Exploratory study on noninvasive evaluation of renal histopathology by ultrasonic shear wave elastography / 中华肾脏病杂志

Objective:To determine a relationship between ultrasound shear wave elastography (SWE) and pathological lessions of renal tissues in children with chronic kidney disease (CKD).Methods:It was a cross-sectional observational study, involving children admitted to the Department of Pediatrics of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from January to December 2021 with definite pathological diagnosis through kidney biopsy. The SWE was used to determine the Young's modulus (elastic modulus) of the cortex and medulla of the upper, middle, and lower poles of the kidney. The renal histopathology was classified or graded. The statistical method was used to analyze the relationship between Young's modulus of the inferior polar cortex (YM cor) and medulla (YM med) of the right kidney and renal pathology. Results:The study included 110 children with definite pathological diagnosis through renal biopsy, aged (10.1±3.4) years old (2-17 years old), with 55 males (50.0%). The body mass index was (20.6±2.4) kg/m 2, and mean arterial pressure was (95±24) mmHg. There were 94 patients (85.4%) with CKD stage 1, 8 patients (7.3%) with CKD stage 2, and 8 patients (7.3%) with CKD stage 3. There was no significant difference of YM cor and YM med in the upper and middle poles of the right kidneys, and YM med in the lower poles of right kidneys in CKD patients with different stages (all P>0.05). Both YM cor [(15.75±3.36) kPa] and YM med [(13.50±2.43) kPa] of CKD stage 3 patients were significantly higher than those of CKD stage 1 patients [(12.94±2.45) kPa, (11.88±2.23) kPa](both P<0.05). There was no significant difference of YM cor and YM med in the lower poles of right kidneys between stage 1 and stage 2 CKD patients (both P>0.05). YM cor[(17.93±3.23) kPa] and YM med [(15.50±1.48) kPa] in patients with crescentic glomerulonephritis were higher than those in patients with focal segmental glomerulosclerosis [(12.71±2.42) kPa, (11.57±2.63) kPa] and mesangial proliferative glomerulonephritis [(12.73±2.04) kPa, (11.48±2.10) kPa](all P<0.05). There was no significant difference of YM cor and YM med between focal segmental glomerulosclerosis and mesangial proliferative glomerulonephritis (both P>0.05). YM cor [(16.30±2.63) kPa] and YM med [(15.54±1.59) kPa] of Lee's Ⅳ grade of IgA nephropathy were higher than those of Lee's Ⅲ grade [(13.32±2.70) kPa, (12.57±2.50) kPa](both P<0.05), while the International Study of Kidney Disease in Children grade of purpura nephritis had no significant correlation with YM cor and YM med (both P>0.05). YM cor [(15.41±2.37) kPa] and YM med [(13.82±2.59) kPa] of interstitial fibrosis/tubular atrophy (T1/T2) group of IgA nephropathy mixed with purpura nephritis were significantly higher than those of T0 group's [(12.99±2.40) kPa, (11.79±2.05) kPa] (both P<0.05). Moreover, crescent formation (C1) group had a higher YM cor [(14.21±2.77) kPa] and YM med [(12.80±2.47) kPa] than those in C0 group [(12.73±2.15) kPa, (11.59±1.97) kPa] (both P<0.05), while YM cor and YM med were unrelated to the mesangial hypercellularity (M), endocapillary cellularity (E), segmental sclerosis or adhesion (S) indicators (all P>0.05). In lupus nephritis patients, YM cor ( r=0.744, P=0.035) and YM med ( r=0.728, P=0.009) were favorably linked with the chronic index, but not with the activity index (both P>0.05). Conclusions:Renal interstitial fibrosis/tubular atrophy and crescentic development are connected with YM cor and YM med at the lower pole of the kidney as measured by SWE. SWE can be used to assess the chronic renal lesions in children with CKD in the early and middle stages. It may develop into a new noninvasive way to assess renal pathology.

Genotype and phenotype analysis of children with autosomal dominant inheritance Alport syndrome / 中华实用儿科临床杂志

Objective:To analyze the clinicopathological and gene mutation characteristics of children with autosomal dominant inheritance Alport syndrome (ADAS), and to improve the understanding of ADAS.Methods:Ten children with ADAS diagnosed in the Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from September 2016 to February 2020 were enrolled.The clinicopathological and gene mutation features were retrospectively analyzed, and the patients were followed up.Results:(1) The median age at diagnosis was 5.7 (2.4, 9.8) years.Of 10 children, 6 cases (60.0%) showed a family history of renal failure, 4 cases (40.0%) presented with hematuria and proteinuria at diagnosis, and 2 cases (20.0%) suffered a high-frequency hearing loss.Renal biopsy showed extensive splitting and lamellation of the glomerular basement membrane (GBM) dense layer in 4 cases (40.0%), and segmental splitting and lamellation in 6 cases (60.0%). (2)Among 10 children, 4 cases (40.0%) were heterozygous mutations of COL4A3 gene, including 2 point mutations of glycine, and 2 splicing mutations.The other 6 cases (60.0%) were heterozygous mutations of COL4A4 gene, including collagen glycine point mutations in 4 cases, nonsense mutation in 1 case and large deletion in 1 case.Six mutations were new and never reported before. Conclusions:The early clinical presentations of children with ADAS are often atypical and extrarenal manifestations are less common.The GBM dense layer is mainly featured by segmental splitting and lamellation.Glycine point mutations account for the majority of the gene mutations.

Analysis of clinical phenotype and genotype of LAMB2 mutation / 中华肾脏病杂志

Objective:To report two cases of steroid-resistant nephrotic syndrome (SRNS) caused by LAMB2 gene mutation, and summarize the characteristics of genotype, clinical and pathological phenotypes of children with LAMB2 gene mutation. Methods:Two cases with SRNS caused by LAMB2 gene mutation were from Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology in December 2013 and September 2019. The demographic, family history and clinical data of two cases were collected, and the peripheral blood genomic DNA was captured and sequenced by whole exome sequencing. PubMed, Medline, CNKI and Wanfang databases were searched to summarize the clinicopathological phenotypes and genotypes of patients with LAMB2 mutation. Results:Among the two cases with SRNS caused by LAMB2 gene mutation, the clinical phenotypes were all manifested as nephrotic level of proteinuria and hypoalbuminemia, and there was no extrarenal clinical manifestation. One case presented with basement membrane delamination and the other with focal segmental glomerulosclerosis (FSGS). LAMB2 mutations of two cases were Exon32 c.5390G>T(p.Cys1797Phe), Exon19 c.2557C>T(p.Arg853*) and Exon27 c.4370G>A(p.R1457Q), Exon23 c.3325G>A(p.E1109K), respectively. In literature retrieval, there were 37 cases with LAMB2 gene mutation, including 24 cases with renal biopsy data, 13 cases of focal segmental glomerulosclerosis (FSGS), 4 cases of minimal change disease, one case of diffuse mesangial sclerosis, one case of IgM nephropathy, two cases of thin basement membrane nephropathy, and three cases of mesangial hyperplasia. Among them, eight cases had basement membrane delamination tear. Among the 37 cases, 11 cases were homozygous, 22 cases were complex heterozygosity, and 4 cases were heterozygous mutation. Conclusions:LAMB2 mutation may cause delamination tear of glomerular basement membrane. The clinical phenotype is congenital nephrotic syndrome or SRNS. The literature review shows the extrarenal manifestations caused by LAMB2 mutation are mostly various ocular abnormalities, as well as respiratory, digestive and nervous system abnormalities, and the time of progression to end-stage renal disease is also different.

Clinical case analysis of 2019 coronavirus disease (COVID-19) with living-related kidney transplantation / 中华器官移植杂志

Objective:To explore the clinical characteristics of one living-related kidney transplant recipient infected with 2019 coronavirus disease(COVID-19).Methods:The clinical diagnosis and treatment of one living-related kidney transplant recipient after the occurrence of COVID-19 were analyzed retrospectively. Course of onset, clinical manifestations, laboratory and image enamination, outpatient and inpatient therapies and outcomes.Results:The renal transplant recipient was diagnosed as COVID-19(severe) with influenza A virus infection based upon epidemiological survey, clinical manifestations, laboratory examinations, imaging findings and etiological tests. The clinical symptoms were gradually relieved and lung lesions became absorbed after tapering and withdrawing immunosuppressants, antiviral therapy of abidol/oseltamivir, antibiotic therapy, hormonal anti-inflammation, oxygen inhalation, nutritional supports and adequate rest.Conclusions:Living-related kidney transplant recipients have specific immunosuppressive states.The long-term effect of covid-19 on recipients should be determined through long-term follow-ups.

Clinical analysis of 2019 coronavirus disease (COVID-19) on one case with living-related kidney transplantation / 中华器官移植杂志

Objective@#To analyze the clinical characteristics of one living-related kidney transplant recipient infected with 2019 coronavirus disease (COVID-19) .@*Method@#The clinical diagnosis and treatment of one relative renal transplant recipient after the occurrence of COVID-19 were analyzed retrospectively, including the course of onset, clinical manifestations, blood routine test, renal function, lung CT scan, nucleic acid detection, outpatient and inpatient therapies and outcomes.@*Result@#The case was diagnosed as COVID-19 (severe type) with influenza A virus infection. The clinical symptoms were gradually relieved and the lung lesions were absorbed through the treatment of reduce and stop taking immunosuppressant, antiviral therapy of abidol/oseltamivir, prevention of bacterial infection, hormone anti-inflammatory, oxygen inhalation, nutritional support and adequate rest.@*Conclusion@#This case present typical characteristics of COVID-19 in epidemiological investigation, clinical manifestation, examination, pulmonary imaging and etiology. After comprehensive treatment including reduce and stop immunosuppressive therapy, clinical cure was achieved. The long-term effect of COVID-19 on this immunosuppressive patient remains follow-up.

Renal re-transplantation in a pre-sensitized small infant and literature review / 中华器官移植杂志

Objective To explore the feasibility and safety of kidney transplantation for pre-sensitized infants using deceased donors and summarize the relevant literature reports .Methods A second kidney transplantation was successfully performed for an 8-month-old pre-sensitized girl in July 2017 .She had a low level of donor specific antibody (DSA ) against human leucocyte antigen (HLA ) B62 due to severe acute rejection (AR) after her first kidney transplantation .For desensitization , plasmapheresis and intravenous immunoglobulin plus anti-CD20 antibodies were offered on operative day .Clinical data and outcomes were retrospectively analyzed .Results Renal graft regained immediate function after transplantation .Preformed DSA could be detected at 1 week .However ,there was no de novo DSA .At 1 year post-transplantation ,preformed DSA turned negative .During a follow-up period of 2 years ,renal graft showed an excellent function with a serum creatinine of 31 μmol/l and eGFR of 110 ml/min/1 .73m2 .No AR episode or proteinuria occurred .DSA stayed negative .Simultaneously physical development also caught up .Her height of 93 cm tall and weight of 13 .5 kg at month 24 & 8 months corresponded to normal grow th curve of her age .Conclusions Pre-sensitized infant could tolerate desensitization therapy well and achieve satisfactory outcomes .With surgical precisions and optimized managements ,kidney transplantation provides excellent renal functions and survivals for infants with organs from deceased donors .

Clinical characterization and diagnosis of cystic fibrosis through exome sequencing in Chinese infants with Bartter-syndrome-like hypokalemia alkalosis / 医学前沿

Cystic fibrosis (CF) is a fatal autosomal-recessive disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. CF is characterized by recurrent pulmonary infection with obstructive pulmonary disease. CF is common in the Caucasian population but is rare in the Chinese population. The symptoms of early-stage CF are often untypical and may sometimes manifest as Bartter syndrome (BS)-like hypokalemic alkalosis. Therefore, the ability of doctors to differentiate CF from BS-like hypokalemic alkalosis in Chinese infants is a great challenge in the timely and accurate diagnosis of CF. In China, sporadic CF has not been diagnosed in children younger than three years of age to date. Three infants, who were initially admitted to our hospital over the period of June 2013 to September 2014 with BS-like hypokalemic alkalosis, were diagnosed with CF through exome sequencing and sweat chloride measurement. The compound heterozygous mutations of the CFTR gene were detected in two infants, and a homozygous missense mutation was found in one infant. Among the six identified mutations, two are novel point mutations (c.1526G > C and c.3062C > T) that are possibly pathogenic. The three infants are the youngest Chinese patients to have been diagnosed with sporadic CF at a very early stage. Follow-up examination showed that all of the cases remained symptom-free after early intervention, indicating the potential benefit of very early diagnosis and timely intervention in children with CF. Our results demonstrate the necessity of distinguishing CF from BS in Chinese infants with hypokalemic alkalosis and the significant diagnostic value of powerful exome sequencing for rare genetic diseases. Furthermore, our findings expand the CFTR mutation spectrum associated with CF.

Clinical and pathological features of dense deposit disease in children / 临床儿科杂志

10.3969/j.issn.1000-3606.2013.06.020

The clinical and pathological features of Alport syndrome in children / 临床儿科杂志

Objective To analyze the clinical and pathological characteristics of Alport syndrome in children. Methods Clinical and pathological information gathered from 62 patients during March 1989 to August 2012 was retrospectively analyzed. Results Four autosomal recessive Alport syndromes (AR-AS) and 58 X-linked Alport syndromes (XL-AS) were analyzed. Of the XL-AS, 47 were boys and 11 were girls. Most of patients induced by upper respiratory tract infections, and onset with hematuria and proteinuria. There was no signiifcant gender difference in family history, impaired renal tubular proteins, hypertension, im-paired renal function, hearing loss, ocular abnormalities or renal pathological changes under light microscopy. However, extensive lamination and split of glomerular basement membrane (GBM) dense layers were found in 83.0%male and 18.2%female patients (P=0.000) and the rest patients were presented with limited distribution of typical GBM changes. Proteinuria progressed signiif-cantly with age in XL-AS males (r=0.501, P=0.000). Five XL-AS patients developed to end stage renal disease (ESRD) between 11 to 16 years old. Conclusions XL-AS is the main inherited type and severe changes of GBM are common in XL-AS males. Proteinuria increases remarkably with age. The detection of type IV collagen in renal tissue or skin is helpful to diagnose Alport syndrome and conifrm inheritance modes.

SEB superantigen induces steroid resistance in PBMCs / 中国病理生理杂志

AIM: To establish a model of staphylococcal enterotoxin B (SEB)-induced steroid resistance in human peripheral blood mononuclear cells (PBMCs), and to investigate the potential mechanism of SEB superantigen-induced steroid resistance in vitro. METHODS: PBMCs were isolated from normal children blood by Ficoll-Hypaque gradient centrifugation and stimulated with SEB at different concentrations. The proliferation rate of cells was measured by MTT assay. The subcellular localization of glucocorticoid receptor α (GRα) was examined by confocal microscopy. Protein phosphorylation was measured by means of Western blotting. RESULTS: SEB induced steroid resistance in a range of 10-500 μg/L and no significant difference among concentrations was observed. In SEB-stimulated PBMCs, the GRα did not translocate to the nuclear after dexamethasone treatment. ERK inhibitor U0126 significantly attenuated the inhibition of GRα nuclear translocation in SEB-stimulated PBMCs. SEB also induced more rapid and sustained phosphorylation of ERK1/2 in PBMCs. CONCLUSION: This study demonstrates that SEB may contribute to steroid resistance through ERK pathway and is associated with abrogation of GRα nuclear translocation.