even so, the small number of people in one specific geographic area cannot be considered representative of the adult Japanese population. In addition to MEHP, the secondary metabolites of DEHP, which are more suitable biomarkers should be measured in the future.

Estimating pesticide dose from urinary pesticide concentration data by creatinine correction in the Third National Health and Nutrition Examination Survey (NHANES-III).

The Third National Health and Nutrition Examination Survey (NHANES-III) of the Centers for Disease Control and Prevention (CDC) recorded data on the urinary concentrations of 12 chemicals (analytes), which were either pesticides or their metabolites, that represent exposure to certain pesticides, in urine samples collected from 1988 to 1994 from a cohort of 978 volunteer subjects, aged 20-59 years. We have used each subject's urinary creatinine concentration and their individual daily creatinine excretion rate (g/day) computed from their age, gender, height and weight, to estimate their daily excretion rate in microg analyte/kg/day. We discuss the mechanisms of excretion of the analytes and certain assumptions needed to compute the equivalent daily dietary intake (microg/kg/day) of the most likely parent pesticide compounds for each excreted analyte. We used literature data on the average amount of parent compound ingested per unit amount of the analyte excreted in the urine, and compared these estimated daily intakes to the US EPA's reference dose (RfD) values for each of those parent pesticides. A Johnson S(B) distribution (four-parameter lognormal) was fit to these data to estimate the national distribution of exclusive exposures to these 12 parent compounds. Only three such pesticides had a few predicted values above their RfD (lindane 1.6%; 2,4-dichlorophenol 1.3%; chlorpyrifos 0.02%). Given the possibility of a subject's dietary intake of a pesticide's metabolites incorporated into treated food, our results show that few, if any, individuals in the general US population aged 20-59 years and not employed in pesticide application were likely to have exceeded the USEPA RfD for these parent compounds during the years studied.