Management of urinary stones by experts in stone disease (ESD 2025)

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 supersaturation 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 associated with urinary stones include crystal deposition within the renal parenchyma, associated comorbidities, repeated obstructive and infectious episodes, as well as the potential adverse effects of stone removal procedures. Most hereditary stones may 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 phosphoribosyltransferase (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 evaluation, 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, 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 formation, such as nucleation sites, crystal growth patterns, and the presence of specific lithogenic processes. The ideal analytical 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 modifications, dietary interventions, and pharmacological therapies. Among pharmacological options, alkaline citrate salts, particularly 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 polyphosphorylated carbohydrate, exibits a potent inhibitory effect on calcium salt’s nucleation, growth, and aggregation. Theobromine, another natural compound, has been shown to effectively inhibit 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 and to reduce the risk of excessive alkalinization and subsequent sodium urate precipitation. Struvite stones are caused by urinary tract infection with urease- producing microorganisms. Their treatment requires specific measures including complete surgical stone removal, short or long-term antibiotic treatment, to maintain urinary acidification 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 disease is treatment adherence, which depends on perceived benefit, 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 recommendations, 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 fragmentation and dusting capabilities. However, their use exposes the renal parenchyma to high temperatures 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 pressure 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 fragments. 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 efficacy of fURS or RIRS which can be an alternative treatment (salvage 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, morbid obesity, renal anatomical abnormalities (e.g., horseshoe or pelvic kidneys), urinary diversion, calyceal diverticula, and altered urinary tracts. In such scenarios it demonstrated favorable outcomes with stone-free rates ranging from 55.6% to 64% for stones > 2 cm. Although non-invasive, extracorporeal and endoscopic treatments for renal and ureteral stones carry a risk of complications that can be classified according to the Clavien-Dindo system. 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 transfusion 2-7%, urosepsis 1-2%, bowel injury < 1%) as well as severe events (arteriovenous fistula 0.5-1%, thoracic complications < 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-effectiveness 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 evolution. Using disposable devices brings numerous benefits but also leads to a further increase in costs. Finally, in the cost-benefit assessment, the rate of reintervention associated with some types of procedures must be considered.

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