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R Selgas

Publications and source records attributed to R Selgas.

At least 55 records · Page 3Linked to original sources
PubMed1999

Long-term effects of recombinant human erythropoietin therapy on growth hormone secretion in uremic patients undergoing peritoneal dialysis.

Recombinant human erythropoietin (rhEPO) is being successfully used for the treatment of uremic anemia. Short-term studies have proved that correction of anemia with rhEPO therapy is accompanied by several changes in growth hormone (GH) secretion in uremic patients. The present study aimed to assess the influence of long-term rhEPO therapy on baseline and stimulated GH concentrations in a group of uremic patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Seven well-nourished and clinically stable CAPD patients were studied. Ten normal subjects were studied as controls. GH responses to direct pituitary stimulation with GH-releasing hormone (GHRH) (100 microg intravenously [i.v.]) and indirect hypothalamic stimulation with insulin-induced hypoglycemia (0.1 U/kg body weight i.v.) and clonidine (0.15 mg/m2 orally), were assessed before and after 3, 6, and 12 months of subcutaneously administered rhEPO therapy. After rhEPO administration, an increase of the hemoglobin concentration was observed in all patients and maintained at about 12 g/dL throughout the study period. rhEPO therapy did not induce any significant change in baseline concentrations of GH and insulin-like growth factor I. Correction of the anemia was accompanied by a clear increase in the area under the curve (AUC) and the area above the baseline (AAB) of GH secretion in response to GHRH stimulation. These changes were statistically significant after 3 and 6 months of therapy, although at 12 months no significant differences in relation to pretreatment values could be observed. rhEPO treatment was associated with a progressive decrement in the GH AUC and AAB in response to hypoglycemic challenge, reaching statistically significant values at months 6 and 12. On the other hand, compared with the control group, GH responses to clonidine were blunted at the start of the study in CAPD patients, and rhEPO therapy was not accompanied by any modification. In conclusion, long-term treatment with rhEPO in CAPD patients is associated with complex and profound effects on somatotrope cell function, characterized by diverse effects on GH responses to stimuli that release GH through different mechanisms. Some of these rhEPO-induced alterations in somatotrope function are dependent on the duration of treatment.

Adrenergic alpha-Agonists↗
PubMed1999

Effects of cholinergic muscarinic blockade on growth hormone responses to growth hormone-releasing hormone in uraemic patients.

BACKGROUND: Several alterations in growth hormone (GH) secretion have been reported in patients with chronic renal insufficiency. However, cholinergic modulation of somatotopic cell function has not been fully clarified in uraemic patients. To gain further insight into the disrupted mechanism of GH regulation in chronic renal failure, we investigated whether the blockade of cholinergic muscarinic receptor with pirenzepine could modify the response of GH to its physiological releasing hormone. METHODS: Eight uraemic male patients on peritoneal dialysis and six normal controls were studied. All subjects underwent two endocrine tests in random order. In one of them placebo was administered 60 min before the injection of GH-releasing hormone (GHRH, 100 microg, i.v. in bolus at 0 min). In another the muscarinic blocking agent pirenzepine, 100 mg p.o., was administered at that time. Blood samples for GH were collected at -60, 0, 15, 30, 45, 60 and 90 min. RESULTS: Baseline plasma GH concentrations were similar in patients and controls. GH responses to GHRH were characterized by great interindividual variability in uraemic patients with regard to the amount and the time to maximal peak. In the placebo plus GHRH test, the maximum GH concentrations in patients (14.0 +/- 3.2 microg/l) were similar to those reached by controls (18.0 +/- 3.1 microg/l), although GH secretion was more sustained in patients. The area under the secretory curve (AUC) of GH secretion in patients was also similar to that found in controls (14.4 +/- 2.9 vs 15.4 +/- 3.3 microg/h/l). When subjects were given pirenzepine before GHRH injection an abolishment of GHRH-induced GH release was observed in all controls and in all but one of the uraemic patients. The AUC of GH secretion was, therefore, significantly reduced both in uraemic patients (4.1 +/- 2.0 microg/h/l, P<0.05) and in control subjects (2.0 +/- 0.3 microg/h/l, P<0.05). CONCLUSION: These results suggest that GH secretion in uraemic patients is modulated, at least in part, by a cholinergic mechanism. The muscarinic blockade, possibly acting via an increase in somatostatin release, is able to inhibit GH release in response to direct pituitary stimulation with GHRH.

Administration, Oral↗
PubMed1999

Effects of recombinant human erythropoietin on functional and injury endothelial markers in peritoneal dialysis patients.

Clinical effects of recombinant human erythropoietin (rHuEPO) such as thrombosis, convulsions, hyperviscosity, hypertension, and angiogenic effect in culture cells have been described. We studied the rHuEPO effect on endothelial damage markers and endothelial function markers: tissue-type plasminogen activator (t-PA), nitrate (NO3), thrombomodulin (TM), and von Willebrand factor (vWF). Twenty-six peritoneal dialysis patients treated with rHuEPO and 19 controls were included. The study design for rHuEPO patients consisted of four periods: long-term treatment (rHuEPO-1); 2 months of withdrawal (rHuEPO-2); and 4 months on 5000 IU/week rHuEPO subcutaneously, with markers being measured after 2 months (rHuEPO-3) and after 4 months (rHuEPO-4). After 2 months of rHuEPO withdrawal, a decrease in hemoglobin level appeared (11+/-1.8 g/dL to 9.2+/-1.5 g/dL, p < 0.01). After rHuEPO reintroduction, this value reached 10.6+/-1.5 g/dL at two months, and 11.1+/-1.4 g/dL at four months. A significant increase in t-PA ratio was observed from two months without rHuEPO to two months on rHuEPO, returning to previous values after four months. Similarly, TM increased for patients with creatinine clearances (CrC) < 5 mL/min. No changes in the higher-than-normal plasma vWF levels were found during the various periods. A statistically significant lower value was found in controls compared with rHuEPO-4 patients. A statistically significant increase in NO3 levels was observed in the pre-venous occlusion (VO) test immediately after the re-introduction of rHuEPO. This increment returned to prior values four months after rHuEPO was reintroduced. Our results show that rHuEPO treatment causes an increase in some endothelial damage markers (TM, t-PA) and modifies endothelial function markers (t-PA ratio, NO3). These changes might favor thrombosis and atherosclerosis.

Adult↗
PubMed1999

Peritoneal kinetics of cancer antigen 125 in peritoneal dialysis patients: the relationship with peritoneal outcome.

Cancer antigen 125 (CA125) is a mesothelial product that has been directly related with mesothelial bulk in peritoneal dialysis (PD) patients. Here, we evaluate CA125 levels in peritoneal effluent over time on PD, and relate them to changes in peritoneal function. We analyzed 27 peritoneal kinetic studies in 20 stable PD patients. Three patients dropped out of PD for peritoneal membrane failure after the last kinetic study, and six patients required a peritoneal rest period as treatment for membrane failure type I. We recorded the standardized daily ultrafiltration capacity, net ultrafiltration during the kinetic study, peritoneal mass transfer coefficients, time from onset of PD, and incidence of peritonitis prior to the study. A linear increase in CA125 levels over time was observed, and a strong correlation appears among the levels at different dwell times (r: 0.85-0.98, p < 0.05). At 180 minutes, the mean CA125 concentration was 48.5 +/- 39.7 U/mL. We observed significant differences in CA125 levels in effluent between the group of patients who later required a peritoneal rest period and the group of stable patients (27.7 +/- 26.3 U/mL vs 55.7 +/- 41.5 U/mL respectively, p < 0.05). Patients who left PD showed lower CA125 levels in effluent (31.4 +/- 30.6 U/mL vs 52.3 +/- 41.1 U/mL, p < 0.1). No correlation was seen between CA125 levels in effluent and time on PD, episodes of peritonitis, accumulated days of peritoneal inflammation, ultrafiltration capacity, or urea and creatinine mass transfer coefficients (MTCs). In conclusion, we believe that serial determinations of peritoneal effluent CA125 levels may help in the early identification of patients who show abnormal responses to peritoneal dialysis or its complications.

CA-125 Antigen↗
PubMed1999

Tumor necrosis factor alpha as a uremic toxin: correlation with neuropathy, left ventricular hypertrophy, anemia, and hypertriglyceridemia in peritoneal dialysis patients.

Tumor necrosis factor alpha (TNF alpha) is usually excreted by the kidney. In dialysis patients, it accumulates. TNF alpha has been implicated in the pathogenesis of malnutrition, diabetic neuropathy, and erythropoietin resistance. We studied TNF alpha plasma levels in 49 stable peritoneal dialysis (PD) patients, with the aim of correlating those levels with the presence and severity of peripheral neuropathy, hypertrophic cardiomyopathy, and anemia. Kt/Vurea' residual renal creatinine clearance (CrC), nutritional markers, and general biochemistry were also determined. The average plasma level of TNF alpha was 67 +/- 32 pg/mL (range: 18.1-156.3 pg/mL; normal value 3-20 pg/mL). No correlation was observed between TNF alpha and KT/Vurea' but a negative correlation with CrC was seen (r: -0.37, p < 0.05). TNF alpha levels were higher in patients with neuropathy as compared to patients with normal results (72.5 +/- 32 pg/mL vs 44 +/- 22 pg/mL, p < 0.05). Patients with neuropathy also showed a lower CrC value (1.5 +/- 1.7 mL/min vs 3.9 +/- 2.6 mL/min, p < 0.01). TNF alpha levels were higher in patients with left ventricular hypertrophy (LVH) with respect to normal individuals (70.4 +/- 32 pg/mL vs 38.5 +/- 20.8 pg/mL, p < 0.05). Patients with severe LVH showed the lowest CrC value. A direct, significant relationship was found between TNF alpha levels and weekly erythropoietin dose (r: 0.41, p < 0.05). Patients with hypertriglyceridemia or taking lipid-lowering agents showed a positive linear correlation between TNF alpha and triglycerides (r = 0.7, n = 14, p < 0.05). These data suggest that accumulation of TNF alpha may contribute to the development or maintenance of some neurologic, hematologic, and cardiac complications of uremic syndrome. Loss of residual renal function conditions an increment in TNF alpha levels. These data continue to add support to the idea that TNF alpha may be considered a uremic toxin.

Adult↗
PubMed1998

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↗
PubMed1998

Recombinant human growth hormone therapy in malnourished dialysis patients: a randomized controlled study.

Recombinant human growth hormone (rhGH; Saizen, Serono, Spain) has been recently used as an anabolic agent in several catabolic states, including malnourished chronic dialysis patients. However, up-to-date, comparative studies with control groups of dialysis patients have not been reported. The aim of the present study was to assess the effects of rhGH on nutritional status in a group of malnourished adult chronic dialysis patients undergoing both continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis (HD). The patients were randomly assigned to the control group (nine patients; 6 women, 3 men; mean age, 58.3 +/- 5.6 years; seven undergoing CAPD, two undergoing HD) or the rhGH group (eight patients; three women, five men; mean age, 63.9 +/- 3.1 years; four undergoing CAPD, four undergoing HD). Both groups were similar at baseline. All patients were given dietary prescriptions (35 kcal/kg/d and 1 g protein/kg ideal body weight/d) during 4 weeks. In the rhGH group, rhGH was administered at 0.2 IU/kg/d subcutaneously (SC) during this period. Anthropometric and analytic parameters were assessed before (0 weeks) therapy and at 2 and 4 weeks after starting therapy. The rhGH group showed an increase of 1.238 kg in body weight from 64.3 +/- 4.3 (mean +/- standard error of the mean [SEM]) to 65.6 +/- 4.9 kg (P < 0.05). Serum insulin-like growth factor type 1 (IGF-1) concentrations increased from 216.6 +/- 42.5 to 581.2 +/- 171.5 ng/mL (4 weeks; P < 0.01) and transferrin levels increased from 271.2 +/- 16.3 to 314.5 +/- 21.2 mg/dL (4 weeks; P < 0.05). A significant reduction in blood urea nitrogen (BUN) level was observed (62.1 +/- 1.8 v 46.8 +/- 3.8 mg/dL; 4 weeks; P < 0.05). Mean daily protein intake, determined by individual dietary survey, at 0 and 4 weeks, remained constant in both groups. In conclusion, weight gain and IGF-1 and transferrin level increases and BUN level decreases, despite the constant oral intake, suggest that short-term rhGH administration is associated with an anabolic reaction in malnourished dialysis patients.

Adult↗
PubMed1998

Anorexigen (TNF-alpha, cholecystokinin) and orexigen (neuropeptide Y) plasma levels in peritoneal dialysis (PD) patients: their relationship with nutritional parameters.

BACKGROUND: Malnutrition has definitely been related to mortality among dialysis patients. Persistent loss of appetite is one of the major symptoms found in these patients. It is also well recognized that several substances produce anorexia or disorders of the hunger-satiety cycle in several diseases. The aim of this study was to identify the role of anorexigen substances (TNF-alpha and cholecystokinin or CCK) and an orexigen substance (neuropeptide Y or NPY) in anorexia and malnutrition among 55 clinically stable peritoneal dialysis (PD) patients. RESULTS: High TNF-alpha plasma levels were found in 41 of 42 patients (97.6%) with a mean of 70.5+/-32.3 pg/ml. Patients with anorexia (n=11) or anorexia with nausea or vomiting (n=5) had higher TNF-alpha values than patients without these symptoms (75.9+/-34 vs 52.1 +/-24.5 pg/ml, P<0.05). Eight patients with a prior diagnosis of acid pylori disease showed higher TNF-alpha values (87.2+/-24.3) than 30 unaffected patients (63.6+/-30.5, P<0.05). TNF-alpha showed a significant negative linear correlation with retinol binding protein (RBP) (r=-0.37, n=34, P<0.05), and venous pH (r=-0.4, n=42, P<0.01); also, TNF-alpha values higher than 65 pg/ml were inversely associated with transferrin, cholesterol, blood urea nitrogen (BUN) and CCK. Patients with prealbumin levels lower than 30 mg/dl, a BMI lower than 30 kg/m2, nPCR lower than 1.1 g/kg/day and urea KT/V lower than 2.2 showed higher serum TNF-alpha levels. Patients who had been on CAPD treatment for longer periods showed higher TNF-alpha values. High plasma CCK levels were found in 38 of 45 patients (84%), mean 45.9+/-32.3 pg/ml. Patients with anorexia had no difference in CCK values compared with those without. A direct association was found between CCK levels and some nutritional markers (albumin, fibronectin, triglycerides, folic acid and nPCR in non diabetic patients). Although CCK has a recognized anorectic effect, this direct association might be because of an abnormal stimulation of CCK glucose feedback (trypsin) due to continuous peritoneal glucose absorption. This suggests that CCK could be an immediate food intake marker in PD patients. The NPY plasma levels were normal in 33 patients, high in 6 and low in 11. Patients with anorexia showed lower NPY levels than those without. NPY values greater than 50 pg/ml were directly associated with higher transferrin, prealbumin, RBP, nPCR and urea KT/V values. Importantly, a negative linear correlation between NPY and TNF-alpha was found (r=-0.42, n= 41, P<0.01). There was no significant relationship between residual renal clearance and the serum levels of the three peptides. CONCLUSION: In conclusion, our data suggest that high TNF-alpha and low NPY serum levels are associated with anorexia. High TNF-alpha, low CCK and low NPY serum levels are also related to a poor nutritional status. Further research on these circulating substances is required.

Adult↗
PubMed1998

Ex vivo proliferation of mesothelial cells directly obtained from peritoneal effluent: its relationship with peritoneal antecedents and functional parameters.

The peritoneal membrane requires anatomico-functional integrity to guarantee long-term stability for peritoneal dialysis (PD). Since mesothelial cells (MC) are active cells and the first part of the membrane to contact the dialysate, they are important in maintaining this stability. Mesothelial cells released daily into peritoneal effluent are able to grow in culture. This growth capacity may be related to some of the anatomicofunctional characteristics of each peritoneum. Our aim was to culture mesothelial cells taken from peritoneal effluents drained by 32 PD-stable patients, and relate this growth capacity to individual peritoneal data. Cells were taken from a residual fluid after sedimentation, washed twice with phosphate-buffered saline (PBS), and seeded into 25-cm2 tissue-culture flasks. These flasks were incubated in a humidified 5%-CO2 atmosphere. After MC confluence, cells were detached by trypsinization, passaged into 24-well plates, and finally counted. Cells were identified by morphology and immuno-histochemical characteristics. Cells from 28 out of 32 patients showed an appropriate growth in culture. Mesothelial cell confluence was reached in a mean of 18.2 +/- 8 days. After 7 days of seeding in plate wells, the cell growth showed a significant and progressive increase until day 16. Mesothelial cell growth rate was inversely related to PD duration. Neither peritonitis incidence nor other demographic characteristic were related to MC growth. Creatinine and urea mass transfer coefficients (MTC), but not ultrafiltration (UF) capacity, were significantly related to MC growth rate. In conclusion, the growth in culture of MC taken directly from PD bags is certainly possible. This growth is influenced by some of the intrinsic peritoneal characteristics derived from the peritoneal dialysis process. This tool could be useful in evaluating individual peritoneal conditions and, probably, as a method for peritoneal viability follow-up, although further research is required.

Ascitic Fluid↗
PubMed1998

Consequences of peritonitis episodes appearing late during peritoneal dialysis (PD) in patients able to continue PD.

The lack of specific information on the peritoneal-function consequences of late peritonitis episodes, and the concern about long-term consequences of peritoneal dialysis (PD), have prompted us to study the peritoneal function of long-term PD patients after a late peritonitis episode. The question is: Is the peritoneum more vulnerable to infections, in terms of functional effects, after a long time on PD? Forty-nine patients observed from baseline to the first year of PD with no peritonitis constituted the "early" control group; 31 other patients had one episode of peritonitis in the same period. Twenty-seven patients with no peritonitis from the fourth to fifth years comprised the "late" control group; 15 other patients had one episode during the same period. The results presented here suggest that peritoneal vulnerability to infectious episodes depends on the PD stage in which they appeared. Certainly, episodes with similar aggressive capacity in terms of inflammation duration (3-4 days) happening during the fifth year led to a loss of ultrafiltration (UF) capacity that does not appear in patients who suffer an episode during the first PD year. A remarkable feature is that this UF-capacity decrease is not accompanied by the usual creatinine mass transfer coefficient increase. This fact suggests that the dependence between peritoneal-glucose-gradient maintenance and water transport has been partially modified over time on PD. In conclusion, late mild peritonitis has distinct peritoneal-function consequences relative to early peritonitis. Patients who continue PD after one late episode showed an accentuation of the usual change which happens on long-term PD, the loss of peritoneal ultrafiltration capacity.

Creatinine↗
PubMed1997

Effects of erythropoietin on gonadotropin responses to gonadotropin-releasing hormone in uremic patients.

Long-term therapy with recombinant human erythropoietin (rhEPO) in uremic male patients undergoing hemodialysis has been followed by an increase in plasma levels of testosterone and a decrease in baseline levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). The aim of the present study was to assess the effect of acutely administered rhEPO on FSH and LH responses to gonadotropin-releasing hormone (GnRH) in a group of uremic patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Sixteen clinically stable male patients (age, mean+/-SEM, 45.3+/-3.9 years) with chronic renal insufficiency and 12 healthy volunteers with a normal renal function, matched for age and body mass index, were studied. All patients were on CAPD therapy for at least 3 months, and none of them received rhEPO therapy. Patients were moderately anemic (hemoglobin 11.0+/-0.3 g/dl) and showed testosterone levels significantly lower than those found in control subjects (3.47+/-0.37 vs. 6.91+/-0.49 ng/ml, p < 0.001). Each subject was tested with GnRH (100 microg i.v. as bolus) and with GnRH plus rhEPO (40 U/kg at a constant infusion rate for 30 min, starting 15 min before GnRH injection) on different days. Blood samples for FSH and LH were obtained between -30 and 120 min. In uremic patients the baseline FSH levels were higher than those found in control subjects (18.88+/-5.41 vs. 6.41+/-1.10 mU/ml, p < 0.05). After GnRH administration FSH values reached a maximum of 25.50+/-6.19 mU/ml in patients and of 12.50+/-2.02 mU/ml in controls (p < 0.05). rhEPO infusion produced a significant (p < 0.01) decrease in the area above the baseline value of FSH in uremic patients, with no other change in FSH responses to GnRH both in patients and controls. Baseline LH concentrations were significantly higher in patients than in controls (15.56+/-3.41 vs. 2.58+/-0.36 mU/ml, p < 0.001). LH peak and area under the curve of LH secretion after GnRH were significantly higher in patients than in controls (45.25+/-6.28 vs. 26.83+/-4.62 mU/ml, p < 0.05, and 77.02+/-11.30 vs. 34.40+/-5.22 mU x h/ml, p < 0.005, respectively). When GnRH was injected during the rhEPO infusion, a significant (p < 0.02) reduction in LH concentrations at 60, 90, and 120 min was found in uremic patients. Accordingly, the LH area under the curve was significantly reduced in patients (65.99+/-11.44 mU x h/ml, p < 0.05). rhEPO had no effect on GnRH-induced LH release in control subjects. These results suggest that acute rhEPO administration might reduce the exaggerated LH response to GnRH stimulation found in uremic male patients on CAPD.

Adult↗
PubMed1997

Frequent recurrence of secondary hyperparathyroidism after pulse oral calcitriol withdrawal in PD patients.

The aim of this study was to evaluate the role of pulse oral calcitriol in the control of secondary hyperparathyroidism in peritoneal dialysis (PD) patients, addressing the effects after withdrawal. We studied 15 patients with intact parathyroid hormone (iPTH) plasma levels above 250 pg/mL. The initial calcitriol dose was 8 or 4 micrograms/week, administered in two doses, according to whether the iPTH plasma levels were above or below 400 pg/mL. This dose was modified during the follow-up according to the response. Serum iPTH levels decreased in all patients after the first month (559 +/- 243 to 212 +/- 94 pg/mL, p < 0.001). Serum calcium levels significantly increased during therapy, while serum phosphorus levels did not change. The mean duration of the treatment was 95 +/- 57 days. Nine patients reached the target iPTH levels without complications, and in 6 patients the treatment was interrupted because of hypercalcemia. One month after finishing pulse therapy, a significant decrease in serum calcium levels and an increase in iPTH levels were observed. These values were similar to baseline data and were significantly higher than those found during the pulse calcitriol period. Pulse oral calcitriol administration seems to be a short-term, efficient therapy for secondary hyper-parathyroidism in PD patients. However, after the end of pulse therapy, iPTH serum levels return to baseline values, suggesting long-term therapeutic failure.

Administration, Oral↗
PubMed1996

Immunomodulation of peritoneal macrophages by granulocyte-macrophage colony-stimulating factor in humans.

Colony-stimulating factors are growth factors which induce differentiation of the hematopoietic stem cells. Granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates proliferation and improves functions of neutrophils and monocyte/macrophages. A macrophage submesothelial stratum has been suggested to constitute the first line of peritoneal defense. We have tested whether intraperitoneally administered GM-CSF could increase the number and activation of peritoneal macrophages in peritoneal dialysis patients. Eight stable patients injected 17 micrograms of GM-CSF in each of their four daily CAPD bags over three days. The clinical status, the peritoneal effluent and peripheral blood cell count, membrane receptor expression, phagocytosis activity and cytokine levels were monitored at days 0, 1, 3, 10 and 28. GM-CSF administration caused a large increase in peritoneal macrophage number (89-fold mean increase after 72 hr), returning to baseline seven days after withdrawal. GM-CSF triggered an increase in the expression of CD11b/CD18 (CR3) and its counterreceptor CD54, indicating the cellular progression into a more activated state. Both the number of phagocytic cells (55 +/- 15% to 83 +/- 10%, P < 0.05) and the phagocytic index (137 +/- 29 to 255 +/- 61, P < 0.01) were also augmented. Peritoneal effluent cytokine-chemokine levels demonstrated an increase in IL-6 and MCP-1 levels while TNF-alpha, IL-1, IL-8, MIP-1 alpha and RANTES were not significantly altered. GM-CSF administration did not affect the peritoneal transport of water or solutes. Minor side-effects were registered in two patients. In conclusion, intraperitoneal GM-CSF causes a marked and transient recruitment of primed macrophages into the peritoneum without inducing inflammatory parameters. GM-CSF should improve the peritoneal defensive capacity through potentiation of the effector functions of resident and newly-recruited macrophages.

Adult↗
PubMed1996

Growth hormone responses to growth hormone-releasing hormone and clonidine before and after erythropoietin therapy in CAPD patients.

Correction of anemia with recombinant human erythropoietin (rhEPO) in patients with end-stage renal disease has been associated with improvement of several abnormalities in hypothalamo-hypophyseal functions. The aim of the present work was to evaluate the growth hormone (GH) responses to GH-releasing hormone (GHRH) and clonidine stimulation, as well as the baseline concentrations of insulin-like growth factor I(IGF-I), before and after the correction of anemia with rhEPO in a group of uremic patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Nine clinically stable patients (1 male, 8 female; mean age 55.4 years; mean duration of CAPD 14.1 months) were studied. Twelve normal volunteers were studied as controls. GHRH and clonidine stimulation tests were performed prior to starting rhEPO and again after partial correction of anemia with rhEPO therapy (60-130 U/kg/week, s.c., for 12 weeks). Blood samples for GH were collected during 2 h after GHRH (100 micrograms i.v. in bolus) or clonidine (0.15 mg/m2, p.o.) administration. In basal plasma samples IGF-I concentrations were also measured. Mean (+/- SEM) blood hemoglobin concentration rose from 5.32 +/- 0.25 to 7.22 +/- 0.25 mmol/l (p < 0.001) after rhEPO treatment. GH responses to GHRH were characterized by marked differences in single patients when compared with the control group. However, the GH peak and the area under the secretory curves (AUC) of GH responses in CAPD patients (9.89 +/- 4.01 micrograms/l and 15.06 +/- 6.02 micrograms.h/l, respectively) did not differ from those obtained in control subjects (14.58 +/- 3.25 microgram/l and 16.94 +/- 4.31 microgram.h/l, respectively). The study after correction of anemia showed an evident potentiation of GH values that reached statistically significant values at 60 and 90 min. GH AUC after rhEPO therapy rose to 25.61 +/- 9.25 micrograms.h/l (p = 0.01). In control subjects, clonidine administration was followed by a GH release that reached a maximum at 90 min (7.67 +/- 2.24 micrograms/l). However, CAPD patients exhibited a blunted response to clonidine both before (2.00 +/- 0.78 microgram/l) and after (2.78 +/- 0.76 microgram/l, NS) correction of the anemia with rhEPO. On the other hand, IGF-I concentrations after rhEPO therapy (32.05 +/- 5.52 nmol/l) were not significantly different from those found prior to starting therapy (38.13 +/- 8.44 nmol/l). In conclusion, these results suggest that correction of the anemia with rhEPO therapy potentiates GH responses to direct pituitary stimulation with GHRH although it is unable to restore the blunted response of GH to clonidine that is found in CAPD patients.

Adrenergic alpha-Agonists↗
PubMed1996

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↗
PubMed1996

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↗