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Results for “Focal segmental glomerulosclerosis”

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At least 19 recordsLinked to original sources

PubMed1994

Glomerular hypertrophy and chronic renal failure in focal segmental glomerulosclerosis.

Focal segmental glomerulosclerosis evolves toward chronic renal failure (CRF) with a highly variable rate; in particular, a group of patients with a much more rapid decline of renal function has been described. The purpose of this study was to evaluate the usefulness of morphometry in identifying those cases with a faster decline in renal function. Two groups of patients have been studied: six with rapid evolution toward CRF (group 1) and six without reduction in renal function during a follow-up of up to 10 years (group 2). The results of the morphometric analysis of glomeruli were as follows: mean glomerular area: 30,550 +/- 5,259 microns2 (group 1) versus 22,667 +/- 5,078 microns2 (group 2) (P = 0.01); maximum glomerular area: 40,827 +/- 9,508 microns2 (group 1) versus 30,445 +/- 7,224 microns2 (group 2) (P = 0.02); mean glomerular diameter: 193.9 +/- 15.8 microns (group 1) versus 161.8 +/- 16.8 microns (group 2) (P = 0.003); and caliper diameter: 328.6 +/- 20.6 microns (group 1) versus 260.6 +/- 36 microns (group 2) (P = 0.001). Values of body surface area were not different between the two groups (1.85 +/- 0.34 m2 v 1.6 +/- 0.13 m2) (P = NS). Our results suggest that glomerular hypertrophy in the course of focal segmental glomerulosclerosis is correlated with a faster decline toward CRF. It might represent a compensatory hypertrophy that would immediately precede a rapid decline in renal function or it might be the expression of the preexisting condition (meganephronia), which predisposes to the development of CRF.

Adult↗

PubMed2006

The bioactivity of plasma factors in focal segmental glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS) is a devastating form of nephrotic syndrome, often leading to end-stage renal failure after the failure of a succession of highly toxic therapies. It has long been thought to be caused by a circulating factor(s) that may be produced by cells of the immune system. Much research has focused on identifying such factor(s), including the development of a promising in vitro assay, which estimates glomerular permeability based on the swelling of isolated glomeruli in response to patients' plasma. This assay has also been used as the basis of testing plasma fractions for permeability activity, with no specific factor yet identified. Other studies have attempted to replicate proteinuria in whole animals, by injecting plasma or plasma fractions from focal segmental glomerulosclerosis patients, with inconsistent results. More recently there has been evidence that there may be either inhibitory or missing factor(s) in plasma, with respect to permeability. An additional major biological advance is a growing appreciation of the podocyte as the target cell in this disease, and an understanding of the key molecules involved. Putting together this knowledge, with the latest technological advances in protein identification, provides promising avenues towards finally solving the basis of this enigmatic disease.

Animals↗

PubMed1984

Focal segmental glomerulosclerosis.

Focal segmental glomerulosclerosis is an important cause of the nephrotic syndrome in children and adults. This paper reviews the pathogenesis, clinical manifestations, morphology, and treatment of focal glomerulosclerosis. In addition, it considers the recently described association of focal glomerulosclerosis with nonglomerular renal diseases and the possible role of this glomerular lesion in progressive renal failure.

Glomerulonephritis↗

PubMed2007

Pathophysiology of focal segmental glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS) is a major cause of idiopathic steroid-resistant nephrotic syndrome (SRNS) and end-stage kidney disease (ESKD). In recent years, animal models and studies of familial forms of nephrotic syndrome helped elucidate some mechanisms of podocyte injury and disease progression in FSGS. This article reviews some of the experimental and clinical data on the pathophysiology of FSGS.

Animals↗

PubMed2004

[Focal segmental glomerulosclerosis].

Focal segmental glomerulosclerosis (FSGS) is one of the major causes of nephrotic syndrome in adult as well as in the children. Untreated or steroid-resistant primary FSGS often shows a progressive renal insufficiency and reaches to end-stage renal failure. Concerning the treatment for such patients, the combined immunosuppressive therapy with corticosteroid and other cytotoxic drugs (cyclophosphamide, cyclosporine and tacrolimus etc.) is recommended. Since podocyte injury seems to be the most important primary events in FSGS, the extensive studies have been focused on the role of podocyte-related molecules. Recently slit membrane-associated molecules (CD2AP, alpha-actinin 4 and podocin) and angiotensin II type I receptor in the podocyte have been clearly shown to be relevant for the pathogenesis of FSGS.

Actinin↗

PubMed2000

Treatment of focal segmental glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS) has been increasing in incidence over the past 2 decades and may currently be the most common form of primary nephrotic syndrome in the United States. Nephrotic patients with FSGS who do not achieve a remission in proteinuria usually advance to end-stage renal disease within 5 to 10 years. Although initially felt to be a steroid-resistant disease, especially in adults, studies show significant responsiveness to more prolonged courses of steroids. For patients with steroid-resistant or steroid-dependent FSGS, cyclosporine A and cytotoxic agents have shown efficacy in clinical trials. Other agents used include pulse methylprednisolone, azathioprine, tacrolimus, mycophenolate mofetil, and combination therapy. For recurrent FSGS after renal transplantation, plasmapheresis is often used but appears not to be as efficacious in adults as in the pediatric population.

Adult↗

PubMed1995

Glomerular metalloprotease activity modulates the development of focal segmental glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS) is a common outcome of a variety of renal diseases. Among laboratory animals both puromycin aminonucleoside (PAN) and hypertension produce a similar histological pattern. Since mesangial expansion is a precursor of FGS and decreased degradation of matrix can cause expansion of mesangium we studied the glomerular matrix metalloprotease activities in the development of FSGS. Dahl salt sensitive (SS) and salt resistant (SR) rats were fed 8% salt diet for six weeks. Kidney biopsy showed features of FSGS in SS rats. Glomeruli were isolated and metalloprotease activity was measured. Sprague-Dawley rats were administered subcutaneously either saline (S) or saline containing PAN (1.67 mg/100 g B. W.) daily for 7 days. Kidney biopsy was done at day 7 and the isolation of glomeruli was performed at day 10 and at 6 weeks. Renal histology showed features of FSGS in PAN rats at 6 weeks. Glomerular metalloprotease activity was decreased in SS (SR, 148 +/- 12 vs. SS, 73 +/- 9 cpm/microgram protein, p < 0.01) as well as in PAN rats (S, 31 +/- 5 vs. PAN, 12 +/- 1 cpm/microgram protein, p < 0.01). These results suggest that decreased glomerular metalloprotease activity may play a role in the development of FSGS in SS and PAN rats.

Animals↗

PubMed2026

Disease-driven post-transcriptional alterations and alternative splicing in podocytes in focal segmental glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS) is a major cause of nephrotic syndrome and progression to end-stage renal disease, yet its molecular pathogenesis remains still incompletely defined. While transcriptional alterations in podocytes have been extensively characterized, the contribution of post-transcriptional regulatory mechanisms is poorly understood. Here, we combined a zebrafish podocyte-specific injury model with glomerulus-resolved transcriptomic profiling to dissect RNA regulatory alterations during FSGS progression. Integrated analyses of bulk RNA sequencing, small RNA profiling, and alternative splicing revealed pronounced, time-dependent remodeling of the glomerular transcriptome. We demonstrate that podocyte injury is associated with loss of key podocyte-specific proteins, activation of inflammatory pathways, remodeling of the extracellular matrix, and altered microRNA expression, such as miR-21 and miR-193. Moreover, we found that alternative splicing influences key podocyte gene expression, affecting genes critical for slit diaphragm integrity, actin cytoskeleton organization, and glomerular basement membrane stability. Isoform analyses identified FSGS-associated isoform switches in SRSF3 and EPB41L5. Importantly, these changes were also evident in glomeruli from FSGS patients, demonstrating that the zebrafish model recapitulates key molecular features of human disease and highlighting alternative splicing as a central regulatory mechanism in FSGS.

Animals↗

PubMed1995

A morphometric study of preeclamptic nephropathy with focal segmental glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS) is observed in severe or atypical preeclamptic patients biopsied postpartum. To further define the structural characteristics that might be related to atypical clinical manifestations in this disorder, we analyzed the postpartum renal biopsies of eight preeclamptic patients with FSGS by morphometry and studied the structural-functional relationships. For comparison, three postpartum biopsies with primary FSGS and eight nonpregnant subjects with primary FSGS were also studied. Mesangial volume fraction was increased in the preeclamptic FSGS group being 2 times that of the pregnant or nonpregnant primary FSGS group. Mean surface density of peripheral glomerular basement membrane (PGBM) per glomerulus was markedly decreased in the preeclampsia group being 1/3 that for the pregnant or nonpregnant primary FSGS group. Volume density of cortical interstitium in the preeclamptic FSGS was smaller than that of the primary FSGS group. In preeclamptic FSGS, mesangial volume fraction correlated inversely with PGBM surface area (r = -0.84; p < 0.01) and with creatinine clearance (Ccr) (r = -0.63; p < 0.05). PGBM surface area per glomerulus in preeclamptic FSGS correlated with Ccr (r = +0.63; p < 0.05). Mean volume density of cortical interstitium was not related to Ccr nor with the percentage of glomeruli with FSGS in preeclamptic FSGS. These results suggest that decreased glomerular filtration function in atypical preeclampsia is linked to decreased PGBM surface area, that results from mesangial expansion and particularly from mesangial interposition.

Adult↗

PubMed1999

[Comparative study of two immunosuppressive treatment methods in patients with focal segmental glomerulosclerosis].

Focal segmental glomerulosclerosis (FSGS) is a glomerular disease of varying severity. Most patients, however, develop end-stage renal failure within 10 years from clinical onset. In this retrospective study, the outcome of immunosuppressive treatment in 22 adult patients with biopsy-proven primary FSGS was evaluated. Eleven patients were treated with prednisone, azathioprine and chlorambucil (group A) and 11 with prednisone and pulse cyclophosphamide (group B). The nephrotic syndrome (NS) was found in 4 patients from the group A and in 3 patients from the group B, arterial hypertension in 8 and 9 patients, respectively. During the follow-up lasting about 50 months as the mean, 70% of the patients did not respond to the treatment and complete remission was obtained only in 3 patients from the group B. On the other hand, 7 patients progressed into CFR. Among them, 5 out of 7 patients with NS (4 from the group A) needed dialysis treatment or doubled their Pcr after a mean of 38 months. This study confirms poor outcome of immunosuppressive treatment in patients with FSGS. However, of the two forms of treatment used in the study, the response appeared to be better and more lasting with cyclophosphamide than with azathioprine and chlorambucil. Corticosteroids associated with pulse cyclophosphamide therapy seems to improve the chances of remission and to protect from renal dysfunction.

Adult↗

PubMed2005

Treatment of focal segmental glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS) is not a disease, but a lesion affecting the podocyte. Secondary FSGS may be due to a host of various factors, and patients are rarely nephrotic, requiring symptomatic treatment only. The best prognostic feature of nephrotic FSGS is its response to corticosteroids. Some forms are most likely of immunological origin, relapse in a renal transplant and justify immunosuppressive treatment. In a growing number of cases, genetic profiling of molecules that contribute to the podocyte slit diaphragm permselectivity to albumin has identified defects that do not represent indications for immunosuppression. In the other forms, corticosteroids and cyclosporin A (CsA) remain the mainstay of treatment, with better efficacy when CsA is associated with steroids. The renal tolerability of CsA is reasonably good when the dosage is low. CsA dependency is not constant. Alkylating agents are reluctantly indicated in steroid-sensitive forms, which are rare. They are mostly ineffective in steroid-resistant forms. Tacrolimus seems a promising therapy with low toxicity, but it is usual for dependency on the drug to occur. Sirolimus seems to be ineffective. Azathioprine is not considered indicated, despite rare reports with favourable results, which would deserve further controlled trials. Recent publications indicate that mycophenolate mofetil might usefully find a place in the treatment. Plasmapheresis is of no avail outside the special case of relapse in a transplanted kidney. Immunoabsorption of the elusive substance that causes the nephrotic syndrome and its relapse on a transplant has not led to practical treatment options.

Alkylating Agents↗

PubMed2000

Parvovirus B19 DNA in kidney tissue of patients with focal segmental glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS) represents a clinicopathological syndrome with diverse causes. We examined the possibility that some cases of FSGS are associated with parvovirus B19 infection. We studied renal biopsy tissue from 40 patients, including those with idiopathic FSGS, collapsing FSGS, membranous nephropathy, and minimal change disease, as well as normal renal tissue removed at the time of nephrectomy from 4 patients. DNA was extracted from frozen blocks of kidney tissue and amplified using nested polymerase chain reaction. Parvovirus B19 DNA was amplified from 8 of 10 patients with idiopathic FSGS, 9 of 10 patients with collapsing FSGS, 6 of 10 patients with membranous nephropathy, 5 of 10 patients with minimal change disease, and 2 of 4 cancer nephrectomy samples. The prevalence of parvovirus B19 DNA was greater among patients with idiopathic FSGS and collapsing FSGS compared with patients with other diagnoses (P = 0.05). In situ hybridization studies using digoxigenin-labeled DNA probes failed to detect parvovirus B19 nucleic acid in any of the kidney tissue samples. These results suggest that parvovirus B19 DNA is commonly found in the kidneys of patients with a range of renal diagnoses, possibly representing latent DNA from past infection. The failure to localize parvovirus B19 nucleic acid within kidney argues against ongoing, high-level viral replication. Nevertheless, the increased prevalence of B19 DNA in patients with idiopathic FSGS and collapsing FSGS could indicate a pathogenic role for the virus in the cause of FSGS in certain patients.

Biopsy↗

PubMed2000

Genetic polymorphism in paraoxonase is a risk factor for childhood focal segmental glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS) is an important cause of end-stage renal failure (ESRF) in children. Our previous studies have shown that Arab children in Israel have a worse prognosis compared with Jewish patients despite similar clinical presentation and management. Progression of proteinuric glomerular diseases has been associated with alterations in lipid metabolism, and similarities have been drawn between the mechanisms underlying atherosclerosis and glomerulosclerosis. Paraoxonase (PON) is a high-density lipoprotein (HDL)-associated enzyme involved in preventing the oxidation of low-density lipoprotein (LDL), and an association has been shown between two genetic polymorphisms in PON1 and the risk of coronary artery disease. The aim of this study was to determine the frequency of these genetic polymorphisms in PON1 in Arab and Jewish children with FSGS and to determine any association with severity of outcome. Forty-seven children (21 Arab and 26 Jewish) with biopsy-proven FSGS and 274 healthy controls of matching ethnic origin were studied. The glutamine (A)-192-arginine (B) and the methionine (M)-55-leucine (L) polymorphisms were analyzed. The frequency of the A allele was similar in patients and controls (0.68 versus 0.71), as was that of the L allele (0.63 versus 0.6). When subgroups were analyzed, the prevalence of the LL genotype in Arab patients was significantly greater than in Jewish patients (57.1% versus 26.9%, P: < 0.05) and Arab controls (57.1% versus 28.9%, P: < 0.03). A trend in association was found between homozygosity for the L allele and progression of renal disease in Arab children. Homozygosity for the L allele is a risk factor for developing FSGS in Arab children and may be associated with a worse prognosis.

Adolescent↗

PubMed2001

Long-term outcome of kidney transplantation in adult recipients with focal segmental glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS) is an important cause of nephrotic syndrome and end-stage renal disease. FSGS recurrence after renal transplantation has a potentially detrimental course leading to the loss of renal function. In order to establish FSGS recurrence rates and evaluate the course of the disease on living-related-donor renal transplantation in ethnic Korean adults (> or = 18 years), we reviewed our experiences of 27 kidney transplantations with FSGS over the last 15 years. Of the 27 renal allografts, 13 were found to have recurrent FSGS by graft biopsy. In comparison with background data upon patients with and without recurrence of FSGS, the donor age of patients with recurrent FSGS was significantly higher than that of those without recurrence (median, 39 years vs 26, p < 0.05). In terms of, age at transplantation, length of dialysis period, and mode of dialysis no differences were found between recurrent and nonrecurrent cases. The graft survival rate of recipients from a kidney donor of age less than 40 years was significantly higher than that of recipients from a kidney donor of age more than 40 years, at 5 and 10 years, respectively (87% vs 33%, 41% vs 0%, p < 0.05). The association between clinical variables and recurrence was assessed by multiple logistic regression analysis, and donor age was found to be a risk factor of FSGS recurrence (p<0.05). Variables such as HLA-mismatch numbers and immunosuppression were not found to be associated. In conclusion, the recurrence rate of FSGS in adult recipients with FSGS was 48% and patients that received kidney from an older donor appear to be at higher risk of developing recurrence. The use of a renal graft from a younger donor is considered advisable for adult recipients with FSGS.

Adult↗

PubMed2003

Pathologic classification of focal segmental glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS) is defined as a clinical-pathologic syndrome manifesting proteinuria and focal and segmental glomerular sclerosis with foot process effacement. The pathologic approach to the classification of FSGS is complicated by the existence of primary (idiopathic) forms and multiple subcategories with etiologic associations, including human immunodeficiency virus (HIV)-associated nephropathy, heroin nephropathy, familial forms, drug toxicities, and a large group of secondary FSGS mediated by structural-functional adaptations to glomerular hyperfiltration. A number of morphologic variants of primary and secondary focal sclerosis are now recognized, including FSGS not otherwise specified (NOS), perihilar, cellular, tip, and collapsing variants. The defining features of these morphologic variants and of the major subcategories of FSGS are discussed with emphasis on distinguishing light microscopic patterns and clinical-pathologic correlations.

Disease Progression↗

PubMed2005

Mechanisms of disease: focal segmental glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS), a subtype of "idiopathic nephrotic syndrome", is not a single disease, but a lesion that initially affects the glomerulus followed by the tubulointerstitium and renal vessels. The term 'FSGS' does not accurately encompass the various pathologic features of the glomerulus, which are not always focal, segmental or sclerotic. Particular variants of FSGS, such as collapsing glomerulopathy and the glomerular tip lesion, exemplify the nosologic uncertainty inherent in the classification of glomerular lesions. Pathologic variation notwithstanding, all pathologic processes that affect the podocyte lead to one of the histologic subtypes of FSGS. This specialized cell type has essential roles in maintaining the integrity of glomerular architecture, resisting endocapillary hydraulic pressure and hindering egress of proteins into the urinary space. Once initiated, podocyte lesions and ensuing fibrosis are usually irreversible, at least in human forms of FSGS. Remarkable progress has been made in unraveling the mechanisms of podocyte dysregulation that accompany the cellular variants of FSGS and in identifying genetic mutations affecting proteins of the slit diaphragm. Hopefully, this progress will drastically improve treatments for what is one of the most difficult therapeutic challenges to confront the nephrologist.

Animals↗

PubMed2006

Update in pathophysiology and histopathology of focal segmental glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS) is the leading cause of nephrotic syndrome in an adult worldwide. The prevalence of FSGS is estimated as being 20-30% in adults over the age of 15 years and slightly higher (30-35%) in the elderly (age > 60 years). The diagnosis solely relies on pathologic findings, which sclerosis involves some, but not all glomeruli (focal), and sclerosis affects a portion, but not the entire, glomerular tuft (segmental). The pathogenesis remains inconclusive but podocyte injury has been postulated. Even though steroid is the mainstay treatment, only 20-40% of patients are complete respond.

Adolescent↗

PubMed2003

Approach to the evaluation of heritable diseases and update on familial focal segmental glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS) is a pathological entity that is a significant cause of morbidity and mortality throughout the world. It is also a significant cause of end-stage renal disease (ESRD). Glomerular disease is the third leading cause of ESRD, and FSGS comprises a significant proportion of this subgroup. Up to 20% of individuals with ESRD have FSGS. It has been reported in patients from varied ethnic backgrounds including individuals who are of Spanish, North American, North European and African descent. The diagnosis of FSGS is based on renal pathology and requires the presence of areas of glomerular sclerosis and tuft collapse that are both focal and segmental. The clinical hallmarks of FSGS include proteinuria, nephrotic syndrome and, frequently, the progressive loss of renal function. At present, there are no consistently reliable treatments for FSGS and response rates to available treatments have been estimated at <30-50%. FSGS has been characterized previously as having primary (idiopathic), secondary and familial forms. In the latter category, both autosomal recessive and dominant inheritance patterns have been reported. Advances in molecular genetics technology and mapping, including high-throughput genotyping for genomic screening, provide powerful tools for the analysis of renal diseases. Genes associated with many familial renal disorders that lead to ESRD have been isolated; these include Alport's nephropathy, familial juvenile nephronophthisis and adult polycystic disease. Recently, the genetic mutation (ACTN4) causing a form of autosomal dominant FSGS (ACTN4) and congenital nephrotic syndromes (NPHS2) have been described. The existence of hereditary forms of FSGS permits the use of molecular genetics techniques to study the pathogenesis of this disorder.

Genetic Diseases, Inborn↗