Frontiers in nephrology最新文献

Background: Podocytopathies are a varied set of renal diseases in which podocytes are unable to perform their typical filtration function within the glomerulus. This typically leads to edema, proteinuria, and hypoalbuminemia early in life. Among podocytopathies, focal segmental glomerulosclerosis (FSGS) is characterized by histology demonstrating segmental and focal sclerosis of the glomerular tuft. FSGS affects an estimated 1-20 per one million individuals and leads to significant morbidity and mortality related to renal failure. While FSGS can be attributed to many causes, such as drug reactions and infections, underlying pathogenic genetic variants play an increasingly well-recognized role in this disease.

Case: A 38-year-old 46,XX female patient of self-reported Cambodian ancestry was evaluated due to her history of atypical uterovaginal morphology. She had a history of hypertension and nephrotic range proteinuria that was diagnosed early in adulthood. A kidney biopsy at that time revealed FSGS. Following worsening renal function and subsequent end-stage renal disease (ESRD), she underwent a kidney transplant at 33 years of age. After kidney transplant, she presented with hematocolpos and was found to have distal vaginal atresia and an arcuate uterus. She underwent vaginoplasty and then had regular menses. She was noted to have persistently elevated follicle stimulating hormone levels, consistent with primary ovarian insufficiency, but with normal anti-Müllerian hormone levels. Assessment of her family history was suggestive of other individuals in her family with similar renal disease and uterine differences. Genetic analysis identified a WT1 variant (c.1338A>C; p. =) of uncertain significance that is also present in her similarly affected mother. To help clarify the potential impact of this variant, we completed a mini-gene assay to detect in vitro splicing changes in the presence of the WT1 variant sequence uncovered in this individual. This demonstrated resultant aberrant splicing that further supports the pathogenicity of the uncovered variant for this individual.

Conclusions: To our knowledge, this represents the first case of a podocytopathy with co-occurring uterovaginal anomalies due to exon skipping in WT1. The patient exhibited a severe course of chronic kidney dysfunction requiring a kidney transplant. Clinical RNA sequencing to clarify variants impacting splicing remains challenging due to tissue- specific gene expression for genes such as WT1, thus, research-based assays may be beneficial to understand the consequence of rare or previously uncharacterized variants.

Objectives: Febuxostat, an oral medication for treating hyperuricemia (HUA), is a non-purine xanthine oxidase inhibitor that regulates serum uric acid (SUA) metabolism in patients with chronic kidney disease (CKD). However, the drug's effectiveness in improving renal function in patients with non-dialysis stage 3/4 CKD remains unclear. Our aim is to investigate the efficacy of febuxostat on kidney function. In addition, the cardiac function will be assessed.

Method: We conducted a single-center, interventional, randomized, controlled, open-label study. A total of 316 patients with non-dialysis stage 3/4 CKD, with SUA ≥6mg/dL in women and ≥7mg/dL in men, were assigned to either the febuxostat group (n=156) or the control group (n=160). The primary endpoint was the evaluation of changes in kidney biomarkers from baseline to 12 months of treatment, and any changes in cardiac biomarkers and echocardiographs were the secondary endpoint.

Results: The primary endpoint was a comparison between the two groups from baseline to 12 months of treatment. SUA was significantly decreased in patients treated with febuxostat 40 mg (6.85 ± 0.41mg/dL at baseline and 5.27 ± 0.70mg/dL at 12 months of treatment, P<0.001) and this was associated with increased eGFR (34.48 ± 8.42ml/min at baseline and 38.46 ± 8.87ml/min at 12 months of treatment, P<0.001). There were significant decreases in high-sensitivity troponin T (19.50 ± 7.24ng/L at baseline and 16.98 ± 7.32ng/L at 12 months of treatment, P<0.001) and N-terminal-pro brain natriuretic peptide (941.35 ± 374.30pg/ml at baseline and 762.22 ± 303.32 pg/ml at 12 months of treatment, P<0.001) in the febuxostat group. These changes were also associated with increased left ventricular ejection fraction in the febuxostat group (50.47 ± 3.95% at baseline and 51.12 ± 3.96% at the end of the study, P<0.001).

Conclusion: In the interventional group, febuxostat was well-tolerated and demonstrated a reduction in SUA associated with an increase in eGFR. This slowed down the progression of renal disease in patients with non-dialysis stage 3/4 CKD and improved cardiac function.

Introduction: This study aims to describe the outcome of levamisole (LEVA) treatment in children with frequently relapsing nephrotic syndrome (FRNS).

Methods: This prospective cohort study was conducted at the Department of Pediatric Nephrology, Sindh Institute of Urology and Transplantation from 1 January 2019 to 31 December 2020. Children aged 1-18 years diagnosed with FRNS were included. LEVA was started with a dose of 2-2.5 mg/kg every other day for 2 years along with low-dose prednisolone in the first year.

Results: A total of 70 children with FRNS were enrolled in the study. The median age was 7.5 [interquartile range (IQR) 5.0-9.6 years] with a slight predominance of boys (42, 60%). The mean number of relapses and cumulative dose of steroids significantly decreased after 2 years of LEVA therapy and during the 1-year follow-up. LEVA non-response was observed in half of the studied participants (28, 46%). The responders and non-responders were comparable in terms of cumulative dose of steroids and number of relapses in the year prior to starting LEVA [5,242 ± 1,738 versus 4,910 ± 1,469 (p-value = 0.52) and 5.4 ± 2.4 versus 5.2 ± 2.1 (p-value = 0.85)].

Conclusion: LEVA therapy resulted in a substantial reduction in the frequency of relapses and cumulative dosage, indicating its potential as an alternative option for children with relapsing disease.

Objectives: Kidney injury in patients with lupus nephritis (LN) results in pro-fibrotic biomarker expression, a manifestation also observed with calcineurin inhibitor (CNI) therapy. The second-generation CNI, voclosporin, is approved in the United States and Europe for the treatment of patients with active LN in combination with background immunosuppression, based on successful outcomes from the global phase 2 AURA-LV and phase 3 AURORA 1 studies, which demonstrated the efficacy of voclosporin across diverse racial and ethnic populations, and encompassing multiple biopsy classes of LN, alongside a favorable safety profile. This post hoc analysis examined changes from baseline levels of serum and urinary biomarkers, including pro-fibrotic biomarkers, in a cohort of patients from the parent AURORA 1 study.

Methods: Samples were analyzed from a cohort of patients in AURORA 1 treated with voclosporin (23.7 mg twice daily, n=57) or placebo (n=59) in combination with mycophenolate mofetil (MMF) and low-dose glucocorticoids, including in a subgroup of patients that experienced a ≥30% decline from baseline in estimated glomerular filtration rate (voclosporin, n=26; placebo, n=20).

Results: The addition of voclosporin to MMF and low-dose glucocorticoids for the treatment of LN did not result in significant differences in normalized urinary concentrations of KIM-1, TGF-β1, MCP-1, or NGAL, biomarkers indicative of renal fibrosis and kidney damage, when compared to MMF and low-dose glucocorticoids alone.

Conclusion: These findings further support the safety of voclosporin for the treatment of LN in adult patients.

Clinical trial registration: ClinicalTrials.gov , identifier NCT03021499; EudraCT, identifier 2016-004045-81.

Background: Type 4 cardiorenal syndrome (CRS) involves cardiovascular alterations caused by chronic kidney disease (CKD). Fibroblast growth factor-23 (FGF23), carboxy-terminal propeptide of procollagen type I (PIP), and parathyroid hormone (PTH) have been proposed as biomarkers of pathological cardiac remodeling in CKD. In contrast, it has been suggested that MicroRNA 221 has a cardioprotective role. Available evidence shows that, 12 months after kidney transplantation (KT), type 4 CRS reverts in only half of the patients.

Objective: To assess long-term cardiac reverse remodeling after KT and its association with FGF23, PIP, and PTH levels.

Methods: Patients with end-stage renal disease were assessed before and 28 months after KT using FGF23, PIP, and PTH serum concentrations and transthoracic echocardiography.

Results: Fifty-three patients were followed for 28 months after KT. All the patients showed cardiac abnormalities upon inclusion. A follow-up assessment showed a reduction in left ventricle (LV) mass (121 ± 48 vs. 65 ± 14 gr/m²) and left atrial volume (46 vs. 30 ml/m²). The LV ejection fraction (53 vs. 63%), LV global longitudinal strain (-15.9 vs.-19.4%), and LV diastolic function improved. miR-221 expression increased after KT (8.73 RIQ= 3.7-25 vs. 40.16 RIQ= 24-223, p=0.001) and was correlated with the Ee´ratio (r= -0.32, p= 0.02). Multivariate analysis showed that post-KT LV mass was determined by pre-KT LV mass, serum Cr level, post-KT PIP, and hypertension (R² = 0.65, F=12.1, p=0.001).

Conclusions: Contrary to other evidence, this study demonstrated that type 4 CRS is reversible over the long term. This is a paramount finding because KT normalizes cardiac structure and function independently of the severity of basal cardiac abnormalities.

Objectives: To investigate the validity of bioelectrical impedance analysis (BIA)-derived phase angle (PhA) as a predictor of malnutrition in maintenance hemodialysis (MHD) patients.

Methods: A single-center, cross-sectional study of 126 MHD patients was conducted. A diagnosis of malnutrition was based on the 7-point Subjective Global Assessment (7-p-SGA) criteria. A Bioelectrical Impedance Analyzer was used to determine the PhA, fat mass (FM), muscle mass, and extracellular water/total body water (ECW/TBW) ratio. Biochemical indices and anthropometric measurements were also assessed. Using 7-p-SGA criteria, the patients were categorized into two groups: well-nourished and malnourished. General patient characteristics and the PhA values were compared between the two groups. A correlation analysis examined the relationship between PhA and the nutritional index. Logistic regression models and receiver operating characteristic curve analyses were used to identify independent factors for predicting malnutrition and determining their respective cutoff values.

Results: The malnourished group had a significantly lower PhA than the well-nourished group (5.19° (5.81°, 4.09°) vs 6.13° (6.80°, 5.49°), P < 0.001). The PhA correlated positively with body mass index (BMI), albumin (Alb), and handgrip strength (HGS) (P < 0.05). However, there were no significant associations between PhA and FM or triceps skinfold thickness (TSF) (P > 0.05). Multivariate logistic regression analysis revealed that PhA, Alb, and BMI were independent predictors of malnutrition. Of these, BMI was the strongest predictor [odds ratio (OR) = 0.68; P < 0.001]. PhA also served as a secondary predictor of malnutrition (OR = 0.588; P = 0.035). Receiver operating characteristic curve analysis indicated that a PhA threshold value of approximately 5.78° was optimal for predicting malnutrition.

Conclusion: PhA is a straightforward and reliable predictor of malnutrition in MHD patients, with an optimal cut-off value of 5.78° identified for diagnosing this condition.

Urine electrolytes and indices assessment as a tool for acute kidney injury (AKI) pathophysiological understanding and management is, until these days, a matter of debate. The classic division of AKI in "pre-renal" (functional/transient) and "renal" (structural/persistent) based on the urinary concentration of sodium and the fractional excretions of sodium and urea has gained popularity for decades and is still present in medical textbooks. Nevertheless, the conclusions of the studies that have used these parameters are very heterogenous and controversial. In the last decade, the pre-renal paradigm has been questioned since urine biochemistry (UB) compatible with "pre-renal AKI" was retrieved from experimental animals with increased renal blood flow, leading some authors to conclude that this approach is not useful for AKI monitoring. Our group has also studied the use of UB in AKI and we think that the key point for adequate use of this tool in clinical practice is a complete mindset change in the way we look and interpret data. In this article, we present the "urine biochemical approach" as an alternative way for UB assessment, which we believe that makes more sense and seems to be more useful for AKI monitoring than the traditional approach. Although the real utility of this alternative approach needs to be confirmed in large, prospective studies, the aim of the present article is to open the mind of critical care practitioners for a potential reappraisal of ancient concepts and ideas regarding the use of urine electrolytes in AKI monitoring.

Acute kidney injury (AKI) in pediatric and neonatal populations poses significant diagnostic and management challenges, with delayed detection contributing to long-term complications such as hypertension and chronic kidney disease. Recent advancements in artificial intelligence (AI) offer new avenues for early detection, risk stratification, and personalized care. This paper explores the application of AI models, including supervised and unsupervised machine learning, in predicting AKI, improving clinical decision-making, and identifying subphenotypes that respond differently to interventions. It discusses the integration of AI with existing risk scores and biomarkers to enhance predictive accuracy and its potential to revolutionize pediatric nephrology. However, barriers such as data quality, algorithmic bias, and the need for transparent and ethical implementation are critical considerations. Future directions emphasize incorporating biomarkers, expanding external validation, and ensuring equitable access to optimize outcomes in pediatric AKI care.