Differential Ly6C Expression after Renal Ischemia-Reperfusion Identifies Unique Macrophage Populations

Macrophages are a heterogeneous cell type implicated in injury, repair, and fibrosis after AKI, but the macrophage population associated with each phase is unclear. In this study, we used a renal bilateral ischemia-reperfusion injury mouse model to identify unique monocyte/macrophage populations by differential expression of Ly6C in CD11b⁺ cells and to define the function of these cells in the pathophysiology of disease on the basis of microarray gene signatures and reduction strategies. Macrophage populations were isolated from kidney homogenates by fluorescence-activated cell sorting for whole genome microarray analysis. The CD11b⁺/Ly6C^high population associated with the onset of renal injury and increase in proinflammatory cytokines, whereas the CD11b⁺/Ly6C^intermediate population peaked during kidney repair. The CD11b⁺/Ly6C^low population emerged with developing renal fibrosis. Principal component and hierarchical cluster analyses identified gene signatures unique to each population. The CD11b⁺/Ly6C^intermediate population had a distinct phenotype of wound healing, confirmed by results of studies inhibiting the macrophage colony-stimulating factor 1 receptor,whereas the CD11b⁺/Ly6C^low population had a profibrotic phenotype. All populations, including the CD11b⁺/Ly6C^high population, carried differential inflammatory signatures. The expression of M2-specific markers was detected in both the CD11b⁺/Ly6C^intermediate and CD11b⁺/Ly6C^low populations, suggesting these in vivo populations do not fit into the traditional classifications defined by in vitro systems. Results of this study in a renal ischemia-reperfusion injury model allow phenotype and function to be assigned to CD11b⁺/Ly6C⁺ monocyte/macrophage populations in the pathophysiology of disease after AKI.     

The PROPKD Score: A New Algorithm to Predict Renal Survival in Autosomal Dominant Polycystic Kidney Disease

The course of autosomal dominant polycystic kidney disease (ADPKD) varies among individuals, with some reaching ESRD before 40 years of age and others never requiring RRT. In this study, we developed a prognostic model to predict renal outcomes in patients with ADPKD on the basis of genetic and clinical data. We conducted a cross-sectional study of 1341 patients from the Genkyst cohort and evaluated the influence of clinical and genetic factors on renal survival. Multivariate survival analysis identified four variables that were significantly associated with age at ESRD onset, and a scoring system from 0 to 9 was developed as follows: being male: 1 point; hypertension before 35 years of age: 2 points; first urologic event before 35 years of age: 2 points; PKD2 mutation: 0 points; nontruncating PKD1 mutation: 2 points; and truncating PKD1 mutation: 4 points. Three risk categories were subsequently defined as low risk (0–3 points), intermediate risk (4–6 points), and high risk (7–9 points) of progression to ESRD, with corresponding median ages for ESRD onset of 70.6, 56.9, and 49 years, respectively. Whereas a score ≤3 eliminates evolution to ESRD before 60 years of age with a negative predictive value of 81.4%, a score >6 forecasts ESRD onset before 60 years of age with a positive predictive value of 90.9%. This new prognostic score accurately predicts renal outcomes in patients with ADPKD and may enable the personalization of therapeutic management of ADPKD.     

Phosphorylation of Ribosomal Protein S6 Mediates Mammalian Target of Rapamycin Complex 1–Induced Parathyroid Cell Proliferation in Secondary Hyperparathyroidism

Secondary hyperparathyroidism is characterized by increased serum parathyroid hormone (PTH) level and parathyroid cell proliferation. However, the molecular pathways mediating the increased parathyroid cell proliferation remain undefined. Here, we found that the mTOR pathway was activated in the parathyroid of rats with secondary hyperparathyroidism induced by either chronic hypocalcemia or uremia, which was measured by increased phosphorylation of ribosomal protein S6 (rpS6), a downstream target of the mTOR pathway. This activation correlated with increased parathyroid cell proliferation. Inhibition of mTOR complex 1 by rapamycin decreased or prevented parathyroid cell proliferation in secondary hyperparathyroidism rats and in vitro in uremic rat parathyroid glands in organ culture. Knockin rpS6^p−/− mice, in which rpS6 cannot be phosphorylated because of substitution of all five phosphorylatable serines with alanines, had impaired PTH secretion after experimental uremia- or folic acid–induced AKI. Uremic rpS6^p−/− mice had no increase in parathyroid cell proliferation compared with a marked increase in uremic wild–type mice. These results underscore the importance of mTOR activation and rpS6 phosphorylation for the pathogenesis of secondary hyperparathyroidism and indicate that mTORC1 is a significant regulator of parathyroid cell proliferation through rpS6.     

Perioperative renal protection

AKI is the term to describe an abrupt reduction in kidney function and it replaces all previous terms such as ARF. The new definition for AKI needs to be validated by future research. Further development of biomarkers of AKI may aid in the early diagnosis and treatment of the syndrome. Mortality due to perioperative AKI often exceeds 50% and small changes in SCr correlate to significant increases in mortality. Preoperative risk factors for the development of AKI include a past history of renal dysfunction, elevated SCr, decreased cardiac performance, and cardiac and vascular surgery. Perioperative renal protection should focus on maintenance of euvolemia, preservation of adequate renal perfusion, and avoidance of any nephrotoxins. Intraoperative fluid management should be titrated to hemodynamic parameters and UO while avoiding excess fluid administration. The ideal fluid to administer is unknown as crystalloids and colloids each have their own advantages and disadvantages. Renal perfusion should be maintained by keeping MAP >65 mmHg and research may identify new techniques to monitor and individualize therapy to maintain renal perfusion. Recent data suggest that fenoldopam may alter outcome in patients with AKI.     

囊性肾癌诊治体会

目的 提高囊性肾癌的诊治水平. 方法 回顾分析10例囊性肾癌患者术前影像学特点、病理特征和治疗方法.男7例,女3例.年龄38～74岁,平均56岁.患侧腰酸3例,体检偶然发现7例,有肾囊肿病史者2例.囊腔直径3.5～8.2 cm.术前B超检查诊断为肾癌6例,CT诊断为肾癌7例.8例术中行冰冻病理:肾细胞癌6例,未发现恶性倾向2例.10例均行根治性肾切除术. 结果 术后病理诊断:肾透明细胞癌9例,颗粒细胞癌1例.病理学分型:肾癌囊性坏死6例,多房囊性肾癌2例,肾囊肿恶变型2例.8例随访6个月～5年,6例无瘤存活,2例分别于术后13、20个月死于肿瘤转移. 结论 重视囊性肾癌独特的影像学特点、病理学特征,术中行冰冻病理检查,是提高囊性肾癌诊治水平的关键.     

Factors Associated with Lymph Node Assessment in Ductal Carcinoma in situ: Analysis of 1988–2002 Seer Data

Background  Ductal carcinoma in situ (DCIS) represents 20–30% of mammographically detected breast cancers, but the role of lymph node assessment (LNA) in women with DCIS remains unclear. Methods  Using the 1988–2002 Surveillance, Epidemiology, and End Results (SEER) Program data, we conducted a case–control study to identify variables associated with (1) LNA in DCIS patients and (2) use of axillary lymph node dissection (ALND) compared with sentinel lymph node biopsy (SLNB). Using separate multivariable logistic regression models, we identified patient and tumor-related factors associated with LNA (1988–2002) and with the method used (recorded only in 1998–2002). We report adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Results  Of 23,502 women with DCIS, 37% underwent mastectomy and 63% underwent breast-conservation therapy (BCT); 6,650 cases (28%) underwent LNA. Women younger than 80 years (aOR 1.47; 95% CI 1.24–1.75) or who had mastectomy (aOR 11.06; 95% CI 10.30–11.90), tumor size greater than 9 mm (aORs ranged from 1.27–1.97 for 10-mm increments from 10 to 50 mm or more) or poorly differentiated grade (aOR 1.33; 95% CI 1.11–1.55) were more likely to have had a LNA. From 1998 to 2002, 10,637 women underwent resection for DCIS (21% mastectomy; 79% BCT); of these, 2,219 (21%) had LNA (73% mastectomy; 27% BCT). Mastectomy patients were 3.52 times more likely to receive ALND (95% CI 2.71–4.57) than SLNB, after controlling for other factors. Conclusion  Optimal guidelines for use of LNA in DCIS have not been defined. However, there appeared to be a persistent and excessive utilization of ALND for LNA in women with DCIS (1998–2002).     

肿瘤-睾丸抗原基因在肾透明细胞癌中的表达

目的 研究6种肿瘤.睾丸抗原(CT)基因在肾透明细胞癌中的表达及其临床意义.方法 采用逆转录-聚合酶链反应(RT-PCR)技术检测42例肾透明细胞癌患者癌组织(新鲜标本,T1期16例,12期12例,T3期10例,T4期4例;G1 10例,G2 18例,G3 14例)及其中14例患者癌旁组织的cTAGE-1、cTAGE-2、MAGE-A1、MAGE-A3、MAGE-A12及NY-ESO-1基因mRNA的表达.结果 42例肾透明细胞癌组织中100%(42/42)至少表达6种CT基因中一种,14例癌旁组织表达均阴性.肾透明细胞癌组织中MAGE-A12表达最高,其次为MAGE-A3,MAGE-A1,cTAGE-1,cTAGE-2及NY-ESO-1,分别为71%(30/42),69%(29/42),67%(28/42),64%(27/42),60%(25/42)及48%(20/42).肿瘤不同分期、不同分级之间6种CT基因表达的差异均无统计学意义(Pearson x2检验法,P＞0.05).结论 CT基因在肾透明细胞癌中有较高表达,可望成为肾透明细胞癌特异性免疫治疗的靶基因.     

术中淋巴染色对早期乳腺癌前哨淋巴结判定作用的研究

目的：探讨术中淋巴染色在早期乳腺癌前哨淋巴结判定中的作用。方法：62例Ⅰ、Ⅱ期乳腺癌，术中向乳腺肿块或其周围组织内注入1％亚甲蓝注射液4ml，术后将腋淋巴结按部位统计每例染色淋巴结的数量、转移度，计算用染色淋巴结判断腋淋巴结转移情况的敏感性、特异性、准确性和漏诊率。结果：62例淋巴染色均而获成功。23例腋淋巴结查见转移癌，其中20例染色淋巴结查见转移癌。判断腋淋巴结有无转移敏感性为87．0％（20／23），特异性为100％（39／39），准确性为93．7％（59／62），漏诊率为13．0％。染色淋巴结的转移度34．8％（39／112），与总体淋巴结及未染色淋巴结的转移度（27．5％、29．7％）差异没有统计学意义。结论：采用亚甲蓝作为术中淋巴染色剂，对早期乳腺癌病人有较高的成功率，应用染色淋巴结作为前哨淋巴结来判断腋淋巴结转移情况有较高的漏诊率，其应用价值尚待进一步大样本的研究评价。     

超声引导经直肠前列腺穿刺活检术(附192例报告)

目的评价经直肠超声(TRUS)结合彩色多谱勒血流图象(CDI)对前列腺穿刺活检的指导作用.方法依据TRUS结合CDI选择穿刺点,采用个体化方案对192例PSA＞4ng/m1、可疑前列腺癌(PCA)的患者,行经直肠前列腺穿刺活检,对其中12例PSA持续升高者行重复穿刺.结果 (1)PSA4～10ng/m170例,PCa9例(12.9%)、其中7例CDI有异常血流;阴性61例、其中9例CDI有异常血流.(2)PSA11～150ng/m1122例,PCa47例(38.5%)、其中37例CDI有异常血流;阴性75例、其中14例CDI有异常血流.CDI在PCa与穿刺阴性间比较有极显著性差异(P＜0.001),重复穿刺者12例中发现PCA5例.结论依据TRUS结合CDI采用个体化方案的前列腺穿刺活检术,能提高PCa检出率和减少并发症.