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European Journal of Pediatrics Jun 2024The purpose of this study is to evaluate the efficacy and safety of belimumab combined with the standard regimen in treating children with active lupus nephritis. This...
UNLABELLED
The purpose of this study is to evaluate the efficacy and safety of belimumab combined with the standard regimen in treating children with active lupus nephritis. This single-center, retrospective cohort study used clinical data of children with newly active lupus nephritis hospitalized in the Department of Nephrology between December 2004 and February 2023. Patients were divided into a belimumab or traditional treatment group according to whether or not they received belimumab. Renal remission and recurrence rates and glucocorticoid dose were compared between groups. Forty-seven children (median age 11 years) were enrolled, including 30 and 17 children in the traditional treatment and belimumab groups, respectively. The Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2000) score of children in the belimumab group (23.59 ± 7.78) was higher than that in the traditional treatment group (19.13 ± 6.10) (P = 0.035). The two groups showed no significant difference in the frequency of pyuria, gross hematuria, and the levels of 24-h proteinuria and estimated glomerular filtration rate. The complement C3/C4 in the belimumab group recovered faster than that in the traditional treatment group (P < 0.05). There were no between-group differences in the complete renal remission rate at 6 or 12 months (P = 0.442, P = 0.759). There were no between-group differences in 1-year recurrence rate (P = 0.303). Furthermore, 6 and 12 months after treatment, glucocorticoid doses were lower in the belimumab than the traditional treatment group (17.87 ± 6.96 mg/d vs. 27.33 ± 8.40 mg/d, P = 0.000; 10.00 (5.3) mg/d vs. 13.75 (10.0) mg/d, P = 0.007), respectively.
CONCLUSION
With an equivalent renal remission rate, belimumab combined with the standard traditional regimen might promote the tapering of glucocorticoids, and the incidence of adverse events is low.
WHAT IS KNOWN
• Belimumab is documented as an adjunctive treatment with systemic lupus erythematosus (c-SLE) LN with efficacy. • Due to the paucity of studies, its effects and side effects in children with LN remain unclear.
WHAT IS NEW
• This single-center, retrospective cohort study evaluated the efficacy and safety of belimumab combined with the standard regimen in treating children with proliferative LN. • Belimumab combined with the standard traditional treatment might promote the tapering of glucocorticoids, while exhibiting a low occurrence of adverse events.
PubMed: 38940925
DOI: 10.1007/s00431-024-05662-9 -
Wellcome Open Research 2021When the Avon Longitudinal Study of Parents and Children (ALSPAC) was planned, it was assumed that the clinical obstetric data would be easily accessible from the newly...
BACKGROUND
When the Avon Longitudinal Study of Parents and Children (ALSPAC) was planned, it was assumed that the clinical obstetric data would be easily accessible from the newly developed National Health Service computerised 'STORK' system. Pilot studies, however, showed that, although fairly accurate in regard to aspects of labour and delivery, it was, at the time (1990-2), inadequate for identifying the full antenatal and postnatal details of clinical complications and treatments of the women in the Study.
METHODS
A scheme was therefore developed to train research staff to find and abstract relevant details from clinical records onto proformas designed for the purpose. Extracting such data proved very time consuming (up to six hours for complicated pregnancies) and consequently expensive. Funding for the enterprise was obtained piecemeal using specific focussed grants to extract data for subsamples of the Study, including a random sample to serve as controls.
RESULTS
To date, detailed records have been completed for 8369 pregnancies, and a further 5336 (13,705 in total) have complete details on specific prenatal areas, including serial measures of maternal blood pressure, proteinuria and weight. In this Data Note we describe the information abstracted from the obstetric medical records concerning the mother during pregnancy, labour, delivery and the first two weeks of the puerperium. Information abstracted relating to the fetus (including fetal monitoring, presentation, method of delivery) and neonate (signs of asphyxia, resuscitation, treatment and well-being) have been described in a further Data Note.
CONCLUSIONS
These data add depth to ALSPAC concerning ways in which the signs and symptoms, procedures and treatments of the mother prenatally, intrapartum and postnatally, may impact on the long-term health and development of both mother and child. They augment the data collected from the mothers' questionnaires (described elsewhere) and the 'STORK' digital hospital data.
PubMed: 38939328
DOI: 10.12688/wellcomeopenres.16603.2 -
BioImpacts : BI 2024Urinary extracellular vesicles (uEVs) can be considered biomarkers of kidney diseases. EVs derived from podocytes may reflect podocyte damage in different glomerular...
INTRODUCTION
Urinary extracellular vesicles (uEVs) can be considered biomarkers of kidney diseases. EVs derived from podocytes may reflect podocyte damage in different glomerular diseases. IgA nephropathy (IgAN) is one of the most common forms of glomerulonephritis (GN) characterized by proteinuria and hematuria. This study aimed to analyze the uEVs of IgAN patients to understand the pathophysiological processes of the disease at the protein level.
METHODS
Patients with GN [biopsy-proven IgAN (n = 16) and membranous glomerulonephritis (MGN, n = 16)], and healthy controls (n = 16) were included in this study. The uEVs were extracted, characterized, and analyzed to evaluate the protein levels of candidate markers of IgAN, including vasorin precursor, aminopeptidase N, and ceruloplasmin by western-blot analysis.
RESULTS
Higher levels of both podocytes and EVs-related proteins were observed in the pooled urine samples of GN patients compared to the healthy controls. In IgAN patients, uEV-protein levels of vasorin were statistically lower while levels of ceruloplasmin were significantly higher compared to MGN ( = 0.002, = 0.06) and healthy controls, respectively ( = 0.020, = 0.001).
CONCLUSION
Different levels of the studied proteins in uEVs may indicate podocyte injury and represent a direct association with the pathology of IgAN and MGN.
PubMed: 38938751
DOI: 10.34172/bi.2023.29981 -
Scientific Reports Jun 2024Moderately elevated albuminuria (30-300 mg/g) is a marker of renal dysfunction and a risk factor of cardiovascular disease. Additionally, several recent studies have...
Moderately elevated albuminuria (30-300 mg/g) is a marker of renal dysfunction and a risk factor of cardiovascular disease. Additionally, several recent studies have reported a relationship between moderately elevated albuminuria and triglyceride (TG) levels. Therefore, we aimed to evaluate the relationship between the urine albumin-to-creatinine ratio (UACR) and total cholesterol (TC), TG, and high-density lipoprotein C (HDL-C) levels. We analyzed data from 19,340 patients from the 2011-2014 and 2019-2020 from the Korea National Health and Nutrition Examination Surveys. Multivariate linear regression analysis showed that the UACR was positively associated with TC and TG levels and negatively associated with HDL-C levels in both Korean women and men. These results were reanalyzed according to the degree of proteinuria (normal, moderately elevated albuminuria, and severely elevated albuminuria (≥ 300 mg/g)). We found a positive relationship between UACR and TC and TG levels, but a negative association with HDL-C levels, except for TC (moderately elevated albuminuria) and HDL-C (moderately elevated albuminuria) in Korean men and TC (severely elevated albuminuria), TG (severely elevated albuminuria), and HDL-C (normal range albuminuria) in Korean women. The correlation between albuminuria and lipid profiles became more evident as albuminuria shift from normal to the severely elevated albuminuria. Thus our multivariate linear regression analysis showed that lipid profiles (TG, TC, and HDL-C levels) were associated with the UACR.
Topics: Humans; Female; Male; Albuminuria; Middle Aged; Creatinine; Republic of Korea; Adult; Triglycerides; Cholesterol, HDL; Aged; Lipids; Nutrition Surveys; Cholesterol; Biomarkers
PubMed: 38937496
DOI: 10.1038/s41598-024-65037-w -
Journal of Diabetes and Metabolic... Jun 2024Chronic kidney disease (CKD) is a major global health concern with increasing prevalence and associated complications. Metabolic syndrome (MetS) has been linked to CKD,... (Review)
Review
BACKGROUND
Chronic kidney disease (CKD) is a major global health concern with increasing prevalence and associated complications. Metabolic syndrome (MetS) has been linked to CKD, but the evidence remains inconsistent. We conducted a systematic review and meta-analysis to investigate the association between MetS and kidney dysfunction.
METHOD
We conducted a comprehensive search of databases until December 2022 for cohort studies assessing the association between MetS and incident kidney dysfunction. Meta-analysis was performed using fixed and random effects models. Subgroup analyses were conducted to explore heterogeneity. Publication bias was assessed using Egger's and Begg's tests.
RESULT
A total of 24 eligible studies, involving 6,573,911 participants, were included in this meta-analysis. MetS was significantly associated with an increased risk of developing CKD (OR, 1.42; 95% CI, 1.28, 1.57), albuminuria or proteinuria (OR, 1.43; 95% CI, 1.10, 1.86), and rapid decline in kidney function (OR, 1.25; 95% CI, 1.07, 1.47). Subgroup analyses showed a stronger association as the number of MetS components increased. However, gender-specific subgroups demonstrated varying associations.
CONCLUSION
Metabolic syndrome is a significant risk factor for kidney dysfunction, requiring close renal monitoring. Lifestyle changes and targeted interventions may help reduce CKD burden. Further research is needed to understand the connection fully and assess intervention efficacy.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s40200-023-01348-5.
PubMed: 38932881
DOI: 10.1007/s40200-023-01348-5 -
AIDS (London, England) Jul 2024Twenty-eight individuals who experienced proximal renal tubulopathy (PRT, Fanconi syndrome) while receiving tenofovir disoproxil initiated tenofovir alafenamide (TAF)...
Twenty-eight individuals who experienced proximal renal tubulopathy (PRT, Fanconi syndrome) while receiving tenofovir disoproxil initiated tenofovir alafenamide (TAF) and were followed for 5 years. None developed recurrent PRT or experienced significant changes in estimated glomerular filtration rate (by creatinine or cystatin-C), albuminuria, proteinuria, retinol-binding proteinuria, fractional excretion of phosphate, alkaline phosphatase, or bone mineral density at the lumbar spine. These data suggest that TAF is a well tolerated treatment option for individuals vulnerable to developing PRT.
Topics: Humans; Tenofovir; Alanine; Male; Anti-HIV Agents; HIV Infections; Adenine; Female; Fanconi Syndrome; Adult; Middle Aged
PubMed: 38932750
DOI: 10.1097/QAD.0000000000003916 -
Journal of Clinical Medicine Jun 2024The interplay between thyroid function and kidney graft function following kidney transplantation remains incompletely understood. Thyroid disorders are more prevalent...
The interplay between thyroid function and kidney graft function following kidney transplantation remains incompletely understood. Thyroid disorders are more prevalent in kidney transplant recipients than in the general population and are associated with poorer outcomes. This prospective, single-center study was designed to estimate thyroid function (thyroid-stimulating hormone (TSH), triiodothyronine (T3), free triiodothyronine (FT3), thyroxine (T4), free thyroxine (FT4), as well as anti-thyroid peroxidase antibody (anti-TPO), anti-thyroglobulin antibody (anti-Tg), and thyroid-stimulating immunoglobulin (TSI)) and its influence on kidney graft function among a cohort of 23 kidney transplant recipients during a follow-up period of 12 months. Significantly increased levels of T4 and T3 were observed 12 months post-transplantation, with FT3 levels increasing significantly after 6 months. The prevalence of immeasurably low anti-Tg antibodies rose during follow-up. Initially, 8% of patients showed positive TSI, which turned negative for all after 6 months. A statistically significant correlation was found between the initial TSH and the estimated glomerular filtration rate (eGFR) value 6 months after transplantation ( = 0.023). The graft function was stable. Proteinuria was statistically significantly lower 12 months after transplantation. Identifying additional risk factors, understanding their impact on kidney graft function, and recognizing cardiovascular comorbidities could enhance patient care. Notably, this study marks the first prospective investigation into thyroid function after kidney transplantation in Croatia, contributing valuable insights to the global understanding of this complex interplay.
PubMed: 38930088
DOI: 10.3390/jcm13123559 -
Journal of Clinical Medicine Jun 2024Glomerulopathy is a term used to describe a broad spectrum of renal diseases, characterized by dysfunction of glomerular filtration barrier, especially of podocytes....
Glomerulopathy is a term used to describe a broad spectrum of renal diseases, characterized by dysfunction of glomerular filtration barrier, especially of podocytes. Several podocyte-associated proteins have been found and proved their usefulness as urine markers of podocyte dysfunction. Two of them are nephrin (NEP) and prodocalyxin (PDC). This study aims to evaluate the association of podocyte damage, as it is demonstrated via the concentrations of urinary proteins, with clinical and histological data from patients with several types of glomerulonephritis. We measured urine levels of two podocyte-specific markers, NEP and PDC (corrected for urine creatinine levels), in patients with a wide range of glomerulopathies. Serum and urine parameters as well as histological parameters from renal biopsy were recorded. In total, data from 37 patients with glomerulonephritis and 5 healthy controls were analyzed. PDC and NEP concentrations correlated between them and with serum creatinine levels ( = 0.001 and = 0.013 respectively), and with histological lesions associated with chronicity index of renal cortex, such as severe interstitial fibrosis, severe tubular atrophy and hyalinosis (for PDC/NEP, all 0.05). In addition, the PDC and NEP demonstrated statistically significant correlations with interstitial inflammation ( = 0.018/ = 0.028). Regarding electron microscopy evaluation, PDC levels were correlated with distinct characteristics, such as fibrils and global podocyte foot process fusion, whereas the NEP/CR ratio was uniquely significantly associated with podocyte fusion only in non-immune-complex-mediated glomerulonephritis ( = 0.02). Among the other clinical and histological parameters included in our study, a strong correlation between proteinuria >3 g/24 h and diffuse fusion of podocyte foot processes ( = 0.016) was identified. Podocalyxin and nephrin concentrations in urine are markers of podocyte dysfunction, and in our study, they were associated both with serum creatinine and histological chronicity indices.
PubMed: 38929959
DOI: 10.3390/jcm13123432 -
Journal of Personalized Medicine Jun 2024Kidney stones are becoming increasingly common, affecting up to 10% of adults. A small percentage are of monogenic origin, such as Dent's disease (DD). DD is a syndrome...
Kidney stones are becoming increasingly common, affecting up to 10% of adults. A small percentage are of monogenic origin, such as Dent's disease (DD). DD is a syndrome that causes low-molecular-weight proteinuria, hypercalciuria, nephrolithiasis, and nephrocalcinosis. It is X-linked, and most patients have mutations in the gene. We performed a review of the literature and evaluated the case series ( = 6) of a single center in Spain, reviewing the natural evolution of kidney stones, clinical implications, laboratory analyses, radiological development, and treatment. All patients had a genetically confirmed diagnosis, with the mutation being the most frequent (66%). All patients had proteinuria and albuminuria, while only two and three presented hypercalciuria and phosphate abnormalities, respectively. Only one patient did not develop lithiasis, with most (60%) requiring extracorporeal shock wave lithotripsy or surgery during follow-up. Most of the patients are under nephrological follow-up, and two have either received a renal transplant or are awaiting one. The management of these patients is similar to that with lithiasis of non-monogenic origin, with the difference that early genetic diagnosis can help avoid unnecessary treatments, genetic counseling can be provided, and some monogenic kidney stones may benefit from targeted treatments.
PubMed: 38929844
DOI: 10.3390/jpm14060623 -
Children (Basel, Switzerland) Jun 2024A ~3-kb deletion-type DNA copy number variation (CNV, esv3587290) located at intron 7 of the gene (1p13.1, MIM*610132) has been proposed as a genetic factor in lupus...
Does the esv3587290 Copy Number Variation in the Gene Differ as a Genetic Factor for Developing Nephritis in Mexican Childhood-Onset Systemic Lupus Erythematosus Patients?
A ~3-kb deletion-type DNA copy number variation (CNV, esv3587290) located at intron 7 of the gene (1p13.1, MIM*610132) has been proposed as a genetic factor in lupus nephritis (LN) development in adult systemic lupus erythematosus (SLE) patients across European-descent populations, but its replication in other ethnicities has been inconsistent and its association with LN in childhood-onset SLE (cSLE) remains unknown. Here, we performed an exploratory association study in a sample of 66 unrelated cSLE Mexican patients (11 males, 55 females; ages 7.8 to 18.6 years). Two stratified groups were compared: cSLE patients with (N = 39) or without (N = 27) LN, as diagnosed by renal biopsy (N = 17), proteinuria (N = 33), urinary protein-creatinine ratio > 0.2 (N = 34), and erythrocyturia and/or granular casts in urinary sediment (N = 16). For esv3587290 CNV genotyping, we performed an end-point PCR assay with breakpoint confirmation using Sanger sequencing. We also determined the allelic frequencies of the esv3587290 CNV in 181 deidentified ethnically matched individuals (reference group). The obtained genotypes were tested for Hardy-Weinberg equilibrium using the χ test. Associations between LN and esv3587290 CNV were tested by calculating the odds ratio (OR) and using Pearson's χ tests, with a 95% confidence interval and ≤ 0.05. The esv3587290 CNV allele (OR 0.108, 95% CI 0.034-0.33, = 0.0003) and the heterozygous genotype (OR 0.04, 95% CI 0.119-0.9811, = 0.002) showed a significant protective effect against LN development. Finally, we characterized the precise breakpoint of the esv3587290 CNV to be NG_016548.1(NM_138959.3):c.1314+1339_1315-897del in our population. This report supports the notion that a broad genetic heterogeneity underlies the susceptibility for developing LN.
PubMed: 38929291
DOI: 10.3390/children11060712