Increased urinary CD80 excretion and podocyturia in Fabry disease

Trimarchi, Hernán; Canzonieri, Romina; Schiel, Amalia; Costales-Collaguazo, Cristian; Politei, Juan; Stern, Aníbal; Paulero, Matías; Rengel, Tatiana; Andrews, J. Matthew; Forrester, Mariano; Lombi, M.; Pomeranz, Vanesa; Iriarte, Romina; Muryan, Alexis; Zotta, Elsa; Sanchez-Niño, María Dolores

doi:10.1186/s12967-016-1049-8

Cited by 29 publications

(37 citation statements)

References 37 publications

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“…Early biomarkers of Fabry disease nephropathy have been studied in affected adult patients with some promising results [10] [11] [12]. Several studies suggest the potential role of microRNAs in kidney function [13].…”

Section: Introductionmentioning

confidence: 99%

Urinary Excretion of microRNAs in Young Fabry Disease Patients with Mild or Absent Nephropathy

Jaurretche¹,

Venera²,

Antongiovanni³

et al. 2018

OJNeph

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Fabry disease (FD) clinical manifestations often start in childhood. Among the FD complications, renal failure causes significant morbidity and mortality. Early diagnosis and treatment of FD nephropathy in children may be critical to preserve renal function. In proteinuric progressive nephropathies it has been described that pro-fibrotic miR-21, miR-192, and miR-433 families are activated and that anti-fibrotic miR-29 and miR-200 families are inhibited. Objective: Analyze urinary excretion of microRNAs related to renal fibrosis in FD patients with mild or absent nephropathy. Patients with confirmed diagnosis of FD under 18 years of age were compared with healthy subjects. Patients were classified into two groups: 1) Patients with urinary excretion profile of microRNAs indicative of renal fibrosis; and 2) Patients with urinary excretion profile of microRNAs not indicative of renal fibrosis. Results: 9 healthy subjects were enrolled in the study (18.66 ± 13.43 years), 4 males and 5 females. All of them presented normal eFGR without pathological albuminuria. FD population: 12 patients (10.33 ± 3.93 years) were studied, 5 males and 7 females. Patients presented 2 different genotypes: L415P (6 patients) and E398X (6 patients). The urinary excretion profile of microRNAs indicative of renal fibrosis was present in 4 patients (2 with L415P genotype and 2 with E398X genotype), all of them with a decreased of miR-29 and/or miR-200. No patient presented increased miR-21, miR-192 and/or miR-433. Decreased α-galA activity was the only variable associated with statistical significance (p ≤ 0.01) to urinary excretion profile of microRNA indicative of

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Section: Introductionmentioning

confidence: 99%

Urinary Excretion of microRNAs in Young Fabry Disease Patients with Mild or Absent Nephropathy

Jaurretche¹,

Venera²,

Antongiovanni³

et al. 2018

OJNeph

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“…A decrease in expression of podocyte protein-tyrosine phosphatase (GLEPP1) was associated with partial steroid-sensitivity in several mouse models of podocyte disease, but, in contrast to GLEPP1, upregulated CD80 expression is steroid-resistant. Recent studies have found that CD80 is expressed in renal tissue in several types of glomerulonephritis, such as lupus nephritis, immunoglobulin A nephropathy, diabetic nephropathy, and Fabry disease ( Reiser et al, 2004 ; Fiorina et al, 2014 ; Trimarchi et al, 2016 ; Wu et al, 2004 ; Sui et al, 2010 ), in addition to MCD. B7/CD28 blockade (LEA29Y, Belatacept) in kidney transplant recipients have proven that the replacement of toxic calcineurin inhibitor (CNI) use is feasible in selected populations.…”

Section: Discussionmentioning

confidence: 99%

CD80 and CTLA-4 as diagnostic and prognostic markers in adult-onset minimal change disease: a retrospective study

Zhao

Han

Zhen

et al. 2018

PeerJ

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BackgroundMinimal change disease (MCD) is a form of idiopathic nephrotic syndrome. Compared to children, adult-onset MCD patients are reported to have delayed responses to glucocorticoid treatment. Several studies of children have suggested detecting urinary CD80 levels to diagnose MCD. There are no effective diagnostic methods to distinguish steroid-sensitive MCD from steroid-resistant MCD unless treatments are used.MethodsIn a total of 55 patients with biopsy-proven MCD and 26 patients with biopsy-proven idiopathic membranous nephropathy, CD80 and cytotoxic T-lymphocyte antigen-4 (CTLA-4) levels in serum, urine and renal tissue were analyzed.ResultsSteroid-sensitive MCD patients in remission had lower urinary CD80 levels and higher CTLA-4 levels than patients in relapse (156.65 ± 24.62 vs 1066.40 ± 176.76 ng/g creatinine; p < 0.0001), (728.73 ± 89.93 vs 151.70 ± 27.01 ng/g creatinine; p < 0.0001). For MCD patients in relapse, mean urinary CD80 level was higher, and CTLA-4 level was lower for those who were steroid-sensitive than those who were steroid-resistant (1066.40 ± 176.76 vs. 203.78 ± 30.65 ng/g creatinine; p < 0.0001), but the mean urinary CTLA-4 level was lower (151.70 ± 27.01 vs. 457.83 ± 99.45 ng/g creatinine; p < 0.0001). CD80 expression in glomeruli was a sensitive marker to diagnose MCD. The absent or minimal expression of CTLA-4 in glomeruli could distinguish steroid-sensitive MCD from steroid-resistant MCD.ConclusionsGlucocorticoid treatment may result in complete remission for only MCD patients with strongly positive CD80 expression and negative CTLA-4 expression in glomeruli, or higher urinary CD80 level and lower CTLA-4 level.

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“…The main manifestations are pathological albuminuria and decreased GFR, although tubular dysfunction may also occur [29]. Moreover, podocyturia, a biomarker suggestive of early kidney involvement, is elevated in FD patients [30,31]. According to studies from the Fabry Registry and the Fabry Outcome Survey, kidney involvement is usually less severe and later among female patients, as observed for other organs [25,32].…”

Section: Discussionmentioning

confidence: 99%

A Novel Missense GLA Mutation (p.G35V) Detected in Hemodialysis Screening Leads to Severe Systemic Manifestations of Fabry Disease in Men and Women

Veloso¹,

Ataides²,

Canziani³

et al. 2017

Nephron

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Background/Aims: Fabry disease (FD), an X-linked lysosomal storage disorder, leads to accumulation of globotriaosylceramide. Screening in dialysis patients may identify genetic variants of unknown clinical significance. We aimed to characterize the pathogenicity of a novel GLA gene mutation identified during hemodialysis screening and the histologic findings of early Fabry nephropathy. Methods: One out of 108 male hemodialysis patients screened for FD presented low α-galactosidase A activity. A novel missense mutation (p.G35V) in the GLA gene was detected. Family screening identified 11 additional cases (8 women). Clinical investigation was conducted in 10 patients (index case and 9 relatives). Pathogenicity of the new mutation was investigated by clinical and laboratory tests, cardiac and cranial magnetic resonance imaging, and kidney biopsy. Results: Cardiac manifestations were detected in most patient from both genders, such as left ventricular hypertrophy and short PR interval. White matter lesion was present in 3 women. Pulvinar lesion of the thalamus and ischemic stroke were detected in male patients. Abnormal glomerular filtration rate (GFR) and/or albuminuria were present in 5 patients (3 women). Renal biopsies (n = 7) revealed globotriaosylceramide deposits in different cell types and foot processes effacement in all patients, including women with normal albuminuria. Despite a normal GFR, tubulointerstitial fibrosis ranging from 5 to 20% was present in young women and men with normal or high albuminuria, respectively. Conclusion: The novel missense mutation p.G35V leads to severe systemic manifestations of FD in men and women. Kidney histological changes, including tubulointerstitial fibrosis, may predate albuminuria and GFR changes in adult women. Novel non-invasive markers are required for early detection of Fabry nephropathy.

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Increased urinary CD80 excretion and podocyturia in Fabry disease

Cited by 29 publications

References 37 publications

Urinary Excretion of microRNAs in Young Fabry Disease Patients with Mild or Absent Nephropathy

Urinary Excretion of microRNAs in Young Fabry Disease Patients with Mild or Absent Nephropathy

CD80 and CTLA-4 as diagnostic and prognostic markers in adult-onset minimal change disease: a retrospective study

A Novel Missense GLA Mutation (p.G35V) Detected in Hemodialysis Screening Leads to Severe Systemic Manifestations of Fabry Disease in Men and Women

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