The genetic variants at the HLA-DRB1 gene are associated with primary IgA nephropathy in Han Chinese

BACKGROUND: Immunoglobulin A nephropathy (IgAN), an immune-complex-mediated glomerulonephritis defined immunohistologically by the presence of glomerular IgA deposits, is the most common primary glomerular disease worldwide and a significant cause of end-stage renal disease. Familial clustering of patients with IgAN suggests a genetic predisposition. METHODS: In this study, 192 patients with IgAN and 192 normal controls in the Sichuan cohort and 935 patients with IgAN and 2,103 normal controls in the Beijing cohort were investigated. HLA-DRB1*01–DRB1*10 specificities were genotyped by the PCR–SSP technique in both cohorts. Based on the HLA-DRB1*04-positive results, the subtypes of HLA-DRB1*04 were analyzed using sequencing-based typing (SBT) in 291 IgAN cases and 420 matched controls. RESULTS: The frequency of HLA-DRB1*04 in the IgAN group was significantly higher than that in the control group (0.129 vs. 0.092, P = 8.29 × 10(-5), odds ratio (OR) =1.381, 95% confidence interval (CI) 1.178–1.619). Other alleles at the HLA-DRB1 locus were observed with no significant differences between the case and control groups. The dominant alleles of the HLA-DRB1*04 subtypes were DRB1*0405 in both cohorts. The frequencies of HLA-DRB1*0405 and 0403 were significantly increased in the patients compared to healthy subjects. CONCLUSION: HLA-DRB1*04 was significantly associated with primary IgAN in Chinese population. This result implies that HLA-DRB1 gene plays a major role in primary IgAN

Effect of SGLT2 inhibitors on the proteinuria reduction in patients with IgA nephropathy

BackgroudRecent trials suggest sodium-glucose cotransporter 2 inhibitors (SGLT2i) significantly reduced proteinuria in patients with IgA nephropathy (IgAN). While little was known its efficacy in clinical practice especially in those already received full dose reninangiotensin-aldosterone system (RAAS) inhibitors.MethodsA cohort of 93 Chinese patients with biopsy-proven IgAN and persistent proteinuria underwent full supportive therapy, including optimal blood pressure control and full dose angiotensin-converting enzyme–inhibitor or angiotensin receptor blocker therapy. Proteinuria reduction at three and six months after initiating SGLT2i therapy was analyzed.ResultsA total of 93 patients were enrolled in this study and 62 of them completed the six-month follow-up. After SGLT2i administration, a significant reduction in proteinuria was observed, with a decrease of 22.9% (p < 0.001) at three months and 27.1% (p < 0.001) at six months. During the six-month follow-up period, a decline of 3.0 mL/min/1.73m2 in estimated glomerular filtration rate (eGFR) (p = 0.012) and an increase of 0.8 g/L in albumin (p = 0.017) were observed. The anti-hypertensive effect of SGLT2i was not significant (p > 0.05). Notably, a consistent antiproteinuric effect of SGLT2i was observed across various settings, including different age groups, baseline levels of proteinuria/eGFR, use of immunosuppressive agents, and the presence of comorbid diabetes and hypertension (all p values >0.05).ConclusionThe proteinuria was significantly reduced after SGLT2i administration in IgAN patients with full dose angiotensin-converting enzyme–inhibitor or angiotensin receptor blocker therapy. Importantly, the antiproteinuric effect of SGLT2i was observed independently of immunosuppressive agent therapy, age, baseline eGFR and proteinuria levels, as well as the history of hypertension and diabetes

Distinct characteristics and prognosis of IgA nephropathy patients with nephrotic syndrome: a propensity score-matched cohort study

IntroductionIgA nephropathy (IgAN) is the most prevalent primary glomerulonephritis globally. While nephrotic syndrome (NS) is uncommon in IgAN, its significance remains unclear.MethodsWe conducted a retrospective analysis of 170 IgAN patients, classifying them into NS (n = 85) and non-NS (n = 85) groups. Our study aims to compare their clinical characteristics, treatment responses, and prognoses. Patients were selected based on renal biopsy from 2003 to 2020. Propensity score matching ensured comparability. Clinical, pathological, and immunological data were analyzed. Composite endpoints were defined as end-stage kidney disease (ESKD) or a 30% decline in estimated glomerular filtration rate (eGFR).ResultsNS patients showed higher eGFR (74.3 ± 36.8 vs. 61.5 ± 33.6 mL/min.1.73 m2, p = 0.02), severe hematuria (35.0 (4.7,147.5) vs. 4.0 (1.8,45,0) cells/μl, p < 0.001), severe foot process effacement (p = 0.01), and lower C3 levels (1.0 ± 0.3 vs. 1.1 ± 0.2 g/L, p = 0.03). In contrast, the non-NS group had higher BMI (24.3 ± 4.0 vs. 26.8 ± 3.7 kg/m2, p < 0.001) and elevated serum uric acid levels (376 (316,417) vs. 400 (362, 501) mmol/L, p = 0.001), suggesting metabolic factors might contribute to their condition. Both groups exhibited similar MESTC scores. NS patients had higher complete remission rates (26.2% vs. 14.1%, p = 0.04). Cox regression revealed NS independently associated with a higher risk of composite endpoints (HR = 1.97, 95% CI 1.05–3.72, p = 0.04). Linear mixed models did not show significant eGFR trajectory differences.DiscussionThis study has established that IgAN patients with NS exhibit distinct characteristics, including active disease and increased complement activation. NS is independently associated with a poorer prognosis, emphasizing the need for targeted interventions in this subgroup

Metagenomic Sequencing From Mosquitoes in China Reveals a Variety of Insect and Human Viruses

We collected 8,700 mosquitoes in three sites in China, which belonged to seven species. Their viromes were tested using metagenomic sequencing and bioinformatic analysis. The abundant viral sequences were detected and annotated belonging to more than 50 viral taxonomic families. The results were verified by PCR, followed by phylogenetic analysis. In the present study, we identified partial viral genes of dengue virus (DENV), a novel circovirus (CCV), densovirus (DNV), Japanese encephalitis virus (JEV), and Wuhan mosquito virus (WMV) in mosquitoes. Metagenomic analysis and PCR amplification revealed three DENV sequences, which were as homologous to the NS3 gene of DENV from Singapore isolated in 2005, with at least 91% nucleotide (nt) identity. Seven fragments of JEV encoding structural proteins were identified belonging to genotype I. They all shared high homology with structural protein genes of JEV isolated from Laos in 2009. The production of infectious virus particles of the newly isolated virus YunnanJEV2017-4 increased after passage from the BHK-21 cell line to the Vero cell line. Novel circovirus-related genes were identified and as being related to an unnamed gene of a mosquito circovirus (MCCV) sequence from the USA isolated in 2011, with at least 41% nt identity: this distant relationship suggests that the parent virus might belong to a novel circovirus genus. Additionally, numerous known viruses and some unknown viruses were also detected in mosquitoes from Yunnan province, China, which will be tested for propagation

Prevention of the progression of chronic kidney disease: Practice in China

Prevention of the progression of chronic kidney disease: Practice in China. With the epidemic rise of end-stage renal disease (ESRD) in many countries of the world, there is an urgent need to develop and implement strategies aiming at preventing the development and progression of chronic kidney disease (CKD), and the situation is the same in China. Glomerulonephritis is still the most common cause of ESRD in China; however, epidemiologic studies have revealed that the prevalence of diabetes and hypertension, which both are major causes of ESRD in many developed countries, are increasing dramatically. Additional studies about the prevalence of albuminuria in diabetes mellitus (DM) patients, and the prevalence of kidney lesion in certain high-risk population (e.g., hypertension and atherosclerosis) are undergoing. According to a questionnaire survey and some reports, education program for Chinese nephrologists and practitioners should to be strengthened