Considerations about the inhibition of monophenolase and diphenolase activities of tyrosinase. Characterization of the inhibitor concentration which generates 50 % of inhibition, type and inhibition constants. A review.

Tyrosinase is a copper oxidase enzyme which catalyzes the first two steps in the melanogenesis pathway, L-tyrosine to L-dopa conversion and, then, to o-dopaquinone and dopachrome. Hypopigmentation and, above all, hyperpigmentation issues can be originated depending on their activity. This enzyme also promotes the browning of fruits and vegetables. Therefore, control of their activity by regulators is research topic of great relevance. In this work, we consider the use of inhibitors of monophenolase and diphenolase activities of the enzyme in order to accomplish such control. An experimental design and data analysis which allow the accurate calculation of the degree of inhibition of monophenolase activity (iM) and diphenolase activity (iD) are proposed. The IC50 values (amount of inhibitor that causes 50 % inhibition at a fixed substrate concentration) can be calculated for the two activities and from the values of IC50M (monophenolase) and IC50D(diphenolase). Additionally, the strength and type of inhibition can be deduced from these values. The data analysis from these IC50D values allows to obtain the values of [Formula: see text] or [Formula: see text] , or and [Formula: see text] from the values of IC50M. In all cases, the values of the different must satisfy their relationship with IC50M and IC50D.

Prediction of Effectiveness and Toxicities of Immune Checkpoint Inhibitors Using Real-World Patient Data.

PURPOSE: Although immune checkpoint inhibitors (ICIs) have improved outcomes in certain patients with cancer, they can also cause life-threatening immunotoxicities. Predicting immunotoxicity risks alongside response could provide a personalized risk-benefit profile, inform therapeutic decision making, and improve clinical trial cohort selection. We aimed to build a machine learning (ML) framework using routine electronic health record (EHR) data to predict hepatitis, colitis, pneumonitis, and 1-year overall survival. METHODS: Real-world EHR data of more than 2,200 patients treated with ICI through December 31, 2018, were used to develop predictive models. Using a prediction time point of ICI initiation, a 1-year prediction time window was applied to create binary labels for the four outcomes for each patient. Feature engineering involved aggregating laboratory measurements over appropriate time windows (60-365 days). Patients were randomly partitioned into training (80%) and test (20%) sets. Random forest classifiers were developed using a rigorous model development framework. RESULTS: The patient cohort had a median age of 63 years and was 61.8% male. Patients predominantly had melanoma (37.8%), lung cancer (27.3%), or genitourinary cancer (16.4%). They were treated with PD-1 (60.4%), PD-L1 (9.0%), and CTLA-4 (19.7%) ICIs. Our models demonstrate reasonably strong performance, with AUCs of 0.739, 0.729, 0.755, and 0.752 for the pneumonitis, hepatitis, colitis, and 1-year overall survival models, respectively. Each model relies on an outcome-specific feature set, though some features are shared among models. CONCLUSION: To our knowledge, this is the first ML solution that assesses individual ICI risk-benefit profiles based predominantly on routine structured EHR data. As such, use of our ML solution will not require additional data collection or documentation in the clinic.

Structure of the M. tuberculosis DnaK-GrpE complex reveals how key DnaK roles are controlled.

The molecular chaperone DnaK is essential for viability of Mycobacterium tuberculosis (Mtb). DnaK hydrolyzes ATP to fold substrates, and the resulting ADP is exchanged for ATP by the nucleotide exchange factor GrpE. It has been unclear how GrpE couples DnaK's nucleotide exchange with substrate release. Here we report a cryo-EM analysis of GrpE bound to an intact Mtb DnaK, revealing an asymmetric 1:2 DnaK-GrpE complex. The GrpE dimer ratchets to modulate both DnaK nucleotide-binding domain and the substrate-binding domain. We further show that the disordered GrpE N-terminus is critical for substrate release, and that the DnaK-GrpE interface is essential for protein folding activity both in vitro and in vivo. Therefore, the Mtb GrpE dimer allosterically regulates DnaK to concomitantly release ADP in the nucleotide-binding domain and substrate peptide in the substrate-binding domain.

Results of phase 2 randomized multi-center study to evaluate the safety and efficacy of infusion of memory T cells as adoptive therapy in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia and/or lymphopenia (RELEASE NCT04578210).

BACKGROUND AIMS: There are currently no effective anti-viral treatments for coronavirus disease 2019 (COVID-19)-hospitalized patients with hypoxemia. Lymphopenia is a biomarker of disease severity usually present in patients who are hospitalized. Approaches to increasing lymphocytes exerting an anti-viral effect must be considered to treat these patients. Following our phase 1 study, we performed a phase 2 randomized multicenter clinical trial in which we evaluated the efficacy of the infusion of allogeneic off-the-shelf CD45RA- memory T cells containing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells from convalescent donors plus the standard of care (SoC) versus just the SoC treatment. METHODS: Eighty-four patients were enrolled in three Spanish centers. The patients were randomized into the infusion of 1 × 106/kg CD45RA- memory T cells or the SoC. We selected four unvaccinated donors based on the expression of interferon gamma SARS-CoV-2-specific response within the CD45RA- memory T cells and the most frequent human leukocyte antigen typing in the Spanish population. RESULTS: We analyzed data from 81 patients. The primary outcome for recovery, defined as the proportion of participants in each group with normalization of fever, oxygen saturation sustained for at least 24 hours and lymphopenia recovery through day 14 or at discharge, was met for the experimental arm. We also observed faster lymphocyte recovery in the experimental group. We did not observe any treatment-related adverse events. CONCLUSIONS: Adoptive cell therapy with off-the-shelf CD45RA- memory T cells containing SAR-CoV-2-specific T cells is safe, effective and accelerates lymphocyte recovery of patients with COVID-19 pneumonia and/or lymphopenia. TRIAL REGISTRATION: NCT04578210.

Sevelamer Use and Mortality in People with Chronic Kidney Disease Stages 4 and 5 Not on Dialysis.

Rationale and objective: Data suggest that non-calcium-based binders, and specifically sevelamer, may lead to lower rates of death when compared with calcium-based binders in end-stage renal disease (ESRD) patients. However, the association between sevelamer use and mortality for those with non-dialysis-dependent chronic kidney disease (NDD-CKD) patients has been uncertain. Study design: Our research is presented in a prospective cohort study. Setting and participants: A total of 966 participants with NDD-CKD stages 4-5 were enrolled in the PECERA study from 12 centers in Spain. Exposure: The participants were treated with sevelamer. Outcome: This study yielded all-cause and cardiovascular mortality outcomes. Analytical approach: We conducted an association analysis between mortality and sevelamer use with time-dependent Cox proportional hazards models. Results: After a median follow-up of 29 months (IQR: 13-36 months), death occurred in 181 participants (19%), with cardiovascular (n = 95, 53%) being the leading cause of death. In a multivariable model, the adjusted hazard ratios (HRs) for patients under sevelamer treatment were 0.44 (95% CI, 0.22 to 0.88) and 0.37 (95% CI, 0.18 to 0.75) for all-cause and cardiovascular mortality, respectively, compared with those of untreated patients. Limitations: Some limitations include potential confusion via indication bias; causal statements about these associations cannot be made due to the observational nature of this study. Conclusions: In this prospective NDD-CKD cohort study, the administration of sevelamer was independently associated with lower all-cause and cardiovascular mortality, suggesting that non-calcium-based phosphate binders might be the first-line therapy for phosphate lowering in this population. Further interventional studies clarifying the risks and benefits of phosphate binders in NDD-CKD are warranted.

Hemodiafiltración con reinfusión endógena del ultrafiltrado (HFR): hacia una diálisis convectiva, difusiva y adsortiva / Hemodiafiltration with endogenous reinfusion of the regenerated ultrafiltrate (HFR): Towards a convective, diffusive, and adsorptive dialysis

La hemodiafiltración con reinfusión endógena del ultrafiltrado (HFR) es una técnica de diálisis caracterizada por un cartucho de resina con poder adsorbente que combina los mecanismos difusión, convección y adsorción en un solo esquema terapéutico. Después de cerca de 20 años de experiencia clínica con HFR, el presente artículo revisa la evidencia acumulada con esta técnica, planteando si la adición de la adsorción, como tercer mecanismo depurativo, debería ser el siguiente paso en el tratamiento de los pacientes en hemodiálisis. La HFR, a pesar de producir una extensa eliminación de toxinas urémicas, ha demostrado reducir la pérdida de nutrientes y componentes fisiológicos durante la sesión de diálisis frente a la hemodiafiltración on-line, mitigando el estado inflamatorio y el estrés oxidativo en esta población. Además de su facilidad de uso, la técnica también es altamente biocompatible y puede utilizarse en situaciones de un acceso vascular comprometido. En base a estas observaciones, la HFR parece ser una técnica especialmente útil para pacientes con elevada comorbilidad, incluyendo aquellos con fragilidad, desnutrición o enfermedad cardiovascular. En esta revisión, como panel de consenso de nefrólogos con experiencia clínica en HFR, examinamos la literatura existente y resumimos nuestros puntos de vista sobre cómo usar esta técnica, qué perfil de paciente puede ser más adecuado para la HFR, y cómo prescribir y monitorizar de manera práctica esta modalidad de diálisis (AU)

Hemodiafiltration with endogenous reinfusion of the ultrafiltrate (HFR) is a dialysis technique characterized by a resin cartridge with adsorptive properties that combines the mechanisms of diffusion, convection, and adsorption in a single therapeutic regimen. After nearly 20 years of clinical experience with HFR, this article reviews the accumulated evidence with this technique, considering whether adsorption reduction, as a third purification mechanism, should be the next step in the treatment of hemodialysis patients. HFR, beyond producing an extensive removal of uremic toxins, has demonstrated to reduce the loss of nutrients and other physiological components during the dialysis session as compared to online hemodiafiltration, ameliorating the inflammatory state and oxidative stress in this population. In addition to its ease of use, the technique is also highly biocompatible and can be used in patients with a compromised vascular access. Based on these observations, HFR appears to be an especially useful therapy for high-comorbidity patients, including those with frailty, malnutrition, or cardiovascular disease. In this review, we, as a consensus panel of nephrologists experienced with HFR, survey existing literature and summarize our views on when to use this technique, which patients may be best suited for HFR, and how to effectively prescribe and monitor this modality of dialysis in daily clinical practice (AU)

Quality assessment in initial paediatric trauma care: Systematic review from prehospital care to the paediatric intensive care unit.

BACKGROUND: Trauma is the most common cause of death and disability in the paediatric population. There are a huge number of variables involved in the care they receive from health care professionals. AIM: The aim of this study was to review the available evidence of initial paediatric trauma care throughout the health care process with a view to create quality indicators (QIs). STUDY DESIGN: A systematic review was performed from Cochrane Library, Medline, Scopus and SciELO between 2010 and 2020. Studies and guidelines that examined quality or suggested QI were included. Indicators were classified by health care setting, Donabedian's model, risk of bias and the quality of the publication with the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) assessment. RESULTS: The initial search included 686 articles, which were reduced to 22, with 15 primary and 7 secondary research articles. The snowball sampling technique was used to add a further seven guidelines and two articles. From these, 534 possible indicators were extracted, summarizing them into 39 and grouping the prehospital care indicators as structure (N = 5), process (N = 12) and outcome (N = 3) indicators and the hospital care indicators as structure (N = 4), process (N = 10) and outcome (N = 6) indicators. Most of the QIs have been extracted from US studies. They are multidisciplinary and in some cases are based on an adaptation of the QIs of adult trauma care. CONCLUSIONS: There was a clear gap and large variability between the indicators, as well as low-quality evidence. Future studies will validate indicators using the Delphi method. RELEVANCE TO CLINICAL PRACTICE: Design a QI framework that may be used by the health system throughout the process. Indicators framework will get nurses, to assess the quality of health care, detect deficient areas and implement improvement measures.

Chronic Kidney Disease-Associated Pruritus and Quality of Life: Learning from Our Patients.

Chronic kidney disease-associated pruritus is itching directly related to kidney disease that cannot be explained by any other condition. Despite technological advances in the different aspects of dialysis sessions and the best treatment for chronic kidney disease patients, it is still a common problem in our patients. The many complex physiological mechanisms involved, the different hypotheses made over the years on the aetiology of the condition, and the great clinical variability may partially explain the limited knowledge about this problem and the difficulties in treating it. The presence of all these factors leads to the persistence of unpleasant symptoms, which must affect the disease burden and quality of life of kidney patients. Through the presentation of an illustrative clinical case, the aim of this review article is to highlight the need for adequate diagnosis and an improved approach to all aspects of chronic kidney disease-associated pruritus, in view of the heavy burden of the disease and the huge impact on the patient's quality of life.

Etiopathogenesis of chronic kidney disease-associated pruritus: putting the pieces of the puzzle together.

Defined as the unpleasant sensation that causes the desire to scratch, pruritus is the most common skin symptom associated with uremia and appears in almost half of patients with advanced chronic kidney disease (CKD). Beyond its direct impact on quality of life, CKD-associated pruritus (CKD-aP) is an independent predictor of mortality that also has a synergistic effect with other quality of life-related symptoms, such as insomnia, depression, and anxiety. Although different mechanisms have been proposed to explain the origin of Pa-ERC, its etiopathogenesis is still not fully understood. Since new therapeutic targets have been identified and several clinical trials have recently shown promising results, our current understanding of the interrelationships has expanded significantly and the pathophysiological mechanisms underlying CKD-aP are now considered to be multifactorial. The potential triggers of pruritus in patients with CKD are discussed in this review, including hypotheses about skin xerosis, accumulation of uremic toxins, dysregulation of the immune system and systemic inflammation, uremic neuropathy, and imbalances in the endogenous opioid system. Other non-uremic causes of pruritus are also discussed, with the aim of guiding the physicians to apply an adequate aetiopathogenic approach to CKD-aP in their day-to-day clinical practice.

Targeting tyrosinase in hyperpigmentation: Current status, limitations and future promises.

Hyperpigmentation is a common and distressing dermatologic condition. Since tyrosinase (TYR) plays an essential role in melanogenesis, its inhibition is considered a logical approach along with other therapeutic methods to prevent the accumulation of melanin in the skin. Thus, TYR inhibitors are a tempting target as the medicinal and cosmetic active agents of hyperpigmentation disorder. Among TYR inhibitors, hydroquinone is a traditional lightening agent that is commonly used in clinical practice. However, despite good efficacy, prolonged use of hydroquinone is associated with side effects. To overcome these shortcomings, new approaches in targeting TYR and treating hyperpigmentation are desperately requiredessentialneeded. In line with this purpose, several non-hydroquinone lightening agents have been developed and suggested as hydroquinone alternatives. In addition to traditional approaches, nanomedicine and nanotheranostic platforms have been recently proposed in the treatment of hyperpigmentation. In this review, we discuss the available strategies for the management of hyperpigmentation with a focus on TYR inhibition. In addition, alternative treatment options to hydroquinone are discussed. Finally, we present nano-based strategies to improve the therapeutic effect of drugs prescribed to patients with skin disorders.

Recommendations of the Spanish Society of Nephrology for the management of mineral and bone metabolism disorders in patients with chronic kidney disease: 2021 (SEN-MM).

As in 2011, when the Spanish Society of Nephrology (SEN) published the Spanish adaptation to the Kidney Disease: Improving Global Outcomes (KDIGO) universal Guideline on Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD), this document contains an update and an adaptation of the 2017 KDIGO guidelines to our setting. In this field, as in many other areas of nephrology, it has been impossible to irrefutably answer many questions, which remain pending. However, there is no doubt that the close relationship between the CKD-MBD/cardiovascular disease/morbidity and mortality complex and new randomised clinical trials in some areas and the development of new drugs have yielded significant advances in this field and created the need for this update. We would therefore highlight the slight divergences that we propose in the ideal objectives for biochemical abnormalities in the CKD-MBD complex compared to the KDIGO suggestions (for example, in relation to parathyroid hormone or phosphate), the role of native vitamin D and analogues in the control of secondary hyperparathyroidism and the contribution of new phosphate binders and calcimimetics. Attention should also be drawn to the adoption of important new developments in the diagnosis of bone abnormalities in patients with kidney disease and to the need to be more proactive in treating them. In any event, the current speed at which innovations are taking place, while perhaps slower than we might like, globally drives the need for more frequent updates (for example, through Nefrología al día).

Vitamin D and Chronic Kidney Disease Association with Mineral and Bone Disorder: An Appraisal of Tangled Guidelines.

Chronic kidney disease (CKD) is a highly prevalent condition worldwide in which the kidneys lose many abilities, such as the regulation of vitamin D (VD) metabolism. Moreover, people with CKD are at a higher risk of multifactorial VD deficiency, which has been extensively associated with poor outcomes, including bone disease, cardiovascular disease, and higher mortality. Evidence is abundant in terms of the association of negative outcomes with low levels of VD, but recent studies have lowered previous high expectations regarding the beneficial effects of VD supplementation in the general population. Although controversies still exist, the diagnosis and treatment of VD have not been excluded from nephrology guidelines, and much data still supports VD supplementation in CKD patients. In this narrative review, we briefly summarize evolving controversies and useful clinical approaches, underscoring that the adverse effects of VD derivatives must be balanced against the need for effective prevention of progressive and severe secondary hyperparathyroidism. Guidelines vary, but there seems to be general agreement that VD deficiency should be avoided in CKD patients, and it is likely that one should not wait until severe SHPT is present before cautiously starting VD derivatives. Furthermore, it is emphasized that the goal should not be the complete normalization of parathyroid hormone (PTH) levels. New developments may help us to better define optimal VD and PTH at different CKD stages, but large trials are still needed to confirm that VD and precise control of these and other CKD-MBD biomarkers are unequivocally related to improved hard outcomes in this population.

Perception of Spanish nephrologists on an old unsolved problem: Pruritus associated with chronic kidney disease (CKD-aP).

INTRODUCTION: Pruritus associated with chronic kidney disease is defined as the sensation of itching, in people with chronic kidney disease, in a one area or all over the body that causes the need to scratch, after having ruled out other dermatological or systemic causes. It is an old and known problem whose prevalence has been able to decrease with the improvement of dialytic techniques but which still persists and is underdiagnosed. OBJECTIVES: The objective of this study was to analyse the current perception of nephrologists about this problem that influences the quality of life of people with chronic kidney disease through a survey. RESULTS: 135 nephrologists, most of them engaged in haemodialysis, participated. 86% considered that pruritus associated with chronic kidney disease is still a problem today that affects the quality of life. Most nephrologists believe that the main pathophysiological cause is uremic toxins (60%) and only 16% believe that it is due to the dysregulation of the opioid system/endorphins-dynorphins. Only 16% comment that the prevalence of pruritus in their centre is greater than 20%. 40% believe that the diagnosis is made because it is manifested by the patient and only 27% because it is asked by the doctor. Moreover, it is not usual to use scales to measure it or the codification in the medical records. The main treatment used is antihistamines (96%), followed by moisturizers/anaesthetics (93%) and modification of the dialysis regimen (70%). CONCLUSIONS: Pruritus associated with chronic kidney disease is still a current problem, it is underdiagnosed, not codified and with a lack of indicated, effective and safe treatments. Nephrologists do not know its real prevalence and the different pathophysiological mechanisms involved in its development. Many therapeutic options are used with very variable results, ignoring their efficacy and applicability at the present time. The new emerging kappa-opioid-receptor agonist agents offer us an opportunity to reevaluate this age-old problem and improve the quality of life for our patients with chronic kidney disease.

Technical note: Angular dependence in fiber optic dosimetry using YVO4 :Eu3.

BACKGROUND: Fiber optic dosimetry (FOD) has emerged as a useful technique that can be used in those cases when intracavitary, real time, high spatial resolution dose assessment is required. Among the several factors characterizing a dosimeter, angular response of FOD probes has to be assessed in order to consider possible clinical application. PURPOSE: The objective of this study was to characterize the angular response of a FOD probe based on a cylindrical shaped YVO4 :Eu3+ scintillator under irradiation with a 6 MV photon beam generated by a linear accelerator (LINAC). METHODS: A FOD probe was irradiated inside a plastic phantom using a 6 MV LINAC photon beam at different azimuthal angles (0° to 360°, 15° steps). Scintillation output was measured with a photomultiplier tube. Similar measurements were performed with a second FOD probe having an optical filter interposed between the scintillator and the fiber. Monte Carlo simulations using PENELOPE were carried out in order to interpret the observed results. RESULTS: The FOD output was symmetrical with respect to the scintillator axis. For the unfiltered probe, the signal was maximum at rear incidence (0°) and steadily decreased down to its minimum value at frontal incidence (180°) having a signal ratio of 37%. The output of the filtered probe showed a plateau from 15° up to 115°. The signal was maximum at 60° and minimum at 180° having a signal ratio of 16%. Monte Carlo simulations predicted symmetry of the deposited dose about 0° and 90°, which contrasts with experimental findings. CONCLUSIONS: Photoluminescence (PL) of the scintillator induced by the Cherenkov light increases the angular dependence. Radiation attenuation inside the scintillator and partial light collection of the scintillation yield by the optical fiber (OF) are responsible for asymmetrical response. Results from this study should be considered in order to minimize angular dependence in FOD.

Intradialytic parenteral nutrition for patients on hemodialysis: when, how and to whom?

Hemodialysis is associated with high morbidity and mortality rates as well as low quality of life. Altered nutritional status and protein-energy wasting are important indicators of these risks. Maintaining optimal nutritional status in patients with hemodialysis is a critical but sometimes overlooked aspect of care. Nutritional support strategies usually begin with dietary counseling and oral nutritional supplements. Patients may not comply with this advice or oral nutritional supplements, however , or compliance may be affected by other complications of progressive chronic kidney disease. Intradialytic parenteral nutrition (IDPN) may be a possibility in these cases, but lack of knowledge on practical aspects of IDPN delivery are seldom discussed and may represent a barrier. In this review, we, as a consensus panel of clinicians experienced with IDPN, survey existing literature and summarize our views on when to use IDPN, which patients may be best suited for IDPN, and how to effectively deliver and monitor this strategy for nutritional support.

Etiopatogenia del prurito asociado a la enfermedad renal crónica: recomponiendo las piezas del puzle / Etiopathogenesis of chronic kidney disease-associated pruritus: Putting the pieces of the puzzle together

Definido como la sensación desagradable que provoca el deseo de rascarse, el prurito es el síntoma cutáneo más frecuente asociado a la uremia, pudiendo aparecer en casi la mitad de los pacientes con enfermedad renal crónica (ERC) avanzada. Más allá de su repercusión directa sobre la calidad de vida, el prurito asociado a la ERC (Pa-ERC) es un predictor independiente de mortalidad que además ejerce un efecto sinérgico con otros síntomas también relacionados con la calidad de vida, como la depresión y el insomnio. Aunque se han propuesto diferentes mecanismos para explicar su origen, la etiopatogenia del Pa-ERC sigue sin conocerse por completo. Dado que se han identificado nuevas dianas terapéuticas y recientemente varios ensayos clínicos han mostrado resultados prometedores, nuestra comprensión actual de las interrelaciones se ha ampliado significativamente, considerando multifactoriales los mecanismos fisiopatológicos subyacentes al Pa-ERC. En la presente revisión se discuten los potenciales factores desencadenantes de prurito en el paciente con ERC, incluyendo las hipótesis sobre la xerosis cutánea, el acúmulo de toxinas urémicas, la desregulación del sistema inmune y la inflamación sistémica, la neuropatía urémica y los desequilibrios en el sistema opioide endógeno, así como otras causas no urémicas de prurito, con el objetivo de orientar al clínico para realizar un adecuado abordaje etiopatogénico del Pa-ERC en su día a día. (AU)

Defined as the unpleasant sensation that causes the desire to scratch, pruritus is the most common skin symptom associated with uremia and appears in almost half of patients with advanced chronic kidney disease (CKD). Beyond its direct impact on quality of life, CKD-associated pruritus (CKD-aP) is an independent predictor of mortality that also has a synergistic effect with other quality of life-related symptoms, such as insomnia, depression, and anxiety. Although different mechanisms have been proposed to explain the origin of Pa-ERC, its etiopathogenesis is still not fully understood. Since new therapeutic targets have been identified and several clinical trials have recently shown promising results, our current understanding of the interrelationships has expanded significantly and the pathophysiological mechanisms underlying CKD-aP are now considered to be multifactorial. The potential triggers of pruritus in patients with CKD are discussed in this review, including hypotheses about skin xerosis, accumulation of uremic toxins, dysregulation of the immune system and systemic inflammation, uremic neuropathy, and imbalances in the endogenous opioid system. Other non-uremic causes of pruritus are also discussed, with the aim of guiding the physicians to apply an adequate etiopathogenic approach to CKD-aP in their day-to-day clinical practice. (AU)