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.

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.

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)

Percepción de los nefrólogos españoles sobre un problema antiguo no resuelto: Prurito asociado a la enfermedad renal crónica (Pa-ERC) / Perception of Spanish nephrologists on an old unsolved problem: Pruritus associated with chronic kidney disease (CKD-aP)

Introducción: El prurito asociado a enfermedad renal crónica se define como la sensación desagradable que provoca la necesidad de rascarse en una parte del cuerpo o en todo en personas con enfermedad renal crónica, tras haberse descartado otras causas dermatológicas o sistémicas. Es un problema antiguo y conocido cuya prevalencia ha podido disminuir con la mejoría de la eficacia dialítica pero que todavía persiste y está infradiagnosticado. Objetivos: El objetivo de este estudio fue analizar la percepción y práctica actual de los nefrólogos sobre este problema que impacta en la calidad de vida de las personas con enfermedad renal crónica a través de una encuesta anónima. Resultados: Participaron 135 nefrólogos, la mayoría dedicados a hemodiálisis. Un 86% consideró que el prurito asociado a enfermedad renal crónica sigue siendo un problema en la actualidad que afecta a la calidad de vida. La mayoría de los nefrólogos opinan que la principal causa fisiopatológica son las toxinas urémicas (60%) y solo un 16% cree que se debe a la desregulación del sistema opioide/endorfinas-dinorfinas. Únicamente un 16% comenta que la prevalencia de prurito en su centro es mayor del 20%. Un 40% cree que el diagnóstico se realiza porque lo manifiesta el paciente y solo un 27% porque lo pregunta el facultativo. Además, no es habitual usar escalas ni codificarlo en la historia clínica. El tratamiento más común son los antihistamínicos (96%), seguido de las cremas hidratantes/anestésicas (93%) y la modificación de la pauta de diálisis (70%). (AU)

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 analyze 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 hemodialysis, 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 center 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/anesthetics (93%) and modification of the dialysis regimen (70%). (AU)