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 indiabetes. 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 alow concentration of glucose degradation products. Based on preclinical results, specific targeting of apoptosis regulatory factor should be explored in the clinical setting (AU)

En la diálisis peritoneal (DP) y la diabetes mellitus (DM)altas concentraciones de glucosa se asocian a daño tisular. La apoptosis es uno de los mecanismos de daño tisular. Los productos de degradación de la glucosa (PDGs) se producen a partir de la glucosa tanto in vivo, en diabéticos, como durante el procesamiento de las soluciones de DP e inducen apoptosis en distintos tipos celulares. La apoptosises un modo activo de muerte celular con control molecular, regulada por moléculas intracelulares y extracelulares que dan lugar a distintas vías pro y antiapoptóticas, susceptibles de manipulación terapéutica. Entre estas se encuentran las caspasas, una familia de protein cisteasas que se comportan como moléculas iniciadoras o efectoras de la apoptosis. Entre los PDGs conocidos, la 3,4 dideoxiglucosona(3,4 DGE) es el principal componente letal de las soluciones de DP. La 3,4 DGE induce apoptosis en leucocitos y células tubulares de riñón. La inhibición de la apoptosis de leucocitos mejora la defensa antibacteriana peritoneal. Proponemos que los PDGs pueden estar implicados en el empeoramiento de la defensa antibacteriana y en lapérdida progresiva de la función renal en pacientes diabéticos y en DP. Entre las posibles estrategias terapéuticas destacamos el empleo de soluciones de DP con baja concentración de PDGs, que podrían disminuir la incidencia y gravedad de las peritonitis así como conservar la función renal residual. Otra posible estrategia seria el empleo de fármacos inhibidores de la apoptosis patológica (AU)

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.

[Experience with sevelamer in peritoneal dialysis]. / Experiencia con sevelamer en diálisis peritoneal.

BACKGROUND: Sevelamer is a non-absorbable phosphorus chelator that is not a source of aluminium, calcium or base. The clinical experience with sevelamer in peritoneal dialysis and in daily clinical practice is scarce. The aim of this study is to evaluate the results of therapy of hyperphosphoremia with sevelamer on serum phosphorus and phosphorus chelators requirements, in a peritoneal dialysis clinical practice. METHODS: Sevalamer 400 mg was prescribed to peritoneal dialysis patients with hyperphosphoremia who were treated with aluminium hydroxide or with calcium salts in the absence of hypocalcemia. Fourteen patients completed 12 months of therapy. RESULTS: The initial sevelamer dose was 2,280 +/- 760 mg/day, and was increased to 2,760 +/- 1,160 mg/day at 12 months. At 12 months no patient was on aluminium salts and calcium salts had been significantly reduced. Phosphoremia (5.9 +/- 0.6 to 5.0 +/- 1.4 mg/dL, p = 0.049), calcium-phosphorus product (59.8 +/- 5.8 to 48.6 +/- 12.5 mg2/dL2, p = 0.01) and serum cholesterol (191 +/- 29 to 167 +/- 33 mg/dL, p = 0.02) decreased at 12 months. No significant changes were observed in serum triglycerides, total CO2 or PTH. Serum alkaline phosphatase increased at 6 months, but values returned to normal at 12 months. No changes were observed in serum gamma-glutamyl-transpeptidase. Five patients were started on 1.25 (OH)2 vitamin D therapy. CONCLUSION: In peritoneal dialysis patients, sevelamer allows a satisfactory control of serum phosphorus levels and calcium-phosphorus product, while decreasing the amount of aluminium and calcium salts prescribed.

Experiencia con sevelamer en diálisis peritoneal / Experience with sevelamer in peritoneal dialysis

Introducción: El sevelamer es un quelante del fósforo no absorbible que no aporta aluminio, calcio ni bases. La experiencia con este nuevo quelante en nuestro medio, en diálisis peritoneal y en la práctica clínica diaria es escasa. El objetivo de este estudio es evaluar los resultados del tratamiento con sevelamer sobre la fosforemia y el uso de quelantes del fósforo en diálisis peritoneal. Métodos: En los pacientes del programa de diálisis peritoneal que recibían hidróxido de aluminio o que recibían sales de calcio sin tener tendencia a la hipocalcemia, la hiperfosforemia se trató con sevelamer. Catorce pacientes completaron 12 meses de tratamiento. Resultados: La dosis inicial de sevelamer fue de 2.280 ñ 760 mg/día, repartidos en dos o tres dosis y a los 12 meses era 2.760 ñ 1.160 mg/día. A los 12 meses el hidróxido de aluminio se había suspendido y la dosis de sales de calcio, la fosforemia (5,9 ñ 0,6 a 5,0 ñ 1,4 mg/dL, p = 0,049), el producto calciofósforo (59,8 ñ 5,8 a 48,6 ñ 12,5 mg2/dL2, p = 0,01) y el colesterol (191 ñ 29 a 167 ñ 33 mg/dL, p = 0,02) disminuyeron. No hubo cambios significativos en los triglicéridos, CO2 total ni la PTH. Se objetivó un aumento de la fosfatasa alcalina a los 6 meses, que se había normalizado a los 12 meses, sin cambios en la GGTY. Cinco pacientes comenzaron tratamiento con 1,25 dihidroxivitamina D. Conclusiones: En diálisis peritoneal el sevelamer permite un adecuado control de la fosforemia, a pesar de un menor uso de sales de calcio y de aluminio, y mejora el producto calcio-fósforo (AU)

Test de equilibrio peritoneal con intercambio hipertónico: aplicación práctica en un programa de diálisis peritoneal / Hypertonic peritoneal equilibration test: application to a peritoneal dialysis program

Recientemente se ha recomendado el test de equilibrio peritoneal (TEP) con intercambio hipertónico (3,86 por ciento/4,25 por ciento glucosa) para evaluar la capacidad de ultrafiltración peritoneal y, mediante el análisis de la concentración de sodio del dializado, estudiar ciertas causas de fallo de ultrafiltración, como la disfunción de acuaporinas. Sin embargo, no existe suficiente información sobre la mejor forma de expresar variaciones de la concentración de sodio del dializado, sobre los valores de la normalidad de este parámetro y sobre los posibles efectos adversos de la aplicación del TEP con intercambio hipertónico en la población general de pacientes en diálisis peritoneal.Realizamos un TEP con intercambio hipertónico en 22 pacientes. Siete pacientes presentaron un defecto de ultrafiltración (ultrafiltración < 0,4 L). Los pacientes con defecto de ultrafiltración tenían un transporte peritoneal de solutos pequeños y una concentración de sodio en el dializado más elevados y habían estado más tiempo en diálisis peritoneal. La concentración de sodio en el dializado a los 60 y 240 minutos se correlacionó directamente con el transporte peritoneal de solutos, calculado como D/PCr240 (r = 0,74, p = 0,0008 y r = 0,84, p < 0,0001) e inversamente con la ultrafiltración (r = 0,64, p = 0,0016 y r = 0,72, p = 0,0002). La ausencia de caída de la concentración de sodio en el dializado, sugerente de defecto de acuaporinas, es infrecuente. La concentración de sodio en el dializado a los 60 minutos discrimina mejor a los pacientes con fallo de ultrafiltración que parámetros como el D/PNa o la caída absoluta de los valores de sodio con respecto al tiempo cero. Como efectos adversos observamos hipotensión sintomática en 2 pacientes con ultrafiltración conservada.En conclusión, aunque el TEP hipertónico permite confirmar el diagnóstico de fallo de ultrafiltración, la medida del sodio en el dializado solo aporta información adicional en los raros casos en que existe un defecto severo en la función de acuaporinas. El empleo rutinario del TEP hipertónico puede provocar efectos adversos en pacientes sin defecto de ultrafiltración. (AU)

[Peritoneal equilibrium test with hypertonic exchange: practical application in a peritoneal dialysis program]. / Test de equilibrio peritoneal con intercambio hipertónico: aplicación práctica en un programa de diálisis peritoneal.

Peritoneal equilibration test (PET) employing a 2.27%/2.5% glucose exchange is the most widely used method of to evaluating peritoneal function and small solute transport. Hypertonic (3.86%/4.25% glucose) PET has been recently recommended for the evaluation of ultrafiltration and to study certain causes of ultrafiltration failure, such as aquaporin dysfunction, through the analysis of dialysate sodium. However, there is not enough information on the optimal way to express the changes in dialysate sodium concentration, the normal range of values for this parameter, and possible adverse effects of hypertonic PET in the general population of peritoneal dialysis patients. A hypertonic PET was performed in 22 patients. Ultrafiltration failure (ultrafiltration < 0.4 L) was present in seven patients. Patients with ultrafiltration failure had higher small solute peritoneal transport and dialysate sodium concentration and had been treated with peritoneal dialysis for longer periods of time. Dialysate sodium concentration at 60 and 240 minutes was directly correlated with small solute peritoneal transport calculated as D/PCr240 (r = 0.74, p = 0.0008 y r = 0.84, p < 0.0001) and inversely correlated with ultrafiltration (r = 0.64, p = 0.0016 y r = 0.72, p = 0.0002). An absence of a dip in dialysis sodium, suggestive of aquaporin dysfunction, was only observed in one patient with a high-average small solute peritoneal transport. Dialysate sodium concentration at 60 minutes is a better discriminator between ultrafiltration failure patients than parameters such as D/PNa or the absolute dip in dialysate sodium with respect to time zero. We observed the following adverse effects: symptomatic hypotension in 2 patients with preserved ultrafiltration. In conclusion, hypertonic PET allows to confirm the diagnosis of ultrafiltration failure, but monitoring dialysate sodium concentration offers additional information only in patients with severe aquaporin dysfunction. Hypertonic PET may have adverse effects in patients without ultrafiltration failure.

Aspirin protected the nitric oxide/cyclic GMP generating system in human peritoneum.

OBJECTIVE: Changes in the expression of endothelial nitric oxide synthase (eNOS) in the peritoneum could be involved in the peritoneal dysfunction associated with peritoneal inflammation. The aim of the present study was to analyze the effect of Escherichia coli lipopolysaccharide (LPS) on eNOS expression in samples of human peritoneum. The effect of aspirin, a drug with anti-inflammatory properties, was also determined. RESULTS: The eNOS protein expressed in human peritoneal tissue was reduced by LPS (10 microg/mL) in a time-dependent manner. The eNOS was expressed mainly in capillary endothelial cells and mesothelial cells. Anti-inflammatory doses of aspirin (1-10 mmol/L) restored eNOS expression in LPS-stimulated human peritoneal tissue samples. The main intracellular receptor of NO, soluble guanylate cyclase (sGC), was also downregulated by LPS. This effect was prevented by aspirin (5 mmol/L). CONCLUSION: Protein expression of the eNOS-sGC system in the peritoneal tissue was downregulated by LPS. High doses of aspirin protected both eNOS protein expression and sGC in human peritoneum. These findings suggest a new mechanism of action of aspirin that could be involved in the prevention of peritoneal dysfunction during inflammation.

Papel regulador de la apoptosis en la celularidad peritoneal / Role and regulation of apoptosis in peritoneal cell number

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Three year prospective follow up of the peritoneal access.

Peritoneal access-related complications were prospectively studied in 54 peritoneal catheters placed in 49 patients between January 1994 and December 96 in a single centre. There were no perioperative complications. Five (9%) catheters were removed because of catheter-derived complications (3 outflow obstruction, 2 leak), 4 (7.4%) because of peritonitis and 1 was spontaneously extruded. Complications included 4 (7.4%) migrations with outflow obstruction, 6 (11%) leaks and 27 episodes of exit site infection occurring in 16 (30%) catheters. Six catheters suffered more than one infection. Exit site infection in the first month after catheter placement is a risk factor for multiple exit site infections by different bacteria and for catheter removal.

A nursing approach: towards the integral health care of renal patients.

In February 1993, after several multicentre meetings held together with nephrologists, the decision was taken to create the Peritoneal Dialysis Nursing Group for the Central Area; having as its primary purpose the provision of integrated medical care to renal patients.

Peritonitis involving a Capnocytophaga sp. in a patient undergoing continuous ambulatory peritoneal dialysis.

Capnocytophaga is a genus of gram-negative rods involved mainly in bacteremia in immunocompromised hosts. Here we report a case of Capnocytophaga peritonitis in a patient undergoing continuous ambulatory peritoneal dialysis. The disease appeared as a superinfection during antimicrobial therapy of a previous episode of peritonitis.

Evidence against transmission of hepatitis C virus through hemodialysis ultrafiltrate and peritoneal fluid.

Hepatitis C virus (HCV) infection is highly prevalent in the chronic renal failure population treated in dialysis units. Transmission of HCV via blood transfusions is becoming an increasing problem, but, nevertheless, the routes by which this transmission occurs are incompletely known. We have searched for the presence of HCV RNA by the polymerase chain reaction (PCR) in serum and dialysis ultrafiltrate in 12 hemodialysis and 5 continuous ambulatory peritoneal dialysis (CAPD) patients, all of whom were HCV-antibody-positive. Serum PCR were positive for HCV RNA in all the cases, whereas PCR performed on samples of hemodialysis ultrafiltrate or peritoneal effluent were always negative for HCV RNA. In addition, 13 patients tested positive for HCV antibodies and 19 out of 32 patients sharing the dialysis monitors with 17 PCR-positive individuals remained negative. From these findings, we conclude that the dialysis ultrafiltrate or peritoneal fluid seems to be an improbable source of HCV dissemination in the dialysis setting. Moreover, a significant group of patients remained HCV-antibody-negative although they shared the same dialysis machine with positive patients. Therefore, the importance of other sources of HCV transmission, namely blood-contaminated material, should be emphasized.