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Biomedical subjects

A Argilés

Publications and source records attributed to A Argilés.

At least 37 records · Page 2Linked to original sources
PubMed1996

Oral vitamin D or calcium carbonate in the prevention of renal bone disease?

It is well known that hyperparathyroidism begins early in renal failure and progresses, probably not linearly, throughout the natural course of renal diseases and dialysis therapy. Recent progress in basic medical science has improved our understanding of the mechanisms by which the classically known stimuli for parathyroid hormone synthesis and secretion may act, including hypocalcaemia, hyperphosphataemia and vitamin D3 metabolism disturbances. In the treatment of hyperparathyroidism, although some authors stress the benefit of treating one of these stimuli, it is probably more effective to combine the treatment of them all. There is conclusive recent work showing the efficacy of using both CaCO3 and vitamin D3, either in chronic renal failure or in dialysis patients at every stage of hyperparathyroidism. Therefore, the treatment of hyperparathyroidism should start early, long before dialysis, and it should aim to correct any of the causal factors. Both CaCO3 and vitamin D3 derivatives may be used in the prevention and treatment of renal bone disease. The limits of this association are the increasingly often reported adynamic bone disease, which in our experience has not yet given major clinical problems, and hyperphosphataemia. Uncontrolled serum phosphate levels would counterbalance the beneficial effect of vitamin D3 derivatives on hyperparathyroidism.

Administration, Oral↗
PubMed1996

Renal transplantation relieves the symptoms but does not reverse beta 2-microglobulin amyloidosis.

Renal transplantation is considered to be the treatment of choice of dialysis-related beta 2-microglobulin amyloidosis (DRA), as it provides near-normal serum levels of beta 2-microglobulin and obviates the need for dialysis. However, the long-term outcome of DRA after transplantation has not been fully assessed, and its evolution after transplant failure has not been reported. This study examined 17 patients with histologically confirmed DRA who underwent kidney transplantation and had a dialysis-free follow-up period in excess of 1 yr. Immunosuppressive treatment included low-dose prednisolone, cyclosporine, and/or azathioprine. Symptoms related to DRA were sought at every outpatient visit, and bone x-rays were performed at time of transplantation and annually thereafter. The number and size of the bone cysts were determined. Most of the DRA symptoms, and particularly shoulder stiffness, disappeared within the first wk after transplantation and this persisted throughout the transplant follow-up period (58.5 +/- 9 months). However, the number of bone cysts remained remarkably constant even in those patients with still-functioning grafts (12 +/- 7.5 and 12.1 +/- 7.7, before and at last transplantation follow-up examination, respectively). Beta 2-microglobulin amyloid was found to be present in one patient operated on for hip fracture 2 yr after receiving a well-functioning transplant. Seven patients experienced graft failure and returned to dialysis after 47 +/- 39 months of transplantation. Severe DRA symptoms reappeared strikingly early after resuming hemodialysis, and five out of the seven patients required surgery for carpal tunnel syndrome, three of them within the first yr (mean, 17 +/- 12 months). The number of cysts significantly increased from 17 +/- 11 to 21 +/- 11 during the second dialysis period. These findings provide further evidence suggesting that although the clinical expression of DRA is arrested during transplantation, the anatomical lesions and the pathological processes underlying it are unlikely to be reversed.

Adult↗
PubMed1995

Beta 2 microglobulin isoforms in healthy individuals and in amyloid deposits.

beta 2 microglobulin (beta 2m) is classically known to have isoforms with isoelectric points (pI) 5.7 and 5.3. New isoforms of beta 2m with lower pI, probably due to modifications with advanced glycation end products, were found in the amyloid deposits of dialysis related amyloidosis (DRA), and they were proposed as the amyloidogenic forms of beta 2m. The other modifications in beta 2m from amyloid deposits are partial proteolysis and single amino acid replacement (Asn by ASp at position 17). However, there are no data on the sequence of the different isoforms of beta 2 m from amyloid deposits. Amyloid deposits surgically obtained from the carpal tunnel from 13 dialysis treated patients and urine from 10 healthy volunteers and 5 living-related kidney donors were analyzed for beta 2m content. Two-dimensional gel electrophoresis (2D-PAGE) of beta 2m from amyloid deposits showed the presence of four or more isoforms with pIs < 5.7. All the spots migrating at 12 kDa Mr region and between 4 and 6 pH reacted with rabbit anti-human beta 2m antibody by Western blotting, confirming that they were beta 2m isoforms. beta 2m isoforms from the amyloid deposits were then separately purified with an IEF column (PB94, Pharmacia) for analysis. Enough quantities of three pure beta 2m isoforms could be obtained in two cases. The sequence analysis showed an intact N-terminus in all the isoforms. There was Asn in the 17th residue in all the isoforms sequenced. 2D-PAGE of urine from 8 out of the 10 healthy volunteers showed the presence of beta 2m. In two of them beta 2m also displayed four different isoforms. At least four isoforms were observed in urine of all the kidney donors. The present study shows that the elution peaks of three different beta 2m isoforms in gel isoelectrofocusing contain beta 2m with intact N-terminus. None of them have deamidated their 17th residue. More importantly, the beta 2m isoforms with lower pI are not specific for amyloidosis as they were found in urine from kidney donors and in normal volunteers. These results bring into question the hypothesis that dialysis related amyloidosis is due to the known modifications on beta 2m. They suggest that the precipitation of beta 2m into amyloid fibrils should result from the interaction of beta 2m with other factors with amyloid enhancing activity.

Adult↗
PubMed1995

Calcium balance and intact PTH variations during haemodiafiltration.

BACKGROUND: Recent approaches to prevent and treat secondary hyperparathyroidism in dialysis patients include decreasing dialysate Ca content from 1.75 to 1.5 mM or lower. We have recently observed that by decreasing dialysate Ca to 1.25 mM a rise in intact parathormone serum levels occurs despite adequately controlled predialysis Ca and phosphate serum levels. In that study complementary treatment with high-dose 1 alpha(OH) vitamin D3 was required to suppress the parathormone. In the present study we aimed to assess the total Ca balance as well as the modifications in parathormone induced by the dialysis session in order to understand the reasons for which the rise in parathormone was induced. METHODS: Fourteen HD patients treated with haemodiafiltration three times/week gave their informed consent for the study. They were distributed in two groups with identical treatment but for the dialysate Ca content which was 1.5 and 1.25 mM respectively and for the amount of oral CaCO3 received. Total and ionized Ca, phosphate, pH, and albumin as well as parathormone were measured in serum before and after dialysis and in the spent dialysate during two dialysis sessions. RESULTS: Serum ionized Ca (normalized to pH 7.4) did not change during 1.25 mM dialysate Ca and significantly increased with 1.5 mM (P < 0.001). The end-dialysis values being 1.25 +/- 0.02 and 1.38 +/- 0.02 mM respectively. Total Ca significantly decreased with 1.25 mM dialysate Ca (P < 0.04) and increased with 1.5 mM (P < 0.003), the end-dialysis values being 2.51 +/- 0.03 and 2.75 +/- 0.04 mM respectively. In the dialysate the difference in ionized Ca concentrations, fresh minus spent dialysate was -1.78 +/- 1.12 mmol/l (NS) and 4.26 +/- 1.47 mmol/l (P < 0.02) respectively for 1.25 and 1.5 mM dialysate Ca. The difference in total Ca concentrations, fresh minus spent dialysate was -0.1 +/- 0.01 mmol/l (P < 0.05) and -0.002 +/- 0.01 mmol/l (NS) respectively. Phosphate removal was higher in 1.25 mM dialysate-Ca-treated patients (40.4 +/- 1.75 mmol/session versus 34 +/- 1.3 mmol/session respectively, P < 0.015). The use of 1.25 mM dialysate Ca did not result in a change in serum parathormone, while the use of 1.5 mM resulted in a decrease of 43 +/- 15% (P < 0.02) in patients with marked hyperparathyroidism. CONCLUSIONS: Our data remind us of the difficulty in assessing Ca balances and identifies the phosphate content as one of the factors influencing the amount of ionized Ca in the dialysate. Although the long-term parathormone increase we observed using 1.25 mM dialysate Ca may well not be explained only by the acute intradialytic modifications, the negative Ca balance identified here (which was missed with the analysis of ionized Ca alone), and the lack of parathormone inhibition may participate in the relapse of hyperparathyroidism.

Adult↗
PubMed1994

Regulation of human renal adenocarcinoma cell growth by retinoic acid and its interactions with epidermal growth factor.

Retinoic acid (RA) is a natural derivative of vitamin A which regulates the growth and differentiation of epithelia. We have previously proposed that RA participates in compensatory kidney growth and reported that RA inhibits rat mesangial cell growth. This paper describes the effects of RA on a human renal adenocarcinoma cell line (PAD) under different growth conditions, and its interactions with epidermal growth factor (EGF). PAD cells were shown to express RA receptors alpha and beta by Northern blot analysis. In serum free cultures, addition of RA (10(-7) M) markedly increased thymidine incorporation by PAD cells (155 +/- 7% mean +/- SE vs. control in 6 separate experiments; P < 0.0001). RA also caused a significant increase in thymidine incorporation by PAD cells under conditions of rapid growth in serum supplemented medium (115 +/- 2% vs. control; P < 0.001). RA by itself was unable to reverse contact inhibition of PAD cell growth (NS vs. control), but it synergistically enhanced the mitogenic effect of EGF on confluent monolayers (110 +/- 0.6% vs. EGF alone; P < 0.05). Northern blot analysis demonstrated that PAD cells express EGF receptor mRNA, and this was not significantly modified by the addition of RA. Growth arrested (serum starved) PAD cells expressed RAR-alpha mRNA which was upregulated eightfold at three hours following the addition of 10% FCS. Thus, our data show that RA is directly mitogenic for serum starved human renal adenocarcinoma cells and that it exerts complex modulation of cell growth in the presence of EGF and serum components.

Adenocarcinoma↗
PubMed1994

Cells surrounding haemodialysis-associated amyloid deposits are mainly macrophages.

Dialysis-related amyloidosis is a type of amyloidosis which had beta 2-microglobulin as the major protein constituent and occurs predominantly in haemodialysis patients. Its prevalence is very high with increasing time on dialysis treatment and its pathogenesis is not completely understood. While remarkable progress has been made in the identification of the components of the deposits, there are no reports characterizing the cells surrounding the amyloid fibrils. To characterize the cellular composition of the amyloid material, specimens from seven patients treated by maintenance haemodialysis were studied with immunoperoxidase labelling using monoclonal antibodies to leukocytes (CD3, CD14, CD68, CD4, CD8, CD45). The results were very reproducible for the seven deposits assessed: Of the 182 +/- 26 leukocytes/0.2 mm2 of amyloid tissue expressing the 71.5-CD45 marker (common leukocyte), 91 +/- 6% were CD68 (KP1) positive (monocyte macrophage). No CD3-positive cells (T-cell marker) were found in six of the seven patients, with only 1.6% in the remaining one. The present study shows that although amyloidosis has classically been considered as an acellular pathology, clearly there are cells surrounding amyloid fibrils. Strikingly, these cells are almost exclusively macrophages; there are no lymphocytes or granulocytes. The putative role of macrophages in the pathogenesis of beta 2-microglobulin amyloidosis remains to be established. However, the identification and quantitation of the cells surrounding the amyloid deposits may be important for subsequent studies to elucidate amyloid pathogenesis and particularly protein-cell interactions.

Adult↗
PubMed1993

Calcium kinetics and the long-term effects of lowering dialysate calcium concentration.

The optimal dialysate calcium (Ca) content for hemodialysis has been classically fixed at 1.75 mM. However, this dialysate Ca concentration (dCa) with its positive intradialytic Ca balance combined with the use of CaCO3 as a phosphate binder may result in hypercalcemia. To prevent or treat hypercalcemia, a decrease in dCa has been proposed. In the present study both the acute and the long-term effects of lowering dCa were assessed. Additionally, given the results obtained after one year with low dCa the effectiveness of i.v. 1 alpha vitamin D3 in lowering PTH serum levels in two groups of patients dialyzed with different dCa was also studied. (a) Ca kinetics during hemodialysis (HD) and on line hemodiafiltration (HDF) were studied in a group of nine stable patients who were sequentially treated with 1.75, 1.5 and 1.25 mM dCa. Dialysate was the same but for the dCa which was lowered stepwise. Na, K, tCa, ionized Ca (iCa), proteins, phosphate and pH were measured from blood inlet and outlet and dialysate outlet at the start, one hour, two hours and after the treatments. At the same time weight, blood pressure and heart rate were recorded. The sieving of iCa was significantly different in HDF versus HD (F = 6.73; P < 0.01); intravenous infusion of 18 liters of filtered ultrapure dialysate compensated the Ca loss due to the convective component of HDF, as iCa was similar at the blood inlet in HD and HDF in the three dCa tested (F = 2.59; NS). Intradialytic iCa kinetics measured in the blood inlet were significantly different with different dCa (P < 0.001 for 1.75 mM vs. 1.5 mm and P < 0.001 for 1.5 mM vs. 1.25 mM). A significant increase in post-dialysis iCa was observed with dCa of 1.75 and 1.5 while no modification was observed with 1.25 mM dCa. (b) Regarding long-term effects of lowering dCa, seven of the nine patients acutely studied were followed for a one year period after changing from dCa = 1.5 to dCa = 1.25 mM. A control group of six patients was maintained with dCa = 1.5 for the same period of time and with the same treatment schedule but for dCa. Total Ca, phosphate and alkaline phosphatase were assessed monthly, and phosphate binders and oral vitamin D derivative doses were adapted accordingly. Intact PTH was determined quarterly. CaCO3 oral intake was more than doubled in the low dCa group. Total Ca, phosphate and ALP were similar in both groups over the assessed year.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1993

Serum alpha 2-macroglobulin in haemodialysis patients: baseline and kinetic studies.

The pathogenesis of dialysis related amyloidosis remains unresolved despite the identification of beta 2-microglobulin (beta 2M) as the major protein constituent, as well as other proteins being present in the deposits. Among the latter we have assessed the serum concentrations of alpha 2-macroglobulin (alpha 2M) both in the baseline stage and during the haemodialysis (HD) procedure. We have also assessed the influence of the membrane on alpha 2M kinetics. Fifteen HD patients with histologically proven dialysis-related amyloidosis (DRA group) and 15 HD patients clinically and radiologically considered dialysis-related amyloidosis free (control group) were included in the baseline study. Blood was sampled the day before the second dialysis of the week and alpha 2M, beta 2M and alpha 1 antitrypsin were determined along with the routine biological analysis of these patients. Serum alpha 2M was greater in dialysis-related amyloidosis than in control patients (t = 2.35; P < 0.026). Serum beta 2M was similar in both groups. The serum alpha 2M and beta 2M correlated in patients with dialysis-related amyloidosis (r = 0.64; P < 0.01), while no correlation was found in controls (r = 0.17; NS). Stepwise analysis taking the presence of dialysis-related amyloidosis as the dependent variable retained the serum alpha 2M concentration as the first variable in the model (F = 4.4; partial r = 0.38; P < 0.046).(ABSTRACT TRUNCATED AT 250 WORDS)

Amyloidosis↗
PubMed1993

Accuracy of Kt/V estimations in high-flux haemodiafiltration using per cent reduction of urea: incorporation of urea rebound.

The estimation of Kt/V by utilization of the pre- and postdialysis urea concentrations (per cent reduction in urea and In(Upre/Upost)) provides a simple, quick technique that can be applied at the bedside. However, the accuracy of such techniques has been questioned. One possible reason for this inaccuracy may be the frequently observed postdialysis rebound in serum urea. We assessed the urea rebound at 30 min postdialysis in 34 haemodiafiltered patients and compared the calculation of Kt/V using this urea concentration with that using the immediate postdialysis concentration. These results were then compared to the Kt/V calculated by urea kinetic modelling (UKM), also utilizing the delayed serum urea concentration. The degree of urea rebound observed was large, 21.4%, being a reflection of the short-duration, rapid-flux dialysis. The formulae for calculation of Kt/V all significantly correlated with Kt/V by UKM but all gave results significantly different from Kt/V by UKM (P < 0.001 by paired t test). For assessment of Kt/V by these formulae or by UKM, the urea rebound is too large to ignore in the setting of short-duration, rapid-flux dialysis.

Blood Proteins↗
PubMed1992

Epidermal growth factor and transforming growth factor alpha stimulate or inhibit proliferation of a human renal adenocarcinoma cell line depending on cell status: differentiation of the two pathways by G protein involvement.

Transforming growth factor alpha production by renal tumors, acting through the epidermal growth factor receptor, has been implicated in malignant transformation by studies which compared gene expression in neoplastic and normal human tissue. We sought confirmation of this hypothesis by measuring the growth responses of a human renal tumor cell line to the addition of epidermal growth factor and transforming growth factor alpha. Surprisingly, it was found that both growth factors could induce either mitogenic or inhibitory signals depending on the growth status of the cultures. Confluent cultures were stimulated by both growth factors, and nonconfluent cultures were inhibited, as determined by thymidine incorporation, cell cycle analysis, and direct cell counting. These signals appear to use different transduction pathways, as growth factor induced inhibition was reversed by Bordetella pertussis toxin (which affects G protein signaling), whereas the stimulatory effects were not reversed. Two clones isolated from these cells responded in the same manner as the main cell isolate. These data show that the same cell may display opposite responses to equivalent concentrations of the same growth factor, depending on the transduction pathway used after triggering by receptor occupancy of either ligand (epidermal growth factor or transforming growth factor alpha).

Adenocarcinoma↗