Urinary Protein Levels Research Articles

Genetic Loci of the Renin-Angiotensin System and IgA Nephropathy.

Background: IgA nephropathy (IgAN) is the most common primary glomerular disease. The renin-angiotensin system (RAS) plays an important role in the development of IgAN. Polymorphisms in genetic loci coding for the RAS may be associated with IgAN progression. Methods: We analyzed the M235T, A1166C, and A1675G polymorphisms in 297 IgAN patients, and analyzed their associations with clinical manifestations, pathological damage, effects of RAS-inhibitor treatment, and IgAN patient prognosis. Results: In patients with the A1675G polymorphism, creatinine levels were significantly lower in those with the AG genotype than in those with the AA genotype (p = 0.023). However, this difference was not significant when creatinine levels were analyzed according to sex. Patients with endocapillary proliferation according to the Oxford Classification of IgAN were less likely to have the AG genotype than the AA genotype (p = 0.025). In IgAN patients treated with angiotensin-II-receptor blockers, 24-h urine protein levels were lower in patients with the AC genotype of A1166C than in those with the AA genotype at baseline and follow-up (Base p = 0.013, 1 month p = 0.0035, 3 months p = 0.009). Cox regression analysis implied that the three gene polymorphisms were not independent risk factors for the prognosis of IgAN. Conclusion: The AG genotype of A1675G may confer protection against the development of IgAN, with a stronger protective effect observed in females. M235T, A1166C, and A1675G do not appear to be independent risk factors for IgAN.

A single-center retrospective study of ectopic lymphoid tissues in idiopathic membranous nephropathy: clinical pathological characteristics and prognostic value

Background In recent years, ectopic lymphoid tissue (ELT) has been increasingly confirmed as a new biomarker for kidney injury or inflammation. However, there is insufficient research on the relationship between ELT grading and the progression of idiopathic membranous nephropathy (IMN). Methods A total of 147 patients with biopsy-proven IMN in our institution from March 2020 to June 2022 were classified into five grades based on the different distribution of lymphocyte subsets in renal tissue (G0: no B cells or T cells, G1: scattered B and T cells, G2: clustered B and T cells, G3: an aggregation region of B and T cells without a central network, G4: highly organized and formed zones of B and T cells with a central network of follicular dendritic cells and scattered macrophages), and were further divided into low-grade group (G0+G1), intermediate-grade group (G2) and high-grade group (G3+G4). The clinicopathological data, induction treatment response and prognosis among the three groups were analyzed and compared retrospectively. Results As the grading of ectopic lymphoid tissues increased, patients were older, with a higher prevalence of hypertension, a higher 24-h urinary protein level, lower baseline hemoglobin and estimated glomerular filtration rate (eGFR) levels, and more severe renal pathological damage. Logistic regression analysis showed that after 6 months of induction treatment, patients in the high-grade group were more likely to be in non-remission than those in the low-grade group (odds ratios [ORs] of the three adjusted models were 4.310, 4.239, and 5.088, respectively, P-values were 0.005, 0.006, and 0.001, respectively). Kaplan-Meier survival analysis indicated that patients in the intermediate- and high-grade groups had significantly lower renal cumulative survival rate than those in the low-grade group (P = 0.025). Univariate Cox analysis showed that the risk of adverse renal outcome was 3.662 times higher in the intermediate- and high-grade groups than in the low-grade group (95% confidence interval [CI] [1.078–12.435]; P = 0.037). Multivariate Cox analysis revealed that failure of remission at the first 6 months (hazard ratio [HR] = 5.769; 95% CI [1.854–17.950]; P = 0.002) remained an independent risk factor for poor renal outcome in patients with IMN. Conclusions Grading of renal ectopic lymphoid tissues correlates with disease activity and severity in IMN patients and can be used as an indicator to assess the risk of IMN progression.

A multicenter retrospective study on comparing the efficacy and safety of the therapy of intermittent cyclophosphamide and corticosteroids versus rituximab for primary membranous nephropathy.

Few clinical studies compare the long-term remission, relapse, and safety of rituximab (RTX) or a combination of intermittent intravenous infusion of cyclophosphamide (CTX) and oral corticosteroid for primary membranous nephropathy (PMN) patients. We collected multicenter retrospective data on PMN patients with nephrotic syndrome who received RTX or intermittent intravenous CTX with oral corticosteroids between 1 January 2019 and 31 January 2024. Patients were followed up until two years after receiving immunotherapy. The primary outcomes were a composite of complete or partial remission rates at 6, 12, and 24months. The secondary outcomes were the relapse and safety evaluation. Forty patients treated with RTX and 27 with the CTX regime were available for analysis. No significant difference in the remission rate at 6, 12, or 24months was observed between the two groups (p>.05). Kaplan-Meier's survival analysis showed that the relapse-free cumulative survival rate of the RTX group was superior to that of the CTX group (p=.023). Compared with baseline, both the media of urine protein and serum albumin levels in the two groups showed a significant improvement at 6months and maintained through to the second year. No significant difference in the occurrence of total side effects between the two groups (p=.160). There was no difference in remission rates and safety between RTX versus intermittent intravenous CTX combined with oral corticosteroid treatment for patients with PMN within 2years. RTX appeared to have benefits in terms of prolonging relapse-free survival.

Shen-Qi-Di-Huang Decoction induces autophagy in podocytes to ameliorate membranous nephropathy by suppressing USP14.

Shen-Qi-Di-Huang decoction (SQDHD) is a renowned decoction in traditional Chinese medicine, dating back to the Qing Dynasty. SQDHD has been widely applied in treating renal diseases, including Membranous nephropathy (MN), with its proven positive clinical outcomes. Nevertheless, the precise mechanism by which SQDHD exerts its therapeutic effects on MN remains uncertain. The present research aimed to observe whether SQDHD promotes podocyte autophagy by inhibiting USP14 to increase the K63 ubiquitination of Beclin1, thereby improving MN. An MN model was established in rats using Passive Heyman Nephritis (PHN) to explore the underlying mechanisms in vivo. The kidney function parameters were evaluated, and the histomorphology of glomerular tissues was examined. Autophagy-related protein expression was assessed using immunofluorescence staining and western blotting assays. Co-immunoprecipitation (Co-IP) was used to detect the K63 ubiquitination of Beclin1. MPC5 cells were treated in vitro with serum obtained from several rat groups. Subsequently, the expression of autophagy-related proteins, formation of autophagosomes, expression of USP14, and K63 ubiquitination of Beclin1 were quantified. Our results demonstrated that SQDHD intervention reduced urinary protein levels, mitigated podocyte damage in MN model rats, and improved kidney tissue pathology. Furthermore, in vitro and in vivo data revealed that SQDHD therapy significantly increased podocyte autophagy, decreased USP14 expression, and raised Beclin1's K63 ubiquitination. These results provided a scientific rationale supporting the ability of SQDHD to substantially alleviate MN progression by inducing podocyte autophagy through the inhibition of USP14 expression.

Enhancing Renal Autophagy via Yangshen Paidu Decoction: AMPK/mTOR Pathway Modulation in Chronic Renal Failure Management

Objective: Chronic Renal Failure (CRF) refers to the gradual decline in renal function caused by various chronic kidney diseases, eventually leading to end-stage renal failure. Yangshen Paidu Decoction (YPD) is a Traditional Chinese medicine (TCM) formula utilized in CRF treatment. This work has analyzed the effects of YPD on CRF and the specific mechanism. Methods: Network pharmacology was performed to screen effective components and targets of YPD, from which key targets and signaling pathways contributing the most to the treatment effects on CRF were determined. Subsequently, we validated the therapeutic role of YPD and the underlying pathological mechanisms using the 5/6-nephrectomy rat model. Results: Network pharmacology analysis showed the mTOR pathway to be a pivotal mechanism underlying the effectiveness of YPD in CRF treatment. YPD significantly suppressed urine protein levels, blood urea nitrogen, and serum creatinine in 5/6 nephrectomized rats. Furthermore, YPD remarkably improved renal pathological injuries. Western blot analysis revealed that YPD enhanced autophagy and upregulated the expression of nephrin, podocin, beclin1, p-AMPK/AMPK, and p- ULK1/ULK1, and attenuated the ratios of p-mTOR/mTOR to its downstream protein phosphorylated eIF4E-binding protein (p-4EBP1). However, these effects were notably reversed by the AMPK inhibitor compound C. Conclusion: Our findings have demonstrated YPD to suppress the mTOR pathway and stimulate autophagy by modulating AMPK pathways, thereby mitigating podocyte injury and enhancing renal function. Our study has confirmed autophagy and the AMPK/mTOR pathway as potential targets for YPD in CRF treatment.

Loss of the Endothelial Glycocalyx Component EMCN Leads to Glomerular Impairment.

EMCN (endomucin), an endothelial-specific glycocalyx component, was found to be highly expressed by the endothelium of the renal glomerulus. We reported an anti-inflammatory role of EMCN and its involvement in the regulation of VEGF (vascular endothelial growth factor) activity through modulating VEGFR2 (VEGF receptor 2) endocytosis. The goal of this study is to investigate the phenotypic and functional effects of EMCN deficiency using the first global EMCN knockout mouse model. Global EMCN knockout mice were generated by crossing EMCN-floxed mice with ROSA26-Cre mice. Flow cytometry was used to analyze infiltrating myeloid cells in the kidneys. The ultrastructure of the glomerular filtration barrier was examined by transmission electron microscopy, whereas urinary albumin, creatinine, and total protein levels were analyzed from freshly collected urine samples. Expression and localization of EMCN, EGFP, CD45, CD31, CD34, podocin, and albumin were examined by immunohistochemistry. Mice were weighed regularly, and their systemic blood pressure was measured using a noninvasive tail-cuff system. Glomerular endothelial cells and podocytes were isolated by fluorescence-activated cell sorting for RNA sequencing. Transcriptional profiles were analyzed to identify differentially expressed genes in both endothelium and podocytes, followed by gene ontology analysis. Protein levels of EMCN, albumin, and podocin were quantified by Western blot. The EMCN-/- mice exhibited increased infiltration of CD45+ cells, with an increased proportion of Ly6GhighLy6Chigh myeloid cells and higher VCAM-1 (vascular cell adhesion molecule 1) expression. EMCN-/- mice displayed albuminuria with increased albumin in the Bowman's space compared with the EMCN+/+ littermates. Glomeruli in EMCN-/- mice revealed fused and effaced podocyte foot processes and disorganized endothelial fenestrations. We found no significant difference in blood pressure between EMCN knockout mice and their wild-type littermates. RNA sequencing of glomerular endothelial cells revealed downregulation of cell-cell adhesion and MAPK (mitogen-activated protein kinase)/ERK (extracellular signal-regulated kinase) pathways, along with glycocalyx and extracellular matrix remodeling. In podocytes, we observed reduced VEGF signaling and alterations in cytoskeletal organization. Notably, there was a significant decrease in both mRNA and protein levels of podocin, a key component of the slit diaphragm. Our study demonstrates a critical role of the endothelial marker EMCN in supporting normal glomerular filtration barrier structure and function by maintaining glomerular endothelial tight junction and homeostasis and podocyte function through endothelial-podocyte crosstalk.

Correlation analysis of AVPR1a and AVPR2 with abnormal water and sodium and potassium metabolism in rats.

In clinical practice, an increasing number of patients exhibit concurrent cardiac and renal dysfunction, known as "cardiorenal syndrome," where each condition exacerbates the other, resulting in poorer patient prognosis. Fluid and sodium retention can lead to excessive fluid overload in the body; therefore, correcting fluid and sodium metabolic disorders is crucial for alleviating patient symptoms. This study was to investigate the abnormalities in water and sodium metabolism, as well as the expression levels of arginine vasopressin receptor 1a (AVPR1a) and arginine vasopressin receptor 2 (AVPR2), in a rat model of chronic renal failure-chronic heart failure (CRF-CHF). One hundred male Sprague-Dawley rats were randomly assigned into four groups: the CG group (normal feeding), the CRF group (3/4 nephrectomy using a "two-step surgical method"), the CHF group (subcutaneous injection of isoproterenol at 100 mg/kg), and the CRF-CHF group (3/4 nephrectomy followed by a subcutaneous injection of isoproterenol at 100 mg/kg 1 week later). 4 weeks post-surgery, urine and blood samples were collected to measure 24 h urinary protein, sodium, and potassium levels. Serum creatinine (SCr) and blood urea nitrogen (BUN) levels were determined using assay kits. Left ventricular end diastolic pressure (LVEDP) and left ventricular systolic pressure (LVSP) were measured via left ventricular catheterization. The heart was weighed to calculate the left ventricular weight to body weight ratio (LVW/BW). The renal cortex and medulla were isolated to assess the relative mRNA and protein expression levels of AVPR1a and AVPR2. Compared to the CG group, the CRF and CRF-CHF groups exhibited significantly elevated levels of 24 h urinary protein, SCr, BUN, and relative expression levels of AVPR1a and AVPR2 in the renal cortex and medulla. The CHF and CRF-CHF groups showed significant increases in LVEDP and LVW/BW (P < 0.05). Additionally, compared to the CG group, the other three groups had significantly increased urinary sodium and blood potassium levels, and significantly decreased urinary potassium and blood sodium levels (P < 0.05). Compared to the CRF and CHF groups, the CRF-CHF group exhibited significantly higher levels of 24 h urinary protein, SCr, BUN, and relative expression levels of AVPR1a and AVPR2 in the renal cortex and medulla, along with significantly increased LVEDP and LVW/BW, significantly reduced LVSP, significantly increased urinary sodium and blood potassium levels, and significantly decreased urinary potassium and blood sodium levels (P < 0.05). Rats with CRF-CHF experienced exacerbated renal and cardiac failure, characterized by significant disturbances in water and sodium metabolism and abnormal expression of AVPR1a and AVPR2.

Longitudinal analysis of urinary I-FABP in extremely preterm infants that develop necrotizing enterocolitis.

Intestinal fatty acid binding protein (I-FABP) is an intestinal epithelial protein detectable in infants with necrotizing enterocolitis (NEC). The longitudinal behavior of I-FABP following NEC or its association with gastrointestinal or neurodevelopmental outcomes is unknown. In this secondary analysis of the Preterm Erythropoietin Neuroprotection Trial, we compared infants with and without NEC. Urine I-FABP concentrations in matched infants (n = 70) were measured serially using ELISA and compared using paired analysis. In infants with NEC, the associations of I-FABP levels with short-term outcomes and neurodevelopmental outcomes at 22-26 months corrected age were determined using non-parametric analysis. Infants with NEC were more likely to have cholestasis, death or severe neurodevelopmental impairment, cerebral palsy, and lower Bayley-III motor scores. Baseline urinary I-FABP levels were similar between groups. When compared to controls, infants with NEC had urinary I-FABP concentrations that were higher at diagnosis (median 11 vs 2.6 ng/ml, p = 0.006) and lower post-NEC (median 1 vs 5 ng/ml, p = 0.002). Diagnosis I-FABP levels were not associated with gastrointestinal or neurodevelopmental outcomes at 22-26 months corrected age. In extremely preterm infants, urinary I-FABP was elevated at NEC diagnosis and lower post-NEC compared to matched controls. I-FABP levels were not associated with adverse gastrointestinal or neurodevelopmental outcomes. Urinary intestinal fatty acid binding protein (I-FABP) levels are increased at diagnosis of NEC and fall to below baseline after NEC in extremely preterm infants. Urine I-FABP levels at NEC diagnosis are not associated with cholestasis, intestinal stricture or obstruction, need for additional intestinal surgery after NEC, or neurodevelopmental outcomes at 22-26 months corrected age. Urine I-FABP levels may be useful in the diagnosis of NEC. Diagnostic I-FABP levels do not predict short-term gastrointestinal or neurodevelopmental outcomes after NEC.

The promotive effect of Caspase-11 overexpression in a rat model of chronic kidney disease and the therapeutic efficacy of exosome-delivered siRNA in inhibiting Caspase-11

This study investigates the role of Caspase-11 in Chronic Kidney Disease (CKD) and examines the therapeutic potential of inhibiting Caspase-11 using exosome-mediated siRNA. We established a CKD rat model and analyzed the expression of Caspase-11 through immunohistochemistry. The study involved overexpressing Caspase-11 using an adeno-associated virus (AAV) and constructing exosomes loaded with siRNA targeting Caspase-11 (exo-si-Caspase-11). Renal tissue damage and fibrosis were assessed using H&E staining, Masson's trichrome, TUNEL assay, and Sirius Red staining. Additionally, urinary protein and blood urea nitrogen (BUN) levels were measured, alongside analyses of serum calcium and phosphorus levels. H&E staining was performed to evaluate the effects of exo-si-Caspase-11 on damage to the heart, liver, spleen, and lungs. The results showed that the CKD model group experienced significant weight loss, increased blood pressure, and elevated Caspase-11 expression. AAV-mediated Caspase-11 overexpression led to substantial renal fibrosis, increased apoptosis, and elevated urinary protein and BUN levels. Additionally, the group with Caspase-11 overexpression exhibited elevated serum calcium and phosphorus levels. Conversely, treatment with exo-si-Caspase-11 reduced these pathological changes in renal tissue without causing damage to other major organs. These findings suggest that exosome-mediated siRNA delivery targeting Caspase-11 is an effective therapeutic strategy for CKD.

Evaluation of Proteinuria in Diabetic Patients Attending Gitwe District Hospital

Background: Proteinuria is a serious condition in which body proteins leak into urine due to kidney dysfunction nearly always caused by elevated serum glucose due to prolonged diabetes. Proteinuria occurs and affects individuals with diabetes, approximately 25% of diabetic patients may have proteinuria. Aim: The aim of this study is to assess the levels of serum glucose and proteins in urine and their association in diabetic patients attending Gitwe District Hospital. Methodology: The study population mainly comprised of diabetic patients, 110 study participants were included. Blood was drawn from finger for testing serum glucose using glucometer and urine samples were collected from diabetic patients and samples were analyzed in parasitology service using urine chemistry strips for proteins in urine testing. Results: During data analysis, SPSS version 22 was used, the majority were female with 66.4% while 33.6% were male. The highest frequency of participants presented in this study were 27(24.6%) found in [43-52] years old. The mean age was 53 years ± 13.882 SD (ranged from 23 to 86 years). 53.7% had normal serum glucose level while 46.3% had high serum glucose level. However, 63.6% had no proteinuria while 20.0% had trace, 11.8% had mild and 4.6% had moderate proteinuria levels. Association between serum glucose and proteinuria was analyzed for statistical significance with Chi-square test and it was statistically significant as their p values were below 0.05(P-value of 0.000). Conclusion: The study found that high serum glucose level leads to the presence of proteins in the urine. This study recommends regular monitoring of serum glucose levels, as well as routine urine tests to detect proteinuria as essential components of diabetes management and other researchers to study the effects of proteinuria in diabetic patients. Keywords: Proteinuria, serum glucose, proteins, diabetic patients

A machine learning model for predicting worsening renal function using one-year time series data in patients with type 2 diabetes.

To prevent end-stage renal disease caused by diabetic kidney disease, we created a predictive model for high-risk patients using machine learning. The reference point was the time at which each patient's estimated glomerular filtration rate (eGFR) first fell below 60 mL/min/1.73 m2. The input period spanned the reference point to 1 year prior. The primary endpoint was a 50% decrease in eGFR from the mean of the input period over the 3 year evaluation period. We created predictive models for patients' primary endpoints using time series data of various variables over the input period. Among 2,533 total patients, 1,409 had reference points, 31 had records for their input and evaluation periods and had reached their primary endpoints, and 317 patients had not. The area under the curve (AUC) of the predictive model peaked (0.81) when the minimum eGFR, the difference between maximum and minimum eGFR, and both maximum and minimum urinary protein values were included in the features. The accuracy of prognosis prediction can be improved by considering the variable components of urinary protein and eGFR levels. This model will allow us to identify patients whose renal functions are relatively preserved with eGFR of more than 60 mL/min/1.73 m2 and are likely to benefit clinically from immediate treatment intensification.

Chronic kidney disease and its associated factors in HIV-infected individuals: a comparison of antiretroviral therapy naïve and experienced patients.

Chronic kidney disease (CKD) has emerged as one of the primary comorbidity affecting individuals infected with human immunodeficiency virus (HIV), even after the initiation of highly active antiretroviral therapy (HAART). The main objective of this study was to assess the prevalence of CKD and its associated factors among HIV-infected individuals who are HAART naïve compared to those who are HAART experienced. An institution-based cross-sectional study was conducted at Mizan Tepi University Comprehensive Specialized Hospital from March to May 2022. A double population proportion formula was used to select 250 study participants, with 125 being HAART naïve and 125 being HAART experienced. Socio-demographic and clinical data were collected using a semi-structured questionnaire. Serum creatinine levels were measured using a Mindray BS-200 chemistry analyzer, and the estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease (MDRD) equation. The level of urine protein was measured using a reagent strip within 30 min of collection. Descriptive statistics, independent t-tests, and multivariable logistic regression analysis were performed, with a p-value of <0.05 considered statistically significant. The mean (±SD) age of the HAART-naïve individuals was 35 ± 9.5, while that of the HAART-experienced individuals was 45 ± 9.9 years. Of the total participants, 67.2% participants were women. The overall prevalence of CKD among the HIV-infected study participants was 36.4%. The prevalence of CKD was 33.6% in HAART-naïve individuals and 39.2% in HAART-experienced individuals, with a p-value of 0.03. Male sex was identified as an independent factor associated with CKD in this study. The prevalence of CKD was found to be higher among HAART-experienced individuals than HAART-naïve individuals. Regular renal function assessments should be conducted before and during HAART to mitigate the risk of renal dysfunction.

Association of Urinary Epidermal Growth Factor, Fatty Acid-Binding Protein 3, and Vascular Cell Adhesion Molecule 1 Levels with the Progression of Early Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is a common cause of chronic kidney disease with around 25-40% of patients with diabetes being affected. The course of DKD is variable, and estimated glomerular filtration rate (eGFR) and albuminuria, the currently used clinical markers, are not able to accurately predict the individual disease trajectory, in particular in early stages of the disease. The aim of this study was to assess the association of urine levels of selected protein biomarkers with the progression of DKD at an early stage of disease. We measured 22 protein biomarkers using the Mesoscale Discovery platform in 461 urine samples of the PROVALID cohort, an observational study of patients with type 2 diabetes mellitus followed at the primary health care level for a minimum of 4 years. Odds ratios (ORs) were estimated for the effect of marker values above median on fast progression using unadjusted and adjusted logistic regression models. RNA expression at the single-cell level in kidney biopsy samples obtained from a cohort of young persons with type 2 diabetes mellitus was in addition determined for markers showing significant associations with disease progression. Increased urinary levels of epidermal growth factor (EGF) were linked to lower odds of fast progression (defined as annual eGFR decline greater than 2.58 mL/min per 1.73 m2) with an OR of 0.60 (95% CI: 0.46, 0.78). The association with outcome was even stronger when adjusting for a set of 14 baseline clinical parameters including age, biological sex, eGFR, body mass index, albuminuria, and HbA1c. Elevated urinary levels of fatty acid-binding protein 3 (FABP3) and vascular cell adhesion molecule 1 (VCAM1) were each significantly associated with fast progression with an OR of 1.44 (95% CI: 1.11, 1.87) and an OR of 1.41 (95% CI: 1.08, 1.83), respectively. Enriched expression of EGF and FABP3 was observed in distal convoluted tubular cells and VCAM1 in parietal epithelial cells at single-cell level from biopsies of patients with early DKD. In summary, we show that lower urinary levels of EGF and higher urinary levels of FABP3 and VCAM1 are significantly associated with DKD progression in early-stage disease.

Renal involvement in TAFRO syndrome: a review.

Renal involvement in TAFRO syndrome is characterized clinically by general edema with ascites and pleural effusions and a rapidly progressive decline in renal function, with urinary protein levels of usually less than 1g/day. The histologic features of the kidneys can be described as glomerular microangiopathy characterized by mesangiolysis or mesangial loosening, endothelial cell proliferation, edematous opening in the subendothelial space, and glomerular basement membrane (GBM) doubling due to newly formed basement membrane. Findings such as rupture of the GBM, foot-process effacement or fusion, and epithelial cell loss are rare, and thrombus formation is difficult to identify in the glomerulus. Furthermore, immunodeposits are not seen on immunofluorescence staining or electron microscopy. Unlike adults, in addition to the glomerular lesions described above, adolescents appear to show intimal proliferation of the arterioles and interlobular arteries to the vascular poles and occlusion of the vascular lumen.

Panax notoginseng saponins improves lipid metabolism and prevents atherosclerosis in mice with steroid-resistant lupus nephritis via the SIRT1/PPARγ signaling pathway

Steroids serve as the primary medication for treating lupus nephritis (LN), however, steroid-resistance (SR) occurs sporadically in clinical practice, significantly affecting the therapeutic effect and long-term prognosis of patients. Our previous study found that panax notoginseng saponins (PNS) could partially reverse SR in LN. To further explore the role of PNS in reversing SR and reducing cardiovascular complications in LN, we conducted this study. Lupus mice were induced into SR while simultaneously receiving PNS. SIRT1-siRNA, SIRT1-siRNA NC, normal and lupus mice were used as control groups. Urine protein levels were measured at week 0, 4 and 8. Lipid metabolism-related biomarkers and renal function were assessed. The apoptosis rate of abdominal aortic endothelial cells was detected using flow-cytometry. The expression levels of PPARγ and SIRT1 were measured using RT-PCR and Western Blotting. Immunohistochemistry was performed to examine ACAT1 and VCAM-1 expressions. The results showed that compared to the SR lupus mice, the lupus mice treated with low/high dose PNS presented lower levels of urinary protein, serum creatinine, and blood lipids, a lower apoptosis rate of abdominal aortic endothelial cells, and decreased levels of ACAT1 and VCAM-1 PI in liver tissue, while the high-dose PNS exhibited more evidently. The PPARγ expression in SIRT1-siRNA group, as well as in low-dose and high-dose PNS groups was higher than that in the lupus and SR lupus group. In contrast, the expression of SIRT1 showed the opposite trend. Therefore, we conclude that PNS has the efficacy of reversing SR and ameliorating dyslipidemia in LN by modulating the SIRT1/PPARγ signaling pathway.

Selective peroxisome proliferator-activated receptor-α modulator improves hypertriglyceridemia and muscle quality in patients with chronic kidney disease: A retrospective observational study

Background & AimsPatients with chronic kidney disease (CKD) often have additional health problems, including sarcopenia and sarcopenic obesity. These conditions involve ectopic fat accumulation within muscles. This ectopic fat deposition reduces muscle quality, leading to weaker muscle strength and poorer physical performance. Persistent hypertriglyceridemia contributes to ectopic fat accumulation. Metabolic abnormalities, including dyslipidemia, are major factors in CKD development. Triglycerides (TG) and muscle quality are thus important factors in CKD management. Recently developed selective peroxisome proliferator-activated receptor α modulator (SPPARMα) hold promises for improving hypertriglyceridemia. However, their effectiveness and impact on muscle quality in CKD patients remain unclear. This study aimed to evaluate the effect of SPPARMα on muscle quality and its efficacy in CKD patients. MethodsThis retrospective observational study involved CKD patients with dyslipidemia. We included patients who initiated medications for hypertriglyceridemia. We compared changes in lipid profiles, renal function, and muscle quality, assessed by phase angle, over six months between two groups: those receiving this type of medication and those receiving conventional treatment. ResultsAmong 245 patients diagnosed with CKD and hypertriglyceridemia, 52 started medications for hypertriglyceridemia. Of these, 26 received SPPARMα, and 26 received conventional lipid-lowering medications (statins, ezetimibe, eicosapentaenoic acid, and fibrates). SPPARMα significantly reduced TG (from 296.8 ± 106.1 to 153.0 ± 86.1, p <0.001) without affecting glomerular filtration rate or urinary protein levels. Conventional treatment also improved TG (from 261.6 ± 89.5 to 173.6 ± 81.3, p <0.001). Only patients treated with SPPARMα showed significant improvement in muscle quality. Their phase angle increased from 5.41 ± 0.6 to 5.55 ± 0.6 after six months of treatment (p <0.05). ConclusionsOur study demonstrates that the newly developed SPPARMα significantly lowers TG levels in CKD patients without harming their kidneys. Additionally, only patients treated with SPPARMα showed improvement in muscle quality. These findings suggest that SPPARMα may be a valuable treatment option for CKD patients with dyslipidemia, particularly those with low muscle quality.

Phenotypes of patients with lupus-associated pulmonary hypertension in the Chinese Han population: a cluster analysis.

Pulmonary hypertension (PH) is a severe complication of systemic lupus erythematosus (SLE). This study investigated the clinical features of patients with SLE-PH in China based on disease manifestations and organ involvement to define precise treatment of SLE and early prevention of complications. In total, 205 SLE-PH patients were included in this study. A cluster analysis was applied according to six clinical and serological variables to define different subgroups of patients. The survival rates of SLE-PH patients and risk factors that influenced prognosis were also compared and a clinical prediction model was developed for the diagnosis of associated lupus nephritis (LN). Patients were clustered in five groups. Patients in cluster 1 had severe renal damage (all patients had LN and had the highest creatinine and urea nitrogen and the lowest eGFR levels). Patients in cluster 2 had mild renal damage (more than half of the patients had associated LN and 87.5% had increased urinary protein levels but presented a lower degree of renal damage than those in the first group. Patients in cluster 3 had low-grade proteinuria (all patients had 24h urinary protein < 0.5g). Patients in cluster 4 had hematuria or urinary tubular damage (26% of patients had associated LN, but none of the patients had proteinuria. In cluster 5, patients barely had any major organ involvement. The clinical prediction model for a diagnosis of SLE-PH-LN was anti-dsDNA antibodies > 364.64IU/mL and neutrophil-to-leukocyte ratio (NLR) > 5.55. Our findings provide evidence indicating that SLE-PH presents varying clinical phenotypes and the treatment varies accordingly, suggesting the need for individualized treatment. Key Points • Clustered grouping of patients with SLE-PH is associated with renal injury. • This may be because PH and LN share a common pathogenesis. • The clinical prediction model for a diagnosis of SLE-PH-LN was anti-dsDNA antibodies >364.64 IU/mL and NLR >5.55.

SBP1 contributes to mesangial proliferation and inflammation through mitochondrial respiration in glomerulus during IgA nephropathy

Mesangial expansion and proliferation have been implicated in the pathogenesis of IgA nephropathy (IgAN). Mesangial cells in glomerulus are important contributors to commencement of IgAN. From minimal mesangial expansion to diffuse proliferation, the mesangial alteration is linked to clinical and pathological features of IgAN. Although selenium-binding protein 1 (SBP1) is associated with tissue injury, the roles of SBP1 in mesangial proliferation and inflammation in glomerulus during IgAN remains unclear. In the present study, we found that SBP1 gene levels were elevated in kidney tissues of patients with IgAN. Also, SBP1 protein levels were elevated in proliferative mesangial cells of glomerulus in kidney tissues from patients with IgAN. Urinary SBP1 protein levels were elevated in patients with IgAN. Elevated urinary SBP1 levels were positively correlated with segmental glomerulosclerosis of the Oxford classification related to mesangial proliferation in patients with IgAN. Over-expression of SBP1 induced cellular proliferation via mitochondrial respiration in human renal mesangial cells. Consistently, SBP1 knockdown and mitochondrial respiration inhibition suppressed cellular proliferation and induced mitochondrial oxidative stress in human renal mesangial cells. Furthermore, SBP1 induced pro-inflammatory phenotype by gene expression and production of pro-inflammatory cytokines and chemokines including IL-6, CXCL10, and CCL5 via NF-κB activation in human renal mesangial cells. These results suggest that SBP1 contributes to mesangial proliferation and inflammation via mitochondrial respiration during IgAN.

Cordycepin Alleviates Lipopolysaccharides-Induced Preeclampsia-Like Impairments in Rats

ABSTRACT Introduction Preeclampsia is a serious pregnancy complication that can lead to life-threatening conditions such as seizures, strokes, and even death. A dysregulated inflammatory response in the placenta plays a crucial role in the development of preeclampsia. Cordycepin, known for its anti-inflammatory and antioxidant properties, was the focus of this study, which aimed to investigate its effects on preeclampsia. Methods A preeclampsia-like rat model was established via tail vein injection of lipopolysaccharides (LPS) at a dose of 1 μg/kg in pregnant rats. These rats were then treated with cordycepin at doses of 5, 25, or 50 mg/kg from embryonic day 6 (E6) today 18 (E18). Systolic blood pressures and urinary protein levels were monitored, and pregnancy outcomes, such as fetal body length and weight, were measured. The expression of target genes or proteins was assessed by qPCR, ELISA, and Western blot. Results Our findings revealed that cordycepin significantly reduced systolic blood pressure and proteinuria in preeclampsia-like rats. Additionally, cordycepin improved pregnancy outcomes, as shown by increased fetal body length and weight. The treatment also lowered serum sFlt-1 levels, elevated PIGF levels, decreased placental pro-inflammatory cytokine levels (IL-1β, TNF-α, IL-6, MCP-1, and MIP-2), and raised levels of anti-inflammatory cytokine IL-10 level in preeclampsia-like rats. Furthermore, cordycepin helped restore macrophage population imbalances, increasing M1-type macrophage markers (iNOS, TNF-α, and IL-1β) and reducing M2-type macrophage markers (Arg 1, IL-10, and TGF-β). Conclusion This study suggests that cordycepin alleviates LPS-induced preeclampsia by reducing placental inflammation and correcting the M1/M2 macrophage imbalance, offering potential therapeutic benefits for managing preeclampsia.

Mizhuo Guanchangye enema delays the decline of renal function in rats with chronic kidney disease by intervening in the TLR4/MyD88/NF-κB pathway.

Chronic kidney disease (CKD) is a prevalent chronic condition that poses a significant threat to human health. There is a close connection between the gut and kidneys, jointly influencing the onset and progression of CKD through the "gut-kidney axis." Traditional Chinese medicine has shown potential in CKD treatment, but the specific mechanisms require further investigation. This study aims to explore the protective effects of Mizhuo Enema (MZGCY) on kidney function in CKD rats by regulating the TLR4/MyD88/NF-κB signaling pathway. The researcher employed a CKD rat model, which was divided into four groups: Control, Model, half-dose Mizhuo Guanchangye (1/2 MZGCY), and full-dose Mizhuo Guanchangye (MZGCY). Post enema administration, assessments were conducted on kidney function indicators, which included blood urea nitrogen (BUN), serum creatinine (SCR), and 24-h urinary protein. Additionally, measurements were taken for intestinal toxic substances such as indoxyl sulfate (IS) and lipopolysaccharide (LPS), as well as inflammatory factors interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). Examinations of pathological changes in both the intestines and kidneys were also performed. During this process, immunofluorescence was utilized to detect the expression levels of proteins toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), and nuclear factor kappa B (NF-κB) in the intestinal tissues. It was found that after enema treatment, the BUN, SCR, and 24-h urinary protein levels in the MZGCY and 1/2 MZGCY groups significantly decreased, indicating notable improvement in kidney function. Compared to the model group, the IS, LPS, IL-6, and TNF-α levels in the MZGCY and 1/2 MZGCY groups were significantly reduced. Immunofluorescence showed a marked decrease in the expression of TLR4, MyD88, and NF-κB proteins in the intestines of the MZGCY group. MZGCY significantly reduces the levels of intestinal toxins and inflammatory factors in the serum of CKD rats by interfering with the TLR4/MyD88/NF-κB signaling pathway, thereby improving intestinal and renal pathological changes and delaying CKD progression. This study demonstrates that MZGCY has significant renal protective effects, providing a new potential approach for CKD treatment.