[Efficacy of plasma exchange in severe crescentic IgA nephropathy: A multicentered, cohort study].

OBJECTIVE: To evaluate the efficacy of plasma exchange therapy on crescentic IgA nephropathy (IgAN). METHODS: A retrospective analysis was performed in a cohort of patients with crescentic IgAN from January 2012 to September 2020 at 9 sites across China. Clinical and pathological data, as well as therapeutic regimens, were collected. In order to minimize the effect of potential confounders in baseline characteristics, propensity score matching using a 1 ∶1 ratio nearest neighbor algorithm was performed between the adjunctive plasma exchange therapy group and the intensive immunosuppressive therapy group. The primary outcome was end-stage of kidney disease (ESKD). Kaplan-Meier method was used to compare the difference in renal survival between the two groups. RESULTS: A total of 95 crescentic IgAN patients with acute kidney disease were included in this study, including 37 (38.9%) patients receiving adjunctive plasma exchange therapy, and 58 (61.1%) patients receiving intensive immunosuppressive therapy. In the whole cohort, the baseline eGFR was 12.77 (7.28, 21.29) mL/(min·1.73 m2), 24-hour urinary protein quantification was 5.9 (4.0, 8.9) g, and crescent percentage was 64.71% (54.55%, 73.68%). In the study, 23 patients in each group were matched after propensity score matching The median follow-up time was 7 (1, 26) months. As a whole, 29 patients (63.0%) reached ESKD, including 16 patients (69.6%) in the adjunctive plasma exchange therapy group and 13 (56.5%) patients in the intensive immunosuppressive therapy group.. There were no stastical difference between the two groups in terms of baseline eGFR [14.30 (9.31, 17.58) mL/(min·1.73 m2) vs. 11.45 (5.59, 20.79) mL/(min·1.73 m2)], 24-hour urinary protein (7.4±3.4) g vs. (6.6±3.8) g, crescent percentage 64.49%±13.23% vs. 66.41%±12.65% and the proportion of patients received steroid therapy[23 (100.0%) vs. 21 (91.3%)] (All P>0.05). Kaplan-Meier survival analysis demonstrated that there was no significant difference in renal survival rate between the two groups (Log-rank test, P=0.933). CONCLUSION: The adjunctive plasma exchange therapy in addition to conventional intense immunosuppressive therapy did not additionally improve the prognosis of crescentic IgA nephropathy.

[Chronic kidney disease in community: Current state for screening and management].

OBJECTIVE: To understand the current state and problem of screening and management of chronic kidney disease (CKD) in the community, and to explore the improving strategies. METHODS: We established a community-CKD integrated data science platform based on medical information from 79 community health centers, in Xicheng District, Beijing. Patients who referred to 79 community health centers from 21 June 2015 to 20 November 2021 were retrospectively included in this study using the CKD data platform. The monitoring of the indicator of kidney injury, risk factor control, medicine use and device configuration in community were assessed in the study. RESULTS: In the study, 70.6% of the population were identified with high risk of CKD in the total 374 498 individuals who referred to the community health centers. Hypertension (62.3%), coronary heart disease (43.3%) and diabetes (30.4%) were the most common risk factors in high-risk CKD population. Only 17.2% of the patients with high risk of CKD were screened for kidney injury including at least one serum creatine (Scr) or albuminuria test, among which 10 992 (24.2%) individuals were defined as CKD. 22.7% (11 338/49 908) of the total patients with kidney screening in community were defined as CKD, of whom, 42.6% and 46.1% were identified by estimated glomerular filtration rate (eGFR) < 60 mL/(min·1.73 m2) and abnormalities of urinary proteins, respectively. The overall CKD detection rate in the community was 5.2% (19 299/374 498), and the miss-diagnosis rate of CKD was 38.1%. Of the 79 community health centers, 13 (16.5%) were equipped with ACR testing device, and eGFR was reported directly in 66 (83.5%) centers. Altogether 60.3% and 99.7% of the community CKD patients achieved glucose control and blood pressure control, respectively, and 59.3% of the CKD patients who had proteinuria was treated with renin-angiotensin-aldosterone system (RAAS) inhibitors. CONCLUSION: High-risk CKD population account for a substantial proportion of patients who refer to the community. Early screening, prevention and management of CKD in the community are of great importance to improve the prognosis and decrease the burden of CKD. It's essential to establish a screening and monitoring system, strengthen standardized management and clinician training for improving the ability of CKD management in the community.

[Trans-ethnic analysis of susceptibility variants in IgA nephropathy].

OBJECTIVE: To compare the genetic architecture of susceptibility variants of IgA nephropathy (IgAN) in Chinese and Europeans. METHODS: We selected the independent genome-wide significant variants of IgAN in European population as candidate variants. Their associations, risk alleles, risk allele frequencies, odds ratios and population attributable risk scores were derived and calculated, then compared with those in the current Chinese population, including 1 194 IgAN patients and 902 controls. Using the significant variants, genetic risk scores were calculated and compared between the East Asians and the Europeans. The correlation between the genetic risk scores and clinical manifestations was also evaluated. RESULTS: There were 16 independent single nucleotide polymorphisms (SNPs) located in 11 loci showing significantly association with susceptibility to IgAN in the Europeans. 93.75% (15/16) of them also showed significant associations in the Chinese (P<0.05). The effects of all the associated SNPs were in the same direction, either risk or being protective for IgAN, between the Chinese and the Europeans. On the contrary, remarkable higher risk allelic odds ratio (P=1.94×10-2), higher risk allele frequency (P=3.09×10-2), and higher population attributable risk (P=3.03×10-4) were observed for most of the associated SNPs in the Chinese than in the Europeans. Furthermore, genetic risk scores were significantly larger in the Asian populations compared with the Europeans (P=1.78×10-163). While there was no significance among the subpopulations in both the East Asians and the Europeans. Compared with the healthy controls, the genetic risk score in the IgAN patients was significantly larger (P=3.60×10-27). Clinical analysis showed the genetic risk score was positively associated with serum levels of IgA and IgA1, phases of chronic kidney disease and Haas grades. CONCLUSION: Our study provides further evidence in the shared genetic architecture between Chinese and Europeans, while differences with respect to the effect sizes and risk allele frequencies across ethnicities, contributing partially to the differences of disease prevalence.

DEFA gene variants associated with IgA nephropathy in a Chinese population.

IgA nephropathy (IgAN) is a complex syndrome with high genetic heterogeneity. More recently, a genome-wide association study (GWAS) from Southern Han population revealed that variants within 8p23.1, where the DEFA genes encoding a-defensins assembled, were associated with susceptibility to IgAN. To replicate the association and fine-map the genetic variants, a case-control genetic study from an independent Northern Han cohort was conducted. A total of 60 single-nucleotide polymorphisms in a region spanning 350 kb encompassing the DEFA genes cluster were analyzed in 2096 individuals. Copy number variations of DEFA1A3 within the loci were also checked for the independent association. Functional significance of the associated variants was further examined by the in silico method as well as by cis-acting expression quantitative trait loci analysis with mRNA. It showed that 17 out of 60 (28.3%) variants were associated with susceptibility to IgAN. Two independent signals with functional potentials were discovered (rs2738058, P=4.64 × 10(-5), odds ratio (OR)=0.76, 95% confidence interval (CI) 0.66-0.87 and rs9644778, P=4.78 × 10(-3), OR=1.21, 95% CI 1.06-1.39). Besides, marginally significant association of rs9644778 risk genotype with lower proportion of gross hematuria (CC+CA vs AA 35.2% vs 30.2%, P=0.073) was observed. In conclusion, DEFA gene polymorphisms have potentially pathogenic roles in IgAN, and the role of mucosal immunity in the pathogenesis of IgAN has to be emphasized.

Lycopene protects pancreatic acinar cells against severe acute pancreatitis by abating the oxidative stress through JNK pathway.

This study investigated the anti-oxidative and anti-inflammatory effects of lycopene on severe acute pancreatitis (SAP) in both in vivo and in vitro models. Utilizing a rat model, we found that lycopene administration protected against SAP, as indicated by the decreased levels of serum amylase and C-reactive protein. Pathological changes were alleviated by pretreatment with lycopene. The serum levels of tumor necrosis factor-α, interleukin-6, macrophage inflammatory protein-1α, and monocyte chemotactic protein-1 were decreased by lycopene. The decreased reactive oxygen species (ROS) content in the pancreatic tissues of the lycopene-treated group were indirectly evaluated by measuring the levels of myeloperoxidase, lipid peroxidase, and superoxide dismutase. Lycopene protected acinar cells against necrosis and apoptosis by relieving the mitochondrial and endoplasmic stress caused by ROS which was shown in electron microscopy and immunohistochemistry staining of active nuclear factor-κB p65. The protective effect was also observed in a simulated SAP model in a rat acinar cell line. ROS and apoptotic staining were compared between groups. Lycopene exerts protective effects against SAP in rats that may be related to its anti-inflammatory property through inhibiting the expression of damage-associated molecular patterns, and anti-oxidative property which can thus maintain cellular homeostasis and prevent the phosphorylation of JNK pathway.

Detection of resistance phenotype and genotype of avian Escherichia coli in Hebei Province.

We investigated the resistance of avian Escherichia coli to commonly used clinical antibiotics in Hebei Province. It is of significance to reveal the extent and mechanism of drug resistance, as well as to prevent and control colibacillosis. We investigated the resistance of 132 E. coli isolates to 5 kinds of antibiotics (including ß-lactams, aminoglycosides, tetracyclines, sulfonamides, and chloramphenicol) using the Kirby-Bauer drug susceptibility test, and resistance genes were detected by PCR. The results showed that the E. coli had a higher resistance rate to ampicillin, cephalotin, gentamicin, streptomycin, tetracycline, doxycycline, sulfamethoxazole trimethoprim, sulfamonomethoxine, and florfenicol, but it had higher sensitive rate to cefepime, imipenem, spectinomycin, and minocycline. Of the resistance genes, the TEM, aac(3)-IIa, tetA, Sul1, Sul2, and forl had higher positive rates. Therefore, drug resistance of avian E. coli in Hebei Province is very serious. The resistance mechanisms may include structure changes of the target enzyme mediated by multiresistance genes, and resulting in reduced affinity and increased efflux of antibiotics.

Survey on tetracycline resistance and antibiotic-resistant genotype of avian Escherichia coli in North China.

The experiment was performed to investigate the tetracycline resistance and antibiotic-resistant genotype of avian Escherichia coli in North China and to analyze the correlation of genotype and phenotype. The resistance of 164 E. coli isolates (from Beijing, Tianjin, inner Mongolia, Shanxi, and Hebei regions of China) to tetracycline, doxycycline, and minocycline was investigated by using a drug susceptibility test. The results show that the rate of resistance to tetracycline antibiotics was 89.63% (147/164). The higher resistance rate was 84.76% (139/164) to tetracycline and 70.12% (115/164) to doxycycline, and the lowest resistance rate was 4.88% (8/164) to minocycline. The distribution of tetracycline resistance (Tcr) genes (tetA, tetB, tetC, and tetM) in avian E. coli isolates was detected by PCR. Of the isolates, 82.32% (135/164) carried tetracycline resistance genes. The positive rates of tetA, tetB, and tetM were 57.93% (95/164), 38.41% (63/164), and 10.97% (18/164), respectively. No tetC was amplified in avian E. coli isolates. The total positive rate of resistance genes (82.32%) was almost equal to the total rate of resistance to tetracycline antibiotics (89.63%). Thus, the positive rate of genotype was basically in line with that of phenotype for tetracycline resistance. The tetracycline resistance genes are widely distributed in E. coli and their main resistance mechanism to tetracycline is the active efflux effect mediated by tetA and tetB.

Molecular epidemiological survey on aminoglycoside antibiotics-resistant genotype and phenotype of avian Escherichia coli in North China.

Monitoring drug resistance in Escherichia coli is important for prevention and treatment of colibacillosis. To choose effective drugs to prevent and control avian colibacillosis in North China, we investigated resistance of 205 E. coli isolates (from Beijing, Tianjin, inner Mongolia, Shanxi, and Hebei regions) to commonly used clinical aminoglycoside antibiotics using a drug susceptibility test. The results show that the isolates had varying degrees of resistance to kanamycin, gentamicin, streptomycin, amikacin, neomycin, and spectinomycin. Particularly, the resistance rates of the former 3 antibiotics exceeded 40%. To explore the reasons for wide drug resistance, aminoglycosides modifying enzymes (AME) genes, which are important in generation of aminoglycoside resistance, were detected by PCR. Of the isolates, 60.98% carried AME genes and 38.05% carried commensal multidrug resistance genes. Therefore, resistance of avian E. coli to aminoglycoside antibiotics is very serious in North China, perhaps due to the existence of resistance genes.

Is FCGR2A a susceptibility gene to systemic lupus erythematosus in Chinese?

Recent genome-wide association scans and replication studies reinforce that FCGR2A is a susceptibility gene in systemic lupus erythematosus (SLE) in Caucasians. However, previous case control studies denied such conclusions in Chinese people. Besides genetic heterogeneity among different ethnicities, copy number variation (CNV), non-homogenous phenotypes and insufficient power may be confounders. We performed a case control study with 1066 Chinese (589 SLE patients and 477 healthy controls) and a meta-analysis based on 2328 SLE patients and 2313 healthy controls. FCGR2A CNV and FCGR2A131H/R [rs1801274] were detected by TaqMan assays. No variation of copy numbers of FCGR2A gene was found in Chinese. A further case control study suggested a dose-response character for FCGR2A131H/R and it affected disease activity, severity and prognosis. Finally, meta-analysis indicated FCGR2A that was a susceptibility gene to SLE in Chinese with an odds ratio of 1.094 and population attributable risk proportion of (PARP) 0.031. By an integrative strategy, we validate that FCGR2A bears no population-specific CNV. FCGR2A131H/R contributes to SLE susceptibility in Chinese, and affects disease activity, severity and prognosis. The undetected association in Chinese derives from under-power rather than any methodological obstacle due to CNV or population-specific genetic effect.

Association between polymorphisms in the FCGRT gene and lupus nephritis in Chinese patients.

OBJECTIVE: Studies on mouse models have indicated that the neonatal Fc receptor (FcRn) plays important roles in a variety of autoimmune diseases. A variable number of tandem repeat (VNTR) polymorphisms within the FCGRT gene have been detected, and were found to affect the expression and functioning of FcRn. This study investigated the possible association of FCGRT VNTR polymorphisms with susceptibility and clinical manifestations in patients with lupus nephritis (LN). METHODS: A total of 404 Han Chinese subjects, comprising 200 patients with LN and 204 geographically-matched healthy controls, participated in the study. The FCGRT VNTR polymorphism was genotyped by DNA amplification using a touchdown polymerase chain reaction followed by polyacrylamide gel electrophoresis. RESULTS: The distribution of VNTR polymorphisms within the FCGRT gene in Chinese subjects was different to that in Caucasians. Analysis of allele and genotype frequencies revealed no significant difference between LN patients and controls. There was no significant difference in the clinical features or prognosis in LN patients when stratified by VNTR polymorphism. CONCLUSION: Our results suggest that VNTR polymorphisms within the FCGRT promoter are not associated with LN in the Chinese population.

Activity of alpha2,6-sialyltransferase and its gene expression in peripheral B lymphocytes in patients with IgA nephropathy.

It is known that aberrant sialylation of IgA1 is involved in the pathogenesis of IgA nephropathy (IgAN). We hypothesize that aberrant sialylation of serum IgA1 may result from changes in the activity of alpha2,6-sialyltransferase (alpha2,6-ST) or expression of its coding gene ST6GALNAC2 in peripheral B lymphocytes. Sixty patients with IgAN and 20 healthy controls were enrolled. Peripheral B lymphocytes were isolated by CD-19-positive magnetic beads. The expression level of ST6GALNAC2 was quantitatively analysed by real-time reverse-transcriptase polymerase chain reaction (PCR). Serum IgA1 and sialylation levels were detected by enzyme-linked immunosorbent assay (ELISA) and specific lectin-binding ELISA. Activity of alpha2,6-ST was measured by specific lectin-binding ELISA. Expression of ST6GALNAC2 in B peripheral lymphocytes was significantly lower in patients with IgAN than that in normal controls (3.7 +/- 2.2 versus 6.3 +/- 2.3, P = 0.016); alpha2,6-ST activity in B lymphocytes was correlated positively with the level of alpha2,6-sialic acid in serum IgA1 in patients (n = 42) and controls (n = 12) (r = 0.37, P = 0.007). However, alpha2,6-ST activity did not differ between patients with IgAN and controls (1.19 +/- 1.43 versus 1.06 +/- 1.17, P > 0.05). These data suggested that reduced sialylation of serum IgA1 may result from decreased expression of ST6GALNAC2. The factors affecting activity of alpha2,6-ST in the sialylation of IgA1 need to be further investigated.

Variants of C1GALT1 gene are associated with the genetic susceptibility to IgA nephropathy.

IgA nephropathy (IgAN) is a polygenic disorder and the precise role of genetic factors remains elusive. Increasing evidences have implicated the aberrant galactosylation of IgA1 molecules in the pathogenesis of IgAN. The galactosyltransferase, core 1 beta3-Gal-T, and its chaperone, Cosmc, play important roles in beta1,3 glycosylation of IgA1 molecule. A case-control association study was performed to investigate the association between single-nucleotide polymorphisms (SNPs) of C1GALT1 and C1GALT1C1 genes and the susceptibility to IgAN. A total of 1164 subjects were enrolled, including 670 IgAN patients and 494 geographically matched healthy controls. Five SNPs, -734C/T, -465A/G, -330G/T, -292C/-, and 1365G/A in C1GALT1 were selected as tagging SNPs. The D allele and DD genotype of -292C/- in IgAN patients were significantly lower than in the controls (P<0.01). The frequency of haplotype YATIG (Y=C or T) was significantly lower in patients than in controls (0.0719 vs 0.1168, P=2.775 x 10(-4), odds ratio (OR)=0.70). The haplotype YAGDA (0.1236 vs 0.0791, P=3.815 x 10(-3), OR=1.77) and YATDG (0.0840 vs 0.0298, P=1.258 x 10(-5), OR=3.03) were significantly higher in patients than in controls. The present study suggested that the polymorphisms of C1GALT1 gene were associated with the genetic susceptibility to IgAN in Chinese population.