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G Del Peso

Publications and source records attributed to G Del Peso.

17 recordsLinked to original sources

Tissue models of peritoneal fibrosis.

OBJECTIVE: To evaluate the utility of peritoneal pathologic samples, unrelated to peritoneal dialysis (PD) treatment, for the study of peritoneal fibrosis and inflammation. METHODS: Comparative morphologic and immunohistochemical study of peritoneal pathologic samples unrelated to PD with peritoneal biopsies from PD patients with special emphasis on the expression of myofibroblastic and epithelial-to-mesenchymal transition markers. RESULTS: Regarding morphology, PD-related simple fibrosis was less cellular, with greater stromal hyalinization, determining a homogeneous, hypocellular aspect of the submesothelium. In contrast, non-PD fibrosis was more cellular with an extracellular matrix showing a dense and fibrillar quality with wide bundles of collagen. Hylinazing vasculopathy was only present in PD samples. Myofibroblastic differentiation and epithelial-to-mesenchymal transition were common findings in all situations of peritoneal fibrosis. Calponin and calretinin are useful cellular markers to study such fibrogenic mechanisms and correlate with other well-known markers such as a -SMA and cytokeratins. Their expression was much more intense in those samples showing acute inflammation (peritonitis). CONCLUSIONS: Non-PD models of peritoneal fibrosis seem very useful to evaluate important features of human peritoneal pathology such us fibrogenesis, and inflammation. Fibrogenic events such as myofibroblastic differentiation and epithelial-to-mesenchymal transition are evident in these tissue samples allowing us to use them as an accessible source for in vivo and ex vivo studies. Both events show their maximal expression in situations of acute inflammation supporting the important role that peritonitis episodes play in the progression of fibrosis.

Actins↗

Myofibroblastic differentiation in simple peritoneal sclerosis.

OBJECTIVE: To analyze the presence of myofibroblasts in a series of peritoneal dialysis (PD) patients with simple sclerosis and non-PD, uremic patients. Since there is a close correlation between active fibrosis and myofibroblastic differentiation we wanted to test if myofibroblasts are present in uremic, non-PD peritoneal samples. To determine if there are correlations between myofibroblastic presence and other functional and morphologic peritoneal parameters. METHODS: Biopsies were collected from three patient groups: 1) Normal control samples (n = 15) of parietal and visceral peritoneum 2) non-PD uremic patients (n = 16); and 3) uremic patients on PD (n = 32). Peritoneal morphologic and functional parameters and immunohistochemical expression of alfa-smooth muscle actin was analyzed in each case. Vascular endothelial growth factor (VEGF), bcl-2 anti-apoptotic protein, and progesterone receptor was evaluated in a subset of cases. RESULTS: Myofibroblasts were present in 56.3% of the patients with PD-related simple sclerosis. In most cases they were distributed in the upper submesothelial area. None of the biopsies from normal controls and uremic, non-PD patients showed myofibroblasts. Within the group of PD patients, myofibroblasts showed no correlation with time on dialysis, urea/creatinine MTAC, episodes of peritonitis, submesothelial thickening, hyalinizing vasculopathy or mesothelial status. In a subset of PD patients VEGF expression was observed in submesothelial fibroblastic cells. No expression of progesterone receptor or bcl-2 was observed. CONCLUSIONS: Myofibroblasts are a reliable and simple indicator of fibrosis since they appear in early stages of PD treatment and in patients with minor morphologic anomalies. They are not exclusive of patients with sclerosing peritonitis, ultrafiltration loss or long standing treatment. Their absence in non-PD, uremic patients suggest that uremia-related fibrosis takes place without a significant participation of myofibroblasts.

Adult↗

Effects of rapamycin on the epithelial-to-mesenchymal transition of human peritoneal mesothelial cells.

The preservation of the peritoneal membrane is crucial for long-term survival in peritoneal dialysis. Epithelial-to-mesenchymal transition (EMT) is a process demonstrated in mesothelial cells (MC), responsible for negative peritoneal changes and directly related to PD. EMT enables neovascularization and fibrogenic capabilities in MC. Vascular endothelial growth factor (VEGF) is the mediator for neo-vascularization. Rapamycin is a potent immunosuppressor with antifibrotic action in renal allografts and has a demonstrated anti-VEGF effect. We performed this study with the hypothesis that rapamycin may regulate the EMT of MC. MC from human omentum were cultured. When mesothelial cells reached confluence, some of them were stimulated with r-TGF-beta (1 ng/mL) to induce EMT, co-administered with rapamycin (0.2, 2, 4, 20 and 40 nM). Other groups of cells received similar doses of rapamycin or r-TGF-beta, separately. Cells were analyzed at 6, 24, 48 hours and 7 days. As markers of EMT we included alfa -SMA, E-cadherin and snail nuclear factor by quantitative RT-PCR. EMT markers and regulators demonstrated the following changes with rapamycin: E-cadherin (a protective gene for EMT) increased 2.5-fold relative to controls under 40 nM, at 24h. Importantly, rapamycin inhibited snail expression induced by TGF-beta at 6h, whereas TGF-beta increased snail 10-fold. At day 7, rapamycin showed no anti-EMT properties. An important decrease in alfa -SMA expression by MC after rapamycin addition was observed. In conclusion, rapamycin shows a mild protective effect on EMT, as it increases E-cadherin and decreases alfa -SMA expression. Consequently, rapamycin might partially regulate the epithelial-to-mesenchymal transition of mesothelial cells.

Actins↗

Stability of the peritoneal membrane in long-term peritoneal dialysis patients.

One of main challenges of peritoneal dialysis (PD) is the functional and vital long-term stability of the peritoneal membrane. Few longitudinal and controlled studies on peritoneal function have been published, and the results are somewhat contradictory. We have performed a longitudinal study with 90 patients. The overall analysis has shown that creatinine mass transfer coefficient (MTC) significantly increases and ultrafiltration (UF) capacity decreases over time. Nevertheless, urea MTC remained unaltered and MTC ratios significantly decreased after the third year. Subsequently, we examined the clinical outcomes and identified 19 patients who required peritoneal resting periods for Type I UF failure and 71 patients who did not require such a procedure. The latter patients did not show any significant functional change over time, whereas the former 19 patients showed an increase of peritoneal creatinine transport and a loss of UF capacity. These data corroborate changes in long-term peritoneal function in approximately 20% of PD patients. These changes consist of an increase in effective exchange area, peritoneal permeability, or both, accompanied by signs suggestive of mesothelial regenerative capacity loss. Infectious peritoneal injuries, especially appearing during late PD periods, are deleterious to the peritoneum. The remainder of the functional-structural changes are related to the effects of currently used dialysate. Early diagnosis, preemptive, and therapeutic measures should permit better management of long-term PD patients. The particular response to these injuries has individual characteristics that when addressed permit PD to be used long-term.

Analysis of Variance↗

Peritoneal dialysis in liver disorders.

The purposes of this paper is to review the specific role of peritoneal dialysis (PD) in patients with liver disorders. We will pay attention to the confluence of liver diseases and situations for which chronic dialysis treatment is required. Hemodialysis (HD) and peritoneal membranes are safe barriers against the passage of the hepatitis C virus; consequently, while peritoneal effluent or HD ultrafiltrate drained from hepatitis B patients/carriers is infective, that from hepatitis C patients does not appear to present this risk. An important issue is horizontal transmission, which appears to occur with both viruses in HD units, and which is absent in peritoneal dialysis units. The incidence of hepatitis C among continuous ambulatory peritoneal dialysis (CAPD) patients is quite low, while it may reach almost 50%-60% of HD patients in some units. While hepatitis C transmission mechanisms are not completely understood and a vaccine is not available, PD provides some degree of protection when compared with HD, for and-stage renal disease patients. In summary, our experience and that of others, with a total of 19 PD-treated chronic liver disease patients, supports CAPD as the treatment of choice for cirrhotic patients with ascites who require chronic dialysis. Data on peritoneal diffusion of low molecular weight substances revealed a marked increase in most patients. The ultrafiltration capacity was clearly augmented with respect to noncirrhotic patients, making the use of hypertonic bags unnecessary. Hemodynamic tolerance was excellent. Complications and death were mainly related to liver disease complications. Spontaneous bacterial peritonitis (SBP), caused by gram-negative germs, is the most important complication directly related to ascites and may have some points in common with PD-related peritonitis. However, and in contrast to most PD peritonitis, two pathogenetic mechanisms have been suggested for SBP: (1) translocation of bacteria from the gut to the mesenteric lymph nodes, and (2) bacteremia in these patients is secondary to the general abnormal host defense mechanisms. Local factors such as intrahepatic shunting and the impairment of bactericidal activity in ascitic fluid favor the bacteria ascites. The hypothesis of a direct transmural contamination from bowel to ascitic fluid has been relegated to secondary bacterial peritonitis. Would cirrhotic patients with temporal or permanent renal function compromise benefit from peritoneal catheter placement and other PD practices to perform repetitive small ascitic drainages at home? Perhaps the time has arrived when hepatologists and PD nephrologists begin to work shoulder to shoulder in this particular field, as we have a common problem, the peritoneal cavity filled with fluid.

Ascitic Fluid↗

Peritoneal functional changes induced by dialysate containing bicarbonate instead of lactate.

Lactate (L)-containing dialysate has a low pH, responsible for its poor biocompatibility. Dial-ysate-containing bicarbonate (B) with a physiological pH is available. We compare the peritoneal functional effects of these two solutions. Eight patients were studied two weeks apart using two consecutive peritoneal kinetic tests to determine convective and diffusive mass transfer coefficient (MTC) capacities for different solutes. Both L and B solutions were identical, except for pH and buffer content. Peritoneal equilibration values at four-hour dwell time were similar for all solutes, except for urea (B: 0.91 +/- 0.05 vs L: 0.87 +/- 0.06, p < 0.05). Peritoneal MTC (B vs L) values for urea (19.6 +/- 6.6 vs 18.2 +/- 4.5), creatinine (8.8 +/- 4.8 vs 7.8 +/- 3.5), phosphate (7.7 +/- 4.6 vs 6.0 +/- 2.2), and potassium (13.3 +/- 5.6 vs 11.7 +/- 5.0) were slightly higher for B (NS). Glucose-MTC was slightly lower for B (6.2 +/- 3.3 vs 7.5 +/- 3.2, NS). Ultrafiltration (UF) was lower for B (drained volume: 2120 +/- 204 vs 2443 +/- 285 mL after 4 hr, p < 0.05). Higher transperitoneal calcium [11 +/- 22 L vs -3.1 +/- 11.0 (positive balance) mg, p < 0.05] and sodium (48 +/- 30 L vs 13 +/- 20 mEq) removal were evident. With L, the loss of 43.0 +/- 6.3 mEq of bicarbonate appeared. The linear regression analysis of MTC values showed higher r coefficients for the bicarbonate solution. These results suggest that bicarbonate dial-ysate improves the diffusion capacity of the peritoneum with respect to lactate.

Adult↗

Circulating burst-forming unit-erythroid (BFU-E) colonies as an early marker to measure the recombinant human erythropoietin response in peritoneal dialysis patients.

To evaluate circulating burst-forming unit-erythroid (BFU-E) cells after erythropoietin (EPO) treatment, 7 female continuous ambulatory peritoneal dialysis patients were studied [baseline hemoglobin (HB): 7-10.5 g/dL)]. EPO (4000 U subcutaneously) was administered twice weekly for two months. The control group consisted of 7 healthy women with similar demographic characteristics. Mononuclear cells (MC) (5 x 10(5)) were added to 1 mL of culture medium, supplemented with 30% fetal bovine serum, 2 U/mL of EPO, 1% bovine serum albumin, and 0.3% agar. To enumerate colonies derived from each circulating BFU-E, plates were examined by inverse light microscopy, identifying BFU-E as large aggregates with more than 100 hemoglobinized cells (HC). A remarkable individual response was observed, with Hb values ranging 8.4-13.6 g/dL at week 4 and 8.8-16.5 g/dL at week 8. Baseline levels of BFU-E in patients ranged 0-100/5 x 10(5) MC (0-358 mL of whole blood), and in controls they ranged 6-24/5 x 10(5) MC (29.6-101.3/mL) (NS). Hemoglobin levels after four and eight weeks of EPO showed a significant relationship with circulating BFU-E at baseline (r = -0.873, r = -0.928, respectively). The increment in Hb after eight weeks showed a significant relationship with baseline BFU-E (r = 0.812). Hemoglobin levels at the fourth to eighth week, and the increment in Hb after eight weeks, showed a significant, direct relationship with the increments in circulating BFU-E registered after one to two weeks of treatment. We conclude that, after the first week of EPO treatment, its effect on hemoglobin may be predieted by the increment in circulating BFU-E. Thus; a new tool to measure the earliest EPO effects has become available.

Adult↗

Mitral annular calcification in CAPD patients with a low degree of hyperparathyroidism. An analysis of other possible risk factors.

Chronic renal failure has been suggested as a risk factor for mitral annular calcification (MAC), a degenerative process of the mitral annulus. The objective of the present study was to define MAC risk factors at the start of dialysis and 'de-novo' appearance after medium- or long-term CAPD, in a non-selected population (135 patients) with a low degree of secondary hyperparathyroidism. Echocardiographic studies were performed at the beginning of CAPD and every 1-1.5 years thereafter. Diagnosis of MAC was established by M mode and 2-D study. Seventeen of 135 patients studied at the start of dialysis showed MAC. Patients who showed MAC were older and presented a higher mean systolic blood pressure. The other anthropometric/demographic parameters did not show statistically significant differences. MAC thickness: mean 6.21 +/- 3.65 mm (range 3-17.2 mm). The posterior annulus was universally affected and in four patients the anterior annulus was involved. Seventeen of 76 patients included in the follow-up study developed MAC. No significant differences for demography, except age, with MAC patients being older, were found. Mean time on CAPD until de-novo MAC diagnosis was 49.7 +/- 26.9 months. MAC thickness: mean 4.97 +/- 1.6 mm (range 3-8.42 mm). The posterior annulus was affected in all patients except for one and in four patients the anterior annulus was involved. The most remarkable echocardiographic feature is the almost constant association of MAC with left atrial dilatation (LAD). The last one does not seem a consequence of mitral insufficiency, or systolic dysfunction. Left ventricular hypertrophy was universally found, with no different intensities for patients with or without MAC. In conclusion, a high incidence of mitral annular calcification has been found in CAPD patients. Our data do not confirm the role of classical invoked risk factors. Blood CaP product under 75, a moderate to mild degree of hyperparathyroidism and/or hypertension with left ventricular hypertrophy do not seem to be isolated risk factors during the CAPD period. Length of time on CAPD, for unknown reasons, seems to favour the appearance of MAC. At starting dialysis, high systolic blood pressure and left ventricular hypertrophy seem to be related to MAC. Diabetes appears to represent an additional risk factor. Further research on mitral annular calcification pathogenesis and its consequences is urgently required.

Calcinosis↗

Functional longevity of the human peritoneum: how long is continuous peritoneal dialysis possible? Results of a prospective medium long-term study.

Long-term peritoneal dialysis requires the maintenance of the transport function of the peritoneal membrane, and appropriate studies of possible changes are necessary. The quantification of peritoneal mass transfer coefficients (MTCs) has been judged to be the ideal method for the evaluation of peritoneal diffusion. The aim of the present study was to show the results of the prospective evaluations in long-term continuous ambulatory peritoneal dialysis patients. We have studied the clinical incidents and peritoneal function of 56 patients who started continuous ambulatory peritoneal dialysis between 1980 and 1988, and have completed at least 3 years of follow-up. Ultrafiltration capacity was calculated with a standardized formula. All patients were studied for peritoneal diffusion of urea and creatinine at least once a year. The evaluation consisted of a kinetic study done by means of a peritoneal equilibration curve for urea and creatinine, applying a bicompartmental mathematical model to calculate the MTCs. The sequential mean values for urea-MTC did not show significant changes over the observation period (20.7 +/- 5.9 mL/min for the first year v 19.8 +/- 6 mL/min for the fifth year). Creatinine-MTC values showed a significant increase over this period in the paired data analysis. The decrease of the urea-MTC to creatinine-MTC ratio may be an early and appropriate index for measuring these changes when the individual values are in the normal range. On the other hand, peritoneal ultrafiltration capacity significantly decreased over this period (1,800 +/- 530 mL/d v 1,400 +/- 600 mL/d, P < 0.01). The high rate of accumulated days of peritoneal inflammation was related to these significant changes, and thus may be proposed to be a good prognostic index of long-term peritoneal survival. These long-term functional changes might be related to the effect of injuries on the preservation of the normal peritoneal structure. We conclude that after 5 to 11 years, the human peritoneum shows functional stability (diffusion and water transport) in patients with low rates of peritoneal inflammation. With a few exceptions, represented by patients with a high rate of peritoneal inflammation, long-term peritoneal dialysis accomplished its newly entrusted task.

Adolescent↗

Clinical significance of exit-site infections due to Xanthomonas in CAPD patients: a comparison with Pseudomonas infection.

We have assessed the clinical significance of exit-site infections secondary to Xanthomonas maltophilia in continuous ambulatory peritoneal dialysis (CAPD) patients, and compared them with episodes due to Pseudomonas. The study was a retrospective survey of all episodes of Xanthomonas and Pseudomonas-related exit-site infections (ESI) in all patients treated in our unit between 1984 and 1992. Thirteen episodes of Xanthomonas-related ESI were observed in eight patients and 17 episodes of Pseudomonas-related ESI were seen in 15 patients. Xanthomonas-related ESI was frequently associated with other microorganisms, while Pseudomonas-related ESI was not (66% versus 5%, P < 0.02). Only one episode of Xanthomonas-related ESI resulted in peritonitis and subsequent catheter removal, after 15 months of resistant colonization. Another case was considered to be chronic and indolent, as the Xanthomonas-related ESI continued after 23 months of local treatment. The other 11 episodes were resolved either without treatment or with an antibiotic cream after 7-120 days. However, all but two episodes of Pseudomonas-related ESI required intravenous antibiotics (usually ceftazidime); seven patients developed peritonitis, and 11 required surgical catheter manipulation (five external cuff extrusion, and six catheter removal) (1/13 Xanthomonas-related versus 11/17 Pseudomonas-related ESI, P < 0.03). Most Xanthomonas-related ESI do not lead to peritonitis, and constitute a mild condition, easily treatable without parenteral antibiotics or catheter replacement. The appearance of other associated organisms and the favourable evolution with local treatment suggest a saprophytic behaviour for Xanthomonas in our CAPD patients. On the contrary, Pseudomonas-related ESI is usually severe, requires parenteral antibiotics, frequently leads to peritonitis, and requires catheter replacement.

Adult↗

CAPD for treatment of ESRD patients with ascites secondary to liver cirrhosis.

The treatment of cirrhotic patients with ascites and end-stage renal disease (ESRD) is complex. Continuous ambulatory peritoneal dialysis (CAPD), as a continuous therapy, represents an alternative to hemodialysis-associated hemodynamic intolerance. We report our experience with 5 cirrhotic patients with ascites who were treated by CAPD. Three had been transferred from hemodialysis (HD) for intolerance. The hemodynamic tolerance was excellent in all patients, and solute and water peritoneal transport were increased over the normal range in all cases. Morbidity was principally related to liver disease. Peritoneal protein losses, initially high, decreased over time. Serum albumin was within the low normal range. The incidence of peritonitis was higher than usual in these patients; episodes caused by gram-negative bacteria, streptococci and listeria, were predominant. The cause of death was not CAPD-related. In our experience, CAPD should be the treatment of choice for cirrhotic patients with ascites who require dialysis.

Adult↗

Increased response to subcutaneous erythropoietin on type I diabetic patients on CAPD: is there a synergistic effect with insulin?

OBJECTIVE: To evaluate the effect of subcutaneous erythropoietin (SC EPO) on the treatment of anemia in diabetic and nondiabetic continuous ambulatory peritoneal dialysis (CAPD) patients. DESIGN: A resistance index was designed for measuring the relative EPO response, dividing EPO dose (U/kg/week) by the hemoglobin (Hb) increment with respect to the basal level. PATIENTS: Eleven nonselected type I diabetic patients using subcutaneous insulin compared with 16 nondiabetic controls, all on CAPD therapy. RESULTS: The two groups showed similar mean baseline hemoglobin levels (7.4 D-I and 7.7 non-D, g/dL). There was a statistically significant lower resistance index for diabetics (13.8 +/- 9.7 U/kg/g Hb increment) compared to nondiabetic (55.8 +/- 128, p < 0.001). Multivariate analysis confirmed an independent association between diabetes and resistance index. The response to EPO was slightly better among those diabetic patients with lower levels of serum parathyroid hormone (iPTH) (PTH-resistance index, correlation coefficient, r = 0.7, p < 0.05). No other differences, apart from the use of subcutaneous insulin, were found between diabetics and controls. Although diabetic patients had an increased response to EPO, they had no more frequent side effects than nondiabetics. CONCLUSIONS: According to our results, we suggest that factors related to insulin-dependent diabetes seem to be involved in a favorable response to SC EPO. Hyperinsulinemia derived from subcutaneous use of insulin might act as a comitogen with the induced increments of serum erythropoietin.

Adult↗

Erythropoietin treatment decreases cardiovascular morbidity and mortality in CAPD patients.

OBJECTIVE: To analyze the effects of recombinant human erythropoietin (rHuEPO) therapy on cardiovascular (CV) morbidity and mortality among continuous ambulatory peritoneal dialysis (CAPD) patients. DESIGN: Retrospective comparative study. SETTING: CAPD unit in a university hospital. PATIENTS: Forty-two patients on rHuEPO treatment for at least one year were compared with an rHuEPO nonuser group of 113 patients. Subcutaneous rHuEPO doses were adjusted to a hemoglobin objective level of 10.5-13.5 g/dL. Fifty-seven patients were considered as high cardiovascular risk (HCVR), 17 in the rHuEPO group and 40 in the rHuEPO nonuser group. Ninety-eight patients were classified as low cardiovascular risk (LCVR), 25 of whom were in the rHuEPO group. RESULTS: The incidence of cardiovascular morbidity was more frequent in the rHuEPO nonuser than in the rHuEPO user group (40% vs 22%) and in HCVR than in LCVR patients (59.6% vs 20.4%). By multiple logistic regression analysis, the best model to explain the development of cardiovascular morbidity comprises rHuEPO treatment, CV risk, and age. In the rHuEPO user group, HCVR and LCVR patients did not show significant differences in survival, while in the rHuEPO nonuser group, HCVR patients had a lower survival rate than LCVR patients (p = 0.0003). Cox proportional hazards model revealed that LCVR patients had an excellent prognosis compared with HCVR patients in the rHuEPO nonuser group, but this difference disappeared in the rHuEPO user group. CONCLUSION: These data show a beneficial effect of rHuEPO treatment on cardiovascular morbidity and mortality in CAPD patients, evidenced by the elimination of the correlation between prior cardiovascular risk and subsequent mortality.

Adult↗