Clinical features and pathological analysis of steroid resistant nephrotic syndrome in children in a single center / 中国综合临床

0bjective To analyze the clinical characteristics, pathological types, treatment and prognosis in children with steroid resistant nephrotic syndrome (SRNS) in Northwest China, in order to provide reference for the treatment of SRNS. Methods:The clinical data, renal pathological results, treatment plan and efficacy of 102 children diagnosed with SRNS in the Department of Nephrology, Xi'an Children's Hospital of Shaanxi Province from January 1st, 2018 to December thirty-first, 2020 were analyzed retrospectively. All children were divided into groups according to age, clinical classification, pathological type, treatment scheme and treatment outcome, and the risk factors affecting the prognosis of children with SRNS were discussed. The measurement datas conforming to normal distribution were expressed as xˉ± s, and t test was used for comparison between groups. Measurement datas that did not conform to normal distribution were represented by M ( Q1, Q3), and Kruskall-Wallis test was used for comparison between groups.Enumeration datas were compared by χ 2 test. Risk factors were analyzed by multiple factor Logistic regression analysis. Results:The median age of onset of 102 children with SRNS was 3.0 years. Focal segmental glomerulosclerosis (FSGS) accounted for 36.3% (37/102), minimal lesions accounted for 33.3% (34/102), and mesangial proliferative glomerulonephritis accounted for 23.5% (24/102). The prevalence rates of hypertension (35.1% (13/37)), 24-h urine protein quantification (130.5 (91.5, 159.6) mg/(kg·24 h) and renal insufficiency (21.6% (8/37)) in FSGS group were higher than those in non-FSGS group (13.8% (9/65), 65.8 (51.2,85.5) mg/(kg·24 h), 4.6% (3/65)). The differences between the two groups were statistically significant (statistical values were χ 2=6.32, Z=5.90, χ 2=7.09; P values were 0.012, <0.001, 0.008). Logistic multivariate regression analysis showed that the hypertension ( OR=4.055, 95% CI 1.178-3.962) and 24 hour urinary protein ( OR=1.036, 95% CI 1.020-1.053) were associated with the increased risk of FSGS ( P values were 0.026 and <0.001). ROC curve ananlysis showed that the optimal critical value of 24 hour urinary protein was 85.65 mg/(kg·24 h) in FSGS. After treatment, complete remission was 61.8%(63/102), partial remission was 14.7%(15/102), and no remission was 23.5%(24/102). By the end of follow-up the treatment effective rate in the small lesion group (94.1%(32/34)) was higher than that in the FSGS Group (51.3%(19/37)), and the difference between the two groups was statistically significant (χ 2=16.02, P<0.001). In the initial immunosuppressive treatment, the complete remission rate of hormone combined with calcineurin inhibitor group (77.1%(37/48)) was higher than that of hormone combined with cyclophosphamide Group (11.1%(3/27)). There was significant difference between the two groups ( Z=32.28, P<0.001). Conclusion:The most common pathological type in children with SRNS was FSGS, and the age of onset was generally small. The prognosis of patients with pathological type FSGS was the worst, and the prognosis of small lesions was better. Hypertension and 24-hour urinary protein quantification were the risk factors of FSGS. Calcineurin inhibitors were the first choice for the second-line immunosuppressants of SRNS in children.

Gene mutation and clinical analysis in children with steroid resistant nephrotic syndrome in a single center / 中国医师杂志

Objective:To analyze the gene mutation, clinical manifestations and prognosis of children with steroid resistant nephrotic syndrome (SRNS), and to provide reference for the treatment of hereditary SRNS in children.Methods:The clinical data of 29 patients with SRNS and whole exon sequencing (WES) diagnosed in Xi′an Children′s Hospital from January 1, 2018 to December 31, 2020 were retrospectively analyzed.Results:In 29 cases of SRNS with genetic testing, 10 cases (34.5%) were gene mutations, including 2 cases of congenital nephrotic syndrome. The onset age of the patients with gene mutation ranged from 0.1 to 10.7(4.06±3.73)years, and the median age of onset was 3.3 years. The clinical type was mainly nephritis (8/10), and the pathological type was mainly focal segmental glomerulosclerosis (FSGS) (5/7). The main mutant genes were NPHS1 (2 cases), NPHS2 (2 cases), WT1 (2 cases), SMARCAL1 (1 case), COQ8B (1 case), TRPC6 (1 case) and COL4A3 gene (1 case). The main types of genetic variation were missense mutations, and 6 (60%) cases were new mutations that had never been reported in the database containing human pathogenic mutations before. Compared with the non-gene mutation group, 24 hour urinary protein was higher [(177.92±164.59)mg/(kg·24 h) vs (84.99±40.79)mg/(kg·24 h)] in gene mutation group, with statistically significant difference ( P<0.05). In the gene mutation group, there were 2 cases of complete remission, including 1 case of complete remission treated with coenzyme Q10, 1 case of partial remission, and 8 cases of immunosuppression treatment, with an effective rate of 2/8, while in the non-gene mutation group, the effective rate of immunosuppression treatment was 17/19, with statistically significant difference in prognosis between the two groups ( P<0.05). Conclusions:The pathological type of children with hereditary SRNS is mainly FSGS, which are often ineffective to immunosuppressive therapy, poor prognosis and easy to progress to end-stage renal disease. Gene detection is of great significance for etiological diagnosis, treatment and prognosis evaluation in children with SRNS.

Establishment of a microtubule-fluorescent fusion protein mosaically labeled zebrafish motor neuron system / 生理学报

Motor neurons are an important type of neurons that control movement. The transgenic fluorescent protein (FP)-labeled motor neurons of zebrafish line is disadvantageous for studying the morphogenesis of motor neurons. For example, the individual motor neuron is indistinguishable in this transgenic line due to the high density of the motor neurons and the interlaced synapses. In order to optimize the in vivo imaging methods for the analysis of motor neurons, the present study was aimed to establish a microtubule-fluorescent fusion protein mosaic system that can label motor neurons in zebrafish. Firstly, the promotor of mnx1, which was highly expressed in the spinal cord motor neurons, was subcloned into pDestTol2pA2 construct combined with the GFP-α-Tubulin fusion protein sequence by Gateway cloning technique. Then the recombinant constructs were co-injected with transposase mRNA into the 4-8 cell zebrafish embryos. Confocal imaging analysis was performed at 72 hours post fertilization (hpf). The results showed that the GFP fusion protein was expressed in three different types of motor neurons, and individual motor neurons were mosaically labeled. Further, the present study analyzed the correlation between the injection dose and the number and distribution of the mosaically labeled neurons. Fifteen nanograms of the recombinant constructs were suggested as an appropriate injection dose. Also, the defects of the motor neuron caused by the down-regulation of insm1a and kif15 were verified with this system. These results indicate that our novel microtubule-fluorescent fusion protein mosaic system can efficiently label motor neurons in zebrafish, which provides a more effective model for exploring the development and morphogenesis of motor neurons. It may also help to decipher the mechanisms underlying motor neuron disease and can be potentially utilized in drug screening.

Advances in diagnosis and treatment of urinary tract infection in children / 中华实用儿科临床杂志

Urinary tract infections (UTI) are one of the most common bacterial infections in children up to 30% of who suffer from recurrent infections during the first 6 to 12 months after initial UTI.UTI can be the first sign in almost 30% of children with urinary tract abnormalities, so UTI may be an outpost event of underlying renal disorders.UTI in infants is often associated with congenital abnormalities of the kidney and urinary tract, such as vesicoureteral reflux.Children with recurrent infection are prone to renal damaging and scarring, which further leads to end-stage renal disease.Therefore, early identification, timely treatment and reasonable management are extremely important to improving the prognosis.In this article, domestic and foreign relevant literature in recent years were reviewed to provide reference for diagnosis and treatment of UTI in children.

A single center study of kidney diseases combined with posterior reversible encephalopathy syndrome in children / 中华实用儿科临床杂志

Objective:To investigate the clinical features of children with kidney diseases who developed posterior reversible encephalopathy syndrome (PRES), explore the risk factors of PRES in these children, improve the understanding of the diseases, and help early diagnosis and effective treatment of the diseases.Methods:The clinical manifestations, laboratory inspection results, magnetic resonance imaging(MRI) material as well as the prognosis of 10 children with kidney diseases complicated by PRES who were admitted to the Department of Nephrology, Xi′an Children′s Hospital from November 2016 to August 2018 were analyzed retrospectively.Results:A total of 10 children were recruited, including 1 boy and 9 girls, with the onset age ranging from 4 years and 3 months to 13 years [(8.53±3.09) years]. The diagnosed kidney diseases in these patients were primary nephritic syndrome (6 cases), lupus nephritis (1 case), Hepatitis B-related nephritis (1 case), polyarteritis (1 case) and hemorrhagic fever with renal syndrome (1 case). Eight children received corticosteroids and 4 of them received other immunosuppressants simultaneously.Nine children suffered from the infections.All of them had acute onset, and the main symptoms were hypertension (10/10 cases, 100.0%), headache and dizziness (5/10 cases, 50.0%), nausea and vomiting (5/10 cases, 50.0%), visual disturbance (3/10 cases, 30.0%) and convulsions by the ways of seizures definitely (9/10 cases, 90.0%). There was nothing positive in the examinations of the nervous system and fundus.Computer tomography examinations of 9 cases showed nonspecific low-density foci.The cranial MRI scan showed abnormal signals on the cerebral cortex of frontal lobe, parietal lobe and occipital lobe in all these 10 cases.The hyperintensities were observed on the fluid-attenuated inversion recovery sequences of all the 10 cases.Slight hyperintensities on diffusion-weighted images of 4 cases indicated that PRES progressed from reversible angiogenic edema to irreversible cytotoxic edema, meaning a poor prognosis.After blood purification treatment and reducing intracranial pressure, these 4 cases recovered.After timely treatment upon PRES diagnosis, patients had no recurrence and showed a good outcome.Conclusions:Children with kidney diseases and PRES also suffer from hypertension, and the treatment with immunosuppressive agents may precede the occurrence of PRES.Cranial MRI is important for the diagnosis of PRES.

Horseshoe kidney with retrocaval ureter: one case report / 中华医学杂志(英文版)

Horseshoe kidney and retrocaval ureter are uncommon congenital anomalies of the genitourinary system that are easily diagnosed by typical imaging features. Both anomalies presenting in one patient is a rare disease characterized by isthmus of horseshoe kidney between the abdominal aorta and inferior vena cava. The clinical diagnosis and treatment of horseshoe kidney with retrocaval ureter remain a challenge. Here, we reported a case of a 44-year-old man with the two anomalies who was preoperatively diagnosed by unenhanced computed tomography scanning immediately after retrograde pyelography. The literatures on such combined anomalies are reviewed and the diagnostic evaluation and surgical management of this rare entity are discussed.