Effectiveness and Safety of Spironolactone in the Treatment of IgA Nephropathy: A Retrospective Self-Controlled Study.

Introduction: It is crucial to utilize combination therapy for immunoglobulin A nephropathy (IgAN) patients to reduce proteinuria and maintain stable kidney function. We demonstrate the safety and efficacy of low-dose spironolactone in the management of IgAN patients.

Methods: Adult IgAN patients treated with spironolactone were evaluated.

Renal outcomes in IgA nephropathy following inactivated SARS-CoV-2 vaccination.

Introduction: There are increasing case reports on de novo or relapsing IgA nephropathy (IgAN) following SARS-CoV-2 vaccines, although the follow-up information on renal outcomes in IgAN patients post-SARS-CoV-2 vaccination is limited. In this study, we evaluated the renal outcomes of IgAN patients following inactivated vaccines.

Methods: We investigated the change in eGFR, proteinuria and hematuria in 113 primary IgAN patients post-vaccination.

Effect of Nonimmune Factors on Renal Prognosis in Adult IgA Vasculitis With Nephritis: A Long-Term Retrospective Cohort Study.

Objective: Adult immunoglobulin A vasculitis (IgAV) is documented to be associated with more renal involvement and poorer renal outcomes compared to children, but adult IgAV nephritis (IgAV-N) data are rather limited. The present study aimed to describe the characteristics of adult IgAV-N and investigate the long-term prognostic factors.

Methods: Clinical and morphological data from 106 adult patients with biopsy-proven IgAV-N and follow-up data from 94 patients in a single Chinese center were analyzed in this retrospective study.

An inhibitor with GSK3β and DYRK1A dual inhibitory properties reduces Tau hyperphosphorylation and ameliorates disease in models of Alzheimer's disease.

Since Alzheimer's disease (AD) is a complex and multifactorial neuropathology, the discovery of multi-targeted inhibitors has gradually demonstrated greater therapeutic potential. Neurofibrillary tangles (NFTs), the main neuropathologic hallmarks of AD, are mainly associated with hyperphosphorylation of the microtubule-associated protein Tau. The overexpression of GSK3β and DYRK1A has been recognized as an important contributor to hyperphosphorylation of Tau, leading to the strategy of using dual-targets inhibitors for the treatment of this disorder.

Klotho promotes AMPK activity and maintains renal vascular integrity by regulating the YAP signaling pathway.

The development and formation of mammalian blood vessels are closely related to the regulation of signal transduction pathways. Klotho/AMPK and YAP/TAZ signaling pathways are closely related to angiogenesis, but the internal relationship between them is not clear. In this study, we found that Klotho heterozygous deletion mice (Klotho mice) had obvious thickening of the renal vascular wall, obvious enlargement of vascular volume, and significant proliferation and pricking of vascular endothelial cells.

Exploration of the Components and Pharmacological Mechanisms of Keyin Pill-Induced Liver Injury Based on Network Pharmacology.

Background: Keyin pill (KP), a patented medicine in China, is used to treat psoriasis. However, KP has been reported to have liver toxicity, but its toxic substance basis and underlying mechanisms remain unclear. Therefore, this study aimed to explore the pharmacological mechanisms and components of KP-induced liver injury through animal experiments, UPLC-QTOF/MS combined with network pharmacology.

Mesangial cell-derived tenascin-C contributes to mesangial cell proliferation and matrix protein production in IgA nephropathy.

Aim: Tenascin-C (TNC), a non-structural extracellular matrix glycoprotein, is transiently expressed during development or after injury, playing an important role in injury and repair process. The potential role of TNC in the pathogenesis of IgA nephropathy (IgAN) remains to be clarified.

Methods: Immunohistochemistry staining for TNC was conducted on paraffin-embedded slices from renal biopsies of 107 IgAN patients, and correlation analysis was made between mesangial TNC expression and clinic-pathological parameters.

α-Klotho, Plasma Asymmetric Dimethylarginine, and Kidney Disease Progression.

Rationale & Objective: We aimed to explore the associated factors of endothelial injury in chronic kidney disease (CKD) and the relationship between endothelial dysfunction and CKD prognosis.

Study Design: A prospective observational cohort study.

Setting & Participants: 77 adults with CKD stages 1-5 were enrolled January 2010 to December 2010 and followed up until December 2015.

IgA Vasculitis with Nephritis in Adults: Histological and Clinical Assessment.

Patients with IgA vasculitis (IgAV), an immune complex-mediated disease, may exhibit kidney involvement-IgAV with nephritis (IgAVN). The kidney-biopsy histopathologic features of IgAVN are similar to those of IgA nephropathy, but little is known about histopathologic disease severity based on the interval between purpura onset and diagnostic kidney biopsy. We assessed kidney histopathology and clinical and laboratory data in a cohort of adult patients with IgAVN (n = 110).

Bovine serum albumin aggravates macrophage M1 activation and kidney injury in heterozygous Klotho-deficient mice via the gut microbiota-immune axis.

Klotho expression abnormalities induces kidney injury and chronic kidney disease, however, the underlying mechanism remains unclear. Here, Klotho mice and wild-type mice were treated with low-dose bovine serum albumin (BSA). Pathological examination demonstrated that the area of glomerular collagen deposition and fibrosis in BSA-Kl mice was significantly larger than that in BSA-WT mice.

Ranitidine and finasteride inhibit the synthesis and release of trimethylamine N-oxide and mitigates its cardiovascular and renal damage through modulating gut microbiota.

Trimethylamine N-oxide (TMAO) leads to the development of cardiovascular and chronic kidney diseases, but there are currently no potent drugs that inhibit the production or toxicity of TMAO. In this study, high-fat diet-fed ApoE-/- mice were treated with finasteride, ranitidine, and andrioe. Subsequently, the distribution and quantity of gut microbiota in the faeces of the mice in each group were analysed using 16S rRNA sequencing of the V3+V4 regions.

Abnormal glucose metabolism and galactose-deficient immunoglobulin A1 (IgA1) synthesis: a possible mechanism of IgA nephropathy.

Background/aims: It is widely accepted that a possible etiopathogenic factor associated with IgA nephropathy is the glycosylation of IgA1 molecule O-glycans. The present study aimed to determine if galactose-deficient IgA1 is related to glucose metabolism.

Methods: IgA nephropathy was identified from the renal biopsies of 108 adult patients enrolled in our study with 60 healthy controls.

miR-15b induces premature ovarian failure in mice via inhibition of α-Klotho expression in ovarian granulosa cells.

A thorough understanding of epigenetics regulatory mechanisms of premature ovarian failure (POF) is still lacking. Here, we found that cyclophosphamide induced significantly decrease in α-Klotho (Kl) expression in mouse ovarian granulosa cells (mOGCs), suggesting that cyclophosphamide inhibited Kl expression. Cyclophosphamide also significantly accelerated ageing and led to a decline in the pregnancy rate of C.

Modulation of aldosterone levels by aldosterone synthase promoter polymorphism and association with eGFR decline in patients with chronic kidney disease.

To determine whether -344T/C CYP11B2 promoter polymorphism affects serum aldosterone levels and whether this polymorphism is an indicator of eGFR decline in patients with chronic kidney disease. -344 C/T CYP11B2 gene polymorphism analysis was performed in 96 adults with stages 1-5 CKD by using polymerase chain reaction. Serum aldosterone levels were measured at baseline and at 1.

Aldosterone induces renal fibrosis by promoting HDAC1 expression, deacetylating H3K9 and inhibiting klotho transcription.

Aldosterone has an important role in the progression of renal fibrosis. In the present study, the concentration of aldosterone and klotho (KL) in the serum of patients with chronic kidney disease (CKD) were analyzed. A negative correlation was observed between aldosterone and KL, suggesting that KL may serve a protective role in CKD.

Inflammatory demyelinating neuropathies with focal segmental glomerulosclerosis: Two case reports.

Rationale: Inflammatory demyelinating neuropathies such as Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), and focal segmental glomerulosclerosis (FSGS) are autoimmune disorders that may have a common pathogenesis. Here, we describe 2 unique cases of FSGS, 1 with GBS and the other with CIPD. We believe that reviewing these multisystemic diseases will help in better understanding of FSGS pathogenesis.

Circulating α-Klotho is Related to Plasma Aldosterone and Its Follow-Up Change Predicts CKD Progression.

Background/aims: We aimed to determine if soluble α-klotho level was an indicator of chronic kidney disease (CKD) progression and whether α-klotho interacted with aldosterone during the course of further renal damage.

Methods: 112 adults with stages 1-5 CKD were enrolled into our cohort study. All of the patients were followed up for 6 years (from January 2010 to December 2015).

Membranous nephropathy in a patient with ankylosing spondylitis: A case report.

Rationale: Renal complications in ankylosing spondylitis (AS) were rarely observed, and proteinuria associated with AS can be seen often due to amyloidosis in this kind of complications, while membranous nephropathy (MN) is seldom considered. This article reports a case of coexistence of AS and MN, to provide the exact relationship of these 2 entities and recognized some causes of renal involvement in AS.

Patient Concerns: A 44-year-old female presented with pain of the left leg for 4 years and pedal edema for 2 weeks.

New Insights into the Pathogenesis of IgA Nephropathy.

Background: IgA nephropathy, a frequent cause of end-stage renal disease, is an autoimmune disease wherein immune complexes consisting of IgA1 with galactose-deficient -glycans (autoantigen) and anti-glycan autoantibodies deposit in glomeruli and induce renal injury. Multiple genetic loci associated with disease risk have been identified. The prevalence of risk alleles varies geographically, highest in eastern Asia and northern Europe, fewer in other parts of Europe and North America, and the least in Africa.

Is the serum vitamin D level at the time of hospital-acquired acute kidney injury diagnosis associated with prognosis?

Background: Low circulating vitamin D levels have been suggested to potentially contribute to acute complications in critically ill patients. However, in patients with acute kidney injury (AKI), whether vitamin D deficiency occurs and is a potential contributor to worse early outcomes at the time of AKI diagnosis remains unclear.

Methodology/principal Findings: Two hundred patients with AKI were enrolled in our study.

Dietary salt modulates the sodium chloride cotransporter expression likely through an aldosterone-mediated WNK4-ERK1/2 signaling pathway.

WNK is a serine/threonine kinase. Mutation in WNK1 or WNK4 kinase results in pseudohypoaldosteronism type II (PHA II) featuring hypertension, hyperkalemia and metabolic acidosis. Sodium chloride cotransporter (NCC) is known to be regulated by phosphorylation and trafficking.

Aldosterone promotes fibronectin synthesis in rat mesangial cells via ERK1/2-stimulated Na-H+ exchanger isoform 1.

Background: Aldosterone plays an important role in fibrosis. Recent studies showed that Na(+)-H(+) exchanger isoform 1 (NHE1) is involved in mineralocorticoid-induced organ fibrosis. In this study, we examined the role of NHE1 in aldosterone-induced fibronectin accumulation in rat mesangial cells and the signaling pathway involved.

Aldosterone upregulates vascular endothelial growth factor expression in mouse cortical collecting duct epithelial cells through classic mineralocorticoid receptor.

Accumulating evidence shows that aldosterone plays an important role in the pathogenesis of renal fibrosis but its mechanism has not been completely defined. Recently, exogenous administration of aldosterone significantly alleviated ischemic states in a model of femoral artery ligated rats, accompanied by an obvious enhancement of VEGF upregulation. We hypothesized that aldosterone may also regulate the expression of VEGF in the kidney.