A new pharmacological treatment for itch associated with chronic kidney disease is finally available in our country, representing a therapeutic breakthrough that has been awaited for years. However, access to care is still not guaranteed uniformly across the national territory, with particular critical issues in regions where accredited private dialysis centers are predominant. The Italian nephrology community is calling for urgent action by regional institutions to ensure equity of access to this innovative therapeutic option.

Uremic pruritus: a disabling symptom affecting half of dialysis patients

Itch associated with chronic kidney disease, also known as uremic pruritus, is still largely underestimated but has a devastating impact on patients’ quality of life. According to data collected by the National Association of Hemodialysis Patients (ANED), this symptom affects up to 53.3% of patients on chronic dialysis treatment, with 20.4% experiencing particularly severe forms, described as being almost constantly present, both during the day and at night.

The clinical features of this disorder are particularly disabling. Itch typically appears in the advanced stages of renal failure, mainly affecting the back and legs, but it can extend to the whole body. Its intensity tends to increase during the night, severely impairing sleep and leading to a vicious circle of fatigue, irritability and depression. The consequences go well beyond simple physical discomfort: patients develop excoriations, skin infections and scars caused by incessant scratching, while on the psychological level depressive symptoms and progressive social isolation may emerge.

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Pathogenetic mechanisms and impact on mortality

The pathogenesis of uremic pruritus is multifactorial and complex. The accumulation of uremic toxins in the blood and in the skin layers, as a consequence of the reduced renal clearance capacity, represents only one of the triggering factors. In addition, there are alterations of the skin, which becomes dry, dehydrated and poorly elastic, and changes in the peripheral nerve endings, which become hypersensitive. Even the best dialysis techniques cannot perfectly reproduce the complexity of the natural kidney, leaving an altered and inflamed cutaneous environment.

Epidemiological studies have documented a concerning link between severe itch and increased mortality. Research conducted in Japan has shown that, in patients undergoing hemodialysis, pruritus was associated with a higher risk of mortality even after adjustment for other clinical factors. It is hypothesized that this increase is related to poor sleep quality and to the overall effects that itch exerts on quality of life.

Difelikefalin: the first specific therapy reimbursed in Italy

After years of waiting, in June 2025 the Italian Medicines Agency (AIFA) approved the reimbursement of difelikefalin (Kapruvia), the first drug specifically indicated for the treatment of moderate to severe itch associated with chronic kidney disease in adult patients undergoing hemodialysis. Publication in the Official Gazette on 22 July 2025 made reimbursement by the National Health Service effective.

Difelikefalin is a synthetic selective kappa-opioid receptor agonist that acts by stimulating specific human receptors involved in the control of itch perception. Unlike traditional opioids, this mechanism of action does not produce the typical side effects of opiate drugs, ensuring a more favorable safety profile. The treatment is administered intravenously at the end of each hemodialysis session, with a protocol that fits seamlessly into the therapeutic routine of dialysis patients.

Proven clinical efficacy

Registration clinical trials have shown significant results. According to Professor Filippo Aucella, Director of the Complex Operative Unit of Nephrology and Dialysis at the “Casa Sollievo della Sofferenza” Foundation in San Giovanni Rotondo, “in the registration clinical trials and in the compassionate use experience, difelikefalin has demonstrated an improvement in the condition of patients suffering from moderate and severe pruritus, significantly increasing their quality of life”.

The president of the Italian Society of Nephrology (SIN), Luca De Nicola, has underlined that “the drug is able to reduce a symptom that is both troublesome and disabling in 85% of cases”, defining this result “already a success” in light of the target population of elderly patients who live every day with a severe disturbance.

Barriers to access: an issue of territorial equity

Despite reimbursement by the National Health Service, access to difelikefalin is not uniform across Italy. The drug can be prescribed only in hospital settings or in accredited facilities, creating difficulties especially in those regions where the majority of patients are treated in accredited private dialysis centers. This results in substantial differences in treatment opportunities between patients living in different areas of the country.

Regional disparities in dialysis organization

Variability in regional regulations and in the management models of dialysis centers means that in some areas access to the new drug is more straightforward, while elsewhere delays and administrative barriers are reported that penalize patients. The nephrology community is calling on the Regions to intervene promptly to standardize procedures and guarantee equity in care.

The AIFA registry and treatment monitoring

Prescribing difelikefalin requires the completion of an electronic form on the AIFA portal, which must be accessed by physicians and pharmacists in authorized facilities. Monitoring is important to ensure the safety and traceability of treatment, but it can be perceived as an additional bureaucratic step if it is not accompanied by a clear territorial organization.

The previous therapeutic context: ineffective and off-label treatments 

Before the arrival of difelikefalin, the treatment of uremic pruritus was based on a gradual and often unsatisfactory approach. The main therapeutic options included:

optimization of dialysis and control of metabolic parameters (calcium, phosphorus, PTH)
Skin hydration with emollient and soothing creams Antihistamines, which have not proved effective in uremic pruritus because the pathogenic mechanism predominantly involves non-histaminergic neural pathways Anticonvulsant drugs such as gabapentin and pregabalin, used off label as second- or third-line therapy Ultraviolet B (UVB) phototherapy for resistant cases

As experts have pointed out, “current treatment is largely based on optimizing dialysis and hydrating the skin, but in cases of moderate to severe pruritus off-label drugs are mainly used, with limited efficacy and/or potential side effects”. The availability of difelikefalin therefore represents “an important step forward for this community of patients”, bridging a long-standing therapeutic gap.

The problem of underestimation and underreporting

One of the main critical issues remains the underdiagnosis of uremic pruritus: many patients do not report the symptom to their doctor, often believing that it is “normal” or that there are no useful solutions. European studies also highlight the lack of guidelines and standardized scales to measure the intensity of itch and to monitor the symptom systematically over time.

Future perspectives: towards a more equitable healthcare system 

The recent approval of difelikefalin offers a real opportunity to improve the quality of life of thousands of dialysis patients, but only if all Regions guarantee fair and homogeneous access to the drug. Greater awareness is needed among healthcare professionals and a constant updating of patient care pathways.

The nephrology community, together with patient associations, hopes that the introduction of this therapy will be accompanied by information and training campaigns and by a review of regional policies. Only in this way will it be possible to ensure all patients dignified and up-to-date care, even in the presence of complex symptoms such as uremic pruritus.

The 98th edition of the National Urology Congress of the Italian Urological Society was held in Sorrento at the Hilton Sorrento Palace from 6 to 9 November 2025, bringing together Italian and international professionals around a common mission: putting knowledge at the service of public health. The event represents a crucial moment of scientific exchange where researchers, clinicians, healthcare professionals and residents share the latest developments in the field of urology.

The congress is characterized by a multidisciplinary and human-centred approach based on three fundamental pillars: prevention, health education and the sustainability of care. According to Giuseppe Carrieri, president of SIU, this scientific meeting is an opportunity to reflect on the central role of urology in the quality of life of millions of people, especially in the context of men’s health.

Male frailty at the center of SIU’s prevention campaign

Male frailty is the core theme of the campaign launched by SIU in November, an initiative that overturns the traditional perception of urological care. Andrea Salonia, head of the SIU educational office and full professor of urology at the Vita-Salute San Raffaele University in Milan, underlines how the urologist is the doctor for men in a global sense, addressing not only clinical diseases but also psychological and relational frailties.

According to Salonia, contemporary therapeutic approaches go beyond simple pharmacological or surgical solutions. The combination of expertise that the urologist brings into play makes it possible to build integrated therapeutic strategies, which combine timely diagnosis, prevention and personalized care based on the specific needs of each patient.

Robotics is revolutionizing the treatment of urological cancers

Technological innovation is an increasingly decisive element in the Italian urological landscape. Andrea Minervini, head of the SIU research office and director of urology and andrology at the Careggi University Hospital in Florence, highlights how robotic surgery is now widely used in the specialty.

There are 215 surgical robots in Italy, and the most significant figure concerns urological specialization: 54% of all robotic procedures nationwide are performed precisely in urology. This concentration is not accidental, but reflects the effectiveness of the technology in treating the three main urological cancers: prostate carcinoma, kidney carcinoma and bladder cancer. Robotic surgery offers significant clinical benefits, ensuring less invasiveness, greater precision and shorter recovery times for patients.

The words of the doctors

Prevention through good daily habits

Vincenzo Ficarra, full professor of urology at the University of Messina and head of the SIU scientific office, reiterates the importance of prevention as the primary tool in tackling urological diseases. Good practices do not require extraordinary interventions, but are rooted in conscious daily choices.

Hydration as the first preventive step

Adequate hydration is the first preventive measure. A sufficient intake of fluids significantly reduces the formation of kidney stones and decreases the risk of recurrent cystitis. This simple habit, often underestimated, constitutes a key barrier against frequent conditions in the male population.

Diet: the value of the Mediterranean diet 

Nutrition plays a decisive role in urological prevention. The Mediterranean diet, characterized by an abundance of fruit, vegetables, legumes and whole grains, offers natural protection against numerous urological diseases. It is essential to limit the consumption of cured meats, red meat and foods with a high fat content, which can contribute to inflammation of the urinary tract.

Physical activity and giving up smoking

An active lifestyle, with regular physical activity, counteracts a sedentary routine and reduces risk factors related to urological diseases. Quitting smoking is perhaps the most effective preventive measure: smokers have a nine times higher risk of developing bladder cancer compared to non-smokers.

The concluding message of the Sorrento congress

The 98th SIU National Congress in Sorrento shows how contemporary urology combines technological innovation with a renewed preventive and human approach. The Italian urological community reiterates that men’s health is not merely a medical issue, but a commitment that requires individual awareness, integrated specialist support and the widespread adoption of correct preventive practices.