Serum from minimal change patients in relapse increases CD80 expression in cultured podocytes

Ishimoto, Takuji; Cara-Fuentes, Gabriel; Wang, Heiman; Shimada, Michiko; Wasserfall, Clive; Winter, William E.; Rivard, Christopher J.; Araya, Carlos E.; Saleem, Moin A.; Mathieson, Peter W.; Johnson, Richard J.; Garin, Eduardo H.

doi:10.1007/s00467-013-2498-4

Cited by 40 publications

(25 citation statements)

References 24 publications

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“…CD80 was also detected in the glomeruli of the same patients but were not found in high levels in other NS-causing nephropathies, such as FSGS or membranous nephropathy (MN) 61,62) . These results were confirmed in other populations with MCD 63) , thus leading to the conclusion that high CD80 (B7-1) expression in the urine and glomeruli is a urinary biomarker to distinguish between MCNS and FSGS, which could be used to monitor the activity of the disease 55,66) . Other studies documented the upregulation of glomerular CD80 (B7-1) in patients with diabetic nephropathy 64) and/or with post-transplant FSGS recurrence 65) .…”

Section: Cd80 (B7-1)supporting

confidence: 56%

“…Other studies documented the upregulation of glomerular CD80 (B7-1) in patients with diabetic nephropathy 64) and/or with post-transplant FSGS recurrence 65) . Sera from MCD patients in relapse, but not in remission, stimulated CD80 expression in cultured podocytes along with diminished nephrin phosphorylation in comparison with podocytes incubated with sera from MCD patients in remission 66) . Therefore, B7-1 may be a biomarker of podocyte injury.…”

Section: Cd80 (B7-1)mentioning

confidence: 88%

“…We previously reported that IL-13 increased podocyte permeability through the modulation of ZO-1 110) , modulated the changes of cytoskeletal and adaptor proteins 111) , and increased podocyte apoptosis 112) , resulting in proteinuria and podocyte injury. However, the supposed role of circulating IL-13 in proteinuria in MCD patients is questionable because the elevated serum IL-13 levels were not found in MCD patients during relapse 66) and have been reported in patients with NS during remission compared with the controls 113) . In addi tion, although serum IL-13 is increased in patients with asthma and with atopic dermatitis, only a few present associated proteinuria 114,115) .…”

Section: Interleukin-13 (Il-13)mentioning

confidence: 94%

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Circulating Permeability Factors in Idiopathic Nephrotic Syndrome

2019

Child Kidney Dis

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Nephrotic syndrome (NS) is a common chronic glomerular disease in children characterized by significant proteinuria with resulting hypoalbuminemia, edema, and hyperlipidemia. Renal biopsy findings of diffuse foot processes effacement on electron microscopy and minimal change disease, focal segmental glomerulosclerosis (FSGS), or diffuse mesangial proliferation on light microscopy. It has been speculated that circulating permeability factors would be implicated in the pathogenesis of NS because they have been reportedly detected in the sera of patients and in experimental models of induced proteinuria. Moreover, a substantial portion of the patients with primary FSGS recurrence shortly after trans plantation. This report reviews the current knowledge regarding the role of circu lating permeability factors in the pathogenesis of proteinuria in NS and suggests future targeted therapeutic approaches for NS.

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Section: Cd80 (B7-1)supporting

confidence: 56%

Section: Cd80 (B7-1)mentioning

confidence: 88%

Section: Interleukin-13 (Il-13)mentioning

confidence: 94%

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Circulating Permeability Factors in Idiopathic Nephrotic Syndrome

2019

Child Kidney Dis

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“…The exposure of podocytes to LPS rapidly unregulate CD80 in mice and leads to actin reorganization and nephrotic-range proteinuria, whereas mice lacking CD80 are protected from this damage [4]. Sera from MCD patients in relapse, but not in remission, were found to stimulate CD80 expression in cultured podocytes [93]. In addition, urinary concentrations of soluble CD80 in patients with relapsed MCD were significantly higher than those in patients with MCD in remission and with other glomerular diseases including FSGS and in healthy controls [94].…”

Section: Abataceptmentioning

confidence: 99%

Podocyte directed therapy of nephrotic syndrome—can we bring the inside out?

Müller-Deile

Schiffer

2015

Pediatr Nephrol

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Several of the drugs currently used for the treatment of glomerular diseases are prescribed for their immunotherapeutic or anti-inflammatory properties, based on the current understanding that glomerular diseases are mediated by immune responses. In recent years our understanding of podocytic signalling pathways and the crucial role of genetic predispositions in the pathology of glomerular diseases has broadened. Delineation of those signalling pathways supports the hypothesis that several of the medications and immunosuppressive agents used to treat glomerular diseases directly target glomerular podocytes. Several central downstream signalling pathways merge into regulatory pathways of the podocytic actin cytoskeleton and its connection to the slit diaphragm. The slit diaphragm and the cytoskeleton of the foot process represent a functional unit. A breakdown of the cytoskeletal backbone of the foot processes leads to internalization of slit diaphragm molecules, and internalization of slit diaphragm components in turn negatively affects cytoskeletal signalling pathways. Podocytes display a remarkable ability to recover from complete effacement and to re-form interdigitating foot processes and intact slit diaphragms after pharmacological intervention. This ability indicates an active insideout signalling machinery which stabilizes integrin complex formations and triggers the recycling of slit diaphragm molecules from intracellular compartments to the cell surface. In this review we summarize current evidence from patient studies and model organisms on the direct impact of immunosuppressive and supportive drugs on podocyte signalling pathways. We highlight new therapeutic targets that may open novel opportunities to enhance and stabilize inside-out pathways in podocytes.

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“…Then, Garin et al found children with biopsy proven MCD expressed CD80 in their podocytes and excreted high levels of CD80 in their urine during active nephrotic syndrome (33,34). Following these results, they reported sera from MCD patients in relapse stimulates CD80 expression in cultured podocytes (35). In addition, increased CD80 expression in podocyte, glomerular CD80 and urinary excretion of CD80 can be induced by polyIC, a Toll-like receptor 3 ligand, and were associated with proteinuria (36).…”

Section: Idiopathic Nephrotic Syndrome In Asthmamentioning

confidence: 99%

Risk of idiopathic nephrotic syndrome among children with asthma: a nationwide, population-based cohort study

et al. 2015

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Background:Although clinical and immunological studies have shown a possible link between allergy and idiopathic nephrotic syndrome (INS), the nature of the relationship remains unclear. Asthma is the most common chronic allergic airway inflammation. However, no study has used a longitudinal design with a population cohort to investigate INS in children with asthma. Methods: Using nationwide claims data from 2000 through 2007, we randomly selected 251,698 asthma cases and 1,006,791 frequency-matched controls. Incidence rates of INS and hazard ratios (HRs) were calculated. results: The INS incidence was 3.36-fold greater in the asthma cohort than in the nonasthma control (9.26 vs. 2.76 per 100,000 person-years; 95% confidence interval (CI): 2.65-4.26). The HR for INS increased for those with more asthma-related medical visits per year, from 1.49 (95% CI: 1.06-2.11) for <3 visits to 15.7 (95% CI: 11.5-21.5) for ≥6 visits (trend test, P < 0.0001). The HR for INS slightly decreased during the follow-up period, from 3.41 (95% CI: 2.66-4.38) for ≤5.5 y to 2.90 (95% CI: 1.33-6.30) for >5.5 y. conclusion: We conclude that children with asthma had an increased incidence rate of INS, and increased incidence rate correlated with asthma-related medical visits.i diopathic nephrotic syndrome (INS) is among the most common chronic kidney diseases occurring in childhood (1). Numerous studies have associated INS with allergy risk of clinical and immunological features (2-11). In the 1950s through the 1970s, few anecdotal reports described patients who developed INS after allergic reactions to inhaled allergens, vaccinations, food, or insect stings (2-5). Since 1970, several case-control studies revealed that elevated serum IgE and atopic diathesis were more common in children with INS than non-INS controls (9,(11)(12)(13)(14)(15)(16)(17). Recently, levels of T helper 2 (Th2)-associated cytokine such as interleukin (IL)-4 and IL-13 were found to be elevated in relapsing INS patients (18-21). Children with INS commonly have elevated serum levels of immunoglobulin E (IgE), which also plays a central role in allergic inflammation (11)(12)(13)(14)(15)(16). Although clinical and immunological studies have shown a possible link between allergic diseases and INS for 50 y, human epidemiologic study using a large cohort to investigate the relationship between these disorders are lacking (2-11). Asthma is one of the most common allergic disease in childhood, affects a multitude of patients worldwide (22). It is unknown whether childhood onset asthma would increase the subsequent risk of INS. Therefore, we conducted a nationwide, population-based cohort study to examine the hypothesis that asthma may have positive influence on the development of INS in children. RESULTSA total of 251,698 subjects in the asthma cohort and 1,006,791 in the nonasthma cohort were enrolled in this study (Table 1). Most (67.6%) of the subjects were aged ≤5 y. The asthma cohort had more boys (59.4%), residents of highly urbanized areas (59.8%), and white-collar pa...

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Serum from minimal change patients in relapse increases CD80 expression in cultured podocytes

Cited by 40 publications

References 24 publications

Circulating Permeability Factors in Idiopathic Nephrotic Syndrome

Circulating Permeability Factors in Idiopathic Nephrotic Syndrome

Podocyte directed therapy of nephrotic syndrome—can we bring the inside out?

Risk of idiopathic nephrotic syndrome among children with asthma: a nationwide, population-based cohort study

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