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Biomedical subjects

A Argilés

Publications and source records attributed to A Argilés.

At least 19 recordsLinked to original sources
PubMed2002

Necrotic skin lesions in a dialysis patient: a multifactorial entity.

A female dialysis patient with a consistently high serum calcium phosphate product presented with large necrotic skin lesions with ulcers. The clinical course was highly suggestive of calciphylaxis. Parathyroidectomy was followed by the healing of the lesions. New skin lesions appeared following relapse of hyperparathyroidism. Her clinical records included a long past of hypertension, which was the cause of her renal failure. She had a limited walking range and previously had presented bilateral ulcers of vascular origin. This case presents a type of lesion which bears a serious prognosis in dialysis patients. The clinical context and the presentation of the lesions are compatible with multiple etiology: vascular lesions and calciphylaxis. The documented longitudinal follow-up illustrates the importance of treating the different factors known to participate in the appearance of skin lesions in dialysis patients. Particularly, it stresses the benefit of performing parathyroidectomy, even if the parathyroid hormone level is not in the range normally accepted as requiring surgical removal of parathyroid glands.

Aged↗
PubMed2001

Uremic toxicity: present state of the art.

The uremic syndrome is a complex mixture of organ dysfunctions, which is attributed to the retention of a myriad of compounds that under normal condition are excreted by the healthy kidneys (uremic toxins). In the area of identification and characterization of uremic toxins and in the knowledge of their pathophysiologic importance, major steps forward have been made during recent years. The present article is a review of several of these steps, especially in the area of information about the compounds that could play a role in the development of cardiovascular complications. It is written by those members of the Uremic Toxins Group, which has been created by the European Society for Artificial Organs (ESAO). Each of the 16 authors has written a state of the art in his/her major area of interest.

Cardiovascular Diseases↗
PubMed2000

Influence of convection on small molecule clearances in online hemodiafiltration.

BACKGROUND: Dialysis efficacy is mostly influenced by dialyzer clearance. Urea clearance may be estimated in vitro by total ion clearance, which can be obtained by conductivity measurements. We have previously used this approach to assess in vitro clearances in a system mimicking predilutional and postdilutional online hemodiafiltration with a wide range of QD, QB, and ultrafiltration rates. Our current study elaborates on a formula that allows the prediction of the influence of ultrafiltration on small molecule clearances, and validates the mathematical approach both experimentally in vitro and clinically in vivo data. METHODS: Two conductivimeters in the dialysate side of an E-2008 Fresenius machine were used. HF80 and HF40 polysulfone dialyzers were used; reverse osmosis water and dialysate were used for blood and dialysate compartments, respectively. Study conditions included QB of 300 and 400 mL/min and QD of 500 and 590 mL/min, with a range of ultrafiltration rate from 0 to 400 mL/min in postdilutional hemodiafiltration and to 590 mL/min in predilutional hemodiafiltration. Urea clearances were determined in the in vivo studies, which included 0, 50, 100, and 150 mL/min ultrafiltration rates. RESULTS: The ultrafiltration rate and clearance were significantly correlated (R > 0.9, P < 0.001) and fitted a linear model (P < 0.001) in all of the experimental conditions. The following formula fitted the experimental points with an error <2% for both postdilutional and predilutional online diafiltration in vitro, respectively. K = K0 + [(QB - K0)/(QB)] x ultrafiltration rateK = K0 + [((QD x QB)/(QB + QD) - K0)/QD] x ultrafiltration rate where K is the clearance; K0 is the clearance with nil ultrafiltration rate; QD is the total dialysate produced (in commercial HDF, QD = QDi + Qinf). Since weight loss was maintained at 0, ultrafiltration rate = infusion flow. QB is the "blood" line flow. The formula was also verified in vivo in clinical postdilutional hemodiafiltration with a QB taking into account the cellular and water compartments. DISCUSSION: In vitro, by simply determining the clearance in conventional dialysis, the total clearance for any ultrafiltration rate may be estimated in both predilutional and postdilutional online diafiltration with an error of less than 2%. The same applies to in vivo postdilutional hemodiafiltration when the formula takes into account the cellular and water composition of blood.

Blood↗
PubMed2000

alpha2-Macroglobulin, the main serum antiprotease, binds beta2-microglobulin, the light chain of the class I major histocompatibility complex, which is involved in human disease.

beta(2)-Microglobulin, a 12 kDa protein forming part of the class I HLA (histocompatibility locus antigen) major histocompatibility complex, has been used as a prognosis factor for multiple myeloma and as a marker of renal function, and has been shown to be involved in the pathogenesis of dialysis-related amyloidosis. alpha(2)-Macroglobulin has the ability to bind a wide range of physiologically important molecules, thereby influencing their metabolic impact. In this study we show by Western blotting analysis that beta(2)-microglobulin binds to alpha(2)-macroglobulin in vitro. This binding was confirmed by BIAcore analysis, and was shown by ELISA to be concentration-dependent. The sequences of the binding peptides in the mature beta(2)-microglobulin molecule were identified by Spot multiple peptide synthesis and alpha(2)-macroglobulin binding studies. In conclusion, beta(2)-microglobulin interacts specifically with the universal antiprotease a(2)-macroglobulin. The identification of this interaction brings into question some of the axioms on the metabolism of beta(2)-microglobulin, and may help to explain the clinical findings observed in b(2)-microglobulin-related diseases.

Amyloidosis↗
PubMed1999

Analysis of the influence of the infusion site on dialyser clearances measured in an in vitro system mimicking haemodialysis and haemodiafiltration.

BACKGROUND: Blood flow (QB), dialysate flow (QD), and dialyser characteristics are the three major factors driving dialysis efficacy. Haemodiafiltration has added an increased convective volume to increase efficacy. We aimed to assess the influence of the infusion site of the replacement fluid in an in vitro system emulating haemodiafiltration. METHODS: An in vitro system allowing us to control the dialysate temperature, concentration gradient, the flow of both dialyser sides over a range wider than that compatible with clinic, was set to evaluate the influence of the different parameters on dialysis efficacy. The total ion clearance was used as an accepted method for small molecule clearance assessment. Cellulose triacetate (CT190C, Baxter; FB170U, Nipro) and polysulfone (HF80, Fresenius) dialysers were included in the study. Dialysis as well as on-line diafiltration both with pre- and postdilutional infusion were assessed. The experimental conditions presented in this study included QD 620 and 970 ml/min. The convective flows ranged from 50 to 200 ml/min. RESULTS: For a QD = 620 ml/min and a QB = 350 ml/min the total ion clearance ranged from 269 to 274 for HF80, from 291 to 294 for FB170 and from 294 to 302 for CT190. The variability of the measurements was very low (SD < 1%). Total ion clearance increased by 17-21% when QB was raised from 300 to 400 ml/min. Increasing QD from 420 to 970 ml/min (for QB = 350 ml/min), resulted in an increase in total ion clearance which was more marked at lower QD (from 420 to 620 ml/min) and plateaued thereafter (from 620 to 970 ml/min). Postdilutional on-line diafiltration with 100 ml/min of infusate resulted in an additional increase in total ion clearance of 5.4-8.6%. This increase was proportional to the infused volume. On the contrary, predilutional on-line diafiltration resulted in a decrease in total ion clearance which was also proportional to the infused volume (between -5.1 and -6.9% at 100 ml/min infusion volume and -9.7 to -12.9% at 200 ml/min). CONCLUSIONS: The present in vitro system provided accurate and reproducible results on dialyser clearances. Our experiments confirmed previous studies on the influence of QB and QD on dialyser efficacy. Further, they show that the proportional increase in postdilutional on-line diafiltration is lesser than that previously reported. More importantly, they also show that pre-dilution infusion in high efficiency systems results in a drop in dialyser clearance compared to dialysis alone, again proportional to the infusion rate. Thus, increasing the convective flow may increase dialysis efficacy even more than increasing QD alone. However, the choice of infusion site is crucial to obtaining this benefit in small molecule clearances.

Hemofiltration↗
PubMed1998

Seasonal changes in blood pressure in patients with end-stage renal disease treated with hemodialysis.

BACKGROUND: Many factors contribute to the regulation of blood pressure. The role of climate has received relatively little attention. METHODS: During a four-year period, we determined the influence of climate on blood pressure in 53 patients with end-stage renal disease treated with hemodialysis. For each patient, blood pressure was measured before each of three dialysis treatments per week for an average of 31 months. The dose of dialysis (urea clearance multiplied by the length of dialysis and divided by the distribution volume of urea) and protein catabolism rate were assessed monthly. We then analyzed the monthly mean values for blood pressure, pulse, and body weight in relation to the monthly values for temperature, relative humidity, and atmospheric pressure recorded in Montpellier, France. RESULTS: The maximal monthly temperature varied from 10 degrees C in the winter to 31 degrees C in the summer, and the minimal monthly temperature from 1 degree to 20 degrees C. The mean (+/-SE) systolic and diastolic blood pressure was highest during the winter (153+/-3/82+/-2 mm Hg) and lowest during the summer (141+/-3/75+/-2 mm Hg). The seasonal pattern was evident throughout the four-year period. Blood pressure was correlated inversely with monthly maximal temperature (r= -0.65 and P<0.001 for systolic pressure; r= -0.71 and P<0.001 for diastolic pressure) and directly with minimal humidity (r=0.45 and P=0.002 for systolic pressure; r=0.43 and P=0.003 for diastolic pressure). Changes in protein catabolic rate, weight gain during dialysis, and dialysis dose were not related to changes in blood pressure. CONCLUSIONS: In patients with end-stage renal disease treated with hemodialysis, blood pressure varies seasonally, with higher values in the winter and lower values in the summer.

Blood Pressure↗
PubMed1997

Alpha 2-macroglobulin protects some of the protein constituents of dialysis-associated amyloidosis from protease degradation.

A crucial point to know in the prevention and treatment of beta 2-microglobulin (beta 2-m) amyloidosis is the putative resorption of amyloid fibrils in vivo. Although still controversial, long term clinical studies suggest that there is no resorption of amyloid fibrils in vivo, even after the suppression of the primary cause of amyloidosis. Two in vitro studies on murine and human AA amyloidosis as well as Alzheimer's disease suggest that protein constituents of amyloid fibrils may be resorbed. Protein resorption can be inhibited by the antiprotease amyloid P component. We extended these in vitro studies on beta 2-m amyloidosis, and assessed the effect of alpha 2-macroglobulin (alpha 2-M), a serum antiprotease previously found in this type of amyloidosis, on the putative protease induced protein resorption. Here, we show that amyloid proteins, beta 2-m and light chains of immunoglobulins, were degraded by trypsin. Preincubation of the amyloid proteins with alpha 2-M significantly inhibited the trypsin induced protein degradation of lambda chains. These data add further support to the hypothesis proposing a role for alpha 2-M and other antiproteases in the formation and/or persistence of beta 2-m amyloidosis.

Amyloid↗
PubMed1997

Protein catabolic rate over lean body mass ratio: a more rational approach to normalize the protein catabolic rate in dialysis patients.

Protein catabolic rate (PCR), equivalent to dietary protein intake in "stable" dialysis patients, is widely accepted as a marker of their protein nutritional status. PCR is usually established from urea generation rate using urea kinetic modeling (UKM), but the normalizing factor is still a matter of controversy. By convention, PCR is expressed in grams of protein degraded daily divided by the dry body weight (BW) (nPCRBW). To be valid, this implies that dry BW is close to ideal BW and that body composition is preserved with a lean body mass (LBM) over BW ratio near 0.73. Such conditions being infrequently found in dialysis patients, it has been proposed to normalize PCR to ideal BW or to total body water, but these correction factors are not really appropriate. A more rational approach would be to express PCR as the ratio of protein degraded to the kilograms of LBM (nPCRLBM), thus offering the main advantage of directly coupling PCR to changes in protein or nitrogen reserve. In this study, we developed a combined kinetic model of urea and creatinine applied to the midweek dialysis cycle in 66 end-stage renal disease (ESRD) patients. UKM provided Kt/V and PCR, whereas creatinine kinetic modeling (CKM) was used to calculate LBM. Thirty-four patients with a preserved LBM (LBM/dry BW ratio equal to or greater than 0.70; mean ratio, 0.81 +/- 0.11) and with a dry/ideal BW ratio of 1.01 +/- 0.16 had a mean PCR of 1.14 +/- 0.30 g/kg/24 h when normalized to BW (nPCRBW) and of 1.40 +/- 0.30 g/kg/24 h when normalized to LBM (nPCRLBM). In the 32 patients with a reduced LBM (LBM/dry BW ratio, below 0.70; mean ratio, 0.60 +/- 0.09) and dry/ideal BW ratio of 1.11 +/- 0.23, the mean nPCRBW was 0.99 +/- 0.31 g/kg/24 h, whereas nPCRLBM was 1.62 +/- 0.32 g/kg/24 h. For both subgroups, Kt/V was similar, with mean values of 1.76 +/- 0.34 and 1.69 +/- 0.27. Normalizing PCR to LBM offers a double benefit: it compensates for the error induced by abnormal body composition (eg, obese patients) and permits PCR to be adjusted for the decrease in LBM that occurs with age. We propose nPCRLBM as a more rational index to express PCR in dialysis patients.

Aged↗
PubMed1997

Precise quantification of dialysis using continuous sampling of spent dialysate and total dialysate volume measurement.

The "gold standard" method to evaluate the mass balances achieved during dialysis for a given solute remains total dialysate collection (TDC). However, since handling over 100 liter volumes is unfeasible in our current dialysis units, alternative methods have been proposed, including urea kinetic modeling, partial dialysate collection (PDC) and more recently, monitoring of dialysate urea by on-line devices. Concerned by the complexity and costs generated by these devices, we aimed to adapt the simple "gold standard" TDC method to clinical practice by diminishing the total volumes to be handled. We describe a new system based on partial dialysate collection, the continuous spent sampling of dialysate (CSSD), and present its technical validation. Further, and for the first time, we report a long-term assessment of dialysis dosage in a dialysis clinic using both the classical PDC and the new CSSD system in a group of six stable dialysis patients who were followed for a period of three years. For the CSSD technique, spent dialysate was continuously sampled by a reversed automatic infusion pump at a rate of 10 ml/hr. The piston was automatically driven by the dialysis machine: switched on when dialysis started, off when dialysis terminated and held during the by pass periods. At the same time the number of production cycles of dialysate was monitored and the total volume of dialysate was calculated by multiplying the volume of the production chamber by the number of cycles. Urea and creatinine concentrations were measured in the syringe and the masses were obtained by multiplying this concentration by the total volume. CSSD and TDC were simultaneously performed in 20 dialysis sessions. The total mass of urea removed was calculated as 58038 and 60442 mmol/session (CSSD and TDC respectively; 3.1 +/- 1.2% variation; r = 0.99; y = 0.92x -28.9; P < 0.001). The total mass of creatinine removed was 146,941,143 and 150,071,195 mumol/session (2.2 +/- 0.9% variation; r = 0.99; y = 0.99x + 263; P < 0.001). To determine the long-term clinical use of PDC and CSSD, all the dialysis sessions monitored during three consecutive summers with PDC (during 1993 and 1994) and with CSSD (1995) in six stable dialysis patients were included. The clinical study comparing PDC and CSSD showed similar urea removal: 510 +/- 59 during the first year with PDC and 516 +/- 46 mmol/dialysis session during the third year, using CSSD. Protein catabolic rate (PCR) could be calculated from total urea removal and was 1.05 +/- 0.11 and 1.05 +/- 0.09 g/kg/day with PDC and CSSD for the same periods. PCR values were clearly more stable when calculated from the daily dialysate collections than when obtained with urea kinetic modeling performed once monthly. We found that CSSD is a simple and accurate method to monitor mass balances of urea or any other solute of clinical interest. With CSSD, dialysis efficacy can be monitored at every dialysis session without the need for bleeding a patient. As it is external to the dialysis machine, it can be attached to any type of machine with a very low cost. The sample of dialysate is easy to handle, since it is already taken in a syringe that is sent directly to the laboratory. The CSSD system is currently in routine use in our unit and has demonstrated its feasibility, low cost and high clinical interest in monitoring dialysis patients.

Creatinine↗
PubMed1997

Monomeric and dimeric beta 2-microglobulin may be extracted from amyloid deposits in vitro.

BACKGROUND: There is a controversy as to whether beta 2-microglobulin (beta 2M amyloid deposits may be degraded resulting in regression and cure of amyloidosis. We have recently reported a long-term clinical study involving transplanted patients suggesting that there is no resorption of amyloid deposits in vivo, even after correction of the primary cause of amyloidosis. To progress in the study of the solubility of amyloid fibrils we performed an in vitro study with the intent to remove protein constituents from amyloid fibrils and amyloid deposits. METHODS: Amyloid fibrils were prepurified from three amyloid deposits surgically obtained from carpal tunnel. They were incubated for 2 h with a phosphate-buffered saline (PBS) solution containing trypsin, collagenase, kallikrein, the three of them, or PBS alone. The experiments were repeated in the presence of the antiprotease alpha 2 macroglobulin (alpha 2M). RESULTS: Several bands were observed when the supernatants were run through SDS-PAGE. Western blotting identified in these bands the presence of alpha 2M, light chains of immunoglobulins and beta 2M in mono- and dimeric form. The same proteins were solubilized with PBS alone. Equivalent results were obtained with crude amyloid deposits; however, beta 2M presented almost exclusively in monomeric form. CONCLUSIONS: These results show that the protein constituents may be recovered from amyloid fibrils in vitro. They also show that even the more insoluble beta 2M dimers are resuspended by the action of PBS, with no need for proteases to cleave their attachment to the amyloid deposits.

Amyloid↗
PubMed1996

Dialysis-related amyloidosis: visceral involvement and protein constituents.

beta 2-M amyloidosis mainly concerns dialysis patients and typically presents with osteoarticular symptoms. In order to precise the incidence and gravity of visceral involvement, subcutaneous abdominal fat aspirates, skin and rectal biopsies, as well as echocardiograms were performed in 26 patients with severe beta 2-M amyloidosis. Visceral amyloidosis was confirmed in 58% and the numbers were even higher when including heart abnormalities suggestive of amyloidosis (81%). Clinical manifestations of visceral involvement were usually not severe and include odynophagia, gastrointestinal haemorrhage, intestinal obstruction, kidney stones, myocardial dysfunction and subcutaneous tumours. The removal and synthesis rates of beta 2-M were assessed during dialysis. Serum 131I-beta 2-M levels decreased by 5-10% with cuprophane and by 40-45% with polysulfone and polyacrylonitrile membranes. These reduction rates were higher than those found with unlabelled beta 2-M suggesting an increased synthesis or release during dialysis. The protein constituents of amyloid deposits were studied. Two different preparative methods to extract the proteins from amyloid deposits were used. TCA precipitation showed the presence of several proteins which were not observed with PBS homogenizing and resuspending in guanidine. The protein constituents of amyloid fibrils were studied by both, two dimensional gel electrophoresis (2D-gel) as well as protein sequencing after gel filtration. Similarly, the technical approach used for protein analysis greatly influenced the results. It was observed that 2D-gel displayed the presence of proteins which were missed by the gel filtration technique. Some of the proteins contained in amyloid deposits in addition to beta 2-M, were identified as globin chains, kappa and lambda light chains of immunoglobulins, and alpha 2 macroglobulin. A putative participation of these other protein constituents on the pathogenesis of beta 2-microglobulin amyloidosis is discussed.

Amyloidosis↗