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Introduction: When we administer atezolizumab plus bevacizumab treatment to patients with advanced hepatocellular carcinoma, we often encounter inconsistent results between the qualitative dipstick urinalysis and the urine protein/creatinine ratio(UPCR)measurements. In this study, we investigated the relationship between qualitative dipstick urinalysis and UPCR in these patients, and assessed whether incorporating UPCR into the testing protocol could prevent unnecessary interruptions during bevacizumab treatment., Subjects and Methods: This study analyzed 298 urine samples collected from 61 patients of advanced hepatocellular carcinoma, who were treated with atezolizumab plus bevacizumab at our institution between October 1, 2020, and August 31, 2021. We used UPCR as an alternative test to the 24-hour urine protein and set the discontinuation criteria for bevacizumab at a UPCR of 2.0 or higher., Results: Among the 41 samples that tested positive for 2+ on the dipstick test, only one(2.4%)had a UPCR exceeding 2.0. Additionally, among the 44 samples that showed a 3+ result, 24 samples(54.5%)had a UPCR higher than 2.0. If our decision to discontinue bevacizumab had been based on a dipstick urinalysis result of 2+, we could have continued administering bevacizumab in 97.6%(40/41)of the cases. Even if the decision had been based on a dipstick urinalysis result of 3+, we could have continued administering bevacizumab in almost half of the cases(45.5%, 20/44)., Conclusions: Our findings suggest that the addition of UPCR to the qualitative dipstick urinalysis during atezolizumab plus bevacizumab treatment for patients with advanced hepatocellular carcinoma could help prevent unnecessary interruptions of bevacizumab and offer more clinical benefits in real-world practice, compared to using qualitative dipstick urinalysis alone.

Considering the pharmacological effects of chiral drugs, enantiopure drugs may differ from their racemic mixture formulation in efficacy, potency, or adverse effects. Levomethorphan (LVM) and Dextromethorphan (DXM) act on the central nervous system and exhibit different pharmacological features. LVM, the l-stereoisomer of methorphan, shows many similarities to opiates such as heroin, morphine and codeine, including the potential for addiction, while the d-stereoisomer, DXM, does not have the same opioid effect. In the present study, NMR-based metabolomics were performed on the urine of rats treated with these stereoisomers, and showed significant differences in metabolic profiles. In urine within 24 h after treatment of these samples, levels of citrate, 2-oxoglutarate, creatine, and dimethylglycine were higher in LVM-treated rats than in DXM-treated rats. While urinary levels of hippurate and creatinine gradually increased over 72 h in DXM-treated rats, these metabolites were decreased in the urine by 48-72 h after treatment with LVM. The levels of these changed metabolites may provide the first evidence for different cellular responses to the metabolism of stereoisomers.

In Japan, the number of living renal transplant donors with medical complications has been increasing in recent years due to the.aging of donors. It is important to assess donor renal function properly before donation to ensure donor safety. This study aimed to assess different renal function measures of donors, includ- ing serum creatinine (Cr), creatinine clearance (Ccr), estimated glomerular filtration rate (eGFR), and inulin clearance (Cin). The mean Cr and eGFR values of 64 donors before surgery and at 1 month, 1 year, and 3 years after surgery were 0.74, 1.15, 1.13, and 1.05 mg/dL, respectively, and 71.7, 42.4, 44.9, and 49.5 mL/min/1.73m2, respectively. Values of eGFR 3 years after surgery in 20 out of 36 donors (55.6%) were less than 50 mL/min/1.73m2, showing that moderately decreased levels of GFR persist for a long time after donation. The preoperative renal function of 20 candidate donors was evaluated based on Cr, Ccr, eGFR, and Cin. The mean preoperative values were Cr 0.74 mg/dL, eGFR 71.9 mL/min/1.73m2, Ccr 137.3 mL/min, and Cin 92.9 mL/min. Ccr overestimated Cin in 18 out of 20 donors (90%) and eGFR underestimated Cin in 16 donors (80%). Cin measurements are complicated, which can lead to human errors in measurement. Conversely, eGFR measurements are simple but are inferior to Cin in terms of accuracy; therefore, the pre- operative renal function of donors should be evaluated by Cin, combined with other tests as much as possible to ensure a safe living renal transplant. [Original].

Creatine transporter deficiency (CRTR-D) is an X-linked disorder characterized by hypotonia, developmental delay, and seizures. We report the third Japanese family with CRTR-D. The proband was an 8-year-old boy who presented with hypotonia, severe intellectual disability and two episodes of seizures associated with/without fever. Among 7 siblings (4 males, 3 females), the eldest brother had severe intellectual disability, epilepsy, and sudden death at 17 years of age, while 18-year-old third elder brother had severe intellectual disability, autism, and drug-resistant epilepsy. The proband's urinary creatine/creatinine ratio was increased. A reduced creatine peak on brain magnetic resonance spectroscopy and a known pathogenic mutation in the SLC6A8 gene (c.1661 C > T;p.Pro554Leu) confirmed the diagnosis of CRTR-D. The same mutation was found in the third elder brother. Their mother was a heterozygote. Symptoms of CRTR-D are non-specific. Urinary creatine/creatinine ratio should be measured in patients with hypotonia, developmental delay, seizure and autism whose family history indicates an X-linked inheritance.

Human chorionic gonadotropin (hCG) is generally quantified in serum, but spot urine samples are also used to assess hCG levels in Japan. The purpose of the present study was to elucidate whether urinary hCG can be used clinically as a substitute for serum hCG. A total of 189 samples of serum and spot urine were collected from patients, including cases of normal pregnancy (NP) -13, abortion (AB) -21, extrauterine pregnancy (EP) 25, and hydatidiform mole (MOL) -7, during medical treatment and comparisons were made concerning serum and urinary hCG levels. The histogram of relative urinary/serum hCG(U-hCG.act/S-hCG) of the samples showed a wide distribution of values, but tended to converge to a narrow distribution by creatinine correction (U-hCG.cor/S-hCG). U-hCG.cor/S-hCG of the AB, EP, and MOL groups decreased 1 day to 14 days or was no earlier than 15 days postoperatively compared to preoperatively. The alteration of serum Intact/Total tended to be similar to that of U-hCG.cor/S-hCG in clinical course. The presented case indicated that U-hCG.act/S-hCG did not correspond to serum hCG levels. Because urinary hCG levels are inconsistent depending on whether spot urine is concentrated or diluted, the levels of hCG in spot urine do not always correlate with serum levels of hCG. Therefore, the data of urinary hCG should be interpreted after creatinine correction. Overall, it is recommended to determine serum hCG levels rather than creatinine corrected urinary hCG levels, considering that the relative urinary/serum hCG was not constant postoperatively.

Chronic kidney disease (CKD) significantly contributes to the increased number of dialysis patients with end stage renal disease. A new CKD risk classification (KDIGO 2009) established in 2011, which is defined by albuminuria and estimated glomerular filtration rate (eGFR) values, demonstrates the relative risks of CKD in great detail. In this study, we evaluated the clinical significance of urinary casts by categorizing a risk Group 1 to 5 according to the KDIGO 2009 classification. In the high risk CKD group (risk group 3 and over), we found a significantly higher number of patients who had > 100 hyaline casts/whole field (WF) in their urine than those that had < 100 hyaline casts/WF. Further, we determined the diagnostic accuracy for the high risk CKD group when the cutoff value for the number of hyaline casts was set at > or = 100 hyaline casts/WF (sensitivity: 44.7%, specificity: 96.5%). The eGFR value was significantly lower in the group with > or = 100 hyaline casts/WF, particularly in hypertensive patients, than that in the group with < 100 hyaline casts/ WF. Of interest is that the eGFR value was significantly lower in patients with 100-999 hyaline casts/WF and > or = 1,000 hyaline casts/WF than that in patients with < 100 hyaline casts/WF in A1 stage. Thus, our present study suggests that the presence of > or = 100 hyaline casts/WF indicates decreased eGFR, and the urinary casts counting may be important and useful for the screening and early detection of high-risk CKD.

Aim: We investigate the validity of the assessment of urinary protein excretion by spot urine samples collected by different methods in outpatients with chronic kidney disease (CKD). SUBJECTS AND METHODS We obtained 24-hour urine and two spot urine samples, including the first morning urine and daytime urine in 159 CKD patients. Urinary protein excretion was assessed by the protein/creatinine ratio from spot urine samples (morning: m-UP (g/gCr), daytime: d-UP (g/gCr) ]. We examined the correlations and the differences among m-UP, d-UP and the actual urinary protein excretion obtained by 24-hour urine (a-UP(g/day) ., Results: Significant correlations were found between m-UP and a-UP, and between d-UP and a-UP (r = 0.88, 0.85; p < 0.001). Correlations between m-UP and a-UP were greater relative to those between d-UP and a-UP in patients with less than 3.5 g/day of a-UP and in patients with CKD stages 1 to approximately 3. The percent difference between m-UP and a-UP was--16.0 +/- 40.5%, and that between d-UP and a-UP was 27.1 +/- 72.9%. The absolute value of the percent difference between d-UP and a-UP tended to be greater than that between m-UP and a-UP (34.9 +/- 25.9% vs. 49.9 +/- 59.9%, p = 0.06)., Conclusion: Urinary protein/creatinie ratio of the first morning urine is better approximate the urinary protein excretion obtained by 24-hour urine compared with that of spot urine in the daytime.

A 49-year-old pre-menopausal woman was diagnosed with left breast cancer(T2N0M0, stage II A). She was also diagnosed with chronic renal failure for the first time. We performed left breast conserving surgery and sentinel lymph node biopsy. Afterwards, we administered TC therapy(docetaxel 75mg/m / 2, cyclophosphamide 250 mg/m2)as adjuvant therapy every four weeks. No serious side effects occurred during therapy. TC therapy was a safe regimen for a patient with chronic renal failure in our case.

Bone mass of elderly women reduces after menopause, but the rate of reduction differ individually especially in the elderly, because bone metabolism of the elderly is influenced by many factors such as hormones, fractures, drugs, ability of exercise and/or nutritional level. Therefore, it is quite difficult to determine the normal ranges of the metabolism. As a whole, aging accelerates bone turnover slowly with wide range of individual variation. Subnormal renal function may effect on the excretion or metabolism of bone markers, such as osteocalcin. Urinary markers such as NTX corrected by urinary creatinine may be higher than the real level, because of low creatinine production in the elderly. These factors may influence on the elevated bone metabolism resulting in the discrepancy with morphometric evaluation.

Knowing the amount of protein excreted in the urine is important in determining the severity and activity of renal diseases. In general, screening tests have been carried out using the urine dipstick. However, there are limitations in determining the amount of urinary protein excretion using qualitative tests for protein in spot urine samples due to the concentration and dilution of urine. Therefore, when using spot urine samples, it is helpful to calculate the urine protein/creatinine ratio (P/C) by simultaneous measurement of urinary creatinine for determining daily protein excretion. We examined P/C measurements using the dipstick method in 22,718 subjects who visited our hospital for health examinations. The results showed positive rates for qualitative urinary protein (1 + and more) of 4.2% for males and 2.7% for females. Also positive rates for P/C (150 mg/g.cre and more) were found of 7.7% for males and 10.2% for females. The results showed a reversal of positive rates for males and females compared with the results of qualitative urinary protein. In addition, P/C showed a higher positive rate in 70 years old or older both for males and females. The distribution of urinary creatinine levels simultaneously measured by dipstick method showed that the percentage of diluted urine with urinary creatinine level less than 50 mg/dL was 6.8% for males and 18.3% for females overall. Females showed a higher rate and the percentage tended to increase with age both for males and females. From these results, it was suggested that changes in urinary creatinine excretion with age that affect the P/C ratio are large. We then measured the albumin excretion rate in the 24-hour urine as well as examined the correlation between the urinary creatinine concentration and albumin index with regard to age and sex in 1,280 diabetic patients. The results showed that daily urinary creatinine excretion overall in males, overall in females, in males over 80 years old and in females over 80 years old were 1.063 +/- 0.428 g/day (mean +/- S.D.), 0.714 +/- 0.270 g/day, 0.666 +/- 0.201 g/day, and 0.531 +/- 0.017 g/day, respectively, which showed large variations. From these results, creatinine correction, in which uniformity of daily urinary creatinine excretion is the principle, is useful for assessment of short-term fluctuations in the individuals. However, it is indicated that there is a problem when used for screening, from young people to the elderly.

TS-1 is an oral anti-tumor drug, which contains 5-chloro-2, 4-dihydroxypyridine (CDHP), a compound mainly excreted in urine. Since the CDHP concentration is increased among patients with impaired renal function, the frequency of side effects of TS-1 increases in such patients. Therefore, we constructed a computer-aided system that enables prompt monitoring of creatinine clearance (Ccr) calculated from the serum creatinine levels of patients prescribed TS-1 at the time pharmacists prepare the medicine. With this system, we found two cases who were prescribed TS-1, despite their decreased Ccr. One was a patient whose estimated Ccr was less than 30 mL/min/m2. With such renal malfunction, pharmacokinetics of the drug was considerably changed compared with normal control, and the dosage should be reduced. The other case presented with severe jaundice and had only a mild decrease of renal function (Ccr: 50 mL/min/m2). So we measured the concentration of uracil in the urine and performed a drug lymphocyte stimulation test for further investigation of concomitant affecting factors. Our system is useful because it can show pharmacists both the dosage TS-1 patients take and their renal function at a glance in real time. This system can be adapted for every medicine which might accumulate in patients with renal dysfunction.

Objectives: The quantification of 24 hrs urinary protein excretion is valuable for diagnosing and monitoring renal disease. However, because of its practical difficulties, the spot urinary protein/creatinine (P/C) ratio has been utilized. We aimed to evaluate the analytical performance of P/C ratio by comparing with the qualitative urinary protein values and the microscopic urine sediment analysis., Methods: We obtained 5,538 urinary samples from the outpatients of Juntendo University Hospital. Testing for urinary P/C ratio was performed by Atlas Pro12 (cut-off 150 mg/g x Cr), urinary protein (proteinuria) was detected quantitatively by full-automated system ATLAS XL (cut-off 30 mg/dL). Microscopic exams were conducted following to the JCCLS reference method., Results: The P/C ratio demonstrated higher sensitivity but lower specificity for urinary abnormal casts detected by microscopic exams compared to proteinuria (sensitivity; P/C 87%, proteinuria 77%. specificity; P/C 74%, proteinuria 93%). From the comparative study with microscopic exams, both P/C and proteinuria performed high positive rate (> 80%) for the granular cast type and mixture cast type. For the cellular cast type, however, the positive rate of P/C was 56% and that of proteinuria was only 36%. The overall abnormal casts by microscopic exams showed better correlation with the positive P/C ratio than proteinuria., Conclusion: This study emphasizes that a spot urine P/C ratio is useful in screening for the further microscopic exams. P/C ratio can be a convincing index of urinary protein excretion when attenuation urine is doubted.

Chronic Kidney Disease (CKD) is an important risk factor of the End Stage Renal Disease (ESRD). In this study, we investigated whether the protein to creatinine ratio (the ratio of P/C) determined by the semiquantitative urinary stick test and urinary sediments are useful for the early detection of CKD. One hundred sixty patients were classified to four or five groups by P/C ratio and various biochemical markers were analyzed. As a result, the 300 mg/g x Cr of P/C group showed a significantly increased serum cystatin C level. The positive rate of the P/C ratio in CKD stage was significantly increased compared with the conventional protein qualitative analysis. Further, the amounts of urinary sediments in CKD stage 1 to 2 were increased, such as hyaline cast, and pathological casts were increased in CKD stage 3 to 5. Thus, our present study suggests that the ratio of P/C and urinary sediments are useful for the screening of CKD.

Biapenem has been used in pediatric patients as well as adult patients; however, little information is available on dosing regimens for pediatric patients. This study examined biapenem pharmacokinetics in pediatric population and performed pharmacokinetic-pharmacodynamic analysis. Biapenem plasma concentrations from 10 pediatric patients were pharmacokinetically analyzed. A multi-regression analysis showed the pharmacokinetic parameters were affected by body weight and creatinine clearance of the patients. Using the pharmacokinetic parameters, a Monte Carlo simulation predicted the probabilities of attaining the pharmacodynamic target (40% of the time above the minimum inhibitory concentration for the bacterium). In the case of about 20 kg, biapenem regimens of 5 mg/kg b.i.d. and 10 mg/kg b.i.d. provided sufficient target attainment probabilities against Streptococcus pneumoniae and Pseudomonas aeruginosa isolates, respectively. Our results should provide a PK-PD-based guidance for rationalizing biapenem regimen according to the body weight and renal function of a pediatric patient and the specific bacterium suspected.

Background: Two activated charcoal preparations, Kremezin (K) and Merckmezin (M), are both available in Japan and derived from similar materials. However, their microstructures are distincty different, and possibly reflect differences in their properties of absorbance. To evaluate the difference between K and M, we investigated the effects of K and M on the clinical parameters related to uremia in pre-dialysis patients., Methods: A prospective, randomized, open-label, two-arm, parallel-group comparative clinical trial was planned, as follows. After the 4-week observation period, twenty-two patients who were enrolled in this study were randomly distributed into two groups, K or M, for 8 weeks., Results: There were no significant differences between the K and M groups in the characteristics of the patients. The rate of change of serum indoxyl sulfate was significantly reduced in the K group compared with the M group (p=0.002). Creatinine clearance was preserved in the K group, but decreased in the M group (p=0.045)., Conclusions: K had more favorable effects in adsorbing uremic toxins and preserving renal function in the uremic patients than M.

Background: The carboplatin (CBDCA) dosage is usually calculated using the formula of Calvert. Instead of the glomerular filtration rate (GFR), 24-h creatinine clearance (24 CLcr) is often used in this formula, which is calculated based on 24-h urine collection in clinical practice., Objective: We studied the adequacy of 24 CLcr in calculating the appropriate dosage of CBDCA using the formula of Calvert and compared CLcr and GFR using various substitutable predictive formulas (the formulae of Cockcroft and Gault, Yasuda, Orita, Jellife, Mawer, MDRD, and modified MDRD) when we were not able to use 24 CLcr., Methodology: We retrospectively studied 193 patients who received CBDCA as chemotherapy during the period April 2004 through November 2006. We evaluated the adequacy of 24-h urine collection for measurement of creatinine production and excretion. We also evaluated the appropriate urine collection within a 15% range of the difference. The correlation between the appropriate 24 CLcr resulting in the urine collection and the CLcr or GFR was examined using past predictive formulae in the patients with appropriate urine collection., Results: The accuracy of 24 CLcr was evaluated in 83 patients (43%). There was a significant correlation between CLcr or GFR using various predictive formulas and the appropriate 24 CLcr. There was an especially close and significant correlation with the formulae of Cockcroft and Gault and Yasuda (r>0.950, p<0.001)., Conclusion: When using the Calvert formula, the accuracy of 24 CLcr should be evaluated. Patients evaluated as having inaccurate urinary collection should use the formulae of Cockcroft and Gault and Yasuda.

Purple urine bag syndrome (PUBS) occurs predominantly in chronically catheterized and constipated patients. This syndrome is associated with bacterial urinary tract infections that produce sulfatase or phosphatase. Tryptophan is converted to indole and indigo-producing bacteria have indoxyl phosphatase or sulfatase that can produce indigo (blue) and/or indirubin (red) in patients with urinary tract infection. To further explore the metabolism of these amino acids, we evaluated the serum levels of amino acids in patients with PUBS. A total of 15 patients were enrolled in this case-control study (PUBS-positive case group: 5 patients, PUBS-negative control group: 10 patients). Data from urine tests (pH, sugar, protein, leukocyte counts), renal functions (BUN, creatinine), serum levels of amino acids, and performance status were compared between the two groups. No significant differences were seen between the two groups in urine sugar, protein, leukocyte counts, renal functions, and performance status. The mean urine pH was significantly higher in PUBS patients than in control patients (8.5+/-0.0 vs. 7.3+/-1.16, respectively, p=0.0321), and serum levels of alpha-aminobutyric acid were significantly higher in PUBS patients than in control patients (16.2+/-3.08 vs. 12.4+/-3.20, respectively, p=0.0275). These data suggest that strong alkaline urine acts as an important factor in PUBS, in combination with other facilitating factors.

We propose an improved method to measure urinary D-glucaric acid (GA), which might be of value as an indirect index of the activity of cytochrome P450 (CYP). This method was about 20 times more sensitive than existing methods. Beer's law was obeyed in the concentration range 5.5-66 ng ml(-1) for GA, with the effective molar absorptivity at 533 nm and the relative standard deviation being 9.1 x 10(5) dm(3) mol(-1) cm(-1) and 0.69% (n = 6), respectively. In addition, we introduced the correction value {GA/Cr ratio x10} of urinary GA by measuring urinary creatinine (Cr) at the same time. Based on the proposed method, the GA and Cr values in spot urines of healthy persons and cancer patients were subsequently measured and the correction values of both groups subjected to comparison. As a result, a statistically significant difference was recognized between the two groups.

Immunoglobulin A nephropathy (IgAN) is now recognized as the most common form of primary glomerulonephritis worldwide and is the major cause of end-stage renal disease. As reported, the renal survival rate is 61% at 20 years and the renal prognosis of this disease is relatively poor on long-term observation, hence various protocols have been attempted to control this disease. At Iizuka Hospital, a prospective study of tonsillectomy with methylprednisolone pulse therapy was performed for the treatment of patients with IgA nephropathy from August 2002. We reviewed the clinical efficacy of our protocol. From August 2002 to July 2006, 31 patients whose IgA nephropathy was demonstrated by percutaneous renal biopsy were administered our regimen. In our study, 12 patients had an observation period of more than 24 months. Our protocol consisted of tonsillectomy with one course of methylprednisolone pulse therapy. Methylprednisolone at the daily dose of 1,000 mg for 3 consecutive days followed by oral steroid at the daily dose of 20 mg, was gradually tapered, and discontinued one year later. All of the patients were administered angiotensin-converting enzyme inhibitors or angiotensin receptor blockers with favorable control of hypertension. The mean observation period for the 12 patients with IgA nephropathy was 37.4 months. The mean age at renal biopsy was 34.8 +/- 12.2 years. The male-female ratio was 3:9. At the renal biopsy in our hospital, mean creatinine value was 0.95 +/- 0.38 mg/dL, mean creatinine clearance was 92.1 +/- 34.9 mL/min, and the mean urinary protein and urinary creatinine ratio was 3.52 +/- 4.36. After 24 months, mean creatinine value was 1.03 +/- 0.59 mg/dL, mean creatinine clearance was 91.2 +/- 42.3 mL/min, and the mean urinary protein and urinary creatinine ratio was 0.83 +/- 0.98. Urinary protein and urine occult blood became negative in 66.7% of patients, and the urinary remission rate was 58.3%. On our protocol, mean length of the hospital stay was 11.4 +/- 4.7 days. Our prospective study showed that tonsillectomy with one course of methylprednisolone pulse therapy in IgA nephropathy appears to be beneficial for urinary remission and contributes to a short hospital stay.

Unlabelled: Dipstick urine analysis is the most common and convenient examination in routine health care. The criteria for abnormal proteinuria is a level of more than (+). However, the interference of urine concentration should be considered in the judgement., Objective: The purpose is to demonstrate the effect of the combined use of specific gravity (SG) in the dipstick judgement to evaluate pathological proteinuria in Japanese people., Methods: The hospital laboratory database of Kitano hospital was searched for urine samples, for patients consulted at our nephrology department from Oct. 2004 to Sep. 2005 (n=1767), and simultaneously assayed for dipstick proteinuria(DSP), SG, urinary protein, urine creatinine (UC) and urinary protein-creatinine ratio (UPC ratio). To generate a model table, samples were stratified according to DSP and SG values. A DSP versus SG matrix (5 x 6)was created, and then all 30 cells were color-coded by the pathological proteinuria proportion (white: < 5%, gray: 5-95%, black: <95%)., Results: SG was positively associated with UC. In the patients, SG < or = 1.005 and DSP(-), 12/70 (17.1%) was > or =300 mg/gCr. Moreover in the patients, both 1.005 < SG < or = 1.010 and DSP(+/-), 21/32 (65.6%) had pathological proteinuria. We confirmed the consistency for this combination table in the urine samples of another 1111 out-patients. Moreover, the area under the curve in DSP(+/-) suggests that the patients whose SG was < or = 1.011 might have pathological proteinuria (sensitivity; 82.1%, specificity; 89.3%)., Conclusion: We recognized that the combination of DSP and SG enhances a more accurate proteinuria judgement. DSP(- approximately +/-) in diluted urine (SG < or = 1.1011) has the potential for pathological proteinuria. Therefore, diluted urine samples should be re-examined.

Preanalytical issues in laboratory medicine have been recognized to be important but not so much effort have been focused to them. Urinalysis is one of the most susceptible examinations to preanalytical issues because urine samples are collected by patients themselves and so is stool examination too. Midstream urine catch is well-known appropriate procedure for many urinalysis. Surface scratching is an appropriate method of stool occult blood testing for colorectal cancer and also strategies to avoid the contact of stool with toilet water is another important technique. We also report a case of abnormal results of creatinine clearance (Ccr) caused by the urine collection apparatus as an example of preanalytical issue.

Background: It has been reported that elderly outpatients take at least 6 different kinds of medication., Purpose: To know which formula will best predict creatinine clearance, because 24-hour urine collection is difficult for elderly outpatients., Patients and Methods: We compared four types of formulae (Cockcroft and Gault, Yasuda, Orita, Walser) to estimate creatinine clearance using serum creatinine of 143 elderly inpatients (73 men, 70 women, mean age 82.9 +/- 8.6 years old) including 67 extremely elderly people with various underlying diseases., Result: The formula of Cockcroft and Gault showed the best correlation with creatinine clearance in the extremely elderly subjects (r = 0.74) as well as in people under 85 years (r = 0.76). However, the estimated values of the extremely elderly women were lower than actual creatinine clearance., Conclusion: The formula of Cockcroft and Gault is the best predictive equation of creatinine clearance, except in the extremely elderly women.

Background: In burn patients, microvascular permeability is increased. It is difficult to decide the time to administer albumin because it may induce pulmonary edema in the re-filling period. One report shows that microalbuminuria is correlated with endothelial injury and systemic microvascular permeability., Methods: We measured urinary albumin/creatinine ratio (ACR) in 4 burn patients for 48 hours after injury., Results: In all patients, ACR was elevated in the early period after injury. Moreover, ACR in 2 severe burn patients with burn total body area of over 30% was above the normal range., Conclusions: The present results show that ACR seems to be correlated with the level of microvascular permeability in 4 burn patients. We conclude that ACR may be a useful indicator to decide the time to administer albumin to a burn patient. However, further investigation is required to decide the threshold value of ACR in a severe burn patient whose ACR are kept above the normal range in the long-term.

Steroid myopathy is usually a slowly progressive disease, which causes weakness primarily to the proximal muscles of the upper and lower extremities. The monitoring of this problem is difficult in situations in which the primary disease itself produces muscle weakness. The distinguishing feature in steroid myopathy is the occurrence of creatinuria in the presence of normal muscle enzymes including creatine kinase and aldolase. To evaluate the usefulness of percent creatinuria {urinary excretion of creatine/(urinary excretion of creatine + urinary excretion of creatinine)} in the diagnosis of steroid myopathy, we measured percent creatinuria in 26 patients (14 male and 12 female) without muscle diseases before the initiation of steroid treatment We found that the median values of percent creatinuria of the male and female patients were 2.5% and 17.1%, and that the ratios of the male and female patients presenting with an elevated percent creatinuria (more than 10%) were 3 out of 14 patients (21.4%) and 8 out of 12 patients (66.7%), respectively. We also found one patient with mild renal dysfunction presenting with an elevated percent creatinuria but without muscle weakness or myalgia. These findings suggest that the measurement of percent creatinuria is of little value in the diagnosis of steroid myopathy with a cutoff value of 10%. Furthermore, it is important to measure percent creatinuria before the steroid treatment, while paying close attention to the measurement method, sex, renal function and protein level of the diet.

The influence of concentration and dilution has been the major issue of urinalysis. This study is to evaluate the usefulness of protein (P)/creatinine (C) ratio (P/C ratio) in spot urine by test strips method. For this purpose, the basic performance of creatinine test strips is evaluated and judging criteria for the urine P/C ratio is defined. Our evaluation revealed that the creatinine test strips were basically not affected by substances which have similar composition to creatinine, such as creatine, but by some medical agents and disinfectant. Its minimum detective sensitivity was 6.0 mg/dl, while that of protein test strips was 1.3 mg/dl. We determined judging criteria for the P/C ratio as follows: Below 80 mg/gCr, Normal; 80 to 500mg/gCr, 1 +; over 500 mg/gCr, 2+. The P/C ratio based on the quantitative and test strips methods provided good consistency of 82.2%. In low-creatinine urine samples (11 to 99mg/dl), 181 of 216 samples (83.8%) were tested negative on single-protein tests; while the P/C ratio provided fewer negative results, 134 of 216(62.0%). Moreover, in high-creatinine urine samples (200 to 600 mg/dl), 70 of 122 samples (57.4%) were tested negative on single protein tests; while the P/C ratio provided negative results in almost all the samples, 120 of 122 (98.4%). These urine samples were mostly collected at a medical examination. The results above showed that the P/C ratio obtained by easy and quick test strip method is equivalent to the quantitative method in performance and useful for spot urine testing.

The purpose of this study was to evaluate the clinical usefulness of novel test strip that simultaneously measure urinary albumin and creatinine. Testing was performed on 95 random urine samples from diabetics. Each sample was assayed with following methods: test strip by instrument (AX4280) reading and by visual interpretation, quantitative method for albumin, creatinine, and alpha1-microglobulin and cellulose acetate membrane electrophoresis. The results of test strip had good correlation with quantitative results. In the case of instrument reading, the sensitivity, specificity and consistency were 91.2%, 78.9% and 86.3% for albumin and 94.5%, 87.5% and 91.6% for albumin index (albumin/creatinine ratio; A/C ratio), respectively. The percent same level agreement for creatinine was 63.2%. After correction using creatinine value on test strip, 18.4% of samples defined as negative by albumin quantitative value were turned to be positive, 12.3% of samples defined as positive were turned to be negative. The same level of creatinine correction effect as the quantitative method was obtained at the test strip. When alpha1-microglobulin/creatinine (alpha1 m/g x Cr) ratio was compared with albumin index, percent positive of alpha1 m/g x Cr ratio was 35.0% for samples with albumin index less than 30 mg/g x Cr, 59.5% for those with albumin index between 30 and 300 mg/g x Cr. In addition, on cellulose acetate membrane electrophoresis, both retinol binding protein (RBP) and beta2-microglobulin (beta2 m) were detected in 12.5% of patients in normal condition or pre-nephropathy. Among patients at early-nephropathy, the detection rate of RBP and beta2 m were 20.0% and 15.0% respectively. These results indicate that the renal tubule is also damaged at the early stages of nephropathy.

Inulin clearance (Cin) is widely believed to be the gold standard of the glomerular filtration rate (GFR). However, in Japan, Cin has not been officially recognized by the Ministry of Health, Labour and Welfare of Japan for clinical use. Creatinine clearance (Ccr) has been used to estimate the renal function of patients, but there have been many studies in which Ccr estimates were GFR falsely high because the metabolism and tubular excretion of creatinine widely varied according to the pathophysiological state of the patient. In the present study, we determined Cin and Ccr simultaneously in 116 adult patients with renal diseases and diabetic mellitus. The clearance study was performed by the modified Wesson's method. The inulin preparation was FFI-1010 (Fuji Yakuhin Co. Ltd.). Inulin in serum and urine was determined by the newly devised enzymatic assay (Toyobo Co. Ltd.), which is specific for inulin. The mean Cin was 35.0 +/- 14.4 ml/min/1.73 m2. The mean Ccr(the enzyme assay) was 63.6 +/- 24.1 ml/min/1.73 m2 and that of the kinetic Jaffe assay was 55.3 +/- 19.3 ml/min/1.73 m2. Mean Ccr/Cin was 1.93 +/- 0.73, 1.69 +/- 0.62, respectively. This ratio was significantly different(p < 0.05) in the degree of reduction of Cin, with values of 2.07 +/- 0.82 (Cin < 40 ml/min/1.73 m2) and 1.64 +/- 0.32(40 < Cin < 80 ml/min/1.73 m2), respectively. Only 8 patients were classified into the same degree of reduced renal function (the Guideline of Japanese Society of Nephrology). The findings of this study suggest that the GFR determined by Ccr could misjudge the renal function of patient and delay the administration of proper treatment of the patient. Introduction of Cin into the clinical field is necessary to avoid this delay.

The Diabetic Nephropathy Committee recommends the use of revised criteria for the early diagnosis of diabetic nephropathy in Japan. The new criteria are as follows: 1) Urinary albumin should be determined by immunoassay using a morning spot urine sample in diabetic patients without proteinuria or with dipstick-positive(+ 1) proteinuria. 2) A urinary albumin-to-creatinine ratio ranging from 30 to 299 mg/ gCr in 2 or more of 3 specimens may be diagnosed as microalbuminuria. 3) Two alternatives, i.e. the urinary albumin excretion rate of 30-299 mg/24hr in 24hr urine collection or 20-199 microg/min in timed urine collection can be used to detect microalbuminuria. 4) Renal hypertrophy and elevated urinary type IV collagen may indicate the existence of diabetic renal disease. 5) Microalbuminuria originating in non-diabetic diseases should be excluded.

Proteinuria is quantified for diagnostic and prognostic purposes and to assess responses to therapy. Methods used to assess urinary protein include 24-hour urine collection (24-Up) and determination of the ratio of protein to creatinine concentration (Up/Ucr) in simple voided urine samples (Up/Ucr quantitative method). However, these methods are costly and time consuming. The Multistix PRO 11 (Bayer Medical Co., Ltd., Tokyo, Japan) is a new urine dipstick that allows rapid measurement of Up/Ucr. Results obtained with the Multistix PRO 11 coincided well with those obtained with the 24-Up method (kappa = 0.68) and the Up/Ucr quantitative method (kappa = 0.75). However, Multistix PRO 11 did not accurately measure moderate to severe proteinuria (> or = 500 mg/g. Cr). Our findings suggest that Multistix PRO 11 is useful for the screening, assessment, and follow-up of mild proteinuria.

To collect 24-hour urine of infants and young children is so difficult that 24-hour urinary protein excretion (24 H-UP) has been estimated from single voided urine samples. We investigated the correlation between 24 H-UP and the protein/creatinine ratio of the first voided morning urine samples (MUP/Cr) and evaluated the problems associated with this method. Six hundred and thirty-nine specimens, pairs of morning spot urine and 24-hour collected urine, were collected from 158 patients, aged 3 to 28, who were being followed at Kyoto City Hospital. The study population was divided into different subgroups by age, disease category and inpatient or outpatient status and linear regression analysis was performed for every subgroup. Although MUP/Cr correlated well with 24 H-UP, it was necessary to revise the estimation of 24 H-UP from MUP/Cr, which is lower in infants and young children because of age-related differences in creatinine excretion. If the patient's age is younger, the creatinine excretion rate is lower. The difference in 24 H-UP estimated from MUP/Cr was significant between inpatients and outpatients, with the estimated value being higher in outpatients than inpatients. The estimated value was also different according to disease category. We speculated that the difference in estimated 24 H-UP was affected by different rate of creatinine excretion related to age and other factors.

We calculate the salt intake, the protein intake and the % creatinine generation rate, the index for the muscle volume/exercise, based on the sodium, urea and creatinine level in the urine in patients under home care and retain the data in the database. To date, 45 patients under home care have been enrolled. The mean age is 70.9 years (+/-13.8, SD). The underlying disease treated under home care include malignant tumor in 23 patients (51.1%), cerebrovascular disorders in 11 patients (24.4%), neurological/muscular disorders in 6 patients (13.3%) and other diseases in 5 patients (11.1%). The analysis of the data obtained from the collected urine has revealed that the % creatinine generation rate was significantly low in the patients with neurological/muscular disorders and that the % creatinine generation rate, the protein intake and the salt intake were high in the patients under the central venous nutrition. The analysis has also revealed that the % creatinine generation rate and the protein intake were lower in the patients who are less independent in daily lives. These findings substantiate that the 24-hour urine collection is useful for the assessment of nutritional condition in patients under home care.

To determine the reference intervals of urinary albumin, immunoglobulin G, transferrin, alpha 1 microglobulin, and N-acetyl-beta-D-glucosaminidase, we measured those components and creatinine in urine from men with normal blood pressure(systolic < or = 139 mmHg and diastolic < or = 89 mmHg), HbA1c < or = 5.8% and negative qualitative tests of urinary protein and hematuria. The subjects were 150 men in their thirties, 136 in their forties, and 135 in their fifties. Urines was collected in the morning after at least 12 hours fast and stored at -80 degrees C until assayed. The levels of creatinine decreased with age, whereas no change was observed in the levels of other urinary components. Consequently, the levels of those components expressed as g. creatinine increased with age. The reference intervals per g. creatinine were determined for each age-bracket using the iterative truncation method after logarithmical transformation of the values.

Effects of dopamine and dobutamine on renal function and urinary excretion of prostaglandin E2 (UPGE) were studied in 21 elderly patients who underwent abdominal surgery. Fractional sodium excretion (FeNa), creatinine clearance (Ccr), urinary volume (UV, ml.kg-1.min-1) and UPGE were measured on the first and second postoperative day. These patients were divided into three groups: i.e. C (control), DA (dopamine) and DB (dobutamine) groups. Group DA received dopamine 2 mcg.kg-1.min-1 beginning at six o'clock on the first postoperative day. Group DB received dobutamine 2 mcg.kg-1.min-1. There were no significant differences in UV and UPGE among these three groups. Ccr was significantly higher on the second postoperative day than that on the first postoperative day in DA group. FeNa in DA group was higher than in C group on the second postoperative day. The relationship between UPGE and UV was not determined. These results suggest that DA improve renal functions in the elderly.

When women with kidney disease wish to have children, concerns are raised about the adverse effect on their renal function. Although the situation is less clear in regard to the effects, there is general agreement that a moderately severe decrease in renal function, especially in the presence of significant hypertension, reduces the chance of conception, and a successful outcome of gestation. On the other hand, several reports maintain that in most patients, pregnancy does not change the natural history of glomerular disease. Accordingly, we reported successful cases in whom renal function remained preserved. The three cases suffered from different types of glomerulonephritis (GN) and percutaneous renal biopsies were conducted before pregnancy. All biopsy specimens were examined by light and immunofluorescence microscopy, and were diagnosed as IgA nephropathy, sclerosing GN and membranoproliferative GN, respectively. Since severe histological findings were found and their data worsened (serum creatinine > 1.3 mg/dl, 24-hr creatinine clearance < 70 ml/min), their chance of having children appeared low. However, as we did not observe deterioration of clinical findings and hypertension over the ten-year follow-up, we allowed conception resulting in the birth of normal children. Thus we should mention the relatively favourable courses of nephropathy in some patients with GN, particularly in patients with stable renal disease and normal blood pressure, it should not be considered an indication for termination. It is important to observe the status of glomerular disease for as long as possible.

Bone densities measured by ultrasound at the calcaneus, and urinary hydroxyproline (H.P) and calcium (Ca) concentrations adjusted for creatinine (Cre) were measured in 79 pregnant women, aged 20 to 38 years, at 5-40 weeks of gestation. Stiffness calculated from the combined value of speed of sound and broadband ultrasound attenuation was used as an index of bone density. The relationships between Stiffness and period of gestation, urinary H.P/Cre and Ca/Cre, and such lifestyles as current and past food intake frequency, physical activity and history of participating in sports obtained by questionnaire were examined using stepwise multiple regression analysis, including age and weight as independent variables. 1) The means of Stiffness in women with the gestation period of more than 20 weeks (primipara 79.6, multipara 83.4) are a little lower than those of non-pregnant and healthy women within the same age range. 2) Period of gestation showed a significant negative correlation to Stiffness. Significant positive correlations were found between urinary H.P/Cre and period of gestation. These results suggest that bone resorption increases with stage of gestation and causes bone loss in pregnant women. 3) Significant relationships with Stiffness was found only in frequency of cow's milk intake before pregnancy among various lifestyle factors. Stiffness of the subjects who took cow's milk every day before pregnancy was significantly higher than those who took less than 2-3 times per week or none. This result indicates that cow's milk and dairy products intake before pregnancy may be important for bone mineral maintenance during pregnancy.

Physical activity is known to increase glucose tolerance and insulin sensitivity. To examine the influence of physical inactivity on insulin sensitivity in aged people, insulin sensitivity and secretion was measured by using a two-step euglycemic glucose clamp, a glucagon tolerance test (GTT), an oral glucose tolerance test (OGGT) and urinary CPR excretion in 11 aged patients immobilized in bed for more than 12 weeks. The results were compared with those of nine healthy mobile aged controls. The muscle volume of the immobilized patients decreased by 20-25% compared with that of the controls, and insulin sensitivity decreased 50% in each step. These results mean that the immobilized patients had decreased insulin sensitivity and responsiveness, even when there was muscle atrophy. The glucose and insulin responses in both the GTT and OGTT showed that there was a slight decrease in the initial response of insulin in the immobilized patients and was in the controls compared with adolescent controls. There was no difference in the initial response of insulin between the immobilized patients and the aged controls. The ratio of impaired glucose tolerance in the OGTT was 4/11 of the immobilized patients and 3/9 of the controls. Total insulin secretion was increased and insulin sensitivity and responsiveness was decreased in the immobilized patients. This suggests that the decreased insulin sensitivity was compensated for increased by insulin secretion in the immobilized patients.

Urinary free dopamine (U-f-DA) is derived from renal DA synthesized in the renal proximal tubules, and plays an important role for diuresis and natriuresis. We were previously reported that U-f-DA was the superior marker of renal function as compared with ordinary methods including alpha 1-microglobulin (U-alpha 1 MG), beta 2-microglobulin (U-beta 2 MG) and N-acetyl-beta-D-glucosaminidase (U-NAG) in spot urine samples. U-f-DA can be used as index for the evaluation of renal transplantation. In order to evaluate the clinical usefulness of U-f-DA as a marker of renal function, we investigated as follows; firstly, the age related changes of U-f-DA in healthy out-patients, secondly, the correlation between U-f-DA and creatinine clearance (CCr), serum creatinine (S-Cr) in in-patients, and thirdly, the chronological changes of U-f-DA, U-alpha 1 MG, U-beta 2 MG, CCr and S-Cr in patients with chronic renal failure before and after renal transplantation. There is no age-related changes in U-f-DA from patients with 3 years to 88 years old. U-f-DA was positively correlated with CCr and negatively correlated with S-Cr. There are parallel changes of U-f-DA and CCr in increasing direction, on the other hand, parallel changes of U-alpha 1 MG, U-beta 2 MG and S-Cr in decreasing direction after renal transplantation. In patients with post renal transplantation who were not well controlled, S-Cr increased gradually with the decreasing level of U-f-DA. These results suggest that the measurement of U-f-DA in spot urine samples is useful marker for evaluation of the renal function and can be used an index of viability of the transplanted kidney.

The usefulness of the urinary calcium/creatinine (Ca/Cr) ratio, the oldest marker of bone resorption, is limited because of the influence of sodium intake and urine volume. The urinary Ca/Cr ratio was therefore compared with urinary calcium corrected for the urine osmotic pressure (Ca/OSM). Significant correlations are found between the Ca/Cr ratio and both creatinine (r = -0.386) and osmotic pressure (r = -0.473) in random urine samples from normal subjects, but similar correlations were not found for urine Ca/OSM. No significant correlation was found between Ca/OSM and Na/OSM, but the correlation coefficient between Ca/Cr ratio and Na/Cr ratio was 0.399. Thus, the Ca/Cr ratio is affected by urinary volume and sodium concentration, but the Ca/OSM ratio is not. The Ca/OSM ratio may therefore be a more accurate marker of bone resorption, because one of the main components of urinary osmotic pressure is sodium that inhibits tubular calcium reabsorption. The Ca/OSM ratios measured from 24-hour urine samples were found to be strongly correlated with the values measured from samples obtained during sleep (sleep urine, 0.823) and were slightly less strongly correlated with the values measured from second morning samples (0.641). Because bone resorption is especially active at night, the Ca/OSM ratio in sleep urine may be the most sensitive marker of bone resorption. The Ca/OSM ratio in sleep urine samples increased with age in normal women.

We studied the effects of repeated low-flow sevoflurane anesthesia for 6 hours. Five beagle dogs received 1.3 MAC (3%) sevoflurane anesthesia. Anesthesia of 6 hours was repeated on at the 7th day after the first anesthesia. Compound A gas samples were collected from the inspiratory limb during anesthesia. Concentrations of serum and renal fluoride, hepatic and renal function parameters were measured during and up to 7 days after the first and second anesthesia. The peak concentration of compound A was 23.7 +/- 3.6 ppm at 2 hours and the same level remained during the anesthesia. Plasma fluoride level exceeded 50 mmol.l-1 during anesthesia and rapidly decreased to the preanesthesia level thereafter. Serum GOT increased slightly only on the first postanesthesia day. No significant changes in other blood chemistry studies were observed. The excretion of renal tubular enzymes did not increase during and after anesthesia. Repeated low flow sevoflurane anesthesia in beagles did not affect hepatic and renal function significantly.