scholarly journals Hydroxypropyl-β-cyclodextrin protects from kidney disease in experimental Alport syndrome and focal segmental glomerulosclerosis

2018 ◽  
Vol 94 (6) ◽  
pp. 1151-1159 ◽  
Author(s):  
Alla Mitrofanova ◽  
Judith Molina ◽  
Javier Varona Santos ◽  
Johanna Guzman ◽  
Ximena A. Morales ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Focal Segmental Glomerulosclerosis ◽  
Alport Syndrome ◽  
Segmental Glomerulosclerosis

scholarly journals Utility of Genomic Testing after Renal Biopsy

2019 ◽  
Vol 51 (1) ◽  
pp. 43-53
Author(s):  
Susan L. Murray ◽  
Anthony Dorman ◽  
Katherine A. Benson ◽  
Dervla M. Connaughton ◽  
Caragh P. Stapleton ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Kidney Disease ◽  
Renal Biopsy ◽  
Focal Segmental Glomerulosclerosis ◽  
Alport Syndrome ◽  
Kidney Biopsy ◽  
Genetic Diagnosis ◽  
Pathological Diagnosis ◽  
Genetic Sequencing ◽  
Segmental Glomerulosclerosis

Background: Renal biopsy is the mainstay of renal pathological diagnosis. Despite sophisticated diagnostic techniques, it is not always possible to make a precise pathological diagnosis. Our aim was to identify a genetic cause of disease in patients who had undergone renal biopsy and determine if genetic testing altered diagnosis or treatment. Methods: Patients with suspected familial kidney disease underwent a variety of next-generation sequencing (NGS) strategies. The subset of these patients who had also undergone native kidney biopsy was identified. Histological specimens were reviewed by a consultant pathologist, and genetic and pathological diagnoses were compared. Results: Seventy-five patients in 47 families underwent genetic sequencing and renal biopsy. Patients were grouped into 5 diagnostic categories based on pathological diagnosis: tubulointerstitial kidney disease (TIKD; n = 18); glomerulonephritis (GN; n = 15); focal segmental glomerulosclerosis and Alport Syndrome (n = 11); thrombotic microangiopathy (TMA; n = 17); and nonspecific pathological changes (n = 14). Thirty-nine patients (52%) in 21 families (45%) received a genetic diagnosis; 13 cases (72%) with TIKD, 4 (27%) with GN, 6 (55%) with focal segmental glomerulosclerosis/Alport syndrome, and 10 (59%) with TMA and 6 cases (43%) with nonspecific features. Genetic testing resulted in changes in understanding of disease mechanism in 21 individuals (54%) in 12 families (57%). Treatment would have been altered in at least 26% of cases (10/39). Conclusions: An accurate genetic diagnosis can result in changes in clinical diagnosis, understanding of pathological mechanism, and treatment. NGS should be considered as a complementary diagnostic technique to kidney biopsy in the evaluation of patients with kidney disease.

scholarly journals Dapagliflozin in focal segmental glomerulosclerosis: a combined human-rodent pilot study

2018 ◽  
Vol 314 (3) ◽  
pp. F412-F422 ◽  
Author(s):  
Harindra Rajasekeran ◽  
Heather N. Reich ◽  
Michelle A. Hladunewich ◽  
Daniel Cattran ◽  
Julie A. Lovshin ◽  
...  
Keyword(s):  
Pilot Study ◽  
Kidney Disease ◽  
Focal Segmental Glomerulosclerosis ◽  
Plasma Flow ◽  
Renal Plasma Flow ◽  
Short Term Treatment ◽  
Segmental Glomerulosclerosis ◽  
Renal Hemodynamic ◽  
Hemodynamic Function ◽  
The Impact

Focal segmental glomerulosclerosis (FSGS) is an important cause of nondiabetic chronic kidney disease (CKD). Sodium-glucose cotransporter 2 inhibition (SGLT2i) therapy attenuates the progression of diabetic nephropathy, but it remains unclear whether SGLT2i provides renoprotection in nondiabetic CKD such as FSGS. The primary aim of this pilot study was to determine the effect of 8 wk of dapagliflozin on glomerular filtration rate (GFR) in humans and in experimental FSGS. Secondary end points were related to changes in renal hemodynamic function, proteinuria, and blood pressure (BP). GFR (inulin) and renal plasma flow (para-aminohippurate), proteinuria, and BP were measured in patients with FSGS ( n = 10), and similar parameters were measured in subtotally nephrectomized (SNx) rats. In response to dapagliflozin, changes in GFR, renal plasma flow, and 24-h urine protein excretion were not statistically significant in humans or rats. Systolic BP (SBP) decreased in SNx rats (196 ± 26 vs. 165 ± 33 mmHg; P < 0.001), whereas changes were not statistically significant in humans (SBP 112.7 ± 8.5 to 112.8 ± 11.2 mmHg, diastolic BP 71.8 ± 6.5 to 69.6 ± 8.4 mmHg; P = not significant), although hematocrit increased (0.40 ± 0.05 to 0.42 ± 0.05%; P = 0.03). In archival kidney tissue from a separate patient cohort, renal parenchymal SGLT2 mRNA expression was decreased in individuals with FSGS compared with controls. Short-term treatment with the SGLT2i dapagliflozin did not modify renal hemodynamic function or attenuate proteinuria in humans or in experimental FSGS. This may be related to downregulation of renal SGLT2 expression. Studies examining the impact of SGLT2i on markers of kidney disease in patients with other causes of nondiabetic CKD are needed.

scholarly journals Chronic kidney disease: a review of proteomic and metabolomic approaches to membranous glomerulonephritis, focal segmental glomerulosclerosis, and IgA nephropathy biomarkers

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Amir Taherkhani ◽  
Reyhaneh Farrokhi Yekta ◽  
Maede Mohseni ◽  
Massoud Saidijam ◽  
Afsaneh Arefi Oskouie
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Iga Nephropathy ◽  
Focal Segmental Glomerulosclerosis ◽  
Membranous Glomerulonephritis ◽  
Renal Diseases ◽  
Segmental Glomerulosclerosis ◽  
Therapeutic Procedures ◽  
Definition Of ◽  
End Stage

AbstractChronic Kidney Disease (CKD) is a global health problem annually affecting millions of people around the world. It is a comprehensive syndrome, and various factors may contribute to its occurrence. In this study, it was attempted to provide an accurate definition of chronic kidney disease; followed by focusing and discussing on molecular pathogenesis, novel diagnosis approaches based on biomarkers, recent effective antigens and new therapeutic procedures related to high-risk chronic kidney disease such as membranous glomerulonephritis, focal segmental glomerulosclerosis, and IgA nephropathy, which may lead to end-stage renal diseases. Additionally, a considerable number of metabolites and proteins that have previously been discovered and recommended as potential biomarkers of various CKDs using ‘-omics-’ technologies, proteomics, and metabolomics were reviewed.

scholarly journals Sex and kidney ACE2 expression in primary focal segmental glomerulosclerosis: A NEPTUNE study

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0252758
Author(s):  
Nicholas A. Maksimowski ◽  
James W. Scholey ◽  
Vanessa R. Williams ◽  
Keyword(s):  
Kidney Disease ◽  
Focal Segmental Glomerulosclerosis ◽  
Current Knowledge ◽  
Interstitial Fibrosis ◽  
Linear Regression Analysis ◽  
Renin Angiotensin System ◽  
Multiple Linear Regression Analysis ◽  
Tubular Atrophy ◽  
Kidney Fibrosis ◽  
Segmental Glomerulosclerosis

Background Angiotensin-converting enzyme 2 (ACE2) has been implicated in the pathogenesis of experimental kidney disease. ACE2 is on the X chromosome, and in mice, deletion of ACE2 leads to the development of focal segmental glomerulosclerosis (FSGS). The relationship between sex and renal ACE2 expression in humans with kidney disease is a gap in current knowledge. Methods We studied renal tubulointerstitial microarray data and clinical variables from subjects with FSGS enrolled in the Nephrotic Syndrome Study Network (NEPTUNE) study. We compared relationships between ACE2 expression and age, estimated glomerular filtration rate (eGFR), urinary albumin to creatinine ratio (UACR), interstitial fibrosis, tubular atrophy, and genes implicated in inflammation and fibrosis in male and female subjects. Results ACE2 mRNA expression was lower in the tubulointerstitium of males compared to females (P = 0.0026). Multiple linear regression analysis showed that ACE2 expression was related to sex and eGFR but not to age or treatment with renin angiotensin system blockade. ACE2 expression is also related to interstitial fibrosis, and tubular atrophy, in males but not in females. Genes involved in inflammation (CCL2 and TNF) correlated with ACE2 expression in males (TNF: r = -0.65, P < 0.0001; CCL2: r = -0.60, P < 0.0001) but not in females. TGFB1, a gene implicated in fibrosis correlated with ACE2 in both sexes. Conclusions Sex is an important determinant of ACE2 expression in the tubulointerstitium of the kidney in FSGS. Sex also influences the relationships between ACE2, kidney fibrosis, and expression of genes involved in kidney inflammation.

scholarly journals Proteomic profile of mesothelial exosomes isolated from peritoneal dialysis effluent of children with focal segmental glomerulosclerosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maurizio Bruschi ◽  
Edoardo La Porta ◽  
Isabella Panfoli ◽  
Giovanni Candiano ◽  
Andrea Petretto ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Kidney Disease ◽  
Focal Segmental Glomerulosclerosis ◽  
Mass Spectrometry Analysis ◽  
Causative Role ◽  
Focal Segmental Glomerular Sclerosis ◽  
Segmental Glomerulosclerosis ◽  
Potential Biomarker ◽  
Increased Risk ◽  
Peritoneal Dialysis Effluent

AbstractPeritoneal dialysis (PD) is the worldwide recognized preferred dialysis treatment for children affected by end-stage kidney disease (ESKD). However, due to the unphysiological composition of PD fluids, the peritoneal membrane (PM) of these patients may undergo structural and functional alterations, which may cause fibrosis. Several factors may accelerate this process and primary kidney disease may have a causative role. In particular, patients affected by steroid resistant primary focal segmental glomerulosclerosis, a rare glomerular disease leading to nephrotic syndrome and ESKD, seem more prone to develop peritoneal fibrosis. The mechanism causing this predisposition is still unrecognized. To better define this condition, we carried out, for the first time, a new comprehensive comparative proteomic mass spectrometry analysis of mesothelial exosomes from peritoneal dialysis effluent (PDE) of 6 pediatric patients with focal segmental glomerular sclerosis (FSGS) versus 6 patients affected by other primary renal diseases (No FSGS). Our omic study demonstrated that, despite the high overlap in the protein milieu between the two study groups, machine learning allowed to identify a core list of 40 proteins, with ANXA13 as most promising potential biomarker, to distinguish, in our patient population, peritoneal dialysis effluent exosomes of FSGS from No FSGS patients (with 100% accuracy). Additionally, the Weight Gene Co-expression Network Analysis algorithm identified 17 proteins, with PTP4A1 as the most statistically significant biomarker associated to PD vintage and decreased PM function. Altogether, our data suggest that mesothelial cells of FSGS patients are more prone to activate a pro-fibrotic machinery. The role of the proposed biomarkers in the PM pathology deserves further investigation. Our results need further investigations in a larger population to corroborate these findings and investigate a possible increased risk of PM loss of function or development of encapsulating peritoneal sclerosis in FSGS patients, thus to eventually carry out changes in PD treatment and management or implement new solutions.

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