Primary Nephrotic Syndrome Patients Research Articles

Left ventricular global longitudinal strain can detect subclinical left ventricular systolic dysfunction in adult patients with primary nephrotic syndrome.

It has been shown that there is an increased risk of cardiovascular events such as heart failure and death in nephrotic syndrome. Left ventricle global longitudinal strain (LVGLS) is a more sensitive measure of assessing myocardial dysfunction and is more reproducible than left ventricle ejection fraction (LVEF%). LVGLS can detectsubclinical deterioration in the left ventricle early. In this study, we aimed to investigate LVGLS in Primary Nephrotic Syndrome (PNS) patients with normal LVEF%. Patients with histopathologically confirmed PNS were evaluated for this prospective single-center study. Patients with similar age and gender characteristics without nephrotic syndrome were included as the control group. LVGLS measurements were performed by 2D speckle tracking echocardiography. A total of 171 patients, 57 with PNS and 114 in the control group, were included in the study. The mean age was 38±12 years in the study population, and 95(56%) of the patients were women. LVEF% was 60.2±4.2 in the PNS group and 61.1±3.2 in the control group, and there was no significant difference between the two groups (p=0.111). LVGLS was found to be significantly lower in the PNS group (-19.3±2.3% vs.-20.8±1.5 %, p<0.001). A significant relationship was observed between PNS and LVGLS in the multivariable linear regression analysis (β= 4.428, CI 95% =0.57?1.48, p<0.001). A significant relationship was observed between PNS and LVGLS, and LVGLS was found to be lower in PNS patients. In patients with PNS, subclinical left ventricular systolic dysfunction may be detected in the early period by measuring LVGLS.

Change of circulating lymphocyte subsets is related to disease activity and secondary infection in children with primary nephrotic syndrome-a retrospective study.

Primary nephrotic syndrome (PNS) is an immune-mediated glomerular disease that often reoccurs. However, the characteristics of circulating lymphocyte subsets in PNS children remain unclear. Immunosuppressive therapy can lead to temporary or persistent remissions, but also increases the risk of infection, and whether the circulating lymphocyte subsets can be used to predict the secondary infection also remains unclear. Here, we explored the distribution of lymphocyte subpopulations in the different stages of PNS, and its predictive value of secondary infection in pediatric patients. We included 89 children who were first PNS episodes or diagnosed with PNS admitted to Nanfang Hospital from September 2019 to April 2021, and 19 healthy children were recruited as controls (C). PNS patients were divided into three groups according to their serum biochemical tests: active group (A), partial remission (PR) group, and complete remission (CR) group. PNS patients with infection symptoms were divided into a co-infection group, others were divided into the non-infection group. The peripheral lymphocyte subsets were analyzed by flow cytometry. The relationship between the peripheral lymphocyte subsets and PNS activity or infection was analyzed. Compared to the healthy controls, the PNS patients' CD8+CD28+ T cell (TC) (C: 16.6%, 450.8/µL; A: 29.1%, P=0.000, 886.1/µL, P=0.012; PR: 25.7%, P=0.000, 817.3/µL, P=0.012; CR: 24.9%, P=0.001, 747.9/µL, P=0.020), and CD4+CD45RO+ ("memory" helper) T cells (C: 13.2%, 358.9/µL; A: 15.7%, P=0.036, 578.7/µL, P=0.001; PR: 17.6%, P=0.002, 610.0/µL, P=0.000; CR: 13.7%, P=0.676, 398.1/µL, P=0.525) were elevated. In addition, the regulatory T cells counts (non-infection: 117.9/µL; Co-infection: 73.3/µL, P=0.001) were significantly lower in patients with infection. We found that the predictive value measured by the area under the curve (AUC) showed that the AUC (t) Treg cell counts (61.5-84.5%) were almost always higher than the AUC for the (t) CD4+ T cell counts (55.1-77.1%). In this study, we found that T cell subpopulations had different characteristics in PNS during different disease phases. The CD8+CD28+ T cells, and CD4+CD45RO+ T cells increased at the disease quiescence of PNS. Moreover, CD4+ T cell subsets (regulatory T cell <82.5/µL) had higher predictive value than CD4+ T cell counts for PNS infection.

Does pathological type of primary nephrotic syndrome affect serum concentrations of proprotein convertase subtilisin/kexin type 9?

BackgroundDyslipidemia is a common finding in primary nephrotic syndrome (PNS). Serum PCSK9 level is also increased in PNS and is the main cause of dyslipidemia in such patients. There is a paucity of data on the relation between dyslipidemia and pathological types of PNS. We hypothesized that severity of dyslipidemia varies across different types of PNS, and this variation is due to differences in serum PCSK9 levels.MethodsFifty patients recently diagnosed with PNS were included in this cross-sectional study. Serum PCSK9, albumin, creatinine, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), very low-density lipoprotein cholesterol (VLDL-C), triglycerides (TG), and 24-h urine protein were measured. Comparison of patients’ characteristics between pathological types of PNS and correlations between serum PCSK9 and other parameters were assessed.ResultsSerum PCSK9 levels were significantly higher in PNS patients compared with healthy individuals (314.58 ± 73.83 vs 253.42 ± 36.66 ng/ml, p < 0.001). No differences found between PNS types regarding serum levels of PCSK9 (p = 0.571), TC (p = 0.806), LDL-C (p = 0.950), HDL-C (p = 0.844), VLDL-C (p = 0.472), and TG (p = 0.969). Serum PCSK9 levels correlated significantly with TC (p < 0.001), LDL-C (p < 0.001), HDL-C (p = 0.003), VLDL-C (p = 0.008), TG (p = 0.005), 24-h urine protein (p = 0.005), and male sex (p = 0.014).ConclusionThe pathological type of PNS does not affect serum levels of PCSK9 and components of lipid profile.

Ocular changes in nephrotic syndrome patients with preserved renal functions

BackgroundOptical coherence tomography (OCT) measurements of central choroidal thickness (CCT) and retinal thickness have been proposed as inflammatory indicators for a variety of systemic disorders, particularly those with a vascular component. The relationship between nephrotic syndrome (NS) and visual impairment is not clear. The aim of this study was to evaluate the ocular changes in primary NS patients with preserved renal functions. MethodsA total of 60 participants (30 NS patients, 30 healthy control subjects) was recruited in this cross-sectional and comparative study. Retinal and choroidal examinations were performed via the spectral domain OCT. Enhanced depth imaging (EDI) mode of the OCT was used for choroidal analysis. ResultsAlthough not statistically significant, CCT was found to be higher in the NS group compared to the control group (p = 0.07). Central foveal thickness (CFT) and retinal arteriolar caliber (RAC) values were statistically significantly lower in the patients with nephrotic syndrome, whereas retinal venular caliber (RVC) and choroidal vascularity index (CVI) values were similar in both groups. RAC and RVC were not statistically significantly correlated with CCT or CFT in both groups (p > 0.05). ConclusionThe results of the current study showed a significant difference between the NS group and the control group in terms of some ocular changes (i.e., CFT and RAC). As a result, CCT, CFT and RAC measurements with OCT may be used as a marker of inflammation in NS patients.

Population Pharmacokinetic Evaluation with External Validation of Tacrolimus in Chinese Primary Nephrotic Syndrome Patients.

The generalizability of numerous tacrolimus population pharmacokinetic (popPK) models constructed to promote optimal tacrolimus dosing in patients with primary nephrotic syndrome (PNS) is unclear. This study aimed to evaluate the predictive performance of published tacrolimus popPK models for PNS patients with an external data set. We prospectively collected 223 concentrations from 50 Chinese adult patients with PNS who were undergoing tacrolimus treatment. Data on published tacrolimus popPK models for adults and children with PNS were extracted from the literature. Model predictability was evaluated with prediction-based and simulation-based diagnostics and Bayesian forecasting. In prediction-based evaluation, none of the 11 identified published popPK models of tacrolimus had met a predefined criteria of a mean prediction error ≤ ± 20%, and the prediction error within ± 30% of the identified models didn't exceed 50%. Simulation-based diagnostics also indicated unsatisfactory predictability. Bayesian forecasting demonstrated amelioration in the model predictability with the inclusion of 2-3 prior observations. Moreover, the predictive performance of nonlinear models was not better than that of one-compartment models. The prediction of tacrolimus concentrations for patients with PNS remains challenging; published models are not applicable for extrapolation to other hospitals. Bayesian forecasting significantly improved model predictability and thereby helped to individualize tacrolimus dosing.

Use of mycophenolate mofetil in patients with pediatric and adult primary nephrotic syndrome: information from a Japanese hospital claims database

BackgroundCurrent treatment for frequently relapsing, steroid-dependent, or steroid-resistant nephrotic syndrome focuses on immunosuppressive therapies. Although the clinical guideline suggests the use of mycophenolate mofetil (MMF), limited information is available on patients with primary nephrotic syndrome who receive off-label treatment with MMF in Japan.MethodThe dose, treatment duration, previous treatment, and characteristics of primary nephrotic syndrome patients receiving MMF were investigated using data from a Japanese hospital claims database (April 2008–September 2021).ResultsData on 424 primary nephrotic syndrome patients receiving MMF (146 patients < 18 years old; 278 patients ≥ 18 years old) were captured. The most common initial daily doses of MMF capsules (% of patients < 18 and ≥ 18 years old) were 1000 mg (31.9%, 36.8%), 1500 mg (16.0%, 23.8%), and 500 mg (23.6%, 17.3%), and the most common maximum daily doses were 1000 mg (43.8%, 32.9%), 1500 mg (23.6%, 28.9%), and 2000 mg (6.3%, 16.2%). Most patients (97.9%, 99.3%) were treated with a daily dose of 2000 mg or less. Among patients < 18 years old, the younger the patient, the lower the dose. MMF was used for more than 1 year in 30.8% of patients < 18 years old and in 28.8% of patients ≥ 18 years old.ConclusionsOur study suggested that off-label use of MMF for primary nephrotic syndrome has increased since 2012 in Japan. The dose of MMF used in patients with primary nephrotic syndrome was generally within the approved dose range for lupus nephritis and transplant-related diseases in Japan.

ANGPTL3 impacts proteinuria and hyperlipidemia in primary nephrotic syndrome

BackgroundIt is unclear why primary nephrotic syndrome (PNS) patients often have dyslipidemia. Recent studies have shown that angiopoietin-like protein 3 (ANGPTL3) is an important regulator of lipid metabolism. In this study, we explored how ANGPTL3 impacts dyslipidemia during PNS development.MethodsWe measured the serum levels of ANGPTL3 in PNS patients (n=196). Furthermore, the degree of proteinuria and lipid metabolism were examined in angptl3-overexpressing transgenic (angptl3-tg) mice at different ages. Moreover, in this study, we used the clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR/Cas9) system to create angptl3-knockout (angptl3-/-) mice to investigate lipopolysaccharide (LPS)-induced nephrosis.ResultsCompared with that in the healthy group, the serum level of ANGPTL3 in the PNS group was significantly increased (32 (26.35-39.66) ng/ml vs. 70.44 (63.95-76.51) ng/ml, Z =-4.81, P < 0.001). There were significant correlations between the serum level of ANGPTL3 and the levels of cholesterol (r=0.34, P < 0.001), triglycerides (r= 0.25, P = 0.001) and low-density lipoprotein (r= 0.50, P < 0.001) in PNS patients. With increasing age, angptl3-tg mice exhibited increasingly severe hypertriglyceridemia and proteinuria. The pathological features of angptl3-tg mice included rich lipid droplet deposition in hepatocytes and diffuse podocyte effacement. Compared to wild-type mice, angptl3-/- mice showed significantly lower degrees of lipid dysfunction and proteinuria after stimulation with LPS. The effects of ANGPTL3 on nephrotic dyslipidemia were confirmed in cultured hepatocytes subjected to angptl3 knockdown or overexpression. Finally, significant alterations in lipoprotein lipase (LPL) levels were observed in liver tissues from Angptl3-/- and wild-type mice stimulated with LPS.ConclusionsANGPTL3 could be involved in the development of dyslipidemia, as well as proteinuria, during PNS pathogenesis. Inhibition of LPL expression may the mechanism by which ANGPTL3 induces hyperlipidemia in PNS.

Pneumocystis pneumonia in patients with primary nephrotic syndrome.

The aim of this study was to analyze the clinical features, risk factors, and outcomes of patients with primary nephrotic syndrome (PNS) who developed Pneumocystis pneumonia (PCP). We systematically reviewed medical records from 18 PNS patients with PCP admitted to our hospital from April 2007 to April 2019. A total of 180 cases were randomly selected as controls from PNS inpatients without infection. In PCP patients, the mean age at presentation was 48.5 years, mean duration of prednisone treatment was 3.7 months, and mean prednisone dose on admission was 31.3 mg/d. Eight patients (44.4%) had coexisting infections, most often was Cytomegalovirus (4 patients); 11 patients (61.1%) had ICU admission, and 9 patients (50%) had mechanical ventilation. PCP patients had more prednisone, more immunosuppressive therapy, lower CD4+ cell counts and hemoglobin, and higher serum creatinine than those without infections (p<0.05). All patients survived after treatment. PCP was not unusual in PNS patients, and the most important risk factors were prednisone usage, other immunosuppressive therapy, and a lower CD4+ cell count; however, these patients had a good outcome after sufficient treatment.

Acute kidney injury in patients with primary nephrotic syndrome: influencing factors and coping strategies

BackgroundAcute kidney injury (AKI) is a frequent and serious complication in patients with primary nephrotic syndrome (PNS). We aimed to evaluate the influencing factors of AKI in patients with PNS, to provide implications for the clinical management and nursing care of patients with PNS.MethodsPNS patients who were treated in the Department of Nephrology in our hospital from January 1, 2020 to July 31, 2021 were included. The clinical characteristics and pathological type of PNS patients were evaluated. Pearson correlation and Logistic regression analysis were performed to analyze the related risk factors of AKI in patients with PNS.ResultsA total of 328 patients with PNS were included, the incidence of AKI in PNS patients was 28.05%. Pearson correlation analysis showed that diabetes(r = 0.688), pulmonary infection (r = 0.614), albumin (r = 0.779), serum creatinine (r = 0.617), uric acid (r = 0.522), blood urea nitrogen (r = 0.616), renal tubular casts (r = 0.707) were correlated with AKI in PNS patients (all P < 0.05). Logistic regression analysis indicated that diabetes (OR2.908, 95%CI1.844 ~ 4.231), pulmonary infection(OR3.755, 95%CI2.831 ~ 4.987), albumin ≤ 24 g/L (OR1.923, 95%CI1.214 ~ 2.355), serum creatinine ≥ 90 μmol/L (OR2.517, 95%CI2.074 ~ 3.182), blood urea nitrogen ≥ 6.5 mmol/L (OR1.686, 95%CI1.208 ~ 2.123), uric acid ≥ 390 μmol/L (OR2.755, 95%CI2.131 ~ 3.371), renal tubular casts(OR1.796, 95%CI1.216 ~ 2.208) were the independently influencing factors of AKI in PNS patients (all P < 0.05).ConclusionsAKI is common in PNS patients. Actively controlling diabetes and pulmonary infection, strengthening nutrition support and renal function monitoring are essential to reduce the occurrence of AKI in PNS patients.

Oro-Dental Health and Primary Nephrotic Syndrome among Vietnamese Children.

Primary nephrotic syndrome (PNS) is common in children, affecting the soft and hard tissues of the oral cavity. This study aimed to investigate the percentage of dental caries, gingivitis, hypertrophic gingivitis, and developmental defects of enamel (DDE) in children with PNS. The association of PNS with these diseases and oral care behavior was also assessed. A total of 407 children with PNS and 407 age- and gender-matched controls were recruited. PNS was diagnosed based on blood and urinary tests. The Simplified Oral Hygiene Index (OHI-S), the Gingival Index (GI), the Gingival Overgrowth Index (GOI), the Decayed, Missing, and Filled Teeth Index (dmft/DMFT), and DDE were collected. The PNS patients showed significantly higher scores of OHI-S, GI, and dmft, and higher proportions of dental caries and DDE than those of the controls (p < 0.001). It is necessary to establish a periodic dental protocol for PNS patients to improve their oral health status.

Serum and urine ANGPTL8 expression levels are associated with hyperlipidemia and proteinuria in primary nephrotic syndrome

BackgroundThis study aimed to investigate the expression characteristics of ANGPTL8 in patients with primary nephrotic syndrome and its possible correlation with hyperlipidemia and proteinuria.MethodsANGPTL8 levels were determined using an enzyme-linked immunosorbent assay in 133 subjects with PNS and 60 healthy controls.ResultsCompared with healthy controls, subjects with primary nephrotic syndrome had higher levels of serum and urine ANGPTL8 (P < 0.001). In primary nephrotic syndrome patients, serum ANGPTL8 was positively correlated with cholesterol (r = 0.209, P < 0.05) and triglycerides (r = 0.412, P < 0.001), while there was no correlation with 24 hUTP. Urine ANGPTL8 was positively correlated with high-density lipoprotein cholesterol (r = 0.181, P < 0.05) and was significantly negatively correlated with creatinine (r = − 0.323, P < 0.001), eGFR (r = − 0, P < 0.001) and 24 hUTP (r = − 0.268, P = 0.002). Interestingly, the urine ANGPTL8 concentrations in membranous nephropathy and mesangial proliferative glomerulonephritis pathological types were different.ConclusionsSerum and urine ANGPTL8 levels in primary nephrotic syndrome patients were correlated with blood lipid levels and proteinuria, respectively, suggesting that ANGPTL8 may play a role in the development of primary nephrotic syndrome hyperlipidemia and proteinuria.

Ox-low density lipoprotein (ox-LDL) increased the susceptibility of primary nephrotic syndrome (PNS) by regulating the Treg/Th17 ratio via the MEG3 signaling

IntroductionPatients with primary nephrotic syndrome (PNS) were reported to exhibit the evident imbalance between the number of Th17 and Treg cells in their peripheral blood monocytes (PBMCs), which might be the immunological basis of the disease.Material and methods40 PNS patients and 42 healthy individuals were recruited in this study. FCM assay was used to observe the levels of Treg and Th17 cells.ResultsThe Treg/Th17 ratio was evidently decreased in PNS patients. The levels of MEG3 and RORγt were increased in the PNS group, while the levels of miR-17, miR-125a and FOXP3 mRNA were reduced in the PNS group. Moreover, the levels of IL-6 and IL-1β were highly increased in PNS patients. Ox-low density lipoprotein (ox-LDL) treatment significantly increased the levels of MEG3 and RORγt mRNA/protein while decreasing the levels of miR-17, miR-125a, and FOXP3 mRNA/protein in THP-1 cells, and the transfection of MEG3 siRNA partly alleviated the dysregulation in the expression of MEG3, relevant miRNAs and relevant mRNAs induced by ox-LDL. Also, the expression of miR-17 and miR-125a was evidently decreased upon the successful transfection of MEG3, but the RORγt mRNA/protein levels were promoted while the FOXP3 mRNA/protein levels were inhibited.ConclusionsOur results demonstrated that ox-LDL could promote the inflammatory response of PNS by decreasing the Treg/Th17 ratio via activating the MEG3 signaling. The activation of MEG3/miR-125a/FOXP3 axis and MEG3/miR-17/RORγt axis respectively lead to the Treg/Th17 imbalance, which resulted in up-regulated IL-6 and IL-1β levels, thus increasing the susceptibility of PNS.

SPD-1 and sPD-L1 Levels in Serum and Urine of Patients with Primary Nephrotic Syndrome and their Clinical Significance.

Primary nephrotic syndrome (PNS), a clinically prevalent glomerular disease, mostly results in a large loss of plasma albumin, and its predominant clinical manifestations are proteinuria, hypoalbuminemia, edema, and hyperlipidemia. Research has uncovered [9] that sPD-L1 and sPD-1 modulate the PD and PD-L1 pathway in the development of various autoimmune diseases. We randomly selected 80 PNS patients treated for PNS in our institution from October 2017 to October 2018 as the case group and 78 healthy volunteers examined in our hospital during the same period as the control group. Not only sPD-1 but also sPD-L1 level in serum and urine was assayed via ELISA. We compared the distribution of T lymphocyte subsets in peripheral blood and mALB and NAG levels in urine. Pearson's correlation analysis was adopted for assessing the relationship of serum and urine sPD-1, sPD-L1 with T lymphocyte subsets and mALB. (1) In contrast to the control group, the case group harbored higher pretreatment serum and urine sPD-1 and sPD-L1 contents (p < 0.05). (2) Before treatment, sPD-1 in the serum and urine held a positive relationship with sPD-L1 level (r was 0.683 and 0.235, respectively, p < 0.05); serum sPD-1 harbored a positive link with urine sPD-1 (r = 0.287, p < 0.01), whereas no relationship was discovered in serum sPD-L1 and urine sPD-L1. (3) In contrast to the control group, the CD4+ level in the case group abated, CD8+ increased, the CD4+/CD8+ ratio assuaged, and mALB level in urine increased (all p < 0.05), whereas NAG harbored no statistical difference (p > 0.05). (4) In the case group, the CD4+/CD8+ ratio possessed positive association with serum sPD-1 (r = 0.384, p < 0.001), and the mALB had a positive relationship with urine sPD-1 (r = 0.704, p < 0.001). (5) After treatment, in comparison with the remission group, the serum sPD-1 level of the non-remission group was increased (p < 0.05), whereas sPD-L1 value was not statistically different (p > 0.05); the sPD-1 level in urine was not statistically significant (p > 0.05), while sPD-L1 content was elevated (p < 0.05). Serum and urine sPD-1/sPD-L1 levels of PNS patients change dynamically. Detecting sPD-L1 and sPD-1 has certain clinical value for the prognosis of PNS.

Risk Factors of Acute Kidney Injury Complicating Adult Primary Nephrotic Syndrome

Objective To explore the risk factors of acute kidney injury(AKI)in adult primary nephrotic syndrome(PNS). Methods Totally 185 patients with PNS were divided into AKI group(n=51)and non-AKI group(n=134).The demographic data and clinical and histological features at admission were compared between the two groups.The independent risk factors for AKI were evaluated by Logistics regression analysis. Results In 51 PNS patients with AKI,the common pathological types of AKI included minor glomerular abnormalities(29.4%),IgA nephropathy(25.5%),and membranous nephropathy(17.6%).The incidences of renal tubular casts and epithelial vacuoles in the AKI group were significantly higher than those in the non-AKI group(P=0.004,P=0.030).Males were more likely to suffer from AKI than females(P=0.000).Patients in AKI group had significantly lower albumin level(P=0.015)and higher levels of random urine protein,serum creatinine,uric acid,urea nitrogen,and triglyceride than non-AKI group(P=0.030,P=0.000,P=0.000,P=0.000,and P=0.006),and polyserous and oliguria occurred more often in the AKI group(P=0.000,P=0.002).The AKI group had significantly higher incidences of high blood pressure and infections(P=0.035,P=0.000).Multivariate logistics regression analysis showed albumin(<25 g/L),serum creatinine(>96 μmol/L),urea nitrogen(≥6.8 mmol/L),uric acid(≥400 μmol/L),diabetes,infection,and renal tubular casts were the independent risk factors for AKI. Conclusions AKI complicating PNS is associated with a variety of factors.Its independent risk factors include the levles of albumin,serum creatinine,urea nitrogen,and uric acid,diabetes,infections,and renal tubular casts.

Evaluation of Concentration Errors and Inappropriate Dose Tailoring of Tacrolimus Caused by Sampling-Time Deviations in Pediatric Patients With Primary Nephrotic Syndrome.

Tacrolimus dosing is routinely tailored based on its trough level (C0) drawn by therapeutic drug monitoring in pediatric patients with primary nephrotic syndrome. However, this concentration is often inaccurate owing to inappropriate practice, such as deviation of sampling time (DST). The quantitative relationship between DST and C0 remains unclear. Tacrolimus concentration at nominal sampling times (12 hours after last dose) and 32 deviation scenarios (12 ± 4 hours every 15 minutes) was predicted using a previously validated population pharmacokinetic model based on 162 scenarios of 100 primary nephrotic syndrome patients involved in the population pharmacokinetic model and derived virtual patients. Concentration error (CE) and relative CE (RCE) were evaluated, and the correlation between DST and RCE was evaluated by subgroup analysis using linear regression. Ultimately, the inappropriate dosing possibly misled by incorrect C0 was simulated in a real-patient cohort according to the target range (5-10 ng/mL). Approximately 7% of RCE was caused at every 1-hour of DST. DST was the most major contributor of RCE (r = 0.773-0.804). Patients with early sampling, older age, high body weight, high dose, low aspartate transaminase level, high corticosteroid dose, and without combination of azole antifungal agents were revealed to have high RCE. Approximately 7%-36% and 9%-25% of inappropriate dose tailoring may be caused by early and delayed sampling, respectively. In addition, patients with early sampling or high-dose tacrolimus had a higher risk of inappropriate dosing than patients with delayed sampling [hazard ratio = 1.53, 95% confidence interval (CI): 1.03-2.27, P = 0.048], and low-dose tacrolimus (P < 0.0001). A moderate bias of concentration and dose tailoring was revealed within 4 hours of DST. In addition, a high risk of bias was found in patients with early sampling and high-dose tacrolimus.

Correlation between plasma proprotein convertase subtilisin/kexin type 9 and blood lipids in patients with newly diagnosed primary nephrotic syndrome

Background Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a major post-transcriptional regulator of low-density lipoprotein receptor degradation. Recently, PCSK9 was shown to be overexpressed by liver cells in rats with proteinuria. However, the levels of PCSK9 in newly diagnosed primary nephrotic syndrome (PNS) patients and correlations involving PCSK9 and blood lipids are not clearly understood. Methods One hundred and sixteen patients who were newly diagnosed with PNS were enrolled in this study. Results Plasma PCSK9 levels in PNS patients were significantly higher than those in healthy controls [310.86 (250.87, 390.25) ng/ml vs 255.67 (202.26, 320.26) ng/ml, p = 0.002]. Plasma PCSK9 in PNS patients was positively correlated with total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) (γ = 0.246, p = 0.008, and γ = 0.183, p = 0.049). When plasma PCSK9 was >267.60 ng/ml, the risk of developing hypercholesterolemia significantly increased in PNS patients (OR = 6.40, 95% CI 2.06–19.87, p = 0.001). When plasma PCSK9 was >255.05 ng/ml, the risk of developing higher levels of LDL-C significantly increased in PNS patients (OR = 3.83, 95%CI 1.25–11.68, p = 0.018). Conclusions Plasma PCSK9 levels in newly diagnosed PNS patients were markedly increased, and elevated PCSK9 abundance was positively correlated with elevated serum TC and LDL-C levels, suggesting that PCSK9 may emerge as a novel therapeutic target in NS-associated hypercholesterolemia.

Effects of Huaiqihuang Granules adjuvant therapy in children with primary nephrotic syndrome

ObjectiveThis study aims to observe the curative effect of Huaiqihuang Granules adjuvant therapy on primary nephrotic syndrome (PNS).MethodsA total of 112 children with PNS were randomly divided into three groups, and changes in serum inflammatory cytokines, interleukin, lymphocyte subsets and immunoglobulin were observed.ResultsBefore treatment, IL-18, TNF-α, CD8+ increased, while IL-10, CD4+, NK cells, IgA, IgG and Foxp3+Treg cells decreased. After Huaiqihuang Granules treatment, IL-18, TNF-α, CD8+ decreased, while IL-10, CD4+, NK cells, IgA, IgG and Foxp3+Treg cells increased.ConclusionFunctions of cell immunity and humoral immunity in PNS patients before treatment were suppressed and disordered. Huaiqihuang granules can play a role in immunoregulation, with slight side reactions.

Augmentation index, a predictor of cardiovascular events, is increased in children and adolescents with primary nephrotic syndrome.

Arterial stiffness is associated with an increased risk of cardiovascular diseases. Augmentation index (AIx@75), a measure of arterial stiffness and wave reflection, has not been evaluated in patients with primary nephrotic syndrome (PNS). We investigated whether central and peripheral vascular profiles, hemodynamic parameters, and biochemical tests are associated with AIx@75 in PNS patients. This observational study involved 38 children and adolescents with PNS (12.14 ± 3.65years) and 37 healthy controls (13.28 ± 2.80years). Arterial stiffness and vascular and hemodynamic parameters were measured noninvasively using the Mobil-O-Graph® (IEM, Stolberg, Germany). In the PNS group, biochemical tests and corticosteroid dosage/treatment time were analyzed. Peripheral and central systolic blood pressure (SBPp, SBPc) Z-scores were significantly higher in the PNS patients. AIx@75 was significantly higher in the PNS patients (25.14 ± 9.93%) than in controls (20.84 ± 7.18%). In the control group, AIx@75 negatively correlated with weight (r = - 0.369; p = 0.025), height (r = - 0.370; p = 0.024), and systolic volume/body surface (r = - 0.448; p = 0.006). In the PNS group, a univariate linear correlation showed that AIx@75 negatively correlated with weight (r = - 0.360; p = 0.027), height (r = 0.381; p = 0.18), and systolic volume/body surface (r = - 0.447; p < 0.002) and positively with the Z-score of SBPp (r = 0.407; p = 0.011), peripheral diastolic blood pressure (DBPp, r = 0.452; p = 0.004), SBPc (r = 0.416; p = 0.009), DBPc (r = 0.407; p = 0.011), triglycerides (r = 0.525; p = 0.001), and cholesterol [total (r = 0.539; p < 0.001), LDLc (r = 0.420; p = 0.010), and non-HDLc (r = 0.511; p = 0.001)]. Early abnormalities of AIx@75 and vascular parameters suggest that patients with PNS, even in stable condition, present subclinical indicators for the development of cardiovascular disease.

Identification of a Novel ACTN4 Gene Mutation Which Is Resistant to Primary Nephrotic Syndrome Therapy.

ACTN4, a gene which codes for the protein α-actinin-4, is critical for the maintenance of the renal filtration barrier. It is well known that ACTN4 mutations can lead to kidney dysfunction, such as familial focal segmental glomerulosclerosis (FSGS), a common cause of primary nephrotic syndrome (PNS). To elucidate whether other mutations of ACTN4 exist in PNS patients, we sequenced the ACTN4 gene in biopsies collected from 155 young PNS patients (≤16 years old). The patients were classified into five groups: FSGS, minimal change nephropathy, IgA nephropathy, membranous nephropathy, and those without renal puncture. Ninety-eight healthy people served as controls. Samples were subjected to Illumina's next generation sequencing protocols using FastTarget target gene capture method. We identified 5 ACTN4 mutations which occurred only in PNS patients: c.1516G > A (p.G506S) on exon 13 identified in two PNS patients, one with minimal change nephropathy and another without renal puncture; c.1442 + 10G > A at the splice site in a minimal change nephropathy patient; c.2191-4G > A at the cleavage site, identified from two FSGS patients; and c.1649A > G (p.D550G) on exon 14 together with c.2191-4G > A at the cleavage sites, identified from two FSGS patients. Among these, c.1649A > G (p.D550G) is a novel ACTN4 mutation. Patients bearing the last two mutations exhibited resistance to clinical therapies.

Research and progress of cytokines in pathogenesis of primary nephrotic syndrome

Primary nephrotic syndrome(PNS)is a common renal disease in children and the pathogenesis has not been clarified, but it is considered to be related to cellular immune dysfunction.We collected the reported cytokines associated with PNS and reviewed the resources and the involving pathogenesis of the cytokines.We hope to help to clarify the possible pathogenesis of PNS and to develop new treatments for PNS patients. Key words: Primary nephrotic syndrome; Cytokine; T-lymphocyte; Interleukin