APOL1 risk genotype in European steroid-resistant nephrotic syndrome and/or focal segmental glomerulosclerosis patients of different African ancestries

Boyer, Olivia; Karras, Alexandre; Dantal, Jacques; Fourrage, Cécile; Alibeu, Olivier; Hogan, Julien; Dossier, Claire; Tête, Marie Josèphe; Antignac, Corinne

doi:10.1093/ndt/gfy176

Cited by 18 publications

(12 citation statements)

References 41 publications

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“…As expected (Eddy & Symons, 2003), the children with SRNS were significantly older at presentation, otherwise the groups were demographically similar. Genetics are known to play a role in steroid-responsiveness (Adeyemo et al, 2018;Asharam et al, 2018;Govender et al, 2019;Gribouval et al, 2018Gribouval et al, , 2019. However, while genetic and other mechanisms underlying steroid-responsiveness in this small cohort were not evaluated in the present study, they have been the subject of previously reported biomarker studies (Agrawal et al, 2020;Gooding et al, 2020).…”

Section: Hypercoagulopathy Improves In Children With Steroid-sensitmentioning

confidence: 83%

Nephrotic syndrome‐associated hypercoagulopathy is alleviated by both pioglitazone and glucocorticoid which target two different nuclear receptors

et al. 2020

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Background: Thrombosis is a potentially life-threatening nephrotic syndrome (NS) complication. We have previously demonstrated that hypercoagulopathy is proportional to NS severity in rat models and that pioglitazone (Pio) reduces proteinuria both independently and in combination with methylprednisolone (MP), a glucocorticoid (GC). However, the effect of these treatments on NS-associated hypercoagulopathy remains unknown. We thus sought to determine the ability of Pio and GC to alleviate NS-associated hypercoagulopathy. Methods: Puromycin aminonucleoside-induced rat NS was treated with sham, Lowor High-dose MP, Pio, or combination (Pio + Low-MP) and plasma was collected at day 11. Plasma samples were collected from children with steroid-sensitive NS (SSNS) and steroid-resistant NS (SRNS) upon presentation and after 7 weeks of GC therapy. Plasma endogenous thrombin potential (ETP), antithrombin (AT) activity, and albumin (Alb) were measured using thrombin generation, amidolytic, and colorimetric assays, respectively. Results: In a rat model of NS, both High-MP and Pio improved proteinuria and corrected hypoalbuminemia, ETP and AT activity (p < .05). Proteinuria (p = .005) and hypoalbuminemia (p < .001) were correlated with ETP. In childhood NS, while ETP was not different at presentation, GC therapy improved proteinuria, hypoalbuminemia, and ETP in children with SSNS (p < .001) but not SRNS (p = .330). Conclusions: Both Pio and GC diminish proteinuria and significantly alleviate hypercoagulopathy. Both Pio and MP improved hypercoagulopathy in rats, and successful GC therapy (SSNS) also improved hypercoagulopathy in childhood NS. These data suggest that even a partial reduction in proteinuria may reduce NS-associated thrombotic risk. How to cite this article: Waller AP, Agrawal S, Wolfgang KJ, et al. Nephrotic syndrome-associated hypercoagulopathy is alleviated by both pioglitazone and glucocorticoid which target two different nuclear receptors.

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Section: Hypercoagulopathy Improves In Children With Steroid-sensitmentioning

confidence: 83%

Nephrotic syndrome‐associated hypercoagulopathy is alleviated by both pioglitazone and glucocorticoid which target two different nuclear receptors

et al. 2020

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“…In 2010, 2 mutually exclusive polymorphisms (G1 and G2) in the apolipoprotein L1 (APOL1) gene, commonly found in people of African ancestry, were identified to increase the risk of chronic kidney disease (CKD) in homozygous or compound heterozygote individuals by 7-to 30-fold, accounting for the higher prevalence of kidney failure in African Americans (1)(2)(3)(4). These mutations originated in ancestral populations in West Africa and are now being described as associated with CKD risk in other descendant populations, highlighting West African ancestry as the ethnically linked population (5). The APOL1 risk alleles have been shown to strongly associate with various forms of nondiabetic nephropathy previously thought to be unrelated, including focal segmental glomerulosclerosis (FSGS), HIV-associated nephropathy (HIVAN), hypertensive-attributed kidney disease, lupus nephritis, and IFN therapy-related collapsing glomerulopathy (1,3,6,7).…”

Section: Introductionmentioning

confidence: 99%

Antisense oligonucleotide treatment ameliorates IFN-γ–induced proteinuria in APOL1-transgenic mice

et al. 2019

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“…APOL1 , apolipoprotein L1, encodes a secreted high-density lipoprotein, which binds to apolipoprotein A-I. Some researches indicated APOL1 is related to cardiovascular disease and renal disease [ 41 , 42 ]. H1–2 , H1.2 linker histone, is also called HIST1H1C .…”

Section: Discussionmentioning

confidence: 99%

Construction of a novel mRNA-signature prediction model for prognosis of bladder cancer based on a statistical analysis

Cao

et al. 2021

BMC Cancer

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Background Bladder cancer (BC) is a common malignancy neoplasm diagnosed in advanced stages in most cases. It is crucial to screen ideal biomarkers and construct a more accurate prognostic model than conventional clinical parameters. The aim of this research was to develop and validate an mRNA-based signature for predicting the prognosis of patients with bladder cancer. Methods The RNA-seq data was downloaded from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were screened in three datasets, and prognostic genes were identified from the training set of TCGA dataset. The common genes between DEGs and prognostic genes were narrowed down to six genes via Least Absolute Shrinkage and Selection Operator (LASSO) regression, and stepwise multivariate Cox regression. Then the gene-based risk score was calculated via Cox coefficient. Time-dependent receiver operating characteristic (ROC) and Kaplan-Meier (KM) survival analysis were used to assess the prognostic power of risk score. Multivariate Cox regression analysis was applied to construct a nomogram. Decision curve analysis (DCA), calibration curves, and time-dependent ROC were performed to assess the nomogram. Finally, functional enrichment of candidate genes was conducted to explore the potential biological pathways of candidate genes. Results SORBS2, GPC2, SETBP1, FGF11, APOL1, and H1–2 were screened to be correlated with the prognosis of BC patients. A nomogram was constructed based on the risk score, pathological stage, and age. Then, the calibration plots for the 1-, 3-, 5-year OS were predicted well in entire TCGA-BLCA patients. Decision curve analysis (DCA) indicated that the clinical value of the nomogram was higher than the stage model and TNM model in predicting overall survival analysis. The time-dependent ROC curves indicated that the nomogram had higher predictive accuracy than the stage model and risk score model. The AUC of nomogram time-dependent ROC was 0.763, 0.805, and 0.806 for 1-year, 3-year, and 5-year, respectively. Functional enrichment analysis of candidate genes suggested several pathways and mechanisms related to cancer. Conclusions In this research, we developed an mRNA-based signature that incorporated clinical prognostic parameters to predict BC patient prognosis well, which may provide a novel prognosis assessment tool for clinical practice and explore several potential novel biomarkers related to the prognosis of patients with BC.

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APOL1 risk genotype in European steroid-resistant nephrotic syndrome and/or focal segmental glomerulosclerosis patients of different African ancestries

Abstract: The HR genotype is frequent in FSGS patients with African ancestry in our cohort, especially in those originating from the West Indies, and confer a poor renal prognosis. It is usually not associated with other causative mutations in monogenic SRNS genes.

Cited by 18 publications

References 41 publications

Nephrotic syndrome‐associated hypercoagulopathy is alleviated by both pioglitazone and glucocorticoid which target two different nuclear receptors

Nephrotic syndrome‐associated hypercoagulopathy is alleviated by both pioglitazone and glucocorticoid which target two different nuclear receptors

Antisense oligonucleotide treatment ameliorates IFN-γ–induced proteinuria in APOL1-transgenic mice

Construction of a novel mRNA-signature prediction model for prognosis of bladder cancer based on a statistical analysis

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