DACH1 attenuated PA-induced renal tubular injury through TLR4/MyD88/NF-κB and TGF-ß/Smad signalling pathway.

BACKGROUND: Palmitic acid (PA), the major saturated fatty acid in the blood, often induces the initiation and progression of diabetic kidney disease (DKD). However, the underlying mechanism remains unclear. DACH1 is an important regulator of kidney functions. Herein, we investigated the roles of DACH1 in PA-induced kidney injury. METHODS: Clinical data from the NHANES database were subjected to analyse the association between serum PA (sPA), blood glucose and kidney function. Molecular docking of PA was performed with DACH1. Immunohistochemistry, cell viability, annexin V/7-AAD double staining, TUNEL assay, immunofluorescent staining, autophagic flux analysis, qRT-PCR and western blot were performed. RESULTS: Clinical data confirmed that sPA was increased significantly in the pathoglycemia individuals compared with controls and correlated negatively with renal function. Our findings suggested that PA could dock with DACH1. DACH1 enhances cell viability by inhibiting apoptosis and attenuating autophagy blockage induced by PA. Furthermore, the results demonstrated that DACH1 ameliorated inflammation and fibrosis through TLR4/MyD88/NF-κB and TGF-ß/Smad signalling pathway in PA-treated renal tubular epithelial cell line (HK-2). CONCLUSIONS: This study proved that sPA presents a risk factor for kidney injuries and DACH1 might serve as a protective target against renal function deterioration in diabetic patients.

[Clinical phenotype analysis of 6 cases of TTC21B gene related nephronophthisis].

Objective: To analyze the clinical characteristics of 6 children with TTC21B-related nephronophthisis to provide reference for early clinical diagnosis. Methods: The general condition, clinical manifestations, laboratory tests and other clinical data of 6 children from 4 families diagnosed with nephronophthisis by genetic testing in Shanghai Children's Hospital from January 2015 to December 2020 were analyzed retrospectively. Results: A total of 6 children (3 males and 3 females) developed proteinuria and progressive renal dysfunction in early infancy. The onset age of proteinuria was 18 (6, 25) months. The age at the onset of renal impairment was 22 (10, 36) months. All 6 children progressed to end-stage renal disease (ESRD) within 10 (4, 65) months of onset. Five children had hypertension, 3 children with abnormal liver function, 2 children with visceral translocation and 1 child with growth retardation. The genetic results suggested that all children carried variations TTC21B gene p.C518R. Conclusions: Children with TTC21B gene p.C518R nephronophthisis had proteinuria and progressed to ESRD at the early stage of life. These nephronophthisis patients commonly presented with liver and renal dysfunction.

[Four cases of nephrotic syndrome with TRPC6 gene variations and literature review].

Objective: To investigate the clinical characteristics, treatment and prognosis of TRPC6 variation induced children with steroid-resistant nephrotic syndrome (SRNS). Methods: Clinical data of four patients with nephrotic syndrome carrying TRPC6 variations, who were admitted to the Department of Nephrology and Rheumatology, Children's Hospital of Shanghai from Jan. 2017 to Dec. 2019, was retrospectively analyzed. The literature search was conducted with "nephrotic syndrome" "child" and "TRPC6 variation" as keywords in China National Knowledge Infrastructure (CNKI), Wanfang, Weipu and Pubmed databases until August 2020. Results: One of the four cases was male, and the others were female. Onset age ranged from 4-year-1-month to 12-year-2-month. They presented severe proteinuria, hypoalbuminemia or edema as a first symptom. Four patients had anemia, and two patients had secondary hyperparathyroidism, and one patient had renal atrophy. Renal pathology showed that one case was immune complex associated with glomerulonephritis, and the rest were focal segmental glomerular sclerosis (FSGS). They had been initially treated with corticosteroids for more than four weeks, but they had inadequate responses. They were then treated with corticosteroids combined with immunosuppressants (for example, cyclophosphamide, a calcineurin inhibitor, or mycophenolate mofetil). However, the symptoms did not improve. Additionally, four children progressed to end-stage renal disease within 2 to 6 months.Their whole exon gene testing suggested that the variation types of TRPC6 gene were respectively c.2684G>T, c.523C>T, c.2678G>A, c.2683C>T, and all patients had de novo variations in TRPC6. One article in Chinese and 9 articles in English were found, which made up 27 patients. The data of 31 cases (including this group) were analyzed. There were 18 missense variations, one frameshift variation, one synonymous variation and one splicing variation. The onset age was from 4 months age to 14 years old. Among all patients, 18 cases had massive proteinuria and hypoproteinemia, 6 cases only showed proteinuria. The pathological type of 19 cases were FSGS, 2 cases were IgA nephropathy, 2 cases were minimal change disease, 1 case was collapse glomerulopathy, 1 case was C1q nephropathy, and 1 case was immune complex associated glomerulonephritis. Glucocorticoid therapy was ineffective in 18 cases, and calcineurin inhibitor was ineffective in 11 cases. The prognosis of the disease was poor. Renal failure occurred in 12 cases, and the time to end stage renal disease was from 4 months to 13.8 years. Conclusions: TRPC6 variation can cause SRNS at a young age. FSGS is the primary pathological type of SRNS causing by TRPC6 variation. Glucocorticoid and immunosuppressive therapy are mostly ineffective. The disease progressed rapidly and the prognosis is poor.

[Value of magnetic resonance imaging in assessment of iron deposition among patients with hepatic alveolar echinococcosis: a preliminary evaluation].

OBJECTIVE: To assess the value of MRI combined with serum ferritin analysis in measurement of hepatic iron deposition among patients with hepatic alveolar echinococcosis. METHODS: A total of 96 patients with definitive diagnosis of hepatic alveolar echinococcosis and 30 healthy volunteers were enrolled and underwent routine 1.5T MR scanning, and all laboratory examination data were captured. The liver-to-muscle signal intensity ratio, serum ferritin level and liver functions were analyzed. RESULTS: The liver-to-muscle signal intensity ratio was (1.95 ± 0.57) in patients with hepatic alveolar echinococcosis and (2.22 ± 0.28) in healthy volunteers (t = 2.022, P < 0.05), and the liver-to-muscle signal intensity ratio was negatively associated the serum ferritin level in patients with hepatic alveolar echinococcosis (rs = -0.446, P < 0.01). CONCLUSIONS: Abnormal iron deposition is detected in the liver of patients with hepatic alveolar echinococcosis, and serum ferritin level may be helpful for the identification of abnormal iron deposition in the liver of patients with hepatic alveolar echinococcosis. The liver-to-muscle signal intensity ratio measured by MRI may be a non-invasive approached used to assess the hepatic iron deposition in patients with hepatic alveolar echinococcosis.

[Retrospective analysis of cuffed-tunneled catheters in pediatric patients receiving maintenance hemodialysis].

Objective: To summarize the characteristics of cuffed-tunneled catheters insertion and investigate the values of cuffed-tunneled catheters in pediatric patients. Methods: Between March 2015 and July 2017, all the pediatric patients who received maintenance hemodialysis at least 3 consecutive months in our center were included. Sixteen cuffed-tunneled hemodialysis catheters were inserted in patients for long-term hemodialysis access. The clinical manifestations and complications were retrospectively reviewed. Results: Fifteen pediatric patients with end stage ranal disease (ESRD) were included in this study and they received 16 cuffed-tunneled catheters for long-term vascular access, including 10 males and 5 females; median age at start of catheter insertion was 11.5 (4.2-14.5) years. Body weight was (27.8±8.0)kg (16.0-39.4 kg) . The size and the length of the catheters were based on the height of patients as follows: 28 cm for (115.6±10.6) cm (102.0-130.0 cm) ,36 cm for (148.6±9.9)cm (140.0-167.0 cm) . Cuffed-tunneled catheters outcome: 10 cuffed-tunneled catheters were still functional at the end of the study; 5 catheters were removed after successful kidney transplantation. Catheter failure occurred in 1 out of 16 cuffed-tunneled catheters due to catheter-related infections. The median catheter survival time was 11.9 months (range 3.5-21.3 months). Complications of cuffed-tunneled catheters: Catheter placements operation was successful in 15 cases using ultrasound guidance. No serious complications were observed in any patients receiving catheter inserting operation. The overall rate of catheter-related infections and thrombosis/malposition was 6.3% and 18.7%, respectively. Conclusions: Ultrasound guidance is suggested in pediatric patients during the catheters insertion. The size and the length of the catheters should be based on the height of patients. Cuffed-tunneled hemodialysis catheters could be effectively used for maintenance of hemodialysis vascular access for pediatric patients with ESRD.

[Clinical features and expression of PLA(2)R in renal tissue with idiopathic membranous nephropathy in children].

Objective: To explore the clinical features and expression of PLA(2)R in renal tissue of children with idiopathic membranous nephropathy. Methods: Retrospective study was performed in patients with membranous nephropathy diagnosed through renal biopsy and the follow-up time was at least half a year in Shanghai Children's Hospital from January 2010 to February 2017. We compared their clinicopathological and pathological findings of IMN. Indirect immunofluorescence assay was used to detect glomerular PLA(2)R expression. We analyzed the differences of clinical features between the PLA(2)R negative and positive groups. T test, rank-sum test and Fisher exact test were used. Results: Eleven cases had hematuria and proteinuria, 9 cases presented with nephrotic syndrome, and 2 cases showed isolated proteinuria. Of the 22 cases of children with IMN, 16 patients had complete remission (complete remission rate was 72.8%), and 22 patients had partial remission. The renal function of all cases was normal and in all cases the estimated glomerular filtration rate was > 90 ml/(min·1.73m(2)). Of 22 cases with IMN, 7 cases were PLA(2)R-positive in renal tissue and 15 cases were PLA(2)R-negative. The age of positive group (10 years old) was older than the negative group (6 years old)(Z=-2.483, P<0.05) and the time of positive group (6 months) for urine protein to return to negative was longer than the negative group (2.5 months) through treatment. These differences were significantly different (Z=-2.072, P<0.05). Conclusions: Hematuria and proteinuria can be found in most children with idiopathic primary membranous nephropathy. Prednisone combined with immunosuppressant was effective. The positive rate of PLA(2)R in renal tissue of children with IMN was about 32%. The age of PLA(2)R positive group was older than the negative group. And the time of urine protein turning to negative in positive group was longer than that in the negative group.