Application of percutaneous endoscopic gastrostomy in three infants with chronic kidney disease / 中华肾脏病杂志

The paper summarizes the clinical and follow-up data of percutaneous endoscopic gastrostomy (PEG) in three infants with chronic kidney disease to explore the safety and reliability of using PEG to improve the growth and development, and nutritional status. During follow-up, the weight and height of case 1 and 3 were obviously improved. Case 2 was followed up for 3 months, due to dying of cardiac arrest, and the infant's height and weight were not significantly improved. Serum albumin and prealbumin improved in 3 cases after PEG. No PEG-related infection occurred in 3 infants.

Post-transplantation lymphoproliferative disorders of kidney in children: two cases report and literature review / 中华肾脏病杂志

Objective:To report two cases of post-transplantation lymphoproliferative disorders (PTLD) after kidney transplantation in children and review the literature, and to improve clinicians' understanding of PTLD in children.Methods:The clinical data of two children with PTLD admitted to the Children's Hospital of Fudan University were collected and analyzed. The PTLD-related literature of PubMed, Embase, Web of Science, Scopus, Cochrane Library, Wanfang, CNKI, Weipu Database and China Biomedical Literature Service System from the establishment of the database to January 2020 were collected for literature review. Multivariate logistic regression analysis method was used to analyze the influencing factors of prognostic in children with PTLD.Results:Both of the patients had negative Epstein-Barr virus (EBV) and Cytomegalovirus (CMV) before transplantation and anti-thymocyte immunoglobulin (ATG) were induced during transplantation. PTLD in case 1 and case 2 was diagnosed at 3 and 12 months after transplantation, respectively, with positive EBV and CMV serological reaction. The pathological diagnosis was monomorphic PTLD in case 1 and the case 2 was clinically considered as non-hodgkin lymphoma. They all received thrapies of immunosuppressive reduction combined with anti-CD20 monoclonal antibody and chemotherapy. PTLD was relieved and graft function was normal in 2 cases, while case 1 died two and half years after transplantation due to intracranial fungal infection. According to the analysis of 56 children (including 2 cases in this study) with PTLD from the literature review, the median time of PTLD from transplantation was 41.8 months. The initial involved organs were digestive tract [17 cases (30.4%)], respiratory system [8 cases (14.3%)], nervous system [7 cases (12.5%)] and pharyngeal lymph ring [7 cases (12.5%)], respectively. The main pathologic type of PTLD was monomorphic [34 cases (60.8%)]. Fifty-six cases were all positive in EBV serological reaction when PTLD was diagnosed. The treatment included immunosuppressive reduction combined with anti-CD20 monoclonal antibody and chemotherapy. Forty-eight cases of PTLD were relieved, while 8 cases lost graft function. Eleven cases died, including 3 cases due to infection and the other 8 cases due to PTLD. Multivariate logistic regression showed that monomorphic PTLD was a risk factor of death for PTLD children ( OR=21.616, 95% CI 1.007-464.107, P=0.049). Conclusions:PTLD in children with kidney transplantation is mostly associated with EBV infection, and the clinical manifestations are diverse. Monomorphic PTLD has a poor prognosis and high mortality.

Quality of life in children with end-stage renal disease undergoing renal replacement therapy: a cross-sectional survey / 中华肾脏病杂志

Objective@#To evaluate the quality of life (QOL) of children with uremia who underwent renal replacement therapy (RRT) and identify the influencing factors for QOL in order to improve the QOL of children with uremia.@*Methods@#Children with ESRD who underwent dialysis or kidney transplantation (KT) at Children's Hospital of Fudan University between November 2016 and October 2017 were enrolled. The children and/or their parents completed and returned the Pediatric QOL Inventory Measurement Models (PedsQLTM) 4.0 questionnaire. Moreover, the clinical data of these children were collected. According to the way of RRT, children were divided into dialysis group and KT group. The differences of scores between two groups were compared. Multiple linear regression analysis was used to analyze the factors affecting the QOL of children.@*Results@#A total of 79 children undergoing RRT were enrolled. Among them, 48 cases in the dialysis group and 31 cases in the KT group. For children in KT group, the total PedsQL scores of child-self and parent-proxy assessment were higher than those in dialysis group (P<0.05). The total scores for the QOL of child-self and parent-proxy assessment were roughly the same for KT children (P>0.05). The total scores for the QOL of child-self and parent-proxy assessment were different for dialysis children (P=0.05). Short stature (height<3th percentile) and elevated left ventricular mass index (LVMI) were the independent influencing factors for the QOL of child-self and parent-proxy assessment in children undergoing KT, respectively (B=12.162, t=2.681, P<0.05; B=-0.240, t=-4.276, P<0.01).@*Conclusions@#QOL was higher in children undergoing KT than those on dialysis. Short stature and elevated LVMI were the independent influencing factors for QOL in children undergoing KT.

Injectable peptide hydrogel as intraperitoneal triptolide depot for the treatment of orthotopic hepatocellular carcinoma

Chemotherapy is among the limited choices approved for the treatment of hepatocellular carcinoma (HCC) at intermediate and advanced stages. Preferential and prolonged drug exposure in diseased sites is required to maximize the therapeutic index of the drug. Here, we report an injectable supramolecular peptide hydrogel as an intraperitoneal depot for localized and sustained release of triptolide for the treatment of orthotopic HCC. We chose peptide amphiphile C-GNNQQNYKD-OH-based nanofibers as gelators and carriers for triptolide. Sustained triptolide release from the hydrogel was achieved over 14 days , with higher accumulation in and cytotoxicity against human HCC Bel-7402 in comparison with L-02 fetal hepatocytes. After intraperitoneal injection, the hydrogel showed prolonged retention over 13 days and preferential accumulation in the liver, realizing HCC growth inhibition by 99.7 ± 0.1% and animal median survival extension from 19 to 43 days, without causing noticeable pathological changes in the major organs. These results demonstrate that injectable peptide hydrogel can be a potential carrier for localized chemotherapy of HCC.

Novel mutations in the BBS12 gene of two Chinese Bardet-Biedl syndrome pedigrees / 中华肾脏病杂志

Objective To Summarize and review the clinical data of two Bardet-Biedl syndrome (BBS) children so as to improve our understanding of the disease.Methods Clinical data of two BBS pedigree were collected.Gene analysis was performed by exon capture and next-generation sequencing,validated using Sanger sequencing.Results Both cases were male,Han nationality,born with polydactyly and had rapid weight gain after birth.They went to see the pediatric endocrinologist due to obesity,and found increased serum creatinine level,so were referral to pediatric nephrologists.Case one was further diagnosed rod-cone dystrophy,bilateral renal multiple cysts (chronic kidney disease,stage 4),atrial septal defect,mental retardation,hypertension and abnormal hearing.Two novel heterozygous compound mutation of BBS12 gene [c.1604T ＞ G (p.V535G) paternal,c.173delA (p.E58Efs*5) maternal] and one known BBS4 missense mutation (paternal) were detected.Case two was detected multiple cysts in kidneys by ultrasound in fetal phase.He was suspected to have autism.He had small penis,hypertension and renal injury (chronic kidney disease,stage 3).Two novel heterozygous compound mutation of BBS12 gene [c.1783T ＞ C (p.W595R) paternal,c.1749_1750delA (p.R584Dfs*54) maternal] were detected.All mutations were predicted to be harmful.Conclusions BBS is a rare disease.It is difficult to be diagnosed at early age.Polydactyly and obesity can be the early two symptoms for seeing doctors.Few cases have been diagnosed upon gene analysis.In this study,the mutation of BBS12 in Chinese and 4 novel mutations in BBS12 with severe renal injury are reported for the first time.It will extend the spectrum of BBS gene mutations.

Clinical and genetic characters of 8 Chinese children with ADCK4-associated glomerulopathy / 中华肾脏病杂志

Objective@#To investigate the clinical and genetic character of Chinese children with the aarF domain containing kinase 4 (ADCK4)-associated glomerulopathy.@*Methods@#Applying next generation sequencing to detect possible gene mutation(renal disease associated monogene was pooled as one panel) in 69 children with steroid-resistant nephrotic syndrome (SRNS) or persistent proteinuria of unknown origin. Sanger sequencing was used to confirm the significant mutations found in the children and to validate these mutation sites in their patients. Using online software (PolyPhen2, SIFT, Mutation Taster) to predict whether the detected missense mutations were disease causing or not. Collecting and analyzing clinical data of children with ADCK4-associated glomerulopathy, which included onset age, clinical manifestation, and renal pathology.@*Results@#The ADCK4 gene mutation was detected in 8 children with a positive rate of 11.6% (8 out of 69), among which 3 patients carried homozygous c.748G>C mutation, 3 patients carried homologous c.737G>A mutation, 1 patient carried compound heterozygous mutation(c.748G>C and c.737G>A), and 1 patient carried compound heterologous mutation(c.551A>G and c.737G>A). Collectively, there were only 3 mutation sites found in total 8 patients, in which the mutation sites of c.748G>C and c.737G>A had high detection frequency in these 8 patients. These 3 mutation sites were all missense mutation which were predicted to be disease causing by online software and not reported before. The average onset age was 6.5 years (2 years-11.75 years). Four patients presented with SRNS and the other 4 presented with persistent proteinuria. All 8 patients had no extrarenal manifestation, renal biopsy revealed focal segmental glomerulosclerosis (FSGS) in most patients, among which 3 cases had gone to end-stage renal disease (ESRD) at disease onset, and 2 cases progressed to ESRD 2 and 5 years after onset respectively. Seven patients had received glucocorticoid and/or immunosuppressive drug while only one patient getting partial response. All 8 patients were treated with large amount of coenzyme Q10 (15 mg·kg-1·d-1) after definite diagnosis of ADCK4 mutation-some patients had acquired encouraging curative effect.@*Conclusions@#ADCK4-associated glomerulopathy is not rare especially in the children with SRNS. The onset age is relatively old and the extrarenal manifestation is less common. FSGS is a main pathology type. Patients usually have no response to immunosuppressive therapy, but may benefit from addition of large amount of coenzyme Q10. Some patients may only manifest with insidious proteinuria, causing the early diagnosis to be difficult, which deserves more attention. Three new missense mutations expand disease causing mutation repertoire of ADCK4 gene, among which the two sites of c.748G>C and c.737G>A may be mutation hotspot of ADCK4-associated glomerulopathy in Chinese population, and need further study.

Coenzyme Q10 treatment for one child with COQ6 gene mutation induced nephrotic syndrome and literature review / 中华儿科杂志

Objective@#To summarize the clinical manifestation and molecular characteristics of COQ6 mutation induced nephrotic syndrome, and to evaluate efficacy of CoQ10 therapy.@*Method@#Clinical data of the case with infantile nephrotic syndrome was summarized, including clinical manifestations, laboratory findings and family investigation. The patient received CoQ10 30 mg/(kg·d) therapy. Urine protein/creatinine ratio, serum albumin and creatinine were detected to assess the efficacy of the therapy.@*Result@#(1) The 10 months old boy was presented with nephrotic level proteinuria and hypoalbuminemia. Extra-renal manifestations included cardiovascular abnormality, motor and mental retardation and unilateral ptosis. The patient had no consanguinity. A novel homozygous p. R360W mutation in COQ6 gene was identified and confirmed by next-generation sequencing and Sanger sequencing, respectively. Family analysis showed that homozygous p. R360W mutation in COQ6 gene was inherited from his parents. Missense p. R360W mutation was damaging by prediction online PolyPhen and SIFT software. After 2 months of CoQ10 complementary therapy, the patient′s urine protein/creatinine ratio declined from 7.2 to 1.3, and decreased further to 0.01 mg/mg with normal albumin level and renal function within 3 months. Nephropathy remission was maintained and growth retardation improved significantly during the last follow-up. Nevertheless, the patient manifested with sensorineural deafness at the age of 2 years. (2) There were 6 different mutations in coenzyme Q10 biosynthesis monooxygenase 6 (COQ6) in 13 individuals from 7 families by homozygosity mapping in the whole world. Each mutation was linked to early-onset SRNS with sensorineural deafness. Renal biopsy revealed FSGS in 7 cases and DMS in 1 case. Other manifestations included ataxia, seizures, facial dysmorphism, nephrolithiasis and growth retardation. Four patients received CoQ10 supplementation and responded to the treatment.@*Conclusion@#Renal disease caused by recessive COQ6 gene mutation was nephrotic syndrome. The patient benefited from early CoQ10 complement and reached nephropathy remission.

Phenotype analysis of 9 cases with mutations in PKHD1 gene / 中华肾脏病杂志

Objective To summarize the clinical features of 9 cases with mutations in PKHD1 gene for a better understanding of its phenotype.Methods Clinical data of nine cases with mutations in PKHD1 gene were summarized from January 2011 to December 2016 in our center,including clinical manifestations,laboratory findings,imaging data and family investigation.Next generation sequencing was used to screen 4000 genes in case 1 to 4 and whole exons in case 5 to 9.Significant variants detected by next generation sequencing were confirmed by conventional Sanger sequencing.Segregation analysis was performed using parental DNA samples.Relevant literature was reviewed.Results Among these 9 cases,5 are male,4 are female.The average age of onset was 2.6 years old (ranging from 0.5-5.2 years).Renal ultrasound revealed that all 9 cases had cysts in bilateral kidney,7 cases with enlarged kidney,1 case with normal size kidney,1 case with normal size kidney,and 1 case with bilateral renal atrophy.Two cases with renal artery stenosis,1 case with focal narrowing in left main branch and 1 case with vesico-ureteral reflux were found.Among the 9 cases,3 cases had homozygous mutations,and 6 cases had compound heterozygous mutations,including 1 nonsense mutation,1 frameshift mutation and 15 missense mutations.There were 2 cases with 3 heterozygous mutations,2 c.5935C ＞ T mutations and 2 eases with C.5869G ＞ A mutations.A total of 10 new mutations were identified.Conclusion Patients with mutations in the PKHD1 gene had normal size kidney,or even atrophic kidney.Renal artery stenosis,vesicoureteral reflux and bronchial stenosis were all first reported in patients with mutations in PKHD1 gene.The novel mutations,c.274C ＞ T,c.9059T ＞ C,c.8996delG,c.281C ＞ T,c.10424T ＞ A,c.7092T ＞ G,c.4949T ＞ C,c.5869G ＞ A,c.6197A ＞ G and c.1877A ＞ G further expanded the mutation spectrum of PKHD1 gene.

Etiological analysis of 264 cases with chronic kidney disease stage 2 to 5 in children / 中华儿科杂志

<p><b>OBJECTIVE</b>To study and summarize the etiology of children patients with chronic kidney disease (CKD) stage 2 to 5 seen in Children's Hospital of Fudan University from Jan. 2004 to Dec. 2013.</p><p><b>METHOD</b>By complying with the NKF-K/DOQI guidelines, we collected data of 264 cases of children patients with CKD stage 2-5 from Jan. 2004 to Dec. 2013 in the medical record system of Children's Hospital of Fudan University. And we retrospectively analyzed their age and CKD stage at first diagnosis, primary diseases, complications, etc.</p><p><b>RESULT</b>In the collected 264 cases, 52 cases (19.7%) were diagnosed at stage 2, 67 (25.4%) at stage 3, 52 (19.7%) at stage 4 and 93 (35.2%) at stage 5. For disease causes, 116 cases (43.9%) had congenital anomalies of the kidney and urinary tract (CAKUT), 61 cases (23.1%) had glomerular disease, 15 (5.7%) had hereditary kidney disease, 14 (5.3%) had other diseases and in 58 cases (22.0%) the causes of disease were unknown. In the group with age between 0 and 3.0 and 3.1 and 6.0 years, 57.1% (24 cases) and 60.0% (30 cases) had primary disease with CAKUT. In the group with age older than 10 years, 49.2% (30 cases) had primary disease with glomerular disease and 32.0% (32 cases) with unknown causes.</p><p><b>CONCLUSION</b>The major cause of CKD stage 2-5 in children in our hospital during the last ten years was CAKUT (43.9%), followed by glomerular disease (23.1%). The primary diseases of CKD were significantly different between the 2 age groups. CAKUT was more common in infants and preschool children while for adolescents, glomerular disease was the major cause.</p>