Renal function damage in children with duplex kidneys.

PURPOSE: To evaluate renal function damage in children with duplex kidneys. METHODS: A total of 355 duplex kidneys, 110 urinary tract infection (UTI) kidneys without abnormalities, and 104 kidneys with primary unilateral vesicoureteral reflux (VUR) were reviewed. Clinical data including age at diagnosis, body weight, history of UTI, ureteroceles, ectopic ureteral opening, VUR grade, serum creatinine level, cystatin C level, renal scarring, split renal function in dimercaptosuccinic acid scans, and effective renal plasma flow (ERPF) were analyzed. RESULTS: Duplex kidneys had a higher grade of VUR and renal scarring. Split renal function in unilateral duplex kidneys (45.58 ± 12.85%) was much lower than that in contralateral duplex kidneys (56.33 ± 11.90%) and controls (50.00 ± 11.38%) (P < 0.001 and P = 0.014, respectively). Both left and right split renal functions in bilateral duplex kidneys were similar to those ipsilateral to the controls (P = 0.906 and P = 0.932, respectively). However, the total ERPFs in the left, right, and bilateral duplex kidneys were significantly lower than that in the control group (P = 0.003, P = 0.001, and P = 0.003, respectively). The total ERPFs in the left and right unilateral duplex kidneys were similar. ERPF in unilateral duplex kidneys (106.70 ± 48.05 mL/min/m2) was significantly lower than that in contralateral duplex kidneys (150.18 ± 49.01 mL/min/m2) or those ipsilateral to controls (145.98 ± 41.16 mL/min/m2) (P < 0.001 and P < 0.001, respectively). CONCLUSION: Duplex kidneys are usually accompanied by a higher grade of VUR, more severe renal scarring, and renal function impairment. Split renal function in duplex kidneys often declines significantly. Notably, the evaluation of split renal function in bilateral duplex kidneys should be performed cautiously.

Growth hormone treatment in pre-pubertal short Chinese children with chronic kidney disease prior to transplantation.

BACKGROUND: The effect of recombinant human GH (rhGH) in Chinese children with chronic kidney disease (CKD) is unclear. METHODS: This was a 52-week, multicenter, randomized, open-label, negative-controlled phase 3 study. Prepubertal subjects were randomized 1:1 to either daily subcutaneous injections of rhGH 0.05 mg/kg/day or no treatment for 52 weeks. RESULTS: A total of 68 subjects with a mean age of 7.8 ± 3.27 years were enrolled. At week 52, the height standard deviation score (HT-SDS) in the treated group increased by 0.75 ± 0.58, which was significantly higher compared with 0.17 ± 0.47 in the untreated group (least squares mean 0.58, 95% confidence interval, 0.32-0.84; P < 0.001). At week 52, significant improvements were observed in other growth parameters (height velocity [P < 0.001]), insulin-like growth factor 1 (IGF-1) SDS [P < 0.001], IFG-1/insulin-like growth factor binding protein-3 molar ratio [P < 0.001], and height [P < 0.001]) compared with the untreated control. Seven patients reported treatment-related adverse events (TRAEs) and most TRAEs were mild in severity. Most subjects recovered without further intervention. CONCLUSIONS: Daily rhGH for 52 weeks in children with CKD-induced growth retardation significantly improved HT-SDS and other growth parameters without compromising safety. IMPACT: The efficacy and safety of growth hormone (GH) therapy in Chinese children with chronic kidney disease (CKD) are unclear. This study found that giving short stature Chinese children with CKD daily recombinant human growth hormone (rhGH) for 52 weeks improved growth parameters without compromising safety. This study's information can give physicians the confidence to treat these patients in their clinical practice.

Adding Methylprednisolone and Cyclophosphamide Pulse Therapy Provides No Benefit in Pediatric IgAV Nephritis Grade III.

Although immunoglobulin (Ig) A vasculitis (IgAV) nephritis is a common form of secondary pediatric glomerulonephritis, there is no consensus on an appropriate therapeutic regimen for moderate-to-severe pediatric IgAV nephritis grade III or the effectiveness of aggressive immunosuppressive therapy. The objective is to evaluate the efficacy and renal outcomes of methylprednisolone pulse therapy with or without cyclophosphamide pulse therapy for grade III IgAV nephritis in children. This retrospective, single-center study included 115 children with IgAV nephritis grade III. The primary endpoint was proteinuria reduction from moderate or severe levels to a normal level. The secondary endpoint was stable renal function, that is, an increase of less than 25% from the baseline creatinine level over the 4-month follow-up period. Among 115 children with IgAV nephritis grade III, 59 received methylprednisolone and cyclophosphamide double-pulse treatment; methylprednisolone and cyclophosphamide double-pulses did not significantly improve proteinuria remission. Proteinuria improvement did not show any difference with or without cyclophosphamide treatment. Furthermore, methylprednisolone pulse therapy showed no benefit over steroid therapy alone. The demographic and baseline disease characteristics among the treatment groups were well-balanced. The rates of complete remission in 24-hour proteinuria excretion over the 4-month follow-up period in the methylprednisolone and cyclophosphamide double-pulse, methylprednisolone plus oral prednisolone, and oral prednisolone-only groups were 91.52%, 92.31%, and 100%, respectively. Renal function remained stable in all the patients. Most patients with IgAV nephritis grade III showed a good prognosis. However, the addition of methylprednisolone and/or cyclophosphamide pulses did not offer benefits over steroid-only therapy.

Enthesitis-related arthritis: the clinical characteristics and factors related to MRI remission of sacroiliitis.

BACKGROUND: To describe the clinical characteristics and explore the factors related to the MRI remission of sacroiliitis in patients with enthesitis-related arthritis (ERA). METHODS: Patients with ERA from 2018-2022 in our medical center were retrospectively reviewed, which identified according to Pediatric Rheumatology International Trials Organization (PRINTO) criteria. Demographics, clinical characteristics, examinations, and treatments were described. Univariate and multivariate logistic regression models were used to analyze the factors related to MRI remission of sacroiliitis in ERA. RESULTS: This retrospective study included 160 ERA patients (51.9% male) with a mean onset age of 9.2 ± 3.0 years. There were 144 cases (81.9%) with peripheral arthritis, and the hip, knee, and ankle joints were the most commonly involved joints. Enthesitis occurred in 48 cases (30.0%), and sacroiliitis occurred in 142 cases (88.5%) at diagnosis. Human leukocyte antigen (HLA)-B27 was positive in 33 cases (17.1%), and acute uveitis occurred in 3 cases (1.9%). The majority of patients (93.7%) were treated with disease-modifying anti-rheumatic drugs (DMARDs), and 60% with biologics. Among 62 patients with MRI-defined sacroiliitis, 27 (43.5%) cases showed improvement in the sacroiliac joint lesion after treatment. Multivariate logistic regression analysis showed that duration from onset to diagnosis of less than 3 months (OR = 3.609, 95% CI: 1.068-12.192) and active joints of more than 4 (OR = 4.916, 95% CI: 1.006-24.037) were independent factors. CONCLUSION: We highlighted differences in ERA clinical characteristics. Patients with a shorter diagnosis time and more joint involvement improved more significantly in sacroiliac joint lesions after treatment.

A novel CLCN5 frame shift mutation responsible for Dent disease 1: Case report.

Background: Dent disease is a group of inherited X-linked recessive renal tubular disorders. This group of disorders is characterized by low molecular weight proteinuria (LMWP), nephrocalcinosis, hypercalciuria and renal failure. Case presentation: Here we report one 11-year-old Chinese boy (proband) and one 13-year-old Chinese boy who was proband's cousin, both presented with massive proteinuria. Further laboratory examinations revealed a lack of nephrocalcinosis, nor any other signs of tubular dysfunction, but only LMWP and hypercalciuria. There was no abnormality in growth, renal function or mineral density of the bones. A novel deletion (c.1448delG) in the CLCN5 gene was identified, resulting in a frame shift mutation (p.Gly483fs). The proband's and his cousin's mothers were found to be the carrier of this mutation. Conclusions: In this study, we have found a novel frameshift mutation (c. 1448delG) at exon 11 of the CLCN5 gene which leads to Dent disease 1, expanding the spectrum of CLCN5 mutations.

Associations Between Cessation of Second-Line Therapies and Relapse Rates of Childhood Refractory Minimal-Change Nephrotic Syndrome: A Single-Center, Retrospective Chart Review.

Background: Most patients (≥85%) with minimal-change nephrotic syndrome (MCNS) respond to corticosteroid treatment. However, about 10% to 20% of patients with MCNS have steroid-resistant nephrotic syndrome and 25% to 43% of patients have steroid-dependent nephrotic syndrome or frequent-relapse steroid-sensitive nephrotic syndrome. Patients with refractory MCNS are treated with various second-line therapies. Objectives: This study aimed to evaluate the associations between the use of various second-line therapies and relapse rates in Chinese patients with childhood refractory MCNS. Methods: In this study, patients with childhood nephrotic syndrome renal biopsy proved to be "minimal change" from a single tertiary-care center between January 2002 and July 2018 were identified. A Total of 56 medical charts of patients treated with 1 of these second-line immunosuppressors: cyclophosphamide (CYC), mycophenolate mofetil (MMF), or tacrolimus (TAC) were reviewed. Patients were divided into CYC (n = 24), MMF (n = 20), and TAC (n = 12) groups according to the second-line therapy administered. Baseline characteristics, immune status, immunocomplex deposition in the renal tissue, and treatment outcomes were analyzed. Results: The ratio of patients with steroid-resistant nephrotic syndrome and steroid-dependent nephrotic syndrome in the CYC, MMF, and TAC groups did not differ significantly (P = 0.721). The immunofluorescence assay did not show any significant differences in immunocomplex deposition identified in renal biopsy specimens among the 3 groups. The rate of steroid-free remission in the TAC group (75%) was higher than that in the MMF (55%) and CYC (25%) groups (P = 0.012). At the last follow-up, two-thirds of children in the TAC group had a relapse following discontinuation of therapy. In the TAC group, patients for whom steroids were withdrawn had significantly higher levels of immunoglobulin G at the onset of nephrotic syndrome than those for whom steroids were continued (P = 0.017). In the MMF group, children with relapse had a significantly higher percentage of CD16+CD56+-positive cells than those without relapse (P = 0.042). The relapse rate after treatment discontinuation was significantly different among the 3 groups (P = 0.035). Notably, the relapse rate after treatment discontinuation in the CYC group was lower than those in the other 2 groups (P = 0.035). Conclusions: In this small population of Chinese patients with childhood refractory MCNS, the relapse rate following TAC therapy was higher than that following MMF or CYC therapy. Different proportions of CD16+CD56+-positive cells might be associated with relapse rates in patients with MCNS receiving MMF treatment. (Curr Ther Res Clin Exp. 2022; 83:XXX-XXX).

Chinese Medicine Involving Triple Rehabilitation Therapy for Knee Osteoarthritis in 696 Outpatients: A Multi-Center, Randomized Controlled Trial.

OBJECTIVE: To determine the effects of Chinese medicine (CM) involving triple rehabilitation therapy on the progression of knee osteoarthritis (KOA). METHODS: A total of 722 patients recruited from 38 community health service centers located in China from March 2013 to March 2017 were randomly divided into treatment and control groups equally, using a cluster randomization design. Health education combined with CM involving triple rehabilitation therapy for KOA (electro-acupuncture, Chinese medicinal herb fumigating-washing, and traditional exercises) was administered in the treatment group while conventional rehabilitation therapy (physical factor therapy, joint movement training, and muscle strength training) was administered in the control group. Patients with a visual analog scale (VAS) scores ≽4 were treated with dispersible meloxicam tablets (7.5 mg, once daily). The Lequesne index scores, VAS scores, range of motion (ROM), lower limb muscle strength, knee joint circumference, quantitative scores of KOA symptoms, and the short-form 36 item health survey questionnaire (SF-36) scores were measured for each patient at 5 checkpoints (before treatment, at the 2nd week and the 4th week during the 4-week treatment period, at 1 month and 3 months after end of treatment), and adverse reactions were observed also. RESULTS: A total of 696 patients completed the entire process, with 351 in the treatment group and 345 in the control group. At all treatment checkpoints, the treatment group demonstrated better outcomes than the control group with regard to the total Lequesne index scores, effective rate and improvement rate of the total Lequesne index scores, VAS scores, lower limb muscle strength, knee circumference, quantitative scores of KOA symptoms, and SF-36 scores as well (P<0.05 or P<0.01). No adverse reactions were encountered in this study. CONCLUSIONS: CM involving triple rehabilitation therapy can alleviate KOA-related pain and swelling, improve lower limb muscle strength, promote flexion and activity of the knee and improve the quality of life in patients undergoing KOA. It is suitable for patients with early or mid-stage KOA. (Registration No. ChiCTR-TRC-12002538).

DHX33 promotes colon cancer development downstream of Wnt signaling.

Colon cancer is one of the most common malignancies in the world; there is no effective therapeutic treatment after surgery. Our previous studies indicate that RNA helicase DHX33 plays a critical role in cell proliferation and cell growth. Here in this study, DHX33 is found to be highly expressed in colon cancer tissues and colon cancer cell lines. Knockdown of DHX33 significantly decreased cell proliferation and triggered apoptosis. Mechanistically, DHX33 was found to transcriptionally control multiple critical genes involved in cell cycle, apoptosis and migration. DHX33 deficiency caused decreased tumor growth for colon cancer cells in a xenograft model in vivo. With Wnt/ß-cateninactivator and inhibitors, we further discovered that Wnt/ß-catenin pathway regulates DHX33 transcriptionally. This study for the first time demonstratesthe important role of DHX33 in colon cancer development and reveals the underlying molecular mechanism. We also provide the initial evidence for the relationship between DHX33 and Wnt/ß-catenin signaling pathway in colon cancer development.

Interleukin-13 and RANTES polymorphisms in relation to asthma in children of Chinese Han nationality.

BACKGROUND: IL-13 (interleukin-13) and RANTES (Regulated upon Activation, Normal T cells Expressed and Secreted) are the important asthma inflammatory mediators. OBJECTIVE: The present study aimed to investigate the single and combined associations between the polymorphism (SNP) loci in IL-13 and RANTES genes with the development of asthma in children of Chinese Han nationality. METHODS: The risk associated with genotypes of three IL-13 SNPs and two RANTES SNPs was determined by the Χ2 test in 384 children with asthma and an equal number of healthy controls matched by sex. RESULTS: Between the experimental and control groups, no statistically significant differences (P >0.05) were found in genotype distribution and allele frequency among three loci (IL-13 C-1112T, IL-13 C1923T, and RANTES A-403G). However, significant diversity was observed among IL-13 A2044G (P =0.0001) and RANTES G-28C (P =0.0001). Moreover, the frequency of IL-13 A2044G A/A and RANTES G-28C G/G in the asthma group was significantly higher than in the control group (odds ratio [OR] =2.59, P =0.0001; OR =3.00, P =0.0001, respectively). Carriers of both IL-13 A2044G A/A and RANTES G-28C G/G have a more significant risk for developing asthma than those with only a single polymorphism. CONCLUSIONS: The three loci (IL-13 C-1112T, IL-13 C1923T, and RANTES A-403G) make little contribution to the development of asthma in children of Chinese Han nationality. IL-13 A2044G and RANTES G-28C are significantly associated with childhood asthma. IL-13 A2044G A/A and RANTES G-28C G/G have a significant and combined effect on the development of asthma.