This meeting report highlights the "Rare Kidney Disease Conference" held on December 7-8 in Palm Springs, organized by Loma Linda University.
This meeting report highlights the "Rare Kidney Disease Conference" held on December 7-8 in Palm Springs, organized by Loma Linda University.
Background: It sounds paradoxical that a tiny component of the cellular mantle known as glycocalyx is also the most ubiquitous, more so than mitochondria or nuclei, endowing glycocalyx coverage to every cell with no exceptions. Despite a relatively short history, this organelle has received exponentially growing attention and number of publications as reflected in the last decade. This cellular mantle consists of 4 transmembrane proteins and 6 GPI-anchored proteins, all of which are decorated with glycosaminoglycans like heparan, chondroitin and dermatan sulfates, and hyaluronic acid. All this has been exhaustively reviewed.
Summary: Our goal here will be to briefly sketch the important common features of glycocalyx, especially of endothelial cells, and to focus on clinically pertinent practical aspects of this structure. We will describe visual and biochemical detection challenges, highlight the usefulness of identifying and quantifying glycocalyx fragments in biological fluids while broadening the spectrum of specimens for diagnostic purposes, and discuss how these parameters may provide valuable clues regarding their therapeutic relevance as pharmacological targets.
Key message: The glycocalyx represents a clinically valuable target and advances in its detection can enhance diagnostic precision and strengthen its translational relevance.
Background: Chronic kidney disease (CKD) represents a major global health challenge that leads to considerable morbidity and mortality. The influence of particulate matter (PM)2.5, PM2.5-10, PM10, nitrogen oxides (NOX), nitrogen dioxide (NO2) on renal diseases has raised concerns. However, the etiological relation remains uncertain. This study aimed to establish genetic support for causal links between environmental exposures and renal impairment.
Methods: A two-sample Mendelian randomization (MR) study was launched based on genome-wide association study. The inverse variance weighted method served as the primary analysis, complemented by four other approaches (MR-Egger, MR-Weighted median, weighted mode, and simple mode). The results were reinforced by MR-Egger regression, MR-PRESSO, and leave-one-out analysis.
Results: The MR analysis revealed that exposed to PM2.5-10 significantly increases the risk of developing CKD (OR: 1.631; 95% confidence interval [CI]: 1.161, 2.290), eGFRcrea (β: -0.013; 95% CI: -0.021, -0.004), and eGFRcys (β: -0.024; 95% CI: -0.039, -0.008). NOx exposure correlated with declining eGFRcys (β: -0.016; 95% CI: -0.029, -0.003). NO2 correlated with increased urine albumin-to-creatinine ratio levels (β: 0.039; 95% CI: 0.009, 0.069). However, no significant association was found between exposure to PM2.5 or PM10 and impaired renal function, with no evidence of significant heterogeneity or horizontal pleiotropy.
Conclusion: By employing MR analysis, we found that elevated levels of air pollutants, specifically PM2.5-10, can causally worsen kidney function. These results facilitate a deeper comprehension of the pathogenesis and treatment of air pollution-induced renal damage.
Background: The kidney matrix, once viewed as a static scaffold, is now recognised as a dynamic microenvironment that undergoes continual remodelling in response to physiological cues. Emerging evidence demonstrates that this remodelling follows circadian patterns driven by molecular clocks within specific kidney cell types.
Summary: This review synthesises recent advances on circadian regulation of the kidney matrisome, with emphasis on glomerular compartments. Circadian clocks in the glomerulus coordinate the timing of matrix turnover to preserve structural integrity, maintain filtration, and promote repair. Disruption of these rhythms contributes to maladaptive matrix accumulation, fibrosis, and kidney disease progression.
Key messages: Finally, we discuss mechanistic insights and translational opportunities, including chronotherapy and clock-targeted interventions. Understanding circadian control of glomerular matrix dynamics provides a framework for linking temporal biology to kidney health and disease.
Introduction: Acadian variant Fanconi syndrome (AVFS) is an autosomal recessive disease caused by a mutation in the NDUFAF6 gene which results in mitochondrial dysfunction and oxidative damage to the kidneys. It presents as a slowly progressive chronic kidney disease and proximal tubular dysfunction that, in contrast to typical Fanconi syndrome, leads to end-stage renal disease. It is diagnosed clinically and is present only in Acadian people. The objective of this study was to evaluate the effect of
Case presentation: Chart reviews were conducted on 4 active cases of AVFS not on kidney replacement therapy. Data on age, estimated glomerular filtration rate (eGFR), creatinine, medications, and blood pressure were collected. Progression of eGFR was evaluated in each patient before and after NAC prescription, and the projected time to kidney replacement therapy (eGFR = 10 mL/min/1.73 m2) with and without the use of NAC was calculated for each case. NAC had a positive effect on slowing the rate of eGFR loss in each patient. The projected need for kidney replacement therapy was delayed by an average of 14 years in the treated patients who otherwise would have required it by an estimated mean age of 28 years.
Conclusion: This study suggests that NAC has a beneficial effect on slowing the progression of kidney disease in patients with AVFS. This may be due to the modulation of oxidative stress by NAC. Further studies are needed to evaluate the potential benefits of NAC in other chronic kidney conditions.
Introduction: Cystic fibrosis (CF) is an autosomal recessive genetic disorder caused by pathogenic variants in the CFTR gene, leading to impaired chloride and bicarbonate transport across epithelial tissues. While typically diagnosed in infancy due to classic respiratory and gastrointestinal symptoms, atypical forms can present later in life with subtle or isolated manifestations. This case represents a rare monosymptomatic and atypical adult-onset presentation of CF, with electrolyte disturbances as the sole clinical manifestation.
Case presentation: We present the case of a 31-year-old man who developed recurrent episodes of profound electrolyte imbalance and acute kidney injury following intense physical activity in high environmental temperatures. He exhibited syncope, muscle cramps, and signs of severe dehydration. Laboratory tests revealed hyponatremia, hypokalemia, hypochloremia, hemoconcentration, and elevated creatinine levels, with urine findings consistent with extrarenal salt loss. A similar episode had occurred 6 years earlier. In the absence of an identifiable cause, CF was suspected. Sweat chloride testing confirmed the diagnosis in two separate samples. Genetic analysis revealed compound heterozygosity for a pathogenic CFTR variant and a variant of uncertain significance. Screening for other common manifestations of CF was negative.
Conclusion: This case underscores the diagnostic challenge of adult-onset CF, particularly in regions where neonatal screening was not historically implemented. Electrolyte disturbances, especially in the context of heat stress, may represent the only clinical clue in patients with residual CFTR function. Prompt recognition and diagnosis are essential for initiating appropriate monitoring and treatment, including the potential use of CFTR modulator therapies that can significantly improve quality of life and long-term outcomes.
Background: The determinants of glomerular filtration rate (GFR) and its changes over time are multiple and diverse. Nephron endowment is the starting point for GFR. Low renal endowment due to maternal undernutrition or premature birth as well as the loss of renal mass because of surgical procedures have a major impact on GFR. Eventually low renal mass may lead to organ damage when combined with metabolic syndrome and obesity or diabetes. The kidney has a major role in maintaining homeostasis. Changes in metabolic demand have a major influence in renal function. Increments in metabolic demand may determine a compensatory increase in GFR to cope with the new metabolic status. Clear examples of these conditions are pregnancy and obesity. Also, GFR may vary in response to the stimulation of renal reserve and the ageing process. All these aspects are different in men and women and may explain gender differences in renal function in health and disease.
Summary: In general, women have lower renal mass and lower metabolic demand. However, the study of these aspects in humans is complex. A living donor has two healthy kidneys and after nephrectomy, one of them remains in the same subject undergoing mechanisms of compensation whereas the other is transplanted in a patient with CKD that might have different body size, sex or age, than the donor. This makes the living kidney donation a unique setting to study the determinants of GFR. In this review, we take advantage of data from living kidney donors and recipients to understand diverse determinants of GFR, focusing on gender differences in renal function.
Key messages: In health and disease, several factors influence GFR like renal mass, the presence or absence of renal reserve, metabolic demand, the capacity of the kidney to adapt to it and the effect of ageing and senescence. In all of them, gender differences play a relevant role, making differences between men and women a factor to consider in the analysis of GFR.
Objective: The aim of the study was to explore the positive rate of anti-nephrin antibodies in various podocytopathies and their relationship with the clinical characteristics and outcomes of podocytopathies.
Methods: Medical literature studies from the PubMed database and the Web of science database from the establishment of the databases to July 28, 2025, were retrieved online. The main exploration indicator is the positive rate of anti-nephrin antibody in podocytopathies. Other indicators include the diagnostic role of anti-nephrin antibodies and their relationship with the clinical features and outcomes of podocytopathies. Analysis was conducted using the R software package "Meta" and "Mada."
Results: A meta-analysis included a total of 1,567 patients from 15 studies. The positive rates of anti-nephrin antibodies in adult patients with primary podocytopathies, minimal change disease, primary focal segmental glomerulosclerosis (FSGS), and children with idiopathic nephrotic syndrome (NS) were 41%, 51%, 32%, and 39%, respectively. Anti-nephrin antibodies are almost undetectable in patients with secondary FSGS, membranous nephropathy and other glomerular diseases. In podocytopathies with nephrotic-range proteinuria or without the use of immunosuppressants, the positive rate increased. The sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of anti-nephrin antibody in differentiating steroid-sensitive NS (SSNS) from non-SSNS in children were 0.57, 0.83, 3.40, and 0.55, respectively. Patients positive for anti-nephrin antibody had higher urinary protein levels and lower serum albumin levels and were more prone to recurrence, but there were no statistically significant differences in gender, age, renal function, and remission rate. The heterogeneity of the positive rate results of anti-nephrin antibodies in the literature is very high (I2 >80%), and most subgroup analyses cannot explore the source of the heterogeneity.
Conclusion: Anti-nephrin antibodies have a relatively high positive rate in podocytopathies and have a differentiating effect on SSNS and non-SSNS in children. Anti-nephrin antibodies are associated with the clinical severity and recurrence of podocytopathies.
Introduction: The utility of M-type phospholipase A2 receptor antibody (PLA2R-Ab) for risk stratification in membranous nephropathy (MN) remains suboptimal, while soluble T-cell immunoglobulin and mucin-domain containing-3 (sTim-3) has been confirmed as a critical immune regulator in kidney diseases. This study investigated the prognostic value of sTim-3 in PLA2R-associated MN (PMN) and the efficacy of its combination with PLA2R-Ab.
Methods: Serum PLA2R-Ab and sTim-3 levels were measured at baseline in 50 PMN patients using highly sensitive time-resolved fluorescence immunoassay (TRFIA) method. Patients were stratified into complete remission, partial remission, and no remission (NR) groups according to 12-month treatment outcomes.
Results: Prognostic cut-off discriminating NR from remission: sTim-3 = 17.63 ng/mL; PLA2R-Ab = 50 RU/mL (KDIGO high-risk threshold). The non-remission rate for patients with PLA2R-Ab <50 RU/mL was 23.58%, whereas the sTim-3 + PLA2R-Ab combination achieved 0%. Among 16 "high-risk" patients (PLA2R-Ab >50 RU/mL), sTim-3 demonstrated 93.75% accuracy in predicting outcomes. Remarkably, all 8 patients who achieved actual remission exhibited sTim-3 levels below 17.63 ng/mL. Double positivity (PLA2R-Ab >50 RU/mL and sTim-3 >17.63 ng/mL) identified a refractory subgroup with significantly poorer treatment response compared to other groups.
Conclusion: sTim-3 serves as a complementary biomarker to PLA2R-Ab. Combined detection optimizes PMN risk stratification: PLA2R-Ab >50 RU/mL and sTim-3 >17.63 ng/mL indicates an immune-activated state requiring intensive immunosuppression, preventing overtreatment in PLA2R-Ab-high patients with favorable immune status.
Introduction:
Case presentation: We report a case of acute kidney injury (AKI) as a result of tubular damage in a patient who used 18 grams of
Conclusion: We advise cautious use of
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：