Metabolomics of Plasma in XLH Patients with Arterial Hypertension: New Insights into the Underlying Mechanisms.

X-linked hypophosphatemia (XLH) is a rare genetic disorder that increases fibroblast growth factor 23 (FGF23). XLH patients have an elevated risk of early-onset hypertension. The precise factors contributing to hypertension in XLH patients have yet to be identified. A multicenter cross-sectional study of adult patients diagnosed with XLH. Metabolomic analysis was performed using ultra-performance liquid chromatography (UPLC) coupled to a high-resolution mass spectrometer. Twenty subjects were included, of which nine (45%) had hypertension. The median age was 44 years. Out of the total, seven (35%) subjects had a family history of hypertension. No statistically significant differences were found between both groups for nephrocalcinosis or hyperparathyroidism. Those with hypertension exhibited significantly higher levels of creatinine (1.08 ± 0.31 mg/dL vs. 0.78 ± 0.19 mg/dL; p = 0.01) and LDL-C (133.33 ± 21.92 mg/dL vs. 107.27 ± 20.12 mg/dL, p = 0.01). A total of 106 metabolites were identified. Acetylcarnitine (p = 0.03), pyruvate p = (0.04), ethanolamine (p = 0.03), and butyric acid (p = 0.001) were significantly different between both groups. This study is the first to examine the metabolomics of hypertension in patients with XLH. We have identified significant changes in specific metabolites that shed new light on the potential mechanisms of hypertension in XLH patients. These findings could lead to new studies identifying associated biomarkers and developing new diagnostic approaches for XLH patients.

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.

Role of the Nephrologist in Non-Kidney Solid Organ Transplant (NKSOT).

BACKGROUND: Chronic kidney disease (CKD) is a common complication of a non-kidney solid organ transplant (NKSOT). Identifying predisposing factors is crucial for an early approach and correct referral to nephrology. METHODS: This is a single-center retrospective observational study of a cohort of CKD patients under follow-up in the Nephrology Department between 2010 to 2020. Statistical analysis was performed between all the risk factors and four dependent variables: end-stage renal disease (ESKD); increased serum creatinine ≥50%; renal replacement therapy (RRT); and death in the pre-transplant, peri-transplant, and post-transplant periods. RESULTS: 74 patients were studied (7 heart transplants, 34 liver transplants, and 33 lung transplants). Patients who were not followed-up by a nephrologist in the pre-transplant (p < 0.027) or peri-transplant (p < 0.046) periods and those who had the longest time until an outpatient clinic follow-up (HR 1.032) were associated with a higher risk of creatinine increase ≥50%. Receiving a lung transplant conferred a higher risk than a liver or heart transplant for developing a creatinine increase ≥50% and ESKD. Peri-transplant mechanical ventilation, peri-transplant and post-transplant anticalcineurin overdose, nephrotoxicity, and the number of hospital admissions were significantly associated with a creatinine increase ≥50% and developing ESKD. CONCLUSIONS: Early and close follow-up by a nephrologist was associated with a decrease in the worsening of renal function.

The metabolomic differential plasma profile between dialysates. Pursuing to understand the mechanisms of citrate dialysate clinical benefits.

Background: Currently, bicarbonate-based dialysate needs a buffer to prevent precipitation of bicarbonate salts with the bivalent cations, and acetate at 3-4 mmol/L is the most used. However, citrate is being postulated as a preferred option because of its association with better clinical results by poorly understood mechanisms. In that sense, this hypothesis-generating study aims to identify potential metabolites that could biologically explain these improvements found in patients using citrate dialysate. Methods: A unicentric, cross-over, prospective untargeted metabolomics study was designed to analyze the differences between two dialysates only differing in their buffer, one containing 4 mmol/L of acetate (AD) and the other 1 mmol/L of citrate (CD). Blood samples were collected in four moments (i.e., pre-, mid-, post-, and 30-min-post-dialysis) and analyzed in an untargeted metabolomics approach based on UPLC-Q-ToF mass spectrometry. Results: The 31 most discriminant metabolomic variables from the plasma samples of the 21 participants screened by their potential clinical implications show that, after dialysis with CD, some uremic toxins appear to be better cleared, the lysine degradation pathway is affected, and branched-chain amino acids post-dialysis levels are 9-10 times higher than with AD; and, on its part, dialysis with AD affects acylcarnitine clearance. Conclusion: Although most metabolic changes seen in this study could be attributable to the dialysis treatment itself, this study successfully identifies some metabolic variables that differ between CD and AD, which raise new hypotheses that may unveil the mechanisms involved in the clinical improvements observed with citrate in future research.

Impact of Acetate versus Citrate Dialysates on Intermediary Metabolism-A Targeted Metabolomics Approach.

Acetate is widely used as a dialysate buffer to avoid the precipitation of bicarbonate salts. However, even at low concentrations that wouldn't surpass the metabolic capacity of the Krebs tricarboxylic acid (TCA) cycle, other metabolic routes are activated, leading to undesirable clinical consequences by poorly understood mechanisms. This study aims to add information that could biologically explain the clinical improvements found in patients using citrate dialysate. A unicentric, cross-over, prospective targeted metabolomics study was designed to analyze the differences between two dialysates, one containing 4 mmol/L of acetate (AD) and the other 1 mmol/L of citrate (CD). Fifteen metabolites were studied to investigate changes induced in the TCA cycle, glycolysis, anaerobic metabolism, ketone bodies, and triglyceride and aminoacidic metabolism. Twenty-one patients completed the study. Citrate increased during the dialysis sessions when CD was used, without surpassing normal values. Other differences found in the next TCA cycle steps showed an increased substrate accumulation when using AD. While lactate decreased, pyruvate remained stable, and ketogenesis was boosted during dialysis. Acetylcarnitine and myo-inositol were reduced during dialysis, while glycerol remained constant. Lastly, glutamate and glutarate decreased due to the inhibition of amino acidic degradation. This study raises new hypotheses that need further investigation to understand better the biochemical processes that dialysis and the different dialysate buffers induce in the patient's metabolism.

Lipidic profiles of patients starting peritoneal dialysis suggest an increased cardiovascular risk beyond classical dyslipidemia biomarkers.

Patients on peritoneal dialysis (PD) have an increased risk of cardiovascular disease (CVD) and an atherogenic lipid profile generated by exposure to high glucose dialysis solutions. In the general population, the reduction of classic lipids biomarkers is associated with improved clinical outcomes; however, the same results have not been seen in PD population, a lack of data this study aims to fulfill. Single-center prospective observational study of a cohort of CKD patients who started renal replacement therapy with continuous ambulatory peritoneal dialysis. The differences in the lipid profile and analytical variables before and 6 months after the start of peritoneal dialysis were analyzed. Samples were analyzed on an Ultra-Performance Liquid Chromatography system. Thirty-nine patients were enrolled in this study. Their mean age was 57.9 ± 16.3 years. A total of 157 endogenous lipid species of 11 lipid subclasses were identified. There were significant increases in total free fatty acids (p < 0.05), diacylglycerides (p < 0.01), triacylglycerides, (p < 0.01), phosphatidylcholines (p < 0.01), phosphatidylethanolamines (p < 0.01), ceramides (p < 0.01), sphingomyelins (p < 0.01), and cholesterol esters (p < 0.01) from baseline to 6 months. However, there were no differences in the classical lipid markers, neither lysophosphatidylcholines, monoacylglycerides, and sphingosine levels. 6 months after the start of the technique, PD patients present changes in the lipidomic profile beyond the classic markers of dyslipidemia.

Improvements in Inflammation and Calcium Balance of Citrate versus Acetate as Dialysate Buffer in Maintenance Hemodialysis: A Unicentric, Cross-Over, Prospective Study.

INTRODUCTION: The composition of the dialysate is a crucial feature in the dialysis treatment. Two of its most debated elements are the optimal calcium concentration and the use of acetate as a buffer. Moreover, among the different alternatives to achieve acetate-free dialysis, the use of citrate is postulated as the most suitable option. The objective of this study is to identify the potential beneficial effects of citrate when compared to acetate dialysate (AD) both in short-term effects (especially regarding intradialytic calcium balance and cardiac damage biomarkers) and in medium-term ones with CKD-mineral and bone disorder (CKD-MBD) and inflammatory biomarkers measured after twelve sessions performed with each dialysate. METHODS: This is a unicentric, cross-over, prospective study. Each patient underwent 24 dialysis sessions, 12 with each dialysate buffer. Blood samples were taken in 2 different sessions with each acidifier. They include CKD-MBD and inflammatory biomarkers. The calcium concentration of both dialysates was 1.5 mmol/L, while all other dialysis parameters and patients' treatment remained unchanged during the study period. RESULTS: When comparing AD and citrate dialysate (CD), there were no differences in pre-dialysis ionized calcium (iCa) (1.11 vs. 1.08 mmol/L) in both groups. However, there was a significant increase in iCa with the use of AD in immediate and 30-min post-dialysis blood samples. In contrast, iCa levels remained stable with the use of citrate. Inflammatory biomarkers were also reduced after the use of CD. CONCLUSIONS: The use of citrate provides interesting advantages when compared to acetate. It maintains iCa levels stable during dialysis sessions with a neutral or negative effect on calcium balance, and it improves the chronic inflammatory condition that comes with long-time hemodialysis treatment. These beneficial effects may lead to an improvement in clinical outcomes.

Raquitismo hipofosfatémico ligado al cromosoma X: diagnóstico en la edad adulta y forma paucisintomática / X-linked hypophosphatemic rickets: Diagnosis in adult and paucisymptomatic form

El raquitismo hipofosfatémico ligado al cromosoma X (XLH) es la principal forma de raquitismo hereditario causada por la mutación del gen PHEX y que se manifiesta principalmente en la infancia. Clínicamente cursa con retraso en el crecimiento y deformidades óseas, sin embargo, existen formas de presentación atípicas que dificultan el diagnóstico. Presentamos un caso de XLH con diagnóstico tardío y forma paucisintomática que presenta múltiples fracturas y gran afectación en su calidad de vida, en tratamiento con la terapia clásica para esta enfermedad.(AU)

X-linked hypophosphataemic rickets (XLH) is the main form of hereditary rickets caused by mutation of the PHEX gene and occurs mainly in childhood. Clinically, it causes growth retardation and bone deformities; however, there are atypical forms of presentation that make diagnosis difficult. We present a case of XLH of late diagnosis and paucisymptomatic form with multiple fractures and greatly affecting quality of life, under treatment with traditional therapy for this disease.(AU)

X-linked hypophosphatemic rickets: Diagnosis in adult and paucisymptomatic form. / Raquitismo hipofosfatémico ligado al cromosoma X: diagnóstico en la edad adulta y forma paucisintomática.

X-linked hypophosphataemic rickets (XLH) is the main form of hereditary rickets caused by mutation of the PHEX gene and occurs mainly in childhood. Clinically, it causes growth retardation and bone deformities; however, there are atypical forms of presentation that make diagnosis difficult. We present a case of XLH of late diagnosis and paucisymptomatic form with multiple fractures and greatly affecting quality of life, under treatment with traditional therapy for this disease.

Mosaicismo en 2 casos de hipofosfatemia ligada al cromosoma X / Mosaicism in 2 cases of X-linked hypophosphatemia

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