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Our previous study showed ST6 β-galactoside α2,6-sialyltransferase 1 (ST6Gal-1) levels in plasma were associated with a slower progression of IgA nephropathy (IgAN). Platelets are the crucial regulator of cell surface glycosylation events in circulation by supplying glycosyltransferases.A total of 180 patients with IgAN were included in this study. ST6Gal-1 levels were analyzed before and after activation of platelets by flow cytometry.We found that IgAN patients in the higher platelet counts group exhibited higher levels of ST6Gal-1 compared with the lower platelet counts group. There was a positive correlation between platelet counts and ST6Gal-1 levels in plasma. Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. No differences were found in terms of the eGFR decline and composite kidney endpoints between two groups. Furthermore, we investigated whether platelets were activated and released ST6Gal-1 in patients with IgAN. The expression of CD62P in platelets in patients with IgAN was higher than those of healthy controls. There were no obvious changes in ST6Gal-1 levels between the rest and the activated platelets within 1 to 2-hour, however, the difference in ST6Gal-1 levels became more pronounced after 4-hour of incubation.In conclusion, human circulating platelets contain ST6Gal-1, which may be released by the activation of platelets in IgAN.

The overall effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors in patients with advanced chronic kidney disease (CKD) (estimated glomerular filtration rate (eGFR), 15-30 ml/min per 1.73 mThe Medline, Embase, and Cochrane Library databases were systematically searched for randomized controlled trials (RCTs) published up to March 3, 2022, and reporting effects of SGLT2 inhibitors on kidney, CV, or safety outcomes in patients with advanced CKD.From 2675 records, six RCTs with 2167 participants were included in the quantitative analyses. In patients with advanced CKD, SGLT2 inhibitors reduced the risk of the primary kidney outcome (a composite of worsening kidney function, end-stage kidney disease (ESKD), or kidney death) by 23% (RR 0.77, 95% CI 0.61-0.98, p = 0.04, IAmong patients with advanced CKD, SGLT2 inhibitors reduced the risks of primary kidney and CV outcomes and attenuated the progressive decrease in eGFR compared with placebo, with no evidence of additional safety concerns. These observed benefits may support continuing the use of SGLT2 inhibitors in patients with advanced CKD before initiating maintenance dialysis or kidney transplantation. Future large-scale RCTs are needed to confirm the robustness of these results.

Background Oral sodium zirconium cyclosilicate (SZC) is a novel potassium binder capable of achieving a rapid reduction of serum potassium (sK+) and maintaining a long-term normokalemia. We undertook a meta-analysis to summarize and evaluate the effects surrounding SZC in patients with hyperkalemia. Method We searched data sources from MEDLINE (from 1950 to Sep 2020), EMBASE (from 1970 to Sep 2020), and the Cochrane Library database (from 1950 to Sep 2020) for eligible studies. All randomized controlled trials (RCTs) regarding comparison of therapeutic effects of SZC in hyperkalemia participants were included. Results Seven studies, including 1697 patients with hyperkalemia, were analyzed. SZC significantly reduced mean sK+ (−0.42 mmol/L; 95% CI: −0.63 to −0.20 mmol/L, p = 0.0001) compared with placebo, with a significantly greater proportion of patients with normokalemia (RR 3.48, 95% CI 1.49 to 8.11, p = 0.004). Subgroup analyses showed that the longer durations of SZC treatment, the greater magnitudes of potassium reduction when compared with those of placebo (p between subgroups = 0.01) at correction phase. Besides, it also demonstrated sK+ tended to decrease more in patients who got longer treatment or larger dosage of SZC at maintenance phase; however, the difference did not reach statistical significance. Additionally, the drug was equally effective in studies with larger than 50% of patients with chronic kidney disease (CKD) or diabetes or patients using renin-angiotensin aldosterone system inhibitor (RAAS) inhibitors (all p p = 0.03) in SZC group was higher than those of placebo group. No statistically significant differences in the risks of other adverse events were observed between the two groups. Conclusions SZC effectively decreased the sK+ level in patients with hyperkalemia within 48 h and had benefits in the long-term control of serum potassium in patients who continued to receive SZC with a favorable safety profile from available data.

Background The advantages of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) in reducing risk of cardiovascular events (CVEs) and delaying end-stage kidney disease (ESKD) in patients with chronic kidney disease (CKD) is well-known. However, the efficacy and safety of these agents in non-dialysis CKD stages 3–5 patients are still a controversial issue. Methods Two investigators (Yaru Zhang and Dandan He) independently searched and identified relevant studies from MEDLINE (from 1950 to October 2018), EMBASE (from 1970 to October 2018), and the Cochrane Library database. Randomised clinical trials in non-dialysis CKD3–5 patients treated with renin-angiotensin system (RAS) inhibitors were included. We used standard criteria (Cochrane risk of bias tool) to assess the inherent risk of bias of trials. We calculated the odds ratio (OR) and 95% confidence interval (CI) for each outcome by random-effects model. A 2-sided p value

The role of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in reducing the progression of albuminuria and risk of cardiovascular events in hypertensive patients with diabetic kidney disease (DKD) is well-documented. However, the efficacy and safety of these agents in normotensive patients with DKD are still controversial. MEDLINE, Embase, and Cochrane Library were searched for relevant random controlled trials. The odd risk (OR) reductions were calculated with a random-effects model. Decrease in albuminuria, changes in eGFR, major cardiovascular events, and drug-related adverse events were analyzed. Thirteen RCTs including 1282 patients were retrieved. Compared with placebo or other active agent groups, ACEIs or ARBs significantly decreased albuminuria (MD –80.28 mg/d, 95% CI –104.79 mg/d to –55.77 mg/d), and the efficacy is independent of changes in blood pressure and systolic blood pressure at baseline. The result of subanalysis showed the declining of albuminuria was more significantly in normotensive DKD patients with 2DM (p=0.005). No significant differences were found with regard to the declining of evaluated glomerular filtration rate (eGFR) (MD –0.29 ml/min/1.73 m2, 95% CI –2.99 to 2.41 ml/min/1.73 m2). There were no significant differences in the side effect of the drugs such as hypotension and hyperkalemia. This meta-analysis demonstrated that ACEIs or ARBs can decrease albuminuria to varying degree in normotensive patients with DKD, and better response occurred in patients with 2DM.

Background: Recent genomewide association study suggested that the top single-nucleotide polymorphism, rs978056, in HECW1 gene (which encodes HECT, C2 and WW domain containing E3 ubiquitin protein ligase 1) associated with the levels of galactose-deficient IgA1 (Gd-IgA1) in IgA nephropathy (IgAN). However, HECW1 expression in IgAN has not yet been examined. Methods: In the following study, we have enrolled 40 patients with IgAN and 40 healthy controls. The expression level of HECW1, as well as plasma levels of Gd-IgA1 and IgA1, were determined detected. Results: IgAN patients presented with significantly elevated Gd-IgA1 and IgA1 levels compared with those of the healthy controls (p

The etiology of anemia in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) has not been elucidated. In this cross-sectional study, we tried to investigate the relationship between serum hepcidin and anemia in myeloperoxidase (MPO)-ANCA-AAV. Data of 64 newly diagnosed AAV patients who did not have kidney dysfunction or hemorrhage were analyzed. Serum hepcidin was measured with enzyme linked immunosorbent assay. Twenty-three of 64 patients had anemia. Compared with patients without anemia, patients with anemia had higher Birmingham vasculitis activity score [10 (3, 23) vs. 5 (3, 17), p = 0.020], lower levels of serum iron (5.83 ± 1.63 vs. 9.76 ± 1.54, p

Background: Aberrant galactose-deficient IgA1 molecules (Gd-IgA1) are important causal factors in IgA nephropathy (IgAN); however, the detection of Gd-IgA1 in IgAN is complicated and instable. A monoclonal antibody, KM55, which specifically recognizes Gd-IgA1 has been developed. In the present study, we further explored the clinical significance of Gd-IgA1 using KM55. Methods: In this study, we enrolled 75 patients with IgAN and 80 healthy controls and detected the plasma Gd-IgA1 levels using the KM55 ELISA method. We also stained ­mesangial Gd-IgA1 deposition using KM55. Results: We observed that the levels of plasma Gd-IgA1 in IgAN patients were elevated compared to the corresponding levels of healthy controls. Patients were divided into 2 groups based on the median of Gd-IgA1. Patients with high Gd-IgA1 levels had significantly higher levels of uric acid (UA) and IgA. The other clinical manifestations demonstrated that there were no differences in age, sex, blood pressure, initial proteinuria, hematuria, estimated glomerular filtration rate and Oxford pathological classification between the 2 groups of patients. In addition, positive correlations were observed between Gd-IgA1 and Bb, C3a, C4d and MAC. Mesangial Gd-IgA1 was positive in IgAN but negative in the normal renal tissue adjacent to neoplasm. We next analyzed the correlation between plasma Gd-IgA1 and mesangial Gd-IgA1 deposition. The results showed that a high level of plasma Gd-IgA1 was related to the deposition of mesangial Gd-IgA1, although the difference was not significant. Conclusion: We verified the elevated level of plasma and ­mesangial Gd-IgA1 in patients with IgAN by KM55, which provided an alternative, easy, and reliable tool for diagnosis and activity assessment of IgAN. The level of plasma Gd-IgA1 positively correlated with levels of UA, total IgA levels, and complement activation products.

Galactose‐deficient IgA1 (Gd‐IgA1) plays a crucial role in the development of Immunoglobulin A nephropathy (IgAN), however, the underlying pathogenic mechanisms driving Gd‐IgA1 production in B cells are not well understood. In this study, RNA‐seq analysis identified 337 down‐regulated and 405 up‐regulated genes in B cells from 17 patients with IgAN and 6 healthy controls. Among them, ST6Gal1, which was associated with IgAN in a previous genome‐wide association study (GWAS), was up‐regulated in IgAN and significantly positive correlated with elevated Gd‐IgA1. In addition, we identified increased plasma ST6Gal1 levels in 100 patients with IgAN, which were associated with higher levels of proteinuria, plasma IgA, Gd‐IgA1 levels, greater degrees of systemic complement activation including C3a, Bb, C4d, MAC and a lower proportion classified as C2 grade (crescent proportion ≥25%). Interesting, in vitro, recombinant ST6Gal1 (rST6Gal1) exposure reduced the production of Gd‐IgA1 in cultured peripheral blood mononuclear cells from IgAN patients. rST6Gal1 stimuli also increased expression of C1GALT1, which were well‐known proportional to the decrease in galactose deficiency of IgA1. In conclusions, we identified increased plasma ST6Gal1 levels and the association of ST6Gal1 with disease severity of IgAN. Additionally, rST6Gal1 administration in vitro increased expression of C1GALT1 and reduced the production of Gd‐IgA1.

Increased serum and urinary mitochondrial DNA have been demonstrated in antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Here we investigated the significance of serum nicotinamide adenine dinucleotide-ubiquinone oxidoreductase chain 6 (ND6), which is encoded by mtDNA and can attract neutrophils, in AAV.Thirty-seven AAV patients (32 patients with positive myeloperoxidase-ANCA and 5 patients with proteinase 3-ANCA) were enrolled. Relationship between serum ND6 and clinico-laboratory characteristics were analyzed.The ND6 level of patients was higher than normal people (46.56 ± 23.67 pg/mL vs. 4.95 ± 2.45 pg/mL, P 0.001) The ND6 levels of patients who needed hemodialysis at disease onset and who had pulmonary hemorrhage (PH) were higher than that of the corresponding controls (P = 0.004 and 0.044 respectively). The ND6 level negatively correlated with the percentages of normal glomeruli in kidney biopsy. The AUC of ROC curve to diagnose hemodialysis and PH was 0.804 and 0.750 respectively. ND6 level positively correlated with Birmingham Vasculitis Activity Score in active disease, and returned to normal after remission. Patients with higher serum ND6 had higher mortality (P = 0.023).Serum ND6 increases in active AAV, and its level correlates with the severity of disease. High ND6 level is associated with severe organ injury and predicts poor prognosis of AAV.

Background Renal microstructure and function are closely associated with homeostasis of oxygenation. Analyzing renal blood oxygen level‒dependent (BOLD) magnetic resonance imaging (MRI) examination results will provide information on the biological status of the kidneys. The current study was performed to explore the hypoxia mode of the entire renal parenchyma in patients with lupus nephritis (LN). Methods Twenty-three adult patients with LN and eighteen healthy volunteers were recruited. R2* values were acquired through the use of the BOLD MRI analysis technique. The narrow rectangular region of interest was used to explore the hypoxia configuration in entire depths of renal parenchyma. Acquired sequential R2* data were fitted by using four categories of mathematic functions. The tendency of R2* data in both patients with LN and healthy volunteers was also compared through the use of repeated-measures analysis of variance. Results R2* data from the superficial cortex to deep medulla displayed two patterns, called a sharp uptrend style and a flat uptrend style. After sequential R2* data were fitted individually with the use of four mathematic formulas, the multiple-compartment Gaussian function showed the highest goodness of fit. Compared with two categories of R2* value styles, the R2* tendency of entire parenchyma in patients with LN was different from that in healthy volunteers. Conclusions Deep renal medullary oxygenation was not always overtly lower than oxygenation in superficial renal cortical zone. Renal parenchyma oxygenation manifestation could be described through the use of a Gaussian function model. The deoxygenation tolerance capability was damaged in patients with LN.

Background More and more studies demonstrated that genetic variation at C1GALT1 influences Gd-IgA1 level in IgAN. However, whether the expression of β1, 3-galactosyltransferase (β1, 3Gal-T) was influenced may provide insights into how Gd-IgA1 levels are controlled in IgAN. Methods Thirty IgAN patients diagnosed in Tianjin Medical University General Hospital from April to September 2018 and 30 healthy volunteers whose age and gender matched with patients were enrolled in this study. Total Gd-IgA1 levels in plasma were determined by ELISA and C1GALT1 levels were determined by RT-PCR. Four databases (PubMed, EMBASE, CNKI, WanFang Medical Network) were searched to identify eligible studies that evaluated a difference in the expression of C1GALT1 in IgAN patients compared with total controls (non-IgAN and health controls). The C1GALT1C1 expression levels, which was indispensable to β1, 3Gal-T of IgA1, was also been compared. Results Gd-IgA1 levels were remarkable higher in IgAN patients compared with healthy control. The expression levels of C1GALT1 gene were remarkably down-regulated in IgAN patients compared with healthy control. And the mRNA level of C1GALT1 was inversely correlated to Gd-IgA1 levels. In meta-analysis, six articles including 316 participants that analyzed the expression of β1, 3Gal-T were met inclusion criteria. There was no significant difference in the expression of C1GALT1 between IgAN patients compared with controls. And we found patients with IgAN had lower levels of C1GALT1 gene expression in the B cells compared to controls. The C1GALT1C1 levels in the IgAN patients were not different from the levels in the control group, which were unchanged no matter according to different ethnic population, different control group and different cell source. Two studies including 46 persons compared enzymatic activity of β1, 3Gal-T in B cells, and the result showed the β1, 3Gal-T activity was decreased in B cells. Conclusions We found expression levels of C1GALT1 were remarkably downregulated in IgAN patients and negatively correlated with higher levels of Gd-IgA1. Subsequent meta-analysis validated the low expression and activity of β1, 3Gal-T in B cells in patients with IgAN. However, there was no apparent disparity in the aspect of C1GALT1C1 expression between IgAN and control groups.

Background A systematic review and meta-analysis was performed to assess the kidney and cardiovascular (CV) outcomes of sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) stage 3b-4. Method We conducted a systematic review and meta-analysis of randomized, placebo-controlled trials (RCTs). Medline, Embase, and the Cochrane Central were searched for available trials up to Jan 18, 2021. Results From identifying 1892 citations, we included nine studies into quantitative analyses with a total of 6521 participants. In the patients with T2DM and CKD stage 3b-4, SGLT2 inhibitors significantly decreased the risk of the primary kidney outcome (HR 0.65, 95% CI 0.55–0.76) and slowed the decline in eGFR slope with a difference between treatment and control of 0.46 ml/min/1.73 m2 per year (95% CI 0.37–0.55). SGLT2 inhibitors also reduced the risk of the major adverse cardiovascular events (MACE) (HR 0.75, 95% CI 0.60–0.93). Conclusions SGLT2 inhibitors can reduce the risk of kidney disease and MACE outcomes for patients with T2DM and CKD stage 3b-4, which may be the most beneficial effects observed in the included trials.

Background The role of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) reducing risk of cardiovascular events (CVEs) and preserving kidney function in patients with chronic kidney disease is well-documented. However, the efficacy and safety of these agents in dialysis patients is still a controversial issue. Methods We systematically searched MEDLINE, Embase, Cochrane Library and Wanfang for randomized trials. The relative risk (RR) reductions were calculated with a random-effects model. Major cardiovascular events, changes in GFR and drug-related adverse events were analyzed. Results Eleven trials included 1856 participants who were receiving dialysis therapy. Compared with placebo or other active agents groups, ARB therapy reduced the risk of heart failure events by 33% (RR 0.67, 95% CI 0.47 to 0.93) with similar decrement in blood pressure in dialysis patients. Indirect comparison suggested that fewer cardiovascular events happened during treatment with ARB (0.77, 0.63 to 0.94). The results indicated no significant differences between the two treatment regimens with regard to frequency of myocardial infarction (1.0, 0.45 to 2.22), stroke (1.16, 0.69 to 1.96), cardiovascular death (0.89, 0.64 to 1.26) and all-cause mortality (0.94, 0.75 to 1.17). Five studies reported the renoprotective effect and revealed that ACEI/ARB therapy significantly slowed the rate of decline in both residual renal function (MD 0.93 mL/min/1.73 m2, 0.38 to 1.47 mL/min/1.73 m2) and urine volume (MD 167 ml, 95% CI 21 ml to 357 ml). No difference in drug-related adverse events was observed in both treatment groups. Conclusions This study demonstrates that ACE-Is/ARBs therapy decreases the loss of residual renal function, mainly for patients with peritoneal dialysis. Overall, ACE-Is and ARBs do not reduce cardiovascular events in dialysis patients, however, treatment with ARB seems to reduce cardiovascular events including heart failure. ACE-Is and ARBs do not induce an extra risk of side effects. Electronic supplementary material The online version of this article (doi:10.1186/s12882-017-0605-7) contains supplementary material, which is available to authorized users.

Background/Aims: Nephrologists have pursued ideal, dynamic and noninvasive methods for assessing renal function and disease progression. Blood oxygen level dependent (BOLD) imaging is a useful technique for assessing renal disease. This current study was performed to explore the correlation between the hypoxia iconographical index and renal pathological features in lupus nephritis. Methods: Adult patients with lupus nephritis (LN) and healthy volunteers were recruited for this study. Renal biopsy tissues were characterized based on the LNISN/RPS 2003 classification. R2* values of functional magnetic resonance parameters were acquired using the BOLD technique. The data characteristics of R2* values of different pathological patterns were calculated. Multiple correspondence analysis (MCA) was performed to explore the correlation between R2* values and clinical or pathological features. Results: A total of twenty-three patients and eighteen healthy volunteers were examined with BOLD MRI. Renal pathological patterns included five class III (including 3 class III+V), eight class IV (including 4 class IV+V) and five class IV. The mean renal R2* values in LN patients were higher than those in healthy volunteers. R2* values in class V patients were higher than those in class IV and class III. The MCA showed that higher R2* values were associated with pathological features in class V patients. Conclusions: The extent of renal hypoxia in patients with LN was more serious compared with the healthy volunteers. Differentiated mechanisms of renal oxygenation are possibly involved in proliferative and non-proliferative LN patients. R2* values may be linked with multiple clinical and pathological indexes.

Background Immunoglobulin A nephropathy (IgAN) is the leading cause of end-stage kidney disease. Previous mRNA microarray profiling studies of IgAN revealed inconsistent data. We sought to identify the aberrantly expressed genes and biological pathways by integrating IgAN gene expression datasets in blood cells and performing systematically experimental validation. We also explored the relationship between target genes and galactose-deficient IgA1 (Gd-IgA1) in IgAN. Methods We retrieved Gene Expression Omnibus (GEO) datasets of IgAN. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used for functional analysis. Deep sequencing on RNA isolated from B cells was used for microarray validation. The relationship between target mRNA expressions and Gd-IgA1 levels in serum were also studied. Results Three studies with microarray expression profiling datasets met our inclusion criteria. We identified 655 dyregulated genes, including 319 up-regulated and 336 down-regulated genes in three GEO datasets with a total of 35 patients of IgAN and 19 healthy controls. Based on biological process in GO term, these dyregulated genes are mainly related to pentose-phosphate shunt, non-oxidative branch, post-embryonic camera-type eye development and leukocyte activation. KEGG pathway analysis of microarray data revealed that these aberrantly expressed genes were enriched in human T-cell leukemia virus 1 infection, proteoglycans in cancer, intestinal immune network for IgA production and autophagy. We further performed deep sequencing on mRNAs isolated from B cells of an independent set of five patients with IgAN and three healthy persons with the same clinical and demographic characteristics. Seventy-seven genes overlapped with 655 differentially regulated genes mentioned above, including 43 up-regulated and thirty-four down-regulated genes. We next investigated whether these genes expression correlated with Gd-IgA1 levels in IgAN patients. Pearson correlation analyses showed PTEN (phosphatase and tensin homolog) was the most powerful gene negatively correlated with Gd-IgA1 levels. Conclusions These results demonstrated that dyregulated genes in patients with IgAN were enriched in intestinal immune network for IgA production and autophagy process, and PTEN in B cells might be involved in the mechanism of Gd-IgA1 production.

Aims. We investigated the changes of renal structure and its function in normal glucose tolerance (NGT), impaired glucose tolerance (IGT), diabetes mellitus (DM), and diabetic kidney disease (DKD) stages in OLETF rats and explored the role of the INS/IRS-1/PI3-K/Akt signaling pathway. Methods. OLETF rats were assigned into four groups on the basis of OGTT results and 24 h urinary microalbumin: NGT, IGT, DM, and DKD groups. The changes of renal structure and function and the corresponding pathological changes were observed. The absorption of albumin and the expression of megalin, cubilin, IRS-1, PI3-K, and Akt in NRK-52E cells were measured after being stimulated by different concentrations of insulin. Results. In the IGT group, the index which reflects the function of renal tubule-like N-acetyl-β-glucosaminidase, neutrophil gelatinase-associated lipocalin, retinol-binding protein, and cystatin C was higher than those in the control group and the NGT group (P<0.05). Significant renal structure damages, especially in renal tubules, were observed in the IGT group. In the presence of insulin at a high concentration, the IRS-1/PI3-K/Akt signaling pathway in renal tubular epithelial cells was inhibited, and the expression of megalin and cubilin was significantly downregulated which was accompanied by a minimum uptake of albumin. Conclusions. In contrast to DKD, the renal structural damage and functional changes in the IGT stage, in which we propose the term “IGT kidney disease,” mainly manifest as renal tubular injury. Insulin resistance and compensatory hyperinsulinemia may be involved in its pathogenesis.

Background: Our previous study revealed that plasma levels of a-2,6-sialyltransferase 1 (ST6GAL1) were increased in patients with IgA nephropathy (IgAN). ST6GAL1 catalyzes terminal sialylation of IgG to shift the antibody effector function to the anti-inflammatory pattern. However, the role of plasma ST6GAL1 in the progression of IgAN and underlying mechanisms are still unknown. Methods: A total of 180 IgAN patients were included. The kidney outcomes were defined as the eGFR decline or proteinuria remission. Peripheral blood mononuclear cells (PBMCs) were either stimulated with purified sialylated IgG (SA-IgG) or with non-sialylated IgG (NSA-IgG) from IgAN patients to detect the levels of interleukin (IL)-6 and tumor necrosis factor-α (TNF-α) in supernatant. Results: Compared with the lower ST6GAL1 (reference), the risk of eGFR decline decreased for the higher ST6GAL1 group after adjustment for baseline eGFR, systolic blood pressure (SBP), and proteinuria. The results showed that patients with higher ST6GAL1 levels had a higher rate of proteinuria remission. ST6GAL1, expressed as a continuous variable, was a protective factor for eGFR decline and proteinuria remission. An in vitro study showed that the administration of recombinant ST6GAL1 (rST6GAL1) decreased the levels of IL-6 and TNF-α in PBMCs. Furthermore, the administration of rST6GAL1 resulted in the enrichment of SA-IgG in a concentration-dependent manner. In addition, as compared to control, purified SA-IgG-treated PBMCs showed a significant decrease in the expression of IL-6 and TNF-α. Conclusion: Our study indicated that elevated ST6GAL1 was associated with a slower progression of IgAN, which may play a protective effect by increasing IgG sialylation to inhibit the production of proinflammatory cytokines in PBMCs.

Background: IgA nephropathy (IgAN) is a common chronic glomerular disease that, in most patients, slowly progresses to end-stage kidney disease. The therapy with corticosteroid in IgAN is still a worldwide problem that is confusing the clinicians. Methods: MEDLINE, EMBASE, the Cochrane Library, and article reference lists were searched for randomized controlled trials (RCTs) that compared corticosteroids with placebo and any other non-immunosuppressive agents in treating IgAN. Twelve RCTs involving 1,057 patients were included. Results: Overall, we found that steroids had statistically significant effects in preventing the decline in renal function (relative risk 0.42, 95% CI 0.25–0.71, p < 0.001) and reducing proteinuria (SMD: –0.58 g/day, 95% CI –0.80 to –0.36 g/day) in patients with IgAN. The association between glucocorticoid and risk of kidney outcome was not modified by steroids’ type (prednisone or methylprednisone), dose (≤30 or > 30 mg/day), duration (≤8 or > 8 months), or serum creatinine (< 1.10 or ≥1.10 mg/dL). But steroids increased the risk of side effects such as gastrointestinal and endocrinium symptoms. Conclusion: This study provides the clear beneficial effects of the steroids therapy on the kidney function and proteinuria, although it should be used with caution.

Objective Blood oxygen level-dependent magnetic resonance imaging (BOLD MRI) is a noninvasive technique useful in patients with renal disease. The current study was performed to determine whether BOLD MRI can contribute to the diagnosis of renal pathological patterns. Methods BOLD MRI was used to obtain functional magnetic resonance parameter R2* values. Gray-level co-occurrence matrixes (GLCMs) were generated for gray-scale maps. Several GLCM parameters were calculated and used to construct algorithmic models for renal pathological patterns. Results Histopathology and BOLD MRI were used to examine 12 patients. Two GLCM parameters, including correlation and energy, revealed differences among four groups of renal pathological patterns. Four Fisher’s linear discriminant formulas were constructed using two variables, including the correlation at 45° and correlation at 90°. A cross-validation test showed that the formulas correctly predicted 28 of 36 samples, and the rate of correct prediction was 77.8%. Conclusions Differences in the texture characteristics of BOLD MRI in patients with lupus nephritis may be detected by GLCM analysis. Discriminant formulas constructed using GLCM parameters may facilitate prediction of renal pathological patterns.

Rationale: The relationship between antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) and ANCA-negative vasculitis has not been elucidated. Patient concerns: A 64-year-old female with edema and proteinuria was admitted. A kidney biopsy indicated focal proliferative nephritis with crescents in 25% of glomeruli. Serum ANCA was negative. Eighteen months later, systemic symptoms emerged and acute kidney injury occurred. Serum ANCA against myeloperoxidase (MPO) turned positive. Repeated kidney biopsy showed more severe lesion than last time. Immunoglobulin (Ig)G was purified from serum obtained before the first kidney biopsy. Weak ANCA which could not be detected in serum was found in IgG. Diagnoses: MPO-ANCA-associated AAV developed from ANCA-negative renal-limited AAV. Interventions: The patient was treated with glucocorticoid. Outcomes: The serum creatinine decreased to 2.17 mg/dL a week later. MPO-ANCA turned negative when re-examined 3 weeks later. No relapse has been observed during follow-up for 6 months. Lessons: This is the first reported case about the spontaneous transformation from ANCA-negative renal-limited AAV to ANCA-positive systemic vasculitis. There might be a slow process of epitope spreading in the pathogenesis of disease. Physicians should try their best to detect the ANCA in the diagnose and treatment of ANCA-negative AAV.

Study design: Here we describe a patient who developed myelopathy due to gouty tophi of the ligamentum flavum in the thoracic spine. We also review similar cases previously reported in the literature. Objective: Our aim was to present a case of myelopathy due to thoracic spinal gouty tophus. Methods: We report the case of a 56-year-old male with history of peripheral gout and renal insufficiency. The patient complained of back pain and paraparesis of the left lower limb. Multiple tophi were noted over several interphalangeal and metatarsophalangeal joints. Neurological examination showed decreased left lower limb strength and a positive Babinski sign. Magnetic resonance imaging of the thoracic spine revealed hypertrophy of the ligamentum flavum at the level of T3/T4, T5/T6, T9/T10, T10/T11 and T11/T12. Results: A thoracic laminectomy at T1-T5 was performed. Chalky white granular material was found in the ligamentum flavum during surgery. Histological analysis of the specimen demonstrated a gouty tophus. The patient's back pain and paraparesis of the lower left limb improved. Conclusion: The clinician should include spinal gout in the differential diagnosis when dealing with patients with gout and axial pain with or without neurologic deficits. If this diagnosis is seriously entertained, then a CT scan or magnetic resonance imaging as well as tissue biopsy may be needed to establish the diagnosis.

Background/Aims: Renal pathological changes affect the motion of water molecules, which can be detected using diffusion-weighted imaging (DWI). The current study was performed to explore the correlation between renal tissue pathological injuries and DWI iconographical parameters in lupus nephritis (LN). Methods: Twenty adult patients with LN and 11 healthy volunteers were recruited. Patients with LN received renal biopsies and renal DWI-MRI inspections. The renal biopsy tissues were characterized based on the ISN/RPS 2003 classification. The volunteers, who were of comparable gender and age, only underwent renal DWI-MRI inspection. Four DWI parameters, namely, apparent diffusion coefficient (ADC), pure diffusion coefficient (Dt), pseudo-diffusion coefficient (Dp), and perfusion fraction (fp), were calculated using monoexponential and biexponential functions, respectively. Data from different renal areas and pathological pattern groups were compared. Multiple correspondence analysis (MCA) was performed to explore the correlation between each DWI index and multiple pathological features. Results: ADC, Dt, and fp values were lower in the LN group compared to the controls (P < 0.001) regardless of the renal area in the cortex and medulla. Dp values were higher in the LN group (P = 0.004). A difference in mean DWI parameters was found between three LN subgroups and the healthy volunteers, with the exception of the Dp index in the renal cortex. MCA showed that serious proliferative pathological injuries and lower ADC and Dt values were located in the same quadrant. The MCA plots of Dp and fp provided similar results. Higher Dp and fp values were located in the MCA plot quadrant with more serious proliferative pathological changes. Conclusion: DWI is a noninvasive technique that may be used to detect renal pathophysiological changes. Renal cell proliferation and intestinal fibrosis may impact the movement of water in certain microenvironments. Enhanced perfusion may be a compensatory mechanism that is associated with renal pathological injuries.

Supplemental Digital Content is available in the text, Background: LCZ696 has been introduced in patients with hypertension in several trials. Here, we performed a meta-analysis to evaluate the effect and safety of LCZ696 in hypertensive patients. Methods: PubMed, Embase, the Cochrane Library and ClinicalTrials.gov databases were searched to identify the available randomized controlled trials (RCTs) investigating the effect and safety of LCZ696 in hypertension patients. The last search date was October 31, 2018. Results: Nine RCTs with 6765 subjects were finally included, in which 8 trials compared the effect and safety between LCZ696 and angiotensin receptor antagonists (ARBs). Evidences showed LCZ696, compared with ARBs, achieved a better blood pressure control rate (OR 1.24, 95% CI: 1.14–1.35), specifically, LCZ696 were better at reducing systolic blood pressure [WMD −4.11 mmHg, 95% CI: (−5.13, −3.08) mmHg], diastolic blood pressure [WMD −1.79 mmHg, 95% CI: (−2.22, −1.37) mmHg], mean 24-hour ambulatory systolic blood pressure [WMD −3.24 mmHg, 95% CI: (−4.48, −1.99) mmHg] and mean 24-hour ambulatory diastolic blood pressure [WMD −1.25 mmHg, 95% CI: (−1.81, −0.69) mmHg]. There was no difference in the events of adverse events (risk ratio [RR] 1.01, 95% CI: 0.39–1.09), serious adverse events (RR 0.80, 95% CI: 0.52–1.22) and discontinuation of treatment for any adverse events (RR 0.79, 95% CI: 0.56–1.11) between LCZ696 group and ARB/placebo group, except LCZ696 reduced the rate of headaches (RR 0.69, 95% CI: 0.48-0.99) while increased cough (RR 2.12, 95% CI: 1.11–4.04; P = .02; I2 = 25%). Conclusion: Our finding provides evidence that LCZ 696 was more effective than ARB on blood pressure control and was safe enough in patients with hypertension.

Rationale: Angiotensin receptor blocker (ARB) can increase serum creatinine or potassium levels in patients with renal insufficiency, renal artery stenosis, heart failure or hypovolemia, but hardly cause severe kidney injury in patients without any risk factors. A case of severe acute interstitial nephritis (AIN) induced by valsartan was reported here. Patient concerns: A 62-year-old female with nausea for 1 month and acute deterioration of kidney function for 2 weeks was admitted. She had a history of hypertension for 5 months and had taken valsartan 40 mg daily for 4 months. Although the valsartan had been stopped for 2 weeks, the serum creatinine continuously increased after admission. Kidney biopsy demonstrated the eosinophils infiltration in interstitium. Diagnoses: AIN induced by valsartan. Interventions: The patient was treated with glucocorticoid. Outcomes: The serum creatinine decreased gradually and got back to normal level 5 months later. Then therapy of glucocorticoid was stopped. Renal artery stenosis was excluded by computed tomography angiography (CTA). Lessons: Although valsartan-induced allergy has been reported previously, AIN was firstly recognized as a severe complication of this drug. We suggest when there is a ARB-associated continuous deterioration of kidney function for patients without renal insufficiency, renal artery stenosis, heart failure or hypovolemia, AIN should be thought of and therapy with glucocorticoid should be considered if necessary.

Membranous nephropathy (MN) is a rare manifestation of IgG4-related disease. Interestingly, the significance of IgG4 has also been documented in idiopathic MN (IMN). Previous studies reported that urine IgG4/IgG ratios were significantly higher in IMN compared with other kinds of nephropathy, indicating that impairment of charge selectivity barrier seemed to be an obvious characteristic of IMN. Although high blood concentration of IgG4 is very common in IgG4-related MN, no study about the urine IgG4 has been described before. Here, we present a 55-year-old male with IgG4-related MN. Complete remission of proteinuria was promptly achieved by glucocorticoid treatment without immunosuppressant. Consistent with previous reports, the serum antibody against M-type phospholipase A2 receptor was negative. Surprisingly, although the blood concentration of IgG4/IgG reached as high as 36 %, the urine concentration of IgG4/IgG was only 5 %. The calculated ratio of the renal clearance of IgG4 to IgG of this patient (0.15) was obviously lower than that of five patients with IMN (0.53∼0.81). We speculated that this phenomenon might be a clue of the different pathogenesis between IgG4-related MN and IMN.