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.

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)

A Pilot Randomized Crossover Trial Assessing the Safety and Short-Term Effects of Walnut Consumption by Patients with Chronic Kidney Disease.

The aim of this study of patients with chronic kidney disease (CKD) is to assess the safety of daily consumption of walnuts on the physiological levels of phosphorous, potassium, parathyroid hormone (PTH), and fibroblast growth factor 23 (FGF23), and to assess the short-term benefits of this intervention on risk factors associated with cardiovascular events. This led us to perform a prospective, randomized, crossover, pilot clinical trial examined 13 patients with CKD. Subjects were randomly assigned to a diet of 30 g of walnuts per day or the control diet. After 30 days, each group was given a 30-day washout period, and then switched to the alternate diet for 30 days. Urinary and serum levels of phosphorous and potassium, multiple vascular risk factors, and urinary inositol phosphates (InsPs) were measured at baseline and at the end of the intervention period. Our results showed that the walnut dietary supplement led to reduced blood pressure, LDL cholesterol, and albumin excretion, but had no effect on the physiological levels of phosphorous, potassium, PTH, and FGF23. This is the first report to show that daily consumption of walnuts by patients with CKD does not alter their physiological levels of phosphorous, potassium, PTH, and FGF23 when included in a sodium-, protein-, phosphate-, and potassium-controlled diet, and it could be an effective strategy for reducing cardiovascular risk in patients with CKD.

Tissue Donors in Regional Hospitals: A Reality.

Progress in transplantation means the process of procuring both human organ and tissues has become a daily challenge. Considering that tissues are usually procured from organ donors who have suffered brain death or after controlled cardiac death, the tissue procurement is done mainly in major hospitals. With the aim of highlighting the potential role of regional hospitals in tissue donation, a prospective descriptive study was carried out of all the patients who died at the Regional Hospital of Inca in Mallorca (Spain) from January 2013 to August 2018. To ensure an early detection of all possible tissue donors, the hospital has implemented a computerized alert system that is activated immediately after a patient dies. This strategy has proven to be very useful as in the analyzed period, the hospital had an average of 280 donors per million population, which is one of the highest rates of cornea donation among the Spanish hospitals. Our data and experience show the important role of regional hospitals in tissue donation and the value of implementing screening programs and early selection of potential tissue donors.

Effect of sample time on urinary lithogenic risk indexes in healthy and stone-forming adults and children.

BACKGROUND: The diagnosis and follow-up of stone forming patients is usually performed by analysis of 24-h urine samples. However, crystallization risk varies throughout the day, being higher at night. The main objective of this study is to evaluate the urinary crystallization risk in adults and children by calculating risk indexes based on different collection periods. METHODS: The study included 149 adults (82 healthy and 67 stone-formers) and 108 children (87 healthy and 21 stone-formers). 24-h urine was collected, divided into 12-h daytime sample (8 am to 8 pm), and 12-h overnight sample (8 pm to 8 am next morning). Solute concentrations, the calcium to citrate ratio (Ca/Cit), and the ion activity product of calcium oxalate (AP[CaOx]) and calcium phosphate (AP[CaP]) were calculated in each 12-h sample and in overall 24-h urine. Assessments were also related to stone type. RESULTS: Ca/Cit and AP(CaOx) were significantly higher in stone forming patients than in healthy subjects. The 12-h overnight samples had the highest values for both risk indexes, confirming a greater risk for crystallization at night. The AP(CaP) index was significantly higher in patients with pure hydroxyapatite stones than healthy controls, but was not significantly different between stone-formers overall and healthy controls. CONCLUSIONS: The calculation of risk indexes is a simple method that clinicians can use to estimate crystallization risk. For this purpose, the use of 12-h overnight urine may be a reliable alternative to 24-h collections.

Protective Effect of Myo-Inositol Hexaphosphate (Phytate) on Abdominal Aortic Calcification in Patients With Chronic Kidney Disease.

OBJECTIVE: The aim of this study was to evaluate the relationship between physiological levels of myo-inositol hexaphosphate (phytate) and cardiovascular (CV) calcification in patients with chronic kidney disease (CKD). DESIGN AND METHODS: This was a prospective cross-sectional study conducted from December 2012 to June 2013. SUBJECTS: Sixty-nine consecutive patients with CKD who were not undergoing renal replacement therapy. INTERVENTION: All subjects were given lateral lumbar X-rays to quantify abdominal aortic calcification (AAC). Clinical laboratory analyses and phytate food frequency questionnaires were also performed. MAIN OUTCOME MEASURE: Phytate urinary excretion, estimated phytate consumption (based on food frequency questionnaire) and AAC score. Patients were divided into two groups based on median abdominal aortic calcification (AAC) score: no/mild AAC (AAC ≤ 6, n = 35) and moderate/severe AAC (AAC > 6, n = 34). RESULTS: Patients with no/mild AAC were younger, had lower pulse pressure, greater dietary intake of phytate, greater urinary phytate and the prevalence of prior CV disease was significantly lower compared to patients with moderate/severe AAC. Among the top 10 phytate-rich foods, lentil consumption was significantly greater in patients with no/mild AAC than in those with moderate/severe AAC. Multivariate logistic regression analysis indicated that age, prior CV disease, urinary phytate (or lentil consumption) were independently associated to AAC. CONCLUSION: Our results suggest that adequate consumption of phytate can prevent AAC in patients with CKD. Further prospective studies must be performed to elucidate the benefits of a phytate-rich diet and the associated risk of phosphorus bioavailability in these patients.

Identification of culturable bacteria present in haemodialysis water and fluid.

Water used to prepare haemodialysis fluid is not sterile, and its microbiological control is important for the prevention of haemodialysis-associated illness. Bacterial populations inhabiting a distribution system for haemodialysis water were studied over an 18-month period. 203 planktonic bacteria isolated on R2A medium were identified by restriction analysis and sequencing of 16S rRNA gene. A diverse bacterial community was detected, containing predominantly Gram-negative members of the Alphaproteobacteria and Betaproteobacteria, as well as representatives of the genus Mycobacterium. Ecological and clinical consequences are discussed: bacteria from the genera Novosphingobium, Pseudomonas and Sphingomonas have been described in the build-up of biofilms, and others like Acinetobacter, Mycobacterium or Brevibacterium may represent a health risk to patients under haemodialysis treatment.