Metagenome-wide analysis uncovers gut microbial signatures and implicates taxon-specific functions in end-stage renal disease.

Background: The gut microbiota plays a crucial role in regulating host metabolism and producing uremic toxins in patients with end-stage renal disease (ESRD). Our objective is to advance toward a holistic understanding of the gut ecosystem and its functional capacity in such patients, which is still lacking.

Results: Herein, we explore the gut microbiome of 378 hemodialytic ESRD patients and 290 healthy volunteers from two independent cohorts via deep metagenomic sequencing and metagenome-assembled-genome-based characterization of their feces.

14-3-3ζ targets β-catenin nuclear translocation to maintain mitochondrial homeostasis and promote the balance between proliferation and apoptosis in cisplatin-induced acute kidney injury.

Cisplatin is a chemotherapeutic agent that is used extensively to treat solid tumors; however, its clinical application is limited by side effects, especially nephrotoxicity. Cisplatin-induced acute kidney injury (AKI) is characterized by DNA damage, cell-cycle arrest, and mitochondrial oxidative stress. Recent research demonstrated that 14-3-3ζ plays an important role in cancers, nerve disease, and kidney disease, although the regulatory mechanisms underlying cisplatin-induced AKI have yet to be fully elucidated.

Risk factor mining and prediction of urine protein progression in chronic kidney disease: a machine learning- based study.

Background: Chronic kidney disease (CKD) is a global public health concern. Therefore, to provide timely intervention for non-hospitalized high-risk patients and rationally allocate limited clinical resources is important to mine the key factors when designing a CKD prediction model.

Methods: This study included data from 1,358 patients with CKD pathologically confirmed during the period from December 2017 to September 2020 at Zhongshan Hospital.

Urinary N-Acetyl-Beta-D-Glucosaminidase levels predict immunoglobulin a nephropathy remission status.

Background: Tubulointerstitial lesions play a pivotal role in the progression of IgA nephropathy (IgAN). Elevated N-acetyl-beta-D-glucosaminidase (NAG) in urine is released from damaged proximal tubular epithelial cells (PTEC) and may serve as a biomarker of renal progression in diseases with tubulointerstitial involvement.

Methods: We evaluated the predictive value of urinary NAG (uNAG) for disease progression in 213 biopsy-proven primary IgAN patients from January 2018 to December 2019 at Zhongshan Hospital, Fudan University.

A NOVEL RAT MODEL OF CONTRAST-INDUCED ACUTE KIDNEY INJURY BASED ON RENAL CONGESTION AND THE RENO-PROTECTION OF MITOCHONDRIAL FISSION INHIBITION.

Contrast-induced acute kidney injury (CI-AKI) is a serious and common complication in patients receiving intravenous iodinated contrast medium (CM). Clinically, congestive heart failure is the most critical risk factor for CI-AKI and always leads to renal congestion for increased central venous pressure and fluid overload. Here, we aimed to investigate a novel CI-AKI rat model based on renal congestion.

Temporal trends in prevalence and mortality for chronic kidney disease in China from 1990 to 2019: an analysis of the Global Burden of Disease Study 2019.

Background: This study aimed to characterize the temporal trends of chronic kidney disease (CKD) burden in China during 1990-2019, evaluate their age, period and cohort effects, and predict the disease burden for the next 10 years.

Methods: Data were obtained from the Global Burden of Disease (GBD) 2019 study. Join-point regression model was used to estimate the average annual percentage change (AAPC) of CKD prevalence and mortality, and the age-period-cohort analysis was used to estimate the age, period and cohort effects.

TWIK-related acid-sensitive K channel 2 promotes renal fibrosis by inducing cell-cycle arrest.

TWIK-related acid-sensitive K channel-2 (TASK-2, encoded by ) is essential in cell biological processes, by regulating transmembrane K balance. In the present study, we aimed to clarify the role of TASK-2 in renal fibrosis and explore the underlying mechanism. We found that TASK-2 level was elevated in the renal tubular UUO- and UIR-induced renal fibrosis as well as in patients with renal tubulointerstitial fibrosis.

Social Isolation Is Associated With Rapid Kidney Function Decline and the Development of Chronic Kidney Diseases in Middle-Aged and Elderly Adults: Findings From the China Health and Retirement Longitudinal Study (CHARLS).

There is limited evidence on the relationship between social isolation and renal outcomes. To address this gap, this study estimated the prospective relationship of social isolation with rapid kidney function decline and the development of chronic kidney disease (CKD) in middle-aged and elderly Chinese with normal kidney function. We analyzed data from 3,031 participants aged ≥ 45 years with baseline estimated glomerular filtration rates (eGFR) ≥ 60 ml/min/1.

METTL14 aggravates podocyte injury and glomerulopathy progression through N-methyladenosine-dependent downregulating of Sirt1.

Podocytes are known to play a determining role in the progression of proteinuric kidney disease. N-methyladenosine (m6A), as the most abundant chemical modification in eukaryotic mRNA, has been reported to participate in various pathological processes. However, its role in podocyte injury remains unclear.

Dynamics in perioperative neutrophil-to-lymphocyte*platelet ratio as a predictor of early acute kidney injury following cardiovascular surgery.

Background: In this study, we applied a composite index of neutrophil-lymphocyte * platelet ratio (NLPR), and explore the significance of the dynamics of perioperative NLPR in predicting cardiac surgery-associated acute kidney injury (CSA-AKI).

Methods: During July 1 and December 31 2019, participants were prospectively derived from the 'Zhongshan Cardiovascular Surgery Cohort'. NLPR was determined using neutrophil counts, lymphocyte and platelet count at the two-time points.

Genistein Ameliorates Renal Fibrosis Through Regulation Snail via m6A RNA Demethylase ALKBH5.

Renal tubule-interstitial fibrosis is related to chronic kidney disease progression and a typical feature of the aging kidney. Epigenetic modifications of fibrosis-prone genes regulate the development of renal fibrosis. As a kind of "epigenetic diet", soy isoflavone genistein was reported to have renal protective action and epigenetic-modulating effects.

Caloric restriction alleviates aging-related fibrosis of kidney through downregulation of miR-21 in extracellular vesicles.

Glomerulosclerosis and renal interstitial fibrosis occur with the aging kidney. In this study, we examined the expression of miR-21, peroxisome proliferator-activated receptor(PPARα), hypoxia-inducible factor(HIF-1α) in the kidney of 3-month-old rats fed ad libitum (YAL), 24-month-old rats fed ad libitum (OAL) and 24-month-old rats subjected to a 70% calorie-restricted diet for 8 months (OCR). We found long-term caloric restriction (CR) ameliorated aging and aging-related fibrosis.

METTL14-dependent m6A regulates vascular calcification induced by indoxyl sulfate.

Aims: Although the functional importance of N6-methyladenosine (m6A) in various fundamental bioprocesses are well known, its effect on vascular calcification is not well studied. We investigated the role of methyltransferase-like 14 (METTL14), an m6A methylase, in vascular calcification.

Main Methods: We used clinical human samples as well as rat models and primary human artery smooth muscle cell (HASMC) cultures to study the functional role of m6A and METTL14 in vascular calcification and in HASMCs.

Exogenous biological renal support ameliorates renal pathology after ischemia reperfusion injury in elderly mice.

We established an exogenous biological renal support model through the generation of parabiotic mice. At 72 hours after ischemia reperfusion injury (IRI), the aged mice that received exogenous biological renal support showed significantly higher levels of renal cell proliferation and dedifferentiation, lower levels of renal tubular injury, improved renal function, and a lower mortality than those that did not receive exogenous biological renal support. Using the Quantibody Mouse Cytokine Antibody Array, we found that aged IRI mice that received exogenous biological renal support had an up-regulation of multiple inflammatory related cytokines compared to the group that did not receive exogenous biological renal support.

Acid-sensing ion channel 1a is involved in ischaemia/reperfusion induced kidney injury by increasing renal epithelia cell apoptosis.

Acidic microenvironment is commonly observed in ischaemic tissue. In the kidney, extracellular pH dropped from 7.4 to 6.

Amelioration of Uremic Toxin Indoxyl Sulfate-Induced Osteoblastic Calcification by SET Domain Containing Lysine Methyltransferase 7/9 Protein.

Background: Vascular calcification (VC) is a very common phenomenon in patients with chronic kidney disease (CKD). It has been reported that some histone methylation play a role in VC as an epigenetic regulator. Indoxyl sulfate (IS) is a protein-bound uremic toxin that has been proven as one of the major risk factors of cardiovascular disease in CKD.

Transforming growth factor-β1-overexpressing mesenchymal stromal cells induced local tolerance in rat renal ischemia/reperfusion injury.

Background: Regulatory T cells (Tregs) suppress excessive immune responses and play a crucial protective role in acute kidney injury (AKI). The aim of this study was to examine the therapeutic potential of transforming growth factor (TGF)-β1-overexpressing mesenchymal stromal cells (MSCs) in inducing local generation of Tregs in the kidney after ischemia/reperfusion (I/R) injury.

Methods: MSCs were transduced with a lentiviral vector expressing the TGF-β1 gene; TGF-β1-overexpressing MSCs (designated TGF-β1/MSCs) were then transfused into the I/R-injured kidney via the renal artery.

Youthful systemic milieu alleviates renal ischemia-reperfusion injury in elderly mice.

The incidence of acute kidney injury (AKI) is high in elderly people, and is difficult to prevent and treat. One of its major causes is renal ischemia-reperfusion injury (IRI). A young systemic environment may prevent the senescence of old organs.

Necrostatin-1 Attenuates Cisplatin-Induced Nephrotoxicity Through Suppression of Apoptosis and Oxidative Stress and Retains Klotho Expression.

Cisplatin is an effective chemotherapeutic drug, but the application in clinical is greatly limited by its nephrotoxicity. Necrostatin-1 (Nec-1), an inhibitor of RIP1 kinase, has been reported to inhibit RIP-mediated necroptosis. The aim of this study is to detect the protective effects of Nec-1 on the nephrotoxicity of cisplatin and to investigate its renoprotection mechanism.

Syndecan-1 Shedding Inhibition to Protect Against Ischemic Acute Kidney Injury Through HGF Target Signaling Pathway.

Background: The hepatocyte growth factor (HGF) target pathway plays pivotal renoprotective roles after acute kidney injury. Syndecan-1 (SDC-1) serves as the coreceptor for HGF. Shedding of SDC-1 is involved in various pathological processes.

A Young Blood Environment Decreases Aging of Senile Mice Kidneys.

Whether changes in internal body environment affect kidney aging remains unclear. Specifically, it is unknown whether transplanted kidneys from older donors recover from tissue damage after placement in younger recipients. In this study, a parabiosis animal model was established to investigate the effects of a young internal body environment on aged kidneys.

Alleviation of senescence and epithelial-mesenchymal transition in aging kidney by short-term caloric restriction and caloric restriction mimetics via modulation of AMPK/mTOR signaling.

Renal fibrosis contributes to declining renal function in the elderly. What is unclear however, is whether epithelial-mesenchymal transition (EMT) contributes to this age-related renal fibrosis. Here, we analyzed indicators of EMT during kidney aging and investigated the protective effects and mechanisms of short-term regimens of caloric restriction (CR) or caloric restriction mimetics (CRMs), including resveratrol and metformin.

Anti-Inflamm-Aging Effects of Long-Term Caloric Restriction via Overexpression of SIGIRR to Inhibit NF-κB Signaling Pathway.

Background: Chronic inflammation is thought to be a determinant of the aging rate and longevity. Caloric restriction (CR) attenuates age-related increases in the systemic levels of several pro-inflammatory mediators, but the anti-inflammatory mechanisms of CR in the aging process remain unclear.

Methods: Fisher 344 rats in a CR group were fed an amount of food corresponding to 60% of that fed to an ad libitum-fed (AL) group for 8 months.