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)

Vascular Calcification and the Gut and Blood Microbiome in Chronic Kidney Disease Patients on Peritoneal Dialysis: A Pilot Study.

Vascular calcification (VC) is a frequent condition in chronic kidney disease (CKD) and a well-established risk factor for the development of cardiovascular disease (CVD). Gut dysbiosis may contribute to CVD and inflammation in CKD patients. Nonetheless, the role of gut and blood microbiomes in CKD-associated VC remains unknown. Therefore, this pilot study aimed to explore the link between gut and blood microbiomes and VC in CKD patients on peritoneal dialysis (CKD-PD). Our results showed relative changes in specific taxa between CKD-PD patients with and without VC, namely Coprobacter, Coprococcus 3, Lactobacillus, and Eubacterium eligens group in the gut, and Cutibacterium, Pajaroellobacter, Devosia, Hyphomicrobium, and Pelomonas in the blood. An association between VC and all-cause mortality risk in CKD-PD patients was also observed, and patients with higher mortality risk corroborate the changes of Eubacterium eligens in the gut and Devosia genus in the blood. Although we did not find differences in uremic toxins, intestinal translocation markers, and inflammatory parameters among CKD-PD patients with and without VC, soluble CD14 (sCD14), a nonspecific marker of monocyte activation, positively correlated with VC severity. Therefore, gut Eubacterium eligens group, blood Devosia, and circulating sCD14 should be further explored as biomarkers for VC, CVD, and mortality risk in CKD.

Multi-organ involvement and intratubular calcium phosphate deposition in the kidney biopsy: what should we investigate?

BACKGROUND: Anorexia nervosa is frequently associated with alcohol use disorder. Both of them may adversely affect almost every body system, leading to worse clinical outcomes and high mortality risk. Nonetheless, there is little evidence interrelating anorexia nervosa, alcohol use disorder, and kidney failure. CASE: We report a case of a 30-year-old male with multi-organ involvement at admission, including pancytopenia, electrolyte alterations, impaired liver function, and renal failure. The kidney biopsy revealed calcium phosphate crystalline nephropathy and IgA nephropathy. The bone marrow biopsy and aspiration showed a hypocellular bone marrow and a focal spindle cell infiltrate with atypical vascular proliferation. Nonspecific liver disease was revealed by ultrasound. Further investigation was performed, uncovering a possible masked diagnosis of anorexia nervosa and alcohol use disorder. With the restoration of adequate nutrition and the withdrawal of possible external triggers, a partial recovery was achieved. CONCLUSIONS: Anorexia nervosa and alcohol use disorder may promote tissue injury, including kidney failure, specifically calcium phosphate crystalline nephropathy and IgA nephropathy. This multi-organ involvement may lose its reversibility if anorexia nervosa and alcohol use disorder remain persistent. An early diagnosis and a successful multidisciplinary approach may prevent life-threatening complications. LEVEL OF EVIDENCE: Level V, case report.

Gut microbiome in hemodialysis patients treated with calcium acetate or treated with sucroferric oxyhydroxide: a pilot study.

PURPOSE: It has been proved that the gut microbiome is altered in patients with chronic kidney disease. This contributes to chronic inflammation and increases cardiovascular risk and mortality, especially in those undergoing hemodialysis. Phosphate binders may potentially induce changes in their microbiome. This trial aimed to compare the changes in the gut microbiome of hemodialysis patients treated with calcium acetate to those treated with sucroferric oxyhydroxide. METHODS: Twelve hemodialysis patients were distributed to receive calcium acetate or sucroferric oxyhydroxide for 5 months. Blood samples (for biochemical analysis) and stool samples (for microbiome analysis) were collected at baseline, 4, 12, and 20 weeks after treatment initiation. Fecal DNA was extracted and a 16S rRNA sequencing library was constructed targeting the V3 and V4 hypervariable regions. RESULTS: Regarding clinical variables and laboratory parameters, no statistically significant differences were observed between calcium acetate or sucroferric oxyhydroxide groups. When analyzing stool samples, we found that all patients were different (p = 0.001) among themselves and these differences were kept along the 20 weeks of treatment. The clustering analysis in microbial profiles grouped the samples of the same patient independently of the treatment followed and the stage of the treatment. CONCLUSION: These results suggest that a 5-month treatment with either calcium acetate or sucroferric oxyhydroxide did not modify baseline diversity or baseline bacterial composition in hemodialysis patients, also about the high-variability profiles of the gut microbiome found among these patients.

Characterization of Oral Enterobacteriaceae Prevalence and Resistance Profile in Chronic Kidney Disease Patients Undergoing Peritoneal Dialysis.

Chronic Kidney Disease (CKD) is a growing public-health concern worldwide. Patients exhibit compromised immunity and are more prone to infection than other populations. Therefore, oral colonization by clinically relevant members of the Enterobacteriaceae family, major agents of both nosocomial and dialysis-associated infections with frequent prevalence of antibiotic resistances, may constitute a serious risk. Thus, this study aimed to assess the occurrence of clinically relevant enterobacteria and their antibiotic resistance profiles in the oral cavity of CKD patients undergoing peritoneal dialysis (CKD-PD) and compare it to healthy controls. Saliva samples from all the participants were cultured on MacConkey Agar and evaluated regarding the levels of urea, ammonia, and pH. Bacterial isolates were identified and characterized for antibiotic resistance phenotype and genotype. The results showed that CKD-PD patients exhibited significantly higher salivary pH, urea, and ammonia levels than controls, that was accompanied by higher prevalence and diversity of oral enterobacteria. Out of all the species isolated, only the prevalence of Raoultella ornithinolytica varied significantly between groups, colonizing the oral cavity of approximately 30% of CKD-PD patients while absent from controls. Antibiotic resistance phenotyping revealed mostly putative intrinsic resistance phenotypes (to amoxicillin, ticarcillin, and cephalothin), and resistance to sulfamethoxazole (~43% of isolates) and streptomycin (~17%). However, all isolates were resistant to at least one of the antibiotics tested and multidrug resistance isolates were only found in CKD-PD group (31,6%). Mobile genetic elements and resistance genes were detected in isolates of the species Raoultella ornithinolytica, Klebsiella pneumoniae, Klebsiella oxytoca, Escherichia coli, and Enterobacter asburiae, mostly originated from CKD-PD patients. PD-related infection history revealed that Enterobacteriaceae were responsible for ~8% of peritonitis and ~ 16% of exit-site infections episodes in CKD-PD patients, although no association was found to oral enterobacteria colonization at the time of sampling. The results suggest that the CKD-induced alterations of the oral milieu might promote a dysbiosis of the commensal oral microbiome, namely the proliferation of clinically relevant Enterobacteriaceae potentially harboring acquired antibiotic resistance genes. This study highlights the importance of the oral cavity as a reservoir for pathobionts and antibiotic resistances in CKD patients undergoing peritoneal dialysis.

Acute tubulointerstitial nephritis induced by the tyrosine kinase inhibitor vandetanib.

Few cases of immunoallergic tubulointerstitial nephritis associated with tyrosine kinase inhibitors have been described. We describe the first report case associated with vandetanib, a tyrosine kinase inhibitor indicated for the treatment of aggressive and symptomatic medullary thyroid cancer (CMT) in patients with locally advanced or metastatic non-resectable disease.