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

[Abstract] 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 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

Effect of self-administered intraperitoneal bemiparin on peritoneal transport and ultrafiltration capacity in peritoneal dialysis patients with membrane dysfunction: a randomized, multi-centre open clinical trial

Randomized controlled trial[Abstract] Background: Progressive peritoneal membrane injury and dysfunction are feared repercussions of peritoneal dialysis (PD), and may compromise the long-term feasibility of this therapy. Different strategies have been attempted to prevent or reverse this complication with limited success. Methods: We performed a randomized, open multi-centre trial, aimed at scrutinizing the efficacy of self-administered intraperitoneal (i.p.) bemiparin (BM) to modulate peritoneal membrane dysfunction. The main outcome variables were peritoneal creatinine transport and the ultrafiltration (UF) capacity, estimated during consecutive peritoneal equilibration tests. The trial included a control group who did not undergo intervention. The treatment phase lasted 16 weeks with a post-study follow-up of 8 weeks. Results: Intraperitoneal BM did not significantly improve creatinine transport or the UF capacity, when the whole group was considered. However, we observed a time-limited improvement in the UF capacity for the subgroup of patients with overt UF failure, which was not observed in the control group. Intraperitoneal injection of BM did not carry an increased risk of peritoneal infection or major haemorrhagic complications. Conclusions: Our data do not support the systematic use of BM for management of peritoneal membrane dysfunction in PD patients. Further studies on the usefulness of this approach in patients with overt UF failure are warranted. Intraperitoneal administration of BM is safe in PD patients, provided regulated procedures are respected

Peritoneal water transport characteristics of diabetic patients undergoing peritoneal dialysis: a longitudinal study

[Abstract] 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

Peritoneal protein transport during the baseline peritoneal equilibration test is an accurate predictor of the outcome of peritoneal dialysis patients

[Abstract] Background: Peritoneal protein excretion (PPE) is a potential marker of the outcome in peritoneal dialysis (PD) patients. Method: Observational study of a cohort of 269 patients starting PD in a single unit. Study variables: total PPE during a baseline peritoneal equilibration test (PET; PET-PPE) and 24-hour PPE. Control variables: essential baseline demographic, laboratory and adequacy markers. Main outcomes: mortality, cardiovascular events and risk of peritonitis. We applied univariate and multivariate strategies of survival analysis. Main Results: PET-PPE sustained a significant, yet limited correlation with 24-hour PPE (r = 0.46, p < 0.0005). At baseline, the main study variables showed an independent correlation with peritoneal transport characteristics (D/P240’ creatinine) and cardiovascular comorbidity. PET-PPE (p < 0.0005, model global χ2 59.4) was a more accurate predictor of overall mortality than 24-hour PPE (p = 0.04, χ2 50.5). Moreover, PPE during PET, but not 24-hour PPE, was an independent predictor of the risks of cardiovascular and infectious mortality, and of peritonitis. Conclusions: Baseline PPE represents a strong independent marker of survival of PD patients. Estimation of PPE during PET is more accurate than 24-hour PPE for this purpose, sustains a definite independent association with cardiovascular and infectious mortality, and shows a significant correlation with the risk of peritonitis

Efecto de la modalidad de diálisis y otros factores de prescripción sobre las pérdidas proteicas peritoneales en diálisis peritoneal

[Abstract] Background: There is a deficit of information regarding the factors that influence peritoneal protein excretion (PPE) during PD therapy. In particular, the effects of the modality of PD and other conditions of the dialysis prescription remain unclear. Method: This prospective, observational study analysed the effects of prescription characteristics on 24-hour PPE (study variable) in a cohort of patients starting PD. Our statistical analysis included a multi-level mixed model and standardised estimations of peritoneal protein transport during serial four-hour peritoneal equilibrium tests in order to control for disparities in the characteristics of patients managed on different regimens. Results: We evaluated 284 patients, 197 on CAPD and 87 on automated PD (APD), at the start of PD treatment. The two groups differed in terms of clinical characteristics and peritoneal function. Univariate, serial estimates of 24-hour PPE were marginally higher in CAPD patients, and remained essentially stable over time in both groups. Multivariate analyses identified CAPD (B=888.5mg, 95% CI: 327.5/1448.6), total dialysate volume infused per day (B=275.9 mg/Ll; 153.9/397.9) and ultrafiltration (B=0.41 mg/mL; 0.02/0.80) as independent predictors of 24-hour PPE. The model also revealed a minor trend for a lower 24-hour PPE as time on PD increases. Conclusions: The individual characteristics of peritoneal protein transport are the major determinants of 24-hour PPE. The use of CAPD as the dialysis modality is associated with higher PPE rates than the APD technique, although this difference is counterbalanced by a direct correlation between PPE and the volume of dialysate infused per day. Ultrafiltration and time on dialysis also act as minor independent predictors of PPE during PD therapy.[Resumen] Antecedentes: Existe información insuficiente sobre los factores que influyen en las pérdidas proteicas peritoneales (PPP) durante el tratamiento con diálisis peritoneal (DP). En particular, se desconoce el efecto que la modalidad de DP y otras condiciones de prescripción pueden tener sobre esta variable. Método: Siguiendo un diseño prospectivo y observacional, analizamos el efecto de las condiciones de prescripción de DP sobre las PPP en 24 horas (variable principal) en una cohorte de pacientes incidentes en DP. La estrategia de análisis incluyó análisis estadístico mediante modelos mixtos multinivel y estimaciones estandarizadas del transporte proteico peritoneal durante pruebas de equilibrio peritoneal seriadas, con el fin de ajustar para desigualdades en las características de las poblaciones manejadas con diferentes pautas de prescripción. Resultados: Estudiamos 284 pacientes, 197 en DP continua ambulatoria (DPCA) y 87 en DP automática (DPA) al inicio de seguimiento. Ambos grupos mostraron diferencias significativas en sus características clínicas y de función peritoneal. Las estimaciones seriadas de las PP de 24 horas mostraron valores marginalmente más altos en DPCA, permaneciendo esencialmente estables durante el seguimiento. El análisis multivariante identificó a la DPCA (B = 888,5 mg, intervalo de confianza 95%: 327,5/1448,6), el volumen total de dializado infundido (B = 275,9 mg/l, 153,9/397,9) y la ultrafiltración diaria (B = 0,41 mg/ml, 0,02/0,80) como predictores independientes de las PPP de 24 horas. El modelo también mostró tendencia a disminución en las PPP con el tiempo en DP. Conclusiones: Las características individuales de transporte peritoneal de proteínas son el principal determinante de las PPP en 24 horas. La pauta de cambios largos (DPCA) asocia mayores PPP que la de cambios cortos (DPA), aunque esta diferencia se compensa en la práctica por la correlación positiva entre PPP y volumen infundido. Ultrafiltración y tiempo en diálisis son predictores secundarios de PPP en 24 horas

Low serum levels of vitamin D are associated with progression of subclinical atherosclerotic vascular disease in peritoneal dialysis patients: a prospective, multicenter study

[Abstract] 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

[Abstract] 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 111.1 ng/mL), with PD (25.9 ng/mL) or haemodialysis (61.4 ng/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 39.4 ng/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/min, 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.[Resumen] 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 111,1 ng/mL), en DP (25,9 ng/mL) o hemodiálisis (61,4 ng/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 39,4 ng/mL; p = 0,002) o ERCA (24,4 ng/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.Instituto de Salud Carlos III; PI10/00088Instituto de Salud Carlos III; PI13/00322Xunta de Galicia; IN845B-2010/187Xunta de Galicia; 10CSA916014PRXunta de Galciia; CN2012/31

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

[Abstract] 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.Instituto de Salud Carlos III; PI15/02218Instituto de Salud Carlos III; PI18/01803Instituto de Salud Carlos III; AGRUP2015/05Instituto de Salud Carlos III; AGRUP2018/0