Objective:To define more information for familial hematuria by genetic screening in a pedigree with familial hematuria.Methods:This was a 4 generation pedigree included 20 family members. The clinical data and laboratory manifestations of the family members were reviewed and collected from medical records. Meanwhile, the peripheral blood samples of 11 family members of the pedigree were collected, and then DNA samples were extracted by salting out method for genetic analysis. For genetic analysis, firstly, three family members including the proband were selected for whole exome sequencing, and the genetic variations were screened according to the sequence variation interpretation guidelines from the American College of Medical Genetics and Genomics (ACMG) for diagnostic sequence interpretation. Then PCR and Sanger sequencing were used to verify the identified pathogenic variants in all family members in the pedigree.Results:In the pedigree, 6 female members had persistent hematuria. Among them, 2 died due to end-stage renal disease, 2 died due to non-renal diseases, and 2 maintained stable renal function. One of the two members with stable renal function was diagnosed as IgA nephropathy by renal biopsy. Moreover, diffuse basement membrane lesions were identified in her renal biopsy sample after the electron microscope examination, which resulted in the suspected diagnosis of Alport syndrome. Genetic testing in this pedigree revealed two novel mutations in COL4A4 gene (NM_000092), c.G446T:p.G149V in exon 7 and c.G1249A:p.G417R in exon 20. Conclusion:Two novel mutations of COL4A4 gene (c.G446T:p.G149V in exon 7 and c.G1249A:p.G417R in exon 20) in a hematuria pedigree are related with phenotype of familial hematuria.

Objective To establish the measurement of IgA1 O-glycan-specific antiglycan autoantibodies in patients with IgA nephropathy (IgAN),and evaluate their role in the development and progression of IgAN.Methods In the IgAN regular follow-up cohort of Peking University Institute of Nephrology from January 2006 to December 2015,170 patients drawn by stratified randomization were enrolled in this study.Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of plasma galactose-deficient IgA1 (Gd-IgA1) and antiglycan autoantibody (IgG and IgA1).The correlation between antiglycan autoantibodies and clinicopathological parameters was analyzed by linear correlation and multiple linear regression analysis.The receiver operating characteristic curve (ROC) was used to evaluate the value of plasma anti glycide antibodies in the diagnosis of IgAN.Results IgG and IgA1 antiglycan antoantibodies that specifically recognized Fab-hinge region (Fab-HR) antigens could be detected in both IgAN and healthy control group.Agglutinin inhibition test showed that the specific antigen epitope was N-acetylgalactosamine (GalNAc) residue exposed to galactose deficiency in IgA1 hinged region.There was no significant difference in the absolute levels of plasma IgG antiglycan autoantibodies between IgAN and healthy controls (P=0.963).After adjustment of the plasma level of IgG,the normalized antiglycan autoantibody (ln[IgG antiglycan antibody/IgG]) in patients with IgANwas significantly higher than that in healthy controls (0.58±0.31 vs 0.37±0.11,P ＜ 0.01).The normalized level of IgG antiglycan autoantibody in IgAN patients was positively correlated with 24 h urine protein level during renal biopsy (Spearman r=0.183,P ＜ 0.05),and was also significantly correlated with 24 h urinary protein level after adjusting for baseline clinical and pathological factors (β=0.713,95％CI 0.323-1.102,P ＜ 0.01).The area under ROC curve (AUC) of normalized IgG antiglycan autoantibody in the diagnosis of IgAN was 0.764 (95％ CI 0.682-0.845,P ＜ 0.05).Using the cut-off value of 0.396,the sensitivity and specificity of normalized IgG antiglycan autoantibody for IgAN were 0.729 and 0.700 respectively.There was no significant difference in the absolute or normalized levels of IgA1 antiglycan autoantibodies between IgAN patients and healthy controls.Conclusions Gd-IgA1-specific antiglycan autoantibodies can be detected both in IgAN patients and healthy controls.They are elevated in some patients with IgAN and possibly involved in the development of IgAN.

Objective:To improve the ability of identification and differential diagnosis of severe systemic lupus erythematosus (SLE).Methods:A severe SLE patient with lupus myocarditis, neuropsychiatric lupus, thrombotic microangiopathy (TMA) and other multiple system involvement was reported and discussed.Results:A young female patient developed albuminuria 5 months ago, edema of both lower limbs 3 months ago, change of consciousness 1 month ago and two convulsions attack 2 days ago. She experienced life threatening manifestations such as neuropsychiatric lupus, myocardial involvement of lupus, and TMA. During the course, her condition was generally improved after glucocorticoid pulse therapy and plasma exchange.Conclusion:Various complicated clinical manifestations related to SLE need to be recognized earlier and intervened as soon as possible.

In this retrospective cohort study, we aim to evaluate the effect of endocapillary hypercellularity (E) lesions on the renal prognosis and response to immunosuppressive therapy, especially diffuse endocapillary hypercellularity lesion in IgA nephropathy (IgAN). A total of 365 patients with IgAN and E lesions and 31 patients with diffuse E lesions and over 12-month follow-up period were included in this study. We performed an 1∶1 propensity score to identify controls with matched clinical and pathological features from 769 IgAN patients without E lesions. The end-point was defined as a 30% decrease in estimated glomerular filtration rate (eGFR) or end-stage kidney disease. The kidney survival of the two groups was compared by Kaplan-Meier analysis. During median follow-up period of 41 months, kidney survival rates in patients with E lesions were 96.0% at 1 year, 83.6% at 3 years, 67.7% at 5 years; while they were 96.9% at 1 year, 83.6% at 3 years, and 68.7% at 5 years in patients without E lesions ( P=0.265).The HRof immunosuppressive therapy was 1.038 (95% CI 0.749-1.440) and 1.113 (95% CI 0.770-1.609) in patients not receiving immunosuppressive therapy ( P=0.781). (2) During median follow-up period of 52.5 months, the kidney survival rates in patients with diffuse E-lesion were 100.0% at 1 year, 96.2% at 3 years, 74.5% at 5 years; while they were 96.2% at 1 year, 82.3% at 3 years, and 63.7% at 5 years in patients without E-lesion ( P=0.158). The HR of immunosuppressive therapy was 0.625 (95% CI 0.213-1.839) and 0.447 (95% CI 0.028-7.191) in patients not receiving immunosuppressive therapy ( P=0.825). E lesion or diffuse E lesion may not be associated with prognosis or response to immunosuppressive therapy.

Objective:To evaluate the clinicopathological characteristics and prognosis of IgA nephropathy (IgAN) patients with microangiopathy lesions and with no hypertension.Methods:Adult IgAN patients without hypertension were selected from Peking University First Hospital. All kidney biopsies were independently reviewed by 2 investigators. Patients were divided into three groups (microangiopathy group, simple arterio/arteriolosclerosis group and normal vascular group) by renal arteriolar lesions. Composite kidney end point event defined as a ≥30% reduction in estimated glomerular filtration rate (eGFR) and end-stage kidney disease. Cox regression analysis was used to test the association between microangiopathy lesions and the outcomes.Results:A total of 420 patients were included in this study, of which 37(8.8%) patients had renal arteriolar microangiopathy lesions, 134 (31.9%) patients had simple arterio/ arteriolosclerosis, and the others had no vascular lesion. Compared with simple arterio/arteriolosclerosis group or non-vascular lesion group, patients with renal arteriolar microangiopathy lesions had more severe urine protein ( P=0.002), worse renal function ( P<0.001), higher proportion of segmental glomerulosclerosis and/or balloon adhesion (S1), tubular atrophy/interstitial fibrosis (T1/2), cellular/fibrocellular crescents (C1/2) (all P<0.05). During the follow-up, 20(54.1%) patients with microangiopathy lesions, 45(33.6%) patients with simple arterio/arteriolosclerosis and 82(32.9%) patients without vascular lesion reached the composite kidney end points ( χ2=6.491, P=0.039). In a multivariable Cox regression model, the presence of microangiopathy lesions was an independent risk factor for kidney disease progression in IgAN patients ( HR=1.872, 95% CI 1.044-3.357, P=0.035), and simple arterio/arteriolosclerosis was not a risk factor for kidney disease progression. Conclusion:It is not uncommon for non-hypertensive patients with IgAN having microangiopathy lesions, which suggests that hypertension is not the sole risk factor for microangiopathy lesions.

Objective: To evaluate the quality of clinical practice guidelines for kidney diseases in China and provide reference for selecting suitable high-quality guidelines for primary care and developing standardized guidelines. Methods: The China Guideline Clearinghouse, China Biology Medicine disc, VIP Database, Wanfang Database and CNKI, and other resources were searched from January 2013 to July 2018. In accordance with the criteria for inclusion and exclusion, the published guidelines for kidney diseases were screened. The Appraisal of Guidelines Research and Evaluation-China (AGREE-China) was used to systematically assess the current status of domestic guidelines for kidney diseases. Results: A total of 18 guidelines for kidney diseases were included, covering different types of kidney disease such as glomerulonephritis, nephrotic syndrome, end-stage renal disease and other diseases. The overall score ranged from 30 to 68, with an average score of 47.3. The average scores of these guidelines were 20.1, 12.8, 0.5, 9.9 and 3.9 in five review fields including scientificity/rigorism, effectiveness/safety, economy, availability/feasibility, and conflicts of interest, respectively. Of these 18 guidelines, 8(44.4%) guidelines were strongly recommended, and 10(55.6%) guidelines were weakly recommended. Conclusions There are still deficiencies in scientificity/rigorism and economy in current guidelines for kidney diseases in China. The AGREE-China can be used as an evaluation tool for guidelines for kidney diseases in accordance with China's situation, while its practicability and feasibility still need further verification and improvement.