The urogenital microbiome in chronic kidney disease patients on peritoneal dialysis / El microbioma urogenital en pacientes con enfermedad renal crónica en diálisis peritoneal

Introduction and objectives: Diabetes, dyslipidemia, older age, gender, urinary tract infections, and recent antibiotic intake have been associated with a decrease in the urobiome richness and other fluctuations in this microbiome. Gut and blood microbiome have been reported to be altered in patients with chronic kidney disease (CKD), and specifically in peritoneal dialysis (PD) patients. Still, there are currently no studies describing the urogenital microbiome in CKD-PD patients. In this study we characterized the urobiome profile in 46 PD patients and analyzed its clinical and inflammatory parameters. Materials and methods: Mid-stream urine, fecal and blood samples were collected from 46 patients undergoing PD at Centro Hospitalar Universitário de São João (CHUSJ) in Porto, Portugal. Exclusion criteria were age under 18 years old, inability to give informed consent, history of infection in the last three months, and antibiotic intake in the last three months. The microbiome communities were analyzed by amplification and sequencing of the V3–V4 region of the bacterial 16S rRNA gene. Correlations with the patients’ clinical data and inflammatory profile were performed. Results: CKD-PD patients presented a unique urobiome profile dominated by Bacillota, Actinomycetota and Pseudomonadota and characterized by a lower Shannon diversity than fecal and blood microbiome. The taxonomic profiles of urogenital samples were organized in multiple subtypes dominated by populations of Lactobacillus, Staphylococcus, Streptococcus, Gardnerella, Prevotella, Escherichia-Shigella, being similar to other non-PD-CKD patients. Gender, sCD14, residual diuresis and history of peritonitis were significantly associated to variations in the urobiome. Although not reaching statistical significance, diabetes and the time on PD also showed association with particular taxonomic groups... (AU)

Introducción y objetivos: Diabetes, dislipemia, edad avanzada, género, infecciones del tracto urinario y toma reciente de antibióticos, entre otras, se han asociado a una disminución en la riqueza del urobioma y a otras fluctuaciones de dicho microbioma.Recientemente, se han descrito alteraciones en losmicrobiomas intestinal y en sangreen pacientes con enfermedad renal crónica (ERC) y, específicamente, en pacientes en diálisis peritoneal (DP).A pesar de ello, aún no existen estudios que describan el microbioma urogenital en pacientes en DP. En el presente trabajo, caracterizamos el urobioma en 46 pacientes en DP. Pacientes y métodos: Se recogieron muestras de orina (micción espontánea), heces y sangre de 46 pacientes en DP del Centro HospitalarUniversitário de São João en Oporto, Portugal. Los criterios de exclusión fueron edad menor a 18 años, incapacidad para entenderel consentimiento informado, e historia de infección y toma de antibióticos en los últimos 3 meses. Las comunidades microbiológicas fueron analizadas por amplificación y secuenciación de las regiones V3-V4 del 16S rRNA bacteriano. Se realizaron correlaciones con los datos clínicos y el perfil inflamatorio de los pacientes. Resultados: Los pacientes en DP presentaron un urobioma único dominado por Bacillota, Actinomycetota yPseudomonadota, y caracterizado por una menor diversidad de Shannon que los microbiomas en sangre e intestinal. Los perfiles taxonómicos de las muestras urogenitales se organizaron en múltiples subtipos dominados por poblaciones de Lactobacillus, Staphylococcus, Streptococcus, Gardnerella, Prevotella, Escherichia-Shigella, siendo similar al descrito para otros pacientes con ERC no en DP.Género, factor sCD14, diuresis residual yantecedentes de peritonitis se asociaron de forma significativa a cambios en el urobioma... (AU)

Systemic and local complement activation in peritoneal dialysis patients via conceivably distinct pathways.

BACKGROUND: Despite several advantages compared to haemodialysis (HD), peritoneal dialysis (PD) remains an underused dialysis technique due to its high technique failure rate related to membrane fibrosis and peritonitis events. Previous work has suggested a harmful role for the complement system in these processes, highlighting the need for a more comprehensive examination in PD. METHODS: Plasma levels of C1q, mannose-binding lectin (MBL), Properdin, Factor D, C3d/C3-ratio and soluble membrane attack complex (sC5b-9) were determined in PD patients (n = 55), HD patients (n = 41), non-dialysis chronic kidney disease (CKD) patients (n = 15) and healthy controls (n = 14). Additionally, C1q, MBL, Properdin, Factor D and sC5b-9 levels were assessed in the peritoneal dialysis fluid (PDF). In a subgroup, interleukin-6, matrix metalloproteinase-2 (MMP-2), myeloperoxidase (MPO) and elastase were measured in the PDF. RESULTS: PD patients had significantly higher systemic levels of sC5b-9 compared to healthy controls, CKD and HD patients (p < 0.001). Plasma levels of C1q and C3d/C3-ratios were significantly associated with systemic sC5b-9 levels (p < 0.001). Locally, sC5b-9 was detected in the PDF of all PD patients, and levels were approximately 33% of those in matched plasma, but they did not correlate. In the PDF, only Properdin levels remained significantly associated with PDF sC5b-9 levels in multivariate analysis (p < 0.001). Additionally, PDF levels of sC5b-9 positively correlated with elastase, MPO and MMP-2 levels in the PDF (p < 0.01). CONCLUSIONS: Our data reveal both systemic and local complement activation in PD patients. Furthermore, these two processes seem independent considering the involvement of different pathways and the lack of correlation.

Blood, Gut, and Oral Microbiome in Kidney Transplant Recipients.

Background and Objective: Recent reports describe the existence of a blood microbiome profile not associated with an infection state. Given the high impact that the dysbiotic human microbiome appears to have in chronic kidney disease and, in particular, in the outcome of kidney transplant recipients (KTRs), we aimed to explore the variations and correlations of the gut, oral, and blood microbiome of recipients, 3 months after kidney transplantation. Materials and Methods: We conducted a cross-sectional study where the microbiome of stool, saliva, and blood collected from recipients 3 months after kidney transplantation (N = 6) was analyzed by polymerase chain reaction (PCR) amplification and sequencing of the V3-V4 hypervariable regions of the 16S rRNA gene using MiSeq Illumina® technology. Results: Blood of KTRs harbors a distinct low-abundance microbiome dominated by Proteobacteria and Firmicutes. Gut and oral microbiome of KTRs also present distinct profiles. The existence of a proportion of shared operational taxonomic units among the different body sites is reported, mainly classified as Proteobacteria and Firmicutes. Conclusions: This study provides evidence of existence a blood microbiome in KTRs, different from the gut and the oral microbiome profiles, with a small number of operational taxonomic units representing a shared microbiome. The clinical relevance of this observation should be further explored in these patients.

Lessons from Four Decades of Systemic Amyloidosis with Renal Involvement.

BACKGROUND: Apart from ATTR amyloidosis, the epidemiology and outcomes of the most common subtypes of systemic amyloidosis in Portugal remain primarily unknown. METHODS: This retrospective cohort study evaluated patients with renal biopsy-proven amyloidosis, diagnosed from January 1978 to December 2019. Follow-up started at kidney disease presentation and ended at death or August 2020. Clinical presentation, survival, and prognostic factors were analysed. RESULTS: Of 123 patients with amyloid nephropathy, 111 had definite amyloid typing and were analysed. AA amyloidosis was the most frequent type (56.1%) and was related mainly to chronic infection (47.8%) and chronic inflammatory arthritis (29.0%). AL amyloidosis was present in 25.2% of patients and hereditary forms in 6.5% (4.1% AFibE526V, 2.4% ATTRV30M). During follow-up, 73.9% of AA and 54.8% of AL patients progressed to end-stage renal disease, and 79.7% of AA and 77.4% of AL died; median overall survival was 66.0 (95% CI, 33.0-99.0) and 18.0 (95% CI, 9.3-26.7) months (p = 0.025), respectively. There were no significant differences in renal outcome and survival on dialysis between these two types. In multivariate analysis, cardiac involvement at presentation (HR 6.26 [95% CI, 2.89-13.56]) and estimated glomerular filtration rate <30 mL/min/1.73 m2 (HR 2.05 [95% CI, 1.06-3.99]) independently influenced AA and AL amyloidosis survival. Cardiac involvement at presentation was an independent predictor of death (HR 9.65 [95% CI, 2.91-31.95]) and early mortality in AL amyloidosis. CONCLUSIONS: In Portugal, AA amyloidosis and related chronic infections are still relevant. Regarding AL amyloidosis, the low incidence and advanced disease at presentation result from missed and erroneous diagnoses, leading to delayed referrals and poor outcomes in these patients.

Gut Microbiome and Organ Fibrosis.

Fibrosis is a pathological process associated with most chronic inflammatory diseases. It is defined by an excessive deposition of extracellular matrix proteins and can affect nearly every tissue and organ system in the body. Fibroproliferative diseases, such as intestinal fibrosis, liver cirrhosis, progressive kidney disease and cardiovascular disease, often lead to severe organ damage and are a leading cause of morbidity and mortality worldwide, for which there are currently no effective therapies available. In the past decade, a growing body of evidence has highlighted the gut microbiome as a major player in the regulation of the innate and adaptive immune system, with severe implications in the pathogenesis of multiple immune-mediated disorders. Gut microbiota dysbiosis has been associated with the development and progression of fibrotic processes in various organs and is predicted to be a potential therapeutic target for fibrosis management. In this review we summarize the state of the art concerning the crosstalk between intestinal microbiota and organ fibrosis, address the relevance of diet in different fibrotic diseases and discuss gut microbiome-targeted therapeutic approaches that are current being explored.

Circulating Renalase as Predictor of Renal and Cardiovascular Outcomes in Pre-Dialysis CKD Patients: A 5-Year Prospective Cohort Study.

Chronic kidney disease (CKD) is an independent risk factor for adverse cardiovascular and cerebrovascular events (MACCEs), and mortality since the earlier stages. Therefore, it is critical to identify the link between CKD and cardiovascular risk (CVR) through early and reliable biomarkers. Acknowledging that CKD and CKD progression are associated with increased sympathetic tone, which is implicated in CVR, and that renalase metabolizes catecholamines, we aimed to evaluate the relationship between renalase serum levels (RNLS) and cardiovascular and renal outcomes. The study included 40 pre-dialysis CKD patients (19F:21M) with median age of 61 (IQ 45-66) years. At baseline, we measured RNLS as well as routine biomarkers of renal and cardiovascular risk. A prospective analysis was performed to determine whether RNLS are associated with CKD progression, MACCEs, hospitalizations and all-cause mortality. At baseline, the median level of RNLS and median estimated glomerular filtration rate (eGFR) were 63.5 (IQ 48.4-82.7) µg/mL and 47 (IQ 13-119) mL/min/1.73 m2, respectively. In univariate analysis, RNLS were strongly associated with eGFR, age and Charlson Index. Over the course of a mean follow-up of 65 (47 to 70) months, 3 (7.5%) deaths, 2 (5%) fatal MACCEs, 17 (42.5%) hospital admissions occurred, and 16 (40%) patients experienced CKD progression. In univariate analysis, RNLS were associated with CKD progression (p = 0.001), hospitalizations (p = 0.001) and all-cause mortality (p = 0.022) but not with MACCEs (p = 0.094). In adjusted analysis, RNLS predicted CKD progression and hospitalizations regardless of age, Charlson comorbidity index, cardiovascular disease, hypertension, diabetes and dyslipidemia. Our results suggest that RNLS, closely related with renal function, might have a potential role as predictor of renal outcomes, hospitalizations, and mortality in pre-dialysis CKD patients.

Endothelial Dysfunction Is Associated with Cerebrovascular Events in Pre-Dialysis CKD Patients: A Prospective Study.

BACKGROUND: Patients with chronic kidney disease (CKD) have markedly increased rates of end stage renal disease, major adverse cardiovascular/cerebrovascular events (MACCEs), and mortality. Endothelial dysfunction (ED) is an early marker of atherosclerosis that is emerging as an increasingly important non-traditional cardiovascular risk factor in CKD. There is a lack of clinical studies examining the association between ED and both cardiovascular and renal endpoints in patients with CKD. AIMS: We examined the association between reactive hyperemia index (RHI), a validated measure of endothelial function measured by peripheral arterial tonometry (PAT), with traditional cardiovascular risk factors in pre-dialysis CKD patients and prospectively evaluated the role of RHI as predictor of renal and cardiovascular outcomes in this population. METHODS: One hundred and twenty pre-dialysis patients with CKD stages 1 to 5 (CKD group) and 18 healthy kidney donor candidates (control group) were recruited and had a successful RHI measurement by PAT. General demographic and clinical information including traditional cardiovascular risk factors were registered from all participants. Thereafter, patients were prospectively followed-up for a median time of 47 (IQR 19-66) months to determine associations of RHI with renal outcomes, MACCEs, hospitalizations or mortality. RESULTS: In the CKD patient population, the mean age was 57.7 ± 15.5 years, the mean eGFR was 54.9 ± 36.7 mL/min/1.73 m2 (CKD-EPI) and 57 were males (47.5%). At baseline, in univariate analysis, RHI in the CKD group correlated positively with eGFR (r = 0.332, p < 0.0001) and correlated negatively with age (r = -0.469, p < 0.0001), Charlson index (r = -0.399, p < 0.0001), systolic blood pressure (r = -0.256, p = 0.005), and proteinuria (r = 0.211, p = 0.027). Reactive hyperemia index in the control group did not significantly differ from RHI observed in patients with CKD stages 1 to 5 (2.09 ± 0.40 vs. 2.01 ± 0.06, p = 0.493). In adjusted analysis, only age (ß = -0.014, p = 0.003) remained independently associated with RHI at baseline. During follow-up, 8 patients suffered a MACCEs, 33 patients experienced renal function deterioration, 17 patients were hospitalized for medical reasons and 6 patients died. RHI at baseline was not significantly associated with CKD progression (1.94 vs. 2.02, p = 0.584), hospitalizations (1.90 vs. 2.04, p = 0.334), and all-cause mortality (1.65 vs. 2.01, p = 0.208) or MACCEs (1.77 vs. 2.01, p = 0.356), but was significantly associated with cerebrovascular events (1.27 vs. 2.02, p = 0.004) and with a composite cardiovascular outcome (MACCEs, hospital admissions and death; 1.73 vs. 2.07, p = 0.035). Conclusion: Our results suggest that RHI may be a predictor for the development of cerebrovascular events in pre-dialysis CKD patients who may benefit from more aggressive preventive measures.

Viral Clearance and Serological Response to SARS-CoV-2 in Kidney Transplant Recipients.

OBJECTIVES: Knowledge about the impact of coronavirus disease 2019 (COVID-19) on kidney transplant recipients (KTRs) concerning viral shedding and humoral immune response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is limited. The aim of this study is to analyze viral dynamics and the antibody response to SARS-CoV-2 in KTRs with COVID-19 and study their association with clinical data. MATERIALS AND METHODS: Consecutive KTRs diagnosed with COVID-19 at our center were evaluated for clinical presentation and outcome; duration of viral shedding and viral burden by reverse transcription-polymerase chain reaction assay cycle threshold; and magnitude of seroconversion to SARS-CoV-2. RESULTS: Six KTRs identified with COVID-19 were hospitalized. Presenting symptoms were similar to those in the general population. Four patients had severe disease and, of these, 2 required mechanical ventilation, 4 had acute kidney injury, and 3 had secondary bacterial infections. Immunosuppression was reduced in all patients. Five patients were treated with hydroxychloroquine. No patient required dialysis or died. Patients with severe disease had a longer duration of viral shedding, which lasted more than 40 days, and had IgG antibodies against SARS-CoV-2, which were detected from 3 weeks to as long as 10 weeks after symptom onset. In patients with less severe disease no IgG antibodies where detected between 9 and 14 weeks after symptom onset. CONCLUSIONS: In our series, KTRs with severe COVID-19 had prolonged viral shedding and a stronger humoral immune response to SARS-CoV-2. These preliminary data need to be confirmed with further studies and over a longer period of time.

Soluble CD59 in peritoneal dialysis: a potential biomarker for peritoneal membrane function.

INTRODUCTION: Various studies have reported the importance of complement regulators in preventing mesothelial damage during peritoneal dialysis (PD). Its assessment, however, is limited in clinical practice due to the lack of easy access to the peritoneal membrane. Recently, a soluble form of the complement regulatory protein CD59 (sCD59) has been described. We therefore aimed to investigate the role of sCD59 in PD. METHODS: Plasma sCD59 was measured in 48 PD patients, 41 hemodialysis patients, 15 non-dialysis patients with chronic kidney disease and 14 healthy controls by ELISA (Hycult; HK374-02). Additionally, sCD59 and sC5b-9 were assessed in the peritoneal dialysate. RESULTS: sCD59 and sC5b-9 were detectable in the peritoneal dialysate of all patients, and marginally correlated (r = 0.27, P = 0.06). Plasma sCD59 levels were significantly higher in PD patients than in patients with chronic kidney disease and healthy controls, but did not differ from hemodialysis patients. During follow-up, 19% of PD patients developed peritoneal membrane failure and 27% of PD patients developed loss of residual renal function. In adjusted models, increased sCD59 levels in the dialysate (HR 3.44, 95% CI 1.04-11.40, P = 0.04) and in plasma (HR 1.08, 95% CI 1.01-1.17, P = 0.04) were independently associated with the occurrence of peritoneal membrane failure. Higher plasma levels of sCD59 were also associated with loss of residual renal function (HR 1.10, 95% CI 1.04-1.17, P < 0.001). CONCLUSIONS: Our study suggests that sCD59 has potential as a biomarker to predict peritoneal membrane function and loss of residual renal function in PD, thereby offering a tool to improve patient management.

Clearing the clouds: Case-report and review of the literature.

In peritoneal dialysis (PD), a cloudy dialysate is an alarming finding. Bacterial peritonitis is the most common cause, however, atypical infections and non-infectious causes must be considered. A 46-year-old man presented with asthenia, paraesthesia, foamy urine and hypertension. Laboratory testing revealed severe azotaemia, anaemia, hyperkalaemia and nephrotic-range proteinuria. Haemodialysis was started through a central venous catheter. Later, due to patient preference, a Tenckhoff catheter was inserted. Conversion to PD occurred 3 weeks later, during hospitalization for a presumed central line infection. A month later, the patient was hospitalized for neutropenic fever. He was diagnosed an acute parvovirus infection and was discharged under isoniazid for latent tuberculosis. Four months later, the patient presented with fever and a cloudy effluent. Peritoneal fluid (PF) cytology was suggestive of infectious peritonitis, but the symptoms persisted despite antibiotic therapy. Bacterial and mycological cultures were negative. No neoplastic cells were detected. Mycobacterium tuberculosis eventually grew in PF cultures, despite previous negative molecular tests. Directed therapy was then initiated with excellent response. Thus, facing a cloudy effluent, one must consider multiple aetiologies. Diagnosis of peritoneal tuberculosis is hampered by the lack of highly sensitive and specific exams. Here, diagnosis was only possible due to positive mycobacterial cultures.

Erratum: Borges, I., et al. Exposure of Smaller and Oxidized Graphene on Polyurethane Surface Improves its Antimicrobial Performance. Nanomaterials 2020, 10, 349.

The authors wish to make the following corrections to this paper [...].

Effect of uremic state in intestine through a co-culture in vitro intestinal epithelial model.

The progressive loss of renal function in chronic kidney disease (CKD) leads to the accumulation of uremic toxins. Recent studies related uremic plasma as well dysbiotic gut microbiome to impaired intestinal barrier function, allowing the translocation of microorganisms or by-products from the intestinal lumen to systemic circulation, contributing to systemic inflammation, cardiovascular risk and progression of CKD. Our main goal was to evaluate the impact of different uremic conditions on an improved in vitro intestinal Caco-2/HT29-MTX/Raji B triple co-culture model. For that, the impact of CKD patients' plasma and elevated urea concentration and its by-products on the triple model was assessed. The results showed that uremic conditions did not potentiate the Escherichia coli (E. coli) translocation, although may interfere with the integrity and the permeability of the intestinal barrier. Also, results showed that E. coli translocation was higher in Caco-2 monoculture than in Caco-2/HT29-MTX/Raji B triple model, suggesting that the triple model creates a more effective intestinal barrier. This study allowed to conclude that the uremic state influences the integrity of the intestinal barrier, but this influence could not be directly translated in an increase on the E. coli translocation through the intestinal epithelium, at least in Caco-2/HT29-MTX/Raji B intestinal epithelial barrier model.

Arteriolar C4d in IgA Nephropathy: A Cohort Study.

RATIONALE & OBJECTIVE: Glomerular C4d (C4dG) as an indicator of the lectin pathway of complement activation in immunoglobulin A nephropathy (IgAN) has been associated with more severe kidney damage. Recent studies have suggested that vascular lesions in IgAN biopsy specimens with complement deposition are also associated with disease progression. We aimed to study the clinical significance of arteriolar C4d (C4dA) in IgAN kidney biopsy tissue. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Kidney biopsy specimens from 126 adults with IgAN diagnosed by Oxford classification criteria were stained using immunohistochemistry and classified according to C4dG and C4dA deposition. Additionally, vascular lesions including acute and chronic microangiopathy, arteriolar hyalinosis, and arterial intima fibrosis were characterized. PREDICTOR: C4dA. OUTCOME: Progressive kidney disease, defined as a decline in estimated glomerular filtration rate by≥50% or occurrence of kidney failure. ANALYTICAL APPROACH: The association of C4dA and C4dG with baseline clinical and histologic characteristics, as well as progressive kidney disease, were assessed with survival analysis using multivariable Cox regression analysis. RESULTS: C4dA was identified in 21 (17%) patients and was associated with mean arterial pressure, arterial intima fibrosis, and chronic microangiopathy. C4dA was also significantly associated with C4dG and both were associated with progressive kidney disease. In regression analysis, C4dA remained significantly associated with progressive kidney disease after adjusting for other significant predictors, including baseline estimated glomerular filtration rate, mean arterial pressure, and the presence of crescents. LIMITATIONS: Findings based on the retrospective evaluation of a single center's experience, limited number of events, a small number of patients with a broad range of kidney disease stages, and use of immunohistochemistry rather than immunofluorescence to detect C4d. CONCLUSIONS: C4dA is a potential biomarker for disease progression in IgAN. It should be further investigated in larger cohorts to determine the value of C4dA in improving prediction of IgAN disease progression.

Exposure of Smaller and Oxidized Graphene on Polyurethane Surface Improves its Antimicrobial Performance.

Catheter-related infections are a common worldwide health problem, highlighting the need for antimicrobial catheters. Here, antibacterial potential of graphene nanoplatelets (GNP) incorporated in the commonly used polymer for catheter manufacture-polyurethane (PU)-is investigated. Two strategies are explored: melt-blending, producing a composite, and dip coating, where a composite layer is deposited on top of PU. GNP with different lateral sizes and oxidation degrees-GNP-M5, GNP-M15, GNP-M5ox, GNP-M15ox-are applied in both strategies, and the antimicrobial potential towards Staphylococcus epidermidis of GNP dispersions and GNP-containing PU evaluated. As dispersions, oxidized and smaller GNP powders (GNP-M5ox) inhibit 74% bacteria growth at 128 µg/mL. As surfaces, GNP exposure strongly impacts their antimicrobial profile: GNP absence at the surface of composites yields no significant effects on bacteria, while by varying GNP: PU ratio and GNP concentration, coatings enhance GNP exposure, depicting an antimicrobial profile. Oxidized GNP-containing coatings induce higher antibacterial effect than non-oxidized forms, particularly with smaller GNPox, where a homogeneous layer of fused platelets is formed on PU, leading to 70% reduction in bacterial adhesion and 70% bacterial death. This pioneering work unravels how to turn a polymer clinically used to produce catheters into an antimicrobial surface, crucial to reducing risk of infection associated with catheterization.

Peritoneal Microbiome in End-Stage Renal Disease Patients and the Impact of Peritoneal Dialysis Therapy.

Factors influencing the occurrence of peritoneal dialysis (PD)-related infections are still far from fully understood. Recent studies described the existence of specific microbiomes in body sites previously considered microbiome-free, unravelling new microbial pathways in the human body. In the present study, we analyzed the peritoneum of end-stage kidney disease (ESKD) patients to determine if they harbored a specific microbiome and if it is altered in patients on PD therapy. We conducted a cross-sectional study where the peritoneal microbiomes from ESKD patients with intact peritoneal cavities (ESKD non-PD, n = 11) and ESKD patients undergoing PD therapy (ESKD PD, n = 9) were analyzed with a 16S rRNA approach. Peritoneal tissue of ESKD patients contained characteristically low-abundance microbiomes dominated by Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes. Patients undergoing PD therapy presented lower species richness, with dominance by the Pseudomonadaceae and Prevotelaceae families. This study provides the first characterization of the peritoneal microbiome in ESKD patients, bringing new insight to the human microbiome. Additionally, PD therapy may induce changes in this unique microbiome. The clinical relevance of these observations should be further explored to uncover the role of the peritoneal microbiome as a key element in the onset or aggravation of infection in ESKD patients, especially those undergoing PD.

Administration of Intravenous Iron Formulations Induces Complement Activation in-vivo.

Background: Intravenous (IV) iron is widely used to treat anemia in chronic kidney disease patients. Previously, iron formulations were shown to induce immune activation in-vitro. The current study aimed to investigate the effect of IV iron on complement activation in-vivo, and whether this subsequently induces inflammation and/or oxidative stress. Methods: Two distinct patient groups were included: 51 non-dialysis and 32 dialysis patients. The non-dialysis group received iron sucrose or ferric carboxymaltose, based on physicians' choice. Plasma samples were collected prior to and 1 h after completion of IV iron infusion. The dialysis group received iron sucrose exclusively. Plasma samples were collected at the start and end of two consecutive hemodialysis sessions, one with and one without IV iron. Finally, plasma levels of MBL, C1q, properdin, factor D, sC5b-9, MPO, PTX3 were assessed by ELISA. Results: In the non-dialysis group, sC5b-9 levels significantly increased after IV iron by 32%, while levels of factor D and MBL significantly dropped. Subgroup analysis demonstrated that iron sucrose induced complement activation whereas ferric carboxymaltose did not. In the dialysis group, levels of sC5b-9 significantly increased by 46% during the dialysis session with IV iron, while factor D levels significantly fell. Furthermore, the relative decrease in factor D by IV iron correlated significantly with the relative increase in sC5b-9 by IV iron. MPO levels rose significantly during the dialysis session with IV iron, but not in the session without iron. Moreover, the relative increase in MPO and sC5b-9 by IV iron correlated significantly. PTX3 levels were not affected by IV iron. Conclusions: Iron sucrose but not ferric carboxymaltose, results in complement activation possibly via the lectin and alternative pathway partially mediating oxidative stress but not inflammation.

Peritoneal Dialysis Cuff-Shaving-A Salvage Therapy for Refractory Exit-Site Infections.

Introduction:Cuff-shaving has been described as a salvage technique for refractory exit-site infections, with conflicting data regarding infection and catheter outcomes. We describe our experience with cuff-shaving as a rescue therapy for exit-site infections unresponsive to systemic therapy.Methods:We retrospectively reviewed patients who underwent cuff-shaving between January 2012 and June 2017. Refractory exit-site infection was defined as purulent discharge from the exit site with no clinical response after 3 weeks of systemic antibiotic treatment.Results:Fifty-three cuff-shavings were included, mean age was 53.4 ± 13.4 years, 26 patients were male. Median dialysis vintage was 29 months (interquartile range [IQR] 14.3 - 38), and 39 (73.6%) were on continuous ambulatory peritoneal dialysis (CAPD). The exit-site infection rate before cuff-shaving was 1.12 episodes per patient-year and the median time from infection to shaving was 52 days (IQR 35 - 76). The most frequent agents were Staphylococcus aureus (34%), Corynebacterium spp. (17%) and Pseudomonas aeruginosa (15%). Median follow-up was 9 months (IQR 1 - 18.5), during which time 35 catheters were removed, 5 due to non-infectious reasons. Using the Kaplan-Meier survival analysis, median catheter survival was 24 months (95% confidence interval [CI] 4.17 - 43.83). At 12 months, the probability of catheter survival was 54% and was not statistically different between gram-positive and gram-negative agents, although it was significantly shorter for fungal agents.Conclusion:Cuff-shaving is a feasible rescue therapy to treat refractory exit-site infections. In our experience, it allowed resolution of infections in a significant proportion of cases, except for fungal agents, and therefore extended catheter survival time, besides being associated with a small rate of complications.

Early Versus Late Conversion From Immediate to Prolonged-Release Tacrolimus After Renal Transplantation: Clinical Effects and Treatment Costs.

INTRODUCTION: Prolonged-release tacrolimus (PR-TAC) was associated with improved renal function after transplantation when compared to immediate-release tacrolimus (IR-TAC) although evidence is still scarce. This study aimed to compare clinical outcomes and treatment costs in patients who converted from IR-TAC to PR-TAC during the first year after renal transplantation (RT) (early converters [EC]) or after that period (late converters [LC]). METHODS: We performed a retrospective study including 79 patients (EC, 39; LC, 41) which were followed up over 60 months. A mixed-effects approach was used to investigate the differences between both groups regarding renal and metabolic outcomes as well as treatment costs. RESULTS: The median time from RT to conversion was 3 months for EC and 25 months for LC. For both EC and LC, a significant increase in estimated glomerular filtration rate was observed after conversion (5.2 and 4.9 mL/min per 1.73 m2, respectively). During the first year after RT, EC presented a higher estimated glomerular filtration rate and inferior tacrolimus trough levels when compared to LC, with higher mean treatment costs associated. However, thereafter, these outcomes were similar between groups over the remaining time. At the end of follow-up, no significant differences were found regarding allograft acute rejection (2.6% and 2.4%), new-onset diabetes (15.7% vs 12.2%) or cardiovascular events (5.2% vs 7.3%). CONCLUSIONS: There was a significant benefit on renal function after conversion from IR-TAC to PR-TAC. During the first year after RT, EC presented improved renal function, but higher treatment costs. None of these differences persisted at the end of follow-up.

An integrated program of extracorporeal membrane oxygenation (ECMO) assisted cardiopulmonary resuscitation and uncontrolled donation after circulatory determination of death in refractory cardiac arrest.

AIM: To assess the feasibility of an integrated program of extracorporeal cardiopulmonary resuscitation (ECPR) and uncontrolled donation after circulatory determination of death (uDCDD) in refractory cardiac arrest (rCA). METHODS: Single center, prospective, observational study of selected patients with in-hospital (IHCA) and out-of-hospital (OHCA) rCA occurring in an urban area of ∼1.5 million inhabitants, between October-2016 and May-2018. 65 year old or younger patients without significant bleeding or comorbidities with witnessed nonasystolic cardiac arrests were triaged to ECPR if they had a reversible cause and high quality CPR lasting < 60 min. Otherwise they were considered for uDCDD after a ten minute no touch period using normothermic regional perfusion. RESULTS: 58 patients were included, of which 41 (71%) were OHCA and 18 (31%) had ECPR initiated. Median age was 52 (IQR 45-56) years. Cannulation was successful in 49/58 (84%) cases. Compared to ECPR, patients referred for uDCDD were more frequently OHCA (90 vs. 28%), had bystander CPR (28 vs. 83%) and prolonged low-flow period (40 (35-50) vs. 60 (49-78) min). Survival to hospital discharge with full neurological recovery (cerebral performance category 1) occurred in 6/18 (33%) ECPR patients. uDCDD resulted in transplantation of 44 kidneys. CONCLUSIONS: An integrated program for rCA consisting of a formal pathway to uDCDD referral in ECPR ineligible patients is feasible. ECPR-referred patients had a reasonable survival with full neurologic recovery. Successful kidney transplantation was achieved with uDCDD.