Anabela Rodrigues

Evaluation of peritoneal transport and membrane status in peritoneal dialysis: focus on incident fast transporters.

Background/Aim: The determinants of baseline fast solute transport are still unclear. We prospectively investigated the relationship of peritoneal solute transport with markers of inflammation, angiogenesis, and membrane status, with a focus on fast transporters. Methods: Seventy-one incident peritoneal dialysis patients were assessed with baseline and annual peritoneal equilibration tests, using a 3.86% glucose dialysis solution. Residual renal function and markers of inflammation, including systemic and intraperitoneal interleukin-6 (IL-6), effluent cancer antigen 125 (CA-125), and vascular endothelial growth factor (VEGF) appearance rates (ARs), were investigated. The time course of the dialysate-to-plasma ratio of creatinine (D/P creatinine ratio) and its relationship with the biomarkers were investigated by a mixed linear model. Results: Incident fast/fast average transporters had a similar age, diabetes prevalence, and serum and effluent IL-6 levels, but significantly higher levels of CA-125 and VEGF ARs than the slow/slow average group; the D/P creatinine ratio was not correlated with systemic IL-6, but was correlated with effluent CA-125 AR (r = 0.45, p < 0.0001) and VEGF AR (r = 0.52, p < 0.0001). The D/P creatinine ratio decreased with a U-shaped profile (p = 0.02). Intraperitoneal IL-6 was the significant and positive determinant of the time course of the D/P creatinine ratio (p < 0.0001). Effluent CA-125 decreased with time on peritoneal dialysis (p = 0.013). Conclusions: Baseline peritoneal fast transport was not associated with systemic inflammation, but was related to peritoneal locally produced substances able to mediate transitory hyperpermeability. The D/P creatinine ratio changed during the follow-up period with a U-shaped profile. This was associated with effluent IL-6 and partly with VEGF. CA-125 decreased throughout the follow-up period.

Peritoneal Membrane Phosphate Transport Status: A Cornerstone in Phosphate Handling in Peritoneal Dialysis

BACKGROUND AND OBJECTIVES Phosphate control impacts dialysis outcomes. Our aim was to define peritoneal phosphate transport in peritoneal dialysis (PD) and to explore its association with hyperphosphatemia, phosphate clearance (PPhCl), and PD modality. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Two hundred sixty-four patients (61% on continuous ambulatory PD [CAPD]) were evaluated at month 12. PPhCl was calculated from 24-hour peritoneal effluent. Phosphate (Ph) and creatinine (Cr) dialysate/plasma (D/P) were calculated at a 4-hour 3.86% peritoneal equilibration test. RESULTS D/PPh correlated with D/PCr. PPhCl correlated better with D/PPh than with D/PCr. Prevalence of hyperphosphatemia (>5.5 mg/dl) was 30%. In a multiple regression analysis, only residual renal function was independently, negatively associated with hyperphosphatemia; in anuric patients, only D/PPh was an independent factor predicting hyperphosphatemia. D/PPh was 0.57 ± 0.10, and according to this, 16% of the patients were fast, 31% were fast-average, 35% were slow-average, and 17% were slow transporters. PPhCl was 37.5 ± 11.7 L/wk; it was lower in the slow transporter group (31 ± 14 L/wk). Among fast and fast-average transporters, PPhCl was comparable in both PD modalities. In comparison to automated PD, CAPD was associated with increased PPhCl among slow-average (36 ± 8 versus 32 ± 7 L/wk) and slow transporters (34 ± 15 versus 24 ± 9 L/wk). CONCLUSIONS In hyperphosphatemic, particularly anuric, patients, optimal PD modality should consider peritoneal phosphate transport characteristics. Increasing dwell times and transfer to CAPD are effective strategies to improve phosphate handling in patients with inadequate phosphate control on automated PD.

Deciphering the Contribution of Biofilm to the Pathogenesis of Peritoneal Dialysis Infections: Characterization and Microbial Behaviour on Dialysis Fluids

Infections are major complications in peritoneal dialysis (PD) with a multifactorial etiology that comprises patient, microbial and dialytic factors. This study aimed at investigating the contribution of microbial biofilms on PD catheters to recalcitrant infections and their interplay with PD related-factors. A prospective observational study was performed on 47 patients attending Centro Hospitalar of Porto and Vila Nova de Gaia/Espinho to whom the catheter was removed due to infectious (n = 16) and non-infectious causes (n = 31). Microbial density on the catheter was assessed by culture methods and the isolated microorganisms identified by matrix-assisted laser desorption/ionization time-of-flight intact cell mass spectrometry. The effect of conventional and three biocompatible PD solutions on 16 Coagulase Negative Staphylococci (CNS) and 10 Pseudomonas aeruginosa strains planktonic growth and biofilm formation was evaluated. Cultures were positive in 87.5% of the catheters removed due infectious and 90.3% removed due to non-infectious causes. However, microbial yields were higher on the cuffs of catheters removed due to infection vs. non-infection. Staphylococci (CNS and Staphylococcus aureus) and P. aeruginosa were the predominant species: 32% and 20% in the infection and 43.3% and 22.7% in the non-infection group, respectively. In general, PD solutions had a detrimental effect on planktonic CNS and P. aeruginosa strains growth. All strains formed biofilms in the presence of PD solutions. The solutions had a more detrimental effect on P. aeruginosa than CNS strains. No major differences were observed between conventional and biocompatible solutions, although in icodextrin solution biofilm biomass was lower than in bicarbonate/lactate solution. Overall, we show that microbial biofilm is universal in PD catheters with the subclinical menace of Staphylococci and P. aeruginosa. Cuffs colonization may significantly contribute to infection. PD solutions differentially impact microbial species. This knowledge is important for the development of infection diagnosis, treatment and preventive strategies.

Temporal trends in peritonitis rates, microbiology and outcomes: the major clinical complication of peritoneal dialysis.

Peritonitis remains a common complication of peritoneal dialysis (PD). The aim of this study was to analyze, in a PD center, long-term temporal trends in peritonitis rates, microbiology and outcomes. We treated 588 cases of peritonitis that occurred during 11,833.6 months at risk. Y-set and twin-bag disconnecting systems were introduced in 1990, mupirocin at the exit site in 2000 and fluconazole prophylaxis in 2005. Vancomycin and ceftazidime were the empiric protocol. Global and 5-year cohort rates were expressed as episodes/patient-year (ep/p-y). A global peritonitis rate reduction was found from 1.02 to 0.47 ep/p-y (p = 0.008). Poisson analyses performed in each of the subgroups of Gram-positive and Gram-negative peritonitis revealed no significant changes over time. No case of vancomycin resistance was identified. There was a downward trend in peritonitis-related hospitalization over time to 0.11 ep/p-y (p ≤ 0.001). Trend analysis showed a favorable, but changing evolution, highlighting the importance of accurate longitudinal PD center registry data and quality control.

Two-in-One Protocol: Simultaneous Small-Pore and Ultrasmall-Pore Peritoneal Transport Quantification

♦ Background: Reduced free water transport (FWT) through ultrasmall pores contributes to net ultrafiltration failure (UFF) and should be seen as a sign of more severe functional deterioration of the peritoneal membrane. The modified peritoneal equilibration test (PET), measuring the dip in dialysate Na concentration, estimates only FWT. Our aim was to simultaneously quantify small-solute transport, FWT, and small-pore ultrafiltration (SPUF) during a single PET procedure. ♦ Methods: We performed a 4-hour, 3.86% glucose PET, with additional measurement of ultrafiltration (UF) at 60 minutes, in 70 peritoneal dialysis patients (mean age: 50 ± 16 years; 61% women; PD vintage: 26 ± 23 months). We calculated the dialysate-to-plasma ratios (D/P) of creatinine and Na at 0 and 60 minutes, and the Na dip (DipD/PNa60′), the delta dialysate Na 0-60 (ΔDNa0-60), FWT, and SPUF. ♦ Results: Sodium sieving (as measured by ΔDNa0-60) correlated strongly with the corrected DipD/PNa60′ (r = 0.85, p < 0.0001) and the corrected FWT (r = 0.41, p = 0.005). Total UF showed better correlation with FWT than with indirect measurements of Na sieving (r = 0.46, p < 0.0001 for FWT; r = 0.360, p < 0.0001 for DipD/PNa60′). Corrected FWT fraction was 0.45 ± 0.16. A negative correlation was found between time on PD and both total UF and FWT (r = -0.253, p = 0.035 and r = -0.272, p = 0.023 respectively). The 11 patients (15.7%) diagnosed with UFF had lower FWT (89 mL vs 164 mL, p < 0.05) and higher D/P creatinine (0.75 vs 0.70, p < 0.05) than did the group with normal UF. The SPUF correlated positively with FWT in the normal UF group, but negatively in UFF patients (r = -0.709, p = 0.015). Among UFF patients on PD for a longer period, 44.4% had a FWT percentage below 45%. ♦ Conclusions: Measurement of FWT and SPUF is feasible by simultaneous quantification during a modified 3.86% glucose PET, and FWT is a decisive parameter for detecting causes of UFF in addition to increased effective capillary surface.

Moncrief–Popovich technique is an advantageous method of peritoneal dialysis catheter implantation

BACKGROUND A safe and well-functioning peritoneal catheter is fundamental for adequate peritoneal dialysis (PD) treatment. Peritoneal catheter implantation by Moncrief-Popovich (MP) technique might add several clinical advantages besides allowing timely access implantation. The aim of this study was to investigate the rate of catheter-related complications and survival in a single-centre university hospital PD unit, according to the method of catheter implantation. METHODS Four hundred and sixty-seven consecutive Tenckhoff catheters were implanted after antibiotic prophylaxis in an operating room: surgical mini-laparotomy (ML) was used in 211 (45%), Seldinger technique (S) in 76 (16%) and mini-laparotomy with MP method in 180 (38.5%). RESULTS The MP technique was significantly associated with a lower rate of early exit-site infection (ESI) (P = 0.02), lower rate of leak (P < 0.0001) and also lower rate of obstruction (P = 0.034) in spite of prolonged break-in (median 55 days, range 0-991 days). Catheter survival by MP technique was 92%, 83% and 64% at 12, 24 and 60 months, respectively, and significantly superior in comparison with the previous methods (log-rank, P = 0.032). By Cox multivariate analysis, adjusted for age, sex and diabetes, the MP technique remained independently associated with better catheter survival [hazard ratio (HR) 0.587 (0.397-0.870), P = 0.008]. CONCLUSION Our experience documented improved PD clinical outcomes with the MP method of catheter implantation while assuring timely access management and logistic advantages.

Long-term peritoneal dialysis experience in Portugal

Peritoneal dialysis (PD) penetration varies widely. Since the beginning of this therapy, indications have changed and outcomes have improved. In Portugal, PD still remains clearly underutilized. The results of a 20 year PD programme were evaluated: 312 cumulative patients, 48±16 years, 27% >60 years old, 27% diabetic, 59% with prior hemodialysis (HD). The main reason for admission was vascular access failure (48.7%). Admission due to patient preference has increased significantly between first and second decades of the programme (33% vs 47% (P<0.001)); 98 patients (31.4%) were treated with automated PD but this prescription increased to 43% of the active patients. A total of 376 Tenckhoff catheters were surgically implanted, recently by the Popovich-Moncrief technique (77 catheters): the cumulative survival was 82%, 64% and 50% at 1, 3 and 5 years, respectively. A better catheter survival was found in the last decade (85.7%, 69.6%, 54.8% versus 77.3%, 55.5%, 40.2%, at 1, 3 and 5 years, respectively (P=0.007). The patient and technique cumulative survivals were 91, 74, 55% and 85, 67, 41%, at 1, 3, and 5 years, respectively. The main drop-out was to hemodialysis (35.8%), followed by death (23.7%), and transplantation (21.5%). Peritonitis and access-related infections caused 35% of the transfer to HD. Cardiovascular events caused 58% of deaths. The median PD retention was 35.5 months. The rate of peritonitis has decreased to one episode /30 patient months. Hospital admission has also decreased to 4.8 days/patient year. This is a first report on long-term PD experience in Portugal. It has been an effective modality of renal replacement therapy, reflected by the growing patient preference in our PD programme. Experience, knowledge and new technical solutions have improved the outcomes.

Peritoneal Membrane Evaluation in Routine Clinical Practice

Background/Aims: Establishment of reference values for small solute transport, sodium sieving and effluent CA125 with 3.86% (4 h) peritoneal equilibration test (PET), and comparison with fast-fast PET with regard to small solute transport categories. Methods: Cross-sectional study; 69 prevalent patients. Sodium sieving corrected for sodium diffusion with a formula applicable to the PET. CA125 appearance rate (AR) was measured. Expected and observed 60 min D/Pcreatinine were compared by Bland and Altman. Results: Means (95% CI): D/Pcreatinine 0.73 (0.70–0.76), MTACcreatinine 9.6 (8.4–10.9) ml/min, D/D₀ glucose 0.30 (0.28–0.31), corrected dip 0.17 (0.15–0.18), CA125 150 (125–176) U/min. Both corrected and uncorrected sodium sieving were informative. Peritoneal transport was faster at 60 min dwell. UFF patients presented very low corrected dip and CA125 AR. Conclusion: 3.86% (4 h) PET provided results similar to those from SPA. Correction for diffusion of sodium sieving is dispensable for simple clinical evaluations. D/Pcreatinine at 60 min overestimated small solute transport rate. Effluent CA125 was consistently lower in UFF patients.

Pancreatic autoantibodies after pancreas–kidney transplantation – do they matter?

Type 1 diabetes recurrence has been documented in simultaneous pancreas–kidney transplants (SPKT), but this diagnosis may be underestimated. Antibody monitoring is the most simple, noninvasive, screening test for pancreas autoimmune activity. However, the impact of the positive autoimmune markers on pancreas graft function remains controversial. In our cohort of 105 SPKT, we studied the cases with positive pancreatic autoantibodies. They were immunosuppressed with antithymocyte globulin, tacrolimus, mycophenolate, and steroids. The persistence or reappearance of these autoantibodies after SPKT and factors associated with their evolution and with graft outcome were analyzed. Pancreatic autoantibodies were prospectively monitored. Serum samples were collected before transplantation and at least once per year thereafter. At the end of the follow‐up (maximum 138 months), 43.8% of patients were positive (from pre‐transplant or after recurrence) for at least one autoantibody – the positive group. Antiglutamic acid decarboxylase was the most prevalent (31.4%), followed by anti‐insulin (8.6%) and anti‐islet cell autoantibodies (3.8%). Bivariate analysis showed that the positive group had higher fasting glucose, higher glycated hemoglobin (HbA1c), lower C‐peptide levels, and a higher number of HLA‐matches. Analyzing the sample divided into four groups according to pre‐/post‐transplant autoantibodies profile, the negative/positive group tended to present the higher HbA1c values. Multivariate analysis confirmed the significant association between pancreas autoimmunity and HbA1c and C‐peptide levels. Positivity for these autoantibodies pre‐transplantation did not influence pancreas survival. The unfavorable glycemic profile observed in the autoantibody‐positive SPKT is a matter of concern, which deserves further attention.

Update on the challenging role of biofilms in peritoneal dialysis

Biofilms are commonly associated with an increased risk of patient infection. In peritoneal dialysis (PD), catheter associated infection, especially peritonitis, remains a clinically relevant problem. Although the presence of a biofilm is recognized in relapsing, repeat, and catheter-related peritonitis, it remains poorly characterized. In this review, an update on the role of biofilms in PD infections is presented. The emerging concept that host cells and tissue associated biofilms, in addition to the biofilms on the catheters themselves, contribute to the recalcitrance of infections is discussed. Furthermore, the evidence of biofilms on PD catheters, their developmental stages, and the possible influence of the PD environment are reviewed. The focus is given to ex vivo and in vitro studies that contribute to the elucidation of the interplay between host, microbial, and dialysis factors. The key issues that are still to be answered and the challenges to clinical practice are discussed.