Serum Phosphorus Might Be a Predictor of Kidney Disease Progression in IgA Nephropathy.

INTRODUCTION: High serum phosphorus level has been reported to be a risk factor for disease progression in patients with chronic kidney disease, whereas, its role in IgA nephropathy (IgAN) still remains uncertain. This study aimed to investigate the association between serum phosphorus and progression of IgAN. METHODS: A total of 247 patients diagnosed with IgAN from 2016.11 to 2019.12 at the First Affiliated Hospital of Xi'an Jiaotong University were retrospectively enrolled in this study. The association between serum phosphorus and kidney disease progression events, defined as 30% estimated glomerular filtration rate (eGFR) decline or kidney failure, was evaluated using Cox models. RESULTS: Serum phosphorus was an independent risk factor for poor renal outcome after adjusting for age, gender, urine protein, MAP, eGFR, hemoglobin, Oxford S and T scores (HR, 2.586; 95% CI, 1.238-5.400, p = 0.011). The addition of serum phosphorus to the reference model containing clinical and pathological variables significantly improved the risk prediction of IgAN progression (C statistic, 0.836; 95% CI, 0.783-0.889) as compared with the reference model (C statistic, 0.821; 95% CI, 0.756-0.886). The ability of serum phosphorus level to predict progression was much stronger in IgAN patients without use of immunosuppression (HR 5.173; 95% CI, 1.791-14.944; p = 0.002). CONCLUSION: Higher serum phosphorus levels were independently associated with kidney disease progression in patients with IgAN, especially in those without immunosuppression. The addition of serum phosphorus to clinical and pathological data at the time of biopsy significantly improved risk prediction of IgAN progression.

The association of serum anti-PLA2R antibody and glomerular PLA2R antigen staining with clinical manifestations and outcomes in membranous nephropathy.

BACKGROUND: Phospholipase A2 receptor (PLA2R)-associated membranous nephropathy (MN) was manifested as seropositive for PLA2R antibodies (SAb) and/or glomerular PLA2R antigens' (GAg) deposits. According to the test of SAb and GAg, PLA2R-associated MN can be divided into SAb + /GAg-, SAb-/GAg + , and SAb + /GAg + groups. The clinical characteristics and outcomes of the three groups need to be further evaluated. METHODS: 184 PLA2R-associated MN patients were enrolled. SAb was measured by enzyme-linked immunosorbent assay with a cut-off value of 14 RU/mL. GAg was detected by immunofluorescence using a paraffin section of renal biopsy samples. Clinical characteristics and the decline of eGFR were compared among the 3 groups. RESULTS: There were 33 SAb + /GAg-, 46 SAb-/GAg +, and 105 SAb + /GAg + PLA2R-associated MN patients reviewed. Clinical characteristics, such as the level of proteinuria, serum albumin, as well as eGFR, were comparable between the SAb + /GAg- and SAb + /GAg + patients. While SAb-/GAg + patients exhibited mild clinical manifestations as evidenced by higher serum albumin (P < 0.001) and lower proteinuria (p = 0.049) compared with SAb + /GAg + patients. After 21.96 ± 7.39 month follow-up, the eGFR decrease was no difference between the SAb + /GAg- and SAb + /GAg + patients. SAb-/GAg + patients had a lower rate of the > 20% eGFR decline as well as a 50% eGFR decline compared with the SAb + /GAg + patients (10.87% vs 30.48%, p = 0.013; 0.00% vs 4.76%, p = 0.324). CONCLUSIONS: Our study showed that the clinical manifestations of SAb + /Gag- patients were the same as those of double-positive patients, while SAb-/GAg + patients exhibited mild clinical manifestations and slower eGFR decline compared to the double-positive patients.

Chimeric Fusion between Clostridium Ramosum IgA Protease and IgG Fc Provides Long-Lasting Clearance of IgA Deposits in Mouse Models of IgA Nephropathy.

BACKGROUND: IgA nephropathy is a common primary glomerulonephritis caused by mesangial deposition of poly-IgA complexes. The disease follows a variable course of clinical progression, with a high risk of kidney failure. Although no specific therapy is available, enzymatic strategies to clear IgA deposits are being considered for the treatment of rapidly progressive IgA nephropathy. METHODS: We chose an IgA protease of commensal bacterium Clostridium ramosum, termed AK183, as the template for constructing a recombinant biologic. To extend the t1/2 in blood, we fused AK183 to the Fc segment of human IgG1. Activities of this Fc-AK183 fusion protein toward the cleavage and subsequent clearance of IgA were tested in mouse models. RESULTS: First, we discovered an autocleavage activity of AK183 that separates the N-terminal protease from its C-terminal autotransporter ß domain. Therefore, we grafted Fc to the N terminus of AK183 and demonstrated its week-long enzymatic activity in mice. In addition, the proteolytic fragments of IgA generated in the reaction with Fc-AK183 were effectively removed from circulation via kidney filtration. The combined actions of Fc-AK183-mediated cleavage and subsequent renal clearance of IgA resulted in a lasting obliteration of blood IgA, as demonstrated in a human IgA-injection model and in a humanized α1KI transgenic model. Fc-AK183 was also able to remove chronic IgA and associated complement C3 deposits in the glomerulus. CONCLUSION: We constructed a chimeric fusion of IgA protease with Fc and demonstrated its long-lasting efficacy as a promising targeted therapy for IgA nephropathy in mouse models.

Clinical features and outcomes of patients with antineutrophil cytoplasmic antibody-positive systemic lupus erythematosus.

Purpose: To investigate the clinical characteristics, pathological features, and outcomes of patients with antineutrophil cytoplasmic antibody (ANCA)-positive systemic lupus erythematosus (SLE) in northwest China.Methods: This retrospective study included 491 patients with SLE tested for ANCA antibodies and 171 patients with ANCA-associated vasculitis (AAV) as controls. Subgroup analysis limited to those with renal involvement, and by ANCA antibody subtype (PR3 vs MPO). To compare the proteinuria remission rates between ANCA-positive and ANCA-negative lupus nephritis (LN) groups, a logistic regression model was used for propensity score matching based on age, hemoglobin, and baseline estimated glomerular filtration rate (eGFR).Results: Compared to ANCA-negative SLE (n = 442), ANCA-positive SLE (n = 46) occur in older patients; however, these patients were younger than those with AAV (n = 167). The eGFR of patients with ANCA-positive LN (n = 25) was higher than that of patients having AAV with renal involvement (n = 56) but lower than that of patients with ANCA-negative LN (n = 163). Patients with SLE who had MPO-ANCA (n = 16) had higher levels of serum creatinine compared to those with PR3-ANCA (n = 30) (156.5 µmol/L vs. 45.5 µmol/L, p = 0.005). During the follow-up period, the remission rate of proteinuria in patients with ANCA-positive LN was lower than that of patients with ANCA-negative LN (50% vs. 75%, p = 0.008).Conclusion: Patients with ANCA-positive LN may have worse baseline renal function and lower protein remission rates compared to patients with ANCA-negative LN. ANCA titers should be regularly monitored throughout the follow-up period in patients with SLE, especially in cases of renal involvement.

Renal deposition and clearance of recombinant poly-IgA complexes in a model of IgA nephropathy.

IgA nephropathy (IgAN) is the most common type of glomerulonephritis worldwide, which follows a chronic but nonetheless highly variable course of progression. IgA immune complexes are the primary source of renal deposits in IgAN. Apart from the presence of granular IgA1 deposits in the glomerular mesangium and mesangial hypercellularity as common features, the detailed process of IgA1 deposition and clearance in the kidney remains unclear. We sought to examine the dynamics of IgA deposition and tissue plasticity in response to deposits including their intrarenal clearance. We followed a synthetic approach to produce a recombinant fusion between IgA Fc (rIgA) and a biotin tag, which was subsequently induced with streptavidin (SA) to form an oligomeric poly-IgA mimic. Both uninduced rIgA (mono-rIgA) and polymeric SA-rIgA (poly-rIgA) were injected intravenously into Wistar rats. Plasma IgA levels and renal and liver histology were examined in a time series. In contrast to mono-rIgA, this synthetic poly-rIgA analog formed renal deposits exclusively in the glomerulus and were mostly cleared in 3 h. However, repeated daily injections for 12 days caused long-lasting and stronger glomerular IgA deposition together with IgG and complement C3, in association with mesangial cell proliferation, matrix expansion, and variable degrees of albuminuria and hematuria that phenocopied IgAN. Ex vivo, poly-rIgA bound cultured mesangial cells and elicited cytokine production, in addition to activating plasma C3 that was consistent with the actions of IgA immune complexes in IgAN pathogenesis. Remarkably, the kidneys were able to reverse all pathologic manifestations and restore normal glomerular histology 2 weeks after injections were halted. The synthetic model showed the kinetics between the intricate balance of renal deposition and clearance, as well as glomerular plasticity towards healing. Together, the results revealed a priming effect of existing deposits in promoting stronger and longer-lasting IgA deposition to cause renal damage. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

New soluble angiopoietin analog of Hepta-ANG1 prevents pathological vascular leakage.

Vascular leak is a key driver of organ injury in diseases, and strategies that reduce enhanced permeability and vascular inflammation are promising therapeutic targets. Activation of the angiopoietin-1 (ANG1)-Tie2 tyrosine kinase signaling pathway is an important regulator of vascular quiescence. Here we describe the design and construction of a new soluble ANG1 mimetic that is a potent activator of endothelial Tie2 in vitro and in vivo. Using a chimeric fusion strategy, we replaced the extracellular matrix (ECM) binding and oligomerization domain of ANG1 with a heptameric scaffold derived from the C-terminus of serum complement protein C4-binding protein α. We refer to this new fusion protein biologic as Hepta-ANG1, which forms a stable heptamer and induces Tie2 phosphorylation in cultured cells, and in the lung following intravenous injection of mice. Injection of Hepta-ANG1 ameliorates vascular endothelial growth factor- and lipopolysaccharide-induced vascular leakage, in keeping with the known functions of Angpt1-Tie2 in maintaining quiescent vascular stability. The new Hepta-ANG1 fusion is easy to produce and displays remarkable stability with high multimericity that can potently activate Tie2. It could be a new candidate ANG1 mimetic therapy for treatments of inflammatory vascular leak, such as acute respiratory distress syndrome and sepsis.

O-glycoforms of polymeric immunoglobulin A1 in the plasma of patients with IgA nephropathy are associated with pathological phenotypes.

BACKGROUND: Immunoglobulin A1 (IgA1) O-glycosylation plays an important role in the pathogenesis of IgA nephropathy (IgAN). However, variations in IgA1 O-glycoforms have not been explored. We aimed to investigate the IgA1 O-glycoforms in the hinge region (HR) of polymeric IgA1 (pIgA1) and then evaluate the association between IgA1 O-glycoforms and crescent formation in IgAN. METHODS: The discovery cohort (Cohort 1) comprised 11 crescentic IgAN patients, 10 noncrescentic IgAN patients and 10 healthy controls and the validation cohort (Cohort 2) comprised 11 crescentic IgAN patients, 9 noncrescentic IgAN patients and 9 healthy controls. A total of 143 IgAN patients with different crescent percentages (Cohort 3) were also included. pIgA1 was purified from the plasma of the participants. The variation in O-glycoforms was evaluated by estimating the molecular weights of IgA1 hinge glycopeptides using reversed-phase liquid chromatography and tandem mass spectrometry under electron-transfer/higher-energy collision dissociation fragmentation mode. RESULTS: In the discovery cohort (Cohort 1), the number of N-acetylgalactosamine (GalNAc) bound to one HR was lower in IgAN patients. The proportions of GalNAc3 (defined as O-glycans bound to one HR at three sites) and GalNAc4 were highest in crescentic IgAN patients, followed by noncrescentic IgAN patients, and were lowest in healthy controls [GalNAc 3: 9.92 ± 3.37% versus 6.65 ± 1.53% versus 4.05 ± 1.24% (P < 0.001); GalNAc4: 45.91 ± 4.75% versus 41.13 ± 2.95% versus 40.98 ± 2.95% (P = 0.004), respectively]. The proportions of GalNAc5 and GalNAc6 were lowest in crescentic IgAN patients followed by noncrescentic IgAN patients and were highest in healthy controls [GalNAc5: 50.15 ± 4.27% versus 47.92 ± 4.09% versus 45.87 ± 3.79% (P = 0.028); GalNAc6: 6.58 ± 2.53% versus 6.04 ± 1.35% versus 4.65 ± 2.27% (P = 0.034), respectively]. These results were consistent in the validation cohort (Cohort 2). In another cohort with 143 patients with different crescent percentages (Cohort 3), the number of GalNAc in pIgA1 decreased with an increasing percentage of crescents. CONCLUSIONS: The number of GalNAc in IgA1 HRs was lower in IgAN patients, especially in crescentic IgAN patients, and may be associated with a severe IgAN phenotype.

Plasma galactose-deficient immunoglobulin A1 and loss of kidney function in patients with immunoglobulin A vasculitis nephritis.

BACKGROUND: Immunoglobulin A (IgA) vasculitis nephritis (IgAV-N) is the most common secondary IgA nephropathy (IgAN). Many studies have demonstrated that galactose-deficient IgA1 (Gd-IgA1) in the IgA1 hinge region is associated with the development and also progression of primary IgAN. In this study, we aimed to evaluate the roles of Gd-IgA1 in kidney disease progression in a large Chinese cohort of IgAV-N patients. METHODS: This cohort study enrolled 112 patients with IgAV-N, 15 patients with IgA vasculitis (IgAV) without kidney involvement and 108 patients with IgAN. Plasma IgA1 and Gd-IgA1 levels at kidney biopsy were measured by enzyme-linked immunosorbent assay. The primary endpoint was a 30% decline in estimated glomerular filtration rate or end-stage renal disease or death. RESULTS: The levels of Gd-IgA1 in IgAV-N and IgAN patients were higher than in healthy controls (mean ± SD, 302.86 ± 54.93 U/mL versus 303.16 ± 59.43 U/mL versus 281.30 ± 43.74 U/mL, respectively; P = 0.047), as well as compared with those with IgAV without kidney involvement (272.65 ± 53.14 U/mL; P = 0.036). After adjusting clinical data, higher levels of Gd-IgA1 were found to be independently associated with a greater risk for kidney failure [hazard ratio (HR) = 1.703 per 1 SD, 95% confidence interval (CI) 1.233-2.352; P = 0.001]. Compared with the first Gd-IgA1 quartile group (as reference), the fourth Gd-IgA1 quartile group retained a predictive value for poor renal outcome (HR = 3.740, 95% CI 1.204-11.619; P = 0.023). CONCLUSIONS: These data indicate that Gd-IgA1 levels were similarly elevated in adult patients with IgAN and those with IgAV-N. Moreover, increased Gd-IgA1 levels were associated with both the development and progression of IgAV-N, as observed in IgAN.

What is the impact of human leukocyte antigen mismatching on graft survival and mortality in renal transplantation? A meta-analysis of 23 cohort studies involving 486,608 recipients.

BACKGROUND: The magnitude effects of human leukocyte antigen (HLA) mismatching on post-transplant outcomes of kidney transplantation remain controversial. We aim to quantitatively assess the associations of HLA mismatching with graft survival and mortality in adult kidney transplantation. METHODS: We searched PubMed, EMBASE and the Cochrane Library from their inception to December, 2016. Priori clinical outcomes were overall graft failure, death-censored graft failure and all-cause mortality. RESULTS: A total of 23 cohort studies covering 486,608 recipients were selected. HLA per mismatch was significant associated with increased risks of overall graft failure (hazard ratio (HR), 1.06; 95% confidence interval (CI), 1.05-1.07), death-censored graft failure (HR: 1.09; 95% CI 1.06-1.12) and all-cause mortality (HR: 1.04; 95% CI: 1.02-1.07). Besides, HLA-DR mismatches were significant associated with worse overall graft survival (HR: 1.12, 95% CI: 1.05-1.21). For HLA-A locus, the association was insignificant (HR: 1.06; 95% CI: 0.98-1.14). We observed no significant association between HLA-B locus and overall graft failure (HR: 1.01; 95% CI: 0.90-1.15). In subgroup analyses, we found recipient sample size and ethnicity maybe the potential sources of heterogeneity. CONCLUSIONS: HLA mismatching was still a critical prognostic factor that affects graft and recipient survival. HLA-DR mismatching has a substantial impact on recipient's graft survival. HLA-A mismatching has minor but insignificant impact on graft survival outcomes.

Comparison of LC-MS/MS vs chemiluminescent microparticle immunoassay in measuring the valproic acid concentration in plasma of epilepsy patients in a new perspective.

OBJECTIVES: This study was designed to compare the performance of LC-MS/MS with chemiluminescent microparticle immunoassay (CMIA) for determination of VPA in epilepsy patients in the perspective of metabolites' hepatotoxicity. METHOD: Samples were collected and then analyzed using both LC-MS/MS and CMIA. A LO2 cells (normal human hepatic cells) experiment was carried out to confirm VPA metabolites' hepatotoxicity using AST(Aspertate Aminotransferase, AST), ALT(Alanine aminotransferase, ALT) and LDH(lactate dehydrogenase, LDH) in supernate as index. RESULTS: The regression equation analysis showed as LC-MS/MS=1.0094CMIA-1.8937, with the concordance correlation coefficient of 0.9700, and the CUSUM test proved no significant deviation from linearity (P>.05). CMIA compared to LC-MS/MS gave a positive bias of 1.2 µg/mL. In LO2 experiment, VPA and its metabolites groups showed an obvious increment of AST, ALT, and LDH in supernate. CONCLUSION: The LC-MS/MS is largely consistent with the CMIA in analytical time and quantification ability for VPA, but the LC-MS/MS can simultaneously determinate VPA and its metabolites in plasma, and is also a higher cost-efficiency method in consideration of toxic metabolites monitoring. The overestimation of VPA by CMIA showed no clinical significance. The metabolites 3-OH-VPA and 5-OH-VPA damage the LO2 cells and the results presented a statistical significance (P<.05). It is vital to monitor the metabolites' concentrations for VAP's clinical safety application, and now is the occasion that laboratory and clinic consider the LC-MS/MS method as a more advantageous alternative to CMIA method in therapeutic monitoring of VPA.

Characteristics of patients with coexisting IgA nephropathy and membranous nephropathy.

BACKGROUND: Coexistence of IgA nephropathy (IgAN) and membranous nephropathy (MN) in the same patient is rare. Few studies have reported the clinical and pathological features of patients with combined IgAN and MN (IgAN-MN). METHODS: The clinico-pathological features, levels of galactose-deficient IgA1 (Gd-IgA1) and autoantibodies against M-type transmembrane phospholipase A2 receptor (anti-PLA2R) in sera were compared among IgAN-MN, IgAN, and MN patients. RESULTS: Twenty-six patients with biopsy-proven IgAN-MN were enrolled. The mean age at biopsy was 43.6 ± 15.9 years, and 65.4% were male. Proteinuria and estimated glomerular filtration rate (eGFR) levels in patients with IgAN-MN were similar to that of MN patients. Compared with the IgAN patients, IgAN-MN patients showed a higher median proteinuria level (4.3 vs. 1.2 g/day, p < .001), and a higher mean eGFR level (101.8 ± 25.4 vs. 78.6 ± 26.9 mL/min/1.73 m2, p < .001). IgAN-MN patients presented with milder pathological lesions than IgAN patients according to the Oxford Classification. IgAN-MN patients had comparable serum levels of Gd-IgA1 with those of IgAN patients (353.4 ± 95.5 vs. 347.0 ± 109.6 U/mL, p = .801). Percentage of IgAN-MN patients with detectable serum levels of anti-PLA2R was lower than that of MN patients (38.5% vs. 68.6%, p = .011). CONCLUSIONS: IgAN-MN patients display similar clinical features to MN patients and milder pathological lesions than IgAN patients. IgAN-MN patients have similar levels of Gd-IgA1 to those of IgAN patients, and a lower proportion of anti-PLA2R than MN patients.

Effects of intensive blood pressure lowering on cardiovascular and renal outcomes: updated systematic review and meta-analysis.

BACKGROUND: Recent hypertension guidelines have reversed previous recommendations for lower blood pressure targets in high-risk patients, such as those with cardiovascular disease, renal disease, or diabetes. This change represents uncertainty about whether more intensive blood pressure-lowering strategies are associated with greater reductions in risk of major cardiovascular and renal events. We aimed to assess the efficacy and safety of intensive blood pressure-lowering strategies. METHODS: For this updated systematic review and meta-analysis, we systematically searched MEDLINE, Embase, and the Cochrane Library for trials published between Jan 1, 1950, and Nov 3, 2015. We included randomised controlled trials with at least 6 months' follow-up that randomly assigned participants to more intensive versus less intensive blood pressure-lowering treatment, with different blood pressure targets or different blood pressure changes from baseline. We did not use any age or language restrictions. We did a meta-analysis of blood pressure reductions on relative risk (RR) of major cardiovascular events (myocardial infarction, stroke, heart failure, or cardiovascular death, separately and combined), and non-vascular and all-cause mortality, end-stage kidney disease, and adverse events, as well as albuminuria and progression of retinopathy in trials done in patients with diabetes. FINDINGS: We identified 19 trials including 44,989 participants, in whom 2496 major cardiovascular events were recorded during a mean 3·8 years of follow-up (range 1·0-8·4 years). Our meta-analysis showed that after randomisation, patients in the more intensive blood pressure-lowering treatment group had mean blood pressure levels of 133/76 mm Hg, compared with 140/81 mm Hg in the less intensive treatment group. Intensive blood pressure-lowering treatment achieved RR reductions for major cardiovascular events (14% [95% CI 4-22]), myocardial infarction (13% [0-24]), stroke (22% [10-32]), albuminuria (10% [3-16]), and retinopathy progression (19% [0-34]). However, more intensive treatment had no clear effects on heart failure (15% [95% CI -11 to 34]), cardiovascular death (9% [-11 to 26]), total mortality (9% [-3 to 19]), or end-stage kidney disease (10% [-6 to 23]). The reduction in major cardiovascular events was consistent across patient groups, and additional blood pressure lowering had a clear benefit even in patients with systolic blood pressure lower than 140 mm Hg. The absolute benefits were greatest in trials in which all enrolled patients had vascular disease, renal disease, or diabetes. Serious adverse events associated with blood pressure lowering were only reported by six trials and had an event rate of 1·2% per year in intensive blood pressure-lowering group participants, compared with 0·9% in the less intensive treatment group (RR 1·35 [95% CI 0·93-1·97]). Severe hypotension was more frequent in the more intensive treatment regimen (RR 2·68 [1·21-5·89], p=0·015), but the absolute excess was small (0·3% vs 0·1% per person-year for the duration of follow-up). INTERPRETATION: Intensive blood pressure lowering provided greater vascular protection than standard regimens. In high-risk patients, there are additional benefits from more intensive blood pressure lowering, including for those with systolic blood pressure below 140 mmHg. The net absolute benefits of intensive blood pressure lowering in high-risk individuals are large. FUNDING: National Health and Medical Research Council of Australia.

Comparative Effectiveness of 12 Treatment Strategies for Preventing Contrast-Induced Acute Kidney Injury: A Systematic Review and Bayesian Network Meta-analysis.

BACKGROUND: To simultaneously evaluate the relative efficacy of multiple pharmacologic strategies for preventing contrast-induced acute kidney injury (AKI). STUDY DESIGN: Systematic review containing a Bayesian network meta-analysis of randomized controlled trials. SETTING & POPULATION: Participants undergoing diagnostic and/or interventional procedures with contrast media. SELECTION CRITERIA FOR STUDIES: Randomized controlled trials comparing the active drug treatments with each other or with hydration alone. INTERVENTION: Any of the following drugs in combination with hydration: N-acetylcysteine (NAC), theophylline (aminophylline), fenoldopam, iloprost, alprostadil, prostaglandin E1, statins, statins plus NAC, bicarbonate sodium, bicarbonate sodium plus NAC, ascorbic acid (vitamin C), tocopherol (vitamin E), α-lipoic acid, atrial natriuretic peptide, B-type natriuretic peptide, and carperitide. OUTCOMES: The occurrence of contrast-induced AKI. RESULTS: The trial network included 150 trials with 31,631 participants and 4,182 contrast-induced AKI events assessing 12 different interventions. Compared to hydration, ORs (95% credible intervals) for contrast-induced AKI were 0.31 (0.14-0.60) for high-dose statin plus NAC, 0.37 (0.19-0.64) for high-dose statin alone, 0.37 (0.17-0.72) for prostaglandins, 0.48 (0.26-0.82) for theophylline, 0.62 (0.40-0.88) for bicarbonate sodium plus NAC, 0.67 (0.54-0.81) for NAC alone, 0.64 (0.41-0.95) for vitamins and analogues, 0.70 (0.29-1.37) for natriuretic peptides, 0.69 (0.31-1.37) for fenoldopam, 0.78 (0.59-1.01) for bicarbonate sodium, and 0.98 (0.41-2.07) for low-dose statin. High-dose statin plus NAC or high-dose statin alone were likely to be ranked the best or the second best for preventing contrast-induced AKI. The overall results were not materially changed in metaregressions or subgroup and sensitivity analyses. LIMITATIONS: Patient-level data were unavailable; unable to include some treatment agents; low event rates; imbalanced distribution of participants among treatment strategies. CONCLUSIONS: High-dose statins plus hydration with or without NAC might be the preferred treatment strategy to prevent contrast-induced AKI in patients undergoing diagnostic and/or interventional procedures requiring contrast media.

Effect of human leukocyte antigen mismatching on the outcomes of pediatric kidney transplantation: a systematic review and meta-analysis.

BACKGROUND: Kidney transplantation is regarded as the optimal treatment for pediatric patients with end-stage renal disease. Here, we address a controversial topic in pediatric kidney transplantation by performing a quantitative evaluation of the effect of human leukocyte antigen (HLA) mismatching on the outcomes of pediatric kidney transplantation. METHODS: We systematically searched PubMed, EMBASE and the Cochrane Library from their inception to 31 December 2016 for cohort studies assessing the risk ratio (RR) of HLA mismatching on pediatric kidney transplantation. Outcome measures included graft failure, rejection and all-cause mortality. RRs and 95% confidence intervals (CIs) were used as estimates of effect size in random-effect models. RESULTS: Eighteen studies comprising a total of 26 018 pediatric recipients were included in the evaluation. Compared with 0-1 HLA-DR mismatch, 2 mismatches significantly increased the risk of graft failure at 1 year (RR: 1.41, 95% CI: 1.11-1.80), 3 years (RR: 1.28, 95% CI: 1.08-1.52), 5 years (RR: 1.21, 95% CI: 1.04-1.41) and 10 years (RR: 1.30, 95% CI: 1.02-1.67). For HLA-A + B, the 5-year graft failure risk was higher for 2-4 mismatches compared with 0-1 mismatch (RR: 3.17, 95% CI: 1.20-8.36), but not for 3-4 compared with 0-2 mismatches (RR: 1.49, 95% CI: 0.79-2.80). CONCLUSIONS: Based on pooled analysis, HLA-DR and HLA-A + B are important factors affecting post-transplant outcomes, especially graft failure, in pediatric recipients. Additional randomized controlled trials with higher quality evidence are needed for further investigation.

UV-C treatment on physiological response of potato (Solanum tuberosum L.) during low temperature storage.

The storage of potato tuber (Solanum tuberosum L.) at low temperatures minimizes sprouting and disease but can cause cold-induced sweetening (CIS), which leads to the production of the cancerogenic substance acrylamide during the frying processing. The aim of this research was to investigate the effects of UV-C treatment on CIS in cold stored potato tuber. 'Atlantic' potatoes were treated with UV-C for an hour and then stored at 4 °C up to 28 days. The UV-C treatment significantly prevented the increase of malondialdehyde content (an indicator of the prevention of oxidative injury) in potato cells during storage. The accumulation of reducing sugars, particularly fructose and glucose, was significantly reduced by UV-C treatment possibly due to the regulation of the gene cascade, sucrose phosphate synthase, invertase inhibitor 1/3, and invertase 1 in potato tuber, which were observed to be differently expressed between treated and untreated potatoes during low temperature storage. In summary, UV-C treatment prevented the existence of oxidative injury in potato cells, thus, lowered the amount of reducing sugar accumulation during low temperature storage of potato tubers.

Effect of Statins on Kidney Disease Outcomes: A Systematic Review and Meta-analysis.

BACKGROUND: The effects of statin administration on kidney disease outcomes remain controversial. We undertook a systematic review and meta-analysis to assess the efficacy of statins on kidney outcomes. STUDY DESIGN: We conducted a meta-analysis of randomized controlled trials (RCTs) using MEDLINE (1946 to August 31, 2015), EMBASE (1966 to August 31, 2015), and the Cochrane Library database (no date restriction). SETTING & POPULATION: Adults who were not receiving dialysis, for whom kidney disease outcomes were reported. SELECTION CRITERIA FOR STUDIES: RCTs in which statins were given for at least 6 months and kidney outcomes were measured. INTERVENTION: Statins versus control, including placebo, usual care, and different types or doses of statins. OUTCOMES: Kidney failure events, rate of change in estimated glomerular filtration rate (eGFR) per year, change in proteinuria or albuminuria, and, in patients with chronic kidney disease, major cardiovascular events. RESULTS: 57 eligible studies with 143,888 participants were included. Statin treatment did not produce an apparent beneficial effect for kidney failure events (OR, 0.98; 95% CI, 0.87-1.10; P=0.7) or end-stage renal disease events (OR, 0.98; 95% CI, 0.90-1.07; P=0.7). However, mean difference for rate of decline in eGFR (0.41 [95% CI, 0.11-0.70] mL/min/1.73m(2) per year slower in statin recipients) and standardized mean difference for change in proteinuria or albuminuria (-0.65 [95% CI, -0.94 to -0.37] standard deviation units, statin recipients vs controls) were statistically significant. In addition, statin therapy significantly reduced the risk for cardiovascular events (OR, 0.69; 95% CI, 0.61-0.79; P<0.001) in patients with chronic kidney disease. LIMITATIONS: Inclusion of several post hoc analyses from large RCTs and substantial heterogeneity in secondary outcome analyses. CONCLUSIONS: Statin therapy does not reduce the risk for kidney failure events in adults not receiving dialysis for whom kidney disease outcomes were reported, but may modestly reduce proteinuria and rate of eGFR decline.

Renin-Angiotensin System Inhibitors and Kidney and Cardiovascular Outcomes in Patients With CKD: A Bayesian Network Meta-analysis of Randomized Clinical Trials.

BACKGROUND: There is much uncertainty regarding the relative effects of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) in populations with chronic kidney disease (CKD). STUDY DESIGN: Systematic review and Bayesian network meta-analysis. SETTING & POPULATION: Patients with CKD treated with renin-angiotensin system (RAS) inhibitors. SELECTION CRITERIA FOR STUDIES: Randomized trials in patients with CKD treated with RAS inhibitors. PREDICTOR: ACE inhibitors and ARBs compared to each other and to placebo and active controls. OUTCOME: Primary outcome was kidney failure; secondary outcomes were major cardiovascular events, all-cause death. RESULTS: 119 randomized controlled trials (n = 64,768) were included. ACE inhibitors and ARBs reduced the odds of kidney failure by 39% and 30% (ORs of 0.61 [95% credible interval, 0.47-0.79] and 0.70 [95% credible interval, 0.52-0.89]), respectively, compared to placebo, and by 35% and 25% (ORs of 0.65 [95% credible interval, 0.51-0.80] and 0.75 [95% credible interval, 0.54-0.97]), respectively, compared with other active controls, whereas other active controls did not show evidence of a significant effect on kidney failure. Both ACE inhibitors and ARBs produced odds reductions for major cardiovascular events (ORs of 0.82 [95% credible interval, 0.71-0.92] and 0.76 [95% credible interval, 0.62-0.89], respectively) versus placebo. Comparisons did not show significant effects on risk for cardiovascular death. ACE inhibitors but not ARBs significantly reduced the odds of all-cause death versus active controls (OR, 0.72; 95% credible interval, 0.53-0.92). Compared with ARBs, ACE inhibitors were consistently associated with higher probabilities of reducing kidney failure, cardiovascular death, or all-cause death. LIMITATIONS: Trials with RAS inhibitor therapy were included; trials with direct comparisons of other active controls with placebo were not included. CONCLUSIONS: Use of ACE inhibitors or ARBs in people with CKD reduces the risk for kidney failure and cardiovascular events. ACE inhibitors also reduced the risk for all-cause mortality and were possibly superior to ARBs for kidney failure, cardiovascular death, and all-cause mortality in patients with CKD, suggesting that they could be the first choice for treatment in this population.