PD-1 blockade: promoting endogenous anti-tumor immunity

The co-inhibitory receptor programmed death-1 acts to dampen immune responses in peripheral tissues via interaction with its widely distributed ligand(s). The latter function as a final ‘shield’ to protect tissues from immunological attack by T cells and help to maintain peripheral tolerance and prevent autoimmunity. Upregulation in a variety of cancers is thought to be one mechanism by which they evade immunological eradication. The study by Topalian and colleagues evaluating the role of blockade of this pathway with a monoclonal antibody in patients with advanced cancer is reviewed. This large Phase I study demonstrates encouraging response rates in patients with melanoma, renal cell carcinoma and non-small-cell lung cancer. Although the spectrum of toxicity was similar to that seen with blockade of cytotoxic T-lymphocyte antigen 4, the severity appeared lower in most cases. After a long wait, it finally seems that immune-based anticancer therapies are emerging to become part of the mainstream.     

Ferric citrate spans mineral metabolism and anemia domains in ESRD: a review of efficacy and safety data

Ferric citrate (Zerenex?, Keryx Biopharmaceuticals, Inc.), a phosphate binder drug candidate, recently completed a Phase III program confirming efficacy and demonstrating safety when used to treat hyperphosphatemia in patients with end-stage renal disease. Results of these trials demonstrate that ferric citrate effectively controls serum phosphorus and is well tolerated. Additionally, these studies demonstrate that ferric citrate improves iron parameters and reduces IV iron and erythropoietin stimulating agent utilization while maintaining hemoglobin levels. These unique features may further benefit the management of end-stage renal disease-related anemia.     

Ask-Upmark Kidney and Tubulointerstitial Nephritis in a Woman with Severe Renal Failure

Abstract

Ask-Upmark kidney is a rare diagnosis of segmental hypoplasia in pediatric population clinically characterized by severe hypertension potentially treatable with partial to total nephrectomy. Although originally was described only as a congenital anomaly, recent data suggest to be caused by vesicoureteral reflux, either in utero or in early childhood and pyelonephritis. The case we reported indicates that Ask-Upmark kidney should be considered as potential cause of hypertension and renal failure both in children and adults. The renal biopsy is necessary for early diagnosis and may consent to normalize blood pressure with nephrectomy; however, if renal damage is severe and progressive with tubulointerstitial nephritis, surgical management is excluded and renal transplant should be considered.     

Characterization of clear cell renal cell carcinoma with diffusion kurtosis imaging: correlation between diffusion kurtosis parameters and tumor cellularity

The aim of this study was to evaluate the role of diffusion kurtosis imaging (DKI) in the characterization of clear cell renal cell carcinoma (ccRCC) and to correlate DKI parameters with tumor cellularity. Fifty‐nine patients with pathologically diagnosed ccRCCs were evaluated by DKI on a 3‐T scanner. Regions of interest were drawn on the maps of the mean diffusion coefficient (MD) and mean diffusion kurtosis (MK). All ccRCCs were histologically graded according to the Fuhrman classification system. Tumor cellularity was measured by the nuclear‐to‐cytoplasm (N/C) ratio and the number of tumor cell nuclei (NTCN). ccRCCs were classified as grade 1 (n = 23), grade 2 (n = 24), grade 3 (n = 10) and grade 4 (n = 3). Both MD and MK could readily discriminate between normal renal parenchyma and ccRCCs (p < 0.001), and receiver operating characteristic (ROC) curve analysis showed that MK exhibited a better performance with an area under the ROC curve of 0.874 and sensitivity/specificity of 68.33%/100% (p < 0.001). Further, MD and MK were significantly different between grade 1 and grades 3 and 4 (p = 0.01, p < 0.001) and between grade 2 and grades 3 and 4 (p = 0.015, p < 0.005), respectively. However, no significant difference was found between grade 1 and grade 2 (p > 0.05) for both MD and MK. With regard to NTCN, no significant difference was found between any two grades (p > 0.05), and the N/C ratio changed significantly with grade (p < 0.01, between any two grades). Negative correlations were found between MK and MD (r = –0.56, p < 0.001), and between MD and N/C ratio (r = –0.36, p < 0.005), whereas MK and the N/C ratio were positively correlated (r = 0.45, p = 0.003). DKI could quantitatively characterize ccRCC with different grades by probing non‐Gaussian diffusion properties related to changes in the tumor microenvironment or tissue complexities in the tumor. Copyright © 2016 John Wiley & Sons, Ltd.     

The prevalence of anxiety and depression among end-stage renal disease patients on hemodialysis in Saudi Arabia

Depression commonly overlaps with uremic symptoms, but anxiety is less commonly studied among renal patients. The symptoms of medical illness, along with the psychological and social stresses that often accompany a debilitating chronic disease, are thought to produce deleterious psychological consequences. We sought to determine the prevalence and predictors of anxiety and depression among Saudi dialysis patients in Makkah. A cross-sectional study of anxiety and depression among end-stage renal disease (ESRD) patients in Makkah was conducted in November 2011. The Hospital Anxiety and Depression Scale (HADS) was used to screen for anxiety and depression. Participants’ demographic data, possible stressors and past psychiatric history were obtained. All participants were Saudi ESRD patients on maintenance hemodialysis. According to HADS, 57 (21.1%) patients were probable cases of anxiety and 63 (23.3%) were probable cases of depression. Only 32 (11.3%) were diagnosed with depression or anxiety before ESRD onset. Age was a significant predictor of anxiety and depression diagnoses. Major family problems (p?=?0.001) were also a significant predictor of anxiety. Anxiety and depressive symptoms are prevalent among ESRD patients in Makkah, and anxiety can be predicted by family factors. Early detection, management and family support might improve clinical outcomes.     

MiR-200c-3p inhibits cell migration and invasion of clear cell renal cell carcinoma via regulating SLC6A1

In this study, we investigated the mechanism of miR-200c-3p and SLC6A1 in regulating cell activity of clear cell renal cell carcinoma (CCRCC). The mRNA and miRNA expressions of tissue specimens were analyzed by CapitalBio Corporation (Beijing, China). The expression of SLC6A1 in CCRCC cells was examined through qRT-PCR and western blot. The migration and invasion ability of 786-O cells was testified by transwell assay after transfected. 786-O cell proliferation ability was detected by MTT assay. Dual luciferase reporter assay verified the association between SLC6A1 and miR-200c-3p. SLC6A1 was high expressed and miR-200c-3p was low expressed in CCRCC tissues and cells. Besides, lower SLC6A1 expression indicated longer survival time and higher survival rate. MiR-200c-3p could directly target at SLC6A1 and reduce its expression. MiR-200c-3p inhibited the proliferation, migration and invasion in 786-O cells by down-regulating SLC6A1 expression. The results suggested that the miR-200c-3p served as a suppressor for CCRCC via down-regulating SLC6A1.     

骨化三醇治疗慢性肾功能不全患者肾性骨病的效果观察

目的研究慢性肾功能不全患者肾性骨病应用骨化三醇治疗的临床疗效,并分析其安全性。方法选择2014年7月~2016年11月期间所收治的68例肾性骨病患者作为本次研究病例,对患者进行分组治疗,采用随机数字表法进行分组,对照组和研究组各34例,对照组患者应用常规治疗方法,研究组在此基础上加用骨化三醇治疗,对比分析两组患者的临床各项指标,并分析其不良反应发生情况。结果治疗前,两组临床指标无明显统计学意义(P0.05),经治疗后,研究组患者的血清钙水平为(2.31±0.15)mmol/L,血清无机磷水平为(1.89±0.14)mmol/L,甲状旁腺激素为(202.01±35.87)pg/m L,碱性磷酸酶为(80.46±2.85)U/L,其中血清钙、血清无机磷与甲状旁腺激素水平与对照组比较具有统计学意义(t=4.1607、3.1260、5.7254,P0.05),碱性磷酸酶与治疗前比较无统计学意义(t=1.3055,P0.05);研究组患者不良反应发生率为8.82%(3例),对照组患者不良反应发生率为14.71%(5例),两组患者不良反应比较无统计学意义(χ~2=0.5667,P0.05)。结论慢性肾功能不全患者肾性骨病中应用骨化三醇治疗的效果明显,能够有效改善患者的临床症状,改善钙磷紊乱情况,并且不良反应少,可以在临床中推广使用。