Search Results (139)

Urolithiasis (UL) is increasingly prevalent due to rising cardiorenometabolic diseases, posing significant management challenges despite advances in urological techniques. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, primarily used for type 2 diabetes mellitus, chronic kidney disease, and heart failure, have emerged as a potential novel approach for UL treatment. These inhibitors may help reduce the risk of urolithiasis, particularly in patients with diabetes, by improving glycemic control and altering urinary chemistry, which are crucial factors in stone formation. However, the changes in urinary composition induced by SGLT2 inhibitors might also increase the risk of uric acid stone formation. This review evaluates the potential of SGLT2 inhibitors in managing UL, highlighting both the benefits and the risks. While these inhibitors show promise in reducing new and recurrent urinary stones in patients with diabetes, data on their effects in patients without diabetes who form stones are limited. Current human evidence largely comes from post hoc analyses of randomized controlled trials (RCTs) and large-scale database studies, with only one study providing detailed stone composition data. Experimental studies in animal models and cell lines have focused on calcium oxalate (CaOx) stones, showing that SGLT2 inhibitors specifically target CaOx stone formation and related renal inflammation. Although primarily studied for CaOx stones, their potential impact on other calcium-containing stones, such as calcium phosphate, remains promising. Further research is needed to explore their therapeutic potential and optimize treatment strategies. Full article

Background/Objectives: Damage to renal tubular cells (RTCs) represents a critical pathological manifestation in calcium oxalate (CaOx) stone disease, but the underlying mechanism remains elusive. Energy metabolism reprogramming is a vital influencer of RTC survival, and SMYD2 is a histone methylation transferase that has been extensively implicated in various metabolic disorders. Hence, this research aimed to identify whether SMYD2 induces the reprogramming of energy metabolism in RTCs exposed to CaOx nephrolithiasis. Methods: Kidney samples were obtained from patients who underwent laparoscopic nephrectomy for non-functioning kidneys caused by nephrolithiasis. The glyoxylate-induced CaOx stone mice model was established and treated with AZ505. The SMYD2-knockout HK-2 cell line was constructed. Histological changes were evaluated by HE, VK, Tunel, Masson stainings. The molecular mechanism was explored through co-immunoprecipitation and western blotting. Results: The results found that SMYD2 upregulation led to energy reprogramming to glycolysis in human kidney tissue samples and in mice with CaOx nephrolithiasis. We also identified the substantial involvement of glycolysis in the induction of apoptosis, inflammation, and epithelial–mesenchymal transition (EMT) in HK-2 cells caused by calcium oxalate monohydrate (COM). In vivo and in vitro results demonstrated that SMYD2 inhibition reduces glycolysis, kidney injury, and fibrosis. Mechanistically, SMYD2 was found to promote metabolic reprogramming of RTCs toward glycolysis by activating the AKT/mTOR pathway via methylated PTEN, which mediates CaOx-induced renal injury and fibrosis. Conclusions: Our findings reveal an epigenetic regulatory role of SMYD2 in metabolic reprogramming in CaOx nephrolithiasis and associated kidney injury, suggesting that targeting SMYD2 and glycolysis may represent a potential therapeutic strategy for CaOx-induced kidney injury and fibrosis. Full article

Background/Objectives: Nephrolithiasis (kidney stones) is a frequently occurring urologic condition resulting in significant patient morbidity and healthcare costs. Despite the higher prevalence of metabolic risk factors for nephrolithiasis among Black women, there have been few epidemiologic studies of kidney stones focusing on this group. Methods: We describe demographic and health characteristics, diagnostics, and metabolic profiles of US Black women with self-reported kidney stones. The women were participants in the Black Women’s Health Study (BWHS), a large prospective cohort of US Black women (median age 38 years) begun in 1995. Results: Among the 2750 BWHS participants who completed an online supplemental questionnaire assessing urologic health, 201 women reported nephrolithiasis. Of this number, 62% had completed ≥ 16 years of education, and 82% reported access to health care. Overall, 39% reported experiencing ≥ 2 stones in their lifetime, and 29% required surgery to treat the condition. Thirty-two percent reported having completed a metabolic evaluation, while 70% had undergone a CT scan to diagnose nephrolithiasis. The frequency of metabolic evaluation increased with the number of metabolic components reported: 3% (0 components) to 43% (3–4 components). Conclusions: Our findings are consistent with reports of lower rates of metabolic evaluation among Black patients despite their having multiple risk factors for nephrolithiasis. Further study is needed to identify the barriers and facilitators of metabolic and diagnostic workup of nephrolithiasis in Black women. Full article

Nephrolithiasis, or kidney stone disease, is a significant global health issue in urology, requiring effective management strategies. The management of nephrolithiasis through flexible ureteroscopy (fURS) is increasingly gaining acceptance; however, it is associated with significant costs related to consumables, pharmacotherapy, specialized equipment, and general anesthesia (GA). Limited resources and the need to optimize the cost effectiveness ratio have driven the shift to day-case procedures, offering financial and operational benefits and improving patient satisfaction. This outpatient care approach addresses clinical and economic challenges. For same-day discharge, spinal anesthesia (SA) is essential for fURS, as GA does not permit safe immediate discharge. This retrospective study investigates the feasibility of same-day discharge following fURS procedures performed under SA. Analyzing data from 401 patients who underwent 414 fURS procedures between January 2020 and December 2023, this study aims to evaluate whether same-day discharge is a viable option compared to conventional fURS under GA. The primary objectives are to assess the outcomes, including efficacy, stone-free rate (SFR), pain management, and complication rates, in the context of same-day discharge. Additionally, this study seeks to identify patient and kidney stone characteristics that may influence the suitability of one-day fURS under SA. Outcomes will be measured using the Dindo–Clavien (D-C) classification and Visual Analog Scale (VAS) scores post-procedure. Full article

Dietary factors may be implicated in the formation of kidney stones and should be closely monitored. To achieve this aim, patients are routinely assessed by means of generic dietary recall, a tool widely used by authors in a range of extensive patient populations to record food intake; the findings obtained, however, may be skewed due to dietary variations and underestimation of the effect of food additives. Fifty Frequent Kidney Stone Formers (FKSFs, mean age: 54.3 ± 13.9 years) with normal kidney function, absence of comorbidities, and reliable compliance were selected from a total of 68 patients’ resident in Sardinia, an Italian island where genetic admixtures have been relatively rare for generations. The study, conducted from 1 January 2020 to 31 December 2023, was aimed at assessing nutritional values based on the meticulous recording of food quantities, quality, and potential modifications related to food preparation. Patients were selected during an initial clinical check-up and all efforts made to ensure they were capable of reliably recording all food and drinks consumed. A seven-day food diary was provided in which food and drink intake and their impact on 24 h urine output was recorded. The following parameters were measured in both foods and urine output: citrates, oxalates, calcium, phosphorous, uric acid, proteins and nitrogen compounds, magnesium, sulfates, potassium, carbohydrates, free fatty acids. Study outcomes established the presence of hypocitraturia, hyperoxaluria, hypercalciuria, and moderately high levels of nitrogen compounds. Univariate analysis followed by multivariate analysis for further confirmation were performed and the following observations made. Citrate intake correlated with citraturia but did not promote oxaluria; calcium intake promoted onset of sulfaturia, azoturia, and ammoniuria, whilst magnesium correlated with magnesiuria but not with oxaluria, calciuria, phosphaturia, and azoturia; sulfate intake elicited onset of azoturia but not kaliuresis; potassium intake promoted oxaluria and protein intake resulted in onset of ammoniuria and azoturia. (A) The chemical composition of urine based on dietary intake is hard to predict without taking into account the presence of dietary and urinary interferents; (B) the geographic isolation of patients studied underlines the importance of epigenetics in maintaining a traditional dietary heritage. (C) Moreover, the widespread use of food additives should consistently be taken into account to ensure a correct diagnosis of FKSF and set up a valid treatment plan. Full article

Background and Objectives: Retrograde intrarenal surgery (RIRS) is a minimally invasive technique for nephrolithiasis. RIRS is performed via a monitor screen displaying a magnified surgical site. Respiration can affect the stability of the surgical view during RIRS because the kidneys are close to the diaphragm. The purpose of this trial is to compare the effect of anesthesia type on the stability of the surgical view during RIRS between spinal anesthesia and general anesthesia. Materials and Methods: Patients were allocated to the general anesthesia group or spinal anesthesia group. During surgery, movement of the surgical field displayed on the monitor screen was graded by the first assistant on a 10-grade numeric rating scale (0–10). Next, it was also graded by the main surgeon. After surgery, we evaluated the discomfort with the anesthesia method for all patients. Results: Thirty-four patients were allocated to the general anesthesia group and 32 patients to the spinal anesthesia group. The average values of the two surgeons for surgical field oscillation grade showed vision on the monitor screen was more stable in the general anesthesia group than the spinal anesthesia group (3.3 ± 1.6 vs. 5.0 ± 1.6, p < 0.001). The degrees of the inconvenience of the surgery did not differ between the groups (0.7 ± 1.8 vs. 1.6 ± 2.6, p = 0.114), even though more patients reported inconvenience with a grade of 3 or more in the spinal anesthesia group (8.8% vs. 28.1%, p = 0.042). Conclusions: In terms of the visualization of the surgical site, general anesthesia might provide a more stable surgical view during RIRS compared to spinal anesthesia without increasing inconvenience induced by the type of anesthesia. Full article

Chronic beryllium disease (CBD), or berylliosis, is an interstitial lung disease caused by the chronic inhalation of finely particulate beryllium, frequently mistaken for sarcoidosis. It is rarely associated with skin nodular lesions, asymptomatic granulomatous hepatitis or calcium nephrolithiasis. To date, it has never been reported as a diffused multi-organ granulomatous disease. A 60-year-old Pakistani man, a former excavation worker with ancient history of suspected sarcoidosis, underwent a left nephroureterectomy for suspected papillary kidney carcinoma. The histopathological analysis showed a benign non-necrotic granulomatous infiltration of the renal pelvis and ureter. Six months later, he suffered from two consecutive episodes of acute kidney failure. Bladder biopsies found similar noncaseous granulomatosis and kidney biopsies showed interstitial nephritis. Known for suspected asthma, sleep apnea, and usual interstitial pneumonia, the patient would regularly consult for episodes of pyrexia, chills, nocturnal coughing, and wheezing. As kidney function gradually worsened, he ultimately started hemodialysis and was transferred to our facility. A positive blood beryllium lymphocyte proliferation test confirmed the diagnosis of CBD. This original report is the first description of multi-organ berylliosis with diffused urothelial granulomatosis and pseudo-tumor. The patient’s pulmonary disease is minimal compared with renal and urinary tract involvement, eventually responsible for end-stage kidney disease. Berylliosis usually responds to glucocorticoids. This case report highlights the importance of evoking the diagnosis of CBD in the presence of any granulomatosis, even extra-thoracic, especially if associated with pulmonary symptoms, however atypical. Full article

Dent disease-1 (DD-1) is a rare X-linked tubular disorder characterized by low-molecular-weight proteinuria (LMWP), hypercalciuria, nephrolithiasis and nephrocalcinosis. This disease is caused by inactivating mutations in the CLCN5 gene which encodes the voltage-gated ClC-5 chloride/proton antiporter. Currently, the treatment of DD-1 is only supportive and focused on delaying the progression of the disease. Here, we generated and characterized a Clcn5 knock-in mouse model that carries a pathogenic CLCN5 variant, c. 1566_1568delTGT; p.Val523del, which has been previously detected in several DD-1 unrelated patients, and presents the main clinical manifestations of DD-1 such as high levels of urinary b2-microglobulin, phosphate and calcium. Mutation p.Val523del causes partial ClC-5 retention in the endoplasmic reticulum. Additionally, we assessed the ability of sodium 4-phenylbutyrate, a small chemical chaperone, to ameliorate DD-1 symptoms in this mouse model. The proposed model would be of significant value in the investigation of the fundamental pathological processes underlying DD-1 and in the development of effective therapeutic strategies for this rare condition. Full article

This review addresses the management of urolithiasis in renal transplant recipients, a notably vulnerable group due to the unique anatomical and physiological alterations of the transplanted organ. The prevalence of nephrolithiasis in these patients varies between 0.1% and 6.3%, with a significant impact on graft longevity and function. Surgical access complications due to the renal graft’s position on the iliac vessels and the variety of urinary anastomoses complicate the treatment approaches. This study evaluates the effectiveness and outcomes of percutaneous nephrolithotomy (PCNL) and ureteroscopy (URS), two primary minimally invasive strategies for managing graft stones. Through a narrative review using the PubMed and EMBASE databases, it was found that PCNL offers high stone-free rates especially beneficial for large stones, whereas URS provides a less invasive option with a lower risk of complications for small stones. Both techniques require tailored approaches based on stone composition—mostly calcium oxalate—and specific patient anatomical factors. This review underscores the importance of early diagnosis, appropriate treatment selection, and continuous post-treatment monitoring to mitigate risks and promote long-term renal function in transplant recipients. Full article

Hyperuricemia, i.e., increased plasma uric acid concentration, is a common problem in clinical practice, leading to gout or nephrolithiasis, and is associated with other disorders, such as metabolic syndrome, cardiovascular disease, and chronic renal disease. Xanthine oxidoreductase (XOR) is a critical rate-limiting enzyme involved in uric acid synthesis and a promising target for hyperuricemia therapy. However, XOR inhibitors currently face clinical problems such as a short half-life and side effects. Here, we found that specifically targeting liver Xor with GalNAc-siRNAs had a good therapeutic effect on hyperuricemia. First, siRNAs were designed to target various sites in the homologous region between Homo sapiens and Mus musculus Xor mRNA and were screened in primary mouse hepatocytes. Then, the siRNAs were modified to increase their stability in vivo and conjugated with GalNAc for liver-specific delivery. The effects of GalNAc-siRNAs were evaluated in three hyperuricemia mouse models, including potassium oxonate and hypoxanthine administration in WT and humanized XDH mice and Uox knockout mice. Febuxostat, a specific XOR inhibitor used for hyperuricemia treatment, was used as a positive control. Targeting liver Xor with GalNAc-siRNAs by subcutaneous administration reduced plasma uric acid levels, uric acid accumulation in the kidney, renal inflammation, and fibrosis, thereby alleviating kidney damage in hyperuricemia mouse models without hepatoxicity. The results demonstrated that targeting liver Xor with GalNAc-siRNAs was a promising strategy for hyperuricemia therapy. Full article

Kidney stones represent a serious medical problem, resulting from several factors such as diet, genetics, and certain medical conditions. Visceral adipose tissue has been shown in recent research to play a significant role in kidney stone formation, making it a more precise indicator than traditional obesity indicators such as body mass index. The main aim of this review is to summarize studies on visceral obesity as a predictive marker for nephrolithiasis and to highlight new mechanistic pathways such as adipokine-mediated inflammation and its impact on kidney stone formation. This review emphasizes the importance of considering visceral fat in the prevention and management of kidney stones, suggesting that targeted strategies to reduce visceral fat could decrease the incidence of kidney stones and their management costs. Further prospective studies are needed to validate these findings and propose preventive strategies based on visceral adiposity assessments. Full article

Kidney stone disease has a multifactorial etiology, and evolving dietary habits necessitate continuous updates on the impact of dietary components on lithogenesis. The relationship between diseases influenced by lifestyle, such as obesity and diabetes, and kidney stone risk underscores the need for comprehensive lifestyle analysis. Effective management of kidney stones requires a multidisciplinary approach, involving collaboration among nutritionists, urologists, nephrologists, and other healthcare professionals to address the complex interactions between diet, lifestyle, and individual susceptibility. Personalized dietary therapy, based on each patient’s unique biochemical and dietary profile, is essential and necessitates comprehensive nutritional assessments. Accurate dietary intake evaluation is best achieved through seven-day, real-time dietary records. Key factors influencing urinary risk include fluid intake, dietary protein, carbohydrates, oxalate, calcium, and sodium chloride. Personalized interventions, such as customized dietary changes based on gut microbiota, may improve stone prevention and recurrence. Current research suggests individualized guidance on alcohol intake and indicates that tea and coffee consumption might protect against urolithiasis. There is potential evidence linking tobacco use and secondhand smoke to increased kidney stone risk. The effects of vitamins and physical activity on kidney stone risk remain unresolved due to mixed evidence. For diseases influenced by lifestyle, conclusive evidence on targeted interventions for nephrolithiasis prevention is lacking, though preliminary research suggests potential benefits. Management strategies emphasize lifestyle modifications to reduce recurrence risks, support rapid recovery, and identify predisposing conditions, highlighting the importance of these changes despite inconclusive data. Full article

Background/Objectives: Nephrolithiasis is a heterogeneous disease with a high prevalence and recurrence rate. Although there has been much progress regarding the surgical treatment of stones, a standardized follow-up, especially in recurrent stone formers (SFs), has yet to be decided. This fact leads to the overuse of computed tomography (CT) scans and many reoperations in patients, thus increasing their morbidity and the financial burden on the health systems. This review systematically searched the literature for original articles regarding imaging strategies and endoscopic treatment for patients with recurrent urolithiasis, aiming to identify optimal strategies to deal with these patients. Methods: We systematically searched the Medline database (accessed on 1 April 2024) for articles regarding imaging modalities and endoscopic treatment for patients with recurrent urinary tract lithiasis. Results: No specific follow-up or endoscopic treatment strategy exists for patients with recurrent urolithiasis. CT scan was the imaging modality most used in the studies, followed by X-ray, ultrasonography, and digital tomosynthesis. A transparent algorithm could not be identified. Percutaneous nephrolithotomy (PCNL), retrograde intrarenal surgery (RIRS), and ureteroscopy (URS) were used in the studies for endoscopic treatment. PCNL showed the best stone-free (SFr) rate and lowest hazard ratio (HR) for reoperation. RIRS showed superiority over extracorporeal shockwave lithotripsy for recurrent SFs, but fragments over 4 mm increased the recurrent rate. URS has an increased HR for reoperation for bilateral stones. Conclusions: The heterogeneity of urolithiasis leaves urologists without a standardized plan for recurrent SFs. Thus, each patient’s follow-up should be planned individually and holistically. Pre-stenting is not to be avoided, especially in high-risk patients, and SFr status needs to be the aim. Finally, CT scans should not be generally overused but should be part of a patient’s treatment plan. Prospective studies are required to define SFr status, the size of significant residual fragments, and the modalities of intervention and follow-up. Full article

Kidney stones are becoming increasingly common, affecting up to 10% of adults. A small percentage are of monogenic origin, such as Dent’s disease (DD). DD is a syndrome that causes low-molecular-weight proteinuria, hypercalciuria, nephrolithiasis, and nephrocalcinosis. It is X-linked, and most patients have mutations in the CLCN5 gene. We performed a review of the literature and evaluated the case series (n = 6) of a single center in Spain, reviewing the natural evolution of kidney stones, clinical implications, laboratory analyses, radiological development, and treatment. All patients had a genetically confirmed diagnosis, with the CLCN5 mutation being the most frequent (66%). All patients had proteinuria and albuminuria, while only two and three presented hypercalciuria and phosphate abnormalities, respectively. Only one patient did not develop lithiasis, with most (60%) requiring extracorporeal shock wave lithotripsy or surgery during follow-up. Most of the patients are under nephrological follow-up, and two have either received a renal transplant or are awaiting one. The management of these patients is similar to that with lithiasis of non-monogenic origin, with the difference that early genetic diagnosis can help avoid unnecessary treatments, genetic counseling can be provided, and some monogenic kidney stones may benefit from targeted treatments. Full article

Multiple endocrine neoplasia type 1 (MEN1) is a rare syndrome caused by inactivating mutations in the MEN1 tumor suppressor gene. The three main clinical manifestations of MEN1 are primary hyperparathyroidism (PHPT), duodenal–pancreatic neuroendocrine tumors (DP-NETs) and anterior pituitary tumors. Endocrine tumors in patients with MEN1 differ from sporadic tumors because of their younger age at onset, common multiple presentations and the different clinical course. MEN1 is characterized by a complex clinical phenotype; thus, patients should be followed by a multidisciplinary team of experts that includes an endocrinologist, a surgeon, a oncologist, a radiotherapist, and not least, a nutritionist. It is important to remember the fundamental role that diet plays as a primary prevention tool, together with a healthy and active lifestyle in preventing osteoporosis/osteopenia and reducing the risk of developing kidney stones due to hypercalciuria, two frequent clinical complications in MEN1 patients. Is very important for MEN1 patients to have an adequate intake of calcium, vitamin D, magnesium and phosphate to maintain good bone health. The intake of foods containing oxalates must also be kept under control because in combination with calcium they concur to form calcium oxalate crystals, increasing the risk of nephrolithiasis. Another aspect to consider is the management of patients with pancreatic neuroendocrine tumors undergoing major surgical resections of the pancreas that can lead to alterations in digestion and absorption mechanisms due to partial or total reduction in pancreatic enzymes such as amylase, lipase, and protease, resulting in malabsorption and malnutrition. Therefore, the nutritionist’s aim should be to devise a dietary plan that takes into consideration each single patient, educating them about a healthy and active lifestyle, and accompanying them through various life stages by implementing strategies that can enhance their quality of life. Full article