Long Non-coding RNA NEAT1 , NOD-Like Receptor Family Protein 3 Inflammasome, and Acute Kidney Injury.

Key Points: Long non-coding RNA (lncRNA) nuclear-enriched abundant transcript 1 () was upregulated in human and murine AKI. It returned to baseline after recovery in humans. Its knockdown preserved kidney function in animals.

Add-on astragalus in type 2 diabetes and chronic kidney disease: A multi-center, assessor-blind, randomized controlled trial.

Background: Diabetes leads to chronic kidney disease (CKD) and kidney failure, requiring dialysis or transplantation. Astragalus, a common herbal medicine and US pharmacopeia-registered food ingredient, is shown kidney protective by retrospective and preclinical data but with limited long-term prospective clinical evidence. This trial aimed to assess the effectiveness of astragalus on kidney function decline in macroalbuminuric diabetic CKD patients.

Add-on Rehmannia-6-Based Chinese Medicine in Type 2 Diabetes and CKD: A Multicenter Randomized Controlled Trial.

Background: Diabetes is the leading cause of CKD and kidney failure. We assessed the real-world effectiveness of Rehmannia-6-based Chinese medicine treatment, the most used Chinese medicine formulation, on the change in eGFR and albuminuria in patients with diabetes and CKD with severely increased albuminuria.

Methods: In this randomized, assessor-blind, standard care-controlled, parallel, multicenter trial, 148 adult patients from outpatient clinics with type 2 diabetes, an eGFR of 30-90 ml/min per 1.

Tubulovascular protection from protease-activated receptor-1 depletion during AKI-to-CKD transition.

Background: Thromboembolic events are prevalent in chronic kidney disease (CKD) patients due to increased thrombin generation leading to a hypercoagulable state. We previously demonstrated that inhibition of protease-activated receptor-1 (PAR-1) by vorapaxar reduces kidney fibrosis.

Methods: We used an animal model of unilateral ischemia-reperfusion injury-induced CKD to explore the tubulovascular crosstalk mechanisms of PAR-1 in acute kidney injury (AKI)-to-CKD transition.

Long-term outcomes of add-on direct renin inhibition in igA nephropathy: a propensity score-matched cohort study.

Introduction: The long-term clinical outcomes in biopsy proven IgAN patients treated with aliskiren on top of a maximally tolerated dose of ACEi/ARB remain unknown.

Methods: Patients with IgAN treated with a direct renin inhibitor and ACEi/ARB for at least 6 months were compared with a 1:1 propensityscore-matched cohort (including MEST-C score and the 12-months pre-exposure slope of eGFR matching) who received ACEi/ARB without aliskiren exposure to compute the hazard ratio of reaching the primary endpoint of a composite of 40% reduction in eGFR, initiation of KRT and all-cause mortality. Secondary outcome measures included changes in mean UPCR, blood pressure, eGFR, incidence of hyperkalemia and other adverse events during follow-up.

Tubular β-catenin alleviates mitochondrial dysfunction and cell death in acute kidney injury.

Mitochondria take part in a network of intracellular processes that regulate homeostasis. Defects in mitochondrial function are key pathophysiological changes during AKI. Although Wnt/β-catenin signaling mediates mitochondrial dysfunction in chronic kidney fibrosis, little is known of the influence of β-catenin on mitochondrial function in AKI.

Potential Therapeutic Targets of Rehmannia Formulations on Diabetic Nephropathy: A Comparative Network Pharmacology Analysis.

Previous retrospective cohorts showed that Rehmannia-6 (R-6, Liu-wei-di-huang-wan) formulations were associated with significant kidney function preservation and mortality reduction among chronic kidney disease patients with diabetes. This study aimed to investigate the potential mechanism of action of common R-6 variations in a clinical protocol for diabetic nephropathy (DN) from a system pharmacology approach. Disease-related genes were retrieved from GeneCards and OMIM by searching "Diabetic Nephropathy" and "Macroalbuminuria".

Tubule-specific deletion of ameliorates lipotoxic kidney injury.

Lipotoxicity has been implicated in the pathogenesis of obesity-related kidney damage and propagates chronic kidney injury like diabetic kidney disease; however, the underlying mechanisms have not yet been fully elucidated. To date, reduction of lipid acquisition and enhancement of lipid metabolism are the major, albeit non-specific, approaches to improve lipotoxic kidney damage. In the kidneys of high-fat diet (HFD)-fed mice and tubule cells cultured with palmitic acid (PA), we observed a dramatic upregulation of the long intergenic non-coding RNA-p21 () through a p53-dependent mechanism.

Global REnal Involvement of CORonavirus Disease 2019 (RECORD): A Systematic Review and Meta-Analysis of Incidence, Risk Factors, and Clinical Outcomes.

The quantitative effect of underlying non-communicable diseases on acute kidney injury (AKI) incidence and the factors affecting the odds of death among coronavirus disease 2019 (COVID-19) AKI patients were unclear at population level. This study aimed to assess the association between AKI, mortality, underlying non-communicable diseases, and clinical risk factors. A systematic search of six databases was performed from January 1, 2020, until October 5, 2020.

Spleen Tyrosine Kinase Inhibition Ameliorates Tubular Inflammation in IgA Nephropathy.

Spleen tyrosine kinase (Syk) is a non-receptor tyrosine kinase involved in signal transduction in a variety of immune responses. It has been demonstrated that Syk plays a pathogenic role in orchestrating inflammatory responses and cell proliferation in human mesangial cells (HMC) in IgA nephropathy (IgAN). However, whether Syk is involved in tubular damage in IgAN remains unknown.

Protective role of kallistatin in renal fibrosis via modulation of Wnt/β-catenin signaling.

Kallistatin is a multiple functional serine protease inhibitor that protects against vascular injury, organ damage and tumor progression. Kallistatin treatment reduces inflammation and fibrosis in the progression of chronic kidney disease (CKD), but the molecular mechanisms underlying this protective process and whether kallistatin plays an endogenous role are incompletely understood. In the present study, we observed that renal kallistatin levels were significantly lower in patients with CKD.

The PAR-1 antagonist vorapaxar ameliorates kidney injury and tubulointerstitial fibrosis.

Protease-activated receptor (PAR)-1 has emerged as a key profibrotic player in various organs including kidney. PAR-1 activation leads to deposition of extracellular matrix (ECM) proteins in the tubulointerstitium and induction of epithelial-mesenchymal transition (EMT) during renal fibrosis. We tested the anti-fibrotic potential of vorapaxar, a clinically approved PAR-1 antagonist for cardiovascular protection, in an experimental kidney fibrosis model of unilateral ureteral obstruction (UUO) and an AKI-to-chronic kidney disease (CKD) transition model of unilateral ischemia-reperfusion injury (UIRI), and dissected the underlying renoprotective mechanisms using rat tubular epithelial cells.

Peritoneal dialysis: the ideal bridge from conservative therapy to kidney transplant.

Background: Kidney transplantation offers the best potential for full rehabilitation in patients with end-stage kidney disease who are treated with dialysis. However, due to organ shortage which is a universal phenomenon, most patients need to be maintained on a period of dialysis therapy before the prospect of transplantation. Peritoneal dialysis (PD) could be an ideal form of renal replacement therapy due to its favorable profile toward preservation of residual renal function, patient survival, lower overall burden on cardiovascular morbidity and infection risks.

Direct Renin Inhibition in Non-diabetic chronic Kidney disease (DRINK): a prospective randomized trial.

Background: The potential long-term safety and efficacy of aliskiren in nondiabetic chronic kidney disease (CKD) are unknown. We sought to investigate the renoprotective effect of aliskiren on nondiabetic CKD patients.

Methods: In this open-label, parallel, randomized controlled trial, nondiabetic CKD Stages 3-4 patients were randomized to receive aliskiren added to an angiotensin II receptor blocker (ARB) at the maximal tolerated dose, or ARB alone.

Patients' and clinicians' expectations on integrative medicine Services for Diabetes: a focus group study.

Background: Difference of perspective between patients and physicians over integrative medicine (IM) research and service provision remains unclear despite significant use worldwide. We observed an exceptionally low utilisation of IM and potential underreporting in diabetes. We aimed to explore the barriers and recommendations regarding service delivery and research of IM service among diabetes patients and physicians.

Amelioration of Endoplasmic Reticulum Stress by Mesenchymal Stem Cells via Hepatocyte Growth Factor/c-Met Signaling in Obesity-Associated Kidney Injury.

Recent advances in the understanding of lipid metabolism suggest a critical role of endoplasmic reticulum (ER) stress in obesity-induced kidney injury. Hepatocyte growth factor (HGF) is a pleiotropic cytokine frequently featured in stem cell therapy with distinct renotropic benefits. This study aims to define the potential link between human induced pluripotent stem cell-derived mesenchymal stem cells (iPS-MSCs)/bone marrow-derived MSCs (BM-MSCs) and ER stress in lipotoxic kidney injury induced by palmitic acid (PA) in renal tubular cells and by high-fat diet (HFD) in mice.

Role of Mesangial-Podocytic-Tubular Cross-Talk in IgA Nephropathy.

IgA nephropathy (IgAN), a common primary glomerulonephritis worldwide, is associated with a substantial risk of progression to end-stage renal failure. The disease runs a highly variable clinical course with frequent involvement of tubulointerstitial damage. A subgroup of IgAN with proximal tubular epithelial cells (PTECs) and tubulointerstitial damage often is associated with rapid progression to end-stage renal failure.

Activated renal tubular Wnt/β-catenin signaling triggers renal inflammation during overload proteinuria.

Imbalance of Wnt/β-catenin signaling in renal cells is associated with renal dysfunction, yet the precise mechanism is poorly understood. Previously we observed activated Wnt/β-catenin signaling in renal tubules during proteinuric nephropathy with an unknown net effect. Therefore, to identify the definitive role of tubular Wnt/β-catenin, we generated a novel transgenic "Tubcat" mouse conditionally expressing stabilized β-catenin specifically in renal tubules following tamoxifen administration.

Complement C5a inhibition moderates lipid metabolism and reduces tubulointerstitial fibrosis in diabetic nephropathy.

Background: Complement C5 mediates pro-inflammatory responses in many immune-related renal diseases. Given that the C5a level is elevated in diabetes, we investigated whether activation of C5a/C5aR signalling plays a pathogenic role in diabetic nephropathy (DN) and the therapeutic potential of C5a inhibition for renal fibrosis.

Methods: Human renal biopsies from patients with DN and control subjects were used for immunohistochemical staining of complement C5 components.

Human induced pluripotent stem cell-derived mesenchymal stem cells prevent adriamycin nephropathy in mice.

Human induced pluripotent stem cell-derived mesenchymal stem cells (iPS-MSCs) are emerging as attractive options for use in cell replacement therapy, but their effect in kidney diseases remains unknown. Here, we showed that intravenous injection of iPS-MSCs protect against renal function loss in both short-term and long-term models of adriamycin nephropathy (AN). In the short-term AN model, iPS-MSCs conferred a substantial anti-apoptotic effect on tubular cells, associated with a downregulation of Bax and Bax/Bcl2 ratio and an upregulation of survivin expression.

N-acetyl-seryl-aspartyl-lysyl-proline mediates the anti-fibrotic properties of captopril in unilateral ureteric obstructed BALB/C mice.

Aim: Angiotensin-converting enzyme inhibitors (ACEi) are widely used to deter the progression of chronic kidney disease (CKD). Besides controlling hypertension and reduction of intra-glomerular pressure, ACEi appear to have anti-fibrotic effects in the renal cortex. N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP), an endogenous tetrapeptide that is degraded by ACE, has also been shown to ameliorate the pro-fibrotic phenotype displayed in CKD in our recent study.

Semi-individualised Chinese medicine treatment as an adjuvant management for diabetic nephropathy: a pilot add-on, randomised, controlled, multicentre, open-label pragmatic clinical trial.

Introduction: Diabetes mellitus and diabetic nephropathy (DN) are prevalent and costly to manage. DN is the leading cause of end-stage kidney disease. Conventional therapy blocking the renin-angiotensin system has only achieved limited effect in preserving renal function.

Recent advances in managing and understanding diabetic nephropathy.

Diabetic nephropathy is the commonest cause of end-stage renal disease in most developed economies. Current standard of care for diabetic nephropathy embraces stringent blood pressure control via blockade of the renin-angiotensin-aldosterone system and glycemia control. Recent understanding of the pathophysiology of diabetic nephropathy has led to the development of novel therapeutic options.