ALLOPURINOL TREATMENT IMPROVES INSULIN RESISTANCE IN NON-DIABETIC PATIENTS WITH RENAL STONE.

Hyperuricemia is an objective risk factor of derangement of fasting serum glucose and type 2 diabetes (T2D), yet whether hyperuricemia has a causative influence on insulin resistance is still debatable. In this study, we tested the hypothesis that lowering uric acid in hyperuricemic nondiabetic subjects might improve insulin resistance. Patients with renal stone and hyperuricemia (n=15) were recruited from the private clinic of Ib-Sina Local Teaching Hospital in Mosul city and prospectively placed on allopurinol (300mg/day) for 6 months. Serum uric acid (SUA), fasting serum glucose (FSG), fasting insulin, and C-peptide were measured using commercial kits. Results confirmed that allopurinol has significantly (P<0.05) reduced c-peptide and insulin together with a non-significant (p>0.05) reduction of serum glucose levels. In conclusion, allopurinol has improved insulin level and glycemic control in a healthy individual, these findings could be used as a template for using allopurinol in diabetic patients to improve glycemic control or future studies could be directed toward structural modification of allopurinol which hopefully might lead to innovation of new antidiabetic drugs.

Carboxymethylated Desmodium styracifolium polysaccharide reduces the risk of calcium oxalate kidney stone formation by inhibiting crystal adhesion and promoting crystal endocytosis.

The inhibition of cell surface crystal adhesion and an appropriate increase in crystal endocytosis contribute to the inhibition of kidney stone formation. In this study, we investigated the effects of different degrees of carboxymethylation on these processes. An injury model was established by treating human renal proximal tubular epithelial (HK-2) cells with 98.3 ± 8.1 nm calcium oxalate dihydrate (nanoCOD) crystals. The HK-2 cells were protected with carboxy (-COOH) Desmodium styracifolium polysaccharides at 1.17% (DSP0), 7.45% (CDSP1), 12.2% (CDSP2), and 17.7% (CDSP3). Changes in biochemical indexes and effects on nanoCOD adhesion and endocytosis were detected. The protection of HK-2 cells from nanoCOD-induced oxidative damage by carboxymethylated Desmodium styracifolium polysaccharides (CDSPs) is closely related to the protection of subcellular organelles, such as mitochondria. CDSPs can reduce crystal adhesion on the cell surface and maintain appropriate crystal endocytosis, thereby reducing the risk of kidney stone formation. CDSP2 with moderate -COOH content showed the strongest protective activity among the CDSPs.

Antioxidant activity and Inhibitory effects of Cydonia oblonga Miller. leaves extracts against calcium oxalate stones.

Urinary stone disease is a widespread health problem in both adults and children, and its prevalence has been increasing worldwide. Various plants preparations have already been used since ancient times in order to treat urolithiasis. The aim of this study is to evaluate the antioxidant capacity and litholytic effect on kidney stones of Cydonia oblonga Miller. leaves. The infusion, methanol and acetone extracts were made from Cydonia oblonga Miller. leaf at different concentration. Estimation of mass fractions of total polyphenol, flavonoid, and flavonol contents, as well as the in vitro radical scavenging potential on 2,2'-diphenyl-1-picrylhydrazyl radical (DPPH·) of the investigated extracts was carried out using colorimetric methods. The litholytic property of the extracts was performed by an in-vitro model using experimentally prepared kidney stones- calcium oxalate. As results, the quince leaf extracts revealed stronger antioxidant properties in the DPPH assay, which was proved by the semi-maximal inhibitory concentration values, being about 36.06 ± 3.55, 74.15 ± 6.29, and 142.35 ± 5.09 µg/ml for methanol, acetone and infusion extracts respectively. Furthermore, the tested extracts were found to be more effective in dissolving calcium oxalate stones compared to the control solutions, the mass loss is about 15.13 ± 1.10% with methanol extract, while it is 14.77 ± 1.74% and 11.14 ± 2.86% for acetone and infusion extracts respectively. These findings confirm the quince leaf's richness in phyto-components, offering anti-oxidant property and being able to be used as a remedy for the management of kidney stones by dissolving calcium oxalate stones in the kidneys.

Carboxymethylated Rhizoma alismatis polysaccharides reduces the risk of calcium oxalate stone formation by reducing cellular inflammation and oxidative stress.

This study aims to elucidate the mechanism and potential of Rhizoma alismatis polysaccharides (RAPs) in preventing oxidative damage to human renal proximal tubule epithelial cells. The experimental approach involved incubating HK-2 cells with 100 nm calcium oxalate monohydrate for 24 h to establish a cellular injury model. Protection was provided by RAPs with varying carboxyl group contents: 3.57%, 7.79%, 10.84%, and 15.33%. The safeguarding effect of RAPs was evaluated by analyzing relevant cellular biochemical indicators. Findings demonstrate that RAPs exhibit notable antioxidative properties. They effectively diminish the release of reactive oxygen species, lactate dehydrogenase, and malondialdehyde, a lipid oxidation byproduct. Moreover, RAPs enhance superoxide dismutase activity and mitochondrial membrane potential while attenuating the permeability of the mitochondrial permeability transition pore. Additionally, RAPs significantly reduce levels of inflammatory factors, including NLRP3, TNF-α, IL-6, and NO. This reduction corresponds to the inhibition of overproduced pro-inflammatory mediator nitric oxide and the caspase 3 enzyme, leading to a reduction in cellular apoptosis. RAPs also display the ability to suppress the expression of the HK-2 cell surface adhesion molecule CD44. The observed results collectively underscore the substantial anti-inflammatory and anti-apoptotic potential of all four RAPs. Moreover, their capacity to modulate the expression of cell surface adhesion molecules highlights their potential in inhibiting the formation of kidney stones. Notably, RAP3, boasting the highest carboxyl group content, emerges as the most potent agent in this regard.

Pharmacologic treatment of kidney stones: Current medication and pH monitoring.

Nephrolithiasis is a globally prevalent urologic condition associated with significant morbidity and patient discomfort. Current management of kidney stones includes both surgical and pharmacologic interventions. Though surgery may be necessary under certain circumstances, pharmacologic treatment is a more affordable, readily available, and a less invasive option for patients. A comprehensive scoping review was conducted to summarize the available literature on the pharmacologic strategies for managing the predominant stone types including calcium oxalate, calcium phosphate, uric acid, struvite, and cystine stones. Central to these therapeutic approaches is the regulation of factors such as urine pH, stone crystallization, and patient metabolics that precipitate stone development and growth. This review highlights the pharmacological options available for treating each kidney stone type, emphasizing the importance of patient tailored medical management that should be considered by every physician.

Is it Safe to Continue Aspirin in Patients Undergoing Percutaneous Nephrolithotomy?

OBJECTIVE: To evaluate peri-operative outcomes in patients on chronic aspirin therapy undergoing percutaneous nephrolithotomy (PCNL), with and without discontinuation of aspirin. Anti-coagulation and anti-platelet therapy are contraindications for PCNL per American Urological Association guidelines due to bleeding risk. However, there is potentially increased cardiovascular risk with peri-procedural aspirin withdrawal. METHODS: Patients on chronic aspirin undergoing PCNL between January 2014 and May 2019 were retrospectively reviewed and stratified by continued or discontinued aspirin >5 days preoperatively. Hematologic complications, transfusions, and thrombotic complications were assessed with logistic regression model. RESULTS: Three hundred twenty-five patients on chronic aspirin therapy underwent PCNL-85 continued and 240 discontinued aspirin. There were no significant differences in hemoglobin change, estimated blood loss, transfusions, creatinine change, thrombotic complications, 30-days re-admissions, complications, or 30-day emergency department visits. Patients who continued aspirin had longer length of stay (1.6 vs 1.9 days, P = .03). American Society of Anesthesiologists (ASA) score of 3 (OR 3.2, P = .02, 95% confidence intervals (CI) [1.2-8.4]), ASA score of 4 (OR 4.0, P = .02, 95% CI [1.2-13.1]), Black race, and previous smoking (OR 2.1, P = .02, 95% CI [1.1-3.9]) was associated with continued aspirin. Body mass index ≥30 was associated with aspirin discontinuation (OR 0.9, P = .004, 95% CI [0.9-1.0]). Increased postoperative hematologic complications were associated with additional anticoagulation medication (OR 2.9, P = .04, 95% CI [1.0-4.4]). CONCLUSION: Continued aspirin use did not increase in postoperative complications in patients undergoing PCNL. Patients who are on additional anticoagulation medication are at risk of hematologic complications.

Nonopioid Pain Management Pathways for Stone Disease.

Introduction: New opioid dependency after urologic surgery is a serious adverse outcome that is well-described in the literature. Patients with stone disease often require multiple procedures because of recurrence of disease and hence are at greater risk for repeat opioid exposures. Despite this, opioid prescribing after urologic surgery remains highly variable and in an emergency setting, opioids are still used commonly in management of acute renal colic. Methods: Two literature searches were performed using PubMed. First, we searched available literature concerning opioid-sparing pathways in acute renal colic. Second, we searched available literature for opioid-sparing pathways in ureteroscopy and percutaneous nephrolithotomy (PCNL). Abstracts were reviewed for inclusion in our narrative review. Results: In the setting of acute renal colic, multiple randomized control trials have shown that nonsteroidal anti-inflammatory drugs (NSAIDs) attain greater reduction in pain scores, decreased need for rescue medications, and decreased vomiting events in comparison with opioids. NSAIDs also form a core component in management of postureteroscopy pain and have been demonstrated in randomized trials to have equivalent to improved pain control outcomes compared with opioids. Multiple opioid-free pathways have been described for postureteroscopy analgesia with need for rescue narcotics falling under 20% in most studies, including in patients with ureteral stents. Enhanced Recovery After Surgery protocols after percutaneous nephrolithotomy are less well described but have yielded a reduction in postoperative opioid requirements. Conclusions: In select patients, both acute renal colic and after kidney stone surgery, adequate pain management can usually be obtained with minimal or no opioid medication. NSAIDs form the core of most described opioid-sparing pathways for both ureteroscopy and PCNL, with the contribution of other components to postoperative pain outcomes limited because of lack of head-to-head comparisons. However, medications aimed specifically at targeting stent-related discomfort form a key component of most multimodal postsurgical pain management pathways. Further investigation is needed to develop pathways in patients unable to tolerate NSAIDs.

The effectiveness of citrates and pyridoxine in the treatment of kidney stones.

The prevalence of nephrolithiasis is increasing across all demographic groups. Apart from the morbidity associated with an acute occurrence, preventative treatment is essential for stone disease, which can become a long-term problem. Simple interventions like fluid intake optimization and dietary modification are effective for most stone types. However, patients with specific metabolic abnormalities may require pharmaceutical therapy if lifestyle changes are insufficient to reduce the risk of stone recurrence. The treatment of citrates and/or pyridoxines may help eliminate or prevent recurrences of kidney stones, especially when they are composed of uric acid, calcium oxalate, calcium phosphate, or the latter two together. In cases of struvite stones, which often necessitate a surgical approach, acetohydroxamic acid emerges as a valuable second-line treatment option. Thiol-binding agents may be needed for cystinuria, as well as lifestyle modifications. Successful treatment reduces stone recurrence and the need to remove stones surgically.

Hydroalcoholic Extract of Ziziphus Jujuba Leaf to Prevent Ethylene Glycol and Ammonium Chloride-Induced Kidney Stones in Male Rat: Is it Effective?

PURPOSE: This study aimed to evaluate the effect of Ziziphus jujuba (Z. jujuba) leaf hydroalcoholic extract on the prevention/treatment of kidney stones. MATERIALS AND METHODS: Thirty-six male Wistar rats were randomly divided into six groups: control, Sham (kidney stone induction (KSI) by ethylene glycol 1% + ammonium chloride 0.25% through drinking water for 28 days), Prevention groups 1, 2 (KSI and Z. jujuba leaf (250 and 500 mg/kg, respectively) through gavage for 28 days), and Treatment groups 1, 2 (KSI and Z. jujuba leaf (250 and 500 mg/kg, respectively) from the 15th day). On the 29th day, the rats' 24-hour urine was assessed, the animals were weighed, and blood samples were taken. Finally, after nephrectomy and weighing the kidneys, tissue sections were prepared to examine the number of calcium oxalate crystals and tissue changes. RESULTS: The results indicated a significant increase in kidney weight and index, tissue changes, and the number of calcium oxalate crystals in the Sham group compared to the control; using Z. jujuba leaf considerably reduced them in experimental groups compared to the Sham. Body weight decreased in the Sham and experimental groups (except the prevention 2 group) compared to the control, while this observed reduction was lower in all experimental groups compared to the Sham. The mean urinary calcium, uric acid, creatinine, and serum creatinine in Sham and experimental groups (except the prevention 2 group) indicated a substantial increase compared to the control and decreased significantly in all experimental groups compared to the Sham. CONCLUSION: Hydroalcoholic extract of Z. jujuba leaf is effective in the reduction of calcium oxalate crystals forming, and its most effective dose was 500mg/kg.

Network pharmacology and experimental validation to elucidate the pharmacological mechanisms of Bushen Huashi decoction against kidney stones.

Introduction: Kidney stone disease (KS) is a complicated disease with an increasing global incidence. It was shown that Bushen Huashi decoction (BSHS) is a classic Chinese medicine formula that has therapeutic benefits for patients with KS. However, its pharmacological profile and mechanism of action are yet to be elucidated. Methods: The present study used a network pharmacology approach to characterize the mechanism by which BSHS affects KS. Compounds were retrieved from corresponding databases, and active compounds were selected based on their oral bioavailability (≥30) and drug-likeness index (≥0.18). BSHS potential proteins were obtained from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, whereas KS potential genes were obtained from GeneCards and OMIM, TTD, and DisGeNET. Gene ontology and pathway enrichment analysis were used to determine potential pathways associated with genes. The ingredients of BSHS extract were identified by the ultra-high-performance liquid chromatography coupled with quadrupole orbitrap mass spectrometry (UHPLC-Q/Orbitrap MS). The network pharmacology analyses predicted the potential underlying action mechanisms of BSHS on KS, which were further validated experimentally in the rat model of calcium oxalate kidney stones. Results: Our study found that BSHS reduced renal crystal deposition and improved renal function in ethylene glycol(EG)+ammonium chloride(AC)-induced rats, and also reversed oxidative stress levels and inhibited renal tubular epithelial cell apoptosis in rats. BSHS upregulated protein and mRNA expression of E2, ESR1, ESR2, BCL2, NRF2, and HO-1 in EG+AC-induced rat kidney while downregulating BAX protein and mRNA expression, consistent with the network pharmacology results. Discussion: This study provides evidence that BSHS plays a critical role in anti-KS via regulation of E2/ESR1/2, NRF2/HO-1, and BCL2/BAX signaling pathways, indicating that BSHS is a candidate herbal drug for further investigation in treating KS.

Hyperoside Ameliorates Renal Tubular Oxidative Damage and Calcium Oxalate Deposition in Rats through AMPK/Nrf2 Signaling Axis.

Background: Nephrolithiasis is a common disease that seriously affects the health and life quality of patients. Despite the reported effect of hyperoside (Hyp) against nephrolithiasis, the specific mechanism has not been clarified. Therefore, this study is aimed at investigating the effect and potential mechanism of Hyp on renal injury and calcium oxalate (CaOx) crystal deposition. Methods: Rat and cell models of renal calculi were constructed by ethylene glycol (EG) and CaOx induction, respectively. The renal histopathological damage, CaOx crystal deposition, and renal function damage of rats were assessed by HE staining, Pizzolato staining, and biochemical detection of blood and urine parameters. MTT and crystal-cell adhesion assays were utilized to determine the activity of HK-2 cells and crystal adhesion ability, biochemical detection and enzyme-linked immunosorbent assay (ELISA) to measure the levels of oxidative stress-related substances and inflammatory factors, and western blot to test the expression levels of proteins related to the AMPK/Nrf2 signaling pathway. Results: Briefly speaking, Hyp could improve the renal histopathological injury and impaired renal function, reduce the deposition of CaOx crystals in the renal tissue of rats with renal calculi, and decrease the adhesion of crystals to CaOx-treated HK-2 cells. Besides, Hyp also significantly inhibited oxidative stress response. Furthermore, Hyp was associated with the downregulation of malondialdehyde, lactate dehydrogenase, and reactive oxygen species and upregulation of superoxide dismutase activity. Additionally, Hyp treatment also suppressed inflammatory response and had a correlation with declined levels of interleukin (IL)-1ß, IL-6, IL-8, and tumor necrosis factor. Further exploration of mechanism manifested that Hyp might play a protective role through promoting AMPK phosphorylation and nuclear translation of Nrf2 to activate the AMPK/Nrf2 signaling pathway. Conclusion: Hyp can improve renal pathological and functional damage, decrease CaOx crystal deposition, and inhibit oxidative stress and inflammatory response. Such effects may be achieved by activating the AMPK/Nrf2 signaling pathway.

Polyunsaturated fatty acids ameliorate renal stone-induced renal tubular damage via miR-93-5p/Pknox1 axis.

OBJECTIVES: Polyunsaturated fatty acids (PUFAs) can decrease the risk of calcium oxalate stone formation, which accounts for 80% of all renal stones. This study aimed to investigate the protective mechanisms of PUFAs against renal stones. METHODS: Urine samples of patients with renal stones and biopsy tissue samples from patients with nephrocalcinosis were tested for miR-93-5p expression. A renal stone mouse model was established with intraperitoneal injection of glyoxylic acid, during which mice were treated with PUFAs and/or an miR-93-5p inhibitor adenovirus. Periodic acid-Schiff staining, terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling staining, oil red O staining, triacylglycerol assay, and colorimetry testing were performed to assess glycogen deposition, apoptosis, lipid accumulation, blood urea nitrogen, and serum creatinine levels, respectively. Renal proximal tubular epithelial cells (human kidney 2 [HK-2]) were subjected to gain- and loss-of-function assays before calcium-oxalate monohydrate (COM) induction and PUFA treatment. Cell counting kit 8, flow cytometry, and lactate dehydrogenase activity assays were used to examine cell viability, apoptosis, and damage. A luciferase reporter gene assay verified the interaction between miR-93-5p and Pknox1, and miR-93-5p and Pknox1 levels were assessed using a reverse transcription-quantitative polymerase chain reaction and Western blot analysis. RESULTS: miR-93-5p was downregulated in clinical samples with renal stones and negatively targeted Pknox1. PUFAs increased miR-93-5p expression and reduced apoptosis, glycogen deposition, and lipid accumulation in mice with renal stones, which were annulled by miR-93-5p downregulation. PUFAs increased proliferation and diminished apoptosis, lipid accumulation, and lactate dehydrogenase activity in COM-induced HK-2 cells, which were negated by miR-93-5p inhibition. Pknox1 overexpression reversed the effect of miR-93-5p upregulation on COM-induced HK-2 cells. CONCLUSIONS: PUFAs repressed renal stone-induced renal tubular damage via the miR-93-5p/Pknox1 axis.

In vivo investigation of the inhibitory effect of Peganum harmala L. and its major alkaloids on ethylene glycol-induced urolithiasis in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Peganum harmala L. is a traditional medicinal plant used for centuries in folk medicine. It has a wide array of therapeutic attributes, which include hypoglycemic, sedative, anti-inflammatory, and antioxidant properties. The fruit decoction of this plant was claimed by Avicenna as traditional therapy for urolithiasis. Also, P. harmala seed showed a clinical reduction in kidney stone number and size in patients with urolithiasis. AIM OF THE STUDY: In light of the above-mentioned data, the anti-urolithiatic activities of the seed extracts and the major ß-carboline alkaloids of P. harmala were investigated. MATERIALS AND METHODS: Extraction, isolation, and characterization of the major alkaloids were performed using different chromatographic and spectral techniques. The in vivo anti-urolithiatic action was evaluated using ethylene glycol (EG)-induced urolithiasis in rats by studying their mitigating effects on the antioxidant machinery, serum toxicity markers (i.e. nitrogenous waste, such as blood urea nitrogen, uric acid, urea, and creatinine), minerals (such as Ca, Mg, P, and oxalate), kidney injury marker 1 (KIM-1), and urinary markers (i.e. urine pH and urine output). RESULTS: Two major alkaloids, harmine (P1) and harmalacidine HCl (P2), were isolated and in vivo evaluated alongside the different extracts. The results showed that P. harmala and its constituents/fractions significantly reduced oxidative stress at 50 mg/kg body weight, p.o., as demonstrated by increased levels of glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx), and catalase (CAT) in kidney homogenate as compared to the EG-treated group. Likewise, the total extract, pet. ether fraction, n-butanol fraction, and P1, P2 alleviated malondialdehyde (MDA) as compared to the EG-treated group. Serum toxicity markers like blood urea nitrogen (BUN), creatinine, uric acid, urea, kidney injury molecule-1 (Kim-1), calcium, magnesium, phosphate, and oxalate levels were decreased by total extract, pet. ether fraction, n-butanol fraction, P1, and P2 as compared to the EG-treated group. Inflammatory markers like NFκ-B and TNF-α were also downregulated in the kidney homogenate of treatment groups as compared to the EG-treated group. Moreover, urine output and urine pH were significantly increased in treatment groups as compared to the EG-treated group deciphering anti-urolithiatic property of P. harmala. Histopathological assessment by different staining patterns also supported the previous findings and indicated that treatment with P. harmala caused a gradual recovery in damaged glomeruli, medulla, interstitial spaces and tubules, and brown calculi materials as compared to the EG-treated group. CONCLUSION: The current research represents scientific evidence on the use of P. harmala and its major alkaloids as an effective therapy in the prevention and management of urolithiasis.

Optimizing pain management following kidney stone surgery: can we avoid narcotics?

INTRODUCTION: Opioids 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. METHODS: Patients 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. RESULTS: Analyses 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). CONCLUSIONS: Non-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.

Variation in care between pediatric and adult patients presenting with nephrolithiasis to tertiary care pediatric emergency departments in the United States (2009-2020).

BACKGROUND: Individuals with nephrolithiasis frequently present to the Emergency Department (ED). Safety and quality principles are often applied in pediatric EDs to children presenting with nephrolithiasis, such as limiting ionizing radiation exposure and opioid analgesics. However, it is unknown whether pediatric EDs apply these same principles to adult patients who present with nephrolithiasis. We hypothesized that adult patients would be associated with higher use of radiation-based imaging and opioid analgesics. OBJECTIVE: To assess variations in diagnostic and treatment interventions and hospital utilization between pediatric and adult patients presenting to the pediatric ED with nephrolithiasis. STUDY DESIGN: A retrospective cohort study was conducted, examining outcomes for pediatric (<18-years-old) versus adult (≥18-years-old) patients in 42 pediatric EDs from 2009 to 2020 using the Pediatric Health Information System (PHIS) database. Patients with an ICD-9/10 principal diagnosis code of nephrolithiasis with no nephrolithiasis-related visits within the prior 6 months were included. Primary outcomes were imaging, medications, and surgical interventions. Secondary outcomes were hospital admissions, 90-day ED revisits, and 90-day readmissions. Generalized linear mixed models with random effects were used to adjust for confounding and clustering. RESULTS: In total, 16,117 patients with 17,837 encounters were included. Most hospitals were academic (95.2%), and a plurality were located in the South (38.1%). Most patients were <18-years-old (84.4%, median (interquartile range): 15 (12-17)-years-old), female (57.9%), and White (76.3%), and 17.1% were Hispanic/Latino. Most had no complex chronic conditions (89.2%) and no chronic disease per pediatric medical complexity algorithm (51.5%). For the primary outcome, adults, relative to pediatric patients, who presented to the pediatric ED with nephrolithiasis had higher adjusted odds of receiving computerized tomography (CT) scans (Odds Ratio [OR] 1.43 [95% Confidence Interval [CI] 1.29-1.59]) and opioid analgesics (OR 1.45 [95%CI 1.33-1.58]) (Summary Figure). Secondary outcomes showed that adults, relative to pediatric patients, had lower adjusted odds of hospital admissions, 90-day ED revisits, and 90-day readmissions. DISCUSSION: Our results suggest that certain pediatric safety and quality principles, such as limiting ionizing radiation exposure and opioid analgesic prescriptions, are not being equally applied to pediatric and adult patients who present to pediatric EDs with nephrolithiasis. The mechanism of these findings remains to be elucidated. CONCLUSIONS: Variations in care for individuals with nephrolithiasis reflect an opportunity for quality improvement in pediatric EDs and inform work exploring optimal care pathways for all patients presenting to the pediatric ED with nephrolithiasis.

Sulfated Undaria pinnatifida polysaccharide inhibits the formation of kidney stones by inhibiting HK-2 cell damage and reducing the adhesion of nano­calcium oxalate crystals.

OBJECTIVE: The formation of kidney stone is closely related to cell injury and crystal adhesion. METHOD: The sulfur trioxide-pyridine method was used to sulfate raw Undaria pinnatifida polysaccharide (UPP) with a molecular weight (Mw) of 8.33 kDa. Four polysaccharides with the sulfate group (-OSO3-) contents of 1.59% (UPP0), 6.03% (UPP1), 20.83% (UPP2), and 36.39% (UPP3) were obtained. The antioxidant activity of the four UPPs, the difference in oxidative damage inflicted by nano-CaOx monohydrate (nano-COM) on human proximal tubular epithelial (HK-2) cells before and after protection by UPPs, and the inhibitory effect on nano-COM adhesion were explored. RESULTS: Structural characterization showed that sulfation was successful. As the -OSO3- content in the UPPs was increased, the antioxidant activity and capability of the UPPs to regulate the growth of calcium oxalate (CaOx) crystals gradually increased. The damage caused by nano-COM crystals to HK-2 cells under protection by UPPs was weakened. This effect enhanced cell viability, enabled the maintenance of good cell morphology, reduced reactive oxygen species (ROS) levels, and inhibited the decrease in mitochondrial membrane potential, as well as decreased the eversion of phosphatidylserine (PS) and the expression of the adhesion proteins osteopontin (OPN), heat shock protein (HSP 90), and Annexin A1 (ANXA1). The adhesion of nano-COM to HK-2 cells was inhibited under the protection by UPPs. CONCLUSION: UPP3 with the highest content of -OSO3- presented the best antioxidant activity and crystal regulation ability, while UPP2 with the second highest -OSO3- content showed optimal cell protection ability and crystal adhesion inhibition ability. The biological activity of UPPs was regulated by Mw and -OSO3- content. UPP2 with moderate -OSO3- content may become a potential drug for preventing CaOx stones.

Small-molecule inhibitor of intestinal anion exchanger SLC26A3 for treatment of hyperoxaluria and nephrolithiasis.

Nephrolithiasis is a common and recurrent disease affecting 9% of the US population. Hyperoxaluria is major risk factor for calcium oxalate kidney stones, which constitute two-thirds of all kidney stones. SLC26A3 (DRA, downregulated in adenoma) is an anion exchanger of chloride, bicarbonate, and oxalate thought to facilitate intestinal oxalate absorption, as evidenced by approximately 70% reduced urine oxalate excretion in knockout mice. We previously identified a small-molecule SLC26A3 inhibitor (DRAinh-A270) that selectively inhibited SLC26A3-mediated chloride/bicarbonate exchange (IC50 ~ 35 nM) and, as found here, oxalate/chloride exchange (IC50 ~ 60 nM). In colonic closed loops in mice, luminal DRAinh-A270 inhibited oxalate absorption by 70%. Following oral sodium oxalate loading in mice, DRAinh-A270 largely prevented the 2.5-fold increase in urine oxalate/creatinine ratio. In a mouse model of oxalate nephropathy produced by a high-oxalate low-calcium diet, vehicle-treated mice developed marked hyperoxaluria with elevated serum creatinine, renal calcium oxalate crystal deposition, and renal injury, which were largely prevented by DRAinh-A270 (10 mg/kg twice daily). DRAinh-A270 administered over 7 days to healthy mice did not show significant toxicity. Our findings support a major role of SLC26A3 in intestinal oxalate absorption and suggest the therapeutic utility of SLC26A3 inhibition for treatment of hyperoxaluria and prevention of calcium oxalate nephrolithiasis.

Comparison of Empiric Preventative Pharmacologic Therapies on Stone Recurrence Among Patients with Kidney Stone Disease.

OBJECTIVE: To compare the frequency of stone-related events among patients receiving thiazides, alkali citrate, and allopurinol without prior 24 h urine testing.  It is unknown whether 1 preventative pharmacological therapy (PPT) medication class is more beneficial for reducing kidney stone recurrence when prescribed empirically. MATERIALS AND METHODS: Using medical claims data from working-age adults with kidney stone disease diagnoses (2008-2018), we identified those prescribed thiazides, alkali citrate, or allopurinol. We excluded those who received 24 h urine testing prior to initiating PPT and those with less than 3 years of follow-up. We fit multivariable regression models to estimate the association between the occurrence of a stone-related event (emergency department visit, hospitalization, or surgery for stones) and PPT medication class. RESULTS: Our cohort consisted of 1834 (60%), 654 (21%), and 558 (18%) patients empirically prescribed thiazides, alkali citrate, or allopurinol, respectively. After controlling for patient factors including medication adherence and concomitant conditions that increase recurrence risk, the adjusted rate of any stone event was lowest for the thiazide group (14.8%) compared to alkali citrate (20.4%) or allopurinol (20.4%) (each P < .001). Thiazides, compared to allopurinol, were associated with 32% lower odds of a subsequent stone event by 3 years (OR 0.68, 95% CI 0.53-0.88). No such association was observed when comparing alkali citrate to allopurinol (OR 1.00, 95% CI 0.75-1.34). CONCLUSION: Empiric PPT with thiazides is associated with significantly lower odds of subsequent stone-related events. When 24 h urine testing is unavailable, thiazides may be preferred over alkali citrate or allopurinol for empiric PPT.

Staghorn stone in megapolycalicosis in a child: Still the case for open surgery? Case report.

We here report a rare case of congenital megapolycalicosis in a 14-year-old girl complicated by a 24-mm staghorn stone and numerous calculi at the level of all caliceal groups that had become symptomatic in recent weeks with malaise, hematuria, and urinary tract infection. Among the various therapeutic options, we opted for open surgery. The staghorn stone was removed by pyelotomy, and washout of the caliceal cavities released numerous microcalculi of 1.5-9 mm in size that were then removed. To our knowledge, this is the first case of pediatric megacapolycalicosis complicated by staghorn stone, which presents complex problems for the diagnosis and therapy.