Search Results (172)

Nephrolithiasis, predominantly driven by calcium oxalate (CaOx) crystal deposition, poses a significant global health burden due to its high prevalence and recurrence rates and limited preventive/therapeutic options. Recent research has underscored a pivotal role for macrophage polarization in nephrolithiasis pathogenesis. Pro-inflammatory phenotype macrophages exacerbate crystal-induced injury and foster stone formation by amplifying crystal adhesion via an NF-κB–IL-1β positive-feedback axis that sustains ROS generation and NLRP3 inflammasome activation, whereas anti-inflammatory phenotype macrophages facilitate crystal clearance and tissue repair. We have summarized the research on treating nephrolithiasis and related renal injury by targeting macrophage polarization in recent years, including therapeutic approaches through pharmacological methods, epigenetic regulation, and advanced biomaterials. At the same time, we have critically evaluated the novel therapeutic strategies for macrophage reprogramming and explored the future development directions of targeting macrophage reprogramming for nephrolithiasis treatment, such as using single-cell/spatial omics to reveal the heterogeneity of macrophages in the stone microenvironment, chimeric antigen receptor macrophages (CAR-Ms) as a potential therapy for specific crystal phagocytosis in certain areas, and multi-omics integration to address inter-patient immune differences. This review highlights that macrophage reprogramming is a transformative frontier in nephrolithiasis management and underscores the need for further research to translate these molecular insights into effective clinical applications. Full article

Background/Objectives: Vedolizumab is a gut-selective anti-integrin monoclonal antibody approved for the treatment of inflammatory bowel disease (IBD). While clinical trials have demonstrated a favorable safety profile, real-world studies are essential for identifying rare adverse events (AEs) and evaluating post-marketing safety. This study assessed vedolizumab’s safety in a real-world cohort and supported the detection of potential safety signals. Methods: A retrospective chart review was conducted on adult IBD patients treated with vedolizumab at a tertiary center in the Republic of Serbia between October 2021 and August 2022. Data included demographics, AEs, and newly reported extraintestinal manifestations (EIMs). Exposure-adjusted incidence rates were calculated per 100 patient-years (PYs). Disproportionality analysis using the FDA Adverse Event Reporting System (FAERS) was performed to identify safety signals, employing reporting odds ratios (RORs) and proportional reporting ratios (PRRs) for AEs also observed in the cohort. Prior IBD therapies and reasons for discontinuation were evaluated. Results: A total of 107 patients (42.1% Crohn’s disease, 57.9% ulcerative colitis) were included, with a median vedolizumab exposure of 605 days. There were 92 AEs (56.51/100 PYs), most frequently infections (23.95/100 PYs), gastrointestinal disorders (4.30/100 PYs), and skin disorders (4.30/100 PYs). The most frequently reported preferred terms (PTs) included COVID-19, COVID-19 pneumonia, nephrolithiasis, and nasopharyngitis. Arthralgia (12.90/100 PYs) was the most frequent newly reported EIM. No discontinuations due to vedolizumab AEs occurred. FAERS analysis revealed potential signals for events not listed in prescribing information but observed in the cohort: nephrolithiasis, abdominal pain, diarrhea, malaise, cholangitis, gastrointestinal infection, blood pressure decreased, weight decreased, female genital tract fistula, respiratory symptom, and appendicectomy. Most patients had received three prior therapies, often stopping one due to AEs. Conclusions: Vedolizumab demonstrated a favorable safety profile in the IBD cohort. However, FAERS-identified signals, such as nephrolithiasis, gastrointestinal infections, and decreased blood pressure, warrant further investigation in larger, more diverse populations. Full article

Background/Objectives: Acetazolamide is widely used for acute mountain sickness (AMS) prophylaxis. Whilst generally safe, acute kidney injury (AKI) is a rare but serious adverse event. We present a case of anuric AKI following minimal exposure to acetazolamide, contributing to the limited literature on its nephrotoxicity at prophylactic doses. Methods: A 54-year-old previously healthy male ingested 250 mg/day of oral acetazolamide for two days. He developed acute anuria and lumbar pain. Diagnostic evaluation included laboratory tests, imaging, microbiological cultures, autoimmune panels, and diuretic response. No signs of infection, urinary tract obstruction, or systemic disease were found. Results: The patient met KDIGO 2012 criteria for stage 3 AKI, with peak serum creatinine of 10.6 mg/dL and metabolic acidosis. Imaging confirmed non-obstructive nephrolithiasis. Conservative treatment failed; intermittent hemodialysis was initiated. Renal function recovered rapidly, with the normalization of serum creatinine and urinary output by day 4. Conclusions: This case represents the lowest cumulative dose of acetazolamide reported to cause stage 3 AKI. The findings support a pathophysiological mechanism involving sulfonamide-induced crystalluria and intratubular obstruction. Physicians should consider acetazolamide in the differential diagnosis of AKI, even with short-term prophylactic use. Full article

Acid–base balance is critical to human health and can be significantly influenced by dietary choices. The Western diet, characterized by high meat and cheese consumption, induces excess acidity, highlighting the need for strategies to mitigate this. Recent studies have focused on bicarbonate-rich mineral water as a viable solution. In this context, the present narrative review synthesizes the findings from recent scientific studies on bicarbonate-rich mineral water, specifically those with bicarbonate levels over 1300 mg/L and medium or low PRAL values. This water has been shown to exert beneficial effects on both urinary and blood parameters. The key effects include an increase in the urine pH and a profound reduction in net acid excretion as a sign for a reduced acid load. Additionally, bicarbonate mineral water has been shown to decrease the excretion of nephrolithiasis-related constituents, including calcium and oxalates, as well as inhibitory substances such as magnesium and citrates. In blood, bicarbonate-rich water has been demonstrated to stabilize pH and increase bicarbonate levels, thereby enhancing systemic buffering capacity. Clinically, these changes have been associated with a lowered risk of calcium oxalate stone formation and improved kidney health. Furthermore, bicarbonate-rich water has been shown to support bone health by reducing bone resorption markers. Consequently, the integration of bicarbonate-rich mineral water into the diet has the potential to enhance urinary and blood parameters, mitigate the risk of kidney stones, and strengthen skeletal integrity, thereby serving as a promising strategy for health promotion and disease prevention. While promising, these findings underscore the need for further research to establish long-term recommendations. Future interventional studies should be designed with rigorous randomization, larger sample sizes, cross-over methodologies, and comprehensive dietary assessments to address the methodological limitations of previous research. Full article

Background: Autism spectrum disorder (ASD) is associated with social-communication challenges that can hinder timely diagnosis and treatment during acute medical events (AMEs). The purpose of this report is to review the literature on medical comorbidities and AMEs in adults with profound ASD and highlight how healthcare teams can better understand atypical presentations of acute pain and discomfort in adults with profound ASD to reduce delayed diagnoses, delays in treatment, and ultimately improve health outcomes. Methods: The literature on medical comorbidities and AMEs in adults with profound ASD was reviewed using the following databases: PubMed, PsycINFO, and Google Scholar. The histories of three adults with profound ASD who experienced AMEs—specifically, appendicitis, nephrolithiasis, and eosinophilic esophagitis (EoE)—are described. The clinical cases were selected to illustrate the challenges inherent in diagnosing and treating AMEs in adults with profound ASD in the context of the review. Results: In Case 1, a 31-year-old male with autism was diagnosed with perforated appendicitis after his family noticed behavioral changes. In Case 2, a 36-year-old male with autism experienced intermittent pain from nephrolithiasis and communicated his discomfort through irritability and pointing. In Case 3, a 34-year-old male with autism exhibited atypical behavior due to pain from undiagnosed EoE, identified after years of untreated pain and multiple unsuccessful clinical procedures. Conclusions: This review and the illustrative cases demonstrate the significant role that communication barriers play in delayed medical diagnoses for adults with profound ASD during AMEs. Integrating caregiver insights and recognizing atypical pain expressions are essential for improving the accuracy and timeliness of diagnosis and treatment in this population. Full article

Hyperuricemia, defined as elevated serum uric acid (SUA) levels (>6.8 mg/dL), is traditionally linked to gout and nephrolithiasis but is increasingly implicated in insulin resistance (IR) and type 2 diabetes mellitus (T2DM). Epidemiological studies, such as NHANES, suggest hyperuricemia increases the risk of T2DM by 1.6 to 2.5 times. Mechanistically, uric acid promotes IR via oxidative stress, chronic inflammation, endothelial dysfunction, and adipocyte dysregulation. Despite growing evidence, significant gaps remain in understanding these pathways, with existing studies often limited by observational designs and short intervention durations. A bibliographic analysis of studies from 2004–2024 using Web of Science and VOSviewer highlights a growing focus on hyperuricemia’s interplay with inflammation, oxidative stress, and metabolic disorders. However, inconsistencies in therapeutic outcomes and limited exploration of causality underscore the need for further research. We also explored the importance of gender stratification and the limitations of the binary model for the relationship between hyperuricemia and insulin resistance. This review emphasizes the importance of addressing these gaps to optimize hyperuricemia management as a potential strategy for diabetes prevention and metabolic health improvement. Full article

Background/Objectives: Primary hyperparathyroidism (PHPT) has been associated with systemic inflammation and metabolic disturbances. This study aimed to evaluate changes in the Systemic Immune-Inflammation Index (SII) and Prognostic Nutritional Index (PNI) following parathyroidectomy (PTX) in PHPT patients, and to assess their return toward healthy control values. Materials and Methods: This retrospective study was conducted between January 2010 and March 2022. It analyzed the demographic characteristics, clinical findings, and laboratory results of patients diagnosed with and operated for PHPT, with comparisons to healthy controls. Postoperative values were recorded at least six months after surgery. Bone mineral density was classified according to World Health Organization criteria, and nephrolithiasis was assessed with imaging. Results: After applying exclusion criteria, 415 PHPT patients and 410 controls were included. PHPT patients were older (p < 0.001) and had a higher proportion of females (p = 0.016). Compared to controls, they had lower phosphorus, albumin, high-density lipoprotein cholesterol, total cholesterol, hemoglobin, and PNI (p < 0.001 for all), while triglycerides, monocytes, platelets, CRP, and SII were higher (p < 0.05). Postoperatively, albumin, platelets, total cholesterol, and triglycerides increased (p < 0.001), while calcium, white blood cell count, neutrophils, lymphocytes, and CRP decreased (p < 0.05), approaching healthy control values. In age- and sex-matched comparisons (propensity score matching, n = 259 in each group), platelets (p = 0.002) and hemoglobin (p = 0.018) were found to be higher postoperatively. Conclusions: Preoperative SII and PNI levels were significantly altered in PHPT patients compared to healthy controls. Following PTX, both of these markers and other parameters showed significant improvements, reflecting positive changes in systemic inflammation and nutritional status. Full article

Oxidative stress is a key component in the pathogenesis of a broad number of renal disorders, including acute kidney injury, chronic kidney disease, and various types of nephropathies. Moreover, oxidative stress seems to at least partly explain the intricate relationship the kidney has with other pathological entities, for instance with cardiovascular comorbidities. Renal replacement therapies give end-stage renal disease patients a fighting chance; however, even these interventions may carry the risk of enhancing existing oxidative stress. Even if nutritional components are not currently routinely used, many have shown promise in preclinical or even clinical studies and could counter some of the deleterious pathways that oxidative stress sets in place. This narrative review provides an update on how these natural nutrients could be beneficial to renal disease patients, and it also aims to give an incentive to future research in the field. Full article

Background: Systemic arterial hypertension is one of the leading global health concerns, significantly increasing the risk of cardiovascular and kidney diseases, including nephrolithiasis. The treatment, still far from ideal, is constantly undergoing new alternatives. In this context, medicinal plants rich in flavonoids, such as naringenin—a compound found in citrus fruits—have gained attention for their potential diuretic, nephroprotective, and blood pressure-lowering effects. Objectives: This study aimed to evaluate the effects of naringenin (100 mg/kg, orally) over nine days on blood pressure, renal function, and calcium oxalate crystal formation in normotensive Wistar (NTR) and spontaneously hypertensive male rats (SHR). Methods: Key assessments included blood pressure and heart rate measurements in vivo, urine volume and electrolyte excretion in vivo, in vitro calcium oxalate crystallization, and in silico molecular docking analyses to investigate molecular interactions. Results: Naringenin treatment significantly reduced blood pressure and increased diuresis in both NTR and SHR groups, while a notable natriuretic effect was observed specifically in NTR. In vitro, naringenin reduced the formation of calcium oxalate crystals in urines from NTR. Molecular docking studies suggested that these effects may be mediated by interactions with SGLT1 and SGLT2 transporters, potentially explaining the diuretic and natriuretic outcomes. Additionally, interactions with MMP-9 and β2-adrenergic receptors may contribute to the reduction in crystal formation. Conclusions: Collectively, these findings indicate that repeated administration of naringenin exerts beneficial effects on both cardiovascular and renal parameters, and point to promising molecular targets that may underlie its protective actions. Full article

Managing nephrolithiasis in chronic kidney disease (CKD) poses a therapeutic challenge: preventing stone recurrence while preserving kidney function. Standard urological interventions and preventive strategies, such as high fluid intake, thiazides, and potassium citrate, cut recurrence by 50–60% in healthy kidneys but risk fluid overload, hyperkalemia, and diminished efficacy in CKD as glomerular filtration rate (GFR) declines. Often, stone prevention and CKD care are addressed separately, leaving clinicians without unified guidance for this rising patient group. This review explores the bidirectional relationship between nephrolithiasis and CKD, integrating pathophysiology and therapeutic strategies into a practical, decision-oriented framework. It offers tailored interventions based on GFR category, stone type, and comorbid conditions, emphasizing the potential for dual-purpose therapies. Going beyond previous reviews, it connects clinical practice with existing research gaps, offering tools to balance outcomes and guide future studies. Full article

Background: Revisional bariatric surgery for recurrent weight gain is becoming more common, though it carries higher risks and may be less effective than primary bariatric surgery. This study compares clinical outcomes between primary and revisional duodenal switch (DS) in patients with a body mass index (BMI) > 55 kg/m². Methods: A retrospective cohort study was conducted on 20 patients who underwent either primary or revisional duodenal switch (DS) surgeries, including biliopancreatic diversion with duodenal switch (BPDDS) and Single-Anastomosis Duodeno-Ileal Bypass with Sleeve Gastrectomy (SADI-s), between January 2015 and December 2023. Revisional DS was defined as the conversion from Sleeve Gastrectomy (SG) to either BPDDS (C-BPDDS) or SADI-S (C-SADI-S). Perioperative and postoperative variables were analyzed. A statistical analysis was performed using chi-square and McNemar tests for categorical variables and Student’s t-test for continuous variables. A p-value of <0.05 was considered significant. Results: Eleven primary DS patients (six BPDDS, five SADI-s) and nine revisional DS patients (five C-BPDDS, four C-SADI-s) were included. The revisional group had a slightly higher preoperative BMI (57.56 ± 5.92 kg/m² vs. 55.93 kg/m² ± 6.91 kg/m²). Although operative times were shorter in the revisional group (153.20 ± 53.26 vs. 193.27 ± 46.79 min), the length of stay was longer (2.70 ± 1.25 vs. 2.18 ± 1.16 days). Primary DS patients experienced three minor late complications (dehydration, nephrolithiasis), whereas the revisional group had one major complication (internal hernia requiring reoperation). At the 12-month follow-up, both groups demonstrated similar outcomes in terms of percentage of total weight loss (%TWL) (primary DS: 25.25% ± 12.38 vs. revisional DS: 30.31% ± 10.79) and percentage of excess weight loss (%EWL) (primary DS: 48.41% ± 22.93 vs. revisional DS: 53.24% ± 14.48). Conclusions: Revisional DS was associated with shorter operation times and similar weight loss to primary DS. Additionally, it was accomplished safely and led to adequate and sustained weight loss in patients with a BMI greater than 55 kg/m². Full article

The clinicopathological and molecular features of synchronous parathyroid carcinoma (PC) and thyroid carcinoma in a male patient are presented. At 11, he received mantle field radiotherapy for Hodgkin lymphoma. He had a 26-year adulthood history of recurrent nephrolithiasis treated five times with lithotripsy. At 52, he was referred to our clinic for hypercalcemia. Primary hyperparathyroidism was diagnosed (calcium: 3.46 mmol/L, parathormone: 150 pmol/L, preserved renal function, nephrolithiasis, and osteoporosis). Neck ultrasound revealed a 41 × 31 × 37 mm nodule in the left thyroid and smaller nodules in the right thyroid. Enlarged cervical lymph nodes were not observed. The large nodule was interpreted as parathyroid adenoma on 99Tc-pertechnetate scintigraphy/99Tc-MIBI scintigraphy with SPECT/CT. Total left-sided and subtotal right-sided thyroidectomy were performed. Histopathology confirmed locally invasive, low-grade PC (pT2; positive for parafibromin and E-cadherin, negative for galectin-3 and PGP9.5; wild-type expression for p53 and retinoblastoma protein; Ki-67 index 10%) and incidental papillary thyroid carcinoma (pT1b). Genetic profiling revealed no loss in CDC73, MEN1, CCND1, PIK3CA, CDH1, RB1, and TP53 genes. Deletions in CDKN2A, LATS1, ARID1A, ARID1B, RAD54L, and MUTYH genes and monosomies in nine chromosomes were identified. The tumor mutational burden and genomic instability score were low, and the tumor was microsatellite-stable. The thyroid carcinoma exhibited a TRIM24::BRAF fusion. Following surgery, the parathormone and calcium levels had normalized, and the patient underwent radioiodine treatment for thyroid cancer. The follow-up of 14 months was eventless. In summary, the clinical, laboratory, and imaging features of hyperparathyroidism taken together could have suggested malignancy, then confirmed histologically. The synchronous carcinomas were most likely caused by irradiation treatment diagnosed 41 years after exposure. It seems that the radiation injury initially induced parathyroid adenoma in young adulthood, which underwent a malignant transformation around age fifty. Full article

Suboptimal vitamin D status is commonly observed in primary hyperparathyroidism but is rarely considered in management decisions. The present study aimed to bring additional insights on vitamin D status in primary hyperparathyroidism patients, particularly those presenting with the normocalcemic phenotype. A retrospective study was conducted on 53 confirmed primary hyperparathyroidism patients, stratified into hypercalcemic and normocalcemic groups, hospitalized at the “Pius Brînzeu” Emergency Clinical Country Hospital in Timișoara, Romania. Patients presenting with the normocalcemic phenotype had similar target-organ involvement compared to their counterparts. In this subgroup, 25 hydroxyvitamin D showed an inverse correlation with serum calcium (p = 0.048), and regression analysis identified iPTH and 25OH vitamin D as significant predictors of calcium levels (p < 0.0001; $R^2$ = 0.571). Adenoma volume showed a significant negative correlation with 25OH vitamin D levels (p = 0.021; r = −0.61) but was later found as insignificant after confounder analysis. Postoperative measurements of 25OH vitamin D levels confirmed increasing levels after parathyroidectomy. Our findings highlight a complex relationship between PTH and vitamin D in primary hyperparathyroidism, especially in the often-underdiagnosed normocalcemic phenotype. The inverse correlation between vitamin D and calcium suggests altered homeostasis, rather than true deficiency. Full article

Extracorporeal shock wave lithotripsy (ESWL), although a highly effective method for the treatment of kidney stones, can cause significant kidney damage. Since urinary protein composition directly reflects kidney function, proteomic analysis of this fluid may be useful to identify changes in protein levels induced by patient exposure to ESWL as a sign of kidney damage. To this end, we collected urine samples from 80 patients with nephrolithiasis 2 h before and 24 h after exposure to ESWL, which were concentrated and subsequently processed with a commercially available enrichment method to extract low-abundance urinary proteins. These were then separated by 2D electrophoresis and subsequently analyzed by a proteomic approach. A large number of proteins were identified as being related to inflammatory, fibrotic, and antioxidant processes and changes in the levels of some of them were confirmed by Western blot analysis. Therefore, although further experimental confirmation is needed, our results demonstrate that ESWL significantly influences the low urinary protein profile of patients with nephrolithiasis. Notably, among the identified proteins, matrix metalloproteinase 7, alpha1-antitrypsin, and clusterin, as well as dimethyl arginine dimethyl amino hydrolase 2 and ab-hydrolase, may play an important role as putative biomarkers in the monitoring and management of ESWL-induced renal damage. Full article

Background: Molecular analysis in patients with nephrolithiasis (NL) and/or nephrocalcinosis (NC) enables more accurate evaluation of underlying etiologies. The existing clinical evidence regarding genetic testing in adults with NL comprises only a few cohort studies. Materials and Methods: We retrospectively analyzed 49 adult patients diagnosed with NL and/or NC from a single center, on whom we performed a genetic test using a nephrolithiasis panel. We reviewed the phenotype of the patients and compared the cases with positive and negative molecular diagnosis. Results: In total, 49 adult patients with NL and/or NC underwent genetic testing. Of the tested patients, 29 (59.2%) patients had 24 abnormal variants in 14 genes. Mendelian diseases were diagnosed in 14 (28.6%) cases: cystinuria (SLC3A1, SLC7A9; n = 4), hereditary distal renal tubular acidosis (SLC4A1; n = 3), Dent disease (CLCN5; n = 2), familial hypomagnesaemia with hypercalciuria and nephrocalcinosis (CLDN16; n = 1), infantile hypercalcemia type 1 (CYP24A1; n = 1), primary hyperoxaluria type 1 (AGXT; n = 1), Bartter syndrome type 2 (KCNJ1; n = 1), and autosomal dominant tubulointerstitial kidney disease (UMOD; n = 1). Eight (16.3%) patients had pathogenic or likely pathogenic monoallelic variants as predisposing factors for NL and/or NC, and seven (14.3%) had biallelic or monoallelic variants of uncertain significance. Patients with positive genetic tests had a lower estimated glomerular filtration rate (p = 0.03) and more frequent NL associated with NC (p = 0.007) and were unlikely to have arterial hypertension (p = 0.03) when compared with patients with negative tests. Conclusions: Our study shows an increased effectiveness of molecular diagnosis and highlights the benefits of genetic testing. NL associated with NC and the presence of chronic kidney disease are the characteristics that should prompt the clinician to suspect an inherited form of NL and/or NC. Full article