-
Frontiers in Immunology 2024This study aims to explore the clinical value of low disease activity state (LDAS) in the treat-to-target strategy of pediatric systemic lupus erythematosus (pSLE) and...
Long-term outcomes and predictive factors of achieving low disease activity status in childhood systemic lupus erythematosus: a Chinese bicentric retrospective registered study.
BACKGROUND
This study aims to explore the clinical value of low disease activity state (LDAS) in the treat-to-target strategy of pediatric systemic lupus erythematosus (pSLE) and find the risk factors for never reaching LDAS.
METHODS
A total of 272 children with SLE who were diagnosed and followed up in two tertiary hospitals in China during the period from January 2012 to December 2019 were involved in this study, and the clinical presentation, pathology, and treatment were retrospectively studied.
RESULTS
The male-to-female ratio was 1:5.2, the age at diagnosis was 11.1 years (IQR, 9.8-13.1 years), the disease duration was 1.0 month (IQR, 0.5-2.0 months), and follow-up was 36.5 months (IQR, 25.7-50.9 months). During follow-up, 230 children achieved LDAS, and 42 were never been in. Male ( = 0.018), mucosal ulcer ( = 0.048), liver function damage ( = 0.026), cardiac effusion ( = 0.034), anemia ( = 0.048), urine red blood cells ( = 0.017), urinary leukocytes ( = 0.032), and endothelial cell proliferation in renal biopsy ( = 0.004)-these indexes have statistical differences between the two groups in the baseline. At baseline, endothelial cell proliferation ( = 0.02) is an independent risk factor for never achieving LDAS by multivariate logistic analysis. During follow-up, non-compliance was a risk factor for never achieving LDAS by comparing between groups. Children with biologics achieved LDAS at a higher rate than children without biologics ( = 0.038). The proportion of organ damage in patients never been in LDAS was significantly higher than that in patients who achieved LDAS ( < 0.001).
CONCLUSION
Endothelial cell proliferation in renal biopsy and non-compliance during follow-up were independent risk factors for never achieving LDAS. At the end of the follow-up, the organ damage in the remission group was similar to that in the LDAS group, indicating that LDAS can be used as a target for pSLE treatment.
Topics: Humans; Lupus Erythematosus, Systemic; Male; Female; Child; Retrospective Studies; Adolescent; China; Risk Factors; Severity of Illness Index; Follow-Up Studies; Prognosis; Treatment Outcome; East Asian People
PubMed: 38915395
DOI: 10.3389/fimmu.2024.1369969 -
Journal of the Belgian Society of... 2024Renal failure is relatively common in children presenting to the emergency department, suggesting that the assumption of normal renal function is not always valid....
Renal failure is relatively common in children presenting to the emergency department, suggesting that the assumption of normal renal function is not always valid. Although some computed tomography (CT) scans necessitate the use of intravenous contrast, one should probably consider whether a blood test is necessary to assess the patient's renal function and possibly consider other imaging modalities before proceeding. With no pediatric-specific guidelines and no validated pediatric prevention strategies, further research is needed to establish clear recommendations for contrast-enhanced exams in stable and unstable pediatric patients with unknown renal function.
PubMed: 38915315
DOI: 10.5334/jbsr.3271 -
Vascular Specialist International Jun 2024Paradoxical embolism through the foramen ovale is a rare and devastating event requiring urgent treatment. Herein, we present the case of a 23-year-old male who...
Paradoxical embolism through the foramen ovale is a rare and devastating event requiring urgent treatment. Herein, we present the case of a 23-year-old male who presented with a pulmonary embolism complicated by a left renal artery paradoxical embolism. Urgent vacuum-assisted thrombo-aspiration restored normal perfusion of the left kidney within 5 hours. The patient had a patent foramen ovale and heterozygous thrombophilia. However, a radioisotopic scan performed 2 years later revealed an unexpected decrease in left renal perfusion. Therefore, despite the angiographic success, functional evaluation using a renal scan should be performed to assess renal function.
PubMed: 38915224
DOI: 10.5758/vsi.240022 -
Scientific Reports Jun 2024We have reported that an environmental pollutant, cadmium, promotes cell death in the human renal tubular cells (RTCs) through hyperactivation of a serine/threonine...
We have reported that an environmental pollutant, cadmium, promotes cell death in the human renal tubular cells (RTCs) through hyperactivation of a serine/threonine kinase Akt. However, the molecular mechanisms downstream of Akt in this process have not been elucidated. Cadmium has a potential to accumulate misfolded proteins, and proteotoxicity is involved in cadmium toxicity. To clear the roles of Akt in cadmium exposure-induced RTCs death, we investigated the possibility that Akt could regulate proteotoxicity through autophagy in cadmium chloride (CdCl)-exposed HK-2 human renal proximal tubular cells. CdCl exposure promoted the accumulation of misfolded or damaged proteins, the formation of aggresomes (pericentriolar cytoplasmic inclusions), and aggrephagy (selective autophagy to degrade aggresome). Pharmacological inhibition of Akt using MK2206 or Akti-1/2 enhanced aggrephagy by promoting dephosphorylation and nuclear translocation of transcription factor EB (TFEB)/transcription factor E3 (TFE3), lysosomal transcription factors. TFEB or TFE3 knockdown by siRNAs attenuated the protective effects of MK2206 against cadmium toxicity. These results suggested that aberrant activation of Akt attenuates aggrephagy via TFEB or TFE3 to facilitate CdCl-induced cell death. Furthermore, these roles of Akt/TFEB/TFE3 were conserved in CdCl-exposed primary human RTCs. The present study shows the molecular mechanisms underlying Akt activation that promotes cadmium-induced RTCs death.
Topics: Humans; Proto-Oncogene Proteins c-akt; Autophagy; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Cell Line; Cadmium; Kidney Tubules, Proximal; Phosphorylation; Cadmium Chloride; Heterocyclic Compounds, 3-Ring; Kidney Tubules
PubMed: 38914593
DOI: 10.1038/s41598-024-64579-3 -
Scientific Reports Jun 2024The joint impact of tadalafil (Cilais) as a pharmaceutical residue and microplastics on fish is not well comprehended. The current study examined haematological,...
The joint impact of tadalafil (Cilais) as a pharmaceutical residue and microplastics on fish is not well comprehended. The current study examined haematological, biochemical, and antioxidant parameters, along with immunohistochemical and histological indications in tilapia (Oreochromis niloticus) after being exposed to tadalafil, polyethylene microplastics (PE-MPs), and their mixtures for 15 days. The fish were distributed into 1st group control group (The fish was maintained in untreated water without any supplements); 2nd group exposed to 10 mg/L PE-MPs;3rd group exposed to 20 mg/l tadalafil (Cilais); 4th group exposed to 20 mg/l tadalafil (Cilais) + 10 mg/LPE-MPs (in triplicate). The levels of creatinine, uric acid, glucose, AST, ALT, and albumin in fish treated with tadalafil alone or in combination with PE-MPs were significantly higher than those in the control group. Fish exposed to PE-MPs, tadalafil, and tadalafil plus PE-MPs showed significantly lower levels of RBCs, Hb, Ht, neutrophils, and lymphocytes compared to the control group. Serum levels of total antioxidant capacity and reduced glutathione (GSH) were notably lowered in fish groups subjected to PE-MPs, tadalafil, and tadalafil + PE-MPs combinations in comparison to the control group. Malondialdehyde (MDA) serum levels were notably elevated in fish groups subjected to PE-MPs, tadalafil, and tadalafil + PE-MPs combinations compared to the control group. The most severe impact was observed in the tadalafil + PE-MPs combination group. Interleukin-6 (IL-6) levels were significantly increased in liver tissues following exposure to both tadalafil and microplastics compared to tissues exposed to only one substance or the control group. Changes in the gills, liver, and renal tissues were seen following exposure to PE-MPs, tadalafil, and tadalafil + PE-MPs combination in comparison to the control group of fish. Ultimately, the mixture of tadalafil and PE-MPs resulted in the most detrimental outcomes. Tadalafil and PE-MPs exhibited showed greater adverse effects, likely due to tadalafil being absorbed onto PE-MPs.
Topics: Animals; Tadalafil; Cichlids; Water Pollutants, Chemical; Microplastics; Antioxidants; Tilapia; Glutathione; Gills; Oxidative Stress
PubMed: 38914580
DOI: 10.1038/s41598-024-64282-3 -
Scientific Reports Jun 2024Azole antifungal drugs are commonly used to treat vulvovaginal candidiasis (VVC). The nephrotoxicity and developmental toxicity of azole drugs have not been...
Azole antifungal drugs are commonly used to treat vulvovaginal candidiasis (VVC). The nephrotoxicity and developmental toxicity of azole drugs have not been systematically analyzed in the real world. We used the FDA Adverse Event Reporting System (FAERS) to investigate the adverse events (AEs) associated with imidazole therapy for VVC. FAERS data (from quarter 1 2004 to quarter 3 2022) were retrieved using OpenVigil 2.1, and AEs were retrieved and standardized according to the Medical Dictionary for Regulatory Activities (MedDRA). In the top 10 System Organ Class (SOC), all four drugs have been found to have kidney and urinary system diseases and pregnancy. We found significant signals, including clotrimazole [bladder transitional cell carcinoma, (report odds ratio, ROR = 291.66)], [fetal death, (ROR = 10.28)], ketoconazole[nephrogenic anemia (ROR = 22.1)], [premature rupture of membranes (ROR = 22.91 46.45, 11, 3)], Miconazole[hematuria (ROR = 19.03)], [neonatal sepsis (ROR = 123.71)], [spontaneous abortion (ROR = 5.98)], Econazole [acute kidney injury (ROR = 4.41)], [spontaneous abortion (ROR = 19.62)]. We also discovered new adverse reactions that were not reported. Therefore, when using imidazole drugs for treatment, it is necessary to closely monitor the patient's renal function, pay attention to the developmental toxicity of the fetus during pregnancy, and be aware of potential adverse reactions that may occur.
Topics: Female; Humans; Candidiasis, Vulvovaginal; Antifungal Agents; Imidazoles; United States; United States Food and Drug Administration; Adverse Drug Reaction Reporting Systems; Pregnancy; Adult; Drug-Related Side Effects and Adverse Reactions; Miconazole; Clotrimazole
PubMed: 38914572
DOI: 10.1038/s41598-024-63315-1 -
JCI Insight May 2024Patients with autosomal dominant polycystic kidney disease (ADPKD), a genetic disease due to mutations of the PKD1 or PKD2 gene, show signs of complement activation in...
Patients with autosomal dominant polycystic kidney disease (ADPKD), a genetic disease due to mutations of the PKD1 or PKD2 gene, show signs of complement activation in the urine and cystic fluid, but their pathogenic role in cystogenesis is unclear. We tested the causal relationship between complement activation and cyst growth using a Pkd1KO renal tubular cell line and newly generated conditional Pkd1-/- C3-/- mice. Pkd1-deficient tubular cells have increased expression of complement-related genes (C3, C5, CfB, C3ar, and C5ar1), while the gene and protein expression of complement regulators DAF, CD59, and Crry is decreased. Pkd1-/- C3-/- mice are unable to fully activate the complement cascade and are characterized by a significantly slower kidney cystogenesis, preserved renal function, and reduced intrarenal inflammation compared with Pkd1-/- C3+/+ controls. Transgenic expression of the cytoplasmic C-terminal tail of Pkd1 in Pkd1KO cells lowered C5ar1 expression, restored Daf levels, and reduced cell proliferation. Consistently, both DAF overexpression and pharmacological inhibition of C5aR1 (but not C3aR) reduced Pkd1KO cell proliferation. In conclusion, the loss of Pkd1 promotes unleashed activation of locally produced complement by downregulating DAF expression in renal tubular cells. Increased C5a formation and C5aR1 activation in tubular cells promotes cyst growth, offering a new therapeutic target.
Topics: Animals; Polycystic Kidney, Autosomal Dominant; Mice; CD55 Antigens; Complement C3; Mice, Knockout; Receptor, Anaphylatoxin C5a; Disease Models, Animal; Complement Activation; TRPP Cation Channels; Humans; Cell Proliferation; Male; Cell Line; Receptors, Complement 3b
PubMed: 38912583
DOI: 10.1172/jci.insight.175220 -
Heliyon Jun 2024The aim of this study was to investigate whether quantitative changes in lymphocyte subsets and gene expression in peripheral blood (PB) cells are related to the...
Peripheral blood cells RNA-seq identifies differentially expressed gene network linked to lymphocyte subsets alterations and active lupus nephritis associated with declines in renal function.
BACKGROUND
The aim of this study was to investigate whether quantitative changes in lymphocyte subsets and gene expression in peripheral blood (PB) cells are related to the clinical manifestations and pathogenesis of lupus nephritis (LN).
METHODS
We enrolled 95 pediatric-onset SLE patients with renal involvement who presented with 450 clinical episodes suspicious for LN flare. Percentages of lymphocyte subsets at each episode were determined. We stratified 55 of 95 patients as high or low subset group according to the median percentage of each lymphocyte subset and the association with changes in the eGFR (ΔeGFR) were analyzed. Peripheral blood bulk RNA-seq to identify differentially expressed genes (DEGs) in 9 active LN vs. 9 inactive LN patients and the DEG-derived network was constructed by Ingenuity Pathway Analysis (IPA).
RESULTS
The mean ΔeGFR of low NK-low memory CD4 T-high naive CD4 T group (31.01 mL/min/1.73 m) was significantly greater than that of high NK-high memory CD4 T-low naive CD4 T group (11.83 mL/min/1.73 m; = 0.0175). Kaplan-Meier analysis showed that the median time for ΔeGFR decline to mean ΔeGFR is approximately 10 years for high NK-high memory CD4 T-low naive CD4 T group and approximately 5 years for low NK-low memory CD4 T-high naive CD4 T group (log-rank test = 0.0294).
CONCLUSIONS
Our study highlighted important connections between DEG-derived network, lymphocyte subset composition, and disease status of LN and GN. A novel scoring system based on lymphocyte subset proportions effectively stratified patients into groups with differential risks for declining renal function.
PubMed: 38912505
DOI: 10.1016/j.heliyon.2024.e32303 -
Journal of Indian Association of... 2024The purpose was to study the correlation between age at surgery and functional recovery after infant pyeloplasty.
PURPOSE
The purpose was to study the correlation between age at surgery and functional recovery after infant pyeloplasty.
MATERIALS AND METHODS
All infants who underwent pyeloplasty were analyzed retrospectively in this multicenter study. Anteroposterior diameter (APD) >2 cm, split renal function (SRF) <40%, and Society of Fetal Urology (SFU) grade 3-4 were surgical indications. Based on the age at pyeloplasty, they were divided into Group 1 (1-3 months) and Group 2 (4-12 months). APD and SRF were compared before and after surgery in both groups. The fractional recoverable function (post-SRF-pre-SRF)/(50-pre-SRF) ×100 was correlated with age.
RESULTS
Fifty-one infants underwent pyeloplasty (mean age: 1.6 months - Group 1 and 7.2 months - Group 2). The mean APD decreased from 3 cm to 1.2 cm in Group 1 while 2.8 cm to 2 cm in Group 2 ( = 0.001). The mean SRF increased from 32.28% to 42.81% in Group 1 while 31%-34.18% in Group 2. SRF recovery was significantly higher in Group 1 compared to Group 2 ( = 0.001). Regression analysis showed a weak negative correlation ( = -0.2792) between age at surgery and renal function improvement.
CONCLUSION
Functional recovery after pyeloplasty is better when done earlier (1-3 months), as this gives the growing kidney the best opportunity to recover.
PubMed: 38912019
DOI: 10.4103/jiaps.jiaps_194_23 -
Journal of Indian Association of... 2024The urinary biomarker response precedes the appearance of any renal structural or functional derangement. Transforming growth factor-β1 (TGF-β1), neutrophil gelatinase...
Role of Urinary Biomarkers (Transforming Growth Factor β1, Neutrophil Gelatinase-Associated Lipocalin, and Cystatin C) as a Prognostic Factor of Renal Outcome in the Posterior Urethral Valve.
BACKGROUND
The urinary biomarker response precedes the appearance of any renal structural or functional derangement. Transforming growth factor-β1 (TGF-β1), neutrophil gelatinase associated lipocalin (NGAL), and Cystatin C (CysC) can act as the early prognostic markers in posterior urethral valve (PUV) patients.
AIM
To compare the urinary levels of TGF-β1, NGAL, and CysC between PUV cases and age matched controls and to correlate these with renal structural and functional parameters.
MATERIALS AND METHODS
This prospective study included children with PUV diagnosed using the standard investigations and an equal number of age-matched controls with nonurological problems. For the study subjects, the urinary samples were collected at three different time points (pre- and postoperatively at 3 and 6 months), whereas for controls, only single-voided samples were studied. The urinary levels of TGF-β1, NGAL, and CysC were estimated by the standardized techniques using the ELISA kits. Statistical methods were used to drive the comparisons between cases and controls.
RESULTS
Fifteen children with a median age of 10 (5-48) months were enrolled in each of the two groups. The mean uTGF-β1 in the case group was significantly higher at all three time points (43.20 ± 6.13 pg/ml, 43.33 ± 11.89 pg/ml and 40.71 ± 9.01 pg/ml) as compared to the control group (29.12 ± 8.31 pg/ml) ( ≤ 0.001). The median uNGAL in the case group was also higher (17.78 ng/ml, 2.35 ng/ml and 2.536 ng/ml) as compared to the control group (1.31 ng/ml). However, the difference was significant only preoperatively ( = 0.02). The median uCysC in case group was similarly higher (0.347 μg/ml, 0.439 μg/ml, and 0.382 μg/ml) than the control group (0.243 μg/ml) ( > 0.05). Serum creatinine in the case group (0.49 mg/dl) showed no significant rise above that of control (0.24 mg/dl). A cutoff value of uTGF-β1 = 36.55 pg/ml ( < 0.001), uNGAL = 0.879 ng/ml ( = 0.02), and uCysC = 0.25 μg/ml ( = 0.22) was found to be associated with renal damage in PUV. A significant correlation was found between uNGAL and S. creatinine at 3 months ( = 0.43, = 0.017) and 6 months ( = 0.47, = 0.08).
CONCLUSION
The elevated uTGF-β1, a decline in uNGAL and an increase in uCysC suggests ongoing inflammation, improvement in hydronephrosis and a prolonged proximal tubular dysfunction in PUV patients, respectively.
PubMed: 38912012
DOI: 10.4103/jiaps.jiaps_210_23