Metabolic Pathways Affected in Patients Undergoing Hemodialysis and Their Relationship with Inflammation.

Worldwide, 3.9 million individuals rely on kidney replacement therapy. They experience heightened susceptibility to cardiovascular diseases and mortality, alongside an increased risk of infections and malignancies, with inflammation being key to explaining this intensified risk. This study utilized semi-targeted metabolomics to explore novel metabolic pathways related to inflammation in this population. We collected pre- and post-session blood samples of patients who had already undergone one year of chronic hemodialysis and used liquid chromatography and high-resolution mass spectrometry to perform a metabolomic analysis. Afterwards, we employed both univariate (Mann-Whitney test) and multivariate (logistic regression with LASSO regularization) to identify metabolites associated with inflammation. In the univariate analysis, indole-3-acetaldehyde, 2-ketobutyric acid, and urocanic acid showed statistically significant decreases in median concentrations in the presence of inflammation. In the multivariate analysis, metabolites positively associated with inflammation included allantoin, taurodeoxycholic acid, norepinephrine, pyroglutamic acid, and L-hydroorotic acid. Conversely, metabolites showing negative associations with inflammation included benzoic acid, indole-3-acetaldehyde, methionine, citrulline, alphaketoglutarate, n-acetyl-ornithine, and 3-4-dihydroxibenzeneacetic acid. Non-inflamed patients exhibit preserved autophagy and reduced mitochondrial dysfunction. Understanding inflammation in this group hinges on the metabolism of arginine and the urea cycle. Additionally, the microbiota, particularly uricase-producing bacteria and those metabolizing tryptophan, play critical roles.

Uremic Toxins and Inflammation: Metabolic Pathways Affected in Non-Dialysis-Dependent Stage 5 Chronic Kidney Disease.

Chronic kidney disease (CKD) affects approximately 12% of the global population, posing a significant health threat. Inflammation plays a crucial role in the uremic phenotype of non-dialysis-dependent (NDD) stage 5 CKD, contributing to elevated cardiovascular and overall mortality in affected individuals. This study aimed to explore novel metabolic pathways in this population using semi-targeted metabolomics, which allowed us to quantify numerous metabolites with known identities before data acquisition through an in-house polar compound library. In a prospective observational design with 50 patients, blood samples collected before the initial hemodialysis session underwent liquid chromatography and high-resolution mass spectrometer analysis. Univariate (Mann-Whitney test) and multivariate (logistic regression with LASSO regularization) methods identified metabolomic variables associated with inflammation. Notably, adenosine-5'-phosphosulfate (APS), dimethylglycine, pyruvate, lactate, and 2-ketobutyric acid exhibited significant differences in the presence of inflammation. Cholic acid, homogentisic acid, and 2-phenylpropionic acid displayed opposing patterns. Multivariate analysis indicated increased inflammation risk with certain metabolites (N-Butyrylglycine, dimethylglycine, 2-Oxoisopentanoic acid, and pyruvate), while others (homogentisic acid, 2-Phenylpropionic acid, and 2-Methylglutaric acid) suggested decreased probability. These findings unveil potential inflammation-associated biomarkers related to defective mitochondrial fatty acid beta oxidation and branched-chain amino acid breakdown in NDD stage 5 CKD, shedding light on cellular energy production and offering insights for further clinical validation.

Acquired perforating dermatosis in patients on peritoneal dialysis: a report of 3 cases.

Background: Acquired perforating dermatosis (APD) is a heterogeneous group of unfrequented diseases (2.5 cases for 100,000 habitants) associated with multiple pathologies like end-stage renal disease and other concomitant conditions such as diabetes mellitus (DM). Case Description: We described 3 cases of APD in patients on peritoneal dialysis (PD), one of them with a giant variant of reactive perforating collagenosis (RPC). The first case is a 28-year-old man with chronic kidney disease on PD and a lousy control of disturbances of calcium and phosphorus metabolism that develops an APD. The second case is a 44-year-old man with DM, chronic kidney disease (CKD) on PD, and poor control of disturbances of calcium and phosphorus metabolism that develops an RPC. The third case is a 58-year-old man with DM, rheumatoid arthritis, hypothyroidism, CKD and bad control of calcium and phosphorus metabolism that develops a giant variant of RPC with poor evolution. Conclusions: CKD and concomitant conditions such as DM present an increased risk of developing APD. Poor control of calcium and phosphorus metabolism is frequently found in patients with CKD and seems to be related to the development of APD in our cases. With the description of these cases, we want to emphasize the importance of knowing this rare disease, in order to promptly refer to Dermatology and start treatment.

Therapeutic approach in heart failure with poor diuretic response: peripheral ultrafiltration vs. conventional treatment.

AIMS: Patients with heart failure (HF) admitted for decompensation often require high doses of intravenous diuretics. This study aims to analyse whether the use of peripheral ultrafiltration (UF) in patients hospitalized for acute HF with systemic-predominant congestion results in better hydric control, renal protection, and reduction of hospital stay compared with conventional treatment. METHODS AND RESULTS: This study was a retrospective, comparative, single-centre study of 56 patients admitted for HF with systemic congestion with a poor diuretic response after diuretic escalation. One group underwent peripheral UF (35 patients) and others were maintained on intense diuretic treatment (control group, 21 patients). The diuretic response and days of hospital stay were compared between and within groups. The baseline characteristics of both groups were similar: males with right ventricular failure and renal dysfunction. The inter-group analysis showed that patients who received UF had better glomerular filtration rate (GFR; UF: 39.2 ± 18.2 vs. control: 28.7 ± 13.4 mL/min; P = 0.031) and higher diuresis (UF: 2184 ± 735 vs. control: 1335 ± 297 mL; P = 0.0001) at hospital discharge despite less need for diuretic drugs. Days of hospital stay were shorter in the UF group (UF: 11.7 ± 10.1 vs. control: 19.1 ± 14.4 days; P = 0.027). Intra-group analysis showed that patients receiving UF improved GFR, increased diuresis, and reduced weight at discharge (P < 0.001), whereas patients on conventional treatment only experienced improved weight but worsening renal function at discharge. CONCLUSIONS: In patients with acute HF with systemic congestion and diuretic resistance, UF compared with conventional treatment produces greater decongestion and renal protection, reduces the total diuretic load, and shortens the length of hospital stay.

Characteristics and technical survival of home hemodialysis in the Valencian Community (1976-2020).

INTRODUCTION: Home hemodialysis (HDD) is implemented in the Valencian Community with a higher prevalence than to the rest of the national territory, with a prevalence of 13.4 patients pmp in December 2018. We carried out an assessment of the patients characteristics and the overall and technical survival in HDD depending on the historical moment of onset and its origin. MATERIAL AND METHODS: We conducted a retrospective and descriptive study including patients of the Valencian Registry of Renal Patients from the beginning of data reported until December 2020. We calculated overall survival (combined event death-technical failure, censoring transplantation) and technical survival (event technical failure, censoring exitus and transplantation). Comparing technical survival according to the starting era: ancient (1976-2000) vs modern (2001-2020) and according to the modality of origin. We performed univariate and multivariate Cox regression in the total series for both overall and technical survival. RESULTS: 236 patients on HDD (611.4 patient-years of follow-up), mean age 49.7±16.3 years; median time of prior renal replacement therapy 0.2 years. The ratio of transplantation, death, and technical failure were 13.2, 4.4, and 7 events per 100 patient-years, respectively. In the comparison by ancient (n=57) vs modern (n=179) eras, age (37.5 vs 53.5 years), DM (3.5 vs 13.4%) and chronic tubuleinterstitial nephropathy (24.6 vs 8.9%) as a cause of chronic kidney disease were statistically significant. The probability of coming from outpatient consultation (33.3 vs 48.6%) and peritoneal dialysis (1.8 vs 12.8%) were higher in modern era with statistical significance. In the ancient era a single hospital centralized 57.9% of the patients, and in the modern era between two hospitals centralized 55.8% of the patients. Overall survival in the ancient era was 83.7% at 1year, 77.4% at 2 years, and 61% at 5 years; and in the modern era 87.3% per year, 83% 2 years and 47.8% 5 years (Log Rank 0.521). Technical survival in the ancient era was 85.4% at 1year, 79% 2 years, and 64.1% 5 years; and in the modern era 91.4% per year, 88.5% 2 years and 74.5% 5 years (Log Rank 0.195). There were no statistical differences in the comparison based on technical of provenance. In the Cox regression it was statistically significant for overall survival: the age and being diagnosed with heart disease, vascular disease or active neoplasia and for technical survival liver disease or social problem, both in univariate and multivariate. CONCLUSIONS: In the modern era there is a considerable increase in HDD patients in the Valencian Community. There was a center effect in the development of HDD programs, most of the patients depended on few healthcare centers. The patients were older and had greater comorbidity in the modern era, despite this without affecting the technical and overall survival of the HDD.

Characteristics and technical survival of home hemodialysis in the Valencian Community (1976-2020). / C aracterísticas y supervivencia técnica de la hemodiálisis domiciliaria en la Comunidad Valenciana (1976-2020).

INTRODUCTION: Home hemodialysis (HDD) is implemented in the Valencian Community with a higher prevalence than to the rest of the national territory, with a prevalence of 13.4 patients' pmp in December 2018. We carried out an assessment of the patients' characteristics and the overall and technical survival in HDD depending on the historical moment of onset and its origin. MATERIAL AND METHODS: We conducted a retrospective and descriptive study including patients of the Valencian Registry of Renal Patients from the beginning of data reported until December 2020. We calculated overall survival (combined event death-technical failure, censoring transplantation) and technical survival (event technical failure, censoring exitus and transplantation). Comparing technical survival according to the starting era: ancient (1976-2000) vs modern (2001-2020) and according to the modality of origin. We performed univariate and multivariate Cox regression in the total series for both overall and technical survivals. RESULTS: 236 patients on HDD (611.4 patient-years of follow-up), mean age 49.7±16.3 years; median time of prior renal replacement therapy 0.2 years. The ratio of transplantation, death, and technical failure were 13.2, 4.4, and 7 events per 100 patient-years, respectively. In the comparison by ancient (n=57) vs modern (n=179) eras, age (37.5 vs 53.5 years), DM (3.5 vs 13.4%) and chronic tubuleinterstitial nephropathy (24.6 vs 8.9%) as a cause of chronic kidney disease were statistically significant. The probability of coming from outpatient consultation (33.3 vs 48.6%) and peritoneal dialysis (1.8 vs 12.8%) were higher in modern era with statistical significance. In the ancient era a single hospital centralized 57.9% of the patients, and in the modern era between two hospitals centralized 55.8% of the patients. Overall survival in the ancient era was 83.7% at 1 year, 77.4% at 2 years, and 61% at 5 years; and in the modern era 87.3% per year, 83% 2 years and 47.8% 5 years (Log Rank 0.521). Technical survival in the ancient era was 85.4% at 1 year, 79% 2 years, and 64.1% 5 years; and in the modern era 91.4% per year, 88.5% 2 years and 74.5% 5 years (Log Rank 0.195). There were no statistical differences in the comparison based on technical of provenance. In the Cox regression it was statistically significant for overall survival: the age and being diagnosed with heart disease, vascular disease or active neoplasia and for technical survival liver disease or social problem, both in univariate and multivariate. CONCLUSION: In the modern era there is a considerable increase in HDD patients in the Valencian Community. There was a center effect in the development of HDD programs, most of the patients depended on few healthcare centers. The patients were older and had greater comorbidity in the modern era, despite this without affecting the technical and overall survival of the HDD.

[Results of a healthcare organization model for COVID-19 on hemodialysis in a tertiary hospital and its subsidized centers]. / Resultados de un modelo de organización asistencial para COVID-19 en hemodiálisis en un hospital terciario y sus centros concertados.

The experience of a tertiary hospital and four hemodialysis centers attached to it during the COVID-19 epidemic is described. The organization of care that has been carried out and the clinical course of the 16cases of COVID-19 in hemodialysis patients are summarized. The joint application of measures, including patient screening, the early investigation of possible cases, the isolation of confirmed, investigational or contact cases, as well as the use of individual protection measures, has enabled the epidemic to be controlled. The clinical course of these 16patients is compared with the series published by the Wuhan University Hospital and with the data from the COVID-19 infection registry of the Spanish Society of Nephrology. In our experience, and unlike what was reported by the Wuhan Center, COVID-19 disease in hemodialysis patients is severe in a significant percentage of cases, and high lethality is mostly caused by the infection itself. Measures to contain the epidemic are effective.