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Get Support. Feedback Please let us know what you think of our products and services. Give Feedback. Get Information. Open Access Review. Jacek C. Chronic kidney disease CKD is a condition of widespread epidemiology and serious consequences affecting all organs of the organism and associated with ificant mortality.
The knowledge on CKD is rapidly evolving, especially concerning adults. Recently, more data is also appearing regarding CKD in children. Chronic itch CI is a common symptom appearing due to various underlying dermatological and systemic conditions. CKD-aI is relatively well-described in the literature concerning adults, yet it also affects children. Unfortunately, the data on paediatric CKD-aI is particularly scarce. This narrative review aims to describe various aspects of CKD-aI with an emphasis on children, based on the available data in this population and the data extrapolated from adults.
Its pathogenesis is described in details, focusing on the growing role of uraemic toxins UTsas well as immune dysfunction, altered opioid transmission, infectious agents, xerosis, neuropathy and dialysis-associated aspects. Moreover, epidemiological and clinical aspects are reviewed based on the few data on CKD-aI in children, whereas treatment recommendations are proposed as well, based on the literature on CKD-aI in adults and own experience in managing CI in children.
Keywords: chronic kidney disease; uraemic toxins; children; itch chronic kidney disease ; uraemic toxins ; children ; itch. Introduction Itch also referred to as pruritus is defined as an unpleasant sensation leading to a desire to scratch. Based on its duration itch is classified as acute or chronic CIwith the latter being present for more than 6 weeks in an affected individual [ 1 ].
CI may manifest in a continuous or intermittent manner, yet its long duration clearly implies an underlying disease-related context. Unsurprisingly, various conditions managed by different medical specialists are prone to be associated with CI.
Regardless of the common cutaneous diseases mostly managed by dermatologists which frequently present with CI e. The impact of CKD is vast in all regions of the world. According to Hill et al. In there were This remains valid especially in the context of age groups. Population aging and common crucial risk factors for CKD development, such presence of diabetes and hypertension, have all contributed to the growing magnitude of CKD over the last decades, especially in the elderly [ 5 ].
Unfortunately, the global CKD burden also stems from its presence in paediatric population. The prevalence of CKD varies between 15— Inthe median reported incidence of renal replacement therapy reached 9 per million children worldwide, with values ranging between 4 to 18 per million in different countries [ 7 ].
The aforementioned heterogeneity between different age groups is also expressed via the aetiological factors contributing to the development of CKD. While adults mostly develop CKD due to diabetic nephropathy, hypertension and autosomal dominant polycystic kidney disease ADPKDthe leading causes in children encompass congenital anomalies of the kidney and urinary tract CAKUThereditary nephropathies and glomerulonephritis [ 8 ].
ESRD is associated with 30 times higher likelihood of mortality than in healthy children [ 10 ]. Moreover, young patients with CKD have ificantly reduced health-related quality of life HRQoL in its various domains [ 111213 ]; this also concerns their caregivers [ 13 ]. CI is also a frequent problem in the general population.
The burden of CI may manifest with detrimental effect on an individual through decreased mood, reduced concentration, worse sleep quality, suicidal thoughts, difficult socioeconomic situation, feelings of stigmatization or impaired sexual life, to mention just a few [ 161718192021 ]. Analogously to the CKD population, studies focusing on CI in children are published in the literature less frequently than those referring to the adult population.
Notably, CI in paediatric population occurring due to systemic causes has been relatively rarely investigated in the literature [ 3132333435363738 ], while publications specifically mentioning CKD-aI appear even more exceptionally [ 394041424344 ]. In this narrative review we attempted to gather the data on CKD-aI in the context of paediatric population and demonstrate the areas which require further evaluation in the future.
We also included the data from other relevant online sources on CKD [ 945 ] which we were aware of. The search was executed on 30 April It is important to note that the complicated network of reciprocal associations in certain overlapping of the pathogenetic mechanisms. Therefore, the separate considerations on subsequent factors are provided in this manner for educational purposes.
Uraemic toxins UTs constitute a heterogenous group of substances accumulated in uraemia which interact negatively with biologic functions of the organism [ 47 ]. As of Aprilthe European Uremic Toxins EUTox Database [ 45 ] lists substances based on source publications and includes their serum concentrations in uraemia in comparison to healthy individuals.
It must be noted that such basic small solutes as urea and creatinine Sex forum Funyu excluded from this classification and it is controversial whether they should be regarded as toxic per se [ 4748 ]. It is crucial to acknowledge that the vast majority of data on UT refers to adult population with CKD. As emphasized by Belgian experts in the field [ 49 ], publications strictly focusing on paediatric CKD patients are lacking, while the available knowledge regarding the adults may not be fully translated to younger individuals. Therein, the authors mentioned several relevant disparities between paediatric and adult population, mainly larger body water volume and lower circulating proteins, different dietary needs and intake, the ongoing and unfinished Sex forum Funyu of maturation and growth, distinct aetiology of CKD, and relatively longer survival when compared to adults with ESRD.
Fortunately, as ofnew valuable contributions on paediatric CKD and UTs in particular have already been published [ 50515253545556 ]. Low molecular weight molecules LMWM are water soluble substances which do not bind to proteins [ 57 ]. Nevertheless, at least one compound in this group was linked to the development of CKD-aI, Sex forum Funyu any potential direct causal relationship is debatable. Uric acid UA is an organic substance which arises as an oxidation end-product of purine metabolism in humans and higher primates. Increased UA levels contributed to the risk of CKD disease progression and mortality in adults [ 5960 ].
Similarly, hyperuricaemia was associated with hypertension and CKD progression in children [ 61 ]. However, Solak et al. The majority of MM are peptides and proteins which weigh between 0. If the dialyser pore is not big enough, the removal of these substances is difficult to obtain during dialysis. According to Chmielewski et al.
Its retention in the course of advanced stages of CKD was associated with amyloidosis, malnutrition-inflammation and atherosclerosis syndrome, cardiovascular disease and mortality [ 676869707172 ]. As reviewed by Argyropoulos et al. Narita et al. In a study by Chen et al. Conversely, in a study by Melo et al.
PTH is the major product of chief cells in parathyroid glands, with its initial form containing amino acids and termed preproPTH. PTH is a crucial factor regulating calcium and phosphate homeostasis in the organism, influencing bones, kidneys and gastrointestinal tract [ 80 ]. In the setting of CKD, hyperphosphataemia, hypocalcaemia and decreased concentration of vitamin D 3 result in chronic hyperstimulation of parathyroid glands.
This perpetuates their increased growth initially diffuse, then glandularPTH secretion and release, thereby developing secondary hyperparathyroidism [ 81 ]. PTH and FGF are relevant compounds involved in the pathogenesis of CKD mineral and bone disorder CKD-MBD in children, influencing bone turnover, mineralization, volume, linear growth, structure and strength, as well as contributing to vascular calcification [ 82 ].
InMassry et al. Within 48 h of the procedure, pruritus completely disappeared in 5 patients, with the remaining 2 patients experiencing its disappearance within a week. Similar outcomes were reported by Chou et al. Other studies brought conflictingwith some demonstrating possible correlation between serum iPTH concentration and pruritus [ 748586 ], while others refuted this hypothesis [ 3063878889 ]. Notably, a study by Senturk et al. These factors were also independently associated with pruritus in a stepwise logistic regression model.
Moreover, histochemical analysis of skin biopsies taken from patients on HD was consistently negative for PTH. Consequently, several studies revealed that increased levels of serum calcium favoured the occurrence of severe CKD-aI [ 637489 ], whereas Momose et al. This may predispose to degranulation and release of various pruritogenic mediators from mastocytes MCs and other cells present in the skin. These cytokines share a common pathway of aling through receptor unit glycoprotein gp [ 93 ]. Classic IL-6 aling occurs when the cytokine interacts with a specific membrane bound receptor IL-6R which is present on hepatocytes, megakaryocytes and leukocytes, followed by formation of IL-6R complex with gp homodimer [ 94 ].
Although many cells do not have membrane bound IL-6R, they may still be involved in the so-called trans-aling process which occurs due to interaction between IL-6, soluble IL-6R sIL-6R and gp, as the latter is ubiquitous. In short, IL-6 has been attributed to a variety of biological effects, mainly acute phase inflammatory responses, stimulation of lymphocytes, as well as regulation of glucose metabolism and hypothalamic-pituitary-adrenal HPA axis [ 95 ]. Higher levels of proinflammatory cytokines, including IL-6, were associated with worse renal function during CKD [ 96 ] and its rapid progression [ 97 ].
Moreover, IL-6 levels were proven factor predicting mortality in patients with ESRD who initiated dialysis [ 9899 ]. In children suffering from CKD, the development of anaemia was inversely correlated with IL-6 concentration [ ].
Additionally, IL-6 predicted acute malnutrition and growth impairment among children and adolescents with CKD [ ]. Certain studies revealed a possible link between IL-6 and pruritus occurrence due to chronic sulphur mustard exposure [ ] and in the course of prurigo nodularis PN [ ]. Kimmel et al. It must be noted that certain data in the literature link IL-6 and other inflammatory cytokines to depression, including patients on HD .
Concurrently, the presence depression in patients on HD is a predictor of future CKD-aI occurrence [ ], whereas the coexistence of depressive symptoms in paediatric CKD population does occur in practice .
In the last decade, PBUT Sex forum Funyu finally started to gain more scientific attention as substances interfering with essential biochemical functions of the individuals affected with advanced stages of CKD [ ]. PBUT are chemicals which circulate in blood in a certain equilibrium between free and protein-bound form [ ]. While a ificant fraction of a solute is protein-bound, the remainder can be removed both by glomerular filtration and tubular secretion [ ]. Additionally, if a potentially toxic solute is bound to proteins, its active free form has lower concentration in the circulation and thus the detrimental biological effect is less pronounced.
However, in the setting of ESRD, ificant protein binding also le to a major decrease of solute clearance through dialysis [ ]. As reviewed in details by Rysz et al.Sex forum Funyu
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