Nephrotic Syndrome Patients Research Articles

Risk Factors for Stroke in Patients with Nephrotic Syndrome: Experience from Two Centers in Poland

Objective. Patients with nephrotic syndrome (NS) have an increased risk of developing acute ischemic stroke (aIS) and intracranial hemorrhage (ICH). However, the informations on the risk factors for these outcomes are unknown. The aim of this study was therefore to determine the risk factors for stroke among patients with NS. Methods. A multicentric retrospective cohort of patients who developed aIS or ICH, following a diagnosis of NS between 2010 and 2021 was assembled. NS patients who did not develop stroke at follow-up were assembled as non-matched controls from the same study period. Cox regression yielding a hazard ratio (HR) with a 95% confidence interval was applied to investigate the potential risk factors for stroke among patients with NS. A meta-analysis on the current litterature was also performed. Results. With a mean follow-up of 6 years, a total of 45 patients with NS were included of which 14 were diagnosed with aIS and 4 with ICH at follow-up. Significant risk factors for stroke in patients with NS were diabetes mellitus (DM) (HR 2.85, 95%CI 1.10-7.49; p-value = 0.03), diabetic nephropathy (HR 2.74, 95% CI 1.06-7.07; p-value = 0.038) smoking (HR 8.29, 95% CI 2.20-31.2; p-value = 0.002), prior arterial thromboembolic events (ATEs) (HR 2.86, 95% CI 1.09-7.53: p-value = 0.03) and age > 55 years old (HR 4.84, 95% CI 1.48-15.8; p-value = 0.009). Administration of low molecular weight heparin (LMWH) (HR 0.88, 95% CI 0.22-3.43; p-value = 0.848) did not affect the risk-estimates for developing stroke in patients with NS. Meta-analysis including 1091 patients revealed prior ATEs, diabetes, hypertension and smoking to be risk factors for ATEs among patients with NS. Conclusion. In this study we found older age, DM, prior ATEs and smoking to increase the risk of developing stroke in patients with NS, while notably LMWH had no protective effects. Our findings may serve as an aid for physicians in managing and identifying high-risk patients for stroke in this subpopulation.

Ambulatory blood pressure monitoring in Egyptian children with nephrotic syndrome: single center experience

BackgroundHypertension (HTN), especially masked hypertension, is one of the cardiovascular consequences of nephrotic syndrome. Masked hypertension cannot be identified during routine follow-up visits and adversely effects the patients’ cardiac function. The purpose of this study was to use ambulatory blood pressure monitoring (ABPM) to evaluate the blood pressure status of children with nephrotic syndrome.MethodsNinety children with nephrotic syndrome (NS) participated in this cross-sectional study, which was carried out at Cairo University Children Hospital’s nephrology clinic (CUCH). A sphygmomanometer was used in the clinic to measure blood pressure, and a Meditech monitor was used for 24-hour ambulatory blood pressure monitoring (ABPM). Interventricular septum (IVS) was measured, and heart functions were evaluated, using echocardiography.ResultsTwo groups comprised the included patients: Group1 (n = 70): HTN group included masked and ambulatory hypertension, and Group 2 (n = 20): non-HTN group included normal blood pressure, white coat HTN and well controlled HTN, 35% of the studied cohort (n = 32/90) had masked HTN.The serum urea was significantly higher in HTN group than non-HTN group with p-value: 0.047, while the serum albumin was significantly lower in HTN group than non-HTN group with p-value: 0.017. The cut-off point of 9.9, the sensitivity and specificity of serum urea to predict the occurrence of hypertension in NS patients was 92.9% and 35% respectively, with p-value : 0.024 and 95% CI (0.534–0.798). The z score of IVS is significantly higher in group 1 (2.5 ± 1.2) when compared to group 2 (1.7 ± 2.1) with p-value: 0.025 and Among group 1, it was noticed that 74% (n = 52/70) of them were systolic non-dipper, also it was observed that the mean serum potassium and cholesterol were significantly higher among systolic non-dipper when compared with systolic dipper patients with p-values: 0.045 and 0.005 respectively.ConclusionChildren with nephrotic syndrome are particularly vulnerable to experience ambulatory hypertension and masked hypertension, which may adversely impact their cardiac condition because they are not detectable by standard blood pressure readings at the clinic.

Clinical characteristics and functional dependent risk of intracerebral hemorrhage in patients with nephrotic syndrome

BackgroundWhile an increased incidence of intracerebral hemorrhage (ICH) has been reported in patients with nephrotic syndrome (NS), comprehensive understanding of the characteristics of ICH in this population remains elusive. This study explored the clinical features of ICH in a larger cohort of NS patients. MethodsTo compare the clinical characteristics of ICH in patients with and without NS, we conducted a multi-institutional retrospective cohort study using the data from Chang Gung Research Database of Taiwan from January 1, 2001, to December 31, 2017. ResultsThis study enrolled a total of 120 ICH patients with NS, and 271 ICH patients without NS. Patients with NS had a longer average length of stay in the acute medicine ward (17.7 ± 15.9 days vs 14.4 ±13.3 days, P = 0.047) and higher incidence of urinary tract infection (20.0% vs 10.0%, P = 0.006), gastrointestinal bleeding (16.7% vs 4.8%, P < 0.001), and pulmonary edema (4.2% vs 0%, P = 0.003) compared to those without ICH. Furthermore, the risk of 30-day dependent outcome (modified Rankin Scale score≧3) was significantly higher in ICH patients with NS compared to those without NS (Odds ratio 3.43, 95% confidence interval 1.49 to 7.91, P = 0.004). However, the 30-day mortality rate was similar between the NS patients and the control group. ConclusionsNS is associated with a significantly increased risk of functional dependence following ICH, highlighting the critical need for tailored intensive treatment and rehabilitation specifically for this patient population.

Clinical Value of ABCB1 and PAI-1 Gene Polymorphisms in Predicting Glucocorticoid-induced Adverse Reactions in Nephrotic Syndrome Patients.

Glucocorticoid (GC)-induced adverse reactions (ARs) have been extensively studied due to their potential impact on patients' health. This study aimed to examine the potential correlation between two polymorphisms [adenosine triphosphate-binding cassette B1 (ABCB1) C3435T and plasminogen activator inhibitor-1 (PAI-1) 4G/5G] and various GC-induced ARs in nephrotic syndrome (NS) patients. In this study, 513 NS patients who underwent GC treatment were enrolled. Then, the patients were divided into two groups based on ABCB1 C3435T and PAI-1 4G/5G genotyping, and intergroup comparisons of clinicopathological data and GC-induced ARs were performed. Univariate and multivariate logistic analyses were subsequently conducted to identify potential risk factors for GC-induced ARs, and a nomogram was subsequently established and validated via the area under the ROC curve (AUC), calibration curve and decision curve analysis (DCA). We identified ABCB1 C3435T as an independent risk factor for the development of steroid-associated avascular necrosis of the femoral head (SANFH) (OR: 2.191, 95% CI: 1.258-3.813, P=0.006) but not as a risk factor for the occurrence of steroid diabetes mellitus (S-DM). On the other hand, PAI-1 4G/5G was identified as an independent risk factor for the development of both SANFH (OR: 2.198, 95% CI: 1.267-3.812, P=0.005) and S-DM (OR: 2.080, 95% CI: 1.166-3.711, P=0.013). Notably, no significant correlation was found between the two gene polymorphisms and other GC-induced ARs. In addition, two nomograms were established and validated to demonstrate strong calibration capability and clinical utility. Assessing ABCB1 C3435T and PAI-1 4G/5G before steroid treatment in NS patients could be useful for identifying patients at a high risk of developing SANFH and S-DM.

The impact of severe nephrotic syndrome on thyroid function, nutrition and coagulation.

Nephrotic syndrome (NS) is characterized by urinary loss of proteins, including hormones and their carrier proteins, potentially resulting in endocrine disorders. This study aimed to assess thyroid dysfunction frequency and potential implications in NS. In this case-control study, patients with severe NS (serum albumin ≤2.5g/dl) and controls without proteinuria were evaluated for thyroid, haemostatic and nutritional parameters, including body composition. A total of 42 nephrotic and 40 non-proteinuric patients were enrolled. The NS group showed higher thyroid-stimulating hormone and lower free hormones, corresponding to a higher frequency of both euthyroid sick syndrome {ESS; 36% versus 5%; odds ratio [OR] 10.6 [95% confidence interval (CI) 2.2-50.0]} and hypothyroidism [31% versus 5%; OR 8.5 (95% CI 1.8-40.7)] compared with the control group. Levothyroxine supplementation was required for 11 NS patients (26% of the NS group). In addition, compared with control individuals, NS patients exhibited lower lean tissue mass and a trend towards hypercoagulability, which was evidenced by higher levels of most coagulation factors and fibrinolysis inhibitors, and reduced endogenous anticoagulants activities. Furthermore, NS patients with ESS presented with a 10.4kg (95% CI -18.68 to -2.12) lower lean tissue mass. Those with hypothyroidism had significantly reduced activity of coagulation factor X [by -30% (95% CI -47 to -13)] and protein S [by -27% (95% CI -41 to -13)] compared with euthyroid NS individuals. Thyroid dysfunction is common in severe NS, often necessitating levothyroxine supplementation, which supports routine thyroid workup. A potential link between thyroid, nutritional and coagulation disorders in NS requires further investigation.

Rivaroxaban for Thromboembolism Prophylaxis in Patients with Nephrotic Syndrome: A Single-Arm, Prospective Study

Introduction: Thromboembolism is a recognized complication of nephrotic syndrome (NS). Evidence supporting the use of rivaroxaban to prevent NS-related thrombosis is limited and controversial. This study aimed to explore the impact of NS on rivaroxaban pharmacokinetics and to collect observational data on the efficacy and safety of rivaroxaban as primary thromboprophylaxis in patients with NS. Methods: This prospective study analyzed 141 patients with NS who received rivaroxaban (10 mg/day) for thromboprophylaxis. High-performance liquid chromatography-tandem mass spectrometry was used to measure the trough and peak plasma concentrations (Ctrough and Cmax) of rivaroxaban. The influence of clinical and genetic factors on these concentrations was examined using multivariate logistic regression. Results: The median Cmax and Ctrough were 68.5 ng/mL (interquartile range [IQR], 31.7–105.5 ng/mL) and 4.4 ng/mL (IQR, 1.2–11.9 ng/mL), respectively. The incidence of thromboembolic events (TEs) was 12.8%, while that of bleeding events was 14.2%, although all were classified as minor. Albumin level was the most significant factor affecting Cmax (ρ = 0.55; p < 0.001) and was also significantly associated with TEs (0.81; 0.71–0.91 per 1.0 g/dL increase; p = 0.001) and bleeding risks (1.11; 1.03–1.19 per 1.0 g/dL increase; p = 0.008). Single nucleotide polymorphisms in the ABCB1 gene significantly influenced Ctrough but were not associated with clinical outcomes. Conclusion: Hypoalbuminemia significantly affects the pharmacokinetics of rivaroxaban in NS patients. A dose-adjustment strategy based on rivaroxaban concentrations, accounting for variable albumin levels, may improve the safety and efficacy of thromboprophylaxis in this population.

Urine-derived podocytes from steroid resistant nephrotic syndrome patients as a model for renal-progenitor derived extracellular vesicles effect and drug screening

BackgroundPersonalized disease models are crucial for evaluating how diseased cells respond to treatments, especially in case of innovative biological therapeutics. Extracellular vesicles (EVs), nanosized vesicles released by cells for intercellular communication, have gained therapeutic interest due to their ability to reprogram target cells. We here utilized urinary podocytes obtained from children affected by steroid-resistant nephrotic syndrome with characterized genetic mutations as a model to test the therapeutic potential of EVs derived from kidney progenitor cells (nKPCs).MethodsEVs were isolated from nKPCs derived from the urine of a preterm neonate. Three lines of urinary podocytes obtained from nephrotic patients’ urine and a line of Alport syndrome patient podocytes were characterized and used to assess albumin permeability in response to nKPC-EVs or various drugs. RNA sequencing was conducted to identify commonly modulated pathways after nKPC-EV treatment. siRNA transfection was used to demonstrate the involvement of SUMO1 and SENP2 in the modulation of permeability.ResultsTreatment with the nKPC-EVs significantly reduced permeability across all the steroid-resistant patients-derived and Alport syndrome-derived podocytes. At variance, podocytes appeared unresponsive to standard pharmacological treatments, with the exception of one line, in alignment with the patient’s clinical response at 48 months. By RNA sequencing, only two genes were commonly upregulated in nKPC-EV-treated genetically altered podocytes: small ubiquitin-related modifier 1 (SUMO1) and Sentrin-specific protease 2 (SENP2). SUMO1 and SENP2 downregulation increased podocyte permeability confirming the role of the SUMOylation pathway.ConclusionsnKPCs emerge as a promising non-invasive source of EVs with potential therapeutic effects on podocytes with genetic dysfunction, through modulation of SUMOylation, an important pathway for the stability of podocyte slit diaphragm proteins. Our findings also suggest the feasibility of developing a non-invasive in vitro model for screening regenerative compounds on patient-derived podocytes.

Novel mutation patterns in children with steroid-resistant nephrotic syndrome.

Idiopathic nephrotic syndrome (NS) in children poses treatment challenges, with a subset developing steroid-resistant nephrotic syndrome (SRNS). Genetic factors play a role, yet data on paediatric SRNS genetics in India are scarce. We conducted a prospective study using whole-exome sequencing to explore genetic variants and their clinical correlations. A single-centre prospective study (October 2018-April 2023) enrolled children with SRNS, undergoing renal biopsy and genetic testing per institutional protocol. Clinical, histological, and genetic data were recorded. DNA isolation and next-generation sequencing were conducted for genetic analysis. Data collection included demographics, clinical parameters, and kidney biopsy findings. Syndromic features were evaluated, with second-line immunosuppressive therapy administered. Patient and renal outcomes are presented for patients with and without genetic variants. A total of 680 paediatric NS patients were analysed, with 121 (17.8%) having SRNS and 96 consent to genetic analysis. 69 (71.9%) had early SRNS, 27 (28.1%) late. Among participants, 62 (64.58%) had reportable genetic variants. The most common were in COL4A genes, with 20 (31.7%) positive. Renal biopsy showed focal segmental glomerulosclerosis in 31/42 (74%) with variants, 16/28 (57.1%) without variants. Second-line immunosuppressions varied, with CNIs the most common. Outcomes varied, with partial or complete remission achieved in some while others progressed to ESRD. The study underscores the importance of genetic analysis in paediatric SRNS, revealing variants in 65.7% of cases. COL4A variants were predominant. Variants correlated with varied renal outcomes, highlighting potential prognostic implications. These findings emphasize the value of personalized approaches and further research in managing paediatric SRNS.

Clinical value of adding Dapagliflozin in patients with nephrotic syndrome.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors in nephrotic patients on immunosuppression are underexplored. We evaluated dapagliflozin's impact in non-diabetic primary nephrotic syndrome. Randomized controlled clinical trial was conducted on 60 non-diabetic primary nephrotic syndrome patients, equally assigned to dapagliflozin and control groups. All patients received the standard of care medication and the Dapagliflozin group received 10mg dapagliflozin in addition. Demographic data, nephrotic syndrome etiology, proteinuria levels, eGFR, and immunosuppression doses, were well-matched. After 6months of follow up primary outcomes included changes in and eGFR. Both groups exhibited significant reductions in proteinuria after 6months, with the dapagliflozin group achieving a mean UPCR reduction of - 94.7%, and the control group - 86.7% (p < 0.001). However, the comparative change in proteinuria between both groups did not reach statistical significance (p = 0.158). Dapagliflozin initially led to a transient eGFR decline. Dapagliflozin also resulted in a significant mean body weight reduction (p < 0.001) and notable improvements in triglyceride levels compared to the control group (p = 0.045). In primary nephrotic syndrome patients, adjunct dapagliflozin may enhance the standard of care. While notable, the reduction in proteinuria was comparable to that of the control group by the study's end. Furthermore, after 6months, eGFR remained stable in both groups. However, significant weight loss and serum triglyceride reduction were particularly pronounced in the dapagliflozin group. Further long-term investigations are necessary to address potential immunosuppression-related confounding effects in patients with primary glomerular disease.

Prognostic Impact of Proteinuria at Manifestation in Adult Nephrotic Syndrome Patients: Insights from a Prospective Cohort Study.

Background and objective Nephrotic syndrome is a significant worldwide health concern impacting millions of people and is marked by heavy proteinuria, edema, and decreased serum levels of albumin. Albuminuria arises from abnormal glomerular permeability and impaired tubular reabsorption, contributing to declining kidney function and a heightened risk of cardiovascular complications. The objective of this study was to investigate the prognostic role of proteinuria on the persistent decline in estimated glomerular filtration rate (eGFR) (<30 ml/minute/1.73m2) during follow-up and the dynamics of remission and relapse in various subtypes of nephrotic syndrome. Methods A total of 134 adult patients, diagnosed with various histopathological categories of nephrotic syndrome, were prospectively studied. Urine protein levels were assessed using the pyrogallol red-molybdate (PRM) method. The Kaplan-Meier analysis and log-rank test were utilized to assess the prognostic role of proteinuria at manifestation on persistent decline in estimated glomerular filtration rate(eGFR) (<30 ml/minute/1.73m2) and to evaluate remission and relapse based on proteinuria levels over an 18-month follow-up period. Results Patients with sub-nephrotic levels of proteinuria at manifestation did not progress to end-stage renal disease on follow-up. Patients with sub-nephrotic levels of albuminuria at manifestation were significantly associated with remission on follow-up. The Kaplan-Meier analysis indicated a significant probability of persistent eGFR decline (p < 0.001) in adult nephrotics with higher levels of albuminuria. Furthermore, patients with sub-nephrotic range proteinuria had earlier remission (p < 0.001) compared to those with relapse (p = 0.001) during the follow-up, as demonstrated by log-rank tests. Conclusion This study highlights that sub-nephrotic albuminuria at manifestation is linked to a reduced risk of renal progression and persistent eGFR decline compared to adult nephrotics with higher levels of albuminuria. Early detection and effective management of proteinuria, are crucial for preventing renal function decline and improving patient outcomes.

Effect of finerenone on nephrotic syndrome in patients with diabetic kidney disease

IntroductionDiabetic kidney disease (DKD) is an important complication of diabetes as it results in end-stage renal disease; hence, several drugs have been developed for its treatment. However, even with treatment with renin-angiotensin system inhibitors and sodium-glucose cotransporter-2 inhibitors, the residual risk of DKD remains. While this risk is an issue, the renoprotective effects of finerenone, a novel non-steroidal mineralocorticoid receptor antagonist, are becoming evident. High proteinuria increases the risk of cardiovascular death as well as renal failure. Hence, it is especially important to address cases of urine protein to nephrotic levels in DKD, however, no previous studies have assessed the safety and efficacy of finerenone in patients with DKD and nephrotic syndrome. Therefore, this study aimed to assess whether finerenone has a renoprotective effect in advanced DKD complicated by nephrotic syndrome. MethodsNine patients with DKD and nephrotic syndrome who received 10–20 mg/day of finerenone were retrospectively analyzed. The average observation period was 9.7 ± 3.4 months. Patients with serum potassium levels greater than 5.0 mEq/L at the start of finelenone were excluded. Changes in urinary protein levels, estimated glomerular filtration rate (eGFR), and serum potassium levels were studied before and after finerenone administration. ResultsThe mean changes in the urinary protein creatinine ratio (UPCR) at baseline were 6.6 ± 2.0. After finerenone treatment, the mean UPCR decreased to −0.6 ± 3.9; however, this change was not statistically significant.The eGFR decline slope also tended to decrease with finerenone treatment (before vs. after: 3.1 ± 4.9 vs. −1.7 ± 3.2 mL/min/1.73 m2. Furthermore, finerenone did not increase serum potassium levels. ConclusionsPatients treated with finerenone showed decreased UPCR; hence, it is suggested that finerenone may be effective in treating nephrotic syndrome in patients with DKD. These findings may be applicable to real-world clinical settings. Nonetheless, it is important to note that this study was a retrospective analysis of a single-center cohort and had a limited sample size, highlighting the need for additional large-scale investigations.

#1389 Identification of serum lipidomic profile in nephrotic syndrome patients

Abstract Background and Aims Nephrotic syndrome describes a collection of symptoms, mainly heavy proteinuria leading to kidney function loss, that can be caused by different underlying kidney diseases. Common primary causes of nephrotic syndrome include focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD) and membranous nephropathy (MN). Nephrotic syndrome is often characterized by plasma lipid abnormalities with elevations in cholesterol, triglycerides and lipoproteins. Here we set out to generate a detailed lipidomic analysis of FSGS, MCD and MN patient's plasma to find lipid changes common to nephrotic syndrome or specific for the underlying disease. Method For this lipidomic study, we included patients with primary FSGS (2 cohorts with n = 5), genetic FSGS (n = 5), MCD (n = 5) and MN (n = 5) in whom serum had been collected at the time they presented at our center with active nephrotic syndrome. We compared the serum lipidome of nephrotic syndrome patients with age matched healthy controls (n = 5), and with age matched patients with familial hypercholesterolemia (n = 5) who, like patients with nephrotic syndrome, have significantly elevated lipid values. Serum was analyzed using the Shotgun Lipidomics platform by Lipotype GmbH (Dresden, Germany), as previously described [1]. Results The lipidomic profile of patients with nephrotic syndrome was markedly different compared to control groups (Fig. 1A). In particular, lower levels of lyso-phophatidylcholine (LPC) and higher concentrations of phosphatidylethanolamine (PE) and lyso-PE (LPE) compared to control groups were most prominent (Fig. 1B). Subspecies analysis identified LPC 16:0;0 to be highly downregulated in patients with nephrotic syndrome (Fig. 2A), whereas LPE 18:0;0 and nearly all PE subspecies were increased compared to control groups (Fig. 2B and C). The lipidomic profile was largely comparable between different underlying diseases and we could not identify lipid classes specifically different for certain diseases. Conclusion Our lipidomic data show that patients with nephrotic syndrome have a distinct lipid profile compared to healthy controls or other disease controls. We identified LPCs, PEs and LPEs to be changed in nephrotic syndrome. We could not identify lipids specific for certain diseases underlying nephrotic syndrome, but rather identified a general nephrotic syndrome lipid profile. This suggests that lipid changes are rather a consequence of disease manifestation in these patients with various underlying causes. Further research should focus on confirming this lipid profile in larger cohorts and unraveling the mechanisms leading to the observed lipid changes.

#457 Sparsentan has direct effects on the glomerular capillary wall to attenuate increased permeability after exposure to nephrotic syndrome plasma

Abstract Background and Aims The glomerular endothelial glycocalyx (eGlx), a luminal layer of proteoglycans, glycoproteins and glycolipids, forms the first part of the glomerular filtration barrier (GFB). Nephrotic syndrome (NS) describes a group of pathologies of the renal glomerulus that result in proteinuria and is associated with glomerular endothelial dysfunction. Current treatments are broad and non-specific. Sparsentan is a single-molecule dual endothelin type-A and angiotensin II type 1 receptor antagonist that has received accelerated approval in the United States for the reduction of proteinuria in adults with IgA nephropathy at high risk of disease progression. Our validated glomerular permeability assay directly measures the albumin permeability (Ps’alb)of capillary loops within individually trapped glomeruli [1]. This ex vivo assay is independent of haemodynamic factors and tubular albumin handling – factors known to affect urine protein concentrations. This work examines whether sparsentan could reduce glomerular albumin permeability in NS, by preserving the eGlx to maintain the GFB. Method Human NS plasma samples were collected under ethical consent from 3 patients that had undergone plasma exchange from periods when they were in relapse (RL), or subsequent remission (RM). Adult male Sprague Dawley rats (175–200 g) were perfused with 4% Ringer BSA solution. Glomeruli were isolated on ice by graded sieving from the cortex of each kidney. Glomeruli were incubated, in the presence of AF488-conjugated BSA (AF488-BSA, 30 μg/ml) and R18 (36.5 μg/ml), with 10% plasma from NS patients for 1 hour, and simultaneously treated with sparsentan (0.1 μM, 1 μM and 10 μM) or vehicle. The glomerular Ps’alb assay was used to measure changes in albumin permeability. We applied a fluorescence profile peak-to-peak confocal imaging technique to treated glomeruli to assess glomerular eGlx thickness [2]. Results Human NS patients in RL had a significantly greater proteinuria compared to RM (RL, 10, 000 ± 1, 354 mg/g; RM, 95.3 ± 59.7 mg/g, P = 0.017). Incubation of rat glomeruli with RL plasma induced a significant increase in Ps’alb (RM+vehicle, 6.0 × 10−7 ± 0.12 × 10−7 cm/s; RL+vehicle, 10.9 × 10−7 ± 0.84 × 10−7 cm/s, P &amp;lt; .001) with a significant reduction in glomerular eGlx thickness (RM+vehicle, 210 ± 21.2 nm; RL+vehicle, 109 ± 7.9 nm, P = .027), compared to rat glomeruli incubated with paired RM plasma. Sparsentan-treated RL incubated glomeruli were protected from both the increase in Ps’alb (RL+spars 10 µM, 6.3 × 10−7 ± 0.19 × 10−7 cm/s, P &amp;lt; .001) and the loss in glomerular eGlx (RL+spars 10 µM, 222 ± 8.5 nm, P = .013), to a level comparable to RM incubated glomeruli. The effect of sparsentan on Ps’alb was dose dependent (RL+spars 1 µM, 8.0 × 10−7 ± 0.46 × 10−7 cm/s; RL+spars 0.1 µM, 9.6 × 10−7 ± 0.22 × 10−7 cm/s) with Ps’alb changes correlating inversely with glomerular eGlx thickness (r² = 0.75, P &amp;lt; .0001). In RM glomeruli, sparsentan alone had no effect on Ps’alb compared with vehicle (RM+spars 10 µM, 6.2 × 10−7 ± 0.25 × 10−7 cm/s, P = .590), suggesting no effect on otherwise healthy capillaries. Conclusion We have shown that dual inhibition of endothelin and angiotensin receptors, with sparsentan, preserves the glomerular eGlx resulting in normalised glomerular permeability in NS. These findings suggest that the direct action of sparsentan on the GFB could help maintain barrier integrity in NS, in particular by glycocalyx protection.

#1641 Assessing long-term prognosis in patients with glomerular disease: nephrotic syndrome versus nephrotic range proteinuria comparison

Abstract Background and Aims Although there is considerable research on the role of proteinuria in the progression of chronic kidney disease, a direct comparison between biopsy-diagnosed glomerular disease (GD) patients presenting with nephrotic syndrome (NS) and those with nephrotic range proteinuria (NRP) is lacking. Our study aims to bridge this gap by comparing the long-term outcomes of patients with NS and NRP. Method We conducted a unicentric retrospective study on 240 kidney biopsy-proven GD patients (median age 50 years, 65% men, median eGFR 58 mL/min, median proteinuria 6.0 g/24 h), tracked from 2010-2015 until end-stage kidney disease (ESKD), death, or study end in January 2022. Results The median follow-up was 8.8 years. Diagnoses were predominantly nonproliferative (53%), proliferative (25%) nephropathies, diabetic nephropathy (12%), and paraprotein diseases (10%). NS was observed in 141 (59%) patients, presenting more frequently with arterial hypertension (61 vs 43%, p 0.001), higher eGFR (64.9 vs 51.5 mL/min, p 0.001), increased proteinuria (6.4 vs 5.4g/24 h, p 0.01), and dyslipidemia (serum cholesterol 316 vs 251 mg/dL, p 0.001; serum triglycerides 226 vs 184 mg/dL, p 0.001) than NRP patients. NRP patients more often had proliferative (30 vs 22%) GD and diabetic nephropathy (22 vs 5%) ; their renal chronicity score was higher (2 vs 0, p 0.001). ESKD endpoint occurred in 35% NS and 39% NRP patients (p 0.4). The cohort's mean kidney survival time was 8.2 years. In multivariate analysis, NS (HR 1.79, 95% CI: 1.09, 2.94), lower eGFR (HR 0.97, 95% CI: 0.96, 0.98), higher renal chronicity score (HR 1.12, 95% CI: 1.02, 1.23), and diabetic nephropathy (Ref, p 0.001) were associated with ESKD. 64 patients (27%) died, 73% post-kidney replacement therapy initiation, mostly from cardiovascular disease (63%). Mortality between proteinuria forms showed no difference. Multivariate analysis found lower eGFR (HR 0.98, 95% CI: 0.97, 0.99), higher Charlson comorbidity score (HR 1.38, 95% CI: 1.17, 1.64), and diabetic nephropathy (Ref, p 0.01) associated with mortality. Conclusion Our study found no difference in all-cause mortality between NS and NRP in glomerular diseases. However, adjusted analysis revealed poorer kidney survival for NS patients, emphasizing the need for personalized management to improve renal prognosis.

Do patients with nephrotic syndrome have an increased risk of osteoporosis? A nationwide population-based retrospective cohort study in Taiwan

ObjectivesTo evaluate whether nephrotic syndrome (NS) and further corticosteroid (CS) use increase the risk of osteoporosis in Asian population during the period January 2000–December 2010.DesignNationwide population-based retrospective cohort study.SettingAll healthcare...

A Study of Some Immunological and Hematological Aspects in Children with Renal Disease

This study was carried out between September 17, and December 25, 2023. It included 62 pediatric patients at the age range (1-12) years of both genders: 26 with chronic renal failure (CRF) and 36 with nephrotic syndrome (NS), who were outpatients and in-patients in the dialysis unit in both Al-Mansour pediatric teaching hospital and Child's central teaching hospital. The control group consisted of 26 children. Blood samples were collected from patients and controls. Immunological tests of interleukin-6 (IL-6) and erythropoietin (Epo) measurement were done by using ELISA technique. Biochemical tests, including blood urea and serum creatinine, were applied to evaluate renal function. Hematological aspects referred to anemia presence or not; by measuring PCV and Hb. The results explained significant increase in serum IL-6 levels (P&lt;0.001), significant decrease in serum Epo levels (P&lt;0.001), significant increase in both urea and creatinine concentrations (P&lt;0.001) in serum and significant decrease in both PCV and Hb (P&lt;0.001) in NS and CRF patients in comparison with the control group

Assessment of Biochemical measurements with vitamin D deficiency in nephrotic syndrome patient

OBJECTIVE: To determine the frequency of vitamin D deficiency and bone mineral metabolism abnormalities in patients with nephrotic syndrome.&#x0D; PATIENTS AND METHODS: Between June to December 2019, all patients who fulfilled the inclusion criteria and visited to SIUT, Karachi were included in the study, which is a descriptive cross sectional study. Informed consent was taken after explaining the procedure, risks and benefits of the study. Blood samples of all the patients were taken for measurement of vitamin D and bone mineral metabolism abnormalities.&#x0D; RESULTS: Out of 92 patients, 51(55.4%) were male while 41 (44.6%) were female Mean ± SD of age was 32.76±10.16 years. Vitamin D deficiency was found in 49 (53.3%) patients. Hypocalcemia occurred in 48 (52.2%) patients. Raised Alkaline phosphate was found in 42 (45.7%) patients.&#x0D; CONCLUSION: It is to be concluded that vitamin D deficiency and bone mineral metabolism abnormalities were documented in considerable number of patients presenting with nephrotic syndrome.

Distinct characteristics and prognosis of IgA nephropathy patients with nephrotic syndrome: a propensity score-matched cohort study.

IgA nephropathy (IgAN) is the most prevalent primary glomerulonephritis globally. While nephrotic syndrome (NS) is uncommon in IgAN, its significance remains unclear. We conducted a retrospective analysis of 170 IgAN patients, classifying them into NS (n = 85) and non-NS (n = 5) groups. Our study aims to compare their clinical characteristics, treatment responses, and prognoses. Patients were selected based on renal biopsy from 2003 to 2020. Propensity score matching ensured comparability. Clinical, pathological, and immunological data were analyzed. Composite endpoints were defined as end-stage kidney disease (ESKD) or a 30% decline in estimated glomerular filtration rate (eGFR). NS patients showed higher eGFR (74.3 ± 36.8 vs. 61.5 ± 33.6 mL/min.1.73 m2, p = 0.02), severe hematuria (35.0 (4.7,147.5) vs. 4.0 (1.8,45,0) cells/μl, p < 0.001), severe foot process effacement (p = 0.01), and lower C3 levels (1.0 ± 0.3 vs. 1.1 ± 0.2 g/L, p = 0.03). In contrast, the non-NS group had higher BMI (24.3 ± 4.0 vs. 26.8 ± 3.7 kg/m2, p < 0.001) and elevated serum uric acid levels (376 (316,417) vs. 400 (362, 501) mmol/L, p = 0.001), suggesting metabolic factors might contribute to their condition. Both groups exhibited similar MESTC scores. NS patients had higher complete remission rates (26.2% vs. 14.1%, p = 0.04). Cox regression revealed NS independently associated with a higher risk of composite endpoints (HR = 1.97, 95% CI 1.05-3.72, p = 0.04). Linear mixed models did not show significant eGFR trajectory differences. This study has established that IgAN patients with NS exhibit distinct characteristics, including active disease and increased complement activation. NS is independently associated with a poorer prognosis, emphasizing the need for targeted interventions in this subgroup.

Transcriptional mechanism of E2F1/TFAP2C/NRF1 in regulating KANK2 gene in nephrotic syndrome

The mortality rate linked with nephrotic syndrome (NS) is quite high. The renal tubular injury influences the response of NS patients to steroid treatment. KN motif and ankyrin repeat domains 2 (KANK2) regulates actin polymerization, which is required for renal tubular cells to maintain their function. In this study, we found that the levels of KANK2 in patients with NS were considerably lower than those in healthy controls, especially in NS patients with acute kidney injury (AKI). To get a deeper understanding of the KANK2 transcriptional control mechanism, the core promoter region of the KANK2 gene was identified. KANK2 was further found to be positively regulated by E2F Transcription Factor 1 (E2F1), Transcription Factor AP-2 Gamma (TFAP2C), and Nuclear Respiratory Factor 1 (NRF1), both at mRNA and protein levels. Knocking down E2F1, TFAP2C, or NRF1 deformed the cytoskeleton of renal tubular cells and reduced F-actin content. EMSA and ChIP assays confirmed that all three transcription factors could bind to the upstream promoter transcription site of KANK2 to transactivate KANK2 in renal tubular epithelial cells. Our study suggests that E2F1, TFAP2C, and NRF1 play essential roles in regulating the KANK2 transcription, therefore shedding fresh light on the development of putative therapeutic options for the treatment of NS patients.

The analysis of low-dose glucocorticoid maintenance therapy in patients with primary nephrotic syndrome suffering from COVID-19.

Objectives: This study aimed to describe the effects of low-dose (prednisolone acetate 2.5-7.5mg/day) glucocorticoids (GCs) maintenance therapy in patients with primary nephrotic syndrome (NS) suffering from coronavirus disease 2019 (COVID-19). Methods: A single-center retrospective study of NS patients with COVID-19 infection in Zhongda Hospital Affiliated to Southeast University from 1 February 2022 to 31 March 2023 was conducted. All enrolled patients underwent renal biopsy for the pathological diagnosis and reached complete remission (CR) or near-CR before COVID-19 infection. According to the maintained therapy regimen, patients were divided into low-dose GCs group and non-GCs group. Results: A total of 125 patients were enrolled in the study. Their median age was 46.0 ± 15.6years, and the median value of 24-h urine protein was 0.77g. The majority of these patients received treatment for more than 6months, with a significant portion achieving CR (29.6%) or near-CR (43.2%). The leading cause of NS was membranous nephropathy (52%). There were no significant differences in the baseline characteristics between low-dose GCs and non-GCs group. As compared to those in the non-GCs group, patients receiving low-dose GCs treatment showed less fatigue or muscle weakness, smell disorder, palpitations, decreased appetite, taste disorder, dizziness, sore throat or difficult to swallow and fever (p < 0.05). Moreover, patients in the low-dose GCs group were with higher median quality of life scores (85.0) than in the non-GCs group (p = 0.001). Further serum inflammatory factor analysis indicated that interleukin-6 (IL-6) levels in the non-GCs group were significantly higher than that in the low-dose GCs group (p < 0.05). Conclusion: Patients with NS in low-dose GCs maintenance therapy stage showed milder symptom, higher quality of life and decreased serum IL-6 levels compared to those, who were not on GCs maintenance therapy. These results suggest the beneficial effect of low-dose GCs therapy in NS patients with CR/near-CR suffering from COVID-19 infection.