Assessment of glomerular filtration rate in diabetic nephropathy using the plasma clearance of 51Cr-EDTA

Tumor promotion/progression is known to be due in part to increased signaling through a variety of mitogenic pathways, including protein kinase C (PKC). To determine whether increased PKC activity could play a role in promotion and progression of renal cancer, we monitored PKC activity in normal and progressively transformed renal neoplasias from Eker rats. Eker rats carry a defect in the tumor suppressor TSC2 gene that predisposes them to renal carcinoma, whereas additional factors influence tumor promotion/progression in accordance with a "two-hit" model. We used the phosphorylation of adducins at Ser-660, a known PKC phosphorylation site, as a reporter for endogenous PKC activity. In normal proximal tubules, total adducin levels (measured with a phosphorylation state-insensitive antibody) were relatively high, whereas pSer660-adducin (measured with a phosphorylation state-sensitive antibody) levels were very low. In comparison, in renal carcinomas, total adducin levels were decreased, and pSer-660-adducin levels were increased. Changes in phosphorylation correlated with changes in localization. In normal tissue, alpha- and gamma-adducin are targeted to the apical and basal membranes of proximal tubules, respectively, implying unique functions for these related proteins. In early lesions (atypical tubules), differential targeting is lost, and both alpha- and gamma-adducins localize to the basal membrane. In more advanced lesions, staining in lateral membranes at cell-cell contacts becomes apparent. Furthermore, in cells that have lost basement membrane contact, plasma membrane targeting is no longer apparent. These changes in adducin expression levels, phosphorylation state, and localization parallel the increased growth potential and dedifferentiation of the progressive tumor phenotypes. These data demonstrate the utility of phosphorylation state-selective antibodies in immunohistochemical applications as reporters of endogenous PKC activity in tissue samples. We also provide the first evidence that increased PKC activity and phosphorylation of important target proteins occurs during progressive transformation in a non-phorbol ester tumor promotion model in vivo.     

Comparison of 51Cr-EDTA with 99m-Tc-DTPA slope clearance for estimation of glomerular filtration rate using the one compartment model

AIM: Of this study is to determine the relationship between 51Cr-EDTA and 99mTc-DTPA slope clearance applying the "one-compartment model". METHODS: The "one-compartment model" was chosen to calculate and to compare the glomerular filtration rates of 25 patients with normal and pathological creatinin values after injection of 51Cr-EDTA and 99mTc-DTPA simultaneously. RESULTS: The two clearance values correlated well (r = 0.996), and the 99mTc-DTPA clearance was systematically higher (28%). The 99mTc-DTPA was calculated and compared after taking three plasma samples. Taking two samples, only minor differences were seen and the correlation was high (r = 0.992). CONCLUSION: The results of this study encouraged us to adopt the use of 99mTc-DTPA instead of 51Cr-EDTA in determining the glomerular filtration applying the "one-compartment model" in slope with two plasma samples.     

Measurement of glomerular filtration rate by the 99mTc-DTPA renogram is less precise than measured and predicted creatinine clearance

The work was devised to compare measurements of glomerular filtration rate (GFR) by technetium-99m-diethylenetriaminepentacetic acid (99mTc-DTPA) renogram to those by creatinine clearance (measured and predicted by Cockroft and Gault) and by inulin clearance. A total number of 65 individuals were enrolled: 15 healthy controls and 50 patients with renal disease. Compared to inulin clearance used as the gold standard, 99mTc-DTPA overestimated at low and underestimated at high GFRs. 99mTc-DTPA measurements were less precise than creatinine clearance except for individuals with GFR >100 ml/min x 1.73 m2. Measured creatinine clearance had the highest correlation coefficient with inulin clearance, 99mTc-DTPA clearance the lowest. In correlation analyses, 81.5% of the interindividual variability for measured creatinine clearance could be explained by true differences in inulin clearance; this value dropped to 59.1 and 57.4% for predicted creatinine clearance and 99mTc-DTPA, respectively. In patients with GFR <25 ml/min x 1.73 m2, all 99mTc-DTPA measurements were out of the 95% confidence interval for the inulin measurement. It can be inferred that 99mTc-DTPA clearance from the renogram is less precise than measured and predicted creatinine clearance.     

Comparison of plasma creatinine determined with the Greiner Selective Analyser GSA II and the glomerular filtration rate

1. Reference values for the plasma creatinine were established using the alkaline picrate method with the Greiner Selective Analyzer GSA II in relation to the Cr 51-EDTA Clearance. Individuals with normal GFR between 93 to 159 ml/min/1.73 m2 had creatinine values in men (n = 65) from 53.7 to 119.5 mumol/l (0.61 to 1.35 mg/100 ml) and in women (n = 59) from 37.7 to 107 mumol/l (0.42 to 121 mg/100 ml). 2. The creatine determinations with the GSA II were compared to those on the Technicon Analyzer, the Beckman Creatinine Analyzer, the Gemsaec-Fast Analyzer and to the enzymatic creatinine method. A good correlation (r = 0.9780-0.984) was observed. 3. With the GSA II and the enzymatic method, bilirubin showed a minor interference which was more marked with the Beckman analyzer.     

Benefits of direct glomerular filtration rate (GFR) determination versus creatinine-based tests for evaluating renal function

To diagnose renal disease earlier and thereby reduce the number of patients with endstage renal disease, accurate, specific diagnostic tests are necessary. The author explains the benefits of using tests that rely on the glomerular filtration rate measurement rather than on traditional creatinine-based diagnostic tests.     

Cross sectional longitudinal study of spot morning urine protein:creatinine ratio, 24 hour urine protein excretion rate, glomerular filtration rate, and end stage renal failure in chronic renal disease in patients without diabetes

OBJECTIVE: To evaluate whether the protein:creatinine ratio in spot morning urine samples is a reliable indicator of 24 hour urinary protein excretion and predicts the rate of decline of glomerular filtration rate and progression to end stage renal failure in non-diabetic patients with chronic nephropathy. DESIGN: Cross sectional correlation between the ratio and urinary protein excretion rate. Univariate and multivariate analysis of baseline predictors, including the ratio and 24 hour urinary protein, of decline in glomerular filtration rate and end stage renal failure in the long term. SETTING: Research centre in Italy. SUBJECTS: 177 non-diabetic outpatients with chronic renal disease screened for participation in the ramipril efficacy in nephropathy study. MAIN OUTCOME MEASURES: Rate of decline in filtration rate evaluated by repeated measurements of unlabelled iohexol plasma clearance and rate of progression to renal failure. RESULTS: Protein:creatinine ratio was significantly correlated with absolute and log transformed 24 hour urinary protein values (P = 0.0001 and P < 0.0001, respectively.) Ratios also had high predictive value for rate of decline of the glomerular filtration rate (univariate P = 0.0003, multivariate P = 0.004) and end stage renal failure (P = 0.002 and P = 0.04). Baseline protein:creatinine ratios and rate of decline of the glomerular filtration rate were also significantly correlated (P < 0.0005). In the lowest third of the protein:creatinine ratio (< 1.7) there was 3% renal failure compared with 21.2% in the highest third (> 2.7) (P < 0.05). CONCLUSIONS: Protein:creatinine ratio in spot morning urine samples is a precise indicator of proteinuria and a reliable predictor of progression of disease in non-diabetic patients with chronic nephropathies and represents a simple and inexpensive procedure in establishing severity of renal disease and prognosis.     

Comparison between the scintigraphic uptake and plasma clearance of 99mTc-diethylenetriaminepentacetic acid (DTPA) for the evaluation of the glomerular filtration rate in dogs

Over the last few years, there has been increased emphasis on early discharge of patients following carotid endarterectomy in the United States. Recent studies have shown that short-stay hospitalization for carotid endarterectomy may be safe and cost-effective. However, this is not always possible because of reasons that are not clearly delineated. In order to optimize the early discharge of patients following carotid endarterectomy, an analysis of the causes of delayed discharges was performed in the present series. Since hemodynamic instability has been shown to be the most frequent complication following carotid endarterectomy, the authors investigated whether it was an important factor preventing early postoperative discharge. This study reviewed the data of 100 consecutive patients admitted for elective carotid endarterectomy. The incidence of post-carotid endarterectomy hemodynamic instability was 37% (n = 37), with hypertension occurring in 25 patients (68%) and hypotension occurring in 12 patients (32%). Hemodynamic instability tended to occur with the use of general anesthesia as compared with regional anesthesia. Hemodynamic instability did not correlate with pre-existent history of hypertension, nor with the type of drug used when general anesthesia was applied. All the patients were successfully treated either in the recovery room or in a monitored area. The average total length of stay was 1.65 days with 79% of the patients being discharged on the first postoperative day and 21% having delayed discharge ranging from 2 to 15 days (mean 4 days). The main reasons for delayed discharges were cardiac and urinary tract complications. Blood pressure instability accounted for only 2% of cases. Thus, these data show that hemodynamic instability does not significantly affect early discharge.     

Accuracy of estimated creatinine clearance in obese patients with stable renal function in the intensive care unit

We compared agreement between creatinine clearance values in obese, critically ill patients calculated using three common empirically derived formulas and modifications thereof, with creatinine clearance obtained by conventional 24-hour urine collection. We selected the charts of 22 patients in intensive care units (86% medical, 14% surgical) according to the following criteria: actual body weight greater than 150% of ideal body weight; serum creatinine variation of less than 15% from the day of starting 24-hour urine collection to the day before or after the collection; presence of a urinary bladder catheter; no history of renal dialysis; and clinical indication for renal function assessment. Mean measured 24-hour urinary creatinine clearance for all patients was 72 +/- 64 ml/minute (range 8-248 ml/min). The method of estimating creatinine clearance that showed the least mean bias was the equation of Salazar and Corcoran using a corrected serum creatinine concentration (mean bias -2 ml/min); however, the corresponding 95% confidence intervals were wide (-133-129 ml/min). The narrowest range of 95% confidence intervals were seen with Jelliffe's equation (mean bias 25 ml/min, 95% confidence intervals -41-90 ml/min). In this sample, estimated creatinine clearances did not agree acceptably with measured values. Despite low mean bias values, none of the empirically derived equations that we studied had clinically acceptable 95% confidence intervals. We recommend using the 24-hour urine collection method when assessing creatinine clearance in obese, critically ill patients.     

Tubular compensation for glomerular filtration rate decrease in chronic renal failure - the clinicopharmacologic point of view

The decrease of GFR can be compensated for by the tubular functions of residual nephrons while the homeostasis of the internal milieu is maintained. A new method presented here enables us to estimate the adequacy of tubular compensation on the basis of investigations of fractional excretion (FE) of sodium, water, and potassium. If the extrarenal excretion of the determined substance is small in comparison with the intake (I), the adequate value of FE with respect to GFR and I can be calculated according to the following formula: FE = 1.15 I/GFR . S. In patients with GFR less than 0.17 ml/s, FENa reached the values of 20-25%, FEH2O: 30-35%, and FEK: 150-200%. The estimation of these parameters can help in indicating and controlling therapy by diuretics and dietary restrictions.     

Biological variation of cystatin C: implications for the assessment of glomerular filtration rate

To assess the inherent potential for detecting mild to moderate reductions in glomerular filtration rate, this study determined the biological variability of serum cystatin C and creatinine in 12 healthy subjects. After accounting for analytical variation, interindividual variance accounted for 93% and intraindividual variance accounted for 7% of serum creatinine biological variation. As such, to lie outside the assay reference interval, some subjects must exceed 13 SD from their usual mean value, whereas in others, a change of only 2 SD would be sufficient. For cystatin C, interindividual variation explained 25% and intraindividual variance explained 75% of biological variability. Therefore, the upper limit of the population reference interval for cystatin C is seldom more than 3-4 SD from the mean value of any healthy individual. The critical difference for sequential values significant at P < or = 0.05 was calculated as 37% for serum cystatin C and 14% for serum creatinine. We conclude that cystatin C is potentially a better marker for detecting impaired renal function than serum creatinine, but serum creatinine is probably still the better marker for detecting temporal changes of renal function in individuals with established renal disease.     

Effect of antihypertensive treatment on urinary albumin excretion, glomerular filtration rate, and renal plasma flow in patients with essential hypertension

In 20 patients with essential hypertension the urinary albumin execretion, glomerular filtration rate (GFR),and renal plasma flow (RPF) were examined before and after antihypertensive treatment. Albumin excretion measured by radioimmunoassay was increased before treatment, and there was a significant fall during treatment. In patients responding well to therapy (diastolic pressure below 100 mm Hg), albumin excretion was significantly lower than in patients responding poorly to therapy. There was a positive correlation between albumin excretion before treatment and diastolic pressure during treatment, indicating that the albumin excretion rate may be used to predict the result of antihypertensive treatment. Patients with excretion rates below 25 mug/min generally respond well to the treatment used. No definite changes in GFR and RPF were found during treatment, and there was no correlation between albumin excretion and GFR and RPF. It is suggested that the increased albumin excretion in essential hypertension is due both to functional and morphological alterations in the glomerulus, namely increased glomerular filtration pressure and vascular damage.     

Comparison between the effects of indapamide and hydrochlorothiazide on creatinine clearance in patients with impaired renal function and hypertension

The long-term effects of indapamide or hydrochlorothiazide on blood pressure and renal function were examined in patients with impaired renal function and moderate hypertension. Both drugs controlled hypertension and blood pressure remained normal during the 2 years of the study. Despite this comparable control of hypertension, indapamide therapy was associated with a 28.5 +/- 4.4% increase in creatinine clearance while treatment with hydrochlorothiazide was associated with a 17.4 +/- 3.0% decrease in creatinine clearance. The results of the study indicate that indapamide is superior to hydrochlorothiazide in the treatment of patients with impaired renal function and moderate hypertension.     

血清胱抑素C、内生肌酐清除率及尿微量白蛋白在恶性肿瘤含顺铂化疗患者肾功能评价中的地位

Objective: Chemotherapy drugs such as platinum may cause damage to the renal function, creatinine clearance (Ccr), as a "golden standard" indicator in clinical evaluation of renal function, was limited in application due to complicated detection steps. By detecting the expression of serum Cystatin C (Cys C), Ccr and urinary micro-albumin (UMA), this study was designed to analyze and discuss their roles and status in renal function evaluation for cancer patients before and after chemotherapy with platinum. Methods: We retrospectively reviewed 110 patients who receiving platinum-containing protocols or non-platinum-containing ones, and got the expression of Cys C, Ccr (was calculated by Cockcroft-Gault equation) and UMA, then analyzed whether there were differences for Cys C,Ccr and UMA in those patients; for patients with mildly impaired renal function (Ccr between 50–75 mL/min), whether there were differences for Cys C and UMA before and after chemotherapy with platinum. Results: There was statistical significance for Ccr, Cys C and UMA in patients who receiving platinum-containing protocols (85.01 ± 28.40) vs (76.79 ± 26.63) mL/min, (1.49 ± 0.50) vs (1.80 ± 0.84) mg/L and (14.30 ± 9.15) vs (16.90 ± 10.95) mg/L, P = 0.00, 0.00 and 0.01), and no statistical significance for those receiving non-platinum-containing ones (89.45 ± 29.69) vs (86.78 ± 27.96) mL/min, (1.51 ± 0.78) vs (1.63 ± 0.73)mg/L and (17.31 ± 10.46) vs (16.59 ± 8.33) mg/L, P = 0.45, 0.07 and 0.57); and there were also significant differences for Cys C for patients with mildly impaired renal function before and after chemotherapy (1.68 ± 0.55) vs (2.04 ± 0.68) mg/L, P = 0.03), while no statistical significance for UMA for the same ones (21.11 ± 10.06) vs (21.22 ± 8.81) mg/L, P = 0.93). There were statistical significance both for Cys C and UMA before and after chemotherapy in platinum-containing group, but the AUC for Ccr and Cys C is greater than that for UMA (P < 0.02). Conclusion: Cys C and UMA can both access renal dysfunction early after chemotherapy, but Cys C is more sensitive than UMA in reflecting early renal dysfunction, so Cys C can replace Ccr and become a reliable indicator in the assessment of renal function for cancer patients before and after chemotherapy especially with platinum.     

The effect of renal transplantation on hyperhomocysteinaemia in dialysis patients, and the estimation of renal homocysteine extraction in patients with normal renal function

Cystinuria is an inherited genetic disorder that results in excessive cystine excretion through defects in renal dibasic amino acid transport. Due to the relative insolubility of cystine in urine, patients with this condition are prone to progressive and recurrent episodes of stone formation. Medical treatment is aimed at decreasing the concentration of cystine in the urine as well as increasing its solubility. A standard regimen includes dietary manipulation with hydration and moderate salt restriction, alkalinization, and thiol derivatives. Despite aggressive medical management, cystinuric patients are likely to suffer stone recurrences, and urologic intervention often is required. Contemporary technology permits the use of minimally invasive techniques for the majority of these patients, and advances in shock wave lithotripsy, percutaneous nephrolithotomy, and ureteroscopic lithotripsy obviate the need for open surgery in essentially all instances.     

Effects of four different processing techniques on the microstructure of potatoes: comparison with fresh samples in the ESEM

Four common scanning electron microscope (SEM) processing techniques involving freeze-substitution and chemical fixation were compared with fresh unprocessed samples imaged in an environmental scanning electron microscope (ESEM) using small pieces of potato tubers as test specimens. Potato tubers were chosen for this investigation because of their high moisture content and, consequently, the common need for extensive processing for conventional, high vacuum SEM imaging. ESEM results showed that the fresh unprocessed specimens were essentially unaltered, showing clear potato cell structure, morphology, and cell content. However, processed samples showed strong differences to the fresh samples: freeze-substituted specimens showed fine networks of material stretching across the surface of cells. These structures may represent fibrillar material or may be artifact caused during processing. Chemical fixation almost entirely destroyed the microstructure of these potato samples.     

Sheath pulling immediately after PTCA: comparison of two different deployment techniques for the hemostatic puncture closure device: a prospective, randomized study

Sheath pulling immediately after percutaneous transluminal coronary angioplasty (PTCA) increases patients' comfort, decreases burden for the medical staff, and may reduce hospital costs by shortening the length of stay. Immediate sheath pulling in anticoagulated patients with a low risk of bleeding complications is feasible using hemostatic devices. For the hemostatic puncture closing device (HPCD), published data regarding sheath pulling in patients immediately after PTCA is limited. Furthermore, no study addressed the question whether the recommended deployment time (DT) of 30 min can be reduced to a few minutes. We, therefore, performed a prospective study, randomizing 140 patients to a DT of 5 and 30 min, respectively. There were no statistical differences in gender, age, height, weight, or cardiovascular risk factors between the two groups. Blood pressures measured invasively immediately before sheath removal were comparable. Activated coagulation time just prior to sheath removal was 227 +/- 52 sec in the DT-5 group and 223 +/- 37 sec in the DT-30 group. After deployment, 74% of the DT-5 patients and 71% of the DT-30 patients showed immediate and complete hemostasis. The remaining patients showed only little oozing with complete hemostasis at the time of the final device removal. Hematoma size after 24 hr was 6.2 +/- 4.4 cm2 for DT-5 and 6.8 +/- 8.2 cm2 for DT-30 patients. There was no statistical difference between both groups. No severe bleeding or major complications were observed in either group. Thus, the use of a collagen system with an intra-arterial anchor (HPCD) is effective and safe when sheaths are pulled immediately after PTCA. The reduction of deployment time from 30 to 5 min is not related to an increased risk of bleeding or other vascular complications; patients can be transferred much faster to the ward, therefore reducing the burden on the personnel in the catheterization laboratory and increasing patients' comfort by allowing them to return to their rooms without a sheath.     

Quantitative determination of fibronectin (FN): evaluation of immunoturbidimetric and rate nephelometric techniques for FN assay in the different biologic materials

Aim of this study is to determine fibronectin concentration in the different biological materials to study its changes in the anatomic districts where the cell interactions in which FN participates do occur. The traditional immunoturbidimetric method and the nephelometric method are compared. An alternative method using a support for the collection of very small samples is proposed and the results obtained are discussed. This approach with solid phase immunonephelometry can be used both in amounts of biological fluids too small for traditional methods and in concentrations < 4.5 mg/dL. It is hoped that less complex techniques will be studied, allowing routine tests that can be performed by all laboratories. Unfortunately, at present this method is still investigated, however, it would be useful to adopt it in case of difficult sample collection.     

Methods for estimating HIV prevalence: A comparison of extrapolation from surveys on infection rate and risk behaviour with back-calculation for the Netherlands

SUBJECTS AND METHODS: 227 of subjects with a 2-hour plasma glucose concentration of 120-199 mg/dl were selected from 413 participants who had two or more 75 g OGTT in health examinations from 1987-1995. From these subjects we established 8 groups according to initial 2-hour plasma glucose concentration 120-199 mg/dl stratified by 10 mg/dl, and calculated the total percentages of participants whose 2-hour plasma glucose concentration reached 200 mg/dl or greater over a 1-8 years (2.7 +/- 1.7 years, mean +/- SD) observation period. In 36 subjects who were tested annually over a four year period (4 times), the mean values of their 4 values were analyzed for relationships to coefficients of variation of the 2-hour plasma glucose. RESULTS: By stratified groups (from lowest to highest) of those with an initial plasma glucose concentration of 120-159 mg/dl, 7.4%, 12.1%, 16.1%, and 15.0% attained values of 200 mg/dl and higher, respectively in 1-8 years. On the other hand, 29.6%, 29.6%, 39.1%, and 47.4% of those with an initial plasma glucose concentration of 160-199 mg/dl moved to a diabetic type after 1-8 years, respectively. The percentages of those who ended up with levels of 200 mg/dl and greater at 2-hours tended to increase in subjects whose initial 2-hour plasma glucose concentration was over 160 mg/dl in comparison with patients below that initial level. CONCLUSIONS: From these results, it appears that subjects with 160-199 mg/dl 2-hour glucose concentration, which is considered a borderline status, are at high risk for future abnormal levels (> 200 mg/dl at 2-hours) and should be managed as a high risk level group for prevention of diabetes.     

Changes in cerebrospinal fluid monoamine metabolites, tryptophan, and gamma-aminobutyric acid during the 1st year of life in normal infants. comparison with victims of sudden infant death syndrome

Cerebrospinal fluid (CSF) levels of 3-methoxy-4-hydroxyphenylglycol, 5-hydroxyindoleacetic acid, homovanillic acid, tryptophan, and gamma-aminobutyric acid were measured using high-performance liquid chromatography in 102 infants during the 1st year of life (preterm and term neonates included). CSF levels are expressed versus corrected age (postnatal days - preterm days) which reflects the stage of maturity of the central nervous system. These results are compared to those obtained in CSF of 53 victims of sudden infant death syndrome (SIDS). All components were significantly higher in SIDS than in the age-matched control group. This increase does not seem to be an artefact related to death. Indeed, under the same conditions concerning postmortem time interval before CSF sampling and analysis, the levels are not significantly higher in infants who died from a known pathology than in living infants. Moreover, in living infants as regards a pathology such as asphyxia or hypoventilation in comparison with SIDS, similar profiles are observed in some neurotransmitters or metabolites. Other studies are necessary to explore further neurotransmission systems in SIDS.