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Efficacy of sodium-glucose cotransporter 2 inhibitors for kidney stone prevention in nondiabetic patients is unknown. In a double-blind, placebo-controlled, single-center, crossover phase 2 trial, 53 adults (≥18 and <75 years) with calcium ( n  = 28) or uric acid (UA; n  = 25) kidney stones (at least one previous kidney stone event) without diabetes (HbA1c < 6.5%, no diabetes treatment) were randomized to once daily empagliflozin 25 mg followed by placebo or reverse (2 weeks per treatment). Randomization and analysis were performed separately for both stone types. Primary analyses were conducted in the per protocol set. Primary outcomes were urine relative supersaturation ratios (RSRs) for calcium oxalate (CaOx), calcium phosphate (CaP) and UA—validated surrogates for stone recurrence. Prespecified RSR reductions (≥15%) were met in both groups of stone formers. In patients with calcium stones, empagliflozin reduced RSR CaP (relative difference to placebo, −36%; 95% confidence interval, −48% to −21%; P  < 0.001), but not RSRs CaOx and UA. In patients with UA stones, empagliflozin reduced RSR UA (−30%; 95% confidence interval, −44% to −12%; P  = 0.002) but not RSRs CaOx and CaP. No serious or prespecified adverse events occurred. Thus, empagliflozin substantially reduced RSRs in nondiabetic adults with calcium and UA kidney stones. ClinicalTrials.gov registration: NCT04911660 . As part of the SWEETSTONE trial, the authors report the ability of the sodium-glucose cotransporter 2 inhibitor empagliflozin to reduce the likelihood of kidney stone formation in individuals without diabetes.

IntroductionOpioids are often used to manage postoperative pain. Non-narcotic alternatives have increasingly been used to reduce opioid usage. We conducted an open-label randomized non-inferiority clinical trial to compare non-opioid to opioid therapy for pain management after nephrolithiasis surgery.MethodsPatients undergoing elective ureteroscopy or percutaneous nephrolithotomy between July 2018 and May 2021 were randomized to receive ketorolac (non-opioid) or oxycodone-acetaminophen (opioid). Each patient was surveyed one week postoperatively to assess pain outcomes. Patient demographics, surgical variables, number of pills used, constipation, and adverse events were also assessed. We evaluated whether non-opioid analgesia was non-inferior to opioid analgesia for postoperative pain, assuming a non-inferiority margin of 1.3 in pain score between groups.ResultsAnalyses were based on 90 patients with postoperative pain data: 44 in the ketorolac group and 46 in the oxycodone-acetaminophen group. The groups were similar regarding demographics, type of surgery, ureteral stent placement, and stone burden. Non-inferiority of non-opioids compared to opioids was demonstrated for all outcomes. At follow-up, the average pain scores were 3.20 ± 1.94 (SD) in the non-opioid group and 4.17 ± 1.84 in the opioid group (difference =  − 0.96; 95% CI: − 1.76, − 0.17, p = 0.018). The mean proportions of unused pills were similar between groups (p = 0.47) as were rates of constipation (p = 0.32).ConclusionsNon-opioid analgesia was non-inferior to opioid analgesia in pain management after kidney stone surgery. This trial contributes to the evidence that non-opioid analgesics should be considered an effective option for pain management following non-invasive urologic procedures.

Urolithiasis is one of the most common diseases worldwide, characterized by high morbidity and significant treatment-related costs, with a rising prevalence of up to 20%. The relapse rate within the first 10 years after initial treatment is estimated to be about 60%. Given the increasing prevalence, healthcare-related costs associated with urinary tract stones in the USA are expected to reach up to US $1.24 billion annually by 2030. Current prophylactic therapy for urolithiasis recurrence includes lifestyle modifications, citrate supplementation, and pharmaceuticals. However, a high number of cases remain unresponsive to available pharmacological therapies. Though initially developed for the treatment of Diabetes mellitus, SGLT-2 inhibitors have shown promise in decreasing cardiac and renal endpoints across multiple indications. Recent registry studies have indicated that patients receiving SGLT-2 inhibitors exhibit lower rates of urolithiasis incidence, suggesting a potential reduction in recurrence rates and associated mortality. We hypothesize that SGLT-2 inhibitors (Dapagliflozin), owing to their multiple pleiotropic effects, may offer a viable treatment option for the prophylaxis of high-risk calcium oxalate kidney stones and reduce urinary calcium oxalate output. This study will proceed in two phases: an exploratory phase and a randomized controlled phase. In the exploratory phase, 22 participants with indications for dapagliflozin treatment will be evaluated before and after treatment initiation to ascertain the concrete effect size regarding oxalate and calcium-sparing effects. This data will inform the calculation of the study sample size (ranging from 17 to 104 participants) to include high-risk calcium oxalate kidney stone formers in a randomized controlled crossover study design. Treatment phases-one with dapagliflozin and one with placebo-will alternate with wash-out phases involving placebo. The primary outcome is the reduction of oxalate excretion in 24-hour urine samples compared to baseline values after 8 weeks of therapy. Secondary objectives include analysing effects on kidney function, the frequency of urolithiasis, and treatment tolerance. Additionally, in-depth metabolomics analyses will explore pathophysiological pathways during treatment. Investigators, patients, and research staff will be blinded to the randomization list. This study was initially registered under EudraCT (Nr:2022-000994-13) and has been transitioned to CTIS (Nr: 2024-519371-25-00) to comply with EU Regulation 536/2014, ensuring streamlined management and transparency. Dapagliflozin's pleiotropic effects may provide a novel prophylactic treatment option for urolithiasis. This study aims to evaluate potential treatment effects in a prospective RCT and elucidate potential pathophysiological pathways through in-depth metabolomics analyses. SGLT-2 inhibitors have the potential to transform the landscape of urolithiasis treatment, reduce the healthcare burden on individuals and the system, and significantly improve patient quality of life.

Objectives. To compare the effectiveness of 3 approaches for communicating opioid risk during an emergency department visit for a common painful condition. Methods. This parallel, multicenter randomized controlled trial was conducted at 6 geographically disparate emergency department sites in the United States. Participants included adult patients between 18 and 70 years of age presenting with kidney stone or musculoskeletal back pain. Participants were randomly assigned to 1 of 3 risk communication strategies: (1) a personalized probabilistic risk visual aid, (2) a visual aid and a video narrative, or 3) general risk information. The primary outcomes were accuracy of risk recall, reported opioid use, and treatment preference at time of discharge. Results. A total of 1301 participants were enrolled between June 2017 and August 2019. There was no difference in risk recall at 14 days between the narrative and probabilistic groups (43.7% vs 38.8%; absolute risk reduction = 4.9%; 95% confidence interval [CI] = −2.98, 12.75). The narrative group had lower rates of preference for opioids at discharge than the general risk information group (25.9% vs 33.0%; difference = 7.1%; 95% CI = 0.64, 0.97). There were no differences in reported opioid use at 14 days between the narrative, probabilistic, and general risk groups (10.5%, 10.3%, and 13.3%, respectively; P = .44). Conclusions. An emergency medicine communication tool incorporating probabilistic risk and patient narratives was more effective than general information in mitigating preferences for opioids in the treatment of pain but was not more effective with respect to opioid use or risk recall. Trial Registration. Clinical Trials.gov identifier: NCT03134092. (Am J Public Health. 2022;112(S1):S45–S55. https://doi.org/10.2105/AJPH.2021.306511 )

Background. Uric acid (UA) renal lithiasis has a high rate of recurrence and a prevalence ranging from 10% and 15%, depending on the population. The most important etiological factor is persistence of urinary pH below 5.5 and one of the most common treatments is alkalization with citrate. Recent studies demonstrated that theobromine, which is abundant in chocolate and cocoa, is a potent inhibitor of UA crystallization. Aim. The aim was to compare the efficacy of citrate versus citrate + theobromine as treatment for UA lithiasis. Methods. This randomized cross-over trial investigated the efficacy of two treatments in 47 patients with UA renal lithiasis. Urine volume, pH, UA excretion, theobromine excretion, and risk of UA crystallization (RUAC) at baseline and at the end of each intervention period were measured. Results. Each treatment significantly reduced the risk of UA crystallization compared to basal values. The RUAC after citrate + theobromine was lower than the RUAC after citrate, although this difference was not statistically significant. Conclusion. The combined consumption of citrate and theobromine may be a promising strategy for the prevention of UA kidney stones.

The aim of this article was to review some of the new and commonly used medicinal plants in the treatment of kidney stones, emphasizing medicinal uses, pharmacological activity, and research study of medicinal plants. Renal stones are a common problem worldwide with substantial morbidities and economic costs. The high economic burden associated with kidney stones is linked mainly with healthcare costs. In vitro and in vivo studies on alternative treatment of kidney stones have been searched by using words such as phytotherapy of kidney stones, medicinal plants used in kidney stones, and lithotriptic activity of plants. Articles reviewed showed that medicinal plants have lithotriptic potential. Medicinal plants may be useful in treatment of kidney stones. This study was aimed to explore and elaborate the efficacy and availability of alternative treatment for kidney stones and to provide safe, cost effective, and efficacious management options as well as reduce the burden of disease. Cost effectiveness may enable improvements in treatment efficiency that can benefit patients and the healthcare system. Further randomized clinical trials should be conducted to evaluate the safety and efficacy of medicinal plants.

Our previous study has shown that lime powder (LP) had an inhibitory effect against calcium oxalate stone formation. However, the precise mechanisms underlying such beneficial effect remained unclear. Our present study thus aimed to address the effect of LP on excretory level and compositions of urinary proteins using a proteomics approach. From a total of 80 calcium oxalate stone formers recruited into our 2-year randomized clinical trial of LP effect, 10 patients with comparable age and clinical parameters were selected for this proteomic study. 24-h urine specimens were collected from all subjects, at baseline (before) and after LP treatment for 6 months, and then subjected to quantitative proteomics analysis and subsequent validation by ELISA. Total urinary protein excretion was significantly decreased by LP treatment, but unaffected by placebo. Nanoflow liquid chromatography coupled to tandem mass spectrometry (nanoLC–MS/MS) followed by quantitative analysis revealed 17 proteins whose levels were significantly altered (16 decreased and 1 increased) exclusively by LP treatment. Among these, the decrease of transferrin and increase of uromodulin were validated by ELISA. Moreover, there was a significant correlation between microalbuminuria and urinary transferrin level by Pearson’s correlation test. In summary, LP treatment caused significant reduction in total urinary protein excretion and changes in urinary protein compositions that could be linked to stone inhibitory effects and might be relevant mechanisms responsible for the beneficial effects of LP to prevent kidney stone formation and recurrence.

Our objective was to evaluate the oxidative stress and renal tubular cell damage in patients who have renal stones compared to normal subjects. The patients were re-evaluated after 1-months supplementation with potassium citrate. We recruited 30 patients (11 males and 19 females) diagnosed with kidney stones and scheduled for surgical stone removal the following month, and 30 healthy non-stone formers (14 males and 16 females). Two 24-h urine samples and one heparinized blood sample were collected from each subject. Plasma was separated from the erythrocytes and assayed for creatinine, potassium, sodium, calcium, magnesium, phosphate, malondialdehyde (MDA, a lipid peroxidation product) (P-MDA), protein thiol as an indicator of protein oxidation, and vitamin E. Erythrocytes were analysed for MDA (E-MDA), reduced glutathione (GSH) and cellular glutathione peroxidase (cGPx) activity. The urine was analyzed for pH, creatinine, potassium, sodium, calcium, magnesium, phosphate, oxalate, citrate, MDA (U-MDA), total protein (U-protein) and N-acetyl-beta-glucosaminidase (NAG) activity. For the stone patients, urine and blood samples were re-evaluated after supplementation with potassium citrate (60 mEq/day) for 1 month. Renal stone patients had higher plasma creatinine and lower plasma potassium, urinary pH, potassium, magnesium, phosphate and citrate than the controls. The patients had higher P-MDA, E-MDA, U-MDA, U-protein and NAG activity, but lower GSH, cGPx activity, protein thiol and vitamin E, when compared with controls. After potassium citrate supplementation, P-MDA and E-MDA decreased while plasma vitamin E, urinary NAG activity and citrate increased. Renal stone disease is associated with high oxidative stress and damage to renal tubular cells. These abnormalities are coincident with an increase in blood lipid peroxidation products and a decrease in antioxidant status. Although supplementation with potassium citrate improved urinary citrate levels and oxidative stress, it neither reduced urinary lipid peroxidation products nor remedied the damage to renal tubular cells, probably due to the existence of kidney stones.

According to previous studies oxycodone might have some advantages over morphine in the treatment of visceral pain. This study investigated the opioid consumption (primary outcome), pain relief and side effects (secondary outcomes) of morphine versus oxycodone after percutaneous nephrolithotomy using a method where the somatic pain component was minimized. Forty-four adult patients were studied. The patients were randomised to receive either morphine or oxycodone intravenously as postoperative pain treatment. During the first 4 h after surgery the opioid consumption, pain scores and side effects (nausea, dizziness, sedation, respiratory effects and itching) were registered. The postoperative opioid consumption varied considerably between the patients but the mean opioid consumption in the morphine and oxycodone group was comparable (18.93 mg versus 16.15 mg, P = 0.7). Nausea was significantly less frequent with morphine (P = 0.03). In this study morphine and oxycodone produced similar analgesia the first 4 h after surgery but the frequency of nausea was significantly less patient-reported with morphine. The hypothesis that oxycodone would be superior in the treatment of visceral pain after percutaneous kidney stone operation was not confirmed.[PUBLICATION ABSTRACT]

Puerarin(PUE), an isoflavonoid extracted from Pueraria root, has anti‐apoptotic effects. The objective of this research is to examine the impact of PUE on renal apoptosis and inflammation resulting from renal calculi and to elucidate its mechanism. The approach of network pharmacology and molecular docking was employed to discover potential targets and pathways of PUE. An animal model of calcium oxalate crystal deposition by intraperitoneal injection of glyoxylate and a model of COM‐induced human renal tubular epithelial cells (HK2) were used to investigate the pharmacological mechanisms of PUE against apoptosis and inflammation. We used haematoxylin–eosin (H&E) and Periodic Acid‐Schiff staining (PAS) to assess the effect of PUE on crystal deposition and damage. The mechanism of PUE was elucidated and validated using Western blotting, histology and immunohistochemical staining. Network pharmacology findings indicated that the PI3K/AKT pathway plays a crucial role in PUE. We experimentally demonstrate that PUE alleviated COM‐induced changes in apoptotic proteins, increased inflammatory indicators and changes in oxidative stress‐related indicators in HK2 cells by activating the PI3K/AKT pathway, reduced serum creatinine and urea nitrogen levels in mice caused by CaOx, alleviated crystal deposition and damage, and alleviated apoptosis, oxidative stress and inflammation. Puerarin attenuates renal apoptosis and inflammation caused by kidney stones through the PI3K/AKT pathway.