Thrombotic microangiopathy (TMA) is a major complication after hematopoietic stem cell transplantation (HSCT). In this study, we examined the clinical and pathologic features of 2 patients and 5 autopsy cases with HSCT-associated renal TMA to clarify the association between graft-versus-host disease (GVHD) and renal TMA. The median interval between HSCT and renal biopsy or autopsy was 7 months (range 3-42 months). Clinically, acute and chronic GVHD occurred in 7 and 4 patients, respectively. Clinical evidence for TMA was detected in 2 patients, while chronic kidney disease developed in all patients. The main histopathological findings were diffuse endothelial injury in glomeruli, peritubular capillaries (PTCs), and small arteries. In addition, all cases showed glomerulitis, renal tubulitis, and peritubular capillaritis with infiltration of CD3+ T cells and TIA-1+ cytotoxic cells, suggesting that GVHD occurred during the development of TMA. Diffuse and patchy C4d deposition was noted in glomerular capillaries and PTCs, respectively, in 2 biopsy and 2 autopsy cases, suggesting the involvement of antibody-mediated renal endothelial injury in more than 50% of renal TMA cases. In conclusion, the kidney is a potential target of chronic GVHD that may induce the development of HSCT-associated TMA. Importantly, some cases are associated with chronic humoral GVHD.

Atrial fibrillation (AF) is one of the major risk factor for ischemic stroke, and oral anticoagulation is generally indicated for prevention of stroke. However, the utility of oral anticoagulation for AF in dialysis patients remains controversial. In this single-center, retrospective, observational study, data from 1120 patients on maintenance hemodialysis were analyzed. Baseline medical data were collected from dialysis records including age, gender, the cause of end-stage renal disease, dialysis vintage, and comorbidities. We evaluated outcomes including stroke, major hemorrhage, and death. A total of 106 (11.4 %) patients had AF. After exclusion criteria were applied, 84 patients had analyzable data. Warfarin was prescribed in 30 (35.7 %) of these patients. The remaining 54 patients were classified as the non-warfarin group. CHADS2 score was not significantly different between the warfarin and non-warfarin group. During the mean 47 months of follow up, 7 strokes occurred. However, warfarin use was not associated with the risk for stroke [hazard ratio (HR) 1.07; 95 % confidence interval (CI) 0.20-5.74]. Kaplan-Meier analysis showed no statistically significant difference in the overall survival, stroke-free survival or bleeding-free survival between the warfarin and non-warfarin group. AF is common in Japanese dialysis patients. Despite a certain prevalence of oral anticoagulation, the present study demonstrated neither beneficial nor detrimental effects. A large randomized controlled trial should be considered.

Allogeneic hematopoietic cell or bone marrow transplantation (BMT) causes graft-versus-host-disease (GVHD). However, the involvement of the kidney in acute GVHD is not well-understood. Acute GVHD was induced in Lewis rats (RT1l) by transplantation of Dark Agouti (DA) rat (RT1a) bone marrow cells (6.0×107 cells) without immunosuppression after lethal irradiation (10 Gy). We examined the impact of acute GVHD on the kidney in allogeneic BMT rats and compared them with those in Lewis-to-Lewis syngeneic BMT control and non-BMT control rats. In syngeneic BMT and non-BMT control rats, acute GVHD did not develop by day 28. In allogeneic BMT rats, severe acute GVHD developed at 21–28 days after BMT in the skin, intestine, and liver with decreased body weight (>20%), skin rush, diarrhea, and liver dysfunction. In the kidney, infiltration of donor-type leukocytes was by day 28. Mild inflammation characterized by infiltration of CD3+ T-cells, including CD8+ T-cells and CD4+ T-cells, and CD68+ macrophages to the interstitium around the small arteries was noted. During moderate to severe inflammation, these infiltrating cells expanded into the peritubular interstitium with peritubular capillaritis, tubulitis, acute glomerulitis, and endarteritis. Renal dysfunction also developed, and the serum blood urea nitrogen (33.9±4.7 mg/dL) and urinary N-acetyl-β-D-glucosaminidase (NAG: 31.5±15.5 U/L) levels increased. No immunoglobulin and complement deposition was detected in the kidney. In conclusion, the kidney was a primary target organ of acute GVHD after BMT. Acute GVHD of the kidney was characterized by increased levels of urinary NAG and cell-mediated injury to the renal microvasculature and renal tubules.

The loss of glomerular capillaries with endothelial cell injury is commonly associated with the formation of necrotizing and cellular crescentic lesions, regardless of the pathogeneses associated with different types of crescentic GN, such as pauci-immune type ANCA-associated GN, anti-GBM GN, and immune-complex type GN. In addition, impaired capillary regeneration and a loss of endothelial cells contribute to the development of glomerular sclerosis with fibrous crescents and glomerular collapse.

Purpose In vitro maturation (IVM) of human oocytes offers an invaluable opportunity for infertility treatment. However, in vitro matured oocytes often show lower developmental abilities than their in vivo counterparts, and molecular mechanisms underlying successful maturation remain unclear. In this study, we investigated gene expression profiles of in vitro matured oocytes at the single‐cell level to gain mechanistic insight into IVM of human oocytes. Methods Human oocytes were retrieved by follicular puncture and in vitro matured. In total, 19 oocytes from 11 patients were collected and subjected to single‐cell RNA‐seq analyses. Results Global gene expression profiles were similar among oocytes at the same maturation stage, while a small number of oocytes showed distinct transcriptomes from those at the corresponding maturation stage. Differential gene expression analysis identified hundreds of transcripts that dynamically altered their expression during IVM, and we revealed molecular pathways and upstream regulators that may govern oocyte maturation. Furthermore, oocytes that were delayed in their maturation showed distinct transcriptomes. Finally, we identified genes whose transcripts were enriched in each stage of oocyte maturation. Conclusions Our work uncovers transcriptomic changes during human oocyte IVM and the differential gene expression profile of each oocyte.