Association of urinary excretion rates of uric acid with biomarkers of kidney injury in patients with advanced chronic kidney disease.

BACKGROUND: The potential influence of hyperuricemia on the genesis and progression of chronic kidney disease (CKD) remains controversial. In general, the correlation between blood levels of uric acid (UA) and the rate of progression of CKD is considered to be modest, if any, and the results of relevant trials oriented to disclose the effect of urate-lowering therapies on this outcome have been disappointing. Urinary excretion rates of UA could reflect more accurately the potential consequences of urate-related kidney injury. METHOD: Using a cross-sectional design, we investigated the correlation between different estimators of the rates of urinary excretion of UA (total 24-hour excretion, mean urinary concentration, renal clearance and fractional excretion)(main study variables), on one side, and urinary levels of selected biomarkers of kidney injury and CKD progression (DKK3, KIM1, NGAL, interleukin 1b and MCP)(main outcome variables), in 120 patients with advanced CKD (mean glomerular filtration rate 21.5 mL/minute). We took into consideration essential demographic, clinical and analytic variables with a potential confounding effect on the explored correlations (control variables). Spearman's rho correlation and nonlinear generalized additive regression models (GAM) with p-splines smoothers were used for statistical analysis. MAIN RESULTS: Multivariate analysis disclosed independent correlations between urinary UA concentrations, clearances and fractional excretion rates (but not plasma UA or total 24-hour excretion rates of UA), on one side, and the scrutinized markers. These correlations were more consistent for DKK3 and NGAL than for the other biomarkers. Glomerular filtration rate, proteinuria and treatment with statins or RAA axis antagonists were other independent correlates of the main outcome variables. CONCLUSIONS: Our results support the hypothesis that urinary excretion rates of UA may represent a more accurate marker of UA-related kidney injury than plasma levels of this metabolite, in patients with advanced stages of CKD. Further, longitudinal studies will be necessary, to disclose the clinical significance of these findings.

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.

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.

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.

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.

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

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.

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.

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.

Identification of Targets for Prevention of Peritoneal Catheter Tunnel and Exit-Site Infections in Low Incidence Settings.

UNLABELLED: ♦ 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.

Clinical evolution of chronic renal patients with HIV infection in replacement therapy.

Patients on renal replacement therapy (RRT) infected with the human immunodeficiency virus (HIV) are a special group with growing interest. In order to study the epidemiological data of HIV+ patients on RRT in Spain, we collected individual information from 2004-2011 (period of use of highly active antiretroviral therapy [HAART] in the Autonomous Communities of Andalusia, Aragon, Asturias, Catalonia, Valencia, Castilla la Mancha, Castilla León, Galicia, Madrid, La Rioja and the Basque Country, comprising 85% of the Spanish population. A total of 271 incident and 209 prevalent patients were analysed. They were compared with the remaining patients on RRT during the same period. The annual incidence was 0.8 patients per one million inhabitants, with a significant increase during the follow-up period. The proportion of prevalent HIV+ patients was 5.1 per 1,000 patients on RRT (95% confidence interval [CI] 4.4-5.8. Although glomerular diseases constituted the majority of cases (42%), diabetic nephropathy was the cause in 14% of patients. The nation-wide totals for these percentages were 13 and 25%, respectively. Compared to the total of patients in treatment, the risk of death was significantly higher in the HIV+ group: hazard ratio (HR) adjusted for age, sex and diabetes was 2.26 (95% CI 1.74 - 2.91). Hepatitis C coinfection increased the risk of death in the HIV+ group (HR 1.77; 95% CI 1.10 - 2.85). The probability of kidney transplantation in HIV+ was only 17% after 7 years, comparing with total RTT patients (HR 0.15; 95% CI: 0.10-0.24). Despite the use of HAART, the incidence of HIV+ patients on dialysis has increased; their mortality still exceeds non-HIV patients, and they have a very low rate of transplantation. It is necessary to further our knowledge of this disease in order to improve results.

Correlation between glycemic control and the incidence of peritoneal and catheter tunnel and exit-site infections in diabetic patients undergoing peritoneal dialysis.

BACKGROUND: Diabetes mellitus, especially if complicated by poor glycemic control, portends an increased risk of infection. The significance of this association in the case of diabetic patients undergoing peritoneal dialysis (PD) has not been assessed. METHODS: Using a retrospective observational design, we analyzed the association between glycemic control at the start of PD (estimated from glycosylated hemoglobin levels) and the risk of peritoneal and catheter tunnel and exit-site infections during follow-up in 183 incident patients on PD. We used the median value of glycosylated hemoglobin to classify patients into good (group A) or poor (group B) glycemic control groups. We applied multivariate strategies of analysis to control for other potential predictors of PD-related infection. RESULTS: Groups A and B differed significantly in age, dialysis vintage, use of insulin, and rate of Staphylococcus aureus carriage. Neither the incidence (0.60 episodes in group A vs 0.56 episodes in group B per patient-year) nor the time to a first peritoneal infection (median: 42 months vs 38 months) differed significantly between the study groups. In contrast, group B had a significantly higher incidence of catheter tunnel and exit-site infections (0.23 episodes vs 0.12 episodes per patient-year) and shorter time to a first infection episode (64 months vs 76 months, p = 0.004). The difference persisted in multivariate analysis (adjusted hazard ratio: 2.65; 95% confidence interval: 1.13 to 6.05; p = 0.013). We observed no differences between the study groups in the spectrum of causative organisms or in the outcomes of PD-related infections. CONCLUSIONS: Poor glycemic control is a consistent predictor of subsequent risk of catheter tunnel and exit-site infection, but not of peritoneal infection, among diabetic patients starting PD therapy.

Effect of dialysis modality and other prescription factors on peritoneal protein excretion in peritoneal dialysis.

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.

Getting the right patient on the right renal replacement therapy.

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.

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

BACKGROUND: Malnutrition is common in patients treated with peritoneal dialysis (PD). Previous studies have disclosed disturbances in the hormonal axes regulating appetite in these patients. The effect of newer biocompatible PD solutions on these disorders is undetermined. METHODS: Using a crossover randomized design, 21 patients stable on PD underwent 5 weeks of therapy with each of classic glucose degradation product (GDP)-rich lactate-buffered PD solutions (L) and newer low-GDP bicarbonate-lactate-buffered PD solutions (BL). At the end of each phase, we scrutinized patients for adequacy markers, peritoneal transport (peritoneal equilibration test with 3.86% glucose-based solutions), general biochemical markers and, more specifically, cytokines, adipokines (leptin and adiponectin) and selected gastrointestinal peptides which regulate appetite in the short term [ghrelin, peptide YY, cholecystokinin, glucagon-like peptide 1 (GLP1)]. For plasma GLP1 levels, we analysed a group of healthy, sex-, age- and body mass index-matched controls. RESULTS: Use of BL solutions was associated with higher plasma levels of acylated (but not total) ghrelin (median 243 BL versus 141 pg/mL L, P = 0.05), adiponectin (median 20.2 BL versus 17.6 mcg/mL L, P = 0.008) and growth hormone (median 1.8 BL versus 1.0 ng/mL L, P = 0.013), without significant differences for the other cytokines, leptin or gut peptides scrutinized. We did not observe significant differences between L and BL solutions concerning estimations of adequacy, peritoneal transport or general biochemical markers. CONCLUSIONS: Use of GDP-free, neutral-pH, bicarbonate-lactate-buffered PD solutions is associated with higher plasma levels of acylated ghrelin and adiponectin than classic solutions. These findings may contribute to explaining improved appetite scores and overall survival rates reported with the use of so-called biocompatible PD solutions.

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

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/P(240') creatinine) and cardiovascular comorbidity. PET-PPE (p < 0.0005, model global χ(2) 59.4) was a more accurate predictor of overall mortality than 24-hour PPE (p = 0.04, χ(2) 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.

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

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.

Use of icodextrin during nocturnal automated peritoneal dialysis allows sustained ultrafiltration while reducing the peritoneal glucose load: a randomized crossover study.

BACKGROUND: Optimization of ultrafiltration and preservation of the peritoneal membrane are desirable objectives in peritoneal dialysis (PD) patients. Mixtures of glucose- and non-glucose-based solutions may help to meet both targets simultaneously. AIM: To analyze the effects, in terms of ultrafiltration and peritoneal glucose load, of including icodextrin-based dialysate in the nocturnal schedule of patients undergoing automated PD (APD). METHOD: Following a randomized crossover design, 17 APD patients underwent two 10-day study periods under identical prescription (including amino acid-based solution for the night schedule), except for the substitution of 2 L glucose-based dialysate in the nocturnal mixture (control) by a similar amount of icodextrin-based dialysate (icodextrin phase) in one period. Dependent variables included ultrafiltration, sodium removal, peritoneal glucose load, and residual renal function. We measured serum and urine levels of icodextrin metabolites at the end of each phase. RESULTS: Ultrafiltration was marginally higher during the icodextrin phase (median 815 vs 763 mL/day, p = 0.07), while peritoneal sodium removal was similar in both phases (74 vs 71 mmol/L/day). Peritoneal glucose load (median 67.5 vs 104.0 g/day, p < 0.005) and absorption (14.0 vs 35.6 g/day, p < 0.005) were lower during the icodextrin phase. Diuresis was also modestly lower during the icodextrin phase (500 vs 600 mL/day, p < 0.05). Serum levels of icodextrin metabolites were moderately higher in the icodextrin phase (p < 0.005) in patients both on and off diurnal icodextrin. CONCLUSION: Inclusion of amino acid- and icodextrin-based solutions in the nocturnal schedule of APD patients may allow sustained ultrafiltration and sodium removal while significantly reducing the peritoneal glucose load in these patients.

Serum levels of anti-alphaGalactosyl antibodies predict survival and peritoneal dialysis-related enteric peritonitis rates in patients undergoing renal replacement therapy.

BACKGROUND: Anti-Galalpha1-3Gal antibodies (anti-alphaGal) represent a significant fraction of natural antibodies and were implicated in several disease states, yet their origin and physiological significance remain largely undisclosed. METHODS: Under a prospective observational design, we estimated anti-alphaGal immunoglobulin G (IgG)/IgM and antipig hemolytic antibody (APA) levels in 133 patients starting dialysis therapy and again after a 1-year follow-up. We used baseline data to show correlations with demographic, nutritional, inflammatory, and anemia markers and analyzed their correlation with outcomes by using univariate and multivariate strategies of survival analysis. RESULTS: Serum anti-alphaGal and APA levels showed wide baseline variability, but remained relatively stable in time. Both were measurable in dialysate of peritoneal dialysis (PD) patients, showing close correlation to serum levels. We observed no association between levels of anti-alphaGal/APA and nutritional markers, but showed direct correlations of anti-alphaGal IgM (P = 0.005) and APA levels (P = 0.001) with tumor necrosis factor alpha (TNF-alpha) levels. High APA levels also were associated with severe anemia (P = 0.006). High baseline anti-alphaGal IgM (P = 0.03) and APA levels (P = 0.045) predicted later risk for enteric peritonitis in PD patients. Finally, univariate and multivariate analyses showed a consistent association between high baseline anti-alphaGal IgM (P = 0.014) and APA (P = 0.021) levels and global risk for mortality during follow-up. CONCLUSION: Anti-alphaGal IgM and APA levels at the start of dialysis therapy are significant predictors of later risk for mortality and, in PD patients, enteric peritonitis. Both correlate directly with TNF-alpha levels and, in the case of APA, severity of anemia in these patients.

Incidence and clinical significance of nasal and pericatheter colonization by Gram-negative bacteria among patients undergoing chronic peritoneal dialysis.

BACKGROUND: Nasal and pericatheter colonization by Staphylococcus aureus portends an increased risk of peritonitis and exit-site infection for peritoneal dialysis (PD) patients. The aim of the present study was to examine the incidence of colonization by other peritoneal pathogens, and more specifically by Gram-negative bacteria (GNB), among PD patients, and to disclose its potential correlation with PD-related infections. METHOD: Over a 3-year period, we prospectively screened 152 PD patients and 99 partners every other month for nasal and pericatheter bacterial colonization (total follow-up for patients 3182 months). We performed 1089 studies in patients and 561 in partners. RESULTS: Although S. aureus and coagulase-negative Staphylococcus spp. predominated both in patients and partners, we recovered GNB from 15.8% (nares) and 22.4% (pericatheter) of the patients and from 29.3% of the partners. Most isolations of GNB were transient and only 7.2% of the patients and 7.1% of the partners had the same GNB isolated in at least two controls from the same sampling site. Older age, male gender, longer follow-up on PD, previous immunosuppressive therapy, low socioeconomic conditions, and a high global incidence of peritonitis were predictive of colonization by GNB. Previous pericatheter mupirocin therapy was also associated with later colonization by GNB. Nasal or pericatheter colonization by bacteria other than S. aureus, particularly GNB, had a poor predictive power for PD-related infections. CONCLUSION: Nasal and pericatheter bacterial colonization is protean in PD patients and their partners, and includes the significant presence of potentially pathogenic GNB. Colonization by GNB was not clearly associated with an increased risk of peritonitis or exit-site infection in these patients.