24-h Urinary Protein Levels Research Articles

Effect of Nephritis Rehabilitation Tablets combined with tacrolimus in treatment of idiopathic membranous nephropathy.

BACKGROUNDIdiopathic membranous nephropathy (IMN) has a high incidence in the middle-aged and elderly population, and poses a great threat to the physical and mental health and quality of life of patients. Nephritis Rehabilitation Tablets have many potential effects, such as clearing residual toxins, tumefying the kidney and spleen, replenishing qi, and nourishing yin, and have played an important role in the treatment of a variety of kidney diseases.AIMTo investigate the efficacy and safety of Nephritis Rehabilitation Tablets combined with tacrolimus in the treatment of IMN.METHODSEighty-four patients with IMN recruited from January 2017 to September 2020 were randomly divided into a study group (n = 42) and a control group (n = 42). On the basis of routine symptomatic treatment, both groups were treated with tacrolimus, and the study group was additionally treated with Nephritis Rehabilitation Tablets. Both groups were treated for 12 wk. The therapeutic effect, the levels of renal function indexes [serum creatinine (Scr), serum albumin, and 24-h urinary protein], urinary immunoglobulin (IgG4), membrane attack complex (C5b-9), and the incidence of adverse reactions were measured before and after 12 wk of treatment.RESULTSThe total effective rate in the study group was significantly higher than that of the control group. Before treatment, there was no significant difference in Scr, serum albumin, or 24 h urinary protein between the two groups. After 12 wk of treatment, the levels of Scr and 24-h urinary protein in both groups were significantly lower and serum albumin was significantly higher than those before treatment (P < 0.05), and the levels of Scr and 24-h urinary protein were significantly lower (P = 0.003 and 0.000, respectively), and the level of serum albumin was significantly higher (P = 0.00) in the study group than in the control group. Before treatment, there was no significant difference in urinary IgG4 and C5b-9 levels between the study group and the control group (P = 0.336 and 0.438, respectively). After 12 wk of treatment, the levels of urinary IgG4 and C5b-9 in the two groups were lower than those before treatment, and the levels of urinary IgG4 and C5b-9 in the study group were significantly lower than those in the control group (P = 0.000). There was no significant difference in the incidence of adverse reactions between the two groups (P = 0.710).CONCLUSIONBased on routine intervention, Nephritis Rehabilitation Tablets combined with tacrolimus in the treatment of IMN can effectively improve the renal function of patients and downregulate the expression of urinary IgG4 and C5b-9. In addition, they can improve the overall therapeutic effect while not increasing the risk of adverse reactions.

Efficacy of Modified Huangqi Chifeng decoction in alleviating renal fibrosis in rats with IgA nephropathy by inhibiting the TGF-β1/Smad3 signaling pathway through exosome regulation

IgA nephropathy is the most common form of primary glomerulonephritis and is a major cause of renal failure worldwide. Modified Huangqi Chifeng decoction (MHCD), a traditional Chinese herbal preparation, has clinical efficacy in reducing the 24-h urine protein levels in patients with IgA nephropathy. However, the molecular mechanism of MHCD needs further study. This study aimed to investigate the mechanisms by which MHCD treatment alleviates renal fibrosis. An IgA nephropathy rat model was established using bovine serum albumin, carbon tetrachloride, and lipopolysaccharide. The rats were divided into control, model, telmisartan, low-dose MHCD, medium-dose MHCD, and high-dose MHCD groups. Treatments were administered to these groups for 8 weeks. Subsequently, the 24-h urine protein, serum creatinine, blood urea nitrogen, and blood albumin levels were measured. Pathological changes and degree of fibrosis in renal tissues were observed, and levels of the transforming growth factor-β1 (TGF-β1)/Smad3 signaling pathway components in renal tissues and TGF-β1 in urinary exosomes were measured. Telmisartan and MHCD reduced 24-h urine protein levels, alleviated renal pathological injury, and decreased the renal expression of fibronectin, laminin, and collagen IV in rats with IgA nephropathy. Urinary exosomes were extracted and identified for further investigation of their role in renal fibrosis. MHCD reduced TGF-β1 expression in urinary exosomes and reduced TGF-β1 and p-Smad3 levels in renal tissues. MHCD alleviated renal fibrosis in rats with IgA nephropathy by inhibiting the TGF-β1/Smad3 signaling pathway through the downregulation of TGF-β1 expression in exosomes.

Horseshoe kidney with PLA2R-positive membranous nephropathy

BackgroundHorseshoe kidney (HSK) is a common congenital defect of the urinary system. The most common complications are urinary tract infection, urinary stones, and hydronephrosis. HSK can be combined with glomerular diseases, but the diagnosis rate of renal biopsy is low due to structural abnormalities. There are only a few reports on HSK with glomerular disease. Here, we have reported a case of PLA2R-positive membranous nephropathy occurring in a patient with HSK.Case presentationAfter admission to the hospital due to oedema of both the lower extremities, the patient was diagnosed with nephrotic syndrome due to abnormal 24-h urine protein (7540 mg) and blood albumin (25 g/L) levels. Abdominal ultrasonography revealed HSK. The patient’s brother had a history of end-stage renal disease due to nephrotic syndrome. Therefore, the patient was diagnosed with PLA2R-positive stage II membranous nephropathy through renal biopsy under abdominal ultrasonography guidance. He was administered adequate prednisone and cyclophosphamide, and after 6 months of treatment, urinary protein excretion levels significantly decreased.ConclusionThe risk and difficulty of renal biopsy in patients with HSK are increased due to structural abnormalities; however, renal biopsy can be accomplished through precise positioning with abdominal ultrasonography. In the literature, 20 cases of HSK with glomerular disease have been reported thus far. Because of the small number of cases, estimating the incidence rate of glomerular diseases in HSK is impossible, and the correlation between HSK and renal pathology cannot be stated. Further studies should be conducted and cases should be accumulated to elucidate this phenomenon.

Increased levels of circulating class-switched memory B cells and plasmablasts are associated with serum immunoglobulin G in primary focal segmental glomerulosclerosis patients

BackgroundFocal segmental glomerulosclerosis (FSGS) is a kidney-specific autoimmune disease, but its pathogenesis is not fully known. The present study detected the frequencies of circulating memory B cells and plasmablasts and other clinical parameters in FSGS. MethodsWe monitored 16 primary FSGS patients and 23 healthy controls (HC). Flow cytometry was used to analyze circulating memory B cell and plasmablastspercentages. Serum IgG levels were detected using a cytometric bead array (CBA). ResultsThe proportions of CD27 + IgD- class-switched memory B cells (P = 0.0002), CD27 + IgD-IgG + class-switched memory B cells (P < 0.0001), CD27hiCD38hi plasmablasts (P < 0.0001) and CD138 + plasma cells (P < 0.0001) were markedlyelevated in FSGS patients, and the frequency of CD38 + IgG + plasmablasts (P < 0.0001) and serum IgG levels (P < 0.0001) were lower compared to HC. In the FSGS patients, the frequency of CD27 + IgD-IgG + class-switched memory B cells negatively correlated with CD38 + IgG + plasmablasts (P = 0.0183, R = -0.3375), serum IgG levels (P = 0.0061, R = -0.4263) and estimated glomerular filtration rate (eGFR) (P = 0.0074, R = -0.4114) but positively correlated with 24-h urinary protein levels (P = 0.0077, R = 0.4085). The proportion of CD38 + IgG + plasmablasts positively correlated with serum IgG levels (P = 0.0151, R = 0.3538). ConclusionsWe speculate that alterations in the frequencies of CD27 + IgD-IgG + class-switched memory B cells and plasmablasts may be responsible for the etiopathogenesis of FSGS.

Increased Tim-3+ monocytes/macrophages are associated with disease severity in patients with IgA nephropathy

T-cell immunoglobulin and mucin-domain-containing protein-3 (Tim-3) plays multiple important roles in immune response and participates in the pathogenesis of various inflammatory diseases by regulating macrophage polarization. However, its functions in the development of IgA nephropathy (IgAN) are still unclear. In this study, changes in the relative levels of Tim-3+ monocytes/macrophages in peripheral blood and renal tissue, and their clinical significance in patients with IgAN were investigated. The expression of CD68 and Tim-3 in macrophages from patients with IgAN was determined via immunohistochemistry and immunofluorescence staining assays. Peripheral blood of 48 patients with biopsy-proven IgAN and 18 healthy controls (HCs) was collected to determine the frequency of circulating CD14+Tim-3+ cells using flow cytometry, before and after 24 weeks of prednisolone treatment. Serum interleukin (IL)-10 and tumor necrosis factor α (TNF-α) levels were measured using enzyme-linked immunosorbent assays. The potential association between clinical signs and Tim-3+ monocytes/macrophages was analyzed. The percentages of circulating CD14+Tim-3+ monocytes were higher in samples from patients with IgAN than in those from HCs and were positively associated with the pathological features (segmental glomerulosclerosis and tubular atrophy/interstitial fibrosis) of IgAN, according to the Oxford classification. Tissue staining assays revealed cells positive for both CD68 and Tim-3 in tubulointerstitial lesions of IgAN patients. In addition, elevated levels of serum IL-10 and TNF-α were detected in these patients in comparison to HCs. Furthermore, the frequency of circulating CD14+Tim-3+ monocytes had a positive correlation with levels of 24-h urinary protein and serum IL-10, and was negatively associated with renal function. After 24 weeks of treatment with prednisolone, the percentages of CD14+Tim-3+ cells were significantly reduced. In summary, our findings indicate that Tim-3+ monocytes/macrophages might be involved in the pathogenesisof IgAN and could be used as a potential indicator to evaluate disease severity.

Inflammatory response and matrix metalloproteinases in chronic kidney failure: Modulation by adropin and spexin.

Chronic kidney disease is a major global public health problem. The peptide hormones adropin and spexin modulate many physiological functions such as energy balance and glucose, lipid and protein metabolism. However, it is unclear whether these peptides may exert effects on renal damage, tissue remodeling, and inflammatory conditions. In view of the limited information, we aimed to investigate the effect of adropin and spexin on matrix metalloproteinase and inflammatory response genes a rat model of adenine-induced chronic kidney failure. Chronic kidney failure was induced in rats by administering adenine hemisulfate. Renal function was determined in an autoanalyzer. Histopathological modifications were assessed by H&E staining. mRNA expression levels of ALOX 15, COX 1, COX 2, IL-1β, IL-10, IL-17A, IL-18 IL-21, IL-33, KIM-1, MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-13, NGAL, TGFβ1, TIMP-1, and TNFα in kidney tissue were measured by qPCR. Our results showed an increase of 24-h urine volume, serum creatinine, BUN, and urine protein levels in group with adenine-induced CKF. Adropin and spexin treatments decreased urine protein and 24-h urine volume. Renal damage, TIMP-1, IL-33, and MMP-2 increased after CKF induction, while COX 1, MMP-9, and MMP-13 levels were significantly reduced. Furthermore, KIM-1, TIMP-1, IL-33, and MMP-2 were downregulated by spexin treatment. Renal damage, NGAL, TIMP-1 IL-17A, IL-33, MMP-2, and MMP-3 decreased after adropin treatment, while MMP-13 levels were upregulated. Treatment with adropin+spexin decreased KIM-1, NGAL, TIMP-1, IL-1β, IL-17A, IL-18, IL-33, ALOX 15, COX 1, COX 2, TGFβ1, TNFα, MMP-2, MMP-3, and MMP-7, but increased MMP-13 levels. Our findings revealed that inflammatory response and MMP genes were modulated by adropin and spexin. These peptides may have protective effects on inflammation and chronic kidney damage progression.

Epidemiology, clinical presentation, treatment, and follow\u2010up of chronic mercury poisoning in China: a retrospective analysis

BackgroundThere are no reports on the incidence of chronic mercury poisoning in a large population in China. This study investigated the epidemiology, clinical manifestations, treatment, and follow-up of Chinese patients with chronic mercury poisoning.MethodsData for 288 mercury poisoning patients were collected at our hospital from July 2014 to September 2019, including sex, age, admission time, blood mercury content, urine mercury content, creatinine, urinary mercury/creatinine ratio, 24-h urinary protein levels, electromyography (EMG) findings, renal biopsy, and follow-up. Patient characteristics were evaluated by statistical and correlation analyses.ResultsFirst, mercury poisoning in China mainly occurred through occupational exposure and the inappropriate use of mercury-containing cosmetics and Chinese folk remedies (CFRs). Second, the most common symptoms were nervous system (50.3 %), kidney (16.4 %) and breathing (8.0 %). Mercury poisoning-induced Nephrotic syndrome (NS) and peripheral neuropathy are common long-term complications. The complications of occupational and cosmetics-induced mercury poisoning are consistent with international belief. However, the NS caused by CFRs is mainly membranous nephropathy and the probability of peripheral neuropathy caused by CFRs is higher than other pathogens. Third, follow-up data shows that 13 patients with EMG-confirmed neurological injury, 10 showed full recovery after 38.50 ± 8.03 months. Furthermore, among 18 patients with NS, 15 had normal urine protein and serum albumin levels after 22.67 ± 10.26 months.ConclusionsRegulation of skin-lightening cosmetic products, safety surveillance of CFRs, and prevention and control of occupational exposure must be improved to decrease the incidence of mercury poisoning in China.

Clinicopathological features, risk factors, and outcomes of immunoglobulin A nephropathy associated with hepatitis B virus infection.

Hepatitis B virus (HBV) infections are associated with an increased risk of kidney diseases. However, the effects of HBV infection on the prognosis of immunoglobulin A nephropathy (IgAN) are unclear. A total of 838 patients with biopsy-confirmed IgAN were enrolled in this retrospective cohort study. The patients were categorized into either affected byIgAN and HBV infection (HBsAg-IgAN) or byprimary IgANwith no sign of HBV infection (P-IgAN). A 1:1 propensity-score matching was performed between the twogroups, followed by a Kaplan-Meier survival analysis, to compare the prognoses, and a Cox regression analysis, to identify factors influencing the HBsAg-IgAN outcomes. A total of 176 pairs of patients were successfully matched. A significant difference in the systolic blood pressure and urea, serum creatinine, uric acid, and 24-h urine protein levels was observed between the groups. A renal pathological analysis also revealed a significant difference in the mesangial hypercellularity between the groups. During a median follow-up period of 2.4years, Kaplan-Meier analysis also revealed a significant difference in the renal survival between the groups. Furthermore, multivariate Cox analysis confirmed that HBV infection is an independent risk factor for IgAN progression (hazard ratio [HR] 2.096; 95% confidence interval [CI] 1.091-4.026). Finally, the HBsAg-IgAN patients who received treatment with renin-angiotensin-aldosterone system inhibitors had a better overall prognosis than those who received immunosuppressive therapy and antiviral treatment. Our results indicate that the clinicopathological features and outcomes of patients with IgAN differ significantly between those with and without HBV infection, and that HBV is an independent risk factor for IgAN progression.

Theaflavin ameliorates renal ischemia/reperfusion injury by activating the Nrf2 signalling pathway in vivo and in vitro

Studies have demonstrated that oxidaive stress-induced apoptosis may be the main pathogenic mechanism of renal ischemia/reperfusion (I/R) injury. Theaflavin, a polyphenolic compound extracted from black tea, has been proven to exert strong antioxidant biological function. The objective of the present study was to investigate the potential role of theaflavin on renal I/R injury and its potential molecular mechanism both in vitro and in vivo. C57/BL6 J mice were used to create a model of I/R injury wherein mice were ligated with bilateral renal pedicles for 45 min, and then reperfused for 24 h. A hypoxia/reoxygenation (H/R) model of TCMK-1 cells was used to simulate I/R in vitro. Theaflavin were administered to the treatment group first and then established the model. Kidney Injury Molecule-1 (KIM-1), serum creatinine, urea nitrogen, and 24-h urinary protein levels were evaluated and changes in mitochondrial membrane potential and the ultrastructure of mitochondria were observed. Cell viability, oxidative stress damage, and apoptosis were assessed. The expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream target genes HO-1 and NQO1 were evaluated. Our results revealed that pretreatment with theaflavin significantly inhibited I/R- and H/R-induced renal injury and cell apoptosis. Theaflavin improved mitochondrial dysfunction by attenuating mitochondrial damage and promoting mitochondrial membrane potential. Theaflavin pretreatment significantly reduced malondialdehyde content, while enhancing superoxide dismutase activity in vivo and in vitro. It also reduced oxidative stress and apoptosis mainly by upregulating Nrf2 and its downstream targets in TCMK-1 cells. Thus, theaflavin exerted a protective effect against renal I/R injury by inhibiting oxidative stress and apoptosis via activation of the Nrf2-NQO1/HO-1 pathway as well as correcting mitochondrial dysfunction, thereby presenting its potential as a clinical therapeutic in cases of acute kidney injury.

Diagnostic value of urinary exosomal miR-23b-3p, miR-30a-5p, and miR-151-3p in children with primary nephrotic syndrome.

BackgroundPrimary nephrotic syndrome (NS) is a common disease of the urinary system with an unclear pathogenesis. We aimed to detect the levels of urinary exosomal miR-23b-3p, miR-30a-5p, and miR-151-3p in children with primary NS, and to explore their diagnostic value for NS.MethodsA total of 115 patients with NS who were admitted to the hospital from June 2017 to June 2019 were selected as the observation group. According to the disease progression, they were divided into an active group (acute active phase, n=68) and remission group (remission phase, n=47). In all, 50 healthy children were selected as the control group. Levels of urinary exosomal miR-23b-3p, miR-30a-5p, and miR-151-3p of each group in different periods were detected.ResultsThe 24-h urine protein, serum albumin (ALB), and serum total cholesterol (TC) levels were significantly higher in the observation group than in the control group (P<0.05), while those in the active group were significantly higher than those in the remission group (P<0.05). The levels of miR-23b-3p and miR-30a-5p were significantly higher in the observation group than in the control group, and significantly higher in the active group than in the remission group (P<0.05). No miR-151-3p was detected in the urinary exosomes of the two groups. After treatment, levels of exosomal miR-23b-3p and miR-30a-5p in the two groups both decreased significantly (P<0.05). Results of receiver operating curve (ROC) curve analysis showed that urinary exosomal miR-23b-3p and miR-30a-5p can be used to identify children with NS and healthy children. The area under the ROC curve (AUC) was 0.711 for miR-23b-3p and 0.844 for miR-30a-5p.ConclusionsThe levels of miR-23b-3p and miR-30a-5p in urinary exosomes of children with NS were significantly higher than those in healthy children, and decreased significantly after treatment, indicating that miR-23b-3p and miR-30a-5p in urinary exosomes are potential indicators for diagnosing the progression of NS and monitoring the treatment effect.

Glomerulosclerosis predicts poor renal outcome in patients with idiopathic membranous nephropathy.

This study aimed to investigate the association between the proportion of glomerulosclerosis (focal segmental glomerulosclerosis and/or global glomerulosclerosis) and renal prognosis in patients with idiopathic membranous nephropathy (IMN). A retrospective analysis performed from January 2008 to December 2017 in the First Affiliated Hospital of Shenzhen University by renal biopsy confirmed 200 patients with IMN, and their clinical pathology and prognosis were compared. Patients were divided into three groups on the basis of glomerular sclerosis proportion tertiles: low (Tertile1 group, proportion of glomerulosclerosis, 0-0%), middle (Tertile2 group, proportion of glomerulosclerosis, 0-5.5%) and high (Tertile3 group, proportion of glomerulosclerosis, 5.8-72.7%) tertiles. The follow-up endpoints were decreased estimated glomerular filtration rate (eGFR) by 20%, end-stage renal disease, and all-cause mortality. (1) Both, the Tertile1 and Tertile2, groups had significantly lower albumin level and higher 24-h urine protein level than that in the Tertile3 group. Regarding treatment, as the proportion of glomerulosclerosis increases, a more aggressive treatment with glucocorticoids and immunosuppressants should be provided. (2) Correlation analysis showed that the proportion of glomerulosclerosis was positively associated with age (P < 0.05). However, it was negatively associated with eGFR (P < 0.05). (3) Renal tubular atrophy and renal interstitial inflammatory cell infiltration were considered independent correlative factors for glomerulosclerosis. Kaplan-Meier analysis revealed that renal survival rate was significantly lower in patients with a proportion of glomerulosclerosis ≥ 6.45% than in patients with a proportion of glomerulosclerosis < 6.45%. Cox regression analysis revealed that as the proportion of glomerulosclerosis increases, the risk of renal outcomes increases gradually. Patients in the Tertile3 (higher proportion of glomerulosclerosis) group had more severe renal pathological damage compared to patients in the Tertile1 and Tertile2 groups. Glomerulosclerosis is a risk factor for renal function progression and poor renal prognosis in patients with IMN. As the proportion of glomerulosclerosis increases, the risk of renal endpoint events increases gradually.

Correlation of TNF-α and IL-10 gene polymorphisms with primary nephrotic syndrome.

The study explored the correlations of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) gene polymorphisms with susceptibility and the condition of primary nephrotic syndrome. A total of 200 patients with primary nephrotic syndrome in Qilu hospital were collected as disease group, and 200 healthy people were selected as control group. Genomic deoxyribonucleic acids (DNAs) of nucleated cells in the peripheral blood were extracted to detect the gene polymorphisms of TNF-α (rs1799724 and rs1800629) and IL-10 (rs1800872 and rs141219090). Allele distributions at rs1799724 (P=0.003) and rs1800629 (P=0.011) of TNF-α gene and at rs1800872 (P=0.033) of IL-10 gene in disease group were different from those in control group. In the disease group, allele C frequency at rs1799724 and allele A frequency at rs1800629 of TNF-α gene and allele T frequency at rs1800872 of IL-10 gene were higher. There were differences between rs1799724 (P=0.007) and rs1800629 (P=0.002) of TNF-α gene. In addition, there was a difference in the frequency of the dominant model of TNF-α gene rs1800629 between disease group and control group (P=0.035), and the frequency of dominant model GG+GA was remarkably lower in the disease group. Additionally, TT genotype at rs1799724 of TNF-α gene was obviously related to the plasma TNF-α level (P<0.05), and the plasma TNF-α level was significantly increased in disease group. AA genotype at rs141219090 of IL-10 gene had a notable correlation with the plasma IL-10 level (P<0.05), and the plasma IL-10 level in disease group was markedly raised. Additionally, CT genotype at rs1799724 of TNF-α gene was related to the 24-h urine protein level (P=0.035), GG genotype at rs1800872 of IL-10 gene was associated with the plasma albumin level (P=0.031), and GG genotype at rs141219090 was related to the serum creatinine level (P=0.047). TNF-α and IL-10 gene polymorphisms are predominantly correlated with the susceptibility and the condition of primary nephrotic syndrome.

Clinical features and expression of type I interferon-inducible genes in systemic lupus erythematosus patients harboring rs1143679 polymorphism in China: a single-center, retrospective study.

This case-control study aimed to analyze the clinical features and determine the expression of type I interferon-induced genes in systemic lupus erythematosus (SLE) patients harboring the CD11b rs1143679 single-nucleotide polymorphism (SNP) and elucidate whether it is involved in the relapses of SLE. One hundred twenty-five relatively inactive SLE patients with SLEDAI scores < 6, including 102 CD11b rs1143679 G allele patients as controls and 23 rs1143679 A allele carriers as cases, were enrolled from the SLE patient specimen bank in the Department of Rheumatology and Immunology. The sample set was retrospectively analyzed for differences in clinical features, and quantitative PCR and Western blot analyses were performed to evaluate the relative expression of type I interferon (IFN)-inducible genes. The 24-h urinary protein levels in the case group were significantly elevated, and serum C3 levels were significantly reduced compared with those in the control group (P = 0.019 and P = 0.021, respectively). The relative mRNA levels of IFN-inducible genes IFIT1, IFIT4, and ISG15 in the case group were higher than that in the control group (P = 0.0257, 0.0344, and 0.0311, respectively) and matched with the Western blot results. The relative expression of type I IFN-inducible genes in inactive SLE patients harboring the CD11b rs1143679 polymorphism was higher than that in other lupus patients. These findings suggest that the rs1143679 SNP can precipitate relapses in inactive SLE patients. • The rs1143679 GA genotype was associated with SLE clinical features. • The rs1143679 GA genotype showed higher interferon-inducible gene expression relative to the GG genotype.

Platelet distribution width as a marker for predicting lupus nephritis

BackgroundLupus nephritis (LN) is an important manifestation of systemic lupus erythematosus (SLE). The aim of this study was to investigate the predictive value of platelet distribution width (PDW) in LN. MethodsA retrospective study involving 212 SLE patients and 201 healthy controls were performed. All clinical characteristics and laboratory data were collected from their medical records. ResultsThe level of PDW was significantly decreased in SLE patients, which was negatively correlated with SLE disease activity index 2000 (SLEDAI-2K) score, disease duration, and 24-hour (24-h) urine protein, while positively correlated with serum IgG and IgM. There were more LN patients in low-PDW group than normal-PDW and high-PDW groups. In low-PDW group, SLEDAI-2K score, 24-h urine protein level, and anti-dsDNA antibody level was significantly higher, while serum IgG level was markedly lower. Moreover, PDW was negatively correlated with 24-h urine protein and disease duration, and it was positively correlated with serum IgG in LN patients. In addition, the area under the ROC curve of PDW was 0.87 and the optimal clinical cutoff level was 12.9, which provided a 87.41% sensitivity and a 74.63% specificity. Decreased PDW combined with high 24-h urine protein exhibited an excellent diagnostic value for LN. Importantly, 16.67% LN patients with negative 24-h urine protein can be detected in low PDW group. ConclusionPDW may be a potential marker for predicting LN. Low PDW accompanied with high 24-h urine protein may be a useful indicator for diagnosing LN.

Long-term renal survival and undetected risk factors of IgA nephropathy in Chinese children-a retrospective 1243 cases analysis from single centre experience.

The long-term renal outcome for IgA nephropathy (IgAN) in large cohorts of children remains unclear. IgAN is a progressive disease, to explore novel biomarkers is necessary for predicting the disease activity and progression of IgAN. In addition, there is a hot debate on when to treat with immunosuppression in children. We aimed to confirm the long-term renal survival, find some undetected risk factors and investigate when to treat with immunosuppression can benefit for renal outcome in Chinese children. 1243 Children with IgAN were enrolled and a follow-up of at least 1year after a biopsy from 2000 to 2017. Long-term renal survival, undetected risk factors and the renal survival of immunosuppressive and non-immunosuppressive therapy were evaluated. The primary endpoint of the study was a combined outcome of either ≥50% reduction in estimated glomerular filtration rate (eGFR) or end-stage renal disease (ESRD) or death. The median follow-up time were 86.8months (interquartile range 54.7-140.2months). The 5-, 10- and 15-year renal survival rates were 95.3%, 90.3% and 84%, respectively. Cox multivariate regression and Kaplan-Meier analysis showed that hypertension, hyperuricemia, high 24h urine protein (24h-UP) levels, lower initial eGFR, high urine C3 levels, high retinol-binding protein (RBP) levels, segmental glomerulosclerosis (S) and tubular atrophy and interstitial fibrosis (T) were associated with renal outcome. The statistically significant predictive perfect power for renal outcome was RBP≥0.7µg/ml (AUC = 0.899, sensitivity = 84.00%, specificity = 86.00%), 24h-UP ≥ 1g/24h (AUC = 0.722, sensitivity = 84.20%, specificity = 52.70%), eGFR<60ml/min/1.73m2 (AUC = 0.718, sensitivity = 81.30%, specificity = 39.20%) and S1 lesion (AUC = 0.703, sensitivity = 75.50%, specificity = 65.10%).Children with urinary RBP ≥0.7µg/ml were associated with a 2.513-fold risk than patients with urinary RBP<0.7µg/ml (P = 0.003). Our study suggested that immunosuppressive therapy may reduce the risk of progression in IgAN children had both eGFR>50ml/min/1.73m2 and proteinuria of at least 1g/day. This is the first report that the 15-year renal survival rate of children with IgAN in China was 84%. At the same time, this is the first study to reveal that urinary RBP≥0.7µg/ml may indicate a poor renal outcome. In addition, this study supports immunosuppressive therapy for IgAN children had both proteinuria≥1g/day and initial eGFR>50ml/min/1.73m2.

Effects of exercise training on proteinuria in adult patients with chronic kidney disease: a systematic review and meta-analysis

BackgroundRehabilitation effects of exercise training on adults with chronic kidney disease (CKD) have been generally recognised; however, the effects of exercise training on proteinuria have been underexplored. Our aim was to explore the effects of exercise training on proteinuria in adult CKD patients without renal replacement therapy.MethodsRandomised controlled trials (RCTs) and quasi-experimental studies examining the effects of exercise training on proteinuria in adults CKD patients without renal replacement therapy were searched in 10 electronic databases (MEDLINE, Embase, CINAHL, Cochrane Central Register of Controlled Trials, Allied and Complementary Medicine Database, SPORTDiscus with full text, Web of Science, China Wan Fang Database, China National Knowledge Internet, China Science and Technology Journal Database) until June 2019. The quality of quasi-experimental studies was assessed using the Joanna Briggs Institute Checklist for non-randomised experimental studies. The Cochrane risk of bias tool was used to evaluate the RCT quality.ResultsWe analysed 11 studies (623 participants). The 24-h urinary protein (24 h UP) level significantly decreased after exercise training in the within-group analysis (standard mean difference [SMD], 0.48; 95% confidence interval [CI], 0.08 to 0.88). There was a slight decrease in 24 h UP levels in the between-group analysis (SMD, 0.91; 95% CI, 0.00 to 1.82); however, the subgroup analysis showed that the change was insignificant (RCT: SMD, 0.24; 95% CI, − 0.44 to 0.92; quasi-experimental studies: SMD, 2.50; 95% CI, − 1.22 to 6.23). Exercise resulted in no significant differences in the urinary albumin-to-creatinine ratio in the between-group analysis (SMD, 0.06; 95% CI, − 0.54 to 0.67), but a significant decrease was found in the within-group analysis (SMD, 0.21; 95% CI, 0.04 to 0.38). No evidence of a decreased urinary protein-to-creatinine ratio was found after exercise (between-group analysis: SMD, 0.08 and 95% CI, − 0.33 to 0.48; within-group analysis: SMD, 0.04; 95% CI, − 0.25 to 0.32).ConclusionExercise training does not aggravate proteinuria in adult CKD patients without renal replacement therapy. Further research is warranted in the future to determine the effectiveness of exercise training on proteinuria and to explore the mechanisms by which exercise training influences proteinuria.

Effectiveness and safety of cyclophosphamide or tacrolimus therapy for idiopathic membranous nephropathy.

Guidelines recommend classical combined therapy of steroid and cyclophosphamide (CYC) for patients with idiopathic membranous nephropathy (IMN), while it is associated with severe adverse effects. We conducted an observational and retrospective study to evaluate the effectiveness and safety of steroids plus tacrolimus (TAC) versus steroids plus CYC for IMN. A total of 203 kidney-biopsy-proven IMN patients was enrolled in this study. One group (n = 142) received steroid combined with intravenous CYC (750 mg/m2 body surface) and the other group (n = 61) received steroid combined with oral TAC (target blood concentration of 4-8 ng/mL). The primary outcomes were achievement of remission. The secondary end-points included incidence of adverse events, relapse rates, 24 h urinary protein (UP), serum albumin, serum creatinine and estimated glomerular filtration rate. Over the 18-month observation period, the study suggested that the remission rates at the first 3 months were significantly higher in TAC group than in CYC group (72.1% vs 54.9%, P < 0.05). Although the cumulative incidence of serious and non-serious adverse events was not different significantly between the two groups, the incidence after first 3 months was lower in TAC group. Levels of 24-h UP and serum albumin improved in the TAC group more than in the CYC group (P < 0.05) over the observed period. Because of its short-term effectiveness and long-term safety profile, steroid plus TAC might be a better option for IMN.

Influence of air pollution on renal activity in patients with childhood-onset systemic lupus erythematosus.

Childhood-onset systemic lupus erythematosus (cSLE) is an autoimmune and multifactorial disease that can affect the renal system. Exposure to air pollution can trigger systemic inflammation in cSLE patients and increase risk of disease activity. We evaluated effects of individual real-time exposure to air pollutants on renal activity in cSLE patients using the Systemic Lupus Erythematosus Disease Activity Index 2000. Longitudinal panel study of 108 repetitive measures from 9 pediatric lupus patients. Over three consecutive weeks, daily individual levels of fine particulate matter (PM2.5) and nitrogen dioxide (NO2) were measured, as well as weekly clinical evaluation and laboratory tests. This was repeated every 10weeks over a 1-year period. Specific generalized estimating equation models were used to evaluate the impact of these pollutants on risk of nephritis and anti-dsDNA > 20UI/mL and on 24-h urine protein and serum complement (C3) levels. An interquartile range (IQR) increase of 18.12μg/m3 in PM2.5 daily concentration was associated with increased risk of nephritis and positive results for anti-dsDNA. Moreover, increase in 24-h urine protein and decrease in C3 serum levels also associated with exposure to pollutants. An IQR increase in PM2.57-day moving average was associated with increased risks of leukocyturia (3.4; 95% CI 2.6:4.3), positive anti-dsDNA (3.1; 95% CI 2.1:4.0), and 36.3-mg increase (95% IC 20.2:52.3) in 24-h urine protein. An IQR increase (63.1μg/m3) in 7-day cumulative NO2 levels was associated with decreased serum C3 levels. This prospective study suggests exposure to air pollution can trigger renal activity in cSLE patients.

Effects of adding tripterygium glycosides to angiotensin-converting enzyme inhibitors or angiotensin receptor blockers on albuminuria in patients with diabetic nephropathy

IntroductionTripterygium glycosides (TGs) have been widely used in China to treat diabetic nephropathy (DN); however, proof of their use is scarce. The present study aimed to evaluate the effectiveness and safety of adding TGs to angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs). MethodsBy searching Embase, MEDLINE, Cochrane Library, SINOMED, China National Knowledge Infrastructure, VIP Information/Chinese Scientific Journals, and WANFANG databases, we identified previous studies that met the specific selection criteria and included them in the meta-analysis. Analyses were performed using Review Manager (version 5.3). ResultsNine randomized controlled trials were included in the final meta-analysis. Patients were compared before and after treatment with ACE inhibitors or ARBs plus TGs, or ACE inhibitors or ARBs alone. The results revealed that treatment with ACE inhibitors or ARBs plus TGs resulted in significantly greater reductions in 24-h urinary total protein (UTP) levels (trial duration <2 months, mean difference [MD]: −0.25; 95% confidence interval [CI]: −0.32, −0.18; trial duration between 2 and 6 months, MD: −0.39; 95% CI: −0.44, −0.33; trial duration >6 months, MD: −2.09; 95% CI: −2.89, −1.29) compared with treatment using ACE inhibitors or ARBs alone. Additionally, ACE inhibitors or ARBs plus TGs showed better results after long-term administration. Treatment with ACE inhibitors or ARBs plus TGs resulted in significantly greater reductions in serum creatinine (SCr) compared with ACE inhibitors or ARBs alone (MD: −9.87; 95% CI: −13.76, −5.97). ConclusionIn patients with DN, adding TGs to ACE inhibitors or ARBs significantly lowered both the 24-h UTP and SCr levels. Therefore, ACE inhibitors or ARBs plus TGs might improve the treatment of DN in patients.

A Rat Model with Multivalve Calcification Induced by Subtotal Nephrectomy and High-Phosphorus Diet

Background: Chronic kidney disease (CKD) with known valve calcification (VC) places individuals at high risk of cardiovascular disease. The study of VC in CKD is challenging due to the lack of a suitable research model. Here, we established a rat model of multivalve calcification induced by subtotal nephrectomy and a high-phosphate (HP) diet and analyzed the valve characteristics. Methods: We established a CKD model in Sprague-Dawley rats by performing 5/6 nephrectomy (5/6Nx) followed by feeding with chow containing different phosphate concentrations for 8, 12, or 16 weeks. The rats were divided into 4 groups: sham+normal phosphate (NP, 0.9% P), sham+high phosphate (HP, 2.0% P), 5/6Nx+NP, and 5/6Nx+HP. Serum creatinine (Scr), blood urea nitrogen (BUN), parathyroid hormone (PTH), calcium, phosphorus, and 24-h urine protein levels were investigated. Pathological examinations included histological characterization, safranin staining, Alcian blue staining, and von Kossa staining at different time points. Using nanoanalytical electron microscopy, we examined valves from rats in the 5/6Nx+HP and sham+HP groups and detected spherical particles using energy-dispersive spectroscopy (EDS) to observe microscopic changes in the valves. In addition, the calcified tissues were analyzed for phase and crystallization properties using an X-ray powder diffractometer. Results: The rats in the 5/6Nx+HP and 5/6Nx+NP groups presented with increased levels of Scr, BUN, and 24-h urine protein compared with those of the rats in the sham+HP and sham+NP groups. High levels of PTH were observed, and hematoxylin and eosin staining and immunohistochemistry for proliferating cell nuclear antigen showed parathyroid hyperplasia in rats in the 5/6Nx+HP group but not in the 5/6Nx+NP group. In rats in the 5/6Nx+HP group, extracellular matrix glycosylation was observed in the aortic valve in the 12th week and the mitral valve in the 16th week. In the 16th week, chondrocytes appeared in the aortic valve, as confirmed by immunofluorescence and Western blotting. Calcified particles mainly composed of phosphorus and calcium were observed in both the aortic and mitral valves by transmission electron microscopy and scanning electron microscopy (SEM). The main mineral component of the calcified aortic valve particles was hydroxyapatite [Ca₅(PO₄)₃(OH)], as shown by X-ray diffraction. However, there were no obvious differences in heart function between rats in the 5/6Nx+HP and sham+HP groups. Conclusions: Our findings demonstrate that multivalve calcification is involved in CKD following 16-week HP and that hydroxyapatite [Ca₅(PO₄)₃(OH)] is the main component of the calcified aortic valve particles of rats in the 5/6Nx+HP group.