scholarly journals WNT4 Expression in Primary and Secondary Kidney Diseases: Dependence on Staging

2019 ◽  
Vol 44 (2) ◽  
pp. 200-210 ◽  
Author(s):  
Jolanta Kiewisz ◽  
Agnieszka Skowronska ◽  
Agata Winiarska ◽  
Anna Pawlowska ◽  
Jacek Kiezun ◽  
...  
Keyword(s):  
Gene Expression ◽  
Focal Segmental Glomerulosclerosis ◽  
Kidney Development ◽  
Renal Diseases ◽  
Plasma Sodium ◽  
Mrna Levels ◽  
Glomerular Diseases ◽  
Segmental Glomerulosclerosis ◽  
Renal Biopsies ◽  
Wnt4 Gene

Background/Aims: WNT4 protein is important for kidney development. Its expression was found to be altered in experimental models of chronic kidney disease (CKD). However, the expression of the WNT4 gene has yet not been studied in human renal biopsy samples from patients with broad spectrum of glomerular disease and at different stages of CKD. Thus, the aim of the study was to assess the WNT4 gene expression in renal biopsies of 98 patients using the real-time PCR technique. Materials: In order to assess the relative amounts of mRNA, in samples of patients with manifestation of different renal diseases and separately at different stages of CKD, by QPCR, total RNA was isolated from human kidney tissues collected during renal biopsies. Results of blood and urine samples assessment were used to calculate the correlations of biochemical parameters with WNT4 gene expression in both studied groups. Results: After pathomorphological evaluation, 49 patients were selected as presenting the most common cases in the studied group. Among the patients who developed focal segmental glomerulosclerosis (FSGS; n = 13), IgA nephropathy (IgAN; n = 10), IgAN with morphological presentation of focal segmental glomerulosclerosis (IgAN/FSGS; n = 8), membranous nephropathy (MN; n = 12), and lupus nephritis (LN; n = 6) were included in the analysis. We found that the level of WNT4 mRNA was higher in kidney specimens obtained from patients with MN as compared to those diagnosed with LN or IgAN. A correlation between WNT4 gene expression and serum albumin and cholesterol levels was observed in patients with FSGS, while WNT4 mRNA levels correlated with plasma sodium in patients diagnosed with LN. After consideration of 98 patients, based on the KDIGO classification of CKD, 20 patients were classified as CKD1 stage, 23 as stage 2, 13 as stage 3a, 11 as stage 3b, 13 as stage 4, and 18 as stage 5. WNT4 gene expression was lower in the CKD patients in stage 2 as compared to CKD 3a. Correlations of WNT4 mRNA level at different stages of CKD with indices of kidney function and lipid metabolism such as serum levels of HDL and LDL cholesterol, TG, urea, creatinine, sodium, and potassium were also found. Conclusions: Our results suggest that altered WNT4 gene expression in patients with different types of glomerular diseases and patients at different stages of CKD may play a role in kidney tissue disorganization as well as disease development and progression.

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 Soluble Urokinase Receptors in Focal Segmental Glomerulosclerosis: A Review on the Scientific Point of View

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Andreas Kronbichler ◽  
Moin A. Saleem ◽  
Björn Meijers ◽  
Jae Il Shin
Keyword(s):  
Focal Segmental Glomerulosclerosis ◽  
Point Of View ◽  
Soluble Form ◽  
Glomerular Diseases ◽  
Segmental Glomerulosclerosis ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
End Stage

Focal segmental glomerulosclerosis (FSGS) is one of the primary glomerular disorders in both children and adults which can progress to end-stage renal failure. Although there are genetic and secondary causes, circulating factors have also been regarded as an important factor in the pathogenesis of FSGS, because about 40% of the patients with FSGS have recurrence after renal transplantation. Soluble urokinase-type plasminogen activator receptor (suPAR) is a soluble form of uPAR, which is a membrane-bound protein linked to GPI in various immunologically active cells, including podocytes. It has recently been suggested as a potential circulating factor in FSGS by in vitro podocyte experiments, in vivo mice models, and human studies. However, there have also been controversies on this issue, because subsequent studies showed conflicting results. suPAR levels were also increased in patients with other glomerular diseases and were inversely correlated with estimated glomerular filtration rate. Nevertheless, there has been no balanced review on this issue. In this review, we compare the conflicting data on the involvement of suPAR in the pathogenesis of FSGS and shed light on interpretation by taking into account many points and the potential variables and confounders influencing serum suPAR levels.

scholarly journals The role of interstitial cells in the progression of renal diseases.

1992 ◽  
Vol 2 (10) ◽  
pp. S198 ◽  
Author(s):  
G A Müller ◽  
J Markovic-Lipkovski ◽  
J Frank ◽  
H P Rodemann
Keyword(s):  
Epithelial Cells ◽  
Interstitial Fibrosis ◽  
Interstitial Cells ◽  
Intercellular Adhesion Molecule ◽  
Renal Diseases ◽  
Intercellular Adhesion Molecule 1 ◽  
Glomerular Diseases ◽  
Aberrant Expression ◽  
Hla Dq ◽  
Renal Biopsies

Renal interstitial fibrosis (RIF) is frequently associated with distinct inflammatory and noninflammatory glomerular diseases. RIF is mainly responsible for a decline of excretory renal function and therefore influences the prognosis of several renal diseases. The resident interstitial cells of the kidney, which play a major role in causing RIF, are different renal fibroblasts, which respond to a variety of cytokines released by various cell types. Immunohistochemical analysis of human renal biopsies with different glomerulopathies revealed that CD2+ T lymphocytes are the major cells infiltrating the renal interstitium. In most forms of glomerulonephritis accompanied by interstitial inflammation, an abnormal expression of HLA-DQ/HLA-DP antigens, often associated with an aberrant expression of the intercellular adhesion molecule 1, was observed on proximal tubular epithelial cells, indicating that these cells may play an important role in local immune responses and probably function as antigen-presenting cells. Furthermore, it has been shown by Northern blot analysis that renal epithelial cells in culture express interleukin 6, platelet-derived growth factor and granulocyte-macrophage colony stimulating factor. Cell cultures established from renal biopsies revealed the presence of the three mitotic fibroblast types (MF I through MF III) and the three postmitotic types (PMF IV through PMF VI). The frequencies of the various progenitor fibroblasts MF I, MF II, and MF III differed significantly in cultures established from kidneys with (FKIF cells) and without RIF (NKF cells). In comparison to NKF cells, FKIF cells are characterized by the expression of a "new" protein, called "FIBROSIN," which seems to be specific for FKIF cells.(ABSTRACT TRUNCATED AT 250 WORDS)

P0389THE PREVALENCE, CLINICAL AND PATHOLOGICAL CHARACTERISTICS OF PRIMARY FOCAL SEGMENTAL GLOMERULOSCLEROSIS IN TURKISH ADULTS: THE DATA FROM TSN-GOLD ( TURKISH SOCIETY OF NEPHROLOGY GLOMERULAR DISEASES) WORKING GROUP

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Ilhan Kurultak ◽  
Ozkan Gungor ◽  
Savas Ozturk ◽  
Ahmet Burak Dirim ◽  
Necmi Eren ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Nephrotic Syndrome ◽  
Focal Segmental Glomerulosclerosis ◽  
Pathological Examination ◽  
Glomerular Diseases ◽  
Segmental Glomerulosclerosis ◽  
Hospitalization Period ◽  
The Mean ◽  
Primary Glomerular Diseases ◽  
Turkish Society

Abstract Background and Aims Focal segmental glomerulosclerosis (FSGS) is one of the primary glomerulopathies which is the most common cause of end-stage renal disease among all primary glomerular diseases. In adults, nephrotic syndrome develops 10-35% due to FSGS. However, its frequency has been increasing in recent years. This study was aimed to present the data and the prevalence of primary FSGS patients in Turkey. Method These data were obtained from the National Multicenter (47 centers) Primary Glomerular Diseases registry system, which was entered into the Turkish Society of Nephrology Glomerular Diseases (TSN-GOLD) database between May 2009 and June 2019. The presented data in this study is cross-sectional and includes the recorded data of the patients in the hospitalization period for the kidney biopsy. These demographic, clinic and pathological data of patients were evaluated with using statistically. Results Of the 3875 patients enrolled in the Primary Glomerular Diseases database, 850 (21.9%) had FSGS. The mean age of the patients was 47.1 ± 13.7 and 435 (52%) of patients were male. Two hundred and eighty one (33.1%) had hypertension and 93 (11%) had diabetes. Five hundred and four patients (59.3%) were diagnosed as nephrotic syndrome. At the time of diagnosis, the mean systolic blood pressure was 13.8 ± 18.6 mm Hg and the mean diastolic blood pressure was 81.4± 11.4 mm Hg. The laboratory findings at the time of diagnosis on following; serum creatinine 1.2 ± 0.04 mg / dl, albumin 3.3 ± 0.03 g / dl, and 24 hours urinary proteinuria amounts to 4743 ± 181 mg / day. Demographical and clinical data of the patients at the time of diagnosis were presented on Table 1. In pathological examination; the mean number of glomeruli was 16.8 ± 0.3, global sclerotic glomeruli were 3.1 ± 0.1, and segmental sclerotic glomeruli were 2.4 ± 0.1. Summary of Pathological Findings were presented on Table 2 Conclusion It is very difficult to determine the absolute incidence and prevalence of primary FSGS. Incidence rates have been reported to range from 0.2 to 1.8 / 100,000 per year in the literature. In a United States study, the most common diagnosis in 2501 kidney biopsies was FSGS (35.9%). According to this database, the prevalence of FSGS in primary glomerular diseases in our country is 21.9%.

scholarly journals The transcriptional regulation of Podocin (NPHS2) by Lmx1b and a promoter single nucleotide polymorphism

2009 ◽  
Vol 14 (4) ◽  
Author(s):  
Sigrid Harendza ◽  
Rolf Stahl ◽  
André Schneider
Keyword(s):  
Transcription Factor ◽  
Transcriptional Regulation ◽  
Nephrotic Syndrome ◽  
Focal Segmental Glomerulosclerosis ◽  
Membranous Nephropathy ◽  
Minimal Change ◽  
Renal Diseases ◽  
Single Nucleotide ◽  
Segmental Glomerulosclerosis ◽  
Minimal Change Glomerulonephritis

AbstractPodocin (NPHS2) is a component of the glomerular slit membrane with major regulatory functions in the renal permeability of proteins. A loss of podocin and a decrease in its resynthesis can influence the outcome of renal diseases with nephrotic syndrome, such as minimal change glomerulonephritis, focal segmental glomerulosclerosis (FSGS) and membranous nephropathy. The transcriptional regulation of podocin may play a major role in these processes. We defined the transcriptional regulation of the human podocin gene and the influence of single nucleotide polymorphisms (SNPs) within its promoter region in the podocytes using reporter gene constructs and gel shift analysis. In addition, we took genomic DNA from healthy Caucasian blood donors and from biopsies of kidneys with defined renal diseases and screened it for podocin promoter SNPs. Our data shows that the transcription of podocin is mainly regulated by the transcription factor Lmx1b, which binds to a FLAT-F element and displays enhancer function. With the SNP variant −116T, there was a significant reduction in luciferase activity, and nuclear protein binding was observed, while the SNP −670C/T did not display functionality. The allelic distribution of −116C/T in patients with kidney diseases leading to nephrotic syndrome was not significantly different from that in the control group. Our data indicates that among other factors, podocin is specifically regulated by the transcription factor Lmx1b and by the functional polymorphism -116C/T. However, there is no association between −116C/T and susceptibility to minimal change glomerulonephritis, focal segmental glomerulosclerosis or membranous nephropathy.

scholarly journals Higher Urine Exosomal miR-193a Is Associated With a Higher Probability of Primary Focal Segmental Glomerulosclerosis and an Increased Risk of Poor Prognosis Among Children With Nephrotic Syndrome

2021 ◽  
Vol 9 ◽  
Author(s):  
Lixia Wang ◽  
Jie Wang ◽  
Zhimin Wang ◽  
Jianhua Zhou ◽  
Yu Zhang
Keyword(s):  
Focal Segmental Glomerulosclerosis ◽  
Release Mechanism ◽  
Regulation Mechanism ◽  
Dependent Manner ◽  
Operating Characteristics ◽  
Glomerular Diseases ◽  
Calcium Dependent ◽  
Segmental Glomerulosclerosis ◽  
Increased Risk ◽  
Stage Renal Disease

Background: In children, focal segmental glomerulosclerosis (FSGS) is one of the most common primary glomerular diseases leading to end-stage renal disease. Exosomes facilitate communication between cells by transporting proteins and microRNAs. We aimed to investigate the utility of urine exosomal miR-193a for diagnosis and prognosis estimation among patients with primary FSGS, and preliminarily explore the regulation mechanism of exosome secretion from podocytes.Methods: Specimens of urine were obtained from patients with primary FSGS, minimal change nephropathy (MCN) and IgA nephropathy (IgAN), followed by exosome isolation. We quantified urine exosomal miR-193a based on quantitative reverse transcription-polymerase chain reaction, and evaluated its applicability using area-under-receiver-operating-characteristics curves (AUROCs). The semiquantitative glomerulosclerosis index (GSI) was used to evaluate the degree of glomerulosclerosis according to the method of Raij et al. We further used FAM-labeled miR-193a-5p to examine exosome shuttling using confocal microscopy for visualization, and explored the regulation mechanism of exosomes release from podocytes using Fluo-3AM dye.Results: Urine exosomal miR-193a levels were significantly higher in patients with primary FSGS than those with MCN and IgAN. The AUROCs for discriminating between primary FSGS and MCN or IgAN were 0.85 and 0.821, respectively. Urine exosomal miR-193a levels positively correlated with GSI in patients with primary FSGS. We further found that kidney tissues from these patients had increased CD63 expression involving podocytes in non-sclerotic tufts. Exosomes from cultured podocytes could transport miR-193a-5p to recipient cells, potentially through a calcium-dependent release mechanism.Conclusion: Urine exosomal miR-193a might be harnessed as a non-invasive marker for diagnosis and outcome assessment among patients with primary FSGS. Exosomes were potential vehicles for miRNAs shuttling between podocytes, and released from podocytes in a calcium-dependent manner.

scholarly journals RENAL BIOPSY IN PAEDIATRIC POPULATION

1969 ◽  
Vol 3 (2) ◽  
pp. 314-317
Author(s):  
AHMAD ZEB KHAN ◽  
RIAZ GUL ◽  
AZIZ AHMAD
Keyword(s):  
Nephrotic Syndrome ◽  
Renal Biopsy ◽  
Focal Segmental Glomerulosclerosis ◽  
Minimal Change Disease ◽  
Paediatric Population ◽  
Minimal Change ◽  
Segmental Glomerulosclerosis ◽  
Renal Biopsies ◽  
A Prospective Study ◽  
Nephrotic Range Proteinuria

OBJECTIVE: To find out the pattern of glomerulopathies in paediatric population, undergoing renalbiopsy at Khyber Teaching Hospital, Peshawar.METHODS: This was a prospective study carried out at the department of Nephrology at Khyber TeachingHospital, Peshawar from June 2010 till June 2012. Ultrasound guided percutaneous renal biopsies werecarried out in patients with the finding of; 1 ) Nephrotic range proteinuria in children. 2) Non-Nephroticrange proteinuria with evidence of hypertension / haematuria / deranged renal function or active sedimentson urine microscopy. 3) Steroid resistant nephrotic syndrome in children (patients not responding to steroidin eight weeks time) and 4) Children with nephrotic syndrome who were not tolerant of steroid therapy orwere considered for immunosuppressive drugs.RESULT: A total of 155 renal biopsies were done. Out of these 90 were male patients and 65 were females.The most common histopathological lesion among children population was minimal change disease(42.66%) followed by focal segmental glomerulosclerosis (25.33%) and membranous GN (16.0%). Weobserved that nephrotic range proteinuria was most prevalent in minimal change disease and membranousGN followed by focal segmental glomerulosclerosis. While non-nephrotic range proteinuria was mostlyseen in patients with membranoprolifirative GN.CONCLUSION: In paediatric population, minimal change disease is the most common encounteredglomerulopathy, followed by focal segmental glomerulosclerosisand membranous GN.KEY WORDS: Nephrotic syndrome, Renal biopsy, Proteinuria, Glomerulopathy

scholarly journals Spectrum of Renal Parenchymal Diseases: An Eleven Year Retrospective Review of Renal Biopsy Data from a Tertiary Care Hospital in Pakistan

2017 ◽  
Vol 23 (1) ◽  
Author(s):  
Naila Asif ◽  
Muhammad Nadeem Ahsan ◽  
Shafqat Waqar Khanzada
Keyword(s):  
Renal Biopsy ◽  
Focal Segmental Glomerulosclerosis ◽  
Membranous Nephropathy ◽  
Tertiary Care Hospital ◽  
Tertiary Care ◽  
Glomerular Disease ◽  
Care Hospital ◽  
Glomerular Lesion ◽  
Segmental Glomerulosclerosis ◽  
Renal Biopsies

<p><strong>Objective:</strong><strong>  </strong>To report our experience with renal biopsy and histopathological pattern of renal disease in a tertiary care hospital in Pakistan over 11 years period.</p><p><strong>Methods:</strong><strong>  </strong>All the kidney biopsies performed in our unit from Jan 2001 to Dec 2011 were retrospectively reviewed. We recorded the following data for each patient: name, age, sex, indications for renal biopsy, histopathological diagnosis and lab investigations such as Serum Creatinine, 24 hour urinary protein, urine microscopy, virology (Hbs Ag, Anti HCV) and serology (antids DNA, ANA, C3, C4, C-ANCA and p-ANCA) when indicated. Histopathological examination included Light Microscopy (LM) and Immunofluorescence Microscopy (IF). For LM, six sections were taken and stained with Haemotoxilin and Eosin, and special stains included Periodic acid-Schiff (PAS), Trichome and Grocott’ Smethanamine Silver Stain (GMS). IF study was done using polyclonal antisera against human IgG, IgM, IgA, C3 and Cq. The renal biopsies were performed by a trained Nephrologist.</p><p><strong>Results:</strong><strong>  </strong>A total of 329 consecutive percutaneous renal biopsies of native kidneys were reviewed. A total of thirteen specimens were unsatisfactory. Nineteen cases had incomplete data, therefore were excluded. There were 159 males (53.3%) and 138 females (46.46%). Age distribution showed a total no. of 34 (11.44%) of paediatric cases, 238 (80.13%) adult cases and 25 (10.5 %) elderly cases. The most common clinical indication for renal biopsy was unexplained renal failure (n = 116 39%) followed by nephrotic syndrome (n = 83 27.9%). Of the total biopsies included 248 (82.82%) had glomerular disease and 49 (16.49%) had non glomerular disease. The most frequently found primary glomerular lesion was membranous nephropathy (n = 51 17%) followed by focal segmental glomerulosclerosis (n = 26 8.7%). Amongst the non-glomerular lesions, CIN (chronic interstitial nephritis) was the most frequently found lesion (n = 24 8.08%).</p><p><strong>Conclusion:  </strong>Membranous Nephropathy followed by Focal Segmental Glomerulosclerosis were the most frequently found renal lesion.</p>

scholarly journals Review of Glomerular Diseases: Focal Segmental Glomerulosclerosis (FSGS) and Minimal Change Disease (MCD)

2019 ◽  
pp. 9-17
Author(s):  
Gursharan Kaur Sohi
Keyword(s):  
Focal Segmental Glomerulosclerosis ◽  
Large Scale ◽  
Minimal Change Disease ◽  
Treatment Protocol ◽  
Minimal Change ◽  
Future Research ◽  
Line Treatment ◽  
Glomerular Diseases ◽  
Hand Search ◽  
Segmental Glomerulosclerosis

Purpose: Idiopathic focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) are chronic glomerulopathies which may compromise patients’ quality of life, and for which there is no cure. This literature review aimed to summarize our current understanding of the pathophysiology, clinical characteristics, and best available treatment for the two conditions in order to outline a consolidated treatment protocol and identify future research considerations. Methods: PubMed was systematically searched by a single reviewer in order to identify primary studies pertaining to the diagnosis, treatment and classification of FSGS and MCD. Additionally, a hand search of UpToDate was conducted to glean further information about the best available evidence as summarized for clinician use. Relevant information was extracted and synthesized. Results: Primary FSGS and MCD result from distinct pathogenic mechanisms, hypothesized to involve kidney injury via immune dysregulation. Patients require a kidney biopsy for diagnostic purposes. First-line treatment involves glucocorticoids (i.e. prednisone), although patients’ responsiveness may be inconsistent; second-line treatment is immunotherapy. Conclusion: This review summarized clinically-important information about FSGS and MCD, and emphasized the need for further research in the field of clinical nephrology. Large scale trials such as the Cure Glomerulonephropathy should be conducted to gather information about the affected population.

Breast lobular carcinoma in situ associated podocytopathy

2020 ◽  
Vol 4 (3) ◽  
pp. 132-134
Author(s):  
Abdulrahman Muzib ◽  
Rimda Wanchoo ◽  
Kenar D Jhaveri
Keyword(s):  
Breast Cancer ◽  
Focal Segmental Glomerulosclerosis ◽  
Carcinoma In Situ ◽  
Lobular Carcinoma ◽  
Hematologic Malignancies ◽  
Lobular Carcinoma In Situ ◽  
Glomerular Diseases ◽  
Post Surgery ◽  
Segmental Glomerulosclerosis

Paraneoplastic glomerular diseases are rare. While membranous nephropathy has been classically associated with solid malignancies, minimal change disease has been commonly described with hematologic malignancies. Other podocytopathies such as focal segmental glomerulosclerosis have not been classically associated with solid malignancy. In this case report, we present a case of a 52-year-old female with a diagnosis of focal segmental glomerulosclerosis associated with breast lobular carcinoma in situ. The focal segmental glomerulosclerosis diagnosis preceded the diagnosis of the breast cancer. While the proteinuria came into partial remission with conservative management, a dramatic resolution of focal segmental glomerulosclerosis was noted post-surgery and hormonal therapy for the breast cancer.

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