Acute kidney injury (AKI) is one of the most prevalent complications among hospitalized coronavirus disease 2019 (COVID-19) patients. Here, we aim to investigate the causes, risk factors, and outcomes of AKI in COVID-19 patients. We found that angiotensin-converting enzyme II (ACE2) and transmembrane protease serine 2 (TMPRSS2) were mainly expressed by different cell types in the human kidney. However, in autopsy kidney samples, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleoprotein was detected in ACE2⁺ or TMPRSS2⁺ renal tubular cells, whereas the RNAscope^® Assay targeting the SARS-CoV-2 Spike gene was positive mainly in the distal tubular cells and seldom in the proximal tubular cells. In addition, the TMPRSS2 and kidney injury marker protein levels were significantly higher in the SARS-CoV-2-infected renal distal tubular cells, indicating that SARS-CoV-2-mediated AKI mainly occurred in the renal distal tubular cells. Subsequently, a cohort analysis of 722 patients with COVID-19 demonstrated that AKI was significantly related to more serious disease stages and poor prognosis of COVID-19 patients. The progressive increase of blood urea nitrogen (BUN) level during the course of COVID-19 suggests that the patient’s condition is aggravated. These results will greatly increase the current understanding of SARS-CoV-2 infection.

Background/Aims: To investigate the role of angiopoietin-2 (Ang-2) and IL-18 in the pathogenesis of diabetic nephropathy (DN) and the molecular mechanisms through which alprostadil protects renal function. Methods: DN was induced by streptozotocin and intraperitoneal injection of alprostadil was given to diabetic mice. After 2, 4 and 8 weeks of alprostadil treatment, the mRNA and protein expression of kidney Ang-2 and IL-18 were detected by reverse transcription PCR, Western blot and immunohistochemistry analyses. Mouse glomerular endothelial cells (GEnCs) were cultured in high glucose and treated with alprostadil. After transfection with an Ang-2-pcDNA and Ang-2-siRNA, both Ang-2 and IL-18 expression were measured by Western blot analyses. Results: Alprostadil treatment caused a significant decrease in the renal damage parameters. Both Ang-2 and IL-18 were significantly increased in DN mice and in GEnCs cultured in high glucose; however, their expression was greatly reduced by alprostadil treatment. Ang-2 could also increase IL-18 expression in cultured endothelial cells under high glucose, and this response was partially blocked by Ang-2 siRNA. Conclusions: Ang-2 and IL-18 may be associated with the development and progression of DN in mice. Alprostadil treatment can protect renal function by reducing proteinuria. These effects are mediated, at least in part, through down-regulation of Ang-2 and IL-18 expression.

Aims. To evaluate the levels of angiopoietin-1 (Ang-1), Ang-2, and vascular endothelial growth factor (VEGF) in serum and urine, and their association with albuminuria in patients with type 2 diabetes mellitus.Methods. In 113 type 2 diabetic patients with normoalbuminuria, microalbuminuria, and macroalbuminuria and 30 healthy controls, the levels of Ang-1, Ang-2, and VEGF in serum and urine were measured by enzyme-linked immunosorbent assay (ELISA).Results. Urinary and serum levels of Ang-2 were significantly higher in diabetic patients with normoalbuminuria than in healthy controls. Increased urinary Ang-2 level was positively associated with the degree of albuminuria. Urinary Ang-1 levels were significantly higher in normoalbuminuria patients and lower in macroalbuminuria patients than in controls. The levels of urinary VEGF increased in the albuminuria subgroup, though serum levels of Ang-1 and VEGF did not change. Urinary Ang-2 levels were correlated positively with albuminuria and negatively with glomerular filtration rate (GFR). Stepwise multiple regression analysis identified albuminuria (P<0.001) and GFR (P=0.001) as significant predictors of urinary Ang-2.Conclusions. Our data suggest that urinary Ang-2 is stepwise increased with renal damage in patients with type 2 diabetes mellitus and is associated with albuminuria.

Background: Acute kidney injury (AKI) is one of the postoperative complications following orthotopic liver transplantation (OLT), and is related to the high morbidity and mortality. Although there were numerous propensity factors for AKI, their cumulative influence remains unclear. Our aims were to develop a score model to predict postoperative AKI and to evaluate the impact of AKI on the recipients’ long-term survival. Methods: We retrospectively analyzed 99 adult patients underwent OLT in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology between October 2014 and July 2020. The patients were dichotomized into the non-AKI and the AKI groups according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. We defined stage-1 AKI as mild AKI, stage-2 AKI and stage-3 AKI as severe AKI. Results: Overall, 29 (29.29%) patients developed AKI after OLT, of these, stage-1, stage-2, stage-3 account for 20.20% (20 of 99 patients), 2.02% (2 of 99 patients), 7.07% (7 of 99 patients), respectively; and 13.79% of postoperative AKI patients (4 of 29 patients) accepted renal replacement therapy (RRT). Operative time and MELD-Na score predicted the postoperative AKI, with odds ratio of 1.006, 1.061, respectively. The generated AKI prediction model is as follows: -5.594+0.007×operative time+0.060×MELD-Na. The area under the receiver operating characteristic curve (AUC) for the AKI prediction model was 0.762, and the sensitivity and specificity were 79.3%, 61.4%, respectively. There was no difference in long-term survival among the mild AKI group and the non-AKI group (P=0.751). However, the impact of severe AKI on long-term survival of patients was statistically significant when comparing the non-AKI group and the mild AKI group (P=0.001, P=0.011). Conclusions: AKI occurs frequently in adult patients after OLT, and it poses a threat to patients’ long-term survival. The severe AKI has negative impact on long-term survival, while the mild AKI has limited impact on long-term survival, compared with non-AKI group. The novel AKI prediction model has prognostic value in identifying patients at high risk for postoperative AKI.

Transcytosis is an important intracellular transport process by which multicellular organisms selectively move cargoes from apical to basolateral membranes without disrupting cellular homeostasis. In kidney, macromolecular components in the serum, such as albumin, low-density lipoprotein and immunoglobulins, pass through the glomerular filtration barrier (GFB) and proximal tubular cells (PTCs) by transcytosis. Protein transcytosis plays a vital role in the pathology of albuminuria, which causes progressive destruction of the GFB structure and function. However, the pathophysiological consequences of protein transcytosis in the kidney remain largely unknown. This article summarizes recent researches on the regulation of albumin transcytosis across the GFB and PTCs in both physiological and pathological conditions. Understanding the mechanism of albumin transcytosis may reveal potential therapeutic targets for prevention or alleviation of the pathological consequences of albuminuria.