- Recurrent venous thromboembolism in primary membranous nephropathy despite direct Xa inhibitor therapy. [Journal Article]
- JNJ Nephrol 2018 Nov 12
- Clinically apparent venous thromboembolism (VTE) occurs in approximately 7% of patients with membranous nephropathy. Hypoalbuminemia at diagnosis is an independent risk factor for VTE, and risk incre...
Clinically apparent venous thromboembolism (VTE) occurs in approximately 7% of patients with membranous nephropathy. Hypoalbuminemia at diagnosis is an independent risk factor for VTE, and risk increases significantly as albumin falls. Optimal prophylactic and treatment anticoagulation regimens in the nephrotic syndrome remain unproven but novel oral anti-coagulants have become attractive therapeutic options. We describe a patient diagnosed with anti-phospholipase A2 receptor antibody positive membranous nephropathy and recurrent VTE while on therapeutic dosing of apixaban. A direct factor Xa inhibitor, apixaban has been shown to be non-inferior to warfarin for the treatment of VTE in the general population. However, because it is highly protein-bound, apixaban may have altered pharmacokinetics and pharmacodynamics in patients with nephrotic syndrome and hypoalbuminemia. This case report highlights the need for further studies of direct oral anticoagulants to fully assess their effectiveness in this high-risk population.
- CureGN Study Rationale, Design, and Methods: Establishing a Large Prospective Observational Study of Glomerular Disease. [Journal Article]
- AJAm J Kidney Dis 2018 Nov 09
- CONCLUSIONS: Current follow-up can only detect large differences in ESKD and death outcomes.Study infrastructure will support a broad range of scientific approaches to identify mechanistically distinct subgroups, identify accurate biomarkers of disease activity and progression, delineate disease-specific treatment targets, and inform future therapeutic trials. CureGN is expected to be among the largest prospective studies of children and adults with glomerular disease, with a broad goal to lessen disease burden and improve outcomes.
- The Role of Glucocorticoid Receptors in Podocytes and Nephrotic Syndrome. [Journal Article]
- NRNucl Receptor Res 2018; 5
- Glucocorticoid receptor (GC), a founding member of the nuclear hormone receptor superfamily, is a glucocorticoid-activated transcription factor that regulates gene expression and controls the develop...
Glucocorticoid receptor (GC), a founding member of the nuclear hormone receptor superfamily, is a glucocorticoid-activated transcription factor that regulates gene expression and controls the development and homeostasis of human podocytes. Synthetic glucocorticoids are the standard treatment regimens for proteinuria (protein in the urine) and nephrotic syndrome (NS) caused by kidney diseases. These include minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN) and immunoglobulin A nephropathy (IgAN) or subsequent complications due to diabetes mellitus or HIV infection. However, unwanted side effects and steroid-resistance remain major issues for their long-term use. Furthermore, the mechanism by which glucocorticoids elicit their renoprotective activity in podocyte and glomeruli is poorly understood. Podocytes are highly differentiated epithelial cells that contribute to the integrity of kidney glomerular filtration barrier. Injury or loss of podocytes leads to proteinuria and nephrotic syndrome. Recent studies in multiple experimental models have begun to explore the mechanism of GC action in podocytes. This review will discuss progress in our understanding of the role of glucocorticoid receptor and glucocorticoids in podocyte physiology and their renoprotective activity in nephrotic syndrome.
- Down-regulation of lncRNA XIST ameliorates podocytes apoptosis in membranous nephropathy via miR-217/TLR4 pathway. [Journal Article]
- EPExp Physiol 2018 Nov 10
- What is the central question of this study? Up-regulation of lncRNA XIST in injured podocytes and membranous nephropathy has been noted, but its implication in membranous nephropathy pathogenesis has...
What is the central question of this study? Up-regulation of lncRNA XIST in injured podocytes and membranous nephropathy has been noted, but its implication in membranous nephropathy pathogenesis has not been elucidated in detail. What is the main finding and its importance? We demonstrated that XIST was up-regulated in kidney tissue of membranous nephropathy and in injured podocytes. Down-regulation of XIST inhibited podocytes apoptosis. XIST negatively regulated miR-217, and miR-217 controlled TLR4. XIST modulated TLR4 through miR-217 and inhibition of XIST suppressed podocytes apoptosis induced by Angiotensin II via miR-217.
- Nephrotic syndrome associated with Kimura's disease: a case report and literature review. [Journal Article]
- BNBMC Nephrol 2018 Nov 08; 19(1):316
- CONCLUSIONS: MCD combined with acute renal tubular injury is rare in patients with KD presenting with renal involvement. Corticosteroids may be a beneficial treatment for renal injury in patients with KD.
- Glomerulonephritis Pattern at a Jordanian Tertiary Care Center. [Journal Article]
- IJInt J Nephrol 2018; 2018:2751372
- CONCLUSIONS: LN is the most common GN type in Jordan, followed by MGN and DN. MGN is the predominant primary GN with a higher prevalence among males; LN is the predominant secondary GN and tends to occur in Jordanian females. The GN patterns in this study shifted from membranoproliferative GN to MGN in Jordan, which revealed a shift towards similar patterns exhibited in developed countries. Furthermore, DN is the most frequent GN in the elderly.
- Clinical Management of Glomerular Diseases. [Review]
- NCNurs Clin North Am 2018; 53(4):551-567
- Progressive glomerular damage can occur as a result of various etiologic factors including infections, medications, diseases, and autoimmune disorders. This article discusses the clinical management ...
Progressive glomerular damage can occur as a result of various etiologic factors including infections, medications, diseases, and autoimmune disorders. This article discusses the clinical management of the leading conditions associated with glomerular disease, including glomerulosclerosis, diabetic nephropathy, focal segmental glomerulosclerosis, and membranous nephropathy. Glomerular damage and disease progression may lead to end stage renal disease. Clinical management is individualized, as based on causative factors and clinical manifestations, with the overall goal of limiting glomerular damage. Collaborative and comprehensive care is imperative to improving patient outcomes.
- The calcineurin regulatory subunit polymorphism and the treatment efficacy of tacrolimus for idiopathic membranous nephropathy. [Journal Article]
- IIInt Immunopharmacol 2018 Oct 30; 65:422-428
- Tacrolimus is considered to be one of the main therapeutic options for idiopathic membranous nephropathy (IMN). This study aimed to investigate the association of variants in genes encoding the bindi...
Tacrolimus is considered to be one of the main therapeutic options for idiopathic membranous nephropathy (IMN). This study aimed to investigate the association of variants in genes encoding the binding protein and the drug target (calcineurin) of tacrolimus with the efficacy in IMN patients and the potential mechanism. Sixty-seven IMN patients treated with tacrolimus were enrolled retrospectively. Sanger sequencing was performed to search for variants in all exons of the genes in 8 IMN patients and genotype for the detected variants in the other 59 patients. The molecular mechanism underlying the relationship between the variants and the efficacy was explored in human peripheral blood mononuclear cells (PBMCs) and other cell lines. Single nucleotide polymorphism rs875 (T > C) in the 3'untranslated region (3'UTR) of PPP3R1 encoding calcineurin regulatory subunit was found to be associated with the treatment efficacy of tacrolimus for IMN. Patients carrying TT genotype had a significantly higher remission rate than those carrying TC/CC genotype (83% vs. 47%, P = 0.008). Western blot showed that the TT genotype carriers exhibited reduced PPP3R1 protein levels in PBMCs (P = 0.02). Compared with C allele, T allele displayed increased binding affinity for miR-582-5p in the luciferase reporter assay (P < 0.001). Moreover, knockdown of PPP3R1 in Jurkat T cell line enhanced the immunosuppressive effect of tacrolimus. Our study revealed the association of PPP3R1 3'UTR polymorphism rs875 with the efficacy of tacrolimus in IMN patients. The functional polymorphism might alter PPP3R1 expression via modulating the interaction of miR-582-5p with PPP3R1, which further affected the immunosuppressive effect of tacrolimus.
- Association between the HLA-DQA1 rs2187668 polymorphism and risk of idiopathic membranous nephropathy: A PRISMA-compliant meta-analysis. [Journal Article]
- MMedicine (Baltimore) 2018; 97(44):e13031
- CONCLUSIONS: Our pooled analysis showed a significant association between rs2187668-(A) allele and iMN susceptibility, and the intervention of this mutation might bring new therapeutic strategy for iMN. However, further studies should be performed to confirm this finding.
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- Analysis of native kidney biopsy: Data from a single center from Bihar, India. [Journal Article]
- SJSaudi J Kidney Dis Transpl 2018 Sep-Oct; 29(5):1174-1180
- This is a retrospective study of all native kidney biopsies performed at our center between October 1, 2012 and March 31, 2015. Relevant clinical and laboratory variables were recorded. Biopsy sample...
This is a retrospective study of all native kidney biopsies performed at our center between October 1, 2012 and March 31, 2015. Relevant clinical and laboratory variables were recorded. Biopsy samples were processed for light microscopy and immunofluorescence in all cases. Histological classification was adapted from the World Health Organization recommendations. The indications for kidney biopsy were nephrotic syndrome in adults in 190 cases, rapidly progressive renal failure in 43, unexplained renal failure in 25, and steroid-resistant nephrotic syndrome in children in 12. The mean age of the patients was 31.48 ± 13.46 years. Male-to-female ratio was 1.87:1. Mean serum creatinine (SCr) of the patients was 2.36 ± 2.07 mg/dL. Primary glomerulonephritis accounted for 88.89% of cases (240) while secondary glomerulonephritis accounted for 7.40% of total cases (20). Interstitial disease accounted for 1.5% and vascular disease for 2.2%. The most common lesion among primary glomerulonephritis was focal segmental glomerulosclerosis (FSGS) (31.11%) followed by diffuse proliferative glomerulonephritis (DPGN) (13.33%) and membranous glomerulonephritis (MGN) (12.59%). Among secondary glomerulonephritis, lupus nephritis was the most common (5.56%). In patients with SCr 1.4 mg/dL or less (n = 131), FSGS was the most common histology (17.26%) followed by MGN (23.66%) and minimal change disease (7.63%). Whereas, in patients with SCr more than 1.4 mg/dL (n = 139), DPGN was the most common diagnosis (23.74%) followed by FSGS (17.26%) and IgAN (12.23%). Fourteen patients (5.2%) had one or more episode of gross hematuria, three of whom required blood transfusion. The overall FSGS was the most common lesion seen. When we consider only patients with deranged renal function, DPGN was the most common histopathological lesion. The reason for disproportionate high incidence for DPGN is not clear and requires further research.