Trends in the histopathology of childhood nephrotic syndrome in Ibadan Nigeria: preponderance of idiopathic focal segmental glomerulosclerosis

Asinobi, Adanze Onyenonachi; Ademola, Adebowale D.; Okolo, Clement Abu; Yaria, Joseph O.

doi:10.1186/s12882-015-0208-0

Cited by 33 publications

(39 citation statements)

References 39 publications

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“…1960s) to membranoproliferative GN (ca. 1980s) to FSGS (present) (19). The factors responsible for the increasing incidence and prevalence of FSGS are largely unknown.…”

Section: Epidemiology and Global Burdenmentioning

confidence: 99%

Focal Segmental Glomerulosclerosis

Rosenberg

Kopp

2017

CJASN

434

366

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Focal segmental glomerulosclerosis (FSGS) is a leading cause of kidney disease worldwide. The presumed etiology of primary FSGS is a plasma factor with responsiveness to immunosuppressive therapy and a risk of recurrence after kidney transplant-important disease characteristics. In contrast, adaptive FSGS is associated with excessive nephron workload due to increased body size, reduced nephron capacity, or single glomerular hyperfiltration associated with certain diseases. Additional etiologies arenow recognized asdrivers of FSGS: high-penetrance geneticFSGSdue to mutations in one of nearly 40 genes, virus-associated FSGS, and medication-associated FSGS. Emerging data support the identification of a sixth category: APOL1 risk allele-associated FSGS in individuals with sub-Saharan ancestry. The classification of a particular patient with FSGS relies on integration of findings from clinical history, laboratory testing, kidney biopsy, and in some patients, genetic testing. The kidney biopsy can be helpful, with clues provided by features on light microscopy (e.g., glomerular size, histologic variant of FSGS, microcystic tubular changes, and tubular hypertrophy), immunofluorescence (e.g., to rule out other primary glomerulopathies), and electron microscopy (e.g., extent of podocyte foot process effacement, podocyte microvillous transformation, and tubuloreticular inclusions). A complete assessment of renal histology is important for establishing the parenchymal setting of segmental glomerulosclerosis, distinguishing FSGS associated with one of many other glomerular diseases from the clinical-pathologic syndrome of FSGS. Genetic testing is beneficial in particular clinical settings. Identifying the etiology of FSGS guides selection of therapy and provides prognostic insight. Much progress has been made in our understanding of FSGS, but important outstanding issues remain, including the identity of the plasma factor believed to be responsible for primary FSGS, the value of routine implementation of genetic testing, and the identification of more effective and less toxic therapeutic interventions for FSGS.

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“…1960s) to membranoproliferative GN (ca. 1980s) to FSGS (present) (19). The factors responsible for the increasing incidence and prevalence of FSGS are largely unknown.…”

Section: Epidemiology and Global Burdenmentioning

confidence: 99%

Focal Segmental Glomerulosclerosis

Rosenberg

Kopp

2017

CJASN

434

366

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“…A study among children in Ibadan, in south-western Nigeria, yielded only 56 biopsies in eight years. The authors noted that renal biopsy was limited to patients who could afford it [11]. Okpechi et al reported a low rate of renal biopsies in their review of renal biopsies across Africa.…”

Section: Discussionmentioning

confidence: 99%

“…There is poor consensus on the indications for renal biopsies in children [15]. For instance, in Ibadan, there was a shift in the indication based on the trend of prevailing causes of nephrotic syndrome [11]. Nephrotic syndrome is the commonest indication for renal biopsy in most centres in Nigeria.…”

Section: Discussionmentioning

confidence: 99%

Clinicopathological report of children and young adults with nephrotic syndrome undergoing renal biopsy at workshops in Port Harcourt, Nigeria

Obiorah

Okoro

2018

AJN

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Background: Kidney biopsy is a procedure that is not commonly performed in Nigeria. This study reports the clinical and pathological findings in children who underwent renal biopsies during nephrology workshops held in Port Harcourt in 2014 and 2015. Methods: The native kidney biopsies were processed and evaluated using light microscopy only. Results: Nineteen patients (10 females) were biopsied. The mean age was 11.0 ± 6.5 years and the range was 1.8 to 21 years. Eleven patients had steroid-dependent nephrotic syndrome (SDNS) whereas eight were steroidresistant (SRNS). Hypertension and haematuria were present more often in SDNS. There were 11 cases (58%) with non-proliferative lesions, including minimal change disease (4 cases), focal segmental glomerulosclerosis (4 cases) and collapsing glomerulopathy (3 cases). The proliferative lesions (8 cases) included membranoproliferative (mesangiocapillary) glomerulonephritis (MPGN, 5 cases), mesangial proliferative glomerulonephritis (2 cases) and MPGN with collapsing glomerulopathy (1 case). Overall, the most common pathological diagnosis was MPGN (26%). Hypertension was more common with proliferative than with non-proliferative lesions (63% versus 36%). Conclusions: Although MPGN was the most common morphological lesion among children with nephrotic syndrome, bigger studies are necessary to confirm this. Efforts should be intensified in acquiring the expertise and infrastructure for performing and interpreting renal biopsies in Port Harcourt in order to optimize patient management.

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“…There is a trend of increasing incidence of FSGS caused ESRD in the United States (3) and world (4).…”

Section: Introductionmentioning

confidence: 99%

A Bigenic mouse model of FSGS reveals perturbed pathways in podocytes, mesangial cells and endothelial cells

Potter

Drake

Brunskill

et al. 2019

Preprint

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Short Title: Perturbed molecular pathways in bigenic mouse model of focal segmental glomerulosclerosis AbstractFocal segmental glomerulosclerosis is a major cause of end stage renal disease. Many patients prove unresponsive to available therapies. An improved understanding of the molecular basis of the disease process could provide insights leading to novel therapeutic approaches. In this study we carried out an RNA-seq analysis of the altered gene expression patterns of podocytes, mesangial cells and glomerular endothelial cells of the bigenic Cd2ap+/-, Fyn-/-mutant mouse model of FSGS. In the podocytes we observed upregulation of many genes related to the Tgf family/pathway, including Gdnf, Tgf1, Tgf2, Snai2, Vegfb, Bmp4, and Tnc. The mutant podocytes also showed upregulation of Acta2, a marker of smooth muscle and associated with myofibroblasts, which are implicated in driving fibrosis.GO analysis of the podocyte upregulated genes identified elevated protein kinase activity, increased expression of growth factors, and negative regulation of cell adhesion, perhaps related to the observed podocyte loss. Both podocytes and mesangial cells showed strong upregulation of aldehyde dehydrogenase genes involved in the synthesis of retinoic acid.Similarly, the Cd2ap+/-, Fyn-/-mesangial cells, as well as podocytes in other genetic models, and the glomeruli of human FSGS patients, all show upregulation of the serine protease Prss23, with the common thread suggesting important functionality. Another gene with strong upregulation in the Cd2ap+/-, Fyn-/-mutant mesangial cells as well as multiple other mutant mouse models of FSGS was thrombospondin, which activates the secreted inactive form of Tgf. The Cd2ap+/-, Fyn-/-mutant endothelial cells showed elevated expression of genes involved in cell proliferation, angioblast migration, angiogenesis, and neovasculature, all consistent with the formation of new blood vessels in the diseased glomerulus. The resulting global definition of the perturbed molecular pathways in the three major cell types of the mutant glomerulus provide deeper understanding of the molecular pathogenic pathways.

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Trends in the histopathology of childhood nephrotic syndrome in Ibadan Nigeria: preponderance of idiopathic focal segmental glomerulosclerosis

Cited by 33 publications

References 39 publications

Focal Segmental Glomerulosclerosis

Focal Segmental Glomerulosclerosis

Clinicopathological report of children and young adults with nephrotic syndrome undergoing renal biopsy at workshops in Port Harcourt, Nigeria

A Bigenic mouse model of FSGS reveals perturbed pathways in podocytes, mesangial cells and endothelial cells

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