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.

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.

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.

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.

Compared decline of residual kidney function in patients treated with automated peritoneal dialysis and continuous ambulatory peritoneal dialysis: a multicenter study.

BACKGROUND: There is controversy concerning the compared rates of decline of residual kidney function (RKF) in patients treated with continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis (APD). OBJECTIVES AND METHOD: Following an observational, multicenter design, we studied 493 patients initiating peritoneal dialysis (PD) in four different Spanish units. We explored the effect of the PD modality on the rate of decline of RKF and the probability of anuria during follow-up. We applied logistic regression for intention-to-treat analyses, and linear mixed models to explore time-dependent variables, excluding those affected by indication bias. MAIN RESULTS: Patients started on APD were younger and less comorbid than those initiated on CAPD. Baseline RKF was similar in both groups (p = 0.50). Eighty-seven patients changed their PD modality during follow-up. The following variables predicted a faster decline of RKF: higher (rate of decline) or lower (anuria) baseline RKF, younger age, proteinuria, nonprimary PD, use of PD solutions rich in glucose degradation products, higher blood pressure, and suffering peritonitis or cardiovascular events during follow-up. Overall, APD was not associated with a fast decline of RKF, but stratified analysis disclosed that patients with lower baseline RKF had an increased risk for this outcome when treated with this technique (HR: 2.26, 95% CI: 1.09-4.82, p = 0.023). Moreover, the probability of anuria during follow-up was overtly higher in APD patients (HR: 3.22, 95% CI: 1.25-6.69, p = 0.002). CONCLUSIONS: Starting PD patients directly on APD is associated with a faster decline of RKF and a higher risk of developing anuria than doing so on CAPD. This detrimental effect is more marked in patients initiating PD with lower levels of RKF.

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.

Influence of peritoneal residual volume on the results of the peritoneal equilibration test. Prospective study.

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 60 min. 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. 449 mL, 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 (>200 mL) 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. CONCLUSIONS: Correction for Vr of the capacity of ultrafiltration during a PET carries, as a mean, a minor impact on the categorization of this parameter. However, the results of the test can be significantly affected in 12,9% of the cases. We have been unable to detect demographic or clinical predictors of Vr, which suggests a random component for the mechanics of single peritoneal exchanges. We suggest that Vr should be estimated at the time of categorizing the capacity of ultrafiltration, whenever inconsistencies during serial PET studies are detected.

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.

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.

Cost analysis of the Spanish renal replacement therapy programme.

BACKGROUND: A cost analysis of the Spanish Renal Replacement Therapy (RRT) programme in the year 2010, for end-stage renal disease (ESRD) patients, was performed from the perspective of the Public Administration. METHODS: The costs associated with each RRT modality [hemodialysis (HD), peritoneal dialysis (PD) and kidney transplantation (Tx)] were analysed. The Spanish ESRD incidence and prevalence figures in the year 2010 were forecasted in order to enable the calculation of an aggregate cost for each modality. Costs were mainly computed based on a review of the existing literature and of the Official Bulletins of the Spanish Autonomous Communities. Data from Oblikue Consulting eSalud health care costs database and from several Spanish public sources were also employed. RESULTS: In the year 2010, the forecasted incidence figures for HD, PD and Tx were 5409, 822 and 2317 patients, respectively. The forecasted prevalence figures were 22,582, 2420 and 24,761 patients, respectively. The average annual per-patient costs (incidence and prevalence) were €2651 and €37,968 (HD), €1808 and €25,826 (PD) and €38,313 and €6283 (Tx). Indirect costs amounted to €8929 (HD), €7429 (PD) and €5483 (Tx). The economic impact of the Spanish RRT programme on the Public Administration budget was estimated at ~€1829 million (indirect costs included): €1327 (HD), €109 (PD) and €393 (Tx) million. CONCLUSIONS: HD accounted for >70% of the aggregate costs of the Spanish RRT programme in 2010. From a costs minimization perspective, it would be preferable if the number of incident and prevalent patients in PD were increased.

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.

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.

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.

Categorization of sodium sieving by 2.27% and 3.86% peritoneal equilibration tests--a comparative analysis in the clinical setting.

BACKGROUND: Analysis of the dialysate sodium concentration during a peritoneal equilibration test (PET) provides information on the rates of water and solute transport through different membrane pathways. A hypertonic (3.86%) glucose-based dialysate may enhance the accuracy of analysis. There are still gaps in our knowledge regarding this question, in the clinical setting. Objective. The aim of this study was to compare the categorization of the sodium sieving effect in peritoneal dialysis (PD) patients by 2.27% and 3.86% PETs, and to disclose clinical correlates of this phenomenon. Method. Ninety PD patients underwent prospectively 2.27% and 3.86% modified (dialysate samples at 0, 60, 90, 120 and 240 min) PETs, in a random order. We searched for differences in the time profiles of sodium sieving and its categorization. We correlated sodium sieving with ultrafiltration (UF) and solute transport capacity, as also with selected clinical and demographic variables, using a multivariate approach. RESULTS: The maximum dip in the dialysate sodium concentration (11.1 mM/L, 3.86% versus 7.1 mM/L, 2.27%, P < 0.001) was most common after 90 min in the 3.86% PET, with the 2.27% test somewhere between 60 and 90 min. Low sodium sieving (defined by a dip <5 mM/L at 60 min) was observed in 8.9% of the patients in the 3.86% test. The same limit categorized 34.4% of the patients as low sieving in the 2.27% test (100.0% sensitivity and 72.0% specificity, using 3.86% as a reference). UF and D/P(240 min) creatinine were independent predictors of the sodium sieving effect in both tests. Moreover, multivariate analysis disclosed a consistent inverse correlation between GFR and sodium sieving in both the 2.27% (B = -0.23, 95% CI -0.40, -0.07, P = 0.006) and 3.86% PET (B = -0.46, 95% CI -0.65, -0.26, P < 0.0005). CONCLUSIONS: The standard 2.27% PET permits some categorization of sodium sieving in PD patients. However, the information provided by this test lacks the discriminatory capacity of the 3.86% PET, which should be considered the one for reference for this purpose. GFR keeps a consistent inverse correlation with the intensity of sodium sieving in both the 2.27% and 3.86% PET.

Treatment of peritoneal dialysis-related peritonitis with ciprofloxacin monotherapy: clinical outcomes and bacterial susceptibility over two decades.

BACKGROUND: There is controversy about the preferred initial antibiotic therapy for peritoneal dialysis (PD)-related peritonitis. Quinolones have been used extensively in this setting, yet their long-term effectiveness is unknown. AIM: To analyze the results of a protocol of treatment of PD-related peritonitis with ciprofloxacin, maintained over two decades. METHOD: We analyzed the clinical outcome of 682 episodes of bacterial peritonitis treated with intraperitoneal ciprofloxacin monotherapy, and the time course of bacterial susceptibility to this antimicrobial, in a historical cohort of 641 PD patients (1988-2007). Main outcome variables included changes to initial therapy and rates of hospital admission, catheter removal, relapse, reinfection, PD dropout, and mortality. For comparisons we divided the study period into phases A (1988-1994), B (1995-2000), and C (2001-2007). RESULTS: The incidence of Staphylococcus aureus peritonitis decreased, while the incidences of polymicrobial and negative-culture peritonitis increased after phase A. In vitro susceptibility to ciprofloxacin decreased significantly only among coagulase-negative staphylococci (87.0% susceptible strains in phase A vs 70.0% in B and 70.1% in C, p = 0.006). Overall success rates (catheter not removed and ongoing PD after the episode) remained stable, at over 85%. However, the proportion of patients treated solely with ciprofloxacin declined from 75.7% (A) to 47.3% (B) to 32.4% (C) (p < 0.0005) and admission rates increased from 12.7% to 16.8% to 24.9% respectively (p = 0.001). These changes affected all the etiologic groups except culture-negative peritonitis. In vitro resistance to ciprofloxacin was a marker of multiresistance and correlated strongly with clinical outcome of peritonitis. Among isolates susceptible to ciprofloxacin, changing initial therapy for any reason also predicted a poor outcome. CONCLUSIONS: Following satisfactory early results, the effectiveness of ciprofloxacin as monotherapy for PD-related peritonitis has declined markedly in the long term. This decline cannot be explained solely by a decrease of in vitro susceptibility to this antimicrobial, which was significant only among coagulase-negative staphylococci. Resistance to ciprofloxacin is a strong marker of in vitro multiresistance and poor clinical outcome of peritonitis.

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.

Short-term regulation of peptide YY secretion by a mixed meal or peritoneal glucose-based dialysate in patients with chronic renal failure.

BACKGROUND: Malnutrition is very prevalent among patients with chronic renal failure. The role of derangements in the gut-brain axis for regulation of appetite in the genesis of anorexia of these patients has not been adequately investigated. Design. Following a randomized, crossover design, we analysed plasma levels of peptide YY (PYY)(1-36) and PYY(3-36) both fasting and after a standardized oral mixed meal or intraperitoneal glucose infusion in 10 stable uraemic patients undergoing peritoneal dialysis and 8 healthy controls, matched for age, gender and body mass index. Main results. Median baseline plasma levels of PYY(1-36) in the different provocation tests oscillated between 406 and 460 pg/mL in patients, as compared with 73 and 100 pg/mL in controls (P < 0.001). Corresponding values for PYY(3-36) oscillated between 235 and 267 pg/mL in patients, versus 56 and 70 pg/mL in controls (P < 0.001). The association of high levels of PYY(3-36) and normal levels of acylated ghrelin (when compared with healthy controls) configurated a markedly pro-anorexigenic pattern in patients. Neither oral intake nor intraperitoneal glucose resulted in significant changes in plasma levels of PYY(1-36) or PYY(3-36) in subjects with renal failure, in contrast with the expected postprandial rise observed in healthy controls (41% for PYY(1-36), P = 0.04 and 32% for PYY(3-36), P = 0.02, median values). CONCLUSIONS: Baseline plasma levels of PYY(1-36) or PYY(3-36) are markedly elevated in patients with renal failure undergoing peritoneal dialysis. Provocation studies disclose a marked disregulation in the postprandial secretion of these anorexigenic peptides, when compared with healthy controls. These findings may contribute to clarify the complex pathogenesis of anorexia of chronic renal failure.

Icodextrin does not impact infectious and culture-negative peritonitis rates in peritoneal dialysis patients: a 2-year multicentre, comparative, prospective cohort study.

BACKGROUND: Icodextrin is a glucose polymer derived by hydrolysis of cornstarch. The different biocompatibility profile of icodextrin-containing peritoneal dialysis (PD) solutions may have a positive influence on peritoneal host defence. Furthermore, cases of sterile peritonitis potentially associated with icodextrin have been reported. METHODS: The primary objective of this multicentre, longitudinal, observational, non-interventional, prospective cohort study, which included 722 PD patients, was to evaluate the incidence of overall peritonitis in patients treated with icodextrin-containing PD solutions (Extraneal) used during one long-dwell exchange/day compared with those treated with non-icodextrin-containing PD solutions. The secondary objective was to determine if culture-negative peritonitis rates differed between patients treated with icodextrin from two independent manufacturers. All peritonitis episodes were assessed by a Steering Committee in a blind manner. RESULTS: There was no significant difference between icodextrin-treated and control patients in the adjusted overall, culture-positive or culture-negative peritonitis rates. When stratified by the icodextrin supplier, there was no significant difference in the adjusted rate of culture-negative peritonitis episodes between groups. CONCLUSION: Subjects receiving icodextrin as part of their PD regimen experienced neither a higher rate of culture-negative peritonitis nor a lower rate of infectious peritonitis compared with non-icodextrin users. There was no significant influence of the icodextrin raw material supplier on peritonitis rates.

PYY(1-36) and PYY(3-36) secretory response after a mixed meal in healthy individuals.

BACKGROUND: Peptide YY (PYY) is a 36 amino acid peptide synthesized mostly by intestinal L cells. This peptide reaches its nadir during fasting and increases immediately after meals. After food intake, two molecular forms are released, PYY(1-36) and PYY(3-36). PYY(3-36) reduces food intake in both humans and rodents. There is scarce information about plasmatic concentrations of PYY, especially of PYY(3-36), after food ingestion, and their relationship to ghrelin. OBJECTIVES: To study PYY(1-36) and PYY(3-36) secretory response after a mixed meal, and its relationship to total and acylated ghrelin secretion in healthy subjects. SUBJECTS AND METHOD: We studied eight healthy subjects, 4 women and 4 men, with a median age of 53 (range, 36-59) years. After an overnight fast, the subjects received either a mixed standard meal (400ml Isosource Energy® [159kcal/100ml]) or placebo (400ml of water) orally in random order on two different days. Blood samples were obtained at 0, 30, 45, 60 and 120 min for measurement of PYY(1-36), PYY(3-36), total ghrelin and acylated ghrelin. Comparisons were made by Wilcoxon's test. Numerical correlations were performed using Spearman's test. P-values ≤ 0.05 were considered significant. RESULTS: After a mixed meal, PYY(1-36) reached a peak of (median [range]) 141.5 (81-198) pg/ml. There was no response to placebo, with a peak of 92.5 (46-219) pg/ml (p=0.04). The area under the curve (AUC) of PYY(1-36) levels after a mixed meal were 14,865 (8,032-19,822) pg/ml/min and after placebo were 8,992 (4,455-21,382) pg/ml/min (p=0.06). After ingestion of a mixed meal, PYY(3-36) reached a peak of 92.5 (59-135) pg/ml, with no response to placebo (46.5 [30-66] pg/ml) (p = 0.02). The AUC of PYY(3-36) levels after a mixed meal were 9,086 (6,412-14,970) pg/ml/min, and after placebo were 4,984 (3,142-6,772) pg/ml/min (p=0.012). The quotient between nadir total ghrelin/peak PYY(1-36) was markedly diminished after food ingestion, with preprandial values of 7.44 (3.64-14.56) and postprandial values of 3.55 (1.64-7.16) (p=0.03). The former quotient was unmodified by placebo. The quotient between nadir acylated ghrelin/peak PYY(3-36) was markedly diminished after ingestion of a mixed meal, with preprandial values of 2.03 (0.92-3) and postprandial values of 0.73 (0.26-1.27) (p=0.02). This quotient was unmodified by placebo. CONCLUSIONS: In healthy subjects, blood levels of both PYY(1-36) and PYY(3-36) increase after ingestion of a mixed meal. Simultaneously, total and acylated ghrelin levels diminish. The quotient between nadir acylated ghrelin/peak PYY(3-36) diminishes after a mixed meal. All these data suggest the possible contribution of these peptides to appetite regulation after ingestion.

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.