Are low concentrations of serum triiodothyronine a good marker for long-term mortality in hemodialysis patients?

INTRODUCTION: Low serum free triiodothyronine (FT3) concentrations have been reported in a high percentage of chronic renal failure patients and have been considered as an independent predictor of mortality in dialysis patients. OBJECTIVE: Our aim has been to evaluate the prognostic value of FT3 levels for long-term mortality in stable hemodialysis patients surviving at least 12 months. PATIENTS AND MEASUREMENTS: We retrospectively analyzed 89 stable hemodialysis patients (50 males; mean age 67.9 +/- 11.8 years). All patients had a baseline clinical and analytical evaluation. We analyzed the relationship between baseline FT3 and mortality by means of survival analysis (Kaplan-Meier) and Cox regression analysis. RESULTS: Mean values of thyroid function test were: thyrotropin (TSH) 2.02 +/- 1.5 microU/ml, free thyroxine (FT4) 1.26 +/- 0.23 ng/dl, and FT3 2.7 +/- 0.4 pg/ml. During a median follow-up time of 33.6 +/- 14.9 (12 - 62) months, 41 patients died. FT3 was similar in patients who died or survived (2.6 +/- 0.5 vs. 2.7 +/- 0.4 pg/ml ns). Kaplan-Meier analysis did not show significant differences in mean survival according to tertiles of FT3. In multivariate Cox regression analysis, FT3 was not a predictor of mortality (RR 0,001; 95% CI; 0.000 to 1.73). CONCLUSIONS: These data suggest that low FT3 levels are not predictive for mortality in a subgroup of stable HD patients who could survive more than 12 months.

[Extended hemoperfusion in the treatment of acute carbamazepine intoxication]. / Tratamiento con hemoperfusión prolongada en la intoxicación aguda por carbamazepina.

Carbamazepine is used in the treatment of epilepsy, and also prescribed in neuralgic pain syndromes, and certain affective disorders. Carbamazepine intoxication with suicide attempt is a relatively common clinical problem that can result in coma, respiratory depression, arrhythmia, hemodynamic instability and death. The drug's relatively high molecular weight, elevated volume of distribution and intense protein-binding render it difficult to extracorporeal removal, but published experience with hemoperfusion or hemodialysis present variable results. We describe a case report involving carbamazepine intoxication who was successfully treated with charcoal hemoperfusion. With this treatment the half-life of carbamazepine was reduced with rapid lowering of carbamazepine levels and clinical improvement. Based on our experience in this patient and a review of previously reported cases, extended charcoal hemoperfusion should be considered for serious carbamazepine intoxication because free as well as bound drug fractions are eliminated via this technique.

[Role played by peritoneal dialysis in treating refractory heart failure]. / Papel de la diálisis peritoneal en el tratamiento de la insuficiencia cardíaca refractaria.

Associated renal and cardiac diseases have a high prevalence among the population in several clinical contexts: acute renal failure in the context of decompensated heart failure (HF), HF patients who develop chronic kidney disease (CKD) and patients with CKD who develop HF. In recent years, cardiorenal syndrome has been described as deteriorating kidney function in the context of HF. However, there are other clinical situations for which nephrologists can contribute their knowledge as a part of an integral treatment strategy, as is the case with refractory HF (RHF). All of these situations require an interdisciplinary cooperative effort between cardiologists and nephrologists with the aim of providing integral treatment. This article aims to review the role of the nephrologist in HF treatment, with an emphasis on the subgroup of patients with RHF and current evidence regarding the usefulness of peritoneal dialysis (PD) as a chronic coadjuvant treatment.

[The peritoneal kinetic study performed with hypertonic glucose permits better evaluation of UF capacity and determination of sieving of sodium]. / Las cinéticas con glucosa hipertónica permiten identificar mejor el fallo de ultrafiltración. ¿Qué aporta el cribado de sodio?

INTRODUCTION: The use of solutions containing hypertonic glucose (3.86%/4.25%) has been postulated as the method of choice for study the peritoneal function, and permits a better evaluation of the ultrafiltration (UF) capacity. OBJECTIVE: The aim of our study was to analyze the UF capacity and its relation with the peritoneal permeability and sieving of sodium, performing the peritoneal kinetic study with hypertonic glucose solutions. PATIENTS AND METHODS: We performed 184 peritoneal kinetic studies with hypertonic glucose solutions in stable patients on peritoneal dialysis (PD), with a mean time on PD of 16 +/- 22 months. We measured the mass transfer coefficient of creatinine (CrMTC), dialysate to plasma ratio of creatinine (D/PCr), UF capacity and sieving of sodium at 60 minutes (difNa60). RESULTS: The mean values were: CrMTC: 9.1 +/- 4.5 ml/min, D/PCr: 0.71 +/- 0.09, UF 759 +/- 233 ml/4 h and difNa60: 4.7 +/- 2.3. The best multivariate model that predicts the UF capacity included: difNa60, CrMTC, age and time on PD (r = 0.57; p > 0.0001). In patients with UF lower than 600 ml/4 h (Percentil 25) the correlation between UF and CrMTC was lost, but remains the correlation with difNa60 (r = 0.48). The patients with previous peritonitis (n = 38) showed no differences in UF, CrMTC or D/Pcr, but the had lower difNa60 (3.7 +/- 2.8 vs. 4.9 +/- 2.1; p = 0.002) than the remaining patients. CONCLUSIONS: The peritoneal kinetic study performed with hypertonic glucose allows to standardize the UF capacity and by determination of sieving of sodium, the early detection of water transport alterations, before the UF capacity and small solutes permeability alteration develops.

[Incorporation of a psychologist into a nephrology service: criteria and process]. / Incorporación de un psicólogo en un servicio de nefrología: criterios y proceso.

Chronic kidney disease is associated with a wide range of stressful situations causing important physical and psychological repercussions. It is not usual that psychology professionals are active members of the nephrology teams. In consequence, these alterations are not properly assisted. Our aim is to present the introduction process of a psychologist in a nephrology department and its preliminary results. We designed a clearly defined introduction process, starting with a therapeutic communication training program for all the staff. In the model we have priorized pre-emptive interventions in order to promote the adaptation process, far from simple psychological symptom control. It is assumed the binomial patient-family as the major objective for care, choosing an interdisciplinary approach. We worked more from a health psychology perspective than from a mental health perspective. Over the year 2008 the number of patients assisted by the psychologist were 571 (mean 48 patients/month). The total number of interventions was 1,022. Majority of cases (45.2%) were derived from the advanced chronic kidney disease program, mostly related to demands about emotional impact of renal replacement therapy commencement. Others were: suspect of depression episode, adherence, primary caregiver emotional overwhelming, bereavement, anxiety and support in decision making process. This experience is a stimulus for the integral approach of the renal patient.

[Changing the frequency of administration of darbepoetin alfa (from weekly to fortnightly) maintains the haemoglobin levels in patients undergoing peritoneal dialysis]. / El cambio en la frecuencia de administración de darbepoetin alfa (de semanal a quincenal) mantiene los niveles de hemoglobina en pacientes en diálisis peritoneal.

SUMMARY BACKGROUND: Less frequent dosing regimens during anemia treatment could benefit Peritoneal Dialysis (PD) patients. We investigated the effectiveness of darbepoetin alfa dosed every-other-week (Q2W) for maintaining hemoglobin (Hb) levels (11-13 g/dL). PATIENTS AND METHODS: One hundred and nine PD patients from 14 centers participated in an 8-month observational, prospective study. Patients (Hb 11-13 g/dL) receiving weekly (QW) darbepoetin alfa switched to Q2W dosing at the investigator's discretion. Doses were adjusted according to published guidelines. RESULTS: Sixty-nine percent (75 out of 109) of patients switched to Q2W dosing. Thirty-three percent maintained the g/week, equivalent to twice the previous mean weekly dose (26.1-25.8 g/week, QW dose). Forty-seven percent received a dose reduction (35.8-20.2 equivalent to the previous QW dose). More patients in the maintenance dose group 11 g/dL than those receiving a reduced weekly dose (80% vs. had Hb levels 51.4%, respectively, p = 0.0236). During the Q2W phase, the mean Hb level ranged from 12.0-12.5 g/dL for the maintenance dose group and 11.5-12.0 g/dL for the reduced dose group. From the switch to the end of the study, the mean (SD) change in Hb was -0.7 g/dL (0.98 g/dL, p = 0.0557) and -0.6 g/dL (1.6 g/dL, p = 0.1296) for the maintenance and reduced dose groups, respectively. The Q2W darbepoetin alfa was well tolerated. Only a single treatment-related adverse event (polycythemia) occurred. CONCLUSION: The majority of PD patients receiving QW darbepoetin alfa can be effectively switched to Q2W and still maintain their Hb level.

[Effect of using icodextrin as a starting therapy for peritoneal permeability]. / Efecto del uso de icodextrina de inicio sobre la permeabilidad peritoneal.

UNLABELLED: Peritoneal permeability differs between patients at the time of starting peritoneal dialysis (PD) and it can increase along with time on the technique. This fact is related to peritonitis, the biocompatibility of the dialysis fluids and the use of glucose as osmotic agent. The aim of the present study was to evaluate if the use of one exchange a day of icodextrine from the time of DP initiation affects the evolution of peritoneal permeability. PATIENTS AND METHODS: 56 patients starting PD (mean age: 48.3 +/- 14.0; 62.5% males; 17.9% diabetics) that used one exchange a day with icodextrine from the time of starting PD. We performed a peritoneal transport kinetic study at the time of starting PD and then every 6 months during two years. We calculated the peritoneal mass transfer area coefficient of creatinine (Cr-MTAC) and urea (U-MTAC) as well as the D/P creatinine relationship (D/P Cr). As a control group we used the results of Cr-MTC of 249 patients that had used glucose as the only osmotic agent from the time of starting PD. RESULTS: The peritoneal transport, calculated using Cr-MTC, U-MTC and D/P Cr, diminished at 12 months (11.7+/-5.7 vs. 8.1+/-3.1; 23.5+/-7.3 vs. 18.9+/-3.8; 0.72+/-0.09 vs. 0.67+/-0.08; respectively), staying stable afterwards.We found that high transporters (HA) patients (higher quatril Cr-MTC ) showed a higher diminution of Cr-MTAC along the first year of treatment. The diminution of Cr-MTAC after 12 months using icodextrine was significantly higher (p<0.001) that the one observed in the control group that only used glucose as osmotic agent (10.5+/-5.3 vs. 10.1+/-4.6). We found that high transporters (HA) patients (higher quatril Cr-MTC) showed a higher decrease of Cr-MTAC along the first year of treatment. CONCLUSION: the use of icodextrine at the time of starting PD might help to correct the high transport status observed in some patients during the first months of treatment. The peritoneal transport kinetic studies performed at 6 and 12 months after starting PD are more representative of the long term peritoneal transport characteristics of the patients than those performed at the time of starting PD.

[Connective tissue growth factor (CTGF): a key factor in the onset and progression of kidney damage]. / El factor de crecimiento de tejido conectivo (CTGF): factor clave en el inicio y la progresión del daño renal.

Connective tissue growth factor (CTGF) is increased in several pathologies associated with fibrosis, including multiple renal diseases. CTGF is involved in biological processes such as cell cycle regulation, migration, adhesion and angiogenesis. Its expression is regulated by various factors involved in renal damage, such as transforming growth factor- , Angiotensin II, high concentrations of glucose and cellular stress. CTGF is involved in the initiation and progression of renal damage to be able to induce an inflammatory response and promote fibrosis, identified as a potential therapeutic target in the treatment of kidney diseases. In this paper we review the main actions of CTGF in renal disease, the intracellular action mechanisms and therapeutic strategies for its blocking.

Epithelial-to-mesenchymal transition of mesothelial cells is an early event during peritoneal dialysis and is associated with high peritoneal transport.

Ultrafiltration (UF) failure is a consequence of long-term peritoneal dialysis (PD). Fibrosis, angiogenesis, and vasculopathy are causes of this functional disorder after 3-8 years on PD. Epithelial-to-mesenchymal transition (EMT) of mesothelial cell (MC) is a key process leading to peritoneal fibrosis with functional deterioration. Our purpose was to study the peritoneal anatomical changes during the first months on PD, and to correlate them with peritoneal functional parameters. We studied 35 stable PD patients for up to 2 years on PD, with a mean age of 45.3+/-14.5 years. Seventy-four percent of patients presented loss of the mesothelial layer, 46% fibrosis (>150 microm) and 17% in situ evidence of EMT (submesothelial cytokeratin staining), which increased over time. All patients with EMT showed myofibroblasts, while only 36% of patients without EMT had myofibroblasts. The number of peritoneal vessels did not vary when we compared different times on PD. Vasculopathy was present in 17% of the samples. Functional studies were used to define the peritoneal transport status. Patients in the highest quartile of mass transfer area coefficient of creatinine (Cr-MTAC) (>11.8 ml min(-1)) showed significantly higher EMT prevalence (P=0.016) but similar number of peritoneal vessels. In the multivariate analysis, the highest quartile of Cr-MTAC remained as an independent factor predicting the presence of EMT (odds ratio 12.4; confidence interval: 1.6-92; P=0.013) after adjusting for fibrosis (P=0.018). We concluded that, during the first 2 PD years, EMT of MCs is a frequent morphological change in the peritoneal membrane. High solute transport status is associated with its presence but not with increased number of peritoneal vessels.

[Anatomic-functional correlation of the peritoneal membrane]. / Correlación anátomo-funcional de la membrana peritoneal.

Ultrafiltration failure is the most frequent alteration of peritoneal transport in peritoneal dialysis (PD) patients, and is a frequent cause of technical withdrawal. At the beginning of the therapy, there is a great functional diversity, but alter the third or fourth years the 20% of patients develop progressive ultrafiltration failure and an increase of the small solute transport. In parallel to this functional alteration, the peritoneum of PD patients shows morphological alterations, such as loss or transformation of mesothelial cells, basal membrane reduplication, submesothelial fibrosis, hyalinazing vasculopathy and neoangiogenesis. There are scant comparative studies of morphofunctional correlation. Most of them have been reported on long-term PD patients and showed a progressive increase of fibrosis and vasculopathy with time on PD, specially in patients with ultrafiltration failure and in those with sclerosing peritonitis. The peritoneal vessel number do not always increase with time on PD, and it is associated with advanced ultrafiltration failure. Some short-term studies have demonstrated that the initial lesion related to the high small solute peritoneal transport is the epithelial to mesenchimal transition of the mesothelial cell (the transformation of mesothelial cell into fibroblastic cell). The higher secretion of extracellular matrix and vascular endothelial growth factor by the transformed mesothelial cells should participated on later development of fibrosis and high peritoneal permeability, not always in relation with higher number of peritoneal vessels.

[New peritoneal dialysis solutions and their combinations]. / Nuevas soluciones de diálisis peritoneal y sus combinaciones.

Peritoneal dialysis (PD) treatment has been related to functional and structural changes in peritoneum. The biocompatibility of the PD fluids is one of the most important factors related to this complication. New solutions for PD have been developed in an effort to reduce the bioincompatibility of conventional glucose containing, lactate-buffered solutions, and thereby to improve the clinical outcomes of PD. The use of new manufacturing techniques, buffer presentation, and new osmotic alternatives to glucose (amino acids, icodextrin) have allowed potentially improved peritoneal survival (in terms of structure and function) and improved subjective patient experience. Additional benefits have also included enhanced management of salt and water removal, supported nutritional status and improvement in the systemic metabolic derangements associated with conventional PD treatment, based on glucose-containing lactate-buffered solutions. In vitro and in vivo studies have shown the biocompatibility of these new solutions to be superior to that of standard solutions. This review summarized the characteristics of the next generation of PD fluids currently available and analyzed the potential benefits related to the combination of the different elements.

[Animal models of peritoneal dialysis: relevance, difficulties, and future]. / Modelos animales de diálisis peritoneal: relevancia, dificultades y futuro.

The studies performed with human peritoneal biopsies of peritoneal dialysis -patients have demonstrated that exposure to peritoneal dialysis fluid induce peritoneal deterioration. The main alterations of peritoneal membrane are fibrosis and angiogenesis that ends with the failure of the ultrafiltration capacity of the peritoneal membrane. These studies are descriptivist and scarcely help to investigate the mechanisms and stages involved on the process. Therefore, it is necessary to supply the deficiencies presented by the studies with patients. The experimental models have strongly contributed to the knowledge of the pathologic process that is induced by the continuous exposition of the peritoneal membrane to the dialysis fluids. Most of the peritoneal dialysis studies use the rat as the experimental animal. Due to the difficulty of working with small animals, few studies have been done in mice. However, models in mice offers great advantages, as long as they allow us to employ different strains and genetically modified animals. We have recently developed an experimental model in mouse of exposure of the peritoneal membrane to dialysis fluids, which resembles the process of peritoneal damage that take place during peritoneal dialysis treatment in human patients.

Apoptosis: from advances in PD to therapeutic targets in DM.

A high glucose concentration is shared by peritoneal dialysis (PD) and diabetes mellitus (DM). High glucose leads to tissue injury in diabetes. Peritoneal dialysis research has emphasized the role of glucose degradation products in tissue injury. Apoptosis induction is one of the mechanisms of tissue injury induced both by glucose and glucose degradation products. We now review the role of apoptosis and its regulation by glucose degradation products in antibacterial defense and loss of renal function in diabetes mellitus and peritoneal dialysis. The pathogenic role of the recently identified glucose degradation product 3,4-di-deoxyglucosone- 3-ene (3,4-DGE) is detailed. Available therapeutic strategies include the use of peritoneal dialysis solutions containing a low concentration of glucose degradation products. Based on preclinical results, specific targeting of apoptosis regulatory factor should be explored in the clinical setting.

[Theoretical bases for the proposal of a randomized, controlled, open label clinical trial to assess the efficacy of adding bemiparin to the icodextrin solution in patients on peritoneal dialysis with peritoneal transport disorders [FRIAT-BEM-2005-01]]. / Bases teóricas para la propuesta de un ensayo clínico aleatorizado, controlado y abierto, para evaluar la eficacia de la adición de bemiparina a la solución de icodextrina en pacientes en diálisis peritoneal con trastornos del transporte peritoneal [FRIAT-BEM-2005-01].

Multiple investigations performed on peritoneal pathophysiology during peritoneal dialysis (PD) suggest that intraperitoneal heparin might modify most of the causes of membrane deterioration. The actions described favouring this idea are: 1) Peritoneal Chronic inflammation alters peritoneal function and hepraine has anti-inflammatory properties. 2) Peritoneal fibrosis related to peritoneal dialysis or traumatic injury may be avoided or limited with heparin. 3) Heparine induces tPA synthesis by mesothelial cells, which represents a potentiation of fibrinolytic action. 4) Heparine, specifically low-molecular weight heparin, inhibits angiogenesis. 5) Intraperitoneal heparin favors the removal of advanced glycosilation end products in PD. 6) Animal models and clinical studies with small series of patients have demonstrated an improvement of peritoneal function with intraperitoneal heparine use. 7) Until now, no adverse effects of the intraperitoneal heparin use have been found. In consequence, it is a plausible hypothesis to consider that intraperitoneal heparin may favourably modify peritoneal function in patients under peritoneal dialysis.

[Effectiveness of pre-emptive hemodialysis with high-flux membranes for the treatment of life-threatening alcohol poisoning]. / Eficacia de la hemodiálisis precoz con membranas de alto flujo en el tratamiento de las intoxicaciones graves por alcoholes.

Alcohol intoxication (methanol, ethanol and ethylene glycol) may result in metabolic acidosis with increased anion gap, increased serum osmolal gap, and neurologic abnormalities ranging from drunkenness to coma, and death. The mortality and morbidity rates remain very high despite intensive care therapy. The toxicity of methanol and ethylene glycol is clearly correlated to the degree of metabolic acidosis. The established treatment of severe methanol and ethylene glycol intoxication is ethanol administration and hemodialysis (HD). By inhibiting the main metabolic pathway of methanol and ethylene glycol (alcohol dehydrogenase), ethanol prevents the formation of major toxic metabolites (formic acid, glycolic acid and oxalic acid). Conventional HD can reduce serum methanol, ethanol and ethylene glycol and its metabolites rapidly, but high-flux membranes should be capable of removing more toxic per hour of HD. In this report, we describe 14 cases of life-threatening alcohol intoxication (11 methanol, 1 ethanol, and 2 ethylene glycol) who were treated successfully with supportive care, ethanol infusion (methanol and ethylene glycol), and early HD with a high-flux dialyser. The median pH was 7.04 +/- 0.06 (range 6.60-7.33), median bicarbonate 9.9 +/- 1.9 mmol/l (range 1.4-25), and median base deficit 18.4 +/- 2.6 mmol/l (range 2-33). The median anion gap was 29.1 +/- 2.3 mmol/l (range 16-45) and the median osmolal gap was 119 +/- 47 mOsm/l (range 16-402). On admission there was an excellent linear correlation between the serum toxic alcohol concentrations and the osmolal gaps (R2 = 0.98, p = 0.0006). In all cases early HD corrected metabolic acidosis and osmolal abnormalities. The mortality was 7 % (1 from 14). We conclude that pre-emptive HD should be performed in severe intoxications to remove both the parent compound and its metabolites. The HD prescription should include a large surface area dialyser with high-flux membrane, a blood flow rate in excess of 250 ml/min, a modified bicarbonate bath enriched with phosphorus and potassium, and a long time session. The phosphorus and potassium-enriched bicarbonate-based dialysis solution used in patients with normal phosphorus and potassium serum levels avoided HD-induced hypophosphatemia and hypopotassemia. HD as implemented in these cases is a safe and very effective approach to the management of alcohol poisoning.

[Hemoperfusion in the treatment of acute valproic acid intoxication]. / Tratamiento con hemoperfusión de la intoxicación aguda por ácido valproico.

Valproic acid is increasingly used in the treatment of epilepsy, and also prescribed for bipolar affective disorders, schizoaffective disorders, schizophrenia and migraine prophylaxis. Valproic acid intoxication with suicide attempt is a relatively common clinical problem that can result in coma, respiratory depression, pancytopenia, hemodynamic instability and death. The drug's relatively low molecular weight, small volume of distribution and saturable protein-binding render it potentially amenable to exracorporeal removal (hemodialysis, hemoperfusion or hemofiltration ), but published experience is scarce. We describe a case report involving valproic acid intoxication with ingestion of ethanol, who was successfully treated with charcoal hemoperfusion. With this treatment the half-life of valproic acid was reduced with rapid lowering of valproic acid levels and clinical improvement. Based on our experience in this patient and a review of previously reported cases, charcoal hemoperfusion should be considered for serious valproic acid intoxication because free as well as bound drug fractions are eliminated via this technique.

[Pasteurella multocida and Candida albicans peritonitis]. / Peritonitis por pasteurella multocida y Candida albicans.

Peritonitis is a well-known complication of peritoneal dialysis (PD) treatment. Repetitive episodes may induce an irreversible damage of the peritoneal membrane and are a frequent cause of PD drop-out. The great majority of the episodes are due to Staphylococci, Streptococci or gram- negative organisms. Unusual organisms have been reported, specially in immunosuppressed hosts. Few cases of Pasteurella Multocida (PM) have been described in PD patients. To our knowledge, we describe the first case preceding a Candida Albicans (CA) peritonitis. A review of the literature of PM peritonitis and the relation between these two microorganisms is discussed.

[Treatment of acute lithium intoxication with high-flux haemodialysis membranes]. / Tratamiento de la intoxicación aguda por litio mediante hemodiálisis con dializadores de alta eficiencia.

Lithium carbonate is commonly prescribed for the treatment of bipolar (manic-depressive) disorders. However, because of its narrow therapeutic index an excessive elevation of serum lithium concentration, either during chronic maintenance therapy or after an acute overdose, can result in serious toxicity. In addition to supportive care, the established treatment of severe lithium toxicity is haemodialysis. Conventional haemodialysis can reduce serum lithium rapidly, but post-dialysis rebound elevations with recurrent toxicity have been documented in old publications. High-flux membranes should be capable of removing more lithium per hour of haemodialysis, but published values are not available. We report here three patients with acute lithium intoxication who were treated successfully with bicarbonate and high-flux haemodialysis membranes. Our patients presented with a severe degree of intoxication, based on the amount of drug ingested, the initial serum lithium level, the severity of neurologic symptoms and systemic manifestations. Two patients developed acute renal failure probably as a result of volume depletion since it was rapidly reversible by haemodialysis and infusion therapy. In addition, consecutive haemodialysis sessions and improvement of renal function allowed a rapid decrease in serum lithium levels without haemodynamic instability or rebound elevations in lithium concentration. The effectiveness of the procedure in these cases can be attributed to the use of bicarbonate dialysate and high-efficiency dialysers. This is the first report describing the effect of high-efficiency dialysers on lithium pharmacokinetic. Using this technique the elimination rate of lithium was found to be greater than previously reported with haemodialysis.

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.