Percutaneous Nephrolithotomy Under X-Ray-Free Technique in Upper Urinary Stone Patients with Autosomal Dominant Polycystic Kidney Disease: Experience from a Large-Volume Stone Management Center.

Objectives: To present our large single-center experience in the management of autosomal dominant polycystic kidney disease (ADPKD) with total ultrasound (US)-guided percutaneous nephrolithotomy (PNL) and to evaluate the role of PNL under US in these patients. Patients and Methods: We retrospectively reviewed the charts of patients with ADPKD who underwent PNL from August 2011 to December 2019. A total of 56 patients were included in this study; all procedures were completed by the total US-guided technique. Demographic characteristics, operative parameters, and postoperative data were collected and analyzed. Results: Effective renal access was achieved in all patients. The mean stone size was 3.1 cm (range 1.7-6.5 cm). The initial stone-free rate was 70.6% (36/51); five patients underwent second-look PNL to remove residual stones. The other patients underwent oral medication therapy. No severe intraoperative complications occurred; one patient received selective embolization for bleeding on the contralateral side and one patient needed percutaneous drainage for perinephric abscess. Clavien I or II complications were seen in nine patients. Renal function was improved or stable in most patients; the condition of only one patient deteriorated after surgery. Conclusion: Total US-guided PNL is a safe and efficient treatment for kidney stones in patients with ADPKD; perioperative renal function was not adversely affected and complications were acceptable compared with patients in the general population.

Let-7d inhibits intratumoral macrophage M2 polarization and subsequent tumor angiogenesis by targeting IL-13 and IL-10.

The microRNA let-7d has been reported to be a tumor suppressor in renal cell carcinoma (RCC). Tumor-associated macrophages (TAM) are M2-polarized macrophages that can enhance tumor growth and angiogenesis in many human cancers. However, the role of let-7d in TAM-associated RCC progression remains elusive. First, we observed a strongly inverse correlation between let-7d expression and microvessel density in RCC tissues. Furthermore, the proliferation, migration, and tube formation of HUVECs were significantly inhibited by conditioned medium from a coculture system of the phorbol myristate acetate pretreated human THP-1 macrophages and let-7d-overexpressing RCC cells. Moreover, the proportion of M2 macrophages was significantly lower in the group that was cocultured with let-7d-overexpressing RCC cells. Subcutaneous xenografts formed by the injection of let-7d-overexpressing RCC cells together with THP-1 cells resulted in a significant decrease in the M2 macrophage ratio and microvessel density compared with those formed by the injection of control RCC cells with THP-1 cells. In silico and experimental analysis revealed interleukin-10 (IL-10) and IL-13 as let-7d target genes. Importantly, the addition of IL-10 and IL-13 counteracted the inhibitory effects of the conditioned medium from the coculture system with let-7d-overexpressing RCC cells in vitro. Additionally, overexpression of IL-10 and IL-13 reversed the effects of let-7d on macrophage M2 polarization and tumor angiogenesis in vivo. Finally, the expression of IL-10 and IL-13 were inversely correlated with the expression of let-7d in RCC clinical specimens. These results suggest that let-7d may inhibit intratumoral macrophage M2 polarization and subsequent tumor angiogenesis by targeting IL-10 and IL-13.

MiR-21 promotes calcium oxalate-induced renal tubular cell injury by targeting PPARA.

Kidney stone disease is a crystal concretion formed in the kidneys that has been associated with an increased risk of chronic kidney disease. MicroRNAs are functionally involved in kidney injury. Data mining using a microRNA array database suggested that miR-21 may be associated with calcium oxalate monohydrate (COM)-induced renal tubular cell injury. Here, we confirmed that COM exposure significantly upregulated miR-21 expression, inhibited proliferation, promoted apoptosis, and caused lipid accumulation in an immortalized renal tubular cell line (HK-2). Moreover, inhibition of miR-21 enhanced proliferation and decreased apoptosis and lipid accumulation in HK-2 cells upon COM exposure. In a glyoxylate-induced mouse model of renal calcium oxalate deposition, increased miR-21 expression, lipid accumulation, and kidney injury were also observed. In silico analysis and subsequent experimental validation confirmed the peroxisome proliferator-activated receptor (PPAR)-α gene (PPARA) a key gene in fatty acid oxidation, as a direct miR-21 target. Suppression of miR-21 by miRNA antagomiR or activation of PPAR-α by its selective agonist fenofibrate significantly reduced renal lipid accumulation and protected against renal injury in vivo. In addition, miR-21 was significantly increased in urine samples from patients with calcium oxalate renal stones compared with healthy volunteers. In situ hybridization of biopsy samples from patients with nephrocalcinosis revealed that miR-21 was also significantly upregulated compared with normal kidney tissues from patients with renal cell carcinoma who underwent radical nephrectomy. These results suggested that miR-21 promoted calcium oxalate-induced renal tubular cell injury by targeting PPARA, indicating that miR-21 could be a potential therapeutic target and biomarker for nephrolithiasis.

Analysis of Factors Influencing Mayo Adhesive Probability Score in Partial Nephrectomy.

BACKGROUND To retrospectively explore the factors influencing Mayo Adhesive Probability (MAP) score in the setting of partial nephrectomy. MATERIAL AND METHODS Data of 93 consecutive patients who underwent laparoscopic and open partial nephrectomy from September 2015 to June 2016 were collected and analyzed retrospectively. Preoperative radiological elements were independently assessed by 2 readers. Ordinal logistic regression analyses were performed to evaluate radiological and clinicopathologic influencing factors of MAP score. RESULTS On univariate analysis, MAP score was associated with male sex, older age, higher body mass index (BMI), history of hypertension and diabetes mellitus, and perirenal fat thickness (posterolateral, lateral, anterior, anterolateral, and medial). On multivariate analysis, only posterolateral perirenal fat thickness (odds ratio [OR]=0.88 [0.82-0.95], p=0.001), medial perirenal fat thickness (OR=0.90 [0.83-0.98], p=0.01), and history of diabetes mellitus (OR=5.42 [1.74-16.86], p=0.004) remained statistically significant. Tumor type (malignant vs. benign) was not statistically different. In patients with renal cell carcinoma (RCC), there was no difference in tumor stage or grade. CONCLUSIONS MAP score is significantly correlated with some preoperative factors such as posterolateral and medial perirenal fat thickness and diabetes mellitus. A new radioclinical scoring system including these patient-specific factors may become a better predictive tool than MAP score alone.

Taurine drinking attenuates the burden of intestinal adult worms and muscle larvae in mice with Trichinella spiralis infection.

The parasitic nematode Trichinella spiralis can cause trichinellosis, which leads to pathological processes in the intestine and muscle. The intestinal invasion determines the development, subsequent course, and consequences of the disease. Gastrointestinal nematode infection, including with T. spiralis, is accompanied by a rapid and reversible expansion of mucosal mast cell and goblet cell in the intestinal epithelium, which play important roles in the host immune response to parasite and worm expulsion from the intestine. Taurine and its derivatives have anti-infection and anti-inflammatory properties. We investigated whether taurine supplementation in mice could influence the development and pathological processes of infection with T. spiralis. Supplementing 1% taurine in drinking water in mice infected with T. spiralis could alleviate the burden of intestinal adult worms on days 7 and 10 postinfection (all p < 0.01) and the formation of infective muscle larvae in striated muscle during T. spiralis infection (p < 0.01). As compared with T. spiralis infection alone, taurine treatment increased the number of goblet cells on days 7, 10, and 15 (p < 0.01 and p < 0.05) and alleviated intestinal mucosal mast cell hyperplasia on days 10 and 15 (all p < 0.01). So taurine supplementation in drinking water increased infection-induced intestinal goblet cell hyperplasia and ameliorated mucosal mastocytosis. Thus, taurine can ameliorate the pathological processes of trichinellosis and may be of great value for the treatment and prevention of infection with T. spiralis and other gastrointestinal nematodes.