In the past two decades, major breakthroughs that improve our understanding of the pathophysiology and therapy of kidney stones (KS) have been lacking. The disease continues to be challenging for patients, physicians, and healthcare systems alike. In this context, epidemiological studies are striving to elucidate the worldwide changes in the patterns and the burden of the disease and identify modifiable risk factors that contribute to the development of kidney stones. Our expanding knowledge of the epidemiology of kidney stones is of paramount importance and largely upgrades the modern management of the disease. In this paper, we review the variables affecting prevalence and incidence, including age, gender, race, ethnicity, occupation, climate, geography, systemic diseases, diabetes, vascular disease, chronic kidney disease, and dietary risk factors relevant to kidney stones.

Aim: To present state of the art on the management of urinary stones from a panel of globally recognized urolithiasis experts who met during the Experts in Stone Disease Congress in Valencia in January 2024.Options of treatment: The surgical treatment modalities of renal and ureteral stones are well defined by the guidelines of international societies, although for some index cases more alternative options are possible. For 1.5 cm renal stones, both m-PCNL and RIRS have proven to be valid treatment alternatives with comparable stone-free rates. The m-PCNL has proven to be more cost effective and requires a shorter operative time, while the RIRS has demonstrated lower morbidity in terms of blood loss and shorter recovery times. SWL has proven to be less effective at least for lower calyceal stones but has the highest safety profile. For a 6mm obstructing stone of the pelviureteric junction (PUJ) stone, SWL should be the first choice for a stone less than 1 cm, due to less invasiveness and lower risk of complications although it has a lower stone free-rate. RIRS has advantages in certain conditions such as anticoagulant treatment, obesity, or body deformity.Technical issues of the surgical procedures for stone removal: In patients receiving antithrombotic therapy, SWL, PCN and open surgery are at elevated risk of hemorrhage or perinephric hematoma. URS, is associated with less morbidity in these cases. An individualized combined evaluation of risks of bleeding and thromboembolism should determine the perioperative thromboprophylactic strategy. Pre-interventional urine culture and antibiotic therapy are mandatory although UTI treatment is becoming more challenging due to increasing resistance to routinely applied antibiotics. The use of an intrarenal urine culture and stone culture is recommended to adapt antibiotic therapy in case of postoperative infectious complications. Measurements of temperature and pressure during RIRS are vital for ensuring patient safety and optimizing surgical outcomes although techniques of measurements and methods for data analysis are still to be refined. Ureteral stents were improved by the development of new biomaterials, new coatings, and new stent designs. Topics of current research are the development of drug eluting and bioresorbable stents.Complications of endoscopic treatment: PCNL is considered the most invasive surgical option. Fever and sepsis were observed in 11 and 0.5% and need for transfusion and embolization for bleeding in 7 and 0.4%. Major complications, as colonic, splenic, liver, gall bladder and bowel injuries are quite rare but are associated with significant morbidity. Ureteroscopy causes less complications, although some of them can be severe. They depend on high pressure in the urinary tract (sepsis or renal bleeding) or application of excessive force to the urinary tract (ureteral avulsion or stricture).Diagnostic work up: Genetic testing consents the diagnosis of monogenetic conditions causing stones. It should be carried out in children and in selected adults. In adults, monogenetic diseases can be diagnosed by systematic genetic testing in no more than 4%, when cystinuria, APRT deficiency, and xanthinuria are excluded. A reliable stone analysis by infrared spectroscopy or X-ray diffraction is mandatory and should be associated to examination of the stone under a stereomicroscope. The analysis of digital images of stones by deep convolutional neural networks in dry laboratory or during endoscopic examination could allow the classification of stones based on their color and texture. Scanning electron microscopy (SEM) in association with energy dispersive spectrometry (EDS) is another fundamental research tool for the study of kidney stones. The combination of metagenomic analysis using Next Generation Sequencing (NGS) techniques and the enhanced quantitative urine culture (EQUC) protocol can be used to evaluate the urobiome of renal stone formers. Twenty-four hour urine analysis has a place during patient evaluation together with repeated measurements of urinary pH with a digital pH meter. Urinary supersaturation is the most comprehensive physicochemical risk factor employed in urolithiasis research. Urinary macromolecules can act as both promoters or inhibitors of stone formation depending on the chemical composition of urine in which they are operating. At the moment, there are no clinical applications of macromolecules in stone management or prophylaxis. Patients should be evaluated for the association with systemic pathologies.Prophylaxis: Personalized medicine and public health interventions are complementary to prevent stone recurrence. Personalized medicine addresses a small part of stone patients with a high risk of recurrence and systemic complications requiring specific dietary and pharmacological treatment to prevent stone recurrence and complications of associated systemic diseases. The more numerous subjects who form one or a few stones during their entire lifespan should be treated by modifications of diet and lifestyle. Primary prevention by public health interventions is advisable to reduce prevalence of stones in the general population. Renal stone formers at "high-risk" for recurrence need early diagnosis to start specific treatment. Stone analysis allows the identification of most “high-risk” patients forming non-calcium stones: infection stones (struvite), uric acid and urates, cystine and other rare stones (dihydroxyadenine, xanthine). Patients at “high-risk” forming calcium stones require a more difficult diagnosis by clinical and laboratory evaluation. Particularly, patients with cystinuria and primary hyperoxaluria should be actively searched.Future research: Application of Artificial Intelligence are promising for automated identification of ureteral stones on CT imaging, prediction of stone composition and 24-hour urinary risk factors by demographics and clinical parameters,...

Background: Telomerase preserves telomere length and structure, preventing cellular senescence, which is associated with alteration of the chromosomal ends. We hypothesized that telomerase activity is altered in peripheral blood mononuclear cells (PBMCs) of hemodialysis (HD) patients. To investigate this hypothesis as well as the relationship between telomerase and inflammation, we measured the activity of this reverse transcriptase as well as the level of several inflammatory markers in PBMCs and serum of an end-stage renal failure (ESRF) population and a non-renal-failure group of subjects. Methods: In PBMCs isolated from 42 HD and 39 non-renal-failure subjects of the same age (51.0 ± 12.4 and 51.4 ± 12.1 years, respectively) telomerase activity was measured using PCR-ELISA; the method was based on the telomeric repeat amplification protocol. Results: Telomerase activity in PBMCs was detected in 18 (42.9%) HD and 28 (71.8%) non-renal-failure subjects (p = 0.013). Among positive subjects, percent telomerase activity in PBMCs was significantly higher in non-renal- failure (117 ± 112 %) than in HD (47.6 ± 57.1 %) subjects (p = 0.008). Detectable telomerase activity was lower in long-term than in short-term HD patients (13.3 ± 8.9 vs. 75.0 ± 64.8%, respectively, p = 0.015). Although higher in HD group, inflammatory indexes (C-reactive protein, interleukin-6, IL-6, soluble IL-6 and soluble gp130) were not correlated to telomerase activity in PBMCs. Conclusion: Telomerase activity in PBMCs is reduced in HD patients. It seems that, at least in this type of cell in this population, defense from senescence, as assessed by telomerase activity, is altered and associated with the chronicity of uremia/HD procedure.

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...

Extraskeletal tumoral calcifications (TC) may occur in patients with end-stage renal disease. The TC usually develop in the presence of secondary hyperparathyroidism or a high calcium × phosphate product, while other factors have been also occasionally implicated in their development. At present, no uniformly accepted effective treatment has been described for this condition. We describe a 58-year-old female patient with end-stage renal disease who 7 years after the onset of dialysis presented with pain and movement restriction of various joints. A skeletal X-ray showed huge amounts of periarticular TC. The TC occurred in the absence of hyperparathyroidism or a high calcium × phosphate product as evidenced by hormonal and biochemical examination as well as by a bone biopsy specimen that revealed an adynamic bone disease with significant aluminum staining. Sodium thiosulfate, an inorganic salt that has been claimed to inhibit the formation and to favor the solubility and the mobilization of calcified masses, was administered to the patient, and after a long period of treatment considerable radiological regression of the TC with concurrent clinical recovery was noticed. Aluminum intoxication, along with other factors, was considered to be the cause of TC development. The use of sodium thiosulfate seemed to be a reasonable nonspecific therapeutic approach for the management of TC in this case.