Influencia del volumen peritoneal residual en los resultados de la prueba de equilibrio peritoneal. Estudio prospectivo / Influence of peritoneal residual volume on the results of the peritoneal equilibration test. Prospective study

Introducción y objetivos: La categorización de la capacidad de ultrafiltración durante la prueba de equilibrio peritoneal (PEP) es parte habitual de la monitorización del funcionalismo peritoneal en pacientes tratados con diálisis peritoneal (DP). La estimación del volumen residual (Vr) tras el cambio previo (Vrpre) y el de la propia PEP (Vrpost) podría ayudar a mejorar la precisión de la prueba. Método: Siguiendo un diseño prospectivo, estimamos el Vrpre y Vrpost en 116 pacientes incidentes o prevalentes en DP que fueron sometidos a una o dos (n=27) PEP con solución de glucosa al 3,86/4,25% y drenaje completo a los 60 minutos. Valoramos la consistencia del Vr comparando Vrpre y Vrpost y también estos parámetros en PEP sucesivas. Analizamos la posible influencia de factores demográficos y clínicos en la cuantía del Vr, así como el impacto de la corrección para Vr de la ultrafiltración durante la PEP sobre la categorización de la capacidad de ultrafiltración. Resultados: El Vrpost fue mayor que el Vrpre, por lo que la ultrafiltración corregida para Vr fue signficativamente mayor que la calculada por procedimiento estándar (494 vs. 449mL, p<0,0005). Resultó notable la escasa concordancia de estimaciones sucesivas (Vrpre vs Vrpost y PEP sucesivas) del Vr. Asimismo, ningún parámetro demográfico o clínico escrutado mostró asociación con la magnitud del Vr. Tan solo un 12,9% de los pacientes presentó una desviación clínicamente significativa (>200mL) de la ultrafiltración corregida para Vr frente al valor estándar. Sin embargo, un 21,1% de los pacientes que cumplían criterio de fallo de ultrafiltración por método estándar, no lo hacían si se aplicaba la corrección para Vr. (AU)

Background: Categorization of the capacity of ultrafiltration during a peritoneal equilibration test (PET) is a usual step during the monitoring of peritoneal transport characteristics of peritoneal dialysis (PD) patients. Quantifying the peritoneal residual volume (Vr) after the dwell preceding the PET (Vrpre) and at the end of the test (Vrpost) could help to improve the accuracy of the estimation of this variable. Method: Following a prospective design, we calculated Vrpre and Vrpost in 116 patients, incident or prevalent on DP, who underwent one or two (n=27) PET with 3.86/4.25% glucose-based PD solutions and complete drainage at 60min. We evaluated the consistency of Vr by comparing Vrpre and Vrpost, as also these two parameters in repeated tests. We scrutinized potential associations between demographic and clinical factors, on one side, and the amount of Vr on the other, as also the impact of correcting ultrafiltration during PET for Vr on the categorization of the capacity of ultrafiltration. Results: As a mean, Vrpost was larger than Vrpre. Consequently, correction of ultrafiltration for Vr resulted in significantly higher values than those obtained according to the standard procedure (494 vs 449mL, p<0.0005). We disclosed marked inconsistencies for different estimations of Vr in the same patients (Vrpre vs Vrpost and repeated PET studies). Moreover, no demographic or clinical variable was able to predict the amount of Vr. We observed a significant deviation (>200mL) between both methods of estimation of the capacity of utrafiltration in only 12.9% of the patients. However, 21.1% of the patients categorized as cases of ultrafiltration failure according to the standard procedure did not maintain this condition after correction for Vr. (AU)

Involvement of Mitochondrial Dysfunction in the Inflammatory Response in Human Mesothelial Cells from Peritoneal Dialysis Effluent.

Recent studies have related mitochondrial impairment with peritoneal membrane damage during peritoneal dialysis (PD) therapy. Here, we assessed the involvement of mitochondrial dysfunction in the inflammatory response in human mesothelial cells, a hallmark in the pathogenesis of PD-related peritoneal membrane damage. Our ex vivo studies showed that IL-1ß causes a drop in the mitochondrial membrane potential in cells from peritoneal effluent. Moreover, when mitochondrial damage was induced by inhibitors of mitochondrial function, a low-grade inflammatory response was generated. Interestingly, mitochondrial damage sensitized mesothelial cells, causing a significant increase in the inflammatory response induced by cytokines, in which ROS generation and NF-κB activation appear to be involved, since inflammation was counteracted by both mitoTEMPO (mitochondrial ROS scavenger) and BAY-117085 (NF-κB inhibitor). Furthermore, the natural anti-inflammatory antioxidant resveratrol significantly attenuated the inflammatory response, by reversing the decline in mitochondrial membrane potential and decreasing the expression of IL-8, COX-2 and PGE2 caused by IL-1ß. These findings suggest that IL-1ß regulates mitochondrial function in mesothelial cells and that mitochondrial dysfunction could induce an inflammatory scenario that sensitizes these cells, causing significant amplification of the inflammatory response induced by cytokines. Resveratrol may represent a promising strategy in controlling the mesothelial inflammatory response to PD.

Mitochondrial Dysfunction Plays a Relevant Role in Pathophysiology of Peritoneal Membrane Damage Induced by Peritoneal Dialysis.

Preservation of the peritoneal membrane is an essential determinant of the long-term outcome of peritoneal dialysis (PD). Epithelial-to-mesenchymal transition (EMT) plays a central role in the pathogenesis of PD-related peritoneal membrane injury. We hypothesized that mitochondria may be implicated in the mechanisms that initiate and sustain peritoneal membrane damage in this setting. Hence, we carried out ex vivo studies of effluent-derived human mesothelial cells, which disclosed a significant increase in mitochondrial reactive oxygen species (mtROS) production and a loss of mitochondrial membrane potential in mesothelial cells with a fibroblast phenotype, compared to those preserving an epithelial morphology. In addition, in vitro studies of omentum-derived mesothelial cells identified mtROS as mediators of the EMT process as mitoTEMPO, a selective mtROS scavenger, reduced fibronectin protein expression induced by TGF-ß1. Moreover, we quantified mitochondrial DNA (mtDNA) levels in the supernatant of effluent PD solutions, disclosing a direct correlation with small solute transport characteristics (as estimated from the ratio dialysate/plasma of creatinine at 240 min), and an inverse correlation with peritoneal ultrafiltration. These results suggest that mitochondria are involved in the EMT that human peritoneal mesothelial cells suffer in the course of PD therapy. The level of mtDNA in the effluent dialysate of PD patients could perform as a biomarker of PD-induced damage to the peritoneal membrane.

Does Prior Abdominal Surgery Influence Peritoneal Transport Characteristics or Technique Survival of Peritoneal Dialysis Patients?

INTRODUCTION: Prior abdominal surgery may result in peritoneal membrane adhesions and fibrosis, compromising the success of peritoneal dialysis (PD). The impact of this factor on peritoneal membrane function and PD technique survival has not been adequately investigated. METHODS: Following an observational, retrospective design, we studied 171 incident PD patients, with the main objective of analyzing the influence of prior abdominal surgical procedures (main study variable) on baseline and evolutionary peritoneal transport characteristics (main outcome) and PD patient and technique survival (secondary outcomes). Abdominal surgeries were categorized according to the degree of presumed injury to the peritoneal membrane. We also considered the additive effect of aggressions to the membrane during the first year on PD therapy. RESULTS: All patients had a baseline peritoneal equilibration test with complete drainage at 60', and 113 patients had a second study at the end of the first year. Sixty-one patients (35.7%) had a record of prior abdominal surgery, including 29 patients with at least one major intraperitoneal surgery, 22 having undergone minor intraperitoneal procedures, and 21 with a background of major abdominopelvic extraperitoneal surgery. We did not observe differences, at baseline or after 1 year, among patients with or without previous abdominal procedures regarding small solute transport, overall capacity of ultrafiltration, free water transport, small pore ultrafiltration, or peritoneal protein excretion. Stratified analysis, considering prior and first-year-on-PD peritoneal aggressions, did not reveal any differences, although in this case our analysis was hampered by a limited statistical power. Abdominal surgical events did not influence patient or PD technique survival. CONCLUSION: Prior abdominal surgical procedures do not appear to compromise peritoneal membrane function or technique survival in patients successfully started on PD.

Long-term trends in the incidence of peritoneal dialysis-related peritonitis disclose an increasing relevance of streptococcal infections: A longitudinal study.

BACKGROUND: The selective impact of strategies for prevention of PD-related peritonitis (PDrP) may have modified, in the long term, the causal spectrum, clinical presentation and outcomes of these infections. OBJECTIVES: To compare trends in the incidence of PDrP by different microorganisms during a 30-year period, with a particular focus on streptococcal infections. To analyze the clinical presentation and outcomes of these infections. Secondarily, to investigate how the isolation of different species of streptococci can influence the clinical course of PDrP by this genus of bacteria. METHOD: Following a retrospective, observational design we investigated 1061 PDrP (1990-2019). We used joinpoint regression analysis to explore trends in the incidence of PDrP by different microorganisms, and compared the risk profile (Cox), clinical presentation and outcomes (logistic regression) of these infections. MAIN RESULTS: Our data showed a progressive decline in the incidence of PDrP by staphylococci and Gram negative bacteria, while the absolute rates of streptococcal (average annual percent change +1.6%, 95% CI -0.1/+3.2) and polymicrobial (+1.8%, +0.1/+3.5) infections tended to increase, during the same period. Remarkably, streptococci were isolated in 58.6% of polymicrobial infections, and patients who suffered a streptococcal PDrP had a 35.8% chance of presenting at least one other infection by the same genus. The risk profile for streptococcal infections was comparable to that observed for PDrP overall. Streptococcal PDrP were associated with a severe initial inflammatory response, but their clinical course was generally nonaggressive thereafter. We did not observe a differential effect of different groups of streptococci on the clinical presentation or outcome of PDrP. CONCLUSIONS: Time trends in the incidence of PDrP by different microorganisms have granted streptococci an increasing relevance as causative agents of these infections, during the last three decades. This behaviour suggests that current measures of prevention of PDrP may not be sufficiently effective, in the case of this genus of microorganisms.

Situación de la infección por SARS-CoV-2 en pacientes en tratamiento renal sustitutivo Informe del Registro COVID-19 de la Sociedad Española de Nefrología (S.E.N.) / SARS-CoV-2 infection in patients on renal replacement therapy. Report of the COVID-19 Registry of the Spanish Society of Nephrology (S.E.N.)

La reciente aparición de la pandemia por el coronavirus SARS-CoV-2 ha impactado de forma muy importante en la población general. Los pacientes en tratamiento renal sustitutivo (TRS) no han sido ajenos a esta situación y por sus características resultan especialmente vulnerables. Presentamos los resultados del análisis del Registro COVID-19 de la S.E.N. MATERIAL Y MÉTODOS: EL Registro comenzó a funcionar el 18 de marzo de 2020. Recoge variables epidemiológicas, datos del contagio y diagnóstico, clínica acompañante, tratamientos y desenlace. Se trata de un registro "on line". Los pacientes fueron diagnosticados de infección por SARS-Cov-2 en base a los resultados de la PCR del virus, realizada tanto en pacientes que habían manifestado clínica compatible o tenían signos sospechosos como en aquellos a los que se había hecho como cribado tras algún contacto conocido con otro enfermo. RESULTADOS: A fecha 11 de abril el Registro disponía de datos de 868 pacientes, procedentes de todas las Comunidades Autónomas. La modalidad de TRS más representada es la hemodiálisis en centro (HDC) seguida de los pacientes trasplantados. La clínica de presentación es similar a la población general. Un porcentaje muy elevado (85%) requirió ingreso hospitalario, un 8% en unidades de cuidados intensivos. Los tratamientos más utilizados fueron hidroxicloroquina, lopinavirritonavir y esteroides. La mortalidad es elevada y alcanza el 23%: los pacientes fallecidos estaban con más frecuencia en HDC, desarrollaban más frecuentemente neumonía y recibían en menos ocasiones lopinavir-ritonavir y esteroides. La edad y la neumonía se asociaban de forma independiente al riesgo de fallecer. CONCLUSIONES: La infección por SARS-CoV-2 afecta ya a un número importante de pacientes españoles en TRS, fundamentalmente aquellos que están en HDC, las tasas de hospitalización son muy elevadas y la mortalidad es elevada; la edad y el desarrollo de neumonía son factores asociados a mortalidad

The recent appearance of the SARS-CoV-2 coronavirus pandemic has had a significant impact on the general population. Patients on renal replacement therapy (RRT) have not been unaware of this situation and due to their characteristics they are especially vulnerable. We present the results of the analysis of the COVID-19 Registry of the Spanish Society of Nephrology. MATERIAL AND METHODS: The Registry began operating on March 18th, 2020. It collects epidemiological variables, contagion and diagnosis data, signs and symptoms, treatments and outcomes. It is an "online" registry. Patients were diagnosed with SARS-Cov-2 infection based on the results of the PCR of the virus, carried out both in patients who had manifested compatible symptoms or had suspicious signs, as well as in those who had undergone screening after some contac, acquainted with another patient. RESULTS: As of April 11, the Registry had data on 868 patients, from all the Autonomous Communities. The most represented form of TRS is in-center hemodialysis (ICH) followed by transplant patients. Symptoms are similar to the general population. A very high percentage (85%) required hospital admission, 8% in intensive care units. The most used treatments were hydroxychloroquine, lopinavir-ritonavir, and steroids. Mortality is high and reaches 23%; deceased patients were more frequently on ICH, developed pneumonia more frequently, and received less frequently lopinavir-ritonavir and steroids. Age and pneumonia were independently associated with the risk of death. CONCLUSIONS: SARS-CoV-2 infection already affects a significant number of Spanish patients on RRT, mainly those on ICH, hospitalization rates are very high and mortality is high; age and the development of pneumonia are factors associated with mortality

[SARS-CoV-2 infection in patients on renal replacement therapy. Report of the COVID-19 Registry of the Spanish Society of Nephrology (SEN)]. / Situación de la infección por SARS-CoV-2 en pacientes en tratamiento renal sustitutivo. Informe del Registro COVID-19 de la Sociedad Española de Nefrología (SEN).

INTRODUCTION: The recent appearance of the SARS-CoV-2 coronavirus pandemic has had a significant impact on the general population. Patients on renal replacement therapy (RRT) have not been unaware of this situation and due to their characteristics they are especially vulnerable. We present the results of the analysis of the COVID-19 Registry of the Spanish Society of Nephrology. MATERIAL AND METHODS: The Registry began operating on March 18th, 2020. It collects epidemiological variables, contagion and diagnosis data, signs and symptoms, treatments and outcomes. It is an online registry. Patients were diagnosed with SARS-CoV-2 infection based on the results of the PCR of the virus, carried out both in patients who had manifested compatible symptoms or had suspicious signs, as well as in those who had undergone screening after some contact acquainted with another patient. RESULTS: As of April 11, the Registry had data on 868 patients, from all the Autonomous Communities. The most represented form of RRT is in-center hemodialysis (ICH) followed by transplant patients. Symptoms are similar to the general population. A very high percentage (85%) required hospital admission, 8% in intensive care units. The most used treatments were hydroxychloroquine, lopinavir-ritonavir, and steroids. Mortality is high and reaches 23%; deceased patients were more frequently on ICH, developed pneumonia more frequently, and received less frequently lopinavir-ritonavir and steroids. Age and pneumonia were independently associated with the risk of death. CONCLUSIONS: SARS-CoV-2 infection already affects a significant number of Spanish patients on RRT, mainly those on ICH, hospitalization rates are very high and mortality is high; age and the development of pneumonia are factors associated with mortality.

Analysis of Factors Influencing the Prognostic Significance of Hyponatremia in Peritoneal Dialysis Patients.

BACKGROUND: The evidence linking low serum sodium levels with the risk of mortality in peritoneal dialysis (PD) patients is controversial. Considering the different mechanisms contributing to hyponatremia in these patients, it is conceivable that the prognostic significance of this factor may vary, according to the clinical setting. METHODS: Following a retrospective, observational design, we analyzed the association between hyponatremia and mortality in 748 patients incident on PD. We applied multivariate strategies of analysis, with the main objective of identifying subgroups of patients in whom hyponatremia could sustain different degrees of association with mortality (main outcome variable). For this purpose, we performed preliminary analyses to: (1) disclose predictors of serum sodium levels before and after (mean of first 3 months) initiation of PD (main study variable) and (2) investigate the overall prognostic significance of hyponatremia, in our patients. RESULTS: Comorbidity, hypoalbuminemia, and lower glomerular filtration rate (GFR) were main predictors of hyponatremia. Use of icodextrin was another inverse correlate of serum sodium, and the only consistent predictor of a decline of natremia, once PD was started. Multivariate analysis confirmed early hyponatremia as an independent marker of survival. However, stratified analyses showed that this association was most apparent in specific subsets, namely, hypoalbuminemic, more anemic patients with higher baseline levels of GFR and C-reactive protein and faster peritoneal solute transport rates. Other factors potentially reinforcing the prognostic significance of hyponatremia included lower lean body mass levels, nonprescription of renin-angiotensin-aldosterone system antagonists, and use of icodextrin-based PD solution. On the contrary, baseline overhydration or categorization by classic predictors of mortality (age, comorbidity, diabetes) did not appear to influence the risk pattern associated with lower serum sodium levels. CONCLUSIONS: Our results suggest that hyponatremia performs as a consistent correlate of the risk of mortality mainly in PD patients manifesting direct or indirect signs of inflammation and wasting, while this association is not apparently linked to the presence of overhydration or nominal, preexisting comorbid conditions.

La sobrehidratación persistente asocia un riesgo significativo de infección peritoneal por gérmenes entéricos en pacientes tratados con diálisis peritoneal / Persistent overhydration is associated with a significant risk of peritoneal infection by enteric pathogens in patients treated with peritoneal dialysis

ANTECEDENTES Y OBJETIVOS: La sobrehidratación (SH) es frecuente, y a menudo persistente, en pacientes tratados con diálisis peritoneal (DP), y mantiene una asociación controvertida con el riesgo de infección peritoneal. El objetivo principal de este estudio fue desvelar una posible asociación entre la presencia de SH y el riesgo subsiguiente de infección peritoneal por gérmenes entéricos, en una población relativamente amplia de pacientes tratados con DP. MÉTODO: Según diseño prospectivo, monitorizamos de manera sistemática la composición corporal de pacientes tratados con DP en nuestra unidad (2011-2016), buscando una posible correlación con el riesgo de peritonitis durante el seguimiento, con un interés particular en la asociación entre SH persistente (variable de estudio principal) y el riesgo de infección peritoneal por patógenos entéricos (variable resultado principal). Para el análisis tuvimos en cuenta variables demográficas, clínicas y de laboratorio con influencia potencial en el riesgo de infección peritoneal. Utilizamos técnicas de análisis multivariante para clarificar el efecto específico de diferentes parámetros de composición corporal sobre la variable resultado principal. RESULTADOS PRINCIPALES: Incluimos 139 pacientes, con seguimiento medio de 24 meses. Sesenta y tres pacientes sufrieron al menos una peritonitis, y 17 al menos una infección por gérmenes entéricos. El análisis univariante mostró una tendencia general a mayor riesgo de infección peritoneal entérica en pacientes sobrehidratados, que se hacía evidente cuando se usaba el cociente agua extracelular/agua intracelular (AEC/AIC) (p = 0,007), el cociente SH/AEC (SH/AEG) (p = 0,033), o el cociente AEC/agua corporal total (AEC/ACT) (p = 0,004), pero no cuando se usaba la SH absoluta, como variable de estudio. El análisis multivariante confirmó estas asociaciones o tendencias (RR: 3,48; IC 95%: 1,03-14,59; p = 0,046, tercil mayor versus menor para AEC/AIC, RR: 2,31; IC 95%: 0,98-6,56; p = 0,061, tercil mayor versus menor para SH/AEC, y RR: 6,33; IC 95%: 1,37-19,37; p = 0,011, tercil mayor versus menor para AEC/ACT). Por el contrario, no observamos asociación consistente entre SH y riesgo general de infección peritoneal. CONCLUSIÓN: La SH persistente asocia un riesgo significativo de infección peritoneal por patógenos entéricos, en pacientes tratados con DP

BACKGROUND: Overhydration (OH) complicates frequently the clinical course of Peritoneal Dialysis (PD) patients, and keeps a controversial association with the risk of peritoneal infection. The main objective of this study was to disclose an association between persistent OH and the risk of enteric peritonitis in a relatively large sample of patients undergoing PD. METHOD: Following a prospective design, we monitorized systematically body composition of patients treated with PD in our unit (2011-2016), searching for a correlation with the ensuing risk of peritonitis, with an emphasis on the association between persistent OH (main study variable) and the risk of infection by enteric pathogens (main outcome). Essential demographic, clinical and laboratory variables with a potential influence on the risk of peritonitis were recorded. We used multivariate survival analysis to clarify the specific effect of different body composition parameters on the main outcome. MAIN RESULTS: We included 139 patients for analysis (mean follow-up 24 months). Sixty-three patients suffered at least one peritonitis, and 17 had at least one diagnosis of enteric peritonitis. Univariate analysis disclosed a general trend to an increased risk of enteric peritonitis in overhydrated patients, as evidenced by associations of this outcome with mean extracellular water/intracellular water (ECW/ICW) (p = .007), OH/ECW (p = .033) and ECW/total body water (ECW/TBW) (p = .004) ratios, but not with absolute OH values. Multivariate analysis confirmed similar associations or trends (RR: 3.48, 95% CI: 1.03-14.59; p = .046, highest versus lowest tertile of ECW/ICW, RR: 2.31, 95% CI: 0.98-6.56; p = .061, highest versus lowest tertile of OH/ECW, and RR: 6.33, 95% CI: 1.37-19.37; p = .011, highest versus lowest tertile of ECW/TBW). On the contrary, no apparent association was detected between OH and the overall risk of peritoneal infection. CONCLUSION: Persistent overhydration portends a significant risk of peritoneal infection by enteric pathogens, among patients undergoing chronic PD

Persistent overhydration is associated with a significant risk of peritoneal infection by enteric pathogens in patients treated with peritoneal dialysis. / La sobrehidratación persistente asocia un riesgo significativo de infección peritoneal por gérmenes entéricos en pacientes tratados con diálisis peritoneal.

BACKGROUND: Overhydration (OH) complicates frequently the clinical course of Peritoneal Dialysis (PD) patients, and keeps a controversial association with the risk of peritoneal infection. The main objective of this study was to disclose an association between persistent OH and the risk of enteric peritonitis in a relatively large sample of patients undergoing PD. METHOD: Following a prospective design, we monitorized systematically body composition of patients treated with PD in our unit (2011-2016), searching for a correlation with the ensuing risk of peritonitis, with an emphasis on the association between persistent OH (main study variable) and the risk of infection by enteric pathogens (main outcome). Essential demographic, clinical and laboratory variables with a potential influence on the risk of peritonitis were recorded. We used multivariate survival analysis to clarify the specific effect of different body composition parameters on the main outcome. MAIN RESULTS: We included 139 patients for analysis (mean follow-up 24 months). Sixty-three patients suffered at least one peritonitis, and 17 had at least one diagnosis of enteric peritonitis. Univariate analysis disclosed a general trend to an increased risk of enteric peritonitis in overhydrated patients, as evidenced by associations of this outcome with mean extracellular water/intracellular water (ECW/ICW) (p=.007), OH/ECW (p=.033) and ECW/total body water (ECW/TBW) (p=.004) ratios, but not with absolute OH values. Multivariate analysis confirmed similar associations or trends (RR: 3.48, 95% CI: 1.03-14.59; p=.046, highest versus lowest tertile of ECW/ICW, RR: 2.31, 95% CI: 0.98-6.56; p=.061, highest versus lowest tertile of OH/ECW, and RR: 6.33, 95% CI: 1.37-19.37; p=.011, highest versus lowest tertile of ECW/TBW). On the contrary, no apparent association was detected between OH and the overall risk of peritoneal infection. CONCLUSION: Persistent overhydration portends a significant risk of peritoneal infection by enteric pathogens, among patients undergoing chronic PD.

The Spanish Society of Nephrology (SENEFRO) commentary to the Spain GBD 2016 report: Keeping chronic kidney disease out of sight of health authorities will only magnify the problem / Comentario de la Sociedad Española de Nefrología (SENEFRO) al informe GBD 2016 España: mantener la enfermedad renal crónica fuera del radar de las autoridades sanitarias solo magnificará el problema

The Global Burden of Disease (GBD) study measures the health of populations worldwide and by country on an annual basis and aims at helping guide public policy on health issues. The GBD estimates for Spain in 2016 and recent trends in mortality and morbidity from 2006 to 2016 were recently published. According to these estimates, chronic kidney disease was the 8th cause of death in Spain in 2016. Among the top ten causes of death, chronic kidney disease was the fastest growing from 2006 to 2016, after Alzheimer disease. At the current pace of growth, chronic kidney disease is set to become the second cause of death in Spain, after Alzheimer disease, by 2100. Additionally, among major causes of death, chronic kidney disease also ranked second only to Alzheimer as the fastest growing cause of Years Lived with Disability (YLDs) and Disability Adjusted Life Years (DALYs). Public resources devoted to prevention, care and research on kidney disease should be in line with both its current and future burden

El estudio Global Burden of Disease (GBD) mide la salud de las poblaciones en todo el mundo y en cada país de forma annual, y tiene como objetivo ayudar a orientar las políticas públicas sobre cuestiones de salud. Recientemente se publicaron las estimaciones GBD 2016 para España y las tendencias recientes en mortalidad y morbilidad de 2006 a 2016. Según estas estimaciones, la enfermedad renal crónica fue la octava causa de muerte en España en 2016. Entre las 10 principales causas de muerte, la enfermedad renal crónica fue la que más creció entre 2006 y 2016, después de la enfermedad de Alzheimer. Al ritmo actual de crecimiento, la enfermedad renal crónica se convertirá en la segunda causa de muerte en España, después del Alzheimer, hacia el 2100. Además, entre las principales causas de muerte, la enfermedad renal crónica también ocupa el segundo lugar después del Alzheimer como la que más creció en años vividos con discapacidad (AVD) y en años de vida ajustados por discapacidad (AVAD). Los recursos públicos dedicados a la prevención, atención e investigación de la enfermedad renal deberían estar en línea con su carga actual y futura

High rates of protein intake are associated with an accelerated rate of decline of residual kidney function in incident peritoneal dialysis patients.

BACKGROUND: Preservation of residual kidney function (RKF) is a relevant objective in peritoneal dialysis (PD) patients. The influence of dietary protein intake (PI) on this variable has not been adequately investigated. METHODS: Following an observational design, we studied 336 patients incident on PD, with a minimum follow-up of 6 months. The main study variable was the mean PI [normalized rate of protein nitrogen appearance (nPNA)] during the first 4 months on PD. The main outcome variables were the absolute rate of decline of RKF and the proportion of patients presenting a >50% decay of their RKF during the first year of follow-up. We applied univariate and multivariate strategies of analysis, taking into consideration the main control variables bearing a correlation with nPNA and/or RKF. RESULTS: Mean nPNA (first 4 months) was 1.23 ± 0.33 g/kg/day, while the overall rate of decline of RKF was -0.13 ± 0.29 mL/min/month; 69 patients (25.1%) had lost >50% of their initial RKF by the end of the first year. Univariate analysis disclosed consistent associations between the main study variable on one hand and baseline RKF (r = 0.32, P < 0.0005) and its rate of decline (r = -0.23, P < 0.0005) on the other. The latter two variables were also significantly correlated (r = -0.36, P < 0.0005). Multivariate analysis identified mean nPNA as an independent predictor of the rate of decline of RKF [odds ratio 1.09 per 0.10 g/kg/day, 95% confidence interval (CI) 0.99-1.19, P = 0.058] and, in particular, of the probability of losing >50% of the baseline RKF during the first year of treatment (odds ratio 1.15 per 0.10 g/kg/day, 95% CI 1.04-1.27, P = 0.006). CONCLUSION: Higher rates of PI during the first months of therapy are associated with a faster decline of RKF among patients incident on PD. Our results underline the convenience of keeping an adequate balance between sufficient protein ingestion, to prevent malnutrition and wasting, and sensible restriction in stable, adequately nourished individuals with rates of intake in the higher range or above-recommended allowances.

The Spanish Society of Nephrology (SENEFRO) commentary to the Spain GBD 2016 report: Keeping chronic kidney disease out of sight of health authorities will only magnify the problem.

The Global Burden of Disease (GBD) study measures the health of populations worldwide and by country on an annual basis and aims at helping guide public policy on health issues. The GBD estimates for Spain in 2016 and recent trends in mortality and morbidity from 2006 to 2016 were recently published. According to these estimates, chronic kidney disease was the 8th cause of death in Spain in 2016. Among the top ten causes of death, chronic kidney disease was the fastest growing from 2006 to 2016, after Alzheimer disease. At the current pace of growth, chronic kidney disease is set to become the second cause of death in Spain, after Alzheimer disease, by 2100. Additionally, among major causes of death, chronic kidney disease also ranked second only to Alzheimer as the fastest growing cause of Years Lived with Disability (YLDs) and Disability Adjusted Life Years (DALYs). Public resources devoted to prevention, care and research on kidney disease should be in line with both its current and future burden.

Peritoneal Dialysis Is an Independent Factor Associated to Lower Intima Media Thickness in Dialysis Patients Free From Previous Cardiovascular Disease.

Carotid intima media thickness (cIMT) displays prognostic value as a marker of cardiovascular risk in dialysis patients. However, few data are available regarding the impact of dialysis modality on cIMT. The aim of this study is to determine whether the modality of dialysis influences cIMT values. We compared 237 peritoneal dialysis (PD) and 451 hemodialysis (HD) patients without previous cardiovascular disease included in NEFRONA, a prospective, observational and multicenter study. This cross sectional study included the determination of cIMT in 6 carotid territories by arterial ultrasound. cIMT was determined in territories without atheroma plaque and averaged. A second analysis was performed using all territories, giving a truncated cIMT value of 1,5 mm to territories presenting with atheroma plaque. Age and plaque presence at baseline were the clinical variables more closely associated to cIMT in dialysis patients. The evaluation of the impact of the modality of dialysis on cIMT showed that PD patients had lower cIMT than HD patients, both in territories with no plaques and when using truncated cIMT values. No differences were found between right and left sides, neither in cIMT or truncated cIMT values. Lineal multivariate analysis adjusted by several clinical variables showed a statistically significant association of PD with a lower cIMT (slope -0.036; SD 0.010). These results were also confirmed when truncated cIMT values were used. We conclude that the modality of dialysis has an impact on cITM. HD patients have greater global cIMT than PD patients, and PD is and independent factor associated with a lower cIMT.

Correction: The modality of dialysis does not influence atheromatous vascular disease progression or cardiovascular outcomes in dialysis patients without previous cardiovascular disease.

[This corrects the article DOI: 10.1371/journal.pone.0186921.].

Comprehensive Approach to Peritoneal Dialysis-Related Peritonitis by Enteric Microorganisms. Comparison Between Single Organism and Polymicrobial Infections.

BACKGROUND: Peritoneal infections of enteric origin (EntP) have been classically investigated using partial strategies, focused on particular subgroups of microorganisms. A more comprehensive approach may facilitate the definition of the nomenclature and clinical presentation of these infections. OBJECTIVES: To investigate the clinical presentation and outcomes of a full spectrum of EntP, with a particular interest in the comparison between single-organism and polymicrobial infections. METHOD: Following an observational design, we investigated 165 single-organism and 83 polymicrobial peritonitis episodes with isolation of at least 1 enteric bacteria (Enterobacteriaceae, Enterococcus spp. and/or intestinal anaerobics). We compared the risk of treatment failure for these 2 types of infection and explored the significance of the isolation of specific microorganisms and of their antibacterial susceptibility patterns. RESULTS: Polymicrobial EntP was associated with higher rates of hospitalization, more changes to initial antibiotic therapy, more surgical explorations, and higher mortality and treatment failure rates than monobacterial EntP. However, stratified and multivariate analyses revealed that the burden of these differences rested on the isolation of intestinal anaerobics (odds ratio [OR] 12.05, 95% confidence interval [CI] 2.53-31.09, p < 0.001) and/or Enterococcus faecium (OR 3.37, 95% CI 1.02-11.30, p = 0.046), while other polymicrobial infections were more comparable with single-organism peritonitis, except for even higher mortality rates in the former group. Lower antibiotic susceptibility of the isolations (OR 1.18, 95% CI 0.51-2.70, p = 0.70) did not perform as a predictor of treatment failure. CONCLUSION: A comprehensive approach to peritoneal infections by intestinal microorganisms may provide a focused perspective of the clinical presentation and outcomes of these complications of peritoneal dialysis.

The modality of dialysis does not influence atheromatous vascular disease progression or cardiovascular outcomes in dialysis patients without previous cardiovascular disease.

BACKGROUND: There is limited and inconclusive information regarding the influence of the modality of renal replacement therapy on the atherosclerotic burden of patients on dialysis. The aim of this study was to compare the prevalence of asymptomatic atheromatous carotid disease, as also its rate of progression and cardiovascular outcomes, in two matched populations of patients treated with hemodialysis (HD) and peritoneal dialysis (PD). METHODS: Following a prospective, observational and multicenter design, we compared 237 PD and 237 HD patients without previous cardiovascular disease, included in the NEFRONA study, and matched for age, sex, diabetes and time on dialysis. Carotid ultrasound study was performed at baseline and after two years of follow-up in 6 carotid territories. Atheromatous vascular disease (AVD) progression was defined as any increase in the number of territories with plaques after 2 years. Fatal and non fatal cardiovascular events were also recorded during 36-month of follow-up. MAIN RESULTS: At baseline, PD patients presented a worse general cardiovascular risk profile than HD patients. On the contrary, some markers of prevalent atherosclerotic disease (common carotid intima-media thickness and ankle-brachial index) were more favorable in PD patients. During follow-up, we observed no differences either in the rate of progression of atheromatous vascular disease (OR 1.78, 95% CI 0.80-4.06, p = 0.161) or in the incidence of cardiovascular events (OR 1.51, 95% CI 0.85-2.66, p = 0.159), according to the modality of dialysis. CONCLUSION: Dialysis modality did not impact on atherosclerotic carotid disease progression or cardiovascular outcomes, in two groups of patients treated with PD or HD.

Peritoneal Water Transport Characteristics of Diabetic Patients Undergoing Peritoneal Dialysis: A Longitudinal Study.

BACKGROUND: Volume overload is frequent in diabetics undergoing peritoneal dialysis (PD), and may play a significant role in the excess mortality observed in these patients. The characteristics of peritoneal water transport in this population have not been studied sufficiently. METHOD: Following a prospective, single-center design we made cross-sectional and longitudinal comparisons of peritoneal water transport in 2 relatively large samples of diabetic and nondiabetic PD patients. We used 3.86/4.25% glucose-based peritoneal equilibration tests (PET) with complete drainage at 60 min, for these purposes. MAIN RESULTS: We scrutinized 59 diabetic and 120 nondiabetic PD patients. Both samples showed relatively similar characteristics, although diabetics were significantly more overhydrated than nondiabetics. The baseline PET disclosed lower ultrafiltration (mean 439 mL diabetics vs. 532 mL nondiabetics, p = 0.033) and sodium removal (41 vs. 53 mM, p = 0.014) rates in diabetics. One hundred and nine patients (36 diabetics) underwent a second PET after 12 months, and 45 (14 diabetics) underwent a third one after 24 months. Longitudinal analyses disclosed an essential stability of water transport in both groups, although nondiabetic patients showed a trend where an increase in free water transport (p = 0.033) was observed, which was not the case in diabetics. CONCLUSIONS: Diabetic patients undergoing PD present lower capacities of ultrafiltration and sodium removal than their nondiabetic counterparts. Longitudinal analyses disclose an essential stability of water transport capacities, both in diabetics and nondiabetics. The clinical significance of these differences deserves further analysis.

Low Serum Levels of Vitamin D are Associated with Progression of Subclinical Atherosclerotic Vascular Disease in Peritoneal Dialysis Patients: A Prospective, Multicenter Study.

BACKGROUND: The prevalence of subclinical atherosclerosis and the main predictors of progression of this condition in patients undergoing peritoneal dialysis (PD) have been insufficiently investigated. OBJECTIVES AND METHOD: Following a prospective, multicenter, observational design, we studied 237 patients who were treated with PD for ≥3 months, without any clinical background of cardiovascular (CV) disease. Our objectives were the following: (1) to investigate the prevalence of subclinical atherosclerosis, as compared to a control group of age- and sex-matched healthy individuals, and (2) to disclose PD technique-related predictors of progression of disease during a 24-month follow-up period. We used vascular ultrasound for characterization of subclinical atherosclerotic disease. MAIN RESULTS: A total of 123 patients (51.9%) vs. 79 controls (33.5%) presented ≥1 carotid plaque, and 114 patients (48.3%) vs. 72 controls (30.5%) ≥1 femoral plaque, at baseline evaluation (p < 0.0005). Progression of disease, either in clinical or ultrasound (new plaques) terms, affected 62.6% of patients. Multivariate analysis identified age, carotid intima-media thickness, presence of ≥1 carotid plaque, and serum levels of 25OH vitamin D and C-reactive protein (CRP) at baseline as independent correlates of progression of atherosclerotic disease. On the contrary, PD technique-related variables did not show any association with this outcome. CONCLUSIONS: Atherosclerotic vascular disease is frequent among asymptomatic patients undergoing PD. Older age, pre-existent disease (assessed by vascular ultrasound), and serum levels of 25OH vitamin D and CRP are independent markers of the progression of this condition. These findings may contribute to improve identification of subpopulations with a high risk of CV events, deserving intensified measures of prevention.

Niveles séricos de la adipomioquina irisina en pacientes con enfermedad renal crónica / Serum levels of the adipomyokine irisin in patients with chronic kidney disease

Antecedentes: La irisina es una adipomioquina con posibles efectos antiobesidad y antidiabéticos. Esta hormona ha sido insuficientemente estudiada en pacientes con enfermedad renal crónica (ERC) avanzada. Objetivo: Realizar un análisis exploratorio de los niveles séricos de irisina en pacientes con diferentes modalidades de tratamiento de la ERC. Método: Según diseño transversal, estimamos niveles de irisina en 95 pacientes con ERC manejados conservadoramente (ERCA), con diálisis peritoneal (DP) o con hemodiálisis, comparándolos con un grupo control de 40 individuos sanos. También investigamos las correlaciones entre irisina sérica y variables demográficas, clínicas, metabólicas y de composición corporal. Resultados: Los niveles de irisina fueron más bajos en cualquier grupo de pacientes que en los controles. El análisis univariante desveló correlaciones moderadas entre irisina, por un lado, y masa grasa (pero no magra), filtrado glomerular (GFR) y albúmina y bicarbonato plasmático, por otro. El análisis multivariante confirmó que los pacientes con ERCA (diferencia 111,1ng/mL), en DP (25,9ng/mL) o hemodiálisis (61,4ng/mL) (todos p<0,0005) presentaban niveles ajustados más bajos de irisina que los controles. Asimismo, los pacientes en DP presentaban niveles más altos de la hormona que los de hemodiálisis (diferencia 39,4ng/mL; p=0,002) o ERCA (24,4ng/mL; p=0,036). El análisis multivariante también identificó bicarbonato plasmático (B=3,90 por mM/L; p=0,001) y GFR (B=1,89 por mL/min; p=0,003) como predictores independientes de los niveles de irisina. Por el contrario, no observamos correlación ajustada entre irisina y marcadores de composición corporal. Conclusiones: Los niveles de irisina son bajos en pacientes con ERC, y muestran correlación consistente con GFR y bicarbonato plasmático. Los pacientes en DP presentan niveles más altos de irisina que los manejados conservadoramente o con hemodiálisis. Nuestro estudio confirma una inconsistencia general en los análisis de asociación entre irisina sérica, por un lado, y marcadores metabólicos y de composición corporal, por otro (AU)

Background: Irisin is an adipomyokine with claimed anti-obesity and anti-diabetic effects. This hormone has been insufficiently studied in patients with advanced chronic kidney disease (CKD). Objective: To perform an exploratory analysis of serum irisin levels in patients undergoing different CKD treatments. Method: Following a cross-sectional design, we estimated serum levels of irisin in 95 patients with CKD managed conservatively (advanced CKD), with peritoneal dialysis (PD) or with haemodialysis, and compared our findings with a control group of 40 healthy individuals. We investigated the correlations between serum irisin and demographic, clinical, body composition and metabolic variables. Results: Irisin levels were lower in all the CKD groups than in the control group. The univariate analysis revealed limited correlations between irisin, on the one hand, and fat (but not lean) mass, glomerular filtration rate (GFR) and plasma albumin and bicarbonate, on the other. The multivariate analysis confirmed that advanced CKD patients managed conservatively (difference 111.1ng/ml), with PD (25.9ng/ml) or haemodialysis (61.4ng/ml) (all P<.0005) presented lower irisin levels than the control group. Furthermore, PD patients presented higher serum levels of irisin than those on haemodialysis (difference 39.4ng/ml, P=.002) or those managed conservatively (24.4 ng/ml, P=.036). The multivariate analysis also identified plasma bicarbonate (B=3.90 per mM/l, P=.001) and GFR (B=1.89 per ml/minute,P=.003) as independent predictors of irisin levels. Conversely, no adjusted correlation between irisin and body composition markers was found. Conclusions: Serum irisin levels are low in patients with CKD and show a consistent correlation with GFR and plasma bicarbonate levels. PD patients present higher levels of irisin than those managed conservatively or with haemodialysis. Our study confirms a general inconsistency of the association between serum irisin levels, on the one hand, and body composition and metabolic markers, on the other (AU)