Focal and segmental glomerulosclerosis FSGS is a disease characterized morphologically by segments of sclerosis in some glomeruli. It can be primary or secondary and it usually present as nephrotic syndrome NS. Nevertheless, in FSGS some of the segmental lesions are not sclerosis, but hyaline deposits: Hyalinosis. This feature originated the classical denomination, more of the French school, focal and segmental hyalinosis.
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The Journal publishes articles on basic or clinical research relating to nephrology, arterial hypertension, dialysis and kidney transplants. It is governed by the peer review system and all original papers are subject to internal assessment and external reviews. The journal accepts submissions of articles in English and in Spanish languages.
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In recent years, the nephrological community has witnessed very important discoveries in renal diseases, and within them, in glomerulonephritis. Despite the efforts of many laboratories in recent decades, we have not yet managed to capture this or these intriguing pathogenic agent s.
As is well-known, several clinical arguments, with good reason, make us suspect the existence of this permeabilizing factor: 1 the known possibility of massive proteinuria recurring within a few hours or even minutes of a renal transplantation in patients with primary FSGS, 3 2 the disappearance of this proteinuria whenever kidneys with proteinuria recurrence are retransplanted into a patient without FSGS, 4 3 induction of proteinuria in rats in which patient serum with primary FSGS is injected, 5 and 4 the efficacy of plasmapheresis in cases of proteinuria recurrence in transplanted kidneys.
Several candidates for this mysterious and evasive permeabilizing factor have been proposed over this period, but without any reliable clinical demonstration being achieved.
In , a new candidate was proposed: soluble urokinase-type plasminogen activator receptor or suPAR. After performing plasmapheresis in recurring cases and in parallel with nephrotic syndrome remission, suPAR levels dropped significantly. Knockout animals for the urokinase-type plasminogen activator receptor uPAR coding gene showed notable resistance to proteinuria measured by lipopolysaccharides and puromycin and the administration of a specific antibody against uPAR markedly decreased the severity of renal damage.
These studies stirred up great expectation, given that they presented solid data that indicated that suPAR could be the permeabilizing factor in a majority of primary FSGS cases and also because they demonstrated potential new therapeutic avenues on blocking this factor. The structure of uPAR and its participation in many cell functions have been known for some time reviewed in Maas et al. Nevertheless, various other factors, such as the tumour necrosis factor, may perform similar actions on podocyte integrins and indeed, they exert profound changes on the cellular expression of uPAR.
Moreover, suPAR levels have been studied in very diverse diseases and it has been observed that they are characteristically high in sepsis, tumours, liver diseases and generalised arteriosclerosis. In sepsis and systemic diseases, such as systemic erythematosus lupus, a relationship between suPAR levels and survival or disease activity has been noted.
These data indicate a certain lack of specificity of suPAR levels, highly linked to inflammatory processes of a different kind. Another important piece of evidence, which would go against the proposed permeabilizing role of suPAR, is that in the abovementioned pathological conditions associated with very high suPAR levels, the presence of significant proteinuria was not ascertained.
Therefore, despite the attractive aspects of suPAR as a potential permeabilizing factor, there are still many aspects that need to be clarified before attributing the predominant pathogenic role to it as initial studies suggested. Moreover, we do not have rational hypotheses on mechanisms or factors that may precipitate an increase in suPAR levels in FSGS patients. In the previous edition of this journal, Segarra and collaborators presented two very interesting studies in this regard.
Furthermore, as illustrated by cases of nephrotic syndrome recurrence in transplant patients with FSGS, patients with FSGS have a period of time whose duration has not been defined, although it is probably highly variable with massive proteinuria and complete nephrotic syndrome in which the biopsy only shows data typical of minimal change disease: normal in the optical microscope, negative immunofluorescence and pedicel fusion in the electron microscope.
Only after weeks or months in this situation do lesions typical of glomerulosclerosis begin to appear. Although the results of this study are partially consistent with the two previous studies, 7,8 their results must fit with those of other critical studies with validity of suPAR determination in kidney patients. Bock and collaborators 13 found in children that suPAR levels were higher in cases with non-glomerular renal diseases than in FSGS, although there were no significant differences.
Neither were differences found with healthy controls. In this study, the presence of proteinuria was associated with lower levels of suPAR. Given the disparity of data and the absence of specifically higher values in idiopathic FSGS, the authors concluded that it is unlikely that suPAR is another factor causing FSGS and that its determination is not clinically useful. Other authors have also expressed their criticisms about the usefulness of measuring suPAR for the differential diagnosis of nephrotic syndromes.
As in the previous study, diagnoses of primary or secondary FSGS were based on histological and clinical criteria. As in the studies by Segarra, renal function significantly influenced suPAR levels.
In explaining the lack of concordance found between the different studies carried out, some authors have expressed serious doubts that the commercial test available for measuring suPAR is sufficiently reliable. High suPAR levels are detected in many infectious and inflammatory diseases, without triggering proteinuria and, on the contrary, in many patients with a clear diagnosis of primary FSGS, there are normal and even low circulating levels of suPAR.
All of these data call into question the central pathogenic role of suPAR and its potential usefulness as a diagnostic biomarker. However, further studies are required in larger cohorts, in order to establish conclusions that can be applied to clinical practice in patients with nephrotic syndrome.
In summary, we could say that the expectations created by the first studies on suPAR have been lowered by subsequent studies, whose conflicting results we have summarised. In this regard, as an example of the clinical significance that this research may have, positive results have been published very recently on treatment with abatacept, a B CD80 inhibitor, a T-cell costimulatory molecule, in five patients with nephrotic syndrome due to FSGS.
All of these patients had complete or partial remission of proteinuria. The authors declare that they have no conflicts of interest related to the contents of this article. Home Articles in press Archive. ISSN: Previous article Next article. March Pages DOI: Download PDF. Manuel Praga a. Hospital Universitario 12 de Octubre. Instituto de Investigaci??
Universidad Complutense, Madrid,. This item has received. Article information. Contents In recent years, the nephrological community has witnessed very important discoveries in renal diseases, and within them, in glomerulonephritis. Patients with FSGS have higher suPAR levels than those with other forms of glomerulonephritis, although there is a considerable overlap and not all studies agree.
Age and reduction of renal function increase suPAR values. Very high levels of suPAR in these conditions are not associated with proteinuria, which calls into question its pathogenic role as a proteinuric circulating factor. Given the lack of homogeneity of the clinical results obtained, further studies are required in order that we may recommend suPAR levels as a useful biomarker in clinical practice.
Likewise, more experimental studies are required in order to establish the role of suPAR in FSGS genesis and that of other glomerular processes. M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. N Engl J Med ; Pathobiology of focal segmental glomerulosclerosis: new developments. Curr Opin Nephrol Hypertens ; Podocyte foot process effacement in postreperfusion allograft biopsies correlates with early recurrence of proteinuria in focal segmental glomerulosclerosis.
Transplantation ; Resolution of recurrent focal segmental glomerulosclerosis after retransplantation. Effect of plasma fractions from patients with focal and segmental glomerulosclerosis on rat proteinuria. Kidney Int ; Effect of plasma protein adsorption on protein excretion in kidney transplant recipients with recurrent nephrotic syndrome. Circulating urokinase receptor as a cause of focal segmental glomerulosclerosis.
Nat Med ; J Am Soc Nephrol ; Pediatr Nephrol ; Nat Rev Mol Cell Biol ; Valor diagn?? Nefrologia ;34 1 Valor de los niveles s?? Serum soluble urokinase-type plasminogen activator receptor levels and idiopathic FSGS in children: a single-center report.
Clin J Am Soc Nephrol ; Serum-soluble urokinase receptor concentration in primary FSGS. Plasma soluble urokinase receptor levels are increased but do not distinguish primary from secondary focal segmental glomerulosclerosis. Abatacept in Bpositive proteinuric kidney disease. CD80 and suPAR in patients with minimal change disease and focal segmental glomerulosclerosis: diagnostic and pathogenic significance.
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Focal segmental glomerulosclerosis
Focal segmental glomerulosclerosis FSGS results from scarring of the glomeruli, the tiny structures within the kidney that filter impurities from the blood to create urine. As these scars accumulate, kidney function worsens. Focal segmental glomerulosclerosis FSGS is a disease in which scar tissue develops on the parts of the kidneys that filter waste from the blood glomeruli. FSGS can be caused by a variety of conditions. FSGS is a serious condition that can lead to kidney failure, for which the only treatment options are dialysis or kidney transplant. Treatment options for FSGS depend on the type you have.
Focal Segmental Glomerulosclerosis
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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. 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.