HDF Archivi

Abstract

Il prurito associato a malattia renale cronica (CKD-aP) ha un’elevata incidenza nei pazienti affetti da malattia renale cronica terminale in dialisi e interferisce in maniera rilevante sulla qualità di vita dei pazienti emodializzati. La patogenesi è multifattoriale e tuttora in corso di studio. Alla luce dell’impatto clinico e per l’associazione con aumentata mortalità, non può essere considerato solo un sintomo. Nuovi farmaci e trattamenti sono stati sviluppati. Riportiamo la nostra esperienza con una paziente che abbiamo avuto occasione di trattare con emoperfusione con cartuccia HA130.

Parole chiave: CKD-aP, emoperfusione, prurito uremico, HDF

Ci spiace, ma questo articolo è disponibile soltanto in inglese.

Introduction

Chronic kidney disease-associated pruritus (CKD-aP) is a symptom of common onset in the population affected by chronic kidney disease undergoing haemodialysis treatment, with a prevalence between 10% and 70% [1]. This symptom not only compromises the quality of life, causing alterations in mood and interfering with social relationships and sleep quality [2], but has also been associated with an increase in mortality [2, 3].

The genesis of CKD-aP remains unclear, as a specific causal mechanism has not yet been identified. Traditionally, inadequate dialysis treatment was blamed, however several epidemiological studies have shown no correlation between dialysis efficacy and the rate of CKD-aP onset [4].

Although the central origin of the pathology has not yet been clarified, it is certainly determined by complex peripherical mechanisms involving dermal mast cells, keratinocytes, Th-1 lymphocytes and nerve fibres [1].

In this context, in addition to classic therapies involving topical application of substances such as capsaicin, pramoxine or gamma-linolenic acid, or the administration of systemic agents such as gabapentin, pregabalin or antihistamines, the use of hemoadsorbent cartridges such as HA130 has proven to be a winning strategy [5].

We have evidence of what is reported in the case report that we have had the opportunity to follow and which we report below.

Case Report

55-year-old patient undergoing thrice-weekly hemodialysis with bicarbonate dialysis via femoral CVC and 80 m²polysulfone filter for two years. Medical history of chronic heart failure with dilated cardiomyopathy with reduced systolic function, ejection fraction of 30%, and multi-district vascular disease. After two years of hemodialysis, the patient complained of uncontrollable itching, also present at night, with widespread lesions from scratching. Attempts were made to improve dialysis treatment; however, the patient’s vascular access and intradialytic hemodynamics did not allow for maintenance of treatment with effective flows for an HDF. Therefore, after an assessment using the VAS (Visual Analogue Scale) (Figure 1) and the 5D score (Figure 2) with questionnaires to evaluate the intensity of itching, we began, as a rescue therapy during the hemodialysis session, a hemoperfusion treatment in series with HA130. The parameters set were as follows: Qb 250 mL/min, Qd 500 mL/min, enoxaparin 4000 IU, dialysis time 4 hours, polysulfone filter. In the first two weeks, we performed two treatments per week and subsequently continued with one treatment per week. As shown in Figure 1, the benefit is not immediate but is expected after the second week of treatment. We measured IL-12 at the serum level, but it has not been detected as a sensitive marker to evaluate the course of the treatment.

Figure 1. Evaluation of response to treatment with HA130 performed with VAS.

Discussion

The chronic itching that occurs in patients with end-stage chronic kidney disease is called CKD-aP [6]. It occurs in about half of the cases as widespread itching, while in the remaining cases, it is localized on the back, face, or forearms [2, 7]. The diagnosis is often difficult and is made by excluding other causes as well as based on clinical presentation, location, and characteristics of the itching [8]. Agarwal et al. proposed an algorithm for the management of uremic pruritus according to which an assessment of the impact on quality of life is necessary: if this is moderate to severe, in addition to conventional measures such as adjustment of dialysis treatment, control of calcium-phosphate metabolism, and topical therapy (hydration and skin barriers), it is possible to try innovative therapies such as Difelikefalin, Gabapentinoids, UVB, or SSRIs [9].

The reasons why CKD-aP arises are not yet clear. It has been observed that hemodialysis patients who develop CKD-aP, compared to those who do not experience the complication, have higher proportions of Th-1 cells and elevated levels of CRP and IL-6, suggesting a hypothesized dysregulation of the immune system in a pro-inflammatory direction [10]. Some studies have also shown elevated circulating levels of IL-31, which could indicate a likely involvement in the pathogenesis [11, 12]. It is known that patients with chronic kidney disease have an alteration in calcium-phosphorus metabolism; in particular, when blood levels of phosphorus and calcium increase, they combine to form calcium phosphate, which deposits in the skin, a mechanism that leads to a reduction in circulating calcium and a related increase in PTH levels. High levels of calcium, phosphorus, and PTH have been found to be higher in patients with CKD-aP compared to those without itching, suggesting a role in its pathogenesis [13]. High levels of B-type natriuretic peptide also appear to be associated with worsening itch in patients on hemodialysis [14]. In light of the increase in dermal mast cells in patients with CKD-aP, an involvement of tryptase and an increased release of histamine due to extracorporeal circulation has also been hypothesized [15–17]. There is also evidence that an imbalance of mu and kappa receptors may play a key role in the development of itching, and this is the basis of the mechanism of action of new drugs such as Difelikefalin [18].

The classic treatment of uremic pruritus involves the application of emollients or topical therapy based on capsaicin, pramoxine, cromolyn sodium, gamma-linolenic acid, sericin, vitamin D, menthol, or cannabinoids. In more severe cases, with resistant CKD-aP, systemic therapy with gabapentin, pregabalin, kappa-opioid agonists, Mu receptor antagonists, antihistamines, sertraline, montelukast, or others may be used [1]. Furthermore, phototherapy with UVB seems to play an important role [19].

In addition to what has been reported, scientific literature indicates that hemoperfusion techniques could broadly benefit patients undergoing hemodialysis, even extending their lifespan compared to those subjected to traditional techniques [20].

HDF has been shown to be effective in the molecular removal of beta-2-microglobulin and PTH, which are implicated in the genesis of pruritus [21]. In particular, hemodiafiltration with endogenous reinfusion, such as Supra-HFR, significantly reduces pruritus and its intensity [22]. Comparative data suggest that hemoperfusion with HA130 is superior to HDF in the removal of protein-bound toxins such as indoxyl sulfate and P-cresyl sulfate, with a greater clinical impact on pruritus relief. HDF, however, is more effective in the removal of medium-weight molecules such as beta-2-microglobulin and PTH [23].

It has already been shown that high-flux hemodialysis, compared to traditional or low-flux techniques, is superior in reducing CKD-aP [24, 25]. It has also been observed that hemodiafiltration combined with hemoperfusion is more effective in providing relief from CKD-aP [26].

The Jafron HA130 cartridge is designed to be used in series during hemodialysis or hemodiafiltration treatment. It is a hemoperfusion filter containing neutral macroporous resin with a target range of molecules between 5k and 30k kDa. This action is made possible by the three-dimensional structure of the resin, its hydrophobicity, and the Van Der Waals forces that develop upon contact with blood [27]. These characteristics enable HA130 not only to successfully eliminate a multitude of uremic toxins but also to significantly reduce the manifestations of restless legs syndrome and uremic pruritus, thereby resulting in a marked improvement in the quality of life and sleep in affected patients [28].

Conclusion

Our case documents a good response to hemoperfusion treatments, which currently represent a rescue therapy and thus a valid alternative for patients who cannot improve dialysis efficacy or cannot undergo medical therapy with new drugs like Difelikefalin. Further studies would be necessary to refine the indications and establish a well-defined therapeutic pathway.

Tag

Nuove frontiere di trattamento del prurito associato a malattia renale cronica: un caso di emoperfusione con HA130

Abstract

Introduction

Case Report

Discussion

Conclusion

Bibliography