Amount Of Urinary Protein Research Articles

Jiedu Tongluo Baoshen formula enhances podocyte autophagy and reduces proteinuria in diabetic kidney disease by inhibiting PI3K/Akt/mTOR signaling pathway

Ethnopharmacological relevanceTraditional Chinese medicine (TCM) has been applied to diabetic kidney disease (DKD). A large number of animal trials each year focus on TCM for DKD, but the evidence for these preclinical studies is not clear. Aim of the studyThe aim of this study was to study the therapeutic effect of Jiedu Tongluo Baoshen formula (JTBF) on DKD proteinuria and renal protection. At the same time, it is verified that JTBF can reduce podocyte injury by enhancing autophagy function, and then achieve the effect of proteinuria. Materials and methodsWe use high performance liquid chromatography to detect and analyze the fingerprint of JTBF to find the chemical composition. Subsequently, we constructed a DKD rat model induced by high-fat diet and streptozocin (HFD + STZ). Urine and blood biochemical automatic analyzer were used to detect 24-h urine protein quantification (24 h-UP) and renal function. The renal pathological changes were observed by H&E and transmission electron microscopy (TEM), and the levels of autophagy-related proteins and mRNA in podocytes were detected by immunohistochemistry, RT-qPCR and Western Blot. The chemical composition of JTBF was screened from traditional Chinese medicine systems pharmacol (TCMSP) and PubChem databases, and the potential targets and associated pathways of JTBF were predicted using kyoto encyclopedia of genes and genomes (KEGG) and protein-protein interaction (PPI) network analysis in network pharmacology, and confirmed in animal experiments and histopathological methods. ResultsWe discovered 77 active ingredients of JTBF. Through animal experiments, it was found that JTBF reduced 24 h-UP and promoted the expression of podocin, nephrin, and WT-1 in podocytes, thereby reducing podocyte damage. At the same time, JTBF activates the expression of podocyte autophagy-related proteins (beclin-1, LC3 and P62). Subsequently, through network pharmacology predictions, 208 compounds were obtained from JTBF, and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) was a potential signal pathway. JTBF was obtained in DKD rat kidney tissue to inhibit the expression of PI3K, Akt and mTOR related proteins. ConclusionsJTBF enhance podocyte autophagy to reduce podocyte damage, thereby effectively treating DKD proteinuria and protecting kidney function.

Value of (11)C-PiB PET/MRI in the evaluation of organ involvement in primary systemic light chain amyloidosis

目的分析11C标记的匹兹堡化合物B（11C-PiB）PET/MRI在原发性系统性轻链型淀粉样变（pAL）中评估器官受累的价值。方法回顾性分析2019年1月至2021年10月在华中科技大学同济医学院附属协和医院就诊的20例pAL患者及3名健康志愿者的临床资料，比较临床标准评估器官受累和PET/MRI评估的相关性，分析心脏相关生物学指标、疾病分期与心脏最大标准摄取值（SUVmax）之间的关系及24 h尿蛋白定量与肾脏SUVmax之间的关系。结果①纳入20例患者，初诊患者18例，非初诊患者2例。观察到11C-PiB摄取阳性的脏器分别为：心脏15例（75％），肺部8例（40％），骨髓10例（50％），肌肉10例（50％），舌肌7例（35％），甲状腺6例（30％），唾液腺4例（20％），脾脏2例（10％），胃壁1例（5％）。②11C-PiB在心脏及骨髓摄取的阳性率与临床评估标准具有很好的相关性。在肺组织、脾脏、腺体、肌肉和舌肌中，11C-PiB PET/MRI评估的阳性率明显高于临床标准。但对于神经系统受累和脂肪组织的评估11C-PiB PET/MRI具有局限性。③分析18例初诊患者心脏相关生物学指标与心脏SUVmax之间的关系。左心室射血分数（LVEF）<50％且室间隔厚度（ISV）≥1.2 cm的患者相较LVEF≥50％且ISV<1.2 cm的患者其心脏SUVmax更高（P<0.05）。心脏SUVmax值在Mayo2004分期、Mayo2012分期各期之间差异有统计学意义，分期越晚，SUVmax值越高（P<0.05）。心脏SUVmax与心肌肌钙蛋白酶Ⅰ、N 末端前体脑钠肽水平呈明显正相关（P<0.01），肾脏SUVmax与24 h尿蛋白定量无明显相关性（P>0.05）。结论全身11C-PiB PET/MRI作为一种淀粉样蛋白的可视化系统，若用于器官水平的定性评估，具有提高早期无创性诊断pAL水平的潜力；用于器官水平（尤其是心脏）的定量评估，有望更精准评估器官功能和预测疾病预后。

Efficacy and safety of a low-sodium diet and spironolactone in patients with stage 1-3a chronic kidney disease: a pilot study

BackgroundExcessive salt intake is associated with the deterioration of chronic kidney disease (CKD). Aldosterone is also known as an independent risk factor for kidney injury. Dietary sodium intake acts as a main stimulator in aldosterone-mediated kidney injury. Hence, this study aimed to further investigate the renal protective effects and safety of a low-sodium diet in combination with spironolactone (SPL) in stage 1-3a CKD.MethodsThis single-center, SPL-blinded randomized controlled trial recruited patients with stage 1-3a CKD, randomized into three groups, low-sodium (3 g/d salt) + placebo, medium-sodium (5 g/d salt) + SPL, and low-sodium (3 g/d salt) + SPL. Patients received 12 weeks of intervention. The primary and secondary endpoints were 24-h urine protein and estimated glomerular filtration rate (eGFR) at the end of the intervention, respectively.ResultsA total of 74 patients were analyzed eventually. Significantly decreased 24-h urine protein was found in all three groups, from 0.37 to 0.23 g/d (P = 0.004) in the low-sodium+placebo group, from 0.44 to 0.29 g/d (P = 0.020) in the medium-sodium+SPL group, and from 0.35 to 0.31 g/d (P = 0.013) in the low-sodium +SPL group. There were no significant differences among the three groups in 24-h urine protein amount change after intervention from pre-treatment values (P = 0.760, ITT set). The results of the 24-h urine protein by using PP set analysis was similar to the ITT set. No significant differences in eGFR, nutritional, metabolic, inflammatory, and other biomarkers were observed across all three groups (P > 0.05). No safety signal was observed.ConclusionNo additional benefit was observed when SPL was prescribed to patients already on a low-sodium diet (3.0 g/d). Still, small doses of SPL may benefit patients with poor sodium restriction. A combination of short-term low-dose SPL and ARB is safe for patients with stage 1-3a CKD, but blood potassium must be regularly monitored.Trial registrationName of the registry: Chinese clinical trial registry.Trial registration number: ChiCTR1900026991.Date of registration: Retrospectively registered 28 October 2019.URL of trial registry record: http://www.chictr.org.cn/searchproj.aspx?title=&officialname=&subjectid=&secondaryid=&applier=&studyleader=ðicalcommitteesanction=&spo

Clinical comprehensive evaluation of Huangkui Capsules in treatment of chronic kidney diseases

Based on Guidelines for the Management of Clinical Comprehensive Evaluation of Drugs(trial version 2021), this study aims to sort out the clinical evidence of Huangkui Capsules(HC) in the treatment of chronic kidney diseases in aspects of safety, effectiveness, economy, innovation, suitability, accessibility, and characteristics of traditional Chinese medicine( &quot;6+1&quot; dimensions) from real-world data, secondary literature evaluations, questionnaires, and public data, with the methods in evidence-based medicine, epidemiology, pharmacoeconomics, and health technology. Furthermore, with multi-criteria decision analysis(MCDA) model and CSC v2.0, the clinical value of the medicine is comprehensively assessed. All the above are to highlight the advantages and characteristics of HC and lay a basis for scientific decision-making by the medical management department. The dimensions are graded A, B, C, or D. According to the conclusions from phase Ⅳ clinical trial, spontaneous reporting system(SRS), systematic review and Meta-analysis, acute toxicity and long-term toxicity tests, it mainly results in the adverse reactions of nausea, abdominal distension, vomiting, pruritus, rash, and good prognosis in patients. According to the available research, the safety evidence is sufficient and the risk is controllable, so the safety of this medicine is grade B. According to Meta-analysis, HC in combination with conventional drugs in the treatment of chronic kidney disease is superior to conventional drugs alone in reducing urinary protein, serum creatinine concentration, and blood urea nitrogen. In addition, HC combined angiotensin receptor blocker(ARB) or angiotensin converting enzyme inhibitor(ACEI) is outstanding in improving total clinical effective rate, reducing 24 h urinary protein quantity, urinary albumin excretion rate, serum creatinine concentration, triglyceride, and total cholesterol in the treatment of diabetic nephropathy as compared with ARB or ACEI alone. As for chronic nephritis, the application together with ARB or ACEI can raise the total effective rate, reduce 24 h urinary protein content, serum creatinine concentration, and blood urea nitrogen, and delay the progress of the disease. HC boasts high-quality evidence in treating chronic kidney disease, diabetic nephropathy, and chronic nephritis. It has obvious clinical significance in treating chronic kidney disease and thus its efficacy in this aspect is grade B. It has outstanding clinical significance for diabetic nephropathy and chronic nephritis and corresponding and the effectiveness is grade A. As for the pharmacoeconomic value, HC combined with ARB or ACEI is more economical in the treatment of chronic kidney disease than Bailing Capsules combined with ARB or ACEI, with high-quality evidence, and thus the economy of the formula is grade B. HC is a key solution to the high urinary protein in patients with hypotension and chronic kidney disease. The innovation is evidenced by the methods to ensuring drug supply, community-level supply, drug safety, effectiveness, and reasonable price, as wells as the aspects of enterprise philosophy, equipment management, research and development in process and technology, enterprise management and marketing. Thus, the prescription is grade A in innovation. The suitability, as evidenced in drug administration, technical management, drug storage, information service, and medication, is grade B. The course of the medicine is affordable, and it is accessible in a wide range of areas and hospitals. Thus, the accessibility is grade A. HC was developed from an in-hospital preparation, with application in numerous patients and thus large-scale real-world data. As a result, HC is grade B in terms of characteristics of traditional Chinese medicine. After comprehensive evaluation, the clinical value of HC in treating chronic kidney disease is class B, and that for diabetic nephropathy and chronic nephritis is class A. The result is of great reference value for the basic clinical medication management.

Analysis of the safety and efficacy of tacrolimus combined with glucocorticoid in the treatment of lupus nephritis.

Objective:To evaluate the safety and efficacy of tacrolimus combined with glucocorticoids in the treatment of lupus nephritis.Methods:A total of 80 patients with lupus nephritis were admitted to the Affiliated Hospital of Hebei University and the First Hospital of Baoding from February 2017 to January 2019 randomly divided into two groups: the experimental group and the control group, with 40 cases in each group. Patients in the experimental group were treated with tacrolimus combined with glucocorticoids, while patients in the control group were treated with cyclophosphamide combined with glucocorticoids for one year. Clinical efficacy and adverse drug reactions were evaluated for all patients after treatment. The changes of CRP, IL-6, 24h urinary protein, serum albumin, serum creatinine, urea nitrogen and other indicators after treatment, as well as the differences in the erythrocyte sedimentation rate (ESR), complement C3, C4, anti-dsDNA antibody positive rate and SLEDAI score and other indicators were also evaluated.Results:The total efficacy of the experimental group was 92.5%, which was significantly better than the 75% of the control group (p=0.03); The incidence of adverse reactions was 20% in the experimental group and 42.5% in the control group, with a statistically significant difference (p=0.03). After treatment, the levels of CRP, IL-6 and other inflammatory factors in the experimental group were lower than those in the control group, with a statistical significance (p<0.05); The indicators of the experimental group such as 24h urine protein quantification, serum albumin, blood creatinine, and urea nitrogen were improved compared with the control group, with statistically highly significant differences (p<0.001). In addition, ESR, anti-DSDNA antibody positive rate and SLEDAI score were decreased compared with the control group, while complement C3 and C4 levels were significantly increased (p<0.05).Conclusion:Tacrolimus combined with glucocorticoids is a safe and effective treatment regimen for patients with lupus nephritis, boasting a variety of benefits, such as significant efficacy and fewer adverse reactions. With such a regimen, the level of inflammatory factors can be significantly reduced, renal function indicators can be ameliorated, the ESR, complement C3, C4, anti-dsDNA antibody positive rate and SLEDAI score of the patients can be significantly improved.

Anesthesia Management in Caesarean Section with Preeclampsia and Partial HELLP Syndrome

Introduction. Pre-eclampsia is a significant cause of maternal and fetal mortality and morbidity. Pre-eclampsia is characterized by hypertension (blood pressure ≥ 140/90 mmHg), oedema and amount of protein in urine 300 mg in the 24-hour, which appears after 20 weeks of gestation. Pre-eclampsia can cause complications, one of which is HELLP syndrome. This case report discusses the use of anaesthesia in a patient who underwent a cesarean section with indications for pre-eclampsia and partial HELLP syndrome.&#x0D; Case Presentation. A woman, 41 years old, G4P3A0 34 weeks pregnant with pre-eclampsia + syndrome HELLP will undergo emergency cesarean section with ASA IIE physical statusLabouror pain management was carried out using regional spinal anaesthesia technique, using bupivacaine 0.5% hyperbaric agent 12.5 mg. The operation lasted for 1 hour 30 minutes, with 300 ml bleeding, hemodynamically stable.&#x0D; Conclusion. Difficult intubation in emergency cases can be avoided by choosing of neuraxial anaesthesia technique is recommended. It will lead to better uteroplacental perfusion, good analgesia/anaesthesia quality, reducing surgical stress, reducing drugs that enter the uteroplacental circulation, and maternal psychological to be able to see the baby at birth.

Effect of moxibustion on renal function and hypercoagulable state in patients with idiopathic membranous nephropathy of low to medium risk with spleen-kidney deficiency and blood stasis

To compare the effect of moxibustion combined with basic treatment and simple basic treatment on the clinical symptoms, renal function and hypercoagulable state in patients with idiopathic membranous nephropathy (IMN) of low to medium risk with spleen-kidney deficiency and blood stasis. A total of 60 patients with IMN of low to medium risk with spleen-kidney deficiency and blood stasis were randomized into an observation group (30 cases, 2 cases dropped off) and a control group (30 cases, 1 case dropped off). In the control group, the conventional basic treatment of anti-hypertension, regulating blood lipid and anti-coagulation was adopted. On the basis of the control group, moxibustion was applied at Shenshu (BL 23), Pishu (BL 20), Guanyuan (CV 4), Zusanli (ST 36) and Sanyinjiao (SP 6) in the observation group, once a day, 5 days a week continuously with 2 day interval. The treatment of 6 months was required in the both groups. Before treatment and 3 and 6 months into treatment, the total TCM syndrome score, the renal function indexes (24-hour urinary protein quantity [UTP], albumin [ALB], urea nitrogen [BUN] and creatinine [Scr]), the blood coagulation indexes (fibrinogen [FIB], D-Dimer [D-D], p-selection and von Willebrand factor [vWF]), total cholesterol (TC) and triacylglycerol (TG) levels were observed, and the therapeutic efficacy was evaluated on 3 and 6 months into treatment in the two groups. The effective rates of 3 and 6 months into treatment were 78.6% (22/28) and 89.3% (25/28) in the observation group, which were higher than 62.1% (18/29) and 75.9% (22/29) in the control group respectively (P<0.05). On 3 and 6 months into treatment, the total TCM syndrome scores were decreased compared before treatment in the both groups (P<0.05), and those in the observation group were lower than the control group (P<0.05). On 3 months into treatment, the levels of UTP, FIB, D-D, P-selection and vWF were decreased (P<0.05), the level of ALB was increased (P<0.05) compared before treatment in the observation group; the levels of UTP and FIB were decreased compared before treatment in the control group (P<0.05); the level of ALB in the observation group was higher than that in the control group (P<0.05), the levels of FIB and vWF in the observation group were lower than those in the control group (P<0.05). On 6 months into treatment, the levels of UTP, FIB, D-D, P-selection, vWF, TC and TG were decreased (P<0.05), the levels of ALB were increased (P<0.05) compared before treatment in the both groups (P<0.05); the levels of UTP, FIB, D-D, P-selection, vWF, TC and TG in the observation group were lower than those in the control group, the level of ALB in the observation group was higher than that in the control group (P<0.05). Moxibustion combined with basic treatment can effectively improve the clinical symptoms, renal function and renal microcirculation in patients with idiopathic membranous nephropathy of low to medium risk with spleen-kidney deficiency and blood stasis, the therapeutic effect is superior to the simple basic treatment.

Study on the Effect of Combination of Prednisone and Vitamin D in the Treatment of Primary Nephrotic Syndrome in Children.

Objective To study the effect of prednisone combined with vitamin D in the treatment of primary nephrotic syndrome in children. Method 73 cases of primary nephrotic syndrome admitted to the nephrology department of our hospital were randomly selected and retrospectively analyzed. 36 cases were treated with prednisone as the control group, and 37 cases were treated with prednisone combined with vitamin D as the observation group. The efficacy was compared after 3 months of continuous treatment. Result After 3 months of treatment, the blood calcium of the observation group was higher than that of the control group, PTH was lower than that of the control group, and 25-(OH)2D3 and 1,25-(OH)2D3 were higher than those of the control group (P < 0.05). After 1, 2, and 3 months of treatment in the observation group, Scr and 24-h urine protein quantification were lower than those in the control group and eGFR was higher than that in the control group (P < 0.05). CD4+ and CD4+/CD8+ were lower in the observation group than in the control group after 3 months of treatment (P < 0.05). The serum sTfR and TGF-β1 levels were lower in the observation group than in the control group after 3 months of treatment (P < 0.05). The total effective rate of the observation group was 83.78% after 3 months of combined treatment with prednisone and vitamin D, which was significantly higher than the total effective rate of the control group of 61.11% (P < 0.05). The incidence of nausea and vomiting, heartburn, headache, dry cough, hypercalcemia, and constipation during treatment in the observation group was not statistically different from that in the control group (P > 0.05). Conclusion Combined treatment of primary nephrotic syndrome in children with prednisone and vitamin D can more significantly improve the level of clinical indicators, improve renal function and immune function, and obtain more satisfactory efficacy, without significantly affecting the safety of treatment.

1H Nuclear Magnetic Resonance Spectroscopy-Based Methods for the Quantification of Proteins in Urine.

We described several postprocessing methods to measure protein concentrations in human urine from existing 1H nuclear magnetic resonance (NMR) metabolomic spectra: (1) direct spectral integration, (2) integration of NCD spectra (NCD = 1D NOESY-CPMG), (3) integration of SMolESY-filtered 1D NOESY spectra (SMolESY = Small Molecule Enhancement SpectroscopY), (4) matching protein patterns, and (5) TSP line integral and TSP linewidth. Postprocessing consists of (a) removal of the metabolite signals (demetabolization) and (b) extraction of the protein integral from the demetabolized spectra. For demetabolization, we tested subtraction of the spin-echo 1D spectrum (CPMG) from the regular 1D spectrum and low-pass filtering of 1D NOESY by its derivatives (c-SMolESY). Because of imperfections in the demetabolization, in addition to direct integration, we extracted protein integrals by the piecewise comparison of demetabolized spectra with the reference spectrum of albumin. We analyzed 42 urine samples with protein content known from the bicinchoninic acid (BCA) assay. We found excellent correlation between the BCA assay and the demetabolized NMR integrals. We have provided conversion factors for calculating protein concentrations in mg/mL from spectral integrals in mM. Additionally, we found the trimethylsilyl propionate (TSP, NMR standard) spectral linewidth and the TSP integral to be good indicators of protein concentration. The described methods increase the information content of urine NMR metabolomics spectra by informing clinical studies of protein concentration.

Clinicopathological characteristics and prognosis of hepatitis B associated membranous nephropathy and idiopathic membranous nephropathy complicated with hepatitis B virus infection

The main objective of this study is to analyze the clinical and pathological features and prognosis of patients with Hepatitis B associated membranous nephropathy (HBV-MN) and idiopathic membranous nephropathy (IMN) complicated with hepatitis B virus (HBV) infection. This study will provide more basis for diagnosis and prognosis evaluation. A total of 50 patients with HBV-MN were included in this study. 56 IMN patients complicated with HBV infection diagnosed during the same period formed the control group. Parameters including blood routine, urine routine and plasma levels of albumin (ALB), serum creatinine (SCR), blood urea nitrogen (BUN), urea acid (UA), total cholesterol (T-CHO), triglycerides (TG), complement C3 and C4, glutamic pyruvic transaminase (ALT), glutamic pyruvic transaminase (AST), 24-h urinary protein quantification (24 h-TP), renal phospholipase A2 receptor (PLA2R) and HBV related markers during the hospitalization and outpatient follow-up study period were collected for all the patients. The proportion of male patients was high in both groups. The average age of the HBV-MN group was 37.2 ± 14.187 years old, it was younger compared with the IMN group (P = 0.003). Nephrotic syndrome was the major clinical manifestation among patients. There was no significant difference between the two groups in the levels of anemia, microscopic hematuria, renal dysfunction, liver dysfunction, liver cirrhosis. The level of serum C3 and C4 in the HBV-MN group was lower compared with the IMN group (P = 0.002, P = 0.014). In the HBV-MN group, serum HBV markers were negative in 6 (12%) patients, 4 patients (8%) were positive for PLA2R in serum, and 5 patients (10%) were positive for PLA2R in renal tissue. Stronger IgG1 and C1q and weaker IgG4 staining were found in HBV-MN group renal tissues (P = 0.003, P = 0.025, and P = 0.001, respectively). There were no statistical differences compared with serum and renal PLA2R between HBV-MN and IMN groups (P = 0.098, P = 0.109). During the 1-year follow-up, there was no significant difference in complete remission rate between the two groups (P = 0.7739). Renal biopsy is crucial to diagnose HBV-MN. IgG subtypes in the HBV-MN group were mainly IgG1 deposition, while those in IMN complicated with HBV infection group were mainly IgG4 deposition. When HBV-associated antigen and PLA2R are present in renal tissue, lower level of serum C3 and C4, high intensity of renal C1q and IgG1 is more supportive of HBV-MN. The positive of PLA2R in serum and renal tissue in differentiating HBV from IMN complicated with HBV infection remains to be discussed.

The Related Factors of Hyperuricemia in IgA Nephropathy

Many factors, such as increased serum creatinine, increased blood pressure and abnormal urine protein, may lead to poor prognosis of IgA nephropathy (IgAN). The features of IgAN are also affected by uric acid, but its effect on the prognosis is less reported. We therefore systematically investigated the possible correlation of IgAN with hyperuricemia (HUA) and their prognosis. Two groups (HUA group and uric acid normal group) were included of 178 IgAN patients. The indexes in the clinic and pathology were compared; logistic regression and renal survival were used to speculate the correlated factors of HUA in IgAN and their prognosis. HUA group had higher serum urea nitrogen, serum creatinine, total cholesterol, 24-hour urinary protein quantity, percentage of CKD3⁃5, the thickness of arteriole, glomerular mesangial hyperplasia, tubular atrophy, glomerulosclerosis, interstitial fibrosis and the area of infiltration of inflammatory cells (ICI), lower eGFR and serum albumin-to-creatinine ratios (P < .05). Total cholesterol and ICI in X2 were independent related factors of HUA given by the analysis of logistic regression (P < .05). No correlation was found in HUA and normal group used by Kaplan- Meier (P > .05). Severer renal pathological injures (glomeruli, tubules or interstitium) were found in IgAN. Besides, total cholesterol and the area of infiltration of inflammatory cells were independent related factors of hyperuricemia in IgAN.

Nationwide questionnaire survey on the management of chronic kidney disease for general practitioners in Japan.

In 2019, a nationwide questionnaire survey on the management of chronic kidney disease (CKD) was circulated to general practitioners (GPs) throughout Japan by The Japan Physicians Association. The aim was to assess the current state of CKD medical care in the country and evaluate the utilization of CKD-specific guidelines in the treatment by GPs. The voluntary survey targeted all members of Japan Physicians Association, a nationwide organization consisting primarily of 15,000 GPs in clinics throughout the country. GPs were divided into groups: 171 GPs using and 414 GPs not using the guidelines. Comparisons between the groups' responses were made using propensity score matching and component cluster analysis. Overall responses revealed that the estimated glomerular filtration rate's utilization rate was high (95.1%). However, evidence-practice gaps in urine protein quantification and anemia remedy were prominent. There were significantly favorable answers in terms of CKD management in the user group compared with those in the non-user group, except for the questions about a urine check at the first visit, stopping the use of renin-angiotensin system inhibitors, and the target blood pressure for elderly CKD patients. The differences suggest that utilization of the CKD guidelines has improved CKD management practices by GPs. Further promotion of CKD guidelines utilization (28% in this survey) is considered valid for CKD medical education.

MO305NEPHROTIC SYNDROME AND NEPHROTIC-RANGE PROTEINURIA - CLINICOPATHOLOGICAL DIAGNOSES AND PATIENT CHARACTERISTICS IN A MULTIETHNIC SINGLE CENTRE POPULATION

Abstract Background and Aims Nephrotic syndrome (NS) is a common indication for renal biopsy, and a frequent presenting clinical syndrome for certain glomerulonephritis (GN), particularly minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS) or membranous nephropathy (MN). However, less is known on the spectrum of clinicopathological diagnosis and characteristics in patients with nephrotic-range proteinuria without nephrotic syndrome (NRP). We aim to evaluate the differences in clinicopathological diagnosis and characteristics of patients with NS versus NRP. Method All patients who underwent a renal biopsy from the 1st January 2014 to 31st December 2016 were included in the study. Patients with no urine protein quantification, serum albumin or lipid panel done at the time of renal biopsy or no glomeruli seen on renal histology were excluded. Data for renal histopathology, clinical diagnosis and patient characteristics were obtained from review of medical records. Results A total of 362 patients underwent a renal biopsy from the 1st January 2014 to 31st December 2016. Of these, 76 patients had NS and 106 patients had NRP. Mean age was 51.1±17.0, 51.5% were male and 70.9% were Chinese. In the NS group, there were 25 (32.9%) MCD, 10 (13.2%) FSGS of which 8 were primary, 14 (18.4%) lupus nephritis (LN), 11 (14.5%) MN, 8 (10.5%) diabetic glomerulosclerosis, 2 (2.6%) Immunoglobulin A nephropathy (IgAN), 2 (2.6%) amyloidosis and 4 (5.3%) with other diagnoses (2 membranoproliferative GN, 1 acute interstitial nephritis, 1 chronic glomerulosclerosis). In the NRP group, there were 26 (24.5%) diabetic nephropathy, 21 (19.8%) IgAN, 15 (14.2%) LN, 13 (12.3%) FSGS of which 12 were secondary FSGS, 12 (11.3%) chronic glomerulosclerosis, 8 (7.5%) MN, 4 (3.8%) pauci-immune GN and 7 (6.6%) with other diagnosis (2 infection-related glomerulonephritis, 3 had mild chronic changes with proteinuria attributable to overflow proteinuria from myeloma, 1 Alport syndrome, 1 thrombotic microangiopathy). There were significantly more cases of primary GN in the NS group (63.2% versus 28.3%, p&amp;lt;0.001), while the NRP group had more secondary GN and non-GN cases. The most common cause of primary GN is MCD in the NS group and IgAN in the NRP group. LN is the most common secondary GN in both NS and NRP groups. There was no significant difference in age, gender and race between the NS and NRP group. The NS group had a significantly higher proteinuria (10.8±5.5 versus 6.3±3.5, p&amp;lt;0.001) and lower serum albumin (17.0±5.7 versus 28.0±7.6, p&amp;lt;0.001). The NRP group had significantly more patients with abnormal renal function at the time of biopsy (83 (78.30%) versus 39 (51.32%) patients, p&amp;lt;0.001), a higher mean systolic BP (144.1±26.3mmHg versus 134.2±26.2mmHg, p=0.014) and a higher percentage of diabetes mellitus (38 (35.85%) versus 15 (19.74%) patients, p=0.018) compared to the NS group. Conclusion The clinicopathological diagnosis between patients with NS and NRP differ significantly. Patients with NRP are more likely to have secondary glomerular disease or non-glomerular disease, with abnormal renal function and higher prevalence of hypertension and diabetes mellitus.

Big data-based grey forecast mathematical model to evaluate the effect of Escherichia coli infection on patients with lupus nephritis

The grey predictive mathematical model based on big data was used for analysis on the effect of Escherichia coli infection on patients with lupus nephritis (LN) in this study. Then, 156 patients diagnosed with LN infections by Wuzhong People’s Hospital’s information system (HIS) from October 30, 2017 to October 30, 2019 were selected as the experimental group, and 89 patients without LN infections were selected as the control group. Besides, the grey theory mathematical model was applied to process the integrated data, and feature analysis was employed to screen out disease-related bio-markers for the diagnosis of LN. The two groups were compared for affected organs, treatment, laboratory indicators, pathogenic bacteria, and recovery status. Multivariate logistic regression was used to analyze the related factors of patients with infections. The results showed that the specificity, sensitivity, and accuracy of the big data diagnosis based on the grey theory mathematical model were 78.9%, 87.6%, and 92.1, respectively; hormones, c-reactive protein, procalcitonin, and the daily antibiotic dose were positively correlated with concurrent infections (P < 0.05); 38 cases of Gram-negative bacteria were screened out, accounting for the largest proportion (37.18%); the effective rate of the experimental group was obviously lower than that of the control group (P < 0.05), suggesting that C-reactive protein (CRP), procalcitonin (PCT), antibiotics, daily dose of hormones, and serum albumin were independent risk factors for LN infection. In conclusion, the grey predictive mathematical model based on big data had high specificity, sensitivity, and accuracy in diagnosing the occurrence of infection in patients with LN; LN infection was mainly respiratory infection, and gram-negative bacteria were the main pathogen. Patients with LN infections showed higher serum creatinine, 24-hour urine protein quantification, CRP, and PCT, and lower serum albumin and recovery effect versus those without LN infections.

Development of a multiplex mass spectrometry method for simultaneous quantification of urinary proteins related to respiratory health

Respiratory health of children is a health priority. Club cell protein (CC16) is an interesting biomarker of lung diseases and adverse effects towards the airway epithelium integrity. Osteopontin (OPN) and nuclear factor-kappa B (NF-κB) also play a role in respiratory health. The use of urine as biomarker source is useful in studies involving children but necessitates proper adjustment for physiological confounders influencing the urinary excretion, potentially characterized with beta-2-microglobulin (β2M), retinol binding protein 4 (RBP4) or myoglobin (MYO), as well as adjustment for possible renal dysfunction, characterized by human serum albumin (HSA). The simultaneous quantification of all these proteins in urine could facilitate children’s health monitoring. A multiple reaction monitoring method (MRM) was developed and validated for the relative quantification of the seven mentioned urinary proteins. A total of nine proteotypic peptides were selected and used for the relative quantification of the seven proteins. The MRM method was completely validated for all proteins and partially for OPN. LOQ’s ranged from 0.3 to 42.8 ng/ml, a good reproducibility and a good linearity were obtained across the analytical measurement range (r2 > 0.98). The method yielded varying correlations (r2 of 0.78, 0.71, 0.34 and 0.15 for CC16, β2M, RBP4 and HSA respectively) with available immunoassay data. It also allowed the identification and successful quantification of β2M and RBP4 as a protein candidate for adjustment of renal handling and dysfunction. All proteins were detected in the urine samples except for MYO and NF-κB. Our validated MRM-method is able to simultaneously quantify in urine biomarkers of airway epithelium integrity and biomarkers of variation in renal function and urinary dilution. This will allow to investigate further in future studies if urine can be used as a good surrogate source for biomarkers of airway epithelium integrity, and to understand the complex relationship between cause and effect in children’s respiratory health monitoring.

Clinical and pathological analysis of 101 cases of ANCA-associated vasculitic kidney injury.

To analyze the clinical and pathological features of patients with anti-neutrophilic cytoplasmic antibody (ANCA)-associated vasculitic (AASV)-kidney injury (AASVKI). From January 2015 to December 2018, a total of 101 AASVKI patients treated in the First Hospital of Jilin University were divided into 2 groups (the pANCA-positive group and the cANCA-positive group) for comparison; 63 patients were performed renal biopsy and divided into 3 groups according to pathological results [the non-crescent nephritis group (non-C), the crescent nephritis group (C), and the sclerotic nephritis group (S)] for comparison. Compared with the Group pANCA, Group cANCA exhibited higher incidence of eye involvement (P = 0.039) and skin mucosa destruction (P = 0.045), higher serum creatinine (Scr) (P < 0.001), higher 24-h urine protein quantification (P = 0.045), but lower hemoglobin (Hb) (P < 0.001). Compared with Group non-C, Group C had higher Scr (P < 0.001) and urinary red blood cells (P = 0.010), lower estimated glomerular filtration rate (eGFR) (P = 0.003), hemoglobin (HD)-dependence (P = 0.042), and higher mortality rate within 1year (P = 0.005); compared with Group S, Group C had faster onset of erythrocyte sedimentation rate (ESR) (P = 0.031), higher urinary red blood cells (P = 0.029), and lower incidence of HD-dependence (P = 0.038). AASVKI patients with positive cANCA have poor renal function, among whom the patients with crescent type have poorer renal function than those with non-crescent type, have higher urinary red blood cells while lower HD-dependence than those with sclerotic type.

A systematic review and meta-analysis of integrated traditional Chinese medicine and Western medicine in treating glomerulosclerosis.

Background:The combination of Traditional Chinese medicine and Western medicine (TCM+WM) has been widely used in the treatment of glomerulosclerosis, but the results are still controversial. This study will assess the clinical efficacy of TCM+WM for glomerulosclerosis and provide evidence-based medical data via meta-analysis.Method:The MEDLINE, EMBASE, PubMed, Cochrane Central Registry of Controlled Trials, and multiple Chinese databases (Wan Fang, CNKI, and VIP) were searched for randomized controlled trials (RCT) that compared the effects of WM and TCM+WM. Review Manager 5.3 software was used for the meta-analysis of selected studies, and appropriate tests were performed to determine the quality, heterogeneity and sensitivity of these studies.Results:Sixteen RCTs met the inclusion criteria and were selected for the analysis. Compared with the placebo or WM-treated glomerulosclerosis patients, TCM+WM intervention significantly improved renal function indices including 24-hour urine protein quantity (24 h U-Pro), serum creatinine (Scr), blood urea nitrogen (BUN), creatinine clearance (Ccr). In addition, the serum albumin (ALB), triglyceride (TG), and cholesterol (CHOL) levels were also significantly improved (P < .05) in patients receiving the combination therapy. Finally, the combination of TCM+WM reduced the indices of glomerulosclerosis more effectively compared with WM alone.Conclusion:The combination of TCM+WM can significantly improve the renal function and prognosis of patients with glomerulosclerosis.

Efficacy and safety of Shenyankangfu Tablet, a Chinese patent medicine, for primary glomerulonephritis: A multicenter randomized controlled trial

BackgroundShenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease. ObjectiveThis trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium. Design, setting, participants and interventionThis was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18–70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m2, and 24-hour proteinuria level of 0.5–3.0 g, were recruited in 41 hospitals across 19 provinces in China and were randomly divided into five groups: SYKFT, losartan potassium 50 mg or 100 mg, SYKFT plus losartan potassium 50 mg or 100 mg. Main outcome measuresThe primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment. ResultsA total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (−3.00 [−6.00, −2.00]) and who did not take SYKFT (−2.00 [−5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group. ConclusionSYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone. Trial registration numberNCT02063100 on ClinicalTrials.gov.

РЕЗУЛЬТАТЫ ИЗУЧЕНИЯ ЭФФЕКТИВНОСТИ ДИАТОМИТА ПРИ ИНТОКСИКАЦИИ ЖИВОТНЫХ КАДМИЕМ И СВИНЦОМ

The combination of cadmium and lead in doses at the level of 10 MPC for feed caused in white rats a decrease in body weight and immunoglobulin content in blood serum, an increase in the summation threshold indicator, a decrease of the amount of protein in urine and SH-groups in blood serum, a significant increase in mass coefficients of the liver and kidneys. The use of diatomite as a means to reduce heavy metal intoxication slightly increased body weight. The use of means did not lead to normalization of the summation threshold indicator, did not significantly affect the content of SH-groups. In the group of animals treated with diatomite, the mass coefficients of the liver remained significantly higher than the control values. The obtained results indicate that diatomite did not show protective properties as a feed additive to reduce lead and cadmium intoxication.

The impact of ramipril on kidney function parameters in the chronic kidney disease patient with hypertension

The administration of angiotensin converting enzyme inhibitors had gain popularity owing to their efficacy and safety in chronic kidney disease (CKD) patients. However, it is certainly necessary to look into the impact of the ramipril in kidney impaired individuals. We had enrolled 190 CKD with hypertensive patients based on the exclusion and inclusion criteria. The elder patients constituted to have a major share in the CKD population on ramipril therapy. From the study, it was found that the high costly brand was chosen the most and least cost was preferred only for 2 patients. The glomerular filtration rate (GFR) and serum creatinine, the major determinants of kidney function, had a small relationship with the dose of ramipril. However, the antihypertensive drug showed to have a favorable impact on patients overall treatment outcome. It is vital to evaluate the amount of protein in urine in case of a CKD patient. The easiest and cost effective technique, the dipstick urine protein test was done. The test value was found to be 1+ (30mg/dl) for majority of the patients and only 2 patients were observed with more than 1000 mg/dl. The ability of ramipril to reduce the progression of CKD can be attributed to the pooling of the data in +1 (30mg/dl) range.