Removal of doravirine by haemodialysis in people living with HIV with end-stage renal disease.

OBJECTIVES: To evaluate the effect of haemodialysis on doravirine concentrations in people living with HIV (PLWH) undergoing routine haemodialysis. METHODS: An exploratory clinical trial that included PLWH undergoing intermittent haemodialysis was undertaken. After enrolment (day 1), doravirine 100 mg once daily was added to stable combined ART for 5 days. On day 6, blood samples were collected from each participant at the beginning and at the end of a dialysis session. Additionally, paired samples of blood entering ('in') and leaving ('out') the dialyser and the resulting dialysate were collected during the dialysis session to evaluate drug removal during dialysis. Doravirine concentrations in plasma and in the dialysate were determined by LC-MS/MS. The ratio of doravirine concentrations in plasma after/before the haemodialysis session and the haemodialysis extraction coefficient were calculated for each participant. The study was registered at https://www.clinicaltrials.gov (NCT04689737). RESULTS: Eight participants (six male) were included. The median (range) age and BMI were 49.5 (28-67) years and 23.6 (17.9-34.2) kg/m2, respectively. The doravirine dialysis extraction ratio was 34.3% (25.8%-41.4%). The ratio of doravirine concentrations in plasma after/before the haemodialysis session was 0.8 (0.6-1.0). At the end of the haemodialysis session (time post-dose 20.8-27.3 h), doravirine concentrations in plasma were 785 (101-1851) ng/mL. CONCLUSIONS: Despite moderate removal of doravirine by haemodialysis, trough doravirine concentrations in plasma after the haemodialysis sessions remained in excess of the protein-binding-adjusted EC50 (5 ng/mL). Doravirine dosage adjustments are unnecessary in PLWH undergoing intermittent haemodialysis.

Removal of Dolutegravir by Hemodialysis in HIV-Infected Patients with End-Stage Renal Disease.

Data on dolutegravir removal by hemodialysis are lacking. To study this, we measured dolutegravir plasma concentrations in samples of blood entering and leaving the dialyzer and of the resulting dialysate from 5 HIV-infected patients with end-stage renal disease. The median dolutegravir hemodialysis extraction ratio was 7%. The dolutegravir concentrations after the dialysis session remained far above the protein-binding-adjusted inhibitory concentration. Our results show minimal dolutegravir removal by hemodialysis, with no specific dolutegravir dosage adjustments required in this setting. (This study is registered at ClinicalTrials.gov under registration number NCT02487706.).

Poor histological lesions in IgA nephropathy may be reflected in blood and urine peptide profiling.

BACKGROUND: IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide, leading to renal failure in 15% to 40% of cases. IgAN is diagnosed by renal biopsy, an invasive method that is not risk-free. We used blood and urine peptide profiles as a noninvasive method of linking IgAN-associated changes with histological lesions by Oxford classification. METHODS: We prospectively studied 19 patients with biopsy-proven IgAN and 14 healthy subjects from 2006 to 2009, excluding subjects with crescentic glomerulonephritis and collecting clinical and biochemical data at the time of diagnosis and during follow-up (24 months). Histological lesions were evaluated by Oxford classification. Proteomic analysis was performed by combining magnetic bead (MB) technology and mass spectrometry (MALDI-TOF MS) to obtain peptide profiles. Doubling of serum creatinine was considered a variable of poor renal prognosis. RESULTS: We identified 55 peptides-13 in serum, 26 in plasma, and 16 in urine-that differentiated IgAN patients from healthy subjects. A significant association was noted between serum/plasma and urine peptides and histological findings-ie, tubulointerstitial damage, segmental glomerulosclerosis, and endocapillary injury. CONCLUSIONS: In patients with IgAN, the use of noninvasive approaches, such as blood and urine proteomics, can provide valuable information beyond that of standard diagnostic techniques, allowing us to identify blood and urine peptide profiles that are associated with poor histological lesions in IgAN patients.

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.

The "FIFTY SHADOWS" of the RALES Trial: Lessons about the Potential Risk of Dietary Potassium Supplementation in Patients with Chronic Kidney Disease.

Hyperkalaemia (HK) is one of the most common electrolyte disorders and a frequent reason for nephrological consultations. High serum potassium (K+) levels are associated with elevated morbidity and mortality, mainly due to life-threatening arrhythmias. In the majority of cases, HK is associated with chronic kidney disease (CKD), or with the use of renin-angiotensin-aldosterone system inhibitors (RAASis) and/or mineral corticoid antagonists (MRAs). These drugs represent the mainstays of treatment in CKD, HF, diabetes, hypertension, and even glomerular diseases, in consideration of their beneficial effect on hard outcomes related to cardiovascular events and CKD progression. However, experiences in relation to the Randomised Aldactone Evaluation Study (RALES) cast a long shadow that extends to the present day, since the increased risk for HK remains a major concern. In this article, we summarise the physiology of K+ homeostasis, and we review the effects of dietary K+ on blood pressure and cardiovascular risk in the general population and in patients with early CKD, who are often not aware of this disease. We conclude with a note of caution regarding the recent publication of the SSaSS trial and the use of salt substitutes, particularly in patients with a limited capacity to increase K+ secretion in response to an exogenous load, particularly in the context of "occult" CKD, HF, and in patients taking RAASis and/or MRAs.

Silver jubilee: 25 years of the first demonstration of the direct effect of phosphate on the parathyroid cell.

Although phosphorus is an essential element for life, it is not found in nature in its native state but rather combined in the form of inorganic phosphates (PO43-), with tightly regulated plasma levels that are associated with deleterious effects and mortality when these are out of bounds. The growing interest in the accumulation of PO43- in human pathophysiology originated in its attributed role in the pathogenesis of secondary hyperparathyroidism (SHPT) in chronic kidney disease. In this article, we review the mechanisms by which this effect was justified and we commemorate the important contribution of a Spanish group led by Dr. M. Rodríguez, just 25 years ago, when they first demonstrated the direct effect of PO43- on the regulation of the synthesis and secretion of parathyroid hormone by maintaining the structural integrity of the parathyroid glands in their original experimental model. In addition to demonstrating the importance of arachidonic acid (AA) and the phospholipase A2-AA pathway as a mediator of parathyroid gland response, these findings were predecessors of the recent description of the important role of PO43- on the activity of the calcium sensor-receptor, and also fueled various lines of research on the importance of PO43- overload not only for the pathophysiology of SHPT but also in its systemic pathogenic role.

Routine Biomarkers for the Severity of COVID-19 Pneumonia May Present Differently in Kidney Transplant Recipients.

BACKGROUND: The treatment of coronavirus disease 2019 (COVID-19) is based on the patient's clinical status and levels of inflammatory biomarkers. The comparative activity of these biomarkers in kidney transplant (KT) patients with COVID-19 pneumonia from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and non-SARS-CoV-2 etiologies is unknown. The aim of this study was to compare the clinical presentation and inflammatory parameters at admission of KT patients with COVID-19 pneumonia and those with non-COVID-19 pneumonia over the same period. METHODS: Biomarkers were measured and compared between KT patients with COVID-19 pneumonia (n = 57) and non-COVID-19 pneumonia (n = 20) from March 2020 to March 2021. RESULTS: Both groups showed comparable demographics. The KT patients with COVID-19 had fewer neutrophils (6824 ± 5000 vs 8969 ± 4206; P = .09) than the non-COVID group, although there was no significant difference in the lymphocyte count. Non-COVID-19 pneumonia was associated with higher d-dimer (median, 921 [interquartile range (IQR), 495-1680] vs median, 2215 [IQR, 879-3934]; P = 0.09) and interleukin-6 (median, 35 [IQR, 20-128] vs median, 222 [IQR, 38-500]; P = 0.006) levels. The ferritin level was higher in the COVID-19 group (median, 809 [IQR, 442-1,330] vs median, 377 [IQR, 276-885]; P = 0.008). In multivariable analysis, only d-dimer (hazard ratio [HR], 1; 95% confidence interval [CI],1-1.002; P = .02) and ferritin (HR, 1; 95% CI, 0.9-0.9; P = .02) increase the statistic signification. CONCLUSION: COVID-19 pneumonia in KT patients shows a different presentation of inflammatory biomarkers than other non-COVID pneumonias. It could be useful to identify KT patients with COVID-19. More detailed studies are necessary to understand the presentation of biomarkers in KT with COVID-19.

Preload dependence of pulmonary haemodynamics and right ventricular performance.

AIMS: Systolic pulmonary artery pressure (SPAP) and right heart adaptation in relation to pre-existing preload are often disregarded. To determine volume-related changes in the pulmonary-right ventricle (RV) unit and the preload dependence of its components, we analysed pulmonary haemodynamics and right ventricular performance, taking advantage of the plasma volume removal associated to haemodialysis (HD). METHODS AND RESULTS: Fifty-three stable patients on chronic HD with LVEF > 50% and without heart failure were recruited (mean age 63.0 ± 12.4 years; 31.2% women; hypertension in 89% and diabetes in 53%) and evaluated just before and after HD (mean ultrafiltration volume 2.4 ± 0.7 l). SPAP from both times were available in 39 patients. After HD, SPAP decreased (42.2 ± 12.6 to 33.7 ± 11.6 mmHg, p < 0.001) without modification of non-invasive pulmonary vascular resistance (1.75 ± 0.44 to 1.75 ± 0.40 eWU, p = 0.94). Age and drop in the E/e' ratio were the variables associated with greater reduction in PASP (p = 0.022 and p = 0.049, respectively). A significant reduction of right chamber sizes was observed, along with a diminution in measures of RV contractility, excluding RV longitudinal strain. Functional tricuspid regurgitation (FTR) diminution was observed in 26% of patients, occurring in every case with more than mild FTR. On multivariate analyses, left atrial size was the only predictor of pulmonary hypertension (defined as SPAP > 40 mmHg) (OR 1.29 (1.07-1.56), p = 0.006). CONCLUSION: Rapid volemic changes may affect FTR grading, RV size and contractility, with RV longitudinal strain being less variable than conventional parameters. SPAP decreases after HD, and this reduction is related to age and greater diminution of the E/e' ratio.

Frail Patient in Hemodialysis: A New Challenge in Nephrology-Incidence in Our Area, Barcelonès Nord and Maresme.

INTRODUCTION: Labeling a patient as "frail" may be useful in assessing the prognosis and therapeutic approach. OBJECTIVE: The aim of the study is to define a pattern of frailty among our dialysis population, to analyse the incidence and clinical evolution of these patients. MATERIALS AND METHODS: We analysed a total of 320 patients with stage V chronic kidney disease (CKD) who were on hemodialysis between September 2014 and September 2015. To define a patient as frail we used the Fried phenotype model, and we added a new criteria-dialysis session length longer than 12 hours/week. RESULTS: 5.6% of the 320 patients were frail. We found statistically significant differences regarding body mass index (BMI), hemoglobin (Hgb), and serum albumin, as well as the ability to perform the basic activities of daily living (p < 0.005), ability to ambulate (p = 0.01) and perform transfers (p < 0.005). We found statistically significant differences between the two groups in terms of hospital admissions (p = 0.005) and mortality (p < 0.005). CONCLUSION: 5.6% of the study population were frail, with lower BMI, serum albumin and hemoglobin, lower capacity for basic activities of daily living, ambulation, and transference, as well as higher morbidity and mortality.

Prevalencia de síntomas asociados al síndrome de intestino irritable, según los criterios de Roma II, en estudiantes de medicina de la Escuela José María Vargas de la Universidad Central de Venezuela: Caracas, mayo 2005

Introducción: El síndrome de intestino irritable (SII) es una entidad clínica idiopática crónica, recurrente y común, de difícil diagnóstico por la falta de exámenes definitivos para identificar esta entidad, siendo la base diagnóstica la evaluación sintomática. Se ha descrito el estrés emocional como un factor predisponerte para la aparición de los síntomas que identifican al SII, pudiéndose presentar con una alta prevalencia en la población joven y universitaria. Objetivos: Determinar la prevalencia de Síndrome de Intestino Irritable, según los Criterios de Roma II, en la población de estudiantes de medicina de la Escuela José María Vargas de Caracas, Venezuela. Materiales Y Métodos: A una muestra de 198 estudiantes, aparentemente sanos, de la Escuela José María Vargas, escogidos al azar, se les aplicó una encuesta, tipo cuestionario, previo consentimiento verbal individual, en la que se interrogaban los criterios de Roma II, en el período de abril-mayo 2005. Resultados: Según los criterios de Roma II la prevalencia del Síndrome de Intestino Irritable en esta población estudiantil es de 21.16%, de los cuales 75% fueron del sexo femenino, mientras que de la población masculina solo el 16,39% cumplieron estos criterios. Con una edad promedio de 20.25 años. Conclusion: Existe una alta prevalencia de SII en la población estudiantil universitaria de medicina, donde se puede presentar como factor predisponente el estrés.

Introduction: Irritable bowel syndrome (IBS) is a clinical, idiopathic, chronic and common disorder of difficult diagnosis because of the lack of definitive tests to identify this disease; the diagnosis is based on symptomatic evaluation. A correlation between the prevalence of this disorder and day to day stress has been found, therefore a high prevalence could be found in populations such as university students, especially those in the health area. Objective: This study attempts to determine the prevalence of this disorder in the population of medical students at the José María Vargas School, according to the Rome II criteria. Caracas - Venezuela. Materials And Methods: A questionnaire -type survey was applied to a sample of 198 apparently healthy, randomly selected students, of the José María Vargas School of Medicine, in the time period of April-May 2005.Results: According to the Roma II criteria the prevalence of IBS in this student population is of 21,16%, 75% of which were females. Among the male population surveyed, only 16,39% fulfilled these criteria. The mean age was 20 years. Conclusion: There is a high prevalence of Irritable Bowel Syndrome in the medical student population, where high levels of stress may act as a predisposing factor.