Getting the right patient on the right renal replacement therapy

[Abstract] Adequate selection of the modality of renal replacement therapy (RRT), ideally based on well-planned predialysis care, informed decision by the patient and timely initiation of dialysis, is essential to optimize the outcome of patients with chronic kidney disease. However, there are important practical limitations to the success of this process. A major consequence is the underutilization of home-based dialysis therapies, including peritoneal dialysis (PD). A wide array of medical and social factors have been invoked as contraindications to PD, but well-designed studies have shown that most patients (probably >70%) starting dialysis are suitable for this technique. PD is feasible and may be preferred by a significant proportion of patients in many claimed unfavorable settings. The practicing nephrologist should be able to: disclose which are insurmountable barriers to PD, clarify the significance of relative contraindications in individual cases, and identify favorable and unfavorable settings for home dialysis. These abilities will permit quality education, justified advice, well-targeted informed decision and, predictably, successful selection of the modality of RRT. This article provides some clues to approach these issues in three different settings: planned start of RRT after predialysis care, unplanned start of dialysis and programmed changes of modality during follow-up

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

Identification of targets for prevention of peritoneal catheter tunnel and exit-site infections in low incidence settings

[Abstract] ♦ Background: Peritoneal catheter tunnel and exit-site infection (TESI) complicates the clinical course of peritoneal dialysis (PD) patients. Adherence to recommendations for catheter insertion, exit-site care, and management of Staphylococcus aureus (SAu) carriage reduces, but does not abrogate the risk of these infections. ♦ Objective: To reappraise the risk profile for TESI in an experienced center with a long-term focus on management of SAu carriage and a low incidence of these infections. ♦ Method: Following a retrospective, observational design, we investigated 665 patients incident on PD. The main study variable was survival to the first episode of TESI. We considered selected demographic, clinical, and technical variables, applying multivariate strategies of analysis. ♦ Main results: The overall incidence of TESI was 1 episode/68.5 patient-months. Staphylococcus aureus carriage disclosed at inception of PD (but not if observed sporadically during follow-up) (hazard ratio [HR] 1.53, p = 0.009), PD started shortly after catheter insertion (HR 0.98 per day, p = 0.011), PD after kidney transplant failure (HR 2.18, p = 0.017), lower hemoglobin levels (HR 0.88 per g/dL, p = 0.013) and fast peritoneal transport rates (HR 2.92, p = 0.03) portended an increased risk of TESI. Delaying PD ≥ 30 days after catheter insertion markedly improved the probability of TESI. Carriage of methicillin-resistant SAu since the start of PD was associated with a high incidence of TESI by these bacteria. On the contrary, resistance to mupirocin did not predict such a risk, probably due to the use of an alternative regime in affected patients. ♦ Conclusions: Adherence to current recommendations results in a low incidence of TESI in PD patients. Interventions on specific risk subsets have a potential to bring incidence close to negligible levels. Despite systematic screening and management, SAu carriage is still a predictor of TESI. Antibiotic susceptibility patterns may help to refine stratification of the risk of TESI by these bacteria. Early insertion of the peritoneal catheter should be considered whenever possible, to reduce the risk of later TESI

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

Analysis of ultrafiltration failure diagnosed at the initiation of peritoneal dialysis with the help of peritoneal equilibration tests with complete drainage at sixty minutes: a longitudinal study

[Abstract] Background: Ultrafiltration failure (UFF) diagnosed at the initiation of peritoneal dialysis (PD) has been insufficiently characterized. In particular, few longitudinal studies have analyzed the time course of water transport in patients with this complication. ♦ Objective: To investigate the time course of peritoneal water transport during the first year on PD in patients presenting UFF since the initiation of this therapy (study group). ♦ Method: Prospective, observational, single-center design. We analyzed, at baseline and after 1 year of follow-up, peritoneal water transport in 19 patients incident on PD with UFF. We used incident patients without UFF as a control group. Water transport was characterized with the help of 3.86/4.25% dextrose-based peritoneal equilibration tests (PETs) with complete drainage at 60 minutes. ♦ Results: The study group revealed a disorder of water transport affecting both small-pore ultrafiltration (SPUF) (p = 0.054 vs incident without UFF) and free water transport (FWT) (p = 0.001). After 1 year of follow-up, FWT displayed a general increasing trend in the study group (mean variation 48.9 mL, 95% confidence interval [CI] 15.5, 82.2, p = 0.012), while the behavior of SPUF was less predictable (-4.8 mL, 95% CI -61.4, 71.1, p = 0.85). These changes were not observed in incident patients without UFF. Neither initial clinical characteristics, baseline PET-derived parameters, or suffering peritoneal infections during the first year predicted the time course of the capacity of UF in the study group. Recovery from incident UFF was apparently linked to improvement of SPUF. ♦ Conclusions: Patients with UFF at the start of PD suffer a disorder of peritoneal water transport affecting both FWT and SPUF. Free water transport increases systematically in these patients after 1 year of follow-up. The evolution of SPUF is less predictable, and improvement of this parameter marks reversibility of this complication

Inhibition of gastric acid secretion by H2 receptor antagonists associates a definite risk of enteric peritonitis and infectious mortality in patients treated with peritoneal dialysis

[Abstract] Background. Evidences linking treatment with inhibitors of gastric acid secretion (IGAS) and an increased risk of serious infections are inconclusive, both in the population at large and in the particular case of patients with chronic kidney disease. We have undertaken an investigation to disclose associations between treatment with IGAS and infectious outcomes, in patients undergoing chronic Peritoneal Dialysis (PD). Method. Observational, historic cohort, single center design. Six hundred and ninety-one patients incident on PD were scrutinized for an association among treatment with IGAS (H2 antagonists H2A or proton pump inhibitors PPI) (main study variable), on one side, and the risks of enteric peritoneal infection (main outcome), overall peritoneal infection, and general and infectious mortality (secondary outcomes). We applied a three-step multivariate approach, based on classic Cox models (baseline variables), time-dependent analyses and, when appropriate, competing risk analyses. Main results. The clinical characteristics of patients treated with H2A, PPI or none of these were significantly different. Multivariate analyses disclosed a consistently increased risk of enteric peritonitis in patients treated with IGAS (RR 1.65, 95% CI 1.08–2.55, p = 0.018, Cox). Stratified analysis indicated that patients treated with H2A, rather than those on PPI, supported the burden of this risk. Similar findings applied for the risk of infectious mortality. On the contrary, we were not able to detect any association among the study variables, on one side, and the general risks of peritonitis or mortality, on the other. Conclusions. Treatment with IGAS associates increased incidences of enteric peritonitis and infectious mortality, among patients on chronic PD. The association is clear in the case of H2A but less consistent in the case of PPI. Our results support the convenience of preferring PPI to H2A, for gastric acid inhibition in PD patients

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

Peritoneal total protein transport assessed from peritoneal equilibration tests using different dialysate glucose concentrations

Randomized controlled trial[Abstract] Background: The peritoneal equilibration test (PET) permits assessment of peritoneal protein transport, but this potential marker of outcome in peritoneal dialysis (PD) patients lacks adequate standardization. ♢ Objectives: To assess various approaches for estimation of peritoneal protein transport in PD patients during 2.27% and 3.86% glucose-based PETs, and to uncover the demographic, clinical, and biochemical correlates of this phenomenon. ♢ Patients and methods: We studied 90 PD patients who underwent 2.27% and 3.86% PETs in random order, and we used multivariate analysis to compare assessments of peritoneal protein transport in both tests, searching for correlations between D₂₄₀' - D₀' protein concentration (PETΔPConc), total peritoneal protein excretion (PET-PPE), or total protein clearance (PET-PC) on the one hand (the main study variables), and PET-derived markers of peritoneal function and selected demographic, clinical, and biochemical variables on the other. ♢ Results: The PETΔPConc was higher during the 2.27% PET (mean: 45.2 mg/dL vs 37.0 mg/dL for the 3.86% test; p = 0.003); the PET-PPE and PET-PC were comparable (1121.8 mg vs 1168.9 mg, p = 0.52, and 17.1 mL vs 17.8 mL, p = 0.66, respectively). All three variables sustained a significant, yet moderate correlation (all r² values < 0.30) with the 24-hour PPE rate. Multivariate analysis identified dialysate-to-plasma ratio (D/P₂₄₀') of creatinine, end-to-initial dialysate ratio (D₂₄₀'/D₀') of glucose, current daily peritoneal glucose load, ultrafiltration during PET, systolic blood pressure, and previous cardiovascular events (3.86% test only) as independent predictors of protein transport during PET. ♢ Conclusions: Either PET-PPE or PET-PC seems preferable to PETΔPConc for characterization of peritoneal protein transport. Small-solute transport characteristics, ultrafiltration, and current peritoneal glucose load sustain independent correlations with peritoneal protein transport. The latter variable shows also a moderate association with markers of cardiovascular disease in PD patients

Effect of low-GDP bicarbonate–lactate-buffered peritoneal dialysis solutions on plasma levels of adipokines and gut appetite-regulatory peptides: a randomized crossover study

This is a pre-cpyedited, author-produced version of an article accepted for publication in "Nephrology Dialysis Transplantation" following peer review. The version of record is avaliable online at Oxford Academic web page.Instituto de Salud Carlos III; PI051024Instituto de Salud Carlos III; PI070413Red de Grupos RGTO; G03/028Red de Grupos RGTO; PI050983Xunta de Galicia; PS07/12Xunta de Galicia; PGIDT05PXIC91605PNXunta de Galicia; INCITE08ENA916110E

Incidence of cardiovascular events after kidney transplantation and cardiovascular risk scores: study protocol

[Abstract] Background: Cardiovascular disease (CVD) is the major cause of death after renal transplantation. Not only conventional CVD risk factors, but also transplant-specific risk factors can influence the development of CVD in kidney transplant recipients. The main objective of this study will be to determine the incidence of post-transplant CVD after renal transplantation and related factors. A secondary objective will be to examine the ability of standard cardiovascular risk scores (Framingham, REGICOR, SCORE, and DORICA) to predict post-transplantation cardiovascular events in renal transplant recipients, and to develop a new score for predicting the risk of CVD after kidney transplantation. Methods/design: Observational prospective cohort study of all kidney transplant recipients in the A Coruna Hospital (Spain) in the period 1981-2008 (2059 transplants corresponding to 1794 patients). The variables included will be: donor and recipient characteristics, chronic kidney disease-related risk factors, pre-transplant and post-transplant cardiovascular risk factors, routine biochemistry, and immunosuppressive, antihypertensive and lipid-lowering treatment. The events studied in the follow-up will be: patient and graft survival, acute rejection episodes and cardiovascular events (myocardial infarction, invasive coronary artery therapy, cerebral vascular events, new-onset angina, congestive heart failure, rhythm disturbances and peripheral vascular disease). Four cardiovascular risk scores were calculated at the time of transplantation: the Framingham score, the European Systematic Coronary Risk Evaluation (SCORE) equation, and the REGICOR (Registre Gironi del COR (Gerona Heart Registry)), and DORICA (Dyslipidemia, Obesity, and Cardiovascular Risk) functions. The cumulative incidence of cardiovascular events will be analyzed by competing risk survival methods. The clinical relevance of different variables will be calculated using the ARR (Absolute Risk Reduction), RRR (Relative Risk Reduction) and NNT (Number Needed to Treat). The ability of different cardiovascular risk scores to predict cardiovascular events will be analyzed by using the c index and the area under ROC curves. Based on the competing risks analysis, a nomogram to predict the probability of cardiovascular events after kidney transplantation will be developed. Discussion: This study will make it possible to determine the post-transplant incidence of cardiovascular events in a large cohort of renal transplant recipients in Spain, to confirm the relationship between traditional and transplant-specific cardiovascular risk factors and CVD, and to develop a score to predict the risk of CVD in these patients.Instituto de Salud Carlos III; PI070986Xunta de Galicia; PS09/26Insituto de Salud Carlos III; G03/170Instituto de Salud Carlos III; RD06/ 001