Acute kidney injury secondary to chlorine dioxide use for COVID-19 prevention

Chlorine dioxide has been historically used as a disinfecting agent for drinking water supplies and surfaces. Widespread use as an alternative option for prevention and treatment of COVID-19 has emerged due to a lack of specific treatment. We present the case of a 55-year-old male who developed acute kidney injury and disseminated intravascular coagulation after chlorine dioxide prophylactic ingestion, with regression after therapy with hemodialysis.     

Comparative anatomy of the podocyte: A scanning electron microscopic study

The three-dimensional structure of the renal glomerular podocyte was comparatively analyzed with special reference to its cellular interdigitation. Kidneys of lampreys, carps, eels, xenopuses, bullfrogs, iguanas, rats, and rabbits were used as materials. Urinary and basal surfaces of podocytes were exposed by a conventional freeze-fracture method and by NaOH maceration, respectively, and subsequently examined by scanning electron microscopy. In accordance with previous reports, each podocyte consisted of a round cell body protruding into Bowman's space, four to six major processes embracing glomerular capillary, and numerous pedicels on both sides of the major processes. The podocyte pedicels exhibited uniform needle-like shapes, about 0.2 microm thick, interdigitated with those of adjoining cells along the entire length of the cell margins in all the animal species examined. This finding suggests that the fine pedicel interdigitation is a primary event in morphogenesis of the podocyte. The basal aspect of the glomerular epithelium was mosaicked with pedicels which were laid at various angles to the capillary axis, in favor of its possible role as a mechanical support of the capillary wall.     

Acute renal failure and chronic kidney disease following liver transplantation

Acute renal failure (ARF) and chronic kidney disease (CKD) are common complications after liver transplantation (LTx). The incidence of ARF post-LTx varies between 48% and 94%; 8% to 17% of patients require renal replacement therapy (RRT). The most common cause of ARF early after LTx is ischemic acute tubular necrosis, followed later by cyclosporine toxicity and sepsis. Preoperative serum creatinine >1.5 mg/dL and early hepatic allograft dysfunction are risk factors for the occurrence of postoperative ARF. Of patients with ARF due to the hepatorenal syndrome, approximately two-thirds will recover, although recovery may be delayed 3 months or longer after LTx. Mortality after LTx is affected modestly by the presence of ARF pretransplant (<2-fold increase), but increases markedly (up to 8-fold) in the face of ARF posttransplant. Mortality does not appear to be influenced by the mode of RRT used. The risk of CKD after LTx is approximately 18% at 5 years and increases to approximately 25% by 10 years after transplantation. Calcineurin inhibitor toxicity is the most common cause. Specific prognosticators for predicting CKD after LTx are presently lacking. The occurrence of CKD after LTx markedly impairs long-term survival.     

肾移植后监测肿瘤坏死因子与环孢素A血药浓度的临床意义

目的 研究肾移植术后患者肿瘤坏死因子(TNF)与全血环孢素A (CsA)浓度的临床意义。方法 采用放射免疫法测定血清和尿 TNF, FPIA 法测定 CsA 全血浓度。结果 急性排斥组患者血、尿 TNF(1.03±0.26 ng/L, 0.44±0.36ng/L)明显高于肾功能稳定组 (0.86±0.21 ng/L, 0.34± 0.29 ng/L), 并且可早于血肌酐升高 1～ 3d。而 CsA 肾中毒组的血 、尿 TNF(0.91±0.22ng/L 、 0.40±0.27ng/L)与肾功能稳定组无明显差别。CsA 血药浓度在急性排斥反应组明显降低, 而 CsA 肾中毒组显著升高。结论 TNF 和 CsA 血药浓度测定有助于鉴别急性排斥反应和CsA 肾中毒, 具有重要的临床意义。     

维生素E对大鼠残肾纤维化的抑制作用

目的 观察维生素E对慢性肾衰残肾组织进行性纤维化的抑制作用。方法 在5/6肾切除大鼠慢性肾衰模型上, 以假手术大鼠为对照, 采用形态计量和生化测定方法, 对比分析术后30、60、90、120 天给予或不给予维生素E 治疗的慢性肾衰大鼠残肾纤维化程度。结果 大鼠行5/6 肾切除术后, 在残存肾小球代偿性肥大、肾小球毛细血管代偿性增生的同时, 肾小球显著硬化, 滤过膜显著增厚, 肾间质显著纤维化, 肾组织羟脯氨酸含量显著增高;而用维生素E 治疗的大鼠, 肾小球硬化、滤过膜增厚、肾间质纤维化和肾组织羟脯氨酸含量增高的程度显著减轻, 肾小球代偿性肥大和肾小球毛细血管代偿性增生的发生时间后移。结论 维生素E 能显著抑制5/6 肾切除所致慢性肾衰残肾组织的纤维化, 对其代偿性肾小球肥大和毛细血管增生无明显直接影响。     

Inflammation and Oxidative Stress in Diabetic Kidney Disease: The Targets for SGLT2 Inhibitors and GLP-1 Receptor Agonists

The incidence of type 2 diabetes (T2D) has been increasing worldwide, and diabetic kidney disease (DKD) remains one of the leading long-term complications of T2D. Several lines of evidence indicate that glucose-lowering agents prevent the onset and progression of DKD in its early stages but are of limited efficacy in later stages of DKD. However, sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor (GLP-1R) agonists were shown to exert nephroprotective effects in patients with established DKD, i.e., those who had a reduced glomerular filtration rate. These effects cannot be solely attributed to the improved metabolic control of diabetes. In our review, we attempted to discuss the interactions of both groups of agents with inflammation and oxidative stress—the key pathways contributing to organ damage in the course of diabetes. SGLT2i and GLP-1R agonists attenuate inflammation and oxidative stress in experimental in vitro and in vivo models of DKD in several ways. In addition, we have described experiments showing the same protective mechanisms as found in DKD in non-diabetic kidney injury models as well as in some tissues and organs other than the kidney. The interaction between both drug groups, inflammation and oxidative stress appears to have a universal mechanism of organ protection in diabetes and other diseases.     

肾脏鳞状细胞癌一例电镜观察

用电镜方法观察了一例已经甲醛固定的肾肿瘤标本,以明确诊断。发现光镜下所见的肿瘤组织内横纹肌肉瘤样细胞,电镜下可见其胞浆内有较多的张力原纤维,未见肌丝,癌细胞间可见成串的桥粒。电镜诊断为（肾脏）鳞状细胞癌。     

Role of DNA-Dependent Protein Kinase in Mediating Cyst Growth in Autosomal Dominant Polycystic Kidney Disease

DNA-dependent protein kinase (DNA-PK) is a serine/threonine protein involved in DNA damage response (DDR) signaling that may mediate kidney cyst growth in autosomal dominant polycystic kidney disease (ADPKD) due to its pleiotropic effects on proliferation and survival. To test this hypothesis, the expression of DNA-PK in human ADPKD and the in vitro effects of DNA-PK inhibition in a three-dimensional model of Madin-Darby Canine Kidney (MDCK) cyst growth and human ADPKD cells were assessed. In human ADPKD, the mRNA expression for all three subunits of the DNA-PK complex was increased, and using immunohistochemistry, the catalytic subunit (DNA-PKcs) was detected in the cyst lining epithelia of human ADPKD, in a focal manner. In vitro, NU7441 (a DNA-PK kinase inhibitor) reduced MDCK cyst growth by up to 52% after long-term treatment over 6–12 days. Although human ADPKD cell lines (WT9-7/WT9-12) did not exhibit synthetic lethality in response to DNA-PK kinase inhibition compared to normal human kidney cells (HK-2), the combination of low-dose NU7441 enhanced the anti-proliferative effects of sirolimus in WT9-7 and WT9-12 cells by 17 ± 10% and 11 ± 7%, respectively. In conclusion, these preliminary data suggest that DNA-PK mediates kidney cyst growth in vivo without a synthetically lethal interaction, conferring cell-specificity in human ADPKD cells. NU7441 enhanced the anti-proliferative effects of rapamycin complex 1 inhibitors, but the effect was modest.     

Understanding the Renal Fibrotic Process in Leptospirosis

Leptospirosis is a neglected infectious disease caused by pathogenic species of the genus Leptospira. The acute disease is well-described, and, although it resembles other tropical diseases, it can be diagnosed through the use of serological and molecular methods. While the chronic renal disease, carrier state, and kidney fibrosis due to Leptospira infection in humans have been the subject of discussion by researchers, the mechanisms involved in these processes are still overlooked, and relatively little is known about the establishment and maintenance of the chronic status underlying this infectious disease. In this review, we highlight recent findings regarding the cellular communication pathways involved in the renal fibrotic process, as well as the relationship between renal fibrosis due to leptospirosis and CKD/CKDu.