Search

Introduction: BK Polyomavirus (BKPyV) infection is a common complication in kidney transplant recipients and can result in poor outcomes and graft failure. Currently, there is no known effective antiviral agent. This study investigated the possible antiviral effects of Interferon alpha (IFNα) and its induced protein, MxA, against BKPyV. Methods: In vitro cell culture experiments were conducted using human primary renal proximal tubular epithelial cells (HRPTECs). We also did animal studies using Balb/c mice with unilateral kidney ischemic reperfusion injury. Results: Our results demonstrated that IFNα effectively inhibited BKPyV in vitro and murine polyomavirus in animal models. Additionally, IFNα and MxA were found to suppress BKPyV TAg and VP1 production. Silencing MxA attenuated the antiviral efficacy of IFNα. We observed that MxA interacted with BKPyV TAg, causing it to remain in the cytosol and preventing its nuclear translocation. To determine MxA's essential domain for its antiviral activities, different mutant MxA constructs were generated. The MxA mutant K83A retained its interaction with BKPyV TAg, and its antiviral effects were intact. The MxA T103A mutant, on the other hand, abolished GTPase activity, lost its protein-protein interaction with BKPyV TAg, and lost its antiviral effect. Conclusion: IFNα and its downstream protein, MxA, have potent antiviral properties against BKPyV. Furthermore, our findings indicate that the interaction between MxA and BKVPyV TAg plays a crucial role in determining the anti-BKPyV effects of MxA.

Immunosenescence refers to the immune system changes observed in individuals over 50 years old, characterized by diminished immune response and chronic inflammation. Recent investigations have highlighted similar immune alterations in patients with reduced kidney function. The immune system and kidney function have been found to be closely interconnected. Studies have shown that as kidney function declines, both innate and adaptive immunity are affected. Chronic kidney disease (CKD) patients exhibit decreased levels of naive and regular T cells, as well as naive and memory B cells, while memory T cell counts increase. Furthermore, research suggests that CKD and end-stage kidney disease (ESKD) patients experience early thymic dysfunction and heightened homeostatic proliferation of naive T cells. In addition to reduced thymic T cell production, CKD patients display shorter telomeres in both CD4+ and CD8+ T cells.Declining kidney function induces uremic conditions, which alter the intestinal metabolic environment and promote pathogen overgrowth while reducing diversity. This dysbiosis-driven imbalance in the gut microbiota can result in elevated production of uremic toxins, which, in turn, enter the systemic circulation due to compromised gut barrier function under uremic conditions. The accumulation of gut-derived uremic toxins exacerbates local and systemic kidney inflammation. Immune-mediated kidney damage occurs due to the activation of immune cells in the intestine as a consequence of dysbiosis, leading to the production of cytokines and soluble urokinase-type plasminogen activator receptor (suPAR), thereby contributing to kidney inflammation.In this review, we delve into the fundamental mechanisms of immunosenescence in CKD, encompassing alterations in adaptive immunity, gut dysbiosis, and an overview of the clinical findings pertaining to immunosenescence.

Leptospirosis is a neglected bacterial disease caused by leptospiral infection that carries a substantial mortality risk in severe cases. Research has shown that acute, chronic, and asymptomatic leptospiral infections are closely linked to acute and chronic kidney disease (CKD) and renal fibrosis. Leptospires affect renal function by infiltrating kidney cells via the renal tubules and interstitium and surviving in the kidney by circumventing the immune system. The most well-known pathogenic molecular mechanism of renal tubular damage caused by leptospiral infection is the direct binding of the bacterial outer membrane protein LipL32 to toll-like receptor-2 expressed in renal tubular epithelial cells (TECs) to induce intracellular inflammatory signaling pathways. These pathways include the production of tumor necrosis factor (TNF)-α and nuclear factor kappa activation, resulting in acute and chronic leptospirosis-related kidney injury. Few studies have investigated the relationship between acute and chronic renal diseases and leptospirosis and further evidence is necessary. In this review, we intend to discuss the roles of acute kidney injury (AKI) to/on CKD in leptospirosis. This study reviews the molecular pathways underlying the pathogenesis of leptospirosis kidney disease, which will assist in concentrating on potential future research directions.

The importance of oxygen to life has been recognized for hundreds of years, but how cells and tissues sense reduced oxygen levels remained elusive until the late twentieth century. The 2019 Nobel Prize in Physiology or Medicine was awarded to William G. Kaelin Jr., Sir Peter J. Ratcliffe, and Gregg L. Semenza for their discovery of hypoxia-inducible factor, a key transcription factor that regulates gene expression in response to decreases in cellular oxygenation. The three scientists provided the first information about the cellular oxygen-sensing mechanism and downstream signal transduction under hypoxic conditions. Their discoveries have also paved the way for promising novel treatments for cancer, renal anemia, and inflammatory disease.

Background: Raising evidence suggested a prognostic utility of tubulointerstitial lesions in lupus nephritis (LN). The exact prevalence of tubulointerstitial abnormalities and its predictive value among pediatric onset systemic lupus erythematous (pSLE) cases, however, remained unknown. Methods: Sixty-seven pSLE subjects diagnosed with LN with initial renal samples available were enrolled and followed for an average of 6.49 ± 3.06 years. Renal histology was evaluated according to the International Society of Nephrology/Renal Pathology Society classification, National Institute of Health classification and tubulointerstitial activity index (TIAI). Results: Tubulointerstitial injuries were observed in 38.81% of all LN cases, including 13.33% with non-proliferative lupus nephritis (nPLN) and 46.15% of with proliferative lupus nephritis (PLN). Tubulointerstitial injuries occurred solitarily in cases with nPLN(13.33%), but always associated glomerular changes and significantly impacted renal survival (p = 0.032) among those with PLN. TIAI associated glomerular abnormalities (p = 0.031) but did not correlate renal performance or subsequent outcome (p = 0.445). Among the chronicity index, it was the chronic tubulointerstitial lesions that provided prognostic information (p = 0.012). None of the individual tubulointerstitial factors, however, reached statistical significance in end-stage renal disease prediction. Finally, considering tubulointerstitial injuries in PLN further discriminated subsequent renal outcome (p = 0.006). Conclusion: Tubulointerstitial abnormalities were found in nearly one-third of all pediatric LN cases. With its importance in early identifying those at risk of renal failure, histologic classification considering tubulointerstitial lesions may potentially assist outcome prediction. Keywords: Lupus nephritis, Pediatric onset systemic lupus erythematosus, Renal survival tubulointerstitial abnormalities

MicroRNAs (MiR, MiRNA) are small single-stranded non-coding RNAs that play an important role in the regulation of gene expression. MircoRNAs exert their effect by binding to complementary nucleotide sequences of the targeted messenger RNA, thus forming an RNA-induced silencing complex. The mircoRNA-17-92 cluster encoded by the miR-17-92 host gene is first found in malignant B-cell lymphoma. Recent research identifies the miR-17-92 cluster as a crucial player in the development of the immune system, the heart, the lung, and oncogenic events. In light of the miR-17-92 cluster's increasing role in regulating the immune system, our review will discuss the latest knowledge regarding its involvement in cells of both innate and adaptive immunity, including B cells, subsets of T cells such as Th1, Th2, T follicular helper cells, regulatory T cells, monocytes/macrophages, NK cells, and dendritic cells, and the possible targets that are regulated by its members. Keywords: MicroRNA-17-92 cluster, Proliferation, Immune regulation

Background: Heart rate variability (HRV), a non-invasive measurement of the sympathetic-vagal balance, has been demonstrated as a predictor of long-term survival in various patient populations. However, its predictive value in patients with end-stage renal disease (ESRD) has not been evaluated in a long-term follow-up study. Methods: Prospective data collected for 41 patients with chronic hemodialysis (age 59 ± 10 years, men 51.3%, diabetes mellitus 31%, and duration of dialysis 64 ± 50 months) who underwent a 5-minute electrocardiogram (ECG) recording as a baseline for frequency domain HRV analysis. Results: During a median follow-up of 150.2 months from 2003 to 2014, 15 (35.7%) patients died (3 due to cardiac causes and 12 due to non-cardiac causes). The Cox proportional hazards model suggested that the low frequency versus high frequency signal (LF/HF) of a high ratio for the HRV and diabetes mellitus were two independent predictors of mortality (hazard ratios 3.028 and 3.494; p = 0.033 and 0.022, respectively). Less reduction in MAP during dialysis showed borderline significance of long-term survival than those with larger drop (p = 0.058). Conclusion: A short ECG recording and an analysis of the frequency domain of the HRV is clinically predictive of the long-term survival of patients with chronic hemodialysis. Keywords: Heart rate variability, Cardiorenal syndrome, Hemodialysis, Survival, End-stage renal disease

Background/Purpose: Acute kidney injury (AKI) developing during extracorporeal membrane oxygenation (ECMO) is associated with very poor outcome. The Kidney Disease: Improving Global Outcomes (KDIGO) group published a new AKI definition in 2012. This study analyzed the outcomes of patients treated with ECMO and identified the relationship between the prognosis and the KDIGO classification. Methods: This study examined total 312 patients initially, and finally reviewed the medical records of 167 patients on ECMO support at a tertiary care university hospital between March 2002 and November 2011. Demographic, clinical, and laboratory variables were retrospectively collected as survival predicators. Results: The overall mortality rate was 55.7%. In the analysis of the areas under the receiver operating characteristic curves, the KDIGO classification showed relatively higher discriminatory power (0.840 ± 0.032) than the Risk of renal failure, Injury to the kidney, Failure of kidney function, Loss of kidney function, and End-stage renal failure (RIFLE) (0.826 ± 0.033) and Acute Kidney Injury Network (AKIN) (0.836 ± 0.032) criteria in predicting in-hospital mortality. Furthermore, multiple logistic regression analysis showed that KDIGO, hemoglobin, and Glasgow Coma Scale score on the first day of patients on ECMO were independent predictors for in-hospital mortality. Finally, cumulative survival rates at 6-month follow-up after hospital discharge differed significantly for KDIGO stage 3 versus KDIGO stage 0, 1, and 2 (p