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Pretreatment cystatin C in children with malignancy: can it predict chemotherapy-induced glomerular filtration rate reduction during the induction phase?

BACKGROUND: Monitoring of kidney function is essential during chemotherapy. Serum creatinine is of limited value in early detection of renal insufficiency. The cystatin C level has been proved to be a good marker for detection of mild reduction in glomerular filtration rate. PURPOSE: To evaluate the validity of the pretreatment serum cystatin C level in predicting significant reduction of the glomerular filtration rate during the induction phase of chemotherapy. PATIENTS AND METHODS: Serum levels of cystatin C and creatinine and corrected creatinine clearance were assessed in 34 children with different types of malignancy just before the start of chemotherapy and again in 33 of them 1 month later. Patients were compared with 14 healthy controls of matched age and sex. RESULTS: Before chemotherapy, all patients when compared with controls had normal levels of cystatin C (P = 0.1) and creatinine (P = 0.62) and normal corrected creatinine clearance (P = 0.76). One month after chemotherapy, patients showed a significant increase in their cystatin C levels (P < 0.001) and a significant decrease in their corrected creatinine clearance (P < 0.001). However, creatinine levels did not change significantly (P = 0.65). Corrected creatinine clearance negatively correlated significantly with both cystatin C and creatinine levels (r = -0.622, P < 0.001; r = -0.346, P = 0.045, respectively) before chemotherapy and also 1 month after chemotherapy (r = -0.577, P < 0.001; r = -0.45, P = 0.009, respectively). When pretreatment levels of cystatin C and creatinine were used to predict patients who developed a reduction in corrected creatinine clearance of more than 20% after therapy, only the cystatin C level was statistically significant (P = 0.03). A cutoff point of 0.57 mg/L with sensitivity of 77.8%, specificity of 63%, and overall accuracy of 74% was suggested. CONCLUSIONS: Children with malignant diseases develop significant reduction in their glomerular filtration rate during the induction phase of chemotherapy, although their serum creatinine level may not change significantly. Cystatin C, as a more sensitive marker than creatinine for the assessment of glomerular filtration rate, can be used to predict patients who would have a higher risk of renal impairment during the induction phase of chemotherapy and who thus would require more frequent renal function assessment to consider adjustment of the chemotherapy dose if indicated.

Adolescent↗

Measuring glomerular filtration rate with cystatin C and beta-trace protein in children with spina bifida.

PURPOSE: We compared the diagnostic performance of cystatin C and beta-trace protein with serum creatinine and the Schwartz formula for the estimation of glomerular filtration rate in children with spina bifida. MATERIALS AND METHODS: Cystatin C, beta-trace protein and serum creatinine in children who underwent routine measurement of glomerular filtration rate were obtained in a prospective study. A spina bifida group (27 measurements in 27 patients 1.4 to 20.0 years old, 15 female, 12 male) was compared with a group of controls (211 measurements in 201 patients with various other renal pathologies 1.0 to 20.2 years old, 89 female, 122 male). All patients underwent nuclear medicine clearance investigations with 99mtechnetium diethylenetetraminepentaacetic acid. Z scores were calculated for body mass index, height and weight. Receiver operating characteristic (ROC) analysis and ROC plots were done to assess their diagnostic accuracy. RESULTS: Serum creatinine and the Schwartz formula did not correlate with glomerular filtration rate in the patients with spina bifida. Correlation coefficients for cystatin C were 0.45 and 0.84 in the spina bifida and control groups, respectively, while correlation coefficients for beta-trace protein were 0.31 and 0.75, respectively. For both groups ROC area was highest for cystatin C (up to 0.97 ROC area in control group). CONCLUSIONS: Only cystatin C served as a suitable marker to estimate glomerular filtration rate in patients with spina bifida. Cystatin C proved to be a superior marker in patients with spina bifida. In the control group the Schwartz formula was comparable to cystatin C and beta-trace protein, although cystatin C remained superior.

Adolescent↗

Rapid elimination by glomerular filtration of free prostate specific antigen and human kallikrein 2 after renal transplantation.

PURPOSE: The low molecular mass and short half-life of free (f) prostate specific antigen (PSA) implies elimination from blood by glomerular filtration. In addition, patients with terminal renal failure have increased fPSA in serum but there have been sparse data reported on the rates and pathways of elimination of PSA complexes and human kallikrein 2 (hK2). We studied glomerular filtration dependent elimination of fPSA and hK2 in patients with renal insufficiency undergoing successful renal transplantation. MATERIALS AND METHODS: We studied 14 patients with immediate onset of renal function after renal transplantation. Blood samples were obtained before and at regular intervals up to 160 hours after transplanted kidney reperfusion. Measurements of fPSA, total PSA and hK2 were performed with immunofluorometric assays and complexed PSA was determined by a chemiluminiscence assay. Glomerular filtration rates were monitored by analyzing serum creatinine and cystatin C. NONMEM, a multivariate pharmacokinetic approach, was used to determine the elimination rates of fPSA and hK2 after renal transplantation. RESULTS: Serum fPSA and hK2 but not PSA complexes, decreased rapidly after renal transplantation. Significant reductions in fPSA and hK2 were observed after only 16 and 8 hours, respectively. fPSA and hK2 showed similar elimination patterns, decreasing to 42% and 44% of their original levels compared to cystatin C, which was at 44% after 160 hours. The median half-lives of fPSA and hK2 were 17.4 and 11.5 hours, respectively. CONCLUSIONS: These results verify the hypothesis that fPSA and hK2 are eliminated from the blood circulation by glomerular filtration and severe renal failure influences the levels of the 2 proteins in serum.

Aged↗

Measuring filtration function in clinical practice.

PURPOSE OF REVIEW: The global prevalence of chronic kidney disease is increasing, as are its complications. Central to the diagnosis, evaluation and management of chronic kidney disease is the estimation of glomerular filtration rate. This article summarizes the various equations used to estimate filtration function and the performance of each in clinical practice. RECENT FINDINGS: During the past year the prediction equations to estimate glomerular filtration rate, especially the Modification of Diet in Renal Disease Study equation, continued to receive much interest. Many studies have compared the performance of the Modification of Diet in Renal Disease Study equation and the Cockcroft-Gault equation. The performance of these equations in various patient populations, such as patients with advanced heart failure, diabetic patients, renal transplantation patients, and the healthy general population, has been extensively studied. Overall, the Modification of Diet in Renal Disease Study equation has had an acceptable validity and has outperformed the Cockcroft-Gault equation in the various populations, but with some limitations that the physician should account for in clinical practice. SUMMARY: The use of the prediction equations to estimate glomerular filtration rate, especially the Modification of Diet in Renal Disease Study equation, should be implemented more frequently in clinical practice. An ever increasing number of studies has validated its use in different patient populations.

Cardiovascular Diseases↗

The particle size of hepatitis C virus estimated by filtration through microporous regenerated cellulose fibre.

To estimate the particle size of hepatitis C virus (HCV), a major causative agent of post-transfusion non-A, non-B hepatitis, we filtered plasma or serum samples through microporous cellulose fibres with different pore sizes. The amount of HCV particles in samples before and after filtration was determined by a quantitative reverse transcriptase polymerase chain reaction (PCR) method. Since there is no quantitative biological assay for HCV, except for that in chimpanzees, the HCV titre obtained from the PCR method was used in an equation constructed previously for application to filtration experiments with a flavivirus which is distantly related to HCV. The particle was estimated to be between 30 and 38 nm in diameter, although the possibility remained that larger HCV particles or HCV aggregates with a diameter of more than 39 nm might exist. Double-step filtration through microporous cellulose fibres with a pore size of 35 nm reduced the HCV content to below levels detectable by our PCR method, indicating that it is possible to eliminate HCV particles by simple filtration techniques.

Base Sequence↗

Increased microvascular water filtration and blood flow in extensive skin disease.

The rate of microvascular fluid transfer was estimated in 11 patients with extensive skin disease from the capillary filtration coefficient as measured by strain-gauge plethysmography on the forearm. Capillary filtration of the patients was significantly increased when compared with the control group (p < 0.001). Blood flow was increased to the same extent as capillary function, thus resulting in a normal mean ratio between the capillary filtration coefficient and the blood flow. On this background it is concluded that an increased capillary surface area available for exchange of fluid can explain the increased microvascular water filtration.

Adult↗

Evaluation of HTLV-I removal by filtration of blood cell components in a routine setting.

BACKGROUND: WBC depletion by filtration may prevent the transmission of HTLV-I, which requires cell-to-cell contact. The removal of HTLV-I-infected cells in routinely filtered blood cell components was measured. STUDY DESIGN AND METHODS: The study was conducted in Martinique where systematic screening for HTLV-I and -II and universal leukoreduction are mandatory. HTLV-I was quantified by use of real-time PCR in 8 RBC units and 4 PLT concentrates before and after filtration. HTLV-I proviral load in PBMNCs was determined in five of the eight HTLV-I-infected blood donors. RESULTS: The amount of MNC-associated HTLV-I DNA in RBC units before filtration was 21 x 10(6)+/- 29 x 10(6) copies (mean +/- SD). HTLV-I was detected in 4 of 8 RBC units after filtration, with a number of copies in the MNC fraction ranging from 20 to 140, following a 4.9 to 5.8 log reduction. Flow cytometry analysis performed in 2 of the filtered RBC units containing detectable HTLV-I showed suboptimal and out-of-range leukoreduction (0.56 x 10(6) and 1.22 x 10(6) residual WBCs). HTLV was not detected in filtered RBCs from the blood donor with the highest percentage of HTLV-I-infected PBMCs (9%). CONCLUSION: This study confirms that HTLV-I-infected cells can be detected in filtered blood cell components and shows that optimal leukoreduction is critical for HTLV-I removal.

Blood Cells↗

Plasma quality after whole-blood filtration depends on storage temperature and filter type.

The study evaluated the quality of plasma obtained after whole-blood filtration with four different polyester filters and one polyurethane filter. The activities of coagulation factors and proteinase inhibitors were not or only negligibly affected by filtration, in all experiments. Filtration did not increase markers of clotting and fibrinolysis. Only a strong neutrophil and complement activation was observed, which depended on the type of filter and whole-blood storage conditions. However, as neutrophil elastase-specific degradation products did not increase and the complement-derived anaphylatoxin C3a was found in its inactivated form, C3a-desArg, these filtration-dependent changes apparently have little impact on the therapeutic quality of whole-blood-filtered fresh frozen plasma for transfusion.

Antithrombins↗

Influence of ureteral catheter size on urinary flow rate and glomerular filtration rate in the rat.

The influence of ureteral catheter diameter on renal function was studied in rats during different diuretic states. Urinary flow rate and glomerular filtration rate were measured on each rat using ureteral catheters of two different internal diameters. In non-diuretic rats, urinary flow rate and glomerular filtration rate did not change according to the catheter diameter. In diuretic rats, urinary flow rate was from 40 to 70% lower with the smaller catheter. Differences became more marked as urinary flow rate increased. Glomerular filtration rates were about 20% lower when measured with small catheters. These results clearly demonstrate that the use of small diameter ureteral catheters during diuretic states leads to a decrease in glomerular filtration rate and urinary flow rate. The results also emphasize the importance of using large diameter catheters during such experimental conditions.

Animals↗

In-line filtration of platelet concentrates obtained with the Omnix blood cell separator.

The quality of platelet concentrates (PC) obtained with the blood cell separator Omnix was investigated before and after in-line filtration. PC were filtered 2h (protocol A) and 4 h (protocol B) after the termination of apheresis. Platelet (PLT) yield after filtration was similar in both protocols (median 3.7 vs. 3.4 x 10(11)). Median white blood cell (WBC) contamination after leucocyte depletion was 0.07 x 10(6) (range 0.02-3.27 x 10(6)) in protocol A and 0.06 x 10(6) (range 0.02-2.1 x 10(6)) in protocol B. Glucose, lactate, lactate dehydrogenase, morphology score and pH value were not statistically different before and after filtration in both protocols. We conclude that in-line filtration results in sufficient leucocyte depletion of the PC. The prefiltration storage time did not influence the studied parameters of product quality.

Blood Cells↗

Effect of filtration on subsequently stored platelet concentrates.

The effect of filtration on the quality of platelet concentrates (PC) during storage was investigated. Two leukocyte depletion filters (Pall PL50HF and Sepacell PL-10A) were applied to filter PC made from a pool of 4 buffy coats. For each experiment 3 PC were pooled and divided into 3 identical PC to eliminate differences between the PC. Two PC were filtered, and the third PC served as an unfiltered control. A total of 12 experiments was performed. Before filtration, volumes of the PC were 263 +/- 11.7 ml (mean +/- SD). Platelet and leukocyte counts per PC were 241 +/- 25.9 x 10(9) and 7.2 +/- 1.8 x 10(6), respectively. After filtration leukocyte counts did not exceed 5 x 10(4) in any of the PC. In the PC filtered with the Pall PL50HF the mean platelet loss was approximately 14% and with the Sepacell PL-10A, 17%. During a 9-day storage period the pH, PO2, PCO2, bicarbonate, lactate and glucose concentration and LDH release as well as the morphology, examined by the swirling effect and microscopically, were not significantly different in filtered and unfiltered units. Filtration through the 2 investigated leukocyte depletion filters for PC did not adversely affect in vitro viability of the platelets during storage.

Bicarbonates↗

Prestorage leukocyte depletion with in-line filtration of whole blood in comparison with blood component leukocyte depletion.

In-line filtration of blood components appears to be an effective method to reduce white-cell-induced adverse reactions. We have investigated whether whole blood filtration (WBF), prior to component preparation, is comparable with filtration of already prepared blood components (CF), i.e. the red cell concentrate (RCC) and fresh plasma. Conventionally prepared nonfiltered blood components served as a control. No significant differences for most parameters investigated were found between leukodepleted RCCs and plasma units prepared by CF or WBF. All filtered RCCs and plasma units (CF and WBF) had white blood cell contaminations < 1 x 10(5) per unit. Platelets were reduced in all filtered components: 95% in plasma and 99% in RCCs. Fresh-frozen plasma (FFP) prepared by CF and WBF had normal amounts of factors V, VIII, von Willebrand factor and thrombin-antithrombin-III complexes, whereas platelet factor 4 (PF-4) was slightly increased in FFP prepared by WBF. RCCs and plasma units prepared from filtered whole blood (n = 20) had a significantly greater volume (RCC: 288 +/- 19 ml; plasma: 274 +/- 20 ml) than conventionally prepared (n = 20) and filtered products (RCC: 257 +/- 19 ml, plasma: 259 +/- 19 ml). For early filtration of blood components, WBF prior to component preparation seems to offer an interesting technique for obtaining a leukocyte-depleted RCC and FFP.

Blood Cell Count↗

Possible factors affecting the cholesterol nucleation time in human bile: a filtration study.

This study examined the hypothesis that filtration through the MW 300 kD cut-off membrane (XM-300) may influence factors affecting the cholesterol nucleation time (the appearance time of cholesterol monohydrate crystal). Differences in biliary lipids, biliary protein, mucous glycoprotein and vesicular composition were examined before and after the XM-300 filtration in control and cholesterol gallstone patients. The nucleation time in the cholesterol gallstone patients was significantly faster than that in the control patients. However, the nucleation time in the gallstone patients was significantly prolonged following the XM-300 filtration resulting in a similar value to that of the control patients. No differences in concentrations of total protein, mucous glycoprotein or lipids composition were observed. The nucleation time did not correlate with the total lipid concentration, the concentrations of biliary mucous glycoprotein or total protein. The prolonged nucleation time of gallstone bile by the XM-300 filtration was primarily ascribed to the removal of vesicles, which was confirmed by gel chromatography. It was concluded that vesicles greater than MW 300 kD are primarily responsible for the rapid nucleation time.

Bile↗

Renal plasma flow, filtration fraction and microalbuminuria in hypertensive patients: effects of chronic smoking.

INTRODUCTION: Albumin excretion rate is usually increased in people who smoke, but the physiological basis of this phenomenon is not fully understood. METHODS: The effect of chronic smoking on renal haemodynamics was studied in a cohort of 66 men. Twenty-seven were smokers and 36 were hypertensive. In all subjects, the albumin excretion rate was evaluated; in hypertensive patients, a renoscintigraphic evaluation of renal plasma flow and glomerular filtration were carried out and the filtration fraction was calculated. RESULTS: The hypertensive smoking population presented an increased urinary albumin excretion rate in comparison with hypertensive non-smoking patients. No significant differences were found for the mean values of renal plasma flow, the glomerular filtration rate and the filtration fraction between hypertensive smokers and hypertensive non-smoking patients. CONCLUSIONS: In hypertensive patients, smoking does not modify typical renal haemodynamic changes of arterial hypertension; however, it significantly increases the albumin excretion rate.

Adult↗

The relation between tissue kallikrein excretion rate, aldosterone and glomerular filtration rate in human pregnancy.

The changes in renal kallikrein synthesis through normal pregnancy and its relation to aldosterone excretion and the glomerular filtration rate was investigated. Overnight urinary kallikrein and aldosterone excretion rates and glomerular filtration rate were measured at 18 weeks, 34 weeks, term and postpartum in normal human pregnancy. Kallikrein excretion was raised at 18 weeks compared with the nonpregnant state (P < 0 x 001) but was significantly reduced at term. The reduction in renal kallikrein was not due to falling aldosterone concentration, which increased in the third trimester, compared with 18 weeks (P = 0 x 002) and remained elevated at term compared with the nonpregnant state (P < 0 x 001). Glomerular filtration rate remained elevated at term despite the reduced kallikrein excretion rate. These data are consistent with the hypothesis that increased aldosterone production is one factor responsible for increased kallikrein synthesis which contributes to elevated glomerular filtration rate in early pregnancy. Other factors clearly inhibit renal kallikrein production at term. In the face of plasma volume expansion associated with increased mineralo-corticoid production, the effects of reduced kallikrein synthesis at term on glomerular perfusion and reabsorption of sodium by the distal tubule may predispose to blood pressure elevation in late pregnancy.

Aldosterone↗

Effects of adrenaline, isoprenaline and histamine on transsinusoidal fluid filtration in the cat liver.

1. Hepatic volume was recorded by a plethysmographic technique in cats anaesthetized with pentobarbitone. It has been shown previously that during an increase of hepatic venous pressure in this preparation, there is a maintained filtration of fluid from the sinusoids into the plethysmograph. The rate of this filtration is directly proportional to the increase in hepatic venous pressure. Infusions of drugs during this period of steady filtration provide a sensitive measure of the effects of the drugs on transsinusoidal fluid transfer.2. Infusions of adrenaline, isoprenaline and histamine had no effect on the steady transsinusoidal filtration produced by an increased hepatic venous pressure. It is concluded that these agents do not change sinusoidal hydrostatic pressure by more than 1.5 mmHg (1 mmHg identical with1.333 mbar) even though they alter hepatic arterial and portal flows. They do not change sinusoidal surface area by more than 20% and histamine does not change sinusoidal permeability.3. The data are discussed in the light of current theories on the application of Starling's hypothesis to the liver sinusoids and to muscle capillaries. The postsinusoidal resistance appears to be very low in the liver and it does not increase during contraction of the capacitance vessels. The liver does not have presinusoidal sphincters, and closed sinusoids analogous to closed capillaries in skeletal muscle do not occur. The major factor controlling hepatic transsinusoidal fluid movements in the anaesthetized cat is hepatic venous pressure.

Animals↗

Extracorporeal membrane differential filtration--a new and safe method to optimize hemorheology in acute ischemic stroke.

OBJECTIVE: Can extracorporeal membrane differential filtration be used on patients with acute stroke to optimize their hemorheology without reducing the number of oxygen carriers (erythrocytes) - and is this form of treatment safe? SUBJECTS AND METHODS: In a prospective pilot study, 10 patients (67+/-4 years) suffering severe middle cerebral artery (MCA) stroke were treated with membrane differential filtration, which was first performed within 12 h following the onset of symptoms and repeated three times at intervals of 24 h. Hemorheological parameters were measured before and after each treatment session. RESULTS: Extracorporeal membrane differential filtration treatment immediately led to a significant and sustained drop in all hemorheological parameters (fibrinogen by 54%, alpha2-macroglobulin by 76%, total cholesterol by 65%, LDL by 82%, and HDL by 38%). Plasma viscosity dropped from 1.3 to 1.1 mPa s, erythrocyte aggregation by 57%. By contrast, hematocrit and the erythrocyte count remained constant. Treatment had no side-effects. CONCLUSIONS: Extracorporeal membrane differential filtration is a safe method to optimize hemorheology in patients with acute ischemic stroke.

Aged↗

A pilot study to investigate the effects of combined dehumidification and HEPA filtration on dew point and airborne mold spore counts in day care centers.

UNLABELLED: Meteorological factors such as relative humidity directly correlate with airborne fungal levels outdoors and indoors. While dehumidification alone is effective at reducing moisture necessary for mold growth, it is inadequate as a single intervention as it does not remove viable and non-viable fungal spores that are potentially allergenic. The purpose of this pilot study was to investigate whether dehumidification in combination with high-efficiency particulate arrestance (HEPA) filtration is effective at reducing airborne mold spore levels in day care centers. Two day care centers within a 2-mile radius of each other were selected. Day care center A was 2 years old with eight rooms while day care center B was 15 years old with six rooms. A high efficiency Santa Fe dehumidification unit equipped with a HEPA filter was installed in half the rooms (intervention) of each day care facility. Electronic HOBO data loggers continuously measured outdoor and indoor room dew point and temperature every 2 h throughout the study. Dew point and airborne fungal spore measurements from selected rooms with controlled air conditions were analyzed by comparing baseline measurements to those obtained at subsequent time periods over 1 year. Regression models accounted for correlations between measurements in the same room over time. Intervention resulted in a lowered average dew point from baseline by 8.8 degrees C compared with a decrease of 7.1 degrees C in non-intervention rooms across all time periods in both facilities (P<0.001). Fungal analyses demonstrated lower baseline (P=0.06) and follow-up means in intervention rooms (P<0.05), however the change from baseline to end of follow-up differed between intervention and non-intervention rooms in the two facilities. Log transformation was applied to approximate normality of fungal measurements. Dehumidification with HEPA filtration was effective at controlling indoor dew point in both facilities and at reducing airborne culturable fungal spore levels in one of the two facilities. These preliminary results provide a scientific rationale for using this intervention in future studies designed to investigate the impact of indoor mold exposure on health outcomes. PRACTICAL IMPLICATIONS: Poor indoor air quality is a recognized cause or contributing factor to health effects. Dampness and humidity have been linked to upper and lower respiratory symptoms in children and adults. This study indicates that reducing indoor relative humidity and airborne mold spore levels using high-efficiency dehumidification units equipped with HEPA filtration is feasible even in work facilities such as day care centers where traffic in and out of the building is difficult to regulate. Clinicians should emphasize to their patients the importance of dehumidification and HEPA filtration to improve indoor air quality in the home and workplace.

Air Pollution, Indoor↗