Stesura Seveso Archivio Italiano di Urologia e Andrologia 2025; 97(2):14085 1 REVIEW The formation of kidney stones is a complex biologic process involving interactions among genetic, anatomic, dietary, and environmental factors. Traditional lithogenic models were based on urine supersatura- tion in relation to the activity of crystallization promoters and inhibitors. However, modern research has added new principles such as the “renal epithelial cell response” and the role of inflammation and oxidative stress leading to the development of a “multi-hit hypothesis”. A strong correlation between urinary stones and kidney damage has been well demonstrated by both cohort and case-control studies. The main contributors to chronic kidney damage associ- ated with urinary stones include crystal deposition within the renal parenchyma, associated comorbidities, repeated obstruc- tive and infectious episodes, as well as the potential adverse effects of stone removal procedures. Most hereditary stones may Management of urinary stones by experts in stone disease (ESD 2025) Athanasios Papatsoris 1, Bogdan Geavlete 2, George Daniel Radavoi 3, Mohammed Alameedee 4, Murtadha Almusafer 5, M. Hammad Ather 6, Alberto Budia 7, Alin Adrian Cumpanas 8, Murat Can Kiremit 9, Athanasios Dellis 10, Mohamed Elhowairis 11, Juan Antonio Galán-Llopis 12, Petrisor Geavlete 13, Jordi Guimerà Garcia 14, Bernat Isern 15, Viorel Jinga 3, Juan Manuel Lopez 16, Juan Antonio Mainez 17, Iraklis Mitsogiannis 1, Jorge Mora Christian 18, Mohammad Moussa 19, Razvan Multescu 2, Yusuf Oguz Acar 20, Kremera Petkova 21, Adria Pinero 22, Elenko Popov 23, Maria Ramos Cebrian 24, Stefan Rascu 3, Roswitha Siener 25, Petros Sountoulides 26, Kyriaki Stamatelou 27, Jaffry Syed 28, Alberto Trinchieri 29 1 National Kapodistrian University of Athens, 2nd University Urology Clinic, Sismanoglio Hospital, Athens, Greece; 2 “Carol Davila” University of Medicine and Pharmacy, "Saint John" Emergency Clinical Hospital, Bucharest, Romania; 3 Clinical Hospital of Urology Prof. Dr. Theodor Burghele, Bucharest, Romania; 4 Diwaniya Teaching Hospital, Diwaniyah, Iraq; 5 University of Basrah, College of Medicine, Basrah, Iraq; 6 Urology Department at the Aga Khan University, Karachi, Pakistan; 7 Urology Department La Fe University and Polytechnic Hospital, Valencia, Spain; 8 Department of Urology, Victor Babeş University of Medicine and Pharmacy, Timisoara, Romania; 9 Koç University School of Medicine, Department of Urology, Istanbul, Turkey; 10 2nd Department of Surgery, Aretaieion Academic Hospital, School of Medicine, National and Kapodistrian University of Athens Athens, Greece; 11 London Clinic, London (UK); 12 Department of Urology, General University Hospital Dr Balmis, ISABIAL, Alicante, Spain; 13 Romanian Academy of Medical Sciences; 14 Lithiasis Unit, Urology Department, Son Espases University Hospital, Palma, Spain; 15 Renal Lithiasis and Pathological Calcification Group (LiRCaP), Research Institute of Health Sciences (IUNICS), University of the Balearic Islands, Spain & Health Research Institute of the Balearic Islands (IdISBa), Spain; 16 Urology Department, ICNU Barcelona University Clinic Hospital, Barcelona, Spain; 17 Urologist, La Paz University Hospital, Madrid, Spain; 18 Urologia Clínica Bilbao, IMQ Zorrotzaurre University Hospital and Deusto University, Bilbao, Spain; 19 Faculty of Medicine at Lebanese University, Beirut, Lebanon; 20 Liv Vadistanbul Hospital, Istanbul, Turkey; 21 Department of Urology and Nephrology, Military Medical Academy, Sofia, Bulgaria; 22 Urology Department, Hospital del Mar, Barcelona, Spain; 23 Medical University - Sofia, Department of Urology, UMHAT “Tzaritza Yoanna-ISUL”, Bulgaria; 24 Renal Transplant Unit Hospital Universitari i Politècnic La Fe, Renal lithiasis, Valencia, Spain; 25 University Stone Center, Department of Urology and Pediatric Urology, University Hospital Bonn, Bonn, Germany; 26 1st Urology Department, Aristotle University of Thessaloniki, Greece; 27 “Mesogeios” Nephrology Center, Athens, Greece; 28 University College Hospital, Galway Clinic and Bons Secours Hospital, Galway, Ireland; 29 CDC Ambrosiana, Cesano B, Milan, Italy. DOI: 10.4081/aiua.2025.14085 Summary cause high urinary saturation levels promoting obstruction of the Bellini ducts and consequent glomerulosclerosis and interstitial fibrosis in the cortex. These include hereditary hypercalciurias, primary hyperoxalurias, cystinuria, adenine phosphoribosyltrans- ferase (APRT) deficiency (associated with 2,8-dihydroxyadenine lithiasis) and xanthinuria. Complete distal renal tubular acidosis occurs in childhood and presents deafness, rickets, and a short life expectancy. The incomplete form usually manifests in adulthood, primarily with recurrent urinary lithiasis, and less frequently with nephrocalcinosis. In all stone formers stone analysis and a basic metabolic evalua- tion, including blood biochemistry, urine sediment examination, urinary pH and culture are mandatory, in contrast high-risk stone formers require a more specific metabolic evaluation, including a 24-hour urine sample to measure calcium, phosphate, citrate, Archivio Italiano di Urologia e Andrologia 2025; 97(2):14085 A. Papatsoris, B. Geavlete, G.D. Radavoi, et al. 2 oxalate, uric acid, magnesium, sodium and proteinuria. The morpho compositional analysis of kidney stones offers essential insights beyond merely identifying their predominant chemical component. This approach reveals key aspets of the stone for- mation, such as nucleation sites, crystal growth patterns, and the presence of specific lithogenic processes. The ideal analyti- cal protocol combines stereoscopic microscopy (StM), scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM-EDS), and, when necessary, Fourier-transform infrared spectroscopy (FTIR). Recurrence prevention and managing residual fragments require complementary strategies such as lifestyle modifica- tions, dietary interventions, and pharmacological therapies. Among pharmacological options, alkaline citrate salts, particu- larly potassium citrate, are widely used due to their ability to modify urinary chemistry and inhibit stone formation. Recently, novel molecules have been introduced into the management of renal stone disease. Phytate a naturally occurring polyphospho- rylated carbohydrate, exibits a potent inhibitory effect on calci- um salt’s nucleation, growth, and aggregation. Theobromine, another natural compound, has been shown to effectively inhib- it uric acid crystallization. The co-administration of urinary alkalinizing agents, such as potassium citrate, alongside theo- bromine has been proposed as a therapeutic strategy to opti- mize uric acid solubility and to reduce the risk of excessive alkalinization and subsequent sodium urate precipitation. Struvite stones are caused by urinary tract infection with ure- ase-producing microorganisms. Their treatment requires specif- ic measures including complete surgical stone removal, short or long-term antibiotic treatment, to maintain urinary acidifica- tion to a pH below 6.2, and a urine volume of at least 2 litres/24 hours. L-methionine has been shown to effectively lower urine pH and the relative supersaturation of struvite. An essential aspect of medical management of urinary stone dis- ease is treatment adherence, which depends on perceived bene- fit, treatment duration, and side effect profile. The side effects of citrate treatment are mild gastrointestinal disorders whereas thiazide diuretics tend to cause hypokalemia-related symptoms and less frequent metabolic and dermatologic side effects. Urease inhibitors for struvite stones and drugs used to enhance cystine solubility are more frequently associated with side effects. The use of smartphone applications can support patients by promoting adequate hydration, adherence to dietary recom- mendations, and compliance with prophylactic medication. Endoscopic techniques currently play a prevalent role in the removal of renal stones, while extracorporeal shock wave lithotripsy is today marginally used for specific indications. Different technical modalities can be used for percutaneous nephrolithotomy (PCNL), each with its own advantages and disadvntages (standard vs. mini, prone vs. supine, fluoroscopic vs ultrasound-guided). Flexible ureteroscopy or retrograde intrarenal renal surgery (RIRS) has extended its indications due to technological advancements in endoscopes and their accessories. The availability of new laser technologies (thulium fiber laser and pulse-modulated Ho:YAG laser) has enhanced stone frag- mentation and dusting capabilities. However, their use exposes the renal parenchyma to high tem- peratures and pressures which could potentially contribute to renal damage. Factors influencing heat release include laser type and settings, exposure time, stone location, fiber-to-stone distance, irrigation volume and fluid circulation. Reduction of heat release can be achieved by limiting the laser settings to reasonable values or by improving fluid circulation with use of ureteral access sheaths, especially those navigable and equipped with suction. High intrarenal pressure is also closely associated with renal damage. Sustained high pressure or even pressure spikes may increase this risk, highlighting the importance of real-time pres- sure monitoring through sensors integrated on guidewires, scopes, access sheath and use of innovative platforms regulating irrigation/suction systems. Direct In-Scope Suction (DISS) system was developed to control intrarenal pressure and facilitate the removal of residual frag- ments. Flexible and Navigable Suction Ureteral Access Sheath (FANS-UAS) is a flexi-bendable UAS equipped with suction capabilities combining mechanical flexibility with continuous irrigation management and stone clearance mechanisms. Ultra-thin scopes (7.5 F) make it easy to perform RIRS without the need for pre-placed double-J stents or with a 9 F sheath achieving more space for stone fragments expulsion or infusion. All these technological advancements have enhanced the effica- cy of fURS or RIRS which can be an alternative treatment (sal- vage fURS) when standard stone management techniques, such as percutaneous nephrolithotomy (PCNL), are contraindicated or fail. Salvage fURS has shown favorable outcomes in complex or high-risk cases, including patients with coagulopathies, mor- bid obesity, renal anatomical abnormalities (e.g., horseshoe or pelvic kidneys), urinary diversion, calyceal diverticula, and altered urinary tracts. In such scenarios it demonstrated favor- able outcomes with stone-free rates ranging from 55.6% to 64% for stones > 2 cm. Although non-invasive, extracorporeal and endoscopic treat- ments for renal and ureteral stones carry a risk of complica- tions that can be classified according to the Clavien-Dindo sys- tem. The complication rate after SWL was estimated at 18.43% for Clavien grade I-II complications (pain, hematuria) and 2.48% for Clavien III-IV complications (hematoma, sepsis). The most frequent complication after RIRS is fever or urinary tract infection observed in 0.2-15% (with 0.1-4.3% of cases of urinary sepsis). Complications after PCNL are more frequent and may include moderate events (hemorrhage requiring trans- fusion 2-7%, urosepsis 1-2%, bowel injury < 1%) as well as severe events (arteriovenous fistula 0.5-1%, thoracic complica- tions < 1% , loss of access tract 1-3%, death < 0.5%). The risk of bleeding complications is significantly increased in patients on antithrombotic therapy. A personalized, interdisciplinary approach enables optimal decision-making in balancing antithrombotic therapy with surgical safety during urological stone interventions Finally, it must be considered that endourological procedures can be harmful to the surgeons themselves and their team due to exposure to ionizing radiation. For this reason, procedures must be carried out in strict accordance with safety guidelines and regulations to minimize radiation exposure. Safety is vital in any surgical intervention, with efficacy being the next most critical consideration. However, cost-effective- ness should be also considered. Endourology involves high costs largely due to the use of sophisticated equipment that requires frequent renewal due to the continuous rapid technological evo- lution. Using disposable devices brings numerous benefits but also leads to a further increase in costs. Finally, in the cost-ben- efit assessment, the rate of reintervention associated with some types of procedures must be considered. KEY WORDS: Urinary calculi; Citrate; Phytate; Theobromine; Shock wave lithotripsy; Retrograde intrarenal lithotripsy; Percutaneous nephrolithotomy; Direct scope suction; Flexible and Navigable Suction Ureteral Access Sheath. Submitted 19 June 2025; Accepted 27 June 2025 Archivio Italiano di Urologia e Andrologia 2025; 97(2):14085 3 Management of urinary stones INTRODUCTION (Almusafer M, Geavlete B, Geavlete P, Jinga V, Mitsogiannis I, Moussa M, Oguz Acar Y, Papatsoris A, Radavoi D) The Experts in Stone Disease (ESD) Conference was found- ed with a clear purpose: to bring together experts world- wide, foster collaboration, and drive innovation in stone disease treatment. Over the years, ESD has become a rec- ognized global platform for exchanging knowledge, com- bining traditional and emerging treatment approaches, and advancing technology and pharmacology. Just as impor- tantly, it continues to inspire and educate the next genera- tion of urologists. The 7th Edition of the ESD Conference was held in Bucharest on 11-12 April 2025 under the pres- idency of Professors Thanos Papatsoris, Bogdan Geavlete and Daniel Radavoi in conjunction with the 10th Romanian Nephro-Urology Conference. ETIOPATHOGENESIS Lithogenesis processes (Kyriaki Stamatelou) The formation of kidney stones is a complex biologic process involving interactions of genetic, anatomic, dietary, and environmental factors. The traditional lithogenesis models emphasize 1. urine supersaturation, 2. the role of crystallization promoters and inhibitors, and 3. Randall’s plaques, as the primary pathophysiologic stone formation mechanisms (1, 2). Modern research has added the “renal epithelial cell response” and the pivotal role of inflammation and oxida- tive stress to form a “multi-hit hypothesis” (3, 4). The scheme describing the physicochemical mechanisms of stone formation has evolved to a multiple-step sequential process involving: supersaturation, oxidative stress, cell apoptosis and/or necrosis, cell injury, crystal nucleation, crystal growth, crystal aggregation, crystal cell interac- tion, crystal adhesion and stone formation. An imbalance between stone inhibitors (magnesium, cit- rate, pyrophosphate, phytate, uromodulin, osteopontin, nephrocalcin, etc) and stone promoters (calcium, sodium, oxalate, uric acid, etc) precedes and triggers supersatura- tion. In the “supersaturation zone of urine” the formation of new crystals occurs spontaneously, the pre-existing crystals may grow, and crystal aggregation is more likely. The pathogenic components of lithogenesis include: • The urinary solute supersaturation that provides the necessary milieu for stone formation. • The nucleus that provides a substrate for crystal growth in supersaturated urine. Injured epithelial cells may serve as nuclei. Nucleation occurs on Randall’s plaques. • The plaques of Randall and plugs which are no longer considered as mere incidental findings but as active pathologic features that act as initiators of calcium- based stones. Chronic inflammation is increasingly viewed as a trigger and amplifier in the lithogenesis. It influences crystal adhesion, growth, and retention in renal tissue: • Crystals induce localized inflammation and oxidative stress, leading to renal epithelial injury. Epithelial injury induces the production of 1.pro-inflammatory cytokines (e.g., IL-6, IL-1β, TNF-α), 2. mineralization modulators (e.g. osteopontin, inter-α-trypsin inhibitor, fibronectin, matrix Gla protein) and 3. promotes osteogenic changes in epithelial cells. • Reactive oxygen species are produced in response to intratubular crystals and induce the expression of mol- ecules known to promote calcification. Oxidative stress and the production of caspases and inflammatory cytokines further promote mitochondrial changes and macrophage infiltration. • Exposure to crystals favors the expression of the pro- inflammatory M-1 phenotype of macrophages thus per- petuating the inflammatory response. • Injured cells promote crystal adhesion and aggregation. Finally, the urinary and gut microbiomes have recently been recognized as pathogenetic elements and modulators of stone risk: oxalate-degrading bacteria (e.g., Oxalobacter formigenes) reduce urinary oxalate, and “dysbiosis” is con- sidered to promote lithogenesis. Research is focusing on probiotic or microbiome-modifying therapies as potential treatments. A better understanding of inflammation acti- vation and modulation of the immune response to urine supersaturation and crystal deposition, as well as effective targeting of inflammatory pathways may provide promis- ing new therapeutic options to reduce lithogenesis and kidney stone recurrence. Renal impairment and ESKD in stone patients (Alberto Trinchieri) The correlation between urinary stones and kidney dam- age has been well described since the beginning of the last century with the description of single cases or small series up to the most recent cohort and case-control studies. Vupputuri et al. (5) demonstrated that a history of kidney stones was more frequent in a large series of patients with chronic kidney disease compared to controls matched for sex and age. The OR for CKD of patients with a history of kidney stones was 1.9. A meta-analysis of seven studies confirmed that the history of kidney stones was associat- ed with an increased adjusted risk estimate for CKD (RR 1.47, CI1.23-1.76) (6). The causes of chronic kidney damage associated with uri- nary stones include crystal deposition in the renal parenchyma, related comorbidities, repeated obstructive and infectious episodes and the effect of treatments for stone removal. In very high urinary saturation levels, obstruction of the Bellini ducts may occur due to crystal plugs with consequent glomerulosclerosis and interstitial fibrosis in the cortex. These conditions are created in the case of most hereditary stones such as hereditary hyper- calciurias (e.g. Dent’s disease), primary hyperoxalurias, deficiency of adenine-phospho-ribosyl transferase (2,8 hydroxyadenine) and, to a lesser extent, cystinuria. Plugging of the Bellini ducts can also be observed in some forms of acquired stones such as brushite stones which are often associated with high levels of calciuria and are resist- ant to SWL. CKD can also be caused by comorbidities frequently asso- ciated with renal stone formation, such as type 2 diabetes. The effects of ureteral obstruction are well demonstrated by experimental studies of ureteral ligation in rats. In clinical conditions, obstruction is incomplete and inter- Archivio Italiano di Urologia e Andrologia 2025; 97(2):14085 A. Papatsoris, B. Geavlete, G.D. Radavoi, et al. 4 mittent, still, repeated and prolonged episodes without relief of the obstruction can be associated with a loss of functional nephrons with hyperfiltration and overload of the residual nephrons resulting in the onset of chronic kidney disease over time. For this reason, urinary tract decompression or treatment of ureteral stones should be timely, especially in case of severe obstruction. The max- imum waiting time is not well defined by the guidelines, although the AUA recommends definitive stone treatment after conservative treatment of 4-6 weeks (7). Studies on urinary excretion of renal tubular damage markers have shown that open renal stone surgery caus- es significant renal tubular damage, especially in treating staghorn renal stones with nephrotomies with temporary clamping of the renal artery (8). However, even noninva- sive treatment can cause transient renal damage. Extracorporeal shock wave lithotripsy induces a measur- able alteration of urinary renal tubular enzymes related to the number and energy of shock waves which is due to renal vasoconstriction and hemorrhagic microlesions. These renal “bioeffects” after SWL are even slightly higher than those observed after percutaneous nephrolithotomy (PCNL) and retrograde intrarenal surgery (RIRS). In con- trast, the bioeffects of PCNL are higher than those of RIRS. Long-term studies after SWL have not shown sig- nificant GFR alterations or unexpected blood pressure increases. However, it must be considered that all these forms of treatment can cause obstructive or vascular com- plications that can cause renal damage in a single case, so their use must be carefully planned to minimize the potential risks of iatrogenic damage. Finally, the recent use of new technologies for intracorporeal lithotripsy potentially exposes the kidney to risks related to high intrarenal pressures or temperatures. These potential causes of morbidity must be carefully evaluated to define better protocols ensuring the safety of the treatment. Rare stones (Maria Ramos) These stones are not prevalent, accounting for just 1-3%. Many have a genetic basis and a high recurrence rate (9-11). Cystinuria is considered one of the most complex condi- tions to treat and is suspected in young patients with a high recurrence rate and weakly radiopaque, bilateral stones. The diagnosis can be made by analysing kidney stones, observing cystine crystals (pathognomonic) in the urinary sediment, or detecting an abnormal excretion of cystine and dibasic amino acids in the urine. Genetic analysis is not mandatory, and the incidence of end-stage kidney disease remains relatively low. Treatment consists of increasing fluid intake, modifying the diet and taking citrate to increase cystine solubility and maintain urine pH at 7-7.5. We use D-penicillamine and tiopronin to bind cystine in the urine in refractory cases. However, they have serious side effects and are often poorly tolerated, which is why some alternative drugs have been investigated, such as tolvaptan, alpha-lipoic acid and iSGLT2, but the results are not conclusive. Adenine phosphoribosyltransferase (APRT) deficiency is an inherited disorder that leads to 2,8-dihy- droxyadenine lithiasis. It can present as urolithiasis or crys- talline nephropathy, and the stones are radiolucent with no metabolic alterations in urine or blood. These stones do not respond to alkali therapy. The treatment consists of high fluid intake and allopurinol. Hereditary xanthinuria is caused by a xanthine oxidase deficiency, resulting in hypouricaemia and hypouricosuria. Since the solubility of xanthine is unaffected by urinary pH, alkalisation is inef- fective. Distal tubular acidosis in idiopathic stone patients (Jordi Guimerà Garcia) Distal renal tubular acidosis (DRTA) has two clinical forms: complete and incomplete. The complete form mainly occurs in childhood and presents deafness, rickets, and a short life expectancy. The incomplete form generally occurs in adulthood and presents recurrent urinary lithi- asis, and, sometimes, nephrocalcinosis. The etiopatho- genesis of incomplete DRTA is the partial inability to excrete acid (H+) into the urine. Incomplete DRTA has the following biochemical characteristics: normal serum pH, alkaline urinary pH (pH > 6), hypercalciuria, and hypocitraturia. Hypercalciuria is due to elevated bone resorption; the patient does not have metabolic acidosis because they compensate with calcium from the bone (buffer effect) (12). Renal stones commonly associated with incomplete DRTA are calcium oxalate dihydrate, hydroxyapatite, and brushite. The diagnosis of incomplete DRTA can be made using the furosemide test or the acid overload test (gold standard). If the furosemide test is performed on patients with the aforementioned characteristics, it has a specificity and sensitivity equivalent to the gold standard (13). Treatment for incomplete DRTA is not well established. Traditionally, treatment involved alkalizing the patient to offset the buffering effect and reduce bone resorption. A recent study demonstrated the efficacy of phytate (300- 400 mg every 12 hours) as an inhibitor of bone resorp- tion and reduction of hypercalciuria in patients with incomplete DRTA (14). DIAGNOSTICS Metabolic workup (Maria Ramos) Metabolic studies are necessary to diagnose and evaluate the response to preventive measures (15-17). The litho- genic risk of a patient is determined by metabolic distur- bances, as well as urine pH and volume. Urine pH is criti- cal in cystinuria, uric acid stones and infectious stones. Changes in urine composition can be caused by increasead crystallization promoters (such as calcium, phosphate, oxalate, uric acid or cystine) or a deficit of crystallization inhibitors (such as citrate, magnesium and phosphate). Stone analysis and basic metabolic evaluation are manda- tory for all stone formers. Crystalluria is valuable in assess- ing the probability of stone recurrence and indicating treat- ment efficacy. Adult patients who have had a single episode of calcium lithiasis require a basic evaluation including blood tests for glucose, urea, creatinine, sodium, potassium, magnesium, chloride, uric acid, calcium, phos- phate, bicarbonate, parathyroid hormone (PTH) and vitamin D, as well as urine tests for sediment, pH and culture. High-risk stone formers (those with recurrent nephrolithi- asis, persistent residual lithiasis or nephocalcinosis, as well as children and young adults) require a more specific meta- Archivio Italiano di Urologia e Andrologia 2025; 97(2):14085 5 Management of urinary stones bolic evaluation, which also includes a 24-hour urine sam- ple to measure calciuria, phosphaturia, citraturia, oxaluria, uricosuria, magnesiuria, natriuresis and proteinuria. Alternatively, spot urine samples can be used, particularly when a 24-hour urine collection is difficult. The first fol- low-up 24-hour urine measurement should be taken eight to twelve weeks after starting pharmacological prevention of stone recurrence. Once urinary parameters have nor- malized, an evaluation every twelve months is sufficient. Stone analysis (Bernat Isern) The morpho-compositional analysis of kidney stones offers essential insights beyond merely identifying their predominant chemical component (18). This type of analysis reveals crucial information about the conditions of stone formation, including nucleation, growth pat- terns, and the presence of specific lithogenic processes. It reconstructs the patient’s lithiasis history sequentially evaluating the stone from nucleus to surface, guiding tai- lored diagnostic and therapeutic decisions. While metabolic analyses are helpful, they often provide only a snapshot of current urinary conditions, which may not reflect the original lithogenic environment. In con- trast, the stone itself serves as a record of past events, making morpho-compositional analysis a more reliable approach to understanding stone formation (19). The ideal analytical protocol combines stereoscopic microscopy (StM), scanning electron microscopy with energy- dispersive X-ray spectroscopy (SEM-EDS), and, when nec- essary, Fourier-transform infrared spectroscopy (FTIR) (20). StM is used first to assess external and internal mor- phology. SEM-EDS provides highly detailed information about elemental composition and minor components often missed by other methods. FTIR complements the analysis in complex or drug-induced stones, though it is limited in detecting minor components and lacks struc- tural context. The Renal Lithiasis Research Laboratory at the University of the Balearic Islands has conducted over 15,000 such analyses, delivering dual reports: one for cli- nicians with specific therapeutic recommendations, and a simplified version for patients. In conclusion, morphocompositional analysis should be routine practice. It significantly enhances diagnostic accuracy, explains stone etiology, and informs more pre- cise treatment strategies, far surpassing the capabilities of traditional chemical or infrared-only methods. MEDICAL TREATMENT AND PREVENTION Dietary measures (Mohamed Elhowairis) Kidney stone formation is a prevalent and recurrent condi- tion influenced significantly by dietary and lifestyle factors. Evidence-based dietary strategies for preventing stones, with a focus on calcium oxalate stones, include increasing fluid intake to achieve optimal urine dilution, maintaining adequate dietary calcium, reducing sodium and animal pro- tein intake, and limiting oxalate-rich foods. Additional emphasis should be placed on enhancing citrate intake through citrus fruits, avoiding excess vitamin C and sugars, and promoting a balanced, plant-rich diet. Special attention is given to patients with malabsorption syndromes or gas- trointestinal surgeries, who are at heightened risk for enteric hyperoxaluria. Emerging therapies are microbiome-targeted probiotics, oxalate-degrading bacteria, and precision nutri- tion. These comprehensive, personalized nutritional inter- ventions aim to reduce stone recurrence and improve patient outcomes through non-pharmacological means. Citrates (M. Can Kiremit) Active treatment modalities remain the cornerstone In the comprehensive management of urinary system stone dis- ease. However, recurrence prevention and managing of residual fragments also require complementary strategies such as lifestyle modifications, dietary interventions, and pharmacological therapies. Among these, alkaline citrate salts (AC), particularly potassium citrate, are widely used due to their ability to alter urinary chemistry and inhibit stone formation (21). The efficacy and safety of AC therapy has been demonstrated in various age groups, including pediatric population (22-24) and therefore it is recom- mended in the current EAU Guidelines (25) for the man- agement of calcium oxalate stones associated with hypoci- traturia, hypercalciuria, hyperoxaluria, or distal renal tubu- lar acidosis, as well as in the management of uric acid and cystine stones. However, there are certain limitations to their use. Although generally well tolerated and associated with minimal side effects, gastrointestinal intolerance may reduce patient adherence. Additionally, regular monitoring of serum elec- trolytes is necessary, to prevent the development of hyper- kalemia, particularly in patients with chronic kidney dis- ease or those receiving potassium-sparing medications. Moreover, monitoring urine pH regularly to adjust the dosage properly is another aspect that might reduce patient compliance. If adherence is lacking, the treatment may become ineffective or the risk of uncontrolled urinary pH elevation (≥ 7.5) by over-alkalinization, particularly if sus- tained over time, may increase the risk of calcium phos- phate stone formation. In conclusion, given its dual role in preventing recurrence and managing residual disease, citrate supplementation is a valuable adjunct to active stone treatment. Its efficacy in stone prevention is well demonstrated, but careful patient selection, individualized dosing, and appropriate moni- toring are essential in optimizing therapeutic outcomes and minimizing adverse effects. Novel molecules (Adrià Pinero) Phytate (myo-inositol hexakisphosphate, InsP 6 ) is a natu- rally occurring polyphosphorylated carbohydrate in seeds, legumes, nuts, and whole grains. In vitro studies have demonstrated that both InsP 6 and its lower phos- phorylated derivatives (InsPs) exhibit a potent inhibitory effect on the nucleation, growth, and aggregation of cal- cium salts, particularly calcium oxalate and calcium phosphate crystals (26). Epidemiological evidence from a large-scale, prospective cohort study involving 96,245 women over eight years revealed that higher dietary phy- tate intake is significantly associated with a reduced risk of developing symptomatic kidney stones (27). Furthermore, experimental data indicate a synergistic interaction between phytate and magnesium, enhancing the inhibitory effect on crystal formation (28). Archivio Italiano di Urologia e Andrologia 2025; 97(2):14085 A. Papatsoris, B. Geavlete, G.D. Radavoi, et al. 6 Theobromine, a naturally occurring dimethylxanthine abundant in cocoa beans, has been shown to effectively inhibit uric acid crystallization (29, 30). Due to its struc- tural similarity to uric acid, theobromine can integrate into forming crystals, altering their morphology by pro- ducing longer and thinner structures with reduced growth kinetics. Unlike calcium-containing stones, phar- macological options for preventing uric acid crystalliza- tion remain limited. Upon ingestion, theobromine is metabolized and excreted in the urine primarily as 7- methylxanthine (36%), unchanged theobromine (21%), 3-methylxanthine (21%), and 3,7-dimethyluric acid (1.3%), all of which retain inhibitory activity against uric acid crystallization. The co-administration of urinary alkalinizing agents, such as potassium citrate, alongside theobromine has been proposed as a therapeutic strategy to optimize uric acid solubility. This combination allows for lower citrate dosages, reducing the risk of excessive alkalinization and subsequent sodium urate precipitation. Additionally, minimizing citrate dosage decreases the risk of hyperkalemia, particularly in patients with impaired renal function or cardiovascular comorbidities. Management of struvite stones (Roswitha Siener) Struvite (magnesium-ammonium-phosphate-hexahy- drate) stones can grow rapidly to large sizes. Struvite stone formers are at high risk for chronic kidney disease and end-stage renal disease. A study of 45,783 stones revealed that 2.1% contained struvite (31). Struvite stones were three times more common in women than men and were most frequent in the youngest and oldest age groups. Factors predisposing to urinary tract infec- tions include vesicoureteral reflux in children and indwelling urinary catheters in the elderly. Struvite stones are always caused by a urinary tract infection with urease- producing microorganisms. The bacterial enzyme urease splits urea to form ammonium and bicarbonate, leading to high urinary ammonium concentrations and pH values above 7.0. Specific measures include complete surgical stone removal, short or long-term antibiotic treatment, urinary acidification to a pH below 6.2, and a urine vol- ume of at least 2 litres/24 hours. Urinary acidification can be achieved with L-methionine. L-methionine is effective in physiologically lowering urine pH and the relative supersaturation of struvite (32). A recent analysis of 1,231 stones containing struvite revealed that only 6% were pure (33). The most common components in mixed struvite stones were carbonate apatite, ammonium urate, calcium oxalate mono- and dihydrate, uric acid and cys- tine. A previous study found metabolic abnormalities in 57% of patients with pure struvite stones and in 81% of patients with mixed stones (34). Therefore, the search for metabolic abnormalities in 24-hour urine after stone removal and infection control is suggested. Side effects of stone medications (Alberto Budia) Patient adherence is one of the most critical aspects of medical treatment for urinary stone disease. If the five dimensions of adherence in these treatments are analyzed (social-economic, healthcare system, condition-related, therapy-related and patient-related), the leading causes of low adherence are a lack of perceived benefit from treat- ment (e.g. lack of symptoms after an acute episode), long duration of therapy and side effects (35, 36). The most common side effects of citrates are gastroin- testinal disorders, such as nausea, diarrhea and abdomi- nal distension. Diuretics can cause weakness, headaches, muscle pain, insomnia and muscle cramps, and long- term thiazide treatment has been associated with non- melanocytic skin cancer. Neurogenic effects (headache and myalgia) have been observed with acetohydroxamic acid and pyridoxine. Specific therapies for cystinuria are associated with a high percentage of side effects (20-30% early and late toxicity). Therefore, to increase adherence to specific treatments for metabolic disorders in stone dis- ease, we must provide accurate information to our patients about the benefits and recommend the use of medical devices such as pH meters or apps that provide immediate feedback on long-term treatment efforts and, of course, ensure continuity of care. Smart apps for stone patients (Juan A. Galán-Llopis) Challenges faced in managing urolithiasis include prob- lems in maintaining adequate hydration tracking, adher- ence to specific diets, and prophylactic medication. Mobile apps have also been changing the management scenario of this disease, and long lists of apps for urolithiasis, includ- ing those for patient information, dietary recording tools, and herbal and drug remedies and advice, have been reported (37). Coaching patients towards maintaining a high compliance to a low-risk lifestyle is a key factor to pre- vent stone recurrence, and the new E- and M-health apps may provide the additional coaching needed (38). These apps may help calculate stone risk, plan specific diets, offer personalized dietary recommendations and hydration advice, a pH diary, and reminders for stent removal. The Lito Diagnostic App allows for precise identification of stone types through the analysis of data on renal stone com- position and patient urinary biochemistry, automatically generating a report. The myLit-Control App provides moni- toring of urine pH, fluid and medication intake, helps patients learning about kidney stones and how to prevent them, and enables a safe and private connection to the patient’s portable pH Meter. Nevertheless, the stone apps need scientific validation to ensure high-quality content and should adhere to clinical guidelines. Recently, the lat- ter app was deemed valid and acceptable by urolithiasis patients as a portable tool for urine pH monitoring at home with high usage compliance and satisfaction rates (39). Future research should explore long-term outcomes and strategies to enhance patient adherence, ensuring effective integration of digital health tools in routine clinical practice (40). PERCUTANEOUS NEPHROLITHOTOMY (PCNL) Supine PCNL (Jorge Mora) (41-43) The supine position offers advantages in anesthetic man- agement, reduced operative time, and lower complication rates, making it suitable for high-risk or pediatric patients. The choice between positions should be individualized based on patient and stone characteristics, surgeon experi- ence and surgical goals (Table 1). Archivio Italiano di Urologia e Andrologia 2025; 97(2):14085 7 Management of urinary stones Table 1. Advantages or disadvantages of supine PCNL. Advantages of supine PCNL Anesthetic Management Easier airway access; reduced cardiopulmonary risks; beneficial for high-risk patients Operative Time Generally shorter due to elimination of patient repositioning and easier stone retrieval Stone-Free Rate (SFR) Slightly better SFR Complication Rate Lower major complication rates; less bleeding and infection risk Radiation Exposure Reduced exposure for the surgeon due to lateral puncture site Access Access to every calyx. Allows access to upper pole Patient Positioning No need for repositioning; facilitates simultaneous retrograde or contraleteral procedures Hospital Stay Shorter hospital stay Ideal Candidates High-risk patients, combined endoscopic procedures, pediatrics Disadvantages of supine PCNL Surgical team Requires more than one urologist if the combined approach is used Access Longer tract can reduce instrument maneuverability, specially in obese patients More expensive Due to more personnel and usage of more instrument and materials * * Probably cost/effective due to reduction in time, complications and hospital stay but needs to be proven. Table 2. Advantages and disadvantages of prone PCNL. Advantages of prone PCNL Better access to the posterior calyces Larger working space for instrument manipulation Lower risk of bowel injury due to retroperitoneal location Disadvantages of prone PCNL Requires repositioning under anesthesia (increased time and complexity) Less favorable for obese patients or those with respiratory compromise Reduced cardiovascular monitoring access during surgery Table 3. Advantages and disadvantages of standard PCNL. Advantages of standard PCNL Good visualization Low intrarenal pressure Low risk of bacterial spread/risk of sepsis Effectiveness/speed of the procedure Disadvantages of standard PCNL Hard access in narrow intrarenal spaces (calycean infundibulum, complete staghorn stone) – Lower intrarenal mobility Table 4. Advantages and disadvantages of mini PNL. Advantages of mini-PNL Higher stone-free rates and shorter operating times compared to RIRS Similar stone-free rates compared to standard PCNL Stone-free rates not affected by stone size and composition Reduced overall complication rates compared to standard PCNL Reduced blood loss compared to standard PCNL Reduced pain compared to standard PCNL Suitable for: • Small and medium sized stones up to 30 mm • Lower pole stones • Stones resistant to SWL • Failed fURS • Special situations (e.g. stones in calyx diverticula) • Additional nephrostomy tracts during a multi-tract PCNL • Pediatric patients Disadvantages of mini-PNL Increased morbidity compared to RIRS Longer hospital stay compared to RIRS Longer convalescence period compared to RIRS Longer OR times compared to standard PCNL Inability to retrieve larger fragments compared to standard PCNL Concerns about raised intrarenal pressures compared to standard PCNL Difficulties in the use of the nephroscopic graspers compared to standard PCNL Table 5. Advantages of fluoroscopy vs. ultrasound guided renal puncture. In favour of fluoroscopy-guided access Comparable results In favour of ultrasound-guided access Radiation exposure Needle puncture time Atone clearance rate Single needle puncture success rate Puncture time Operation time Access to complicated anatomy Intraoperative bleeding rate Blood transfusion requirement Fever/urosepsis rates Prone PCNL (George Daniel Radavoi) (44-46) (Table 2) Fluoroscopy guided renal puncture (Petros Sountoulides) (Table 5) Standard PCNL (Alin Adrian Cumpanas) (Table 3) Mini PCNL (Kremera Petkova) (47-51) (Table 4) Archivio Italiano di Urologia e Andrologia 2025; 97(2):14085 A. Papatsoris, B. Geavlete, G.D. Radavoi, et al. 8 Ultrasound guided renal puncture (Mohammed Alameedee) (52-53) (Table 6) RETROGRADE INTRARENAL SURGERY (RIRS) High power Holmium:YAG laser (Stefan Rascu) (54-57) High Power (HP) Ho:YAG machines represent an improvement over standard Ho:YAG units, allowing a wider variety of settings, with energy settings as low as 0.2 J and frequencies up to 100 Hz. The higher frequen- cies on high-power holmium devices help achieve faster dusting, smaller fragments and a decrease of 50% in las- ing time over the standard machines. Pulse modulation on some HP units (Moses Technology®, Vapour Tunnel and Virtual Basket®) allows for decreased stone movement, improved dusting efficiency and more fragmentation at distance, according to clinical and benchtop studies. While Thulium Fibre Laser (TFL) possesses low peak- power, high-power Ho:YAG benefits from high peak- power. According to my experience, high peak-power matters as laser lithotripsy is not only about dusting. A higher-peak power allows you to fragment stones more efficiently, making the HP unit adequate for all scenarios and locations (embedded, impacted, mobile, small, large, ureteral, kidney or bladder stone). I genuinely believe modern urologists should not be keen on using only one laser device but rather consider each device’s advantages and disadvantages for the case they are fac- ing. Hence, in the following tables, I tried to summarize a few scenarios for using each laser in my daily practice in Table 7 a/b. Table 7a. Scenarios for using each laser: kidney stones. HP HO:YAG TFL Large volume > 2 cm3 Small Size < 1 cm UAS – FANS No UAS High-Power Settings Low-power settings High-Flow Irrigation Low-Flow Irrigation JJ stent No stent Table 7b. Scenarios for using each laser: ureteral stones. HP HO:YAG TFL Impacted Non-Impacted Low-power settings Low-power settings P < 10W, Frequency < 10 Hz P < 10W, Frequency < 10 Hz Table 6. Zero radiation ultrasound-guided PCNL advantages and disadvantages. Advantages 1 No radiation 2 Imaging of structures between skin and kidney, depth of access needle, prevent organ injury (colon, pleura, liver, spleen …etc.). 3 No need for contrast media (in azotemia pt., contrast allergy). 4 Avoids renal vascular injury (color doppler u/s). 5 Used in failed retrograde pyelogram during failure of ureteric catheterization. 6 Safe in pediatric and pregnant patients Can performed in supine position. 7 Cost effective (using a portable ultrasound). 8 No need for lithotomy position and ureter stent fixation. 9 Used even in perinephric extravasated fluid. 10 Use hydro dissection to dissect and separate the colon from the lower pole of the kidney, and early diagnoses of colonic injury especially in obese patients. 11 Use optical hydro dissection in ectopic pelvic kidney to prevent bowel injury. 12 Facilitate reentry to the collecting system in case of tangential entry out of the collecting system. 13 Used in prone, supine, semi prone, semi supine and lateral positions. 14 All the abdomen is the field of entrance from posterior axillary line to the umbilicus. 15 Use the Doppler study to detect the residual stones and also the edges of colon. Disadvantages 1 Difficult identification of the access needle. 2 Technical difficulty in non-dilated PCS. 3 Difficult visualization and manipulation of guide wire and dilaters, especially the non- metallic dilators. 4 Long learning curve. Archivio Italiano di Urologia e Andrologia 2025; 97(2):14085 9 Management of urinary stones Thulium laser (Juan Manuel Lopez) (58-60) (Table 8) Impact of intrarenal pressure and temperature (Razvan Multescu) (61-63) Flexible ureteroscopy is generally a procedure with low morbidity and mild complications. However, while per- forming it we are altering pyelocaliceal system conditions, sometimes with significant clinical consequences. Elevated temperature may impair cell viability and renal function. Many papers are using the critical threshold of 43°C. However, Dewey and Sapareto arbitrarily chose this value and reported it as dangerous if the renal cells were exposed for 120 minutes (61). Factors influencing heat release include laser type and settings, exposure time, stone location, fiber-to-stone distance, irrigation volume, fluid circulation. Efficient irrigation and use of ureteral access sheaths, especially those navigable and with suction (FANS), help temperature control by improving fluid cir- culation. Limiting the laser settings to reasonable values may also prevent such significant lesions. However, exper- imental in vivo porcine models demonstrated that although laser induced thermal lesions were still severe at one week, they may improve by healing in a short period (62). High intrarenal pressure (IRP) is closely associated with septic complications, pain or bleeding. While normal IRP ranges from 0-20 cm H2O, pyelovenous backflow occur beyond 41 cm H2O and fornix ruptures above 81 cm H2O (63). Sustained high pressures or even pressure spikes may increase risk, suggesting importance of real- time monitoring. Innovations include pressure sensors on wires, scopes, UAS and innovative platforms with AI-reg- ulated irrigation/suction systems. FANS and direct in- scope suction help maintaining a low IRP. Understanding and controlling time-dependent changes in temperature and pressure can enhance procedural safety and efficacy. Direct in-scope suction (DISS) (Bogdan Geavlete) Flexible ureteroscopy (fURS) utilization is increasing, sur- passing shock wave lithotripsy (SWL), with experience of over 1,500 procedures a year, worldwide. EAU guidelines suggest percutaneous nephrolithotomy for stones > 20 mm and retrograde renal surgery is not recommended as a first-line treatment for stones > 20 mm (25). However, it may be a first-line option in patients where PCNL is not an option or contraindicated or in selected patients. Technical improvements and disposable tools have increased URS use. Miniaturization of flexible uretero- scopes improves access. Single-use scopes enhance safety, though cost and sustainability remain concerns. The goal is to minimize residual fragments, aiming for < 63 µm. Suction techniques like Irrigation/Suctioning systems and Direct in Scope Suction (DISS) are being developed to con- trol pressure and remove the residual fragments (64-66). Table 8. Comparison of lasers for stone treatment. Technical specifications Ho:YAG TFL p-Tm:YAG Magneto Wavelength ~2100 nm ~1940 nm 2013 nm ~2100 nm Max Power 100–150 W 50–60 W 100 W 100–150 W Frequency 5–80 Hz 10–2400 Hz 5–300 Hz 5–100 Hz Peak Power Up to 10 kW ~0.5 kW ~3.7 kW Up to 10 kW Tissue Penetration ~0.3 mm ~0.08 mm ~0.15–0.2 mm ~0.3 mm Design and operational characteristics Electrical Needs 16–20 A Standard 15 A Standard 15 A 16–20 A Cooling Water cooling Air/water cooling Closed-loop Water cooling Size/Weight >100 kg ~50–60 kg ~97 kg >100 kg Fiber Size ≥200 μm 50–150 μm ≥200 μm 200–1000 μm Noise Loud (~70 dB) Quiet Mid ≤65 dB Loud Lithotripsy performance Feature Ho:YAG TFL p-Tm:YAG Magneto Retropulsion Significant Minimal Low Low-Minimal * Fragmentation Excellent Low Excellent Excellent Dusting Moderate Excellent Excellent Excellent Predominant effect Photomechanical Photothermal Mixed Adjustable Soft tissue surgery Feature Ho:YAG TFL p-Tm:YAG Magneto Coagulation Moderate Excellent Good Improved Dissection Blunt/pulsed Smooth Smooth Versatile Char Low Hi Medium Low Visibility (bleeding) Good Excellent Very Good Excellent * Based on technical characteristics. Archivio Italiano di Urologia e Andrologia 2025; 97(2):14085 A. Papatsoris, B. Geavlete, G.D. Radavoi, et al. 10 Advantages of suction during fURS include lower intrarenal temperature and pressure, reduced infection risk, and improved visibility. Pusen offers single-use fURS with suc- tion (DISS) that can provide low intrarenal pressure and better vision. DISS can be combined with flexible-tip suc- tion UAS. Finally, recent studies support DISS, showing it could be more efficient and helps improve stone-free rates. Large, randomized, multicenter studies are now needed to standardize the results and draw definite conclusions regarding the benefit of these procedures. The true prac- tical impact over the medium- and long-term success rates of the procedure still needs to be further studied. Flexible and Navigable Suction Ureteral Access Sheaths UAS (FANS-UAS) (Petros Sountoulides) Retrograde intrarenal surgery (RIRS) has evolved into a cornerstone of modern endourological management for renal calculi, especially for patients with anatomical con- straints or those at higher surgical risk. A pivotal compo- nent facilitating RIRS is the Ureteral Access Sheath (UAS), which enables repeated scope access, improves irrigation outflow, and contributes to procedural safety and effica- cy. The latest advancements have introduced flexi-bend- able UAS equipped with suction capabilities – Flexible and Navigable Suction UAS (FANS-UAS) – which combine mechanical flexibility with continuous irrigation manage- ment and stone clearance mechanisms (67). The advantages of Flexi-Bendable UAS are: – Enhanced Navigation and Access: traditional UAS are lim- ited by rigidity, potentially restricting access to the lower pole or extreme calyces. Flexi-bendable sheaths feature a soft, passively bendable distal tip that can follow the ureteroscope's movement into difficult-to-reach areas, significantly improving navigation and clinical access in complex renal anatomies (68). – Suction Capability and Improved Visualization: FANS- UAS incorporate a vacuum-assisted side port, allowing active removal of stone dust, blood clots, and irrigation fluid during lithotripsy. This functionality creates a clear operative field (avoiding the 'snow globe' effect), enhanc- ing stone visualization and procedural control. Improved vision correlates with better fragmentation accuracy and shorter operative times (68). – Reduced Intrarenal Pressure (IRP): Elevated IRP during RIRS is associated with pyelovenous backflow, increased risk of urosepsis, and renal injury (69). FANS-UAS have demonstrated the ability to maintain IRP under 20-30 cm H2O, particularly with larger sheaths (> 12/14 Fr) and effective suction mechanisms. Real-time digital uretero- scopes monitoring confirms safer pressure profiles than non-suction approaches (68, 70). Higher Stone-Free Rates (SFR): Clinical trials and multicenter studies show that bendable suction UAS significantly out- perform traditional sheaths in achieving stone-free status. One study reported an 81.3% immediate and 87.5% three- month SFR for FANS-UAS compared to 49.4% and 70% for standard sheaths (70). Real-world data echo these findings, with a 30-day SFR of 86.8% across 25 centers. Decreased Postoperative Complications: Continuous suction and pressure control reduce the risk of infectious compli- cations, including postoperative fever and sepsis. The use of FANS-UAS also minimizes the need for stenting and auxiliary procedures, thus decreasing the overall health- care burden. Clinical Utility and Expanded Indications Flexi-bendable suction UAS are particularly useful in sce- narios involving: – Large stone burdens (> 2 cm) – Pus or turbid urine with infection risk – Solitary kidneys or cases with impaired renal function – Same-session bilateral ureteroscopy (RIRS) – Challenging lower pole stone access. For large stones, FANS-UAS have shown comparable effectiveness to mini-percutaneous nephrolithotomy (mini-PCNL), with lower complication rates and poten- tial for single-session clearance (71). Despite their many advantages, flexi-bendable UAS are not without limitations. Maneuvering the flexible tip requires frequent adjustments, particularly in narrow calyceal infundibula. Fragment removal may still require basketing for stones in the lower calyx due to limited deflection angles (68). Additionally, operator training, cost, and the need for more robust data on long-term out- comes and equipment durability remain essential consid- erations for widespread clinical adoption. In conclusion, FANS-UAS represent a transformative step in endourology, combining flexibility, suction, and safety. They improve access, visibility, pressure control, and stone-free rates, while minimizing complications and inter- vention times. While further research is needed to optimize design and validate cost-effectiveness, these systems have the potential to redefine standard RIRS protocols. Slim disposable fURS (Athanasios Papatsoris) Flexible ureteroscopy (fURS) has been increasingly used as the first-line treatment for urolithiasis (72,73). Disposable (single-use) fURS has enormously progressed because novel slimmer scopes provide both safety and cost/efficacy in retrograde intrarenal surgery (RIRS) (74). The slimmest diameter of most commercially available models is 7.5 Fr (e.g. the EndoView HU-30S by HugeMed). HugeMed was the first to launch the 6.3 Fr fURS in the global market which has already received clinical praise from many colleagues (75). The ultra-thin HU-30S makes it easy to perform RIRS without pre-placed double-J stents (avoidance of another procedure) and insertion of ureteral access sheaths (avoidance of ureteral injury), resulting in lower costs. If a ureteral access sheath is used the HU-30S is easily manipulated through a slim 9 Fr sheath and more stone expelling space is achieved. Moreover, the ultra-thin HU- 30S, provides greater infusion space between the scope and the ureter. This will prevent temperature rise during laser (i.e. Thulium) lithotripsy, relieve renal pressure and improve the stone-clearance rate and reduce the likeli- hood of post op steinstrasse. Weighing less than 300g, the HU-30M effectively prevents the operator’s fatigue during longstanding surgeries. Its standard parameters, including an adjustable angle knob, the 285° bending range in both directions, the 1080P opti- mization algorithm, and the passive bending function, sup- port surgeons in efficiently tackling even the most demand- ing surgical cases. A unique characteristic of the HU-30M is Archivio Italiano di Urologia e Andrologia 2025; 97(2):14085 11 Management of urinary stones that the scope is produced with a 3 or 9 o’clock working channel for right and left FURS, respectively. Additionally, there is no time limit in working with the HU-30M; there- fore, the term disposable is preferred over single use. Having been one of the first endourologists to use the HU-3OM in recent years, it’s my first choice for fURS even for large stones. Once the wire is inserted in the kid- ney the scope can be easily advanced over it just as we advance a 6 Fr JJ stent. With the HU-30M, I’ve stopped pre-stenting patients, and I’ve minimized the use of ureteral access sheaths. I found it ideal for impacted ureteral and lower pole stones, special populations (i.e. children, anatomical anomalies) while slimmer size does not obscure vision or irrigation. Salvage Flexible URS, Pushing the Boundaries (Syed Jaffry) Salvage Flexible Ureterorenoscopy (fURS) is a minimally invasive endourological approach used when standard stone management techniques, such as percutaneous nephrolithotomy (PCNL), are contraindicated or fail. It has become a key alternative in complex or high-risk cases, including patients with coagulopathy, morbid obesity, renal anatomical abnormalities (e.g., horseshoe or pelvic kidneys), urinary diversion, calyceal diverticula, and altered urinary tracts. In salvage scenarios, fURS demon- strates favorable outcomes with stone-free rates (SFRs) ranging from 55.6% to 64% for stones > 2 cm, reaching up to 90% for fragments < 2 mm when multiple sessions are utilized (average 1.6 sessions). Studies show safety and effectiveness across challenging patient groups, with no major intraoperative complications or mortality reported (25). Technological advancements have enhanced the effi- cacy of salvage fURS. High-powered holmium:YAG lasers, particularly systems featuring Vapor Tunnel™ and MasterPULSE™, allow customization of lithotripsy based on stone composition and size. Short pulses deliver aggressive fragmentation for hard stones, while long puls- es enable controlled ablation with minimal retropulsion. Suction access sheaths further optimize outcomes by facil- itating fragment evacuation and maintaining clear visuali- zation. These tools are particularly advantageous in sal- vage procedures involving large or multiple stones. Salvage fURS provides a safe, repeatable, and effective option in modern stone management. Are we truly seeing the end of an era, or are we simply witnessing a redefini- tion of indications? With salvage fURS and suction- enabled RIRS pushing boundaries, perhaps the question is no longer ‘Can we do PCNL?’, but rather ‘Do we need to? COMPLICATIONS OF STONE TREATMENT Classification & Reporting (Elenko Popov) Surgical procedures carry intraoperative or postoperative complications risks, which can have significant out- comes. Therefore, accurate documentation of adverse events and thorough preoperative assessments are cru- cial. These practices help identify systematic errors and improve patient care. Unfortunately, inaccuracies in reporting complications are common among surgeons. A consistent and precise classification system for complica- tions is essential and can only be achieved through a reli- able and validated reporting and grading system recog- nized in clinical practice. The Clavien-Dindo Classification System (CDC) classifies complications based on the inter- ventions required for treatment. Its strengths include applicability across various surgical contexts (76). However, a key limitation is that it only considers the highest-grade complication, potentially underestimating overall patient morbidity. Modifications such as the Memorial Sloan-Kettering Cancer Centre Secondary Events System (77) and the Accordion Severity Grading System (78) have been introduced. Yet they do not fully address the conceptual challenges of the CDC. Each classification and reporting approach has advantages and disadvantages. CDC is the central system for documenting complications due to its ease of use; however, it offers a broad overview of surgical adverse events, creating new reporting frame- works. A urology-specific complication reporting system is needed to monitor complications in urological proce- dures, facilitating better data collection and analysis and enhancing patient safety. The system should be compre- hensive and replicable, ensuring accuracy and reliability. Improving the complication reporting system is essential for Urologists to enhance surgical outcomes. SWL (Athanasios Dellis) The advent of shockwave lithotripsy (SWL) in the 1980s rev- olutionized the management of kidney stones, replacing open surgery and its associated risks of morbidity and mor- tality. However, it became evident that SWL was not uni- versally effective for all stone types and carried its own risks and potential complications. As retrograde intrarenal surgery (RIRS) and percutaneous nephrolithotomy (PCNL) advanced, the scope of SWL applications narrowed. According to the European Association of Urology (EAU) guidelines, SWL remains a first-line treatment for proximal or distal ureteral stones smaller than 1 cm, renal stones up to 2 cm, and lower pole stones in patients with suitable anatomical con- ditions (25). SWL has fewer overall complications com- pared to PCNL and ureteroscopy (URS) (Table 9) (25). Table 9. Complications of SWL. Complications of SWL Regrowth of residual fragments 21–59% Dysrhythmia 11–59% Bacteriuria in non-infection stones 7.7–23% Macroscopic haematuria 17.2% Pain 12.1% Auxiliary procedure 6.9% Steinstrasse 4% Renal colic 2–4% Haematoma, asymptomatic (renal) 1.2% Haematoma, symptomatic (renal) 0.21% Sepsis 0.15% Morbid cardiac events Case reports Liver, spleen haematoma Case reports Bowel perforation Case reports Archivio Italiano di Urologia e Andrologia 2025; 97(2):14085 A. Papatsoris, B. Geavlete, G.D. Radavoi, et al. 12 A meta-analysis of 115 RCTs reported 18.43% Clavien I-II and 2.48% Clavien III-IV complications (79). The connec- tion between SWL and conditions like hypertension or dia- betes remains uncertain. While published data are incon- sistent, no conclusive evidence suggests SWL leads to long- term adverse effects. Management of SWL complications involves monitoring and addressing adverse events such as pain, hematuria, or infection. Pain is managed with anal- gesics, while infections require antibiotics. Persistent obstruction or fragments may need auxiliary pro- cedures like ureteroscopy or nephrostomy placement. Severe complications, including hematoma, require close observation or intervention based on the patient’s clinical stability. RIRS (Elenko Popov) The ongoing advancements in endoluminal endourology in the upper urinary tract have considerably broadened the applicability of retrograde intrarenal surgery (RIRS) within clinical practice. RIRS has transitioned from serv- ing as an alternative modality to a primary intervention for treating renal stones measuring up to 20 mm in max- imum diameter, as stated in both the European and American Association of Urology guidelines. Nonetheless, this technique can be associated with various potential complications akin to any surgical procedure. The most frequently cited complications include discomfort associ- ated with a ureteral stent, injury to the ureteral wall, and the migration of residual stone fragments (1). Among the early and most serious postoperative compli- cations, fever is identified as the most prevalent, closely followed by urinary tract infections, which exhibit an incidence range of 0.2% to 15% (80). A particularly alarming complication is sepsis, with an incidence rate fluctuating between 0.1% and 4.3% (81). In rare instances, sepsis may become life-threatening and is rec- ognized as a primary contributor to postoperative mortal- ity, alongside other significant complications such as car- diac events, respiratory distress, multiorgan failure, and haemorrhagic incidents (80). Table 10. Complications of retrograde intrarenal surgery (RIRS). Complication Incidence Potential Risk Factors Preventive Strategies Ureteral Injury 0.5% - 5% Previous surgeries, anatomical anomalies Preoperative imaging, proper surgical technique Hemorrhage 0.5% - 3% Coagulopathy, significant stone burden, prolonged operative time Monitor operative time and intrarenal pressure Infection 1% - 10% Preexisting urinary tract infections, diabetes, significant stone burden, Prophylactic antibiotics, proper sterile technique, prolonged operative time control of intrarenal pressure and operative time Urinary Leakage 1% - 4% Preexisting urinary conditions, increased intrarenal pressure, forceful technique Control of intrarenal pressure Postoperative Pain 30% - 70% Individual pain threshold, complications, JJ stent Adequate analgesia, multimodal pain management Residual Stone Fragments 5% - 10% Large stone size, inadequate clearance Thorough exploration of renal collecting system, use of adjunctive techniques (ESWL, ECIRS, second stage RIRS) Table 11 Complications of Percutaneous Nephrolithotomy (PCNL). Complication Estimated rate (%) Notes MILD Fever 10–30% Usually self-limited; related to systemic inflammatory response Bleeding (self-limited) 5–10% Minor hematuria, no transfusion required Pain requiring analgesia 10–20% Often resolves within 24–48 hours Urinary leakage (self-limited) 2–5% Usually resolves with conservative management MODERATE Hemorrhage requiring blood transfusion 2–7% Due to vascular injury or significant bleeding Urosepsis 1–2% May require ICU admission if not promptly managed Prolonged urinary leakage 1–2% May require stenting or nephrostomy reinsertion Injury to collecting system requiring repair < 1% Includes pelvic perforation Bowel injury < 1% Requires early detection; may need surgical intervention SEVERE Arteriovenous fistula/pseudoaneurysm 0.5–1% May require angioembolization Thoracic complications (e.g., pneumothorax) < 1% Especially in supracostal access Loss of access tract < 1–3% May necessitate re-puncture or conversion Death < 0.5% Rare; usually related to sepsis or massive hemorrhage PCNL (George Daniel Radavoi) (25, 82, 83) Archivio Italiano di Urologia e Andrologia 2025; 97(2):14085 13 Management of urinary stones Perioperative management of antithrombotic therapy in urological stone surgery (Jaffry Syed) (84-86) The management of anticoagulant and antiplatelet thera- py in patients undergoing urological stone procedures presents a complex balance between minimizing bleeding risk and preventing thromboembolic events. As the prevalence of cardiovascular disease and anticoagulant use increases with an aging population, stone complexity and associated interventions also grow. Commonly used agents include antiplatelets (e.g., aspirin, clopidogrel) for arterial thrombosis and anticoagulants (e.g., warfarin, direct-acting oral anticoagulants or DOACs) for venous thromboembolism and atrial fibrillation. Procedural bleeding risk varies, with low risk for cystoscopy, moder- ate for ureteroscopy, and high for PCNL. Thrombotic risk is stratified based on clinical history, such as mechanical valves or recent venous thromboembolism (VTE). Bridging therapy - typically using low molecular weight heparin (LMWH) - is now limited to high thrombotic risk patients due to increased perioperative bleeding and limited effi- cacy in thrombosis prevention, as shown in recent stud- ies and the BRIDGE trial. DOACs are generally stopped 48-72 hours preoperatively without bridging; warfarin is stopped 5 days prior, with or without bridging depend- ing on risk. Aspirin is usually continued, while clopido- grel requires cessation 5-7 days before surgery, especially if part of dual antiplatelet therapy (DAPT). Multidisciplinary collaboration with cardiology and hematology is advised for complex cases. Evidence-based guidelines, such as those from the EAU and American College of Clinical Pharmacy (ACCP), emphasize individu- alized risk assessment, procedure-specific planning, and structured resumption of therapy postoperatively. For safe outcomes, institutional protocols, pre-assessment planning, and patient education are critical. A personal- ized, interdisciplinary approach enables optimal deci- sion-making in balancing antithrombotic therapy with surgical safety during urological stone interventions. PROTECTION AND ECONOMIC ISSUES Radiation protection (Juan Antonio Mainez) We know that exposure to ionizing radiation is wide- spread in endourology. It’s also known that exposure to high levels of ionizing radiation is associated with an increased risk of cancer and other adverse health effects (87). It’s for this reason that the urologist involved in the care of lithiasis patients should be educated on the safe use of radiation, because the urolithiasis patients will need a multitude of diagnostic and follow-up tests, and surgical interventions (ESWL, URS and fluoroscopy-guided PCNL) in their lives (88). Different international organisms regulate radiation doses and limits. Different countries have been adapting their laws to meet the requirements of the European directive which was published in February 2018. The legislation sets the limits to which healthcare personnel can be exposed annually, regulates how to carry out the records and finally indicates how professionals should be trained. Healthcare personnel should be aware of the different individual protection systems available to reduce the radiation they receive, such as using aprons and glasses, keeping a distance from the source of the radiation, and reducing the time of use (89). All these recommendations are based on the ALARA prin- ciple: As Low As Reasonably Achievable. Many studies are being published in which endourologi- cal interventions are performed without the use of ioniz- ing radiation to reduce exposure (patient and urologist). I believe that these X-ray-free procedures can be carried out with the idea of never subjecting the patient to extra risk by not using fluoroscopic support (90). Laser protection in Endourology (Alin Adrian Cumpanas) The urologists must have a core knowledge about the laser system – both for patients and staff members pro- tection – before starting to use it in a clinical setting. Personnel working in an endourology environment using Ho:YAG, Tm:YAG, or TFLs face minimal ocular risks (if distance from the laser tip to the cornea < 5 cm): safety goggles are optional. Safety goggles are mandatory for Nd:YAG, KTP (Green Light), diode lasers (visible/near infrared < 1400 nm wavelength). Patient complications: the injury is more laser user dependent than laser type dependent. Setting up a cost-effective Endourology Service (Hammad Ather) At the turn of the century, the endourological revolution swept the most formidable invention in urology, extra- corporeal shock wave lithotripsy (ESWL). Surgical interven- tions are assessed on efficacy, safety, and cost-effective- ness. Endourology is superior to ESWL in terms of effica- cy; however, ESWL is a truly minimally invasive modali- ty with a better safety profile. In terms of cost-effective- ness, the jury is still out. Konnopka et al. (91) recently reported that in a German set-up, in 7 years of follow-up, reintervention was need- ed in 15, 23, and 26% of patients undergoing URS, PCNL, and ESWL, respectively. The cost for the primary procedure and reintervention was highest for PCNL (5783€), followed by ESWL (3240€) and URS (2979€). In a recent systematic review by Ghorai and Kumar (92), the authors noted that reusing single-use devices in endourology has financial, environmental, and practical advantages. Safety is vital in any surgical intervention, and efficacy is the second most important consideration. However, the value of cost-effectiveness cannot be underscored. The measures described can significantly reduce the cost of most endourology interventions. CONCLUSIONS (Geavlete B, Papatsoris A, Radavoi D) The 2025 ESD Conference held special significance as a tribute to the late Noor Buchholz (13.02.2024), whose vision and dedication laid the foundation for ESD. Alongside pioneering colleagues, he established an enduring legacy that we honor through our shared com- mitment to excellence and progress. Archivio Italiano di Urologia e Andrologia 2025; 97(2):14085 A. Papatsoris, B. Geavlete, G.D. Radavoi, et al. 14 REFERENCES 1. Rodgers AL. Physicochemical mechanisms of stone formation. Urolithiasis. 2017; 45:27-32. 2. Evan AP, Unwin RJ, Williams JC Jr. Renal stone disease: a com- mentary on the nature and significance of Randall's plaque. Nephron Physiol. 2011; 119:p49-53. 3. Aggarwal KP, Narula S, Kakkar M, Tandon C. Nephrolithiasis: molecular mechanism of renal stone formation and the critical role played by modulators. Biomed Res Int. 2013; 2013:292953. 4. Khan SR, Canales BK, Dominguez-Gutierrez PR. 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Authors' contributions: Conceptualization, A.P., B.G., G.D.R. and A.T.; Methodology, A.T.; Software, N/A.; Validation, A.P., B.G., G.D.R.; Formal analysis, A.T.; Investigation, A.T.; Resources, N/A.; Data curation, A.T.; Writing, A.P., B.G., G.D.R., M.A., M.A., H.A., A.B., A.A.C., M.C.K., A.D., J.A.G.l., P.G., J.G.G., B.I., V.J., J.M.L., J.A.M., I.M., J.M., M.M., R.M., Y.O.A., K.P., A.P., E.P., M.R..C., S.R., R.S., P.S., J.S., K.S., A.T.; Writing-review and editing, A.T.; Visualization, A.T.; Supervision A.P.; Project administration, N/A; Funding acquisition, N/A. All authors have read and agreed to the published version of the man- uscript. Acknowledgments: We thank Vicky Nickolopoulou of InSession Events who helped to superbly organize all the edi- tions of ESD, and we thank Devicare SL for its unconditioned support of the ESD Conference in Bucharest. Archivio Italiano di Urologia e Andrologia 2025; 97(2):14085 15 Management of urinary stones 31. Siener R, Herwig H, Rüdy J, et al. 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J Endourol. 2024; 38:68-76. Correspondence Athanasios Papatsoris MD, MSc, MSc, PhD, FEBU, FES, FPUA agpapatsoris@yahoo.gr Full Professor of Urology, University Department of Urology, Sismanoglio Hospital, National and Kapodistrian University of Athens, Greece Bogdan Geavlete, MD, PhD bogdan_geavlete@yahoo.com Professor of Urology “Carol Davila” University of Medicine and Pharmacy Medical Director “Saint John” Emergency Clinical Hospital, President of the Urological Committee - Romanian Ministry of Health, Bucharest, Romania George Daniel Radavoi, MD radadaniel@yahoo.com Clinical Hospital of Urology “Prof. Dr. Theodor Burghele”, Bucharest, Romania Mohammed Al-Ameedee, MD mohammedalameedee@yahoo.com Consultant Urologist, Diwaniya Teaching Hospital, Iraq Murtadha Almusafer, MD dralmusafer@yahoo.com Prof. & Consultant of Urology, University of Basrah, College of Medicine, Basrah, Iraq M. Hammad Ather, MD hammadather@gmail.com Consultant Urologist, Professor and head of Urology Department at the Aga Khan University, Karachi, Pakistan Archivio Italiano di Urologia e Andrologia 2025; 97(2):14085 17 Management of urinary stones Alberto Budia Alba, MD alberto.budia@hotmail.com Associate Professor, Valencia University, Head of Urology Department La Fe University and Polytechnic Hospital, Spain Murat Can Kiremit, MD mckiremit@gmail.com Koç University, School of Medicine, Department of Urology, Istanbul, Turkey Alin Adrian Cumpanas, MD, PhD, FEBU alincumpanas@hotmail.com Professor and Chairman, Department of Urology, Victor Babeş University of Medicine and Pharmacy, Timisoara, Romania Athanasios E. Dellis MD, PhD, FEBU aedellis@gmail.com Professor of Urology, 2nd Department of Surgery, Aretaieion Academic Hospital School of Medicine, National and Kapodistrian University of Athens, Athens, Greece Mohamed Elhowairis londonclinic1@gmail.com Consultant Urologist, London, UK Juan Antonio Galán-Llopis, MD jagalanllopis@gmail.com Department of Urology, General University Hospital Dr Balmis, ISABIAL, Alicante, Spain Petrisor Geavlete, MD geavlete@gmail.com Professor Emeritus of Urology, Academician (Romanian Academy of Medical Sciences), Board Member of the Romanian Association of Urology, Bucharest, Romania Jordi Guimerà Garcia, MD jordi_guime@hotmail.com Urologist, Lithiasis Unit, urology Department, Son Espases University Hospital, Palma, Spain Bernat Isern, PhD bernat.isern@uib.cat Associate Professor, Renal Lithiasis and Pathological Calcification Group (LiRCaP), Research Institute of Health Sciences (IUNICS), University of the Balearic Islands, Spain Health Research Institute of the Balearic Islands (IdISBa), Spain Viorel Jinga, MD vioreljinga@yahoo.com Professor of Urology, Head and Chairman of Clinical Department of Urology, “Theodor Burghele” Clinical Hospital, Rector of the University Carol Davila of Medicine and Pharmacy, Bucharest, Romania Juan Manuel Lopez, MD urodrlopez@gmail.com Urology Department, ICNU Barcelona University Clinic Hospital, Barcelona, Spain Juan Antonio Mainez, MD Urologist, La Paz University Hospital, Madrid, Spain drmainez@gmail.com Iraklis Mitsogiannis, MD imitsog@med.uoa.gr Professor of Urology, National & Kapodistrian University of Athens Medical School, Greece Jorge Mora Christian, MD jorgemora@urologiaclinica.biz; jmorach2210@gmail.com Urologia Clínica Bilbao, IMQ Zorrotzaurre University Hospital and Deusto University, Blbao, Spain Mohammad Moussa, MD mohamadamoussa@hotmail.com; mohamad.moussa.1@ul.edu.lb Professor of Urology and former Dean of the Faculty of Medicine at Lebanese University, Lebanon Razvan Multescu ,MD, PhD razvanmultescu@yahoo.com Assoc.Professor of Urology, University of Medicine and Pharmacy “Carol Davila” Department of Urology - “Saint John” Emergency Clinica Hospital, Romania Yusuf Oguz Acar, MD oguz.acar@livhospital.com.tr Urologist, Liv Vadistanbul Hospital, Istanbul, Turkey Kremera Petkova, MD dr_petkova@yahoo.com Associate Professor, Department of Urology and Nephrology, Military Medical Academy, Sofia, Bulgaria Adrià Piñero, MD adria.pinero@gmail.com Urology Department, Hospital del Mar, Barcelona, Spain Elenko Popov, MD shennyp@yahoo.com Associate Professor in Urology, Medical University - Sofia, Department of Urology, UMHAT “Tzaritza Yoanna- ISUL”, Bulgaria Maria Ramos Cebrian, MD ramos_marceb@gva.es Nephrologist, Renal Transplant Unit Hospital Universitari i Politècnic La Fe, Renal lithiasis, Valencia, Spain Stefan Rascu, MD, PhD stefanrascu.sr@gmail.com Urology Consultant, Lecturer - Urology Discipline, “Carol Davila” University of Medicine and Pharmacy, Urology Clinic - “Prof. Dr. Th. Burghele” Clinical Hospital, Bucharest, Romania Roswitha Siener, PhD Roswitha.Siener@ukbonn.de Professor, University Stone Center, Department of Urology and Pediatric Urology, University Hospital Bonn, Bonn, Germany Petros Sountoulides, MD psountoulidis@auth.gr Associate Professor of Urology, 1st Urology Department, Aristotle University of Thessaloniki, Greece Kyriaki Stamatelou, MD dr.stamatelou@gmail.com Nephrologist, MBA Scientific Director, “Mesogeios” Nephrology Center, Athens, Greece Jaffry Syed, MD jaffrysyed@gmail.com Consultant Urological Surgeon, University College Hospital, Galway Clinic and Bons Secours Hospital, Ireland Alberto Trinchieri, MD (Corresponding Author) Alberto.trinchieri@gmail.com CDC Ambrosiana, Cesano B., Milano, Italy