Rubén Torres

Separate taurine and chloride efflux pathways activated during regulatory volume decrease

Organic osmolyte and halide permeability pathways activated in epithelial HeLa cells by cell swelling were studied by radiotracer efflux techniques and single-cell volume measurements. The replacement of extracellular Cl- by anions that are more permeant through the volume-activated Cl- channel, as indicated by electrophysiological measurements, significantly decreased taurine efflux. In the presence of less-permeant anions, an increase in taurine efflux was observed. Simultaneous measurement of the 125I, used as a tracer for Cl-, and [3H]taurine efflux showed that the time courses for the two effluxes differed. In Cl--rich medium the increase in I- efflux was transient, whereas that for taurine was sustained. Osmosensitive Cl- conductance, assessed by measuring changes in cell volume, increased rapidly after hypotonic shock. The influx of taurine was able to counteract Cl- conductance-dependent cell shrinkage but only approximately 4 min after triggering cell swelling. This taurine-induced effect was blocked by DIDS. Differences in anion sensitivity, the time course of activation, and sensitivity to DIDS suggest that the main cell swelling-activated permeability pathways for taurine and Cl- are separate.Organic osmolyte and halide permeability pathways activated in epithelial HeLa cells by cell swelling were studied by radiotracer efflux techniques and single-cell volume measurements. The replacement of extracellular Cl- by anions that are more permeant through the volume-activated Cl- channel, as indicated by electrophysiological measurements, significantly decreased taurine efflux. In the presence of less-permeant anions, an increase in taurine efflux was observed. Simultaneous measurement of the125I, used as a tracer for Cl-, and [3H]taurine efflux showed that the time courses for the two effluxes differed. In Cl--rich medium the increase in I- efflux was transient, whereas that for taurine was sustained. Osmosensitive Cl- conductance, assessed by measuring changes in cell volume, increased rapidly after hypotonic shock. The influx of taurine was able to counteract Cl- conductance-dependent cell shrinkage but only ∼4 min after triggering cell swelling. This taurine-induced effect was blocked by DIDS. Differences in anion sensitivity, the time course of activation, and sensitivity to DIDS suggest that the main cell swelling-activated permeability pathways for taurine and Cl- are separate.

Outbreak of Paecilomyces variotii Peritonitis in Peritoneal Dialysis Patients after the 2010 Chilean Earthquake

Fungal peritonitis (FP) accounts for 3 - 6% of all peritonitis episodes in chronic peritoneal dialysis (PD), being associated with high morbidity and mortality. Mortality rates are in the range of 15 - 50%, and loss of the peritoneal membrane function can be over 40% (1). The most common cause of the disease is Candida species (C. albicans, C. parapsilosis, C. glabrata). Other yeasts and filamentous fungi such as Aspergillus, Paecilomyces, Penicillium, and Zygomycetes are found less frequently. The strongest risk factors for FP in PD patients are prolonged use of antibiotics and previous bacterial peritonitis (2). Other suggested risk factors are immunosuppression, malnutrition, bowel perforation, diverticulitis, and, possibly, certain comorbidities such as diabetes or neoplastic diseases (1). Paecilomyces spp is a filamentous fungus like the genus Penicillium and Aspergillus. It is found in soil and water and is one of the main dwellers of house dust. It is rarely associated with human infections. When a disease does occur, it is more often related to foreign bodies or immunosuppressed patients (3,4). After the earthquake of February 27, 2010, in Chile, there was an increase in the rate of FP from 1% to 6%, due to the appearance of 6 cases caused by Paecilomyces variotti (5). Here we describe the clinical characteristics and outcomes of 3 of these patients. Although there was no proof of the precise route of infection in our patients, in all 3 cases there was a major alteration in the storage of the PD fluid bags, resulting especially in exposure to excessive dust and destruction of the architecture of the storage holds. It is quite possible that in the context of a natural disaster like a big earthquake, the risk of infections associated with this fungus could increase because of the excessive dust in the environment.

Human peritoneal mesothelial cell death induced by high-glucose hypertonic solution involves Ca2+ and Na+ ions and oxidative stress with the participation of PKC/NOX2 and PI3K/Akt pathways

Chronic peritoneal dialysis (PD) therapy is equally efficient as hemodialysis while providing greater patient comfort and mobility. Therefore, PD is the treatment of choice for several types of renal patients. During PD, a high-glucose hyperosmotic (HGH) solution is administered into the peritoneal cavity to generate an osmotic gradient that promotes water and solutes transport from peritoneal blood to the dialysis solution. Unfortunately, PD has been associated with a loss of peritoneal viability and function through the generation of a severe inflammatory state that induces human peritoneal mesothelial cell (HPMC) death. Despite this deleterious effect, the precise molecular mechanism of HPMC death as induced by HGH solutions is far from being understood. Therefore, the aim of this study was to explore the pathways involved in HGH solution-induced HPMC death. HGH-induced HPMC death included influxes of intracellular Ca2+ and Na+. Furthermore, HGH-induced HPMC death was inhibited by antioxidant and reducing agents. In line with this, HPMC death was induced solely by increased oxidative stress. In addition to this, the cPKC/NOX2 and PI3K/Akt intracellular signaling pathways also participated in HGH-induced HPMC death. The participation of PI3K/Akt intracellular is in agreement with previously shown in rat PMC apoptosis. These findings contribute toward fully elucidating the underlying molecular mechanism mediating peritoneal mesothelial cell death induced by high-glucose solutions during peritoneal dialysis.

Diagnóstico y seguimiento de 12 casos de peritonitis esclerosante asociada a diálisis peritoneal crónica en Chile: Experience in 12 patients on peritoneal dialysis

BACKGROUND Encapsulating peritoneal sclerosis (EPS) is a complication of peritoneal dialysis (PD) with a low prevalence but high mortality. It is characterized by peritoneal inflammation and fibrosis with subsequent development of intestinal encapsulation. It is associated with a long lapse on PD, frequent episodes of peritonitis, high glucose solution use, and high peritoneal transport status. AIM To report the clinical features of patients on PD, who developed EPS. MATERIAL AND METHODS Review of medical records of 12 patients aged 43 ± 10 years (eight women) who developed EPS. RESULTS The mean time spent on PD was 98 months. The main clinical manifestations were abdominal pain in 82% and ultrafiltration failure in 63%. In 92%, there was a history of peritonitis and 75% had high peritoneal transport at the time of diagnosis. The main findings in computed tomography were peritoneal calcification and thickening. There was a biopsy compatible with the diagnosis in 10 cases. Treatment consisted in withdrawal from PD, removal of PD catheter and the use of corticoids and tamoxifen. After withdrawal from PD 50% of patients became asymptomatic. The rest had intermittent abdominal pain and altered bowel movements. Two patients died (17%). CONCLUSIONS EPS is a serious complication of PD, which should be suspected in any patient with compatible clinical symptoms, long time on PD, multiple episodes of peritonitis and high peritoneal transport profile.Background: Encapsulating peritoneal sclerosis (EPS) is a complication of peritoneal dialysis (PD) with a low prevalence but high mortality. It is characterized by peritoneal inflammation and fibrosis with subsequent development of intestinal encapsulation. It is associated with a long lapse on PD, frequent episodes of peritonitis, high glucose solution use, and high peritoneal transport status. Aim: To report the clinical features of patients on PD, who developed EPS. Material and methods: Review of medical records of 12 patients aged 43 ± 10 years (eight women) who developed EPS. Results: The mean time spent on PD was 98 months. The main clinical manifestations were abdominal pain in 82% and ultrafiltration failure in 63 %. In 92 %, there was a history of peritonitis and 75 % had high peritoneal transport at the time of diagnosis. The main findings in computed tomography were peritoneal calcification and thickening. There was a biopsy compatible with the diagnosis in 10 cases. Treatment consisted in withdrawal from PD, removal of PD catheter and the use of corticoids and tamoxifen. After withdrawal from PD 50% of patients became asymptomatic. The rest had intermittent abdominal pain and altered bowel movements. Two patients died (17 %). Conclusions: EPS is a serious complication of PD, which should be suspected in any patient with compatible clinical symptoms, long time on PD, multiple episodes of peritonitis and high peritoneal transport profile.

The Fortress Becomes a Prison: Calcified Constrictive Pericarditis

PRESENTATION The pericardium, normally so useful in defending the heart from outside invaders, can perform more like a cage when its flexibility is compromised. We present the case of a 50-year-old man who was admitted to the nephrology unit when severe chronic hypotension led to poor hemodynamic tolerance during hemodialysis. He had a 24-year history of kidney disease of unknown etiology. At debut, he presented with pericardial effusion that required urgent initiation of hemodialysis. In 1993, he underwent a kidney transplant. Chronic graft dysfunction evolved, and in 2010, he started hemodialysis again. His medical history included chronic liver damage secondary to venous-occlusive disease induced by azathioprine and mesenteric thrombosis managed with oral anticoagulation. In 2011, he underwent subtotal parathyroidectomy for hyperparathyroidism.

Caso clínico: cistitis enfisematosa asociada a hidronefrosis secundaria

We report a 53 year-old woman with type 2 diabetes mellitus and hypertension, presenting with progressive abdominal pain lasting three weeks, associated with lower abdominal swelling and fever. Clinical examination showed a large increase in abdominal volume, contraction of extracellular compartment, and signs of severe sepsis. Computed tomography showed an over-distended bladder with severe wall and luminal pneumatosis and bilateral hydronephrosis. The diagnosis was of emphysematous cystitis associated to hydronephrosis. Urine and blood cultures were positive for multi-susceptible Escherichia coli. Clinical evolution was favorable after 6 weeks of ceftriaxone and urinary catheter use. Emphysematous cystitis is a rare clinical entity, with an associated mortality of 7%. Known predisposing factors are older age, female gender and presence of diabetes. Microbiological agents most frequently involved are Escherichia coli and Klebsiella pneumoniae (80% of cases). Medical treatment is preferred and is based on urinary tract decompression with a bladder catheter, and prolonged broad spectrum antimicrobial therapy.We report a 53 year-old woman with type 2 diabetes mellitus and hypertension, presenting with progressive abdominal pain lasting three weeks, associated with lower abdominal swelling and fever. Clinical examination showed a large increase in abdominal volume, contraction of extracellular compartment, and signs of severe sepsis. Computed tomography showed an over-distended bladder with severe wall and luminal pneumatosis and bilateral hydronephrosis. The diagnosis was of emphysematous cystitis associated to hydronephrosis. Urine and blood cultures were positive for multi-susceptible Escherichia coli. Clinical evolution was favorable after 6 weeks of ceftriaxone and urinary catheter use. Emphysematous cystitis is a rare clinical entity, with an associated mortality of 7%. Known predisposing factors are older age, female gender and presence of diabetes. Microbiological agents most frequently involved are Escherichia coli and Klebsiella pneumoniae (80% of cases). Medical treatment is preferred and is based on urinary tract decompression with a bladder catheter, and prolonged broad spectrum antimicrobial therapy.

Creación del Comité de Nefrología Diagnóstica e Intervencionista de la Sociedad Chilena de Nefrología

Sr. Editor: El desarrollo dentro de la Nefrologia de un area dedicada tanto a procedimientos diagnosticos como terapeuticos es una aspiracion legitima. En las ultimas decadas los centros de salud han incorporado procedimientos que aportan valiosa informacion diagnostica y permiten implementar medidas terapeuticas efectivas. Complementando el cuidado de los pacientes hipertensos arteriales o insuficientes renales cronicos, creemos que podemos colaborar a su cuidado mediante estas acciones. Esta tendencia se ha reflejado en un incremento en la actividad asistencial asi como en cantidad de publicaciones que han aparecido en relacion a procedimientos invasivos o no invasivos realizados por distintos grupos nefrologicos (1,2). En nuestro medio se han realizado cursos de nefrologia intervencionista con buena acogida de publico y en congresos de la especialidad los trabajos presentados tambien tienden a incrementarse ano a ano. (Libro de resumenes 29o Congreso Conjunto de las Sociedades Chilenas de Nefrologia, Hipertension y trasplante, Pucon Septiembre 2012). leer mas...

Densidad mineral ósea y adecuación de la dieta en pacientes con enfermedad renal crónica en hemodiálisis

BACKGROUND In chronic kidney disease (CKD) patients, malnutrition is common with loss of muscle mass and decreased bone mineral density (BMD), increasing the risk of morbidity. OBJECTIVE To compare body composition, bone mineral density (BMD) and bone mineral content (BMC) between CKD patients and healthy subjects, and relate these parameters with energy, macronutrients and micronutrients intake. METHODS Body composition was assessed 30 haemodialysis patients and compared with 28 healthy volunteers with DEXA. In patients, three 24 hours records of dietary intake were filled. RESULTS A significantly lower BMD (p < 0.01) and BMC (p < 0.0) were found in CKD patients. There was a trend for patients to have lower fat free mass (FFM) than controls (p = 0.06). In men, differences in BMD and BMC lost significance when adjusting for fat mass FM (%) and FFM (kg). In CKD, 34.5% and 27.6% of patients had an adequate intake of energy and protein, respectively. However, it was observed a deficit of energy and protein intake in 31.0% and 44.8% of patients, respectively. No significant correlation was found in CKD patients between macronutrient and calcium intake and BMD or BMC. CONCLUSIONS CKD have lower BMD and BMC than healthy volunteers. These differences lost significance in men, after adjusting for body composition parameters. A poor dietary adequacy was found in most patients with CKD, but no association was observed between these variables and body composition or bone mineral density.