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Hypertension/prehypertension and its determinants in pediatric IgA nephropathy.

ABSTRACT: Immunoglobulin A nephropathy (IgAN) is a major cause of secondary hypertension (HT) of renal origin - a significant prognostic factor of IgAN. In children, similar to HT, prehypertension (pre-HT) is becoming a significant health issue. However, the role of secondary HT and pre-HT (HT/pre-HT) in the progression of pediatric IgAN remains unclear. We investigated the effects of HT/pre-HT on prognosis and its determinants as well as their correlation with clinicopathological parameters to identify more effective therapeutic targets.This single-center retrospective study compared clinicopathological features and treatment outcomes between patients with and without HT/pre-HT in 108 children with IgAN. Independent risk factors for HT/pre-HT were evaluated; segmental glomerulosclerosis was a significant variable, whose relationship with clinicopathological parameters was analyzed.Clinical outcomes of patients with and without HT/pre-HT differed considerably (P?=?.006) on ?6 months follow-up. Patients with HT/pre-HT reached complete remission less frequently than those without HT/pre-HT (P?=?.014). Age, serum creatinine, prothrombin time, and segmental glomerulosclerosis or adhesion were independent risk factors for HT/pre-HT in pediatric IgAN (P?=?.012, P?=?.017, P?=?.002, and P?=?.016, respectively). Segmental glomerulosclerosis or adhesion was most closely associated with glomerular crescents (r?=?0.456, P?

SUBMITTER: Fu QY

PROVIDER: S-EPMC7535649 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Hypertension/prehypertension and its determinants in pediatric IgA nephropathy.

Fu Qing-Ying QY Ma Lu L Li Chang-Chun CC He Zhi-Jun ZJ Wang Wei-Hua WH Luo Kai-Fa KF Liu Yang Y Zhang Zhi-Hao ZH Yang Zai-Bo ZB Tang Hai-Lian HL Yan Jun-Hui JH

Medicine 20201001 40

Immunoglobulin A nephropathy (IgAN) is a major cause of secondary hypertension (HT) of renal origin - a significant prognostic factor of IgAN. In children, similar to HT, prehypertension (pre-HT) is becoming a significant health issue. However, the role of secondary HT and pre-HT (HT/pre-HT) in the progression of pediatric IgAN remains unclear. We investigated the effects of HT/pre-HT on prognosis and its determinants as well as their correlation with clinicopathological parameters to identify m ...[more]

PMID: 33019406

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Project description:BackgroundPeru is a Latin American country with a significant burden of hypertension that presents worrying rates of disparities in socioeconomic determinants. However, there is a lack of studies exploring the association between those determinants, hypertension and prehypertension in Peruvian population.ObjectiveWe aimed to assess the association betwgeen socioeconomic determinants, hypertension and prehypertension using a nationally representative survey of Peruvians.MethodsWe performed a cross-sectional analysis of the Peruvian Demographic and Health Survey (2018), which is a two-staged regional-level representative survey. We used data from 33,336 people aged 15 and older. The dependent variable was blood pressure classification (normal, prehypertension and hypertension) following the Seventh Report of the Joint National Committee (JNC-7) on hypertension management. Independent variables were socioeconomic: age, sex, marital status, wealth index, health insurance, education, region and area of residence. Due to the nature of the dependent variable (more than two categories), we opted to use the multinomial regression model, adjusting the effect of the multistage sample using the svy command. We tested interactions with the adjusted Wald test.ResultsThe prevalence of prehypertension and hypertension was 33.68% and 19.77%, respectively. Awareness was higher in urban than in rural areas (9.61% vs. 8.31%, p = 0.008). Factors associated with a higher prevalence ratio of both prehypertension and hypertension were age (ratios rose with each age group), male sex (prehypertension aRPR 5.15, 95%CI 4.63-5.73; hypertension aRPR 3.85, 95% CI 3.37-4.40) and abdominal obesity (prehypertension aRPR 2.11, 95%CI 1.92-2.31; hypertension aRPR 3.04, 95% CI 2.69-3.43). Factors with a lower prevalence ratio of both diseases were secondary education (prehypertension aRPR 0.76, 95%CI 0.60-0.95; hypertension aRPR 0.75, 95% CI 0.58-0.97), higher education (prehypertension aRPR 0.78, 95%CI 0.61-0.99; hypertension aRPR 0.62, 95% CI 0.46-0.82), being married/cohabiting (prehypertension aRPR 0.87, 95%CI 0.79-0.95; hypertension aRPR 0.77, 95% CI 0.68-0.87), richest wealth index (only prehypertension aRPR 0.76, 95%CI 0.63-0.92) and living in cities different to Lima (rest of the Coastline, Highlands and Jungle). Having health insurance (only hypertension aRPR 1.26, 95%CI 1.03-1.53) and current drinking (only prehypertension aRPR 1.15, 95%CI 1.01-1.32) became significant factors in rural areas.ConclusionsWe evidenced socioeconomic disparities among people with hypertension and prehypertension. Better health policies on reducing the burden of risk factors are needed, besides, policy decision makers should focus on hypertension preventive strategies in Peru.

Project description:IgA nephropathy (IgAN) is one of the most common glomerular diseases leading to end-stage renal failure. Elevation of aberrantly glycosylated IgA1 is a key feature of it. The expression of the specific molecular chaperone of core1ß1, 3galactosyl transferase (Cosmc) is known to be reduced in IgAN. We aimed to investigate whether the methylation of CpG islands of Cosmc gene promoter region could act as a possible mechanism responsible for down-regulation of Cosmc and related higher secretion of aberrantly glycosylated IgA1in lymphocytes from children with IgA nephropathy. Three groups were included: IgAN children (n = 26), other renal diseases (n = 11) and healthy children (n = 13). B-lymphocytes were isolated and cultured, treated or not with IL-4 or 5-Aza-2'-deoxycytidine (AZA). The levels of DNA methylation of Cosmc promotor region were not significantly different between the lymphocytes of the three children populations (P = 0.113), but there were significant differences between IgAN lymphocytes and lymphocytes of the other two children populations after IL-4 (P<0.0001) or AZA (P<0.0001). Cosmc mRNA expression was low in IgAN lymphocytes compared to the other two groups (P<0.0001). The level of aberrantly glycosylated IgA1 was markedly higher in IgAN group compared to the other groups (P<0.0001). After treatment with IL-4, the levels of Cosmc DNA methylation and aberrantly glycosylated IgA1 in IgAN lymphocytes were remarkably higher than the other two groups (P<0.0001) with more markedly decreased Cosmc mRNA content (P<0.0001). After treatment with AZA, the levels in IgAN lymphocytes were decreased, but was still remarkably higher than the other two groups (P<0.0001), while Cosmc mRNA content in IgAN lymphocytes were more markedly increased than the other two groups (P<0.0001). The alteration of DNA methylation by IL-4 or AZA specifically correlates in IgAN lymphocytes with alterations in Cosmc mRNA expression and with the level of aberrantly glycosylated IgA1 (r = -0.948, r = 0. 707). Our results suggested that hypermethylation of Cosmc promoter region could be a key mechanism for the reduction of Cosmc mRNA expression in IgAN lymphocytes with associated increase in aberrantly glycosylated IgA1.

Dataset Information

Hypertension/prehypertension and its determinants in pediatric IgA nephropathy.

Publications

Hypertension/prehypertension and its determinants in pediatric IgA nephropathy.

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