To update a previously published systematic review and meta-analysis on the efficacy and safety of tubeless percutaneous nephrolithotomy (PCNL). A systematic literature search of EMBASE, PubMed, Web of Science, and the Cochrane Library was performed to confirm relevant studies. The scientific literature was screened in accordance with the predetermined inclusion and exclusion criteria. After quality assessment and data extraction from the eligible studies, a meta-analysis was conducted using Stata SE 12.0. Fourteen randomized controlled trials (RCTs) involving 1148 patients were included. Combined results demonstrated that tubeless PCNL was significantly associated with shorter operative time (weighted mean difference [WMD], −3.79 min; 95% confidence interval [CI], −6.73 to −0.85; P = 0.012; I2 = 53.8%), shorter hospital stay (WMD, −1.27 days; 95% CI, −1.65 to −0.90; P < 0.001; I2 = 98.7%), faster time to return to normal activity (WMD, −4.24 days; 95% CI, −5.76 to −2.71; P < 0.001; I2 = 97.5%), lower postoperative pain scores (WMD, −16.55 mm; 95% CI, −21.60 to −11.50; P < 0.001; I2 = 95.7%), less postoperative analgesia requirements (standard mean difference, −1.09 mg; 95% CI, −1.35 to −0.84; P < 0.001; I2 = 46.8%), and lower urine leakage (Relative risk [RR], 0.30; 95% CI 0.15 to 0.59; P = 0.001; I2 = 41.2%). There were no significant differences in postoperative hemoglobin reduction (WMD, −0.02 g/dL; 95% CI, −0.04 to 0.01; P = 0.172; I2 = 41.5%), stone-free rate (RR, 1.01; 95% CI, 0.97 to 1.05; P = 0.776; I2 = 0.0%), postoperative fever rate (RR, 1.05; 95% CI, 0.57 to 1.93; P = 0.867; I2 = 0.0%), or blood transfusion rate (RR, 0.79; 95% CI, 0.36 to 1.70; P = 0.538; I2 = 0.0%). The results of subgroup analysis were consistent with the overall findings. The sensitivity analysis indicated that most results remained constant when total tubeless or partial tubeless or mini-PCNL studies were excluded respectively. Tubeless PCNL is an available and safe option in carefully evaluated and selected patients. It is significantly associated with the advantages of shorter hospital stay, shorter time to return to normal activity, lower postoperative pain scores, less analgesia requirement, and reduced urine leakage.

Hyperoxaluria induces oxidative stress, and inflammation causes renal epithelial cell injury in nephrolithiasis, suggesting that reduced oxalate toxicity may be beneficial. This study aimed to investigate whether nuclear factor (erythroid-derived 2)-like 2 (Nrf2, also called Nfe2l2) induced by dimethyl fumarate (DMF) could protect renal epithelial cells against oxalate-mediated injury both in vivo and in vitro. Glyoxylic acid monohydrate was intraperitoneally injected into Sprague-Dawley rats with or without intragastric administration of DMF. We showed that calcium oxalate crystallisation, accompanied by overexpression of oxidant species and inflammatory cytokines and apoptosis in the rat kidney, was partially reversed by treatment with DMF. Furthermore, oxalate induced a reduction in cell viability, cell damage, oxidant species overexpression, mitochondrial dysfunction, and apoptosis in normal rat kidney epithelial-like (NRK-52E) cells, which were reversed by DMF. Pretreatment of NRK-52E cells with DMF significantly increased Nrf2 levels in the nucleus, with subsequent inhibition of the expression of the nicotinamide adenine dinucleotide phosphate subunits Nox4 and P22, canonical inflammation, and osteogenesis-associated differentiation of target genes in the cytoplasm. This effect was partially inhibited by transfection with Nrf2 siRNA and strengthened by transfection with Kelch-like ECH-associated protein 1 siRNA. These results suggest that DMF exerts beneficial effects in nephrolithiasis by inhibiting inflammation and modulating oxidative stress via regulation of Nrf2.

Many studies compared the serum/plasma 1,25 dihydroxyvitamin D₃ (1,25(OH)₂D) and 25 hydroxyvitamin D₃ (25(OH)D) between people with and without nephrolithiasis, and their results were conflicting. After systematically searching PubMed, Web of Science, The Cochrane Library, CNKI, and the Wanfang Database, we conducted a meta-analysis. Thirty-two observational studies involving 23,228 participants were included. Meta-analysis of these studies showed that of stone formers (SFs), calcium SFs had significantly higher concentrations of 1,25(OH)₂D (weighted mean difference (WMD), 10.19 pg/mL; 95% confidence interval (CI), 4.31–16.07; p = 0.0007 and WMD, 11.28 pg/mL; 95% CI, 4.07–18.50; p = 0.002, respectively) than non-stone formers, while the levels of 25(OH)D (WMD, 0.88 ng/mL; 95% CI, −1.04–2.80; p = 0.37 and WMD, −0.63 ng/mL; 95% CI, −2.72–1.47; p = 0.56, respectively) are similar. Compared with controls and normocalciuria SFs, hypercalciuria SFs had increased circulating 1,25(OH)₂D (WMD, 9.41 pg/mL; 95% CI, 0.15–18.67; p = 0.05 and WMD, 2.75 pg/mL; 95% CI, −0.20–5.69; p = 0.07, respectively) and markedly higher 25(OH)D (WMD, 5.02 ng/mL; 95% CI, 0.99–9.06; p = 0.01 and WMD, 5.02 ng/mL; 95% CI, 2.14–7.90; p = 0.0006, respectively). Normocalciuria SFs had elevated 1,25(OH)₂D level (WMD, 6.85 pg/mL; 95% CI, −5.00–18.71; p = 0.26) and comparable 25(OH)D (WMD, 0.94 ng/mL; 95% CI, −3.55–5.43; p = 0.68). Sensitivity analysis generated similar results. Current evidence suggests that increased circulating 1,25(OH)₂D is associated with urinary stones and a higher level of circulating 25(OH)D is significantly associated with hypercalciuria urolithiasis. Further studies are still needed to reconfirm and clarify the role of vitamin D in the pathogenesis of stones.

As one of the major risks for urolithiasis, hyperoxaluria can be caused by genetic defect or dietary intake. And high oxalate induced renal epithelial cells injury is related to oxidative stress and mitochondrial dysfunction. Here, we investigated whether MitoTEMPO, a mitochondria‐targeted antioxidant, could protect against oxalate mediated injury in NRK‐52E cells via inhibiting mitochondrial dysfunction and modulating oxidative stress. MitoSOX Red was used to determine mitochondrial ROS (mtROS) production. Mitochondrial membrane potential (Δψm) and quantification of ATP synthesis were measured to evaluate mitochondrial function. The protein expression of Nox4, Nox2, and p22 was also detected to explore the effect of oxalate and MitoTEMPO on NADPH oxidase. Our results revealed that pretreatment with MitoTEMPO significantly inhibited oxalate induced lactate dehydrogenase (LDH) and malondialdehyde (MDA) release and decreased oxalate induced mtROS generation. Further, MitoTEMPO pretreatment restored disruption of Δψm and decreased ATP synthesis mediated by oxalate. In addition, MitoTEMPO altered the protein expression of Nox4 and p22 and decreased the protein expression of IL‐6 and osteopontin (OPN) induced by oxalate. We concluded that MitoTEMPO may be a new candidate to protect against oxalate induced kidney injury as well as urolithiasis.

Calcium oxalate (CaOx) is the most common type of urinary stone. Increase of ROS and NADPH oxidase gives rise to inflammation and injury of renal tubular cells, which promotes CaOx stone formation. Recent studies have revealed that the renin‐angiotensin system might play a role in kidney crystallization and ROS production. Here, we investigated the involvement of Ang II/AT1R and losartan in CaOx stone formation. NRK‐52E cells were incubated with CaOx crystals, and glyoxylic acid‐induced hyperoxaluric rats were treated with losartan. Oxidative stress statuses were evaluated by detection of ROS, oxidative products (8‐OHdG and MDA), and antioxidant enzymes (SOD and CAT). Expression of NADPH oxidase subunits (Nox2 and Nox4), NF‐κB pathway subunits (p50 and p65), and stone‐related proteins such as OPN, CD44, and MCP‐1 was determined by Western blotting. The results revealed upregulation of Ang II/AT1R by CaOx treatment. CaOx‐induced ROS and stone‐related protein upregulation were mediated by the Ang II/AT1R signaling pathway. Losartan ameliorated renal tubular cell expression of stone‐related proteins and renal crystallization by inhibiting NADPH oxidase and oxidative stress. We conclude that losartan might be a promising preventive and therapeutic candidate for hyperoxaluria nephrolithiasis.

Intravesical instillation therapy is the mainstay of prophylaxis of tumor recurrence and progression in non‐muscle‐invasive bladder cancer. However, there is no study evaluating the superiority of monotherapy. The aim of this study is to compare the efficacy of preventing recurrence and progression of intravesical monotherapies via network meta‐analysis (NMA) of randomized controlled trials. Database searches were conducted on Embase, Ovid Medline, Web of Science, ScienceDirect, Cochrane Library, and ClinicalTrials.com from the time of establishment to February 6, 2020. The monotherapies included Bacille Calmette‐Guérin (BCG), mitomycin C (MMC), interferon (IFN), adriamycin, epirubicin, gemcitabine (GEM), and thiotepa (THP). A Bayesian consistency network model was generated under a random‐effects model. The superiority of therapy was identified based on the surface under the cumulative ranking curve (SUCRA). Fifty‐seven studies with 12462 patients are included. NMA shows that GEM (SUCRA = 0.92), BCG (SUCRA = 0.82), and IFN (SUCRA = 0.78) are the top three effective drugs to reduce recurrence. GEM (SUCRA = 0.87) is the most effective therapy to prevent progress, followed by BCG, MMC, THP, and IFN with similar efficacy. Subgroup analysis of pairwise meta‐analysis and NMA was performed on publication year, trial initiation year, study origin, center involvement, sample size, drug schedule, tumor characteristics, and trial quality to address confounding factors, which suggests the robustness of the results with stable effect sizes. Network meta‐regression also indicates consistent rank by analyzing year, sample size, and quality. Compared with BCG, GEM is also a promising therapy with favorable efficacy to reduce tumor recurrence and progression. IFN and MMC could be alternative therapies for BCG with slightly inferior efficacy in recurrence prevention and similar efficacy in progression prevention. However, the results of this study should be treated with caution since most of the included studies are of moderate to high risk of bias.