Hypertension has been shown to be an important risk factor in IgA nephropathy (IgAN). The 2021 the Kidney Disease Improving Global Outcomes (KDIGO) Guideline proposes a target systolic blood pressure (SBP) of less than 120 mmHg in patients with Chronic Kidney Disease (CKD) not receiving dialysis. However, whether lowering SBP from <140- <120 mm Hg is renoprotective is unknown. This study aims to evaluate the association of SBP and the progression of IgAN, then explore whether lowering SBP from <140- <120 mm Hg is renoprotective.Overall, 2,240 patients with IgAN were enrolled in this study. Cox proportional hazards models and restricted cubic splines were used to estimate the associations between SBP and kidney failure events which are defined as 50% estimated glomerular filtration rate (eGFR) decline or kidney failure.After a median follow-up of 30.05 months, 217 (9.69%) patients reached composite kidney failure events. The association of SBP and kidney failure events showed a linear relationship. The risk of kidney failure events was greater with higher SBP. Compared with SBP <120 mm Hg, the hazard ratio was 1.85 (1.16-2.97, p = 0.010) for SBP <140 mm Hg after adjustment for traditional risk factors. The renoprotective benefits of therapy targeting SBP <120 mm Hg from SBP <140 mm Hg was detectable within the subgroup with proteinuria >1.0 g/d, CKD 1-3a stage, but not those with proteinuria ≤ 1.0 g/d and CKD 3b-4 stage.In patients with IgAN, SBP was independently associated with composite kidney failure events. Lowering SBP from <140- <120 mm Hg was renoprotective.
Background: Published reports examining the efficacy of RAS blockers: angiotensin converting-enzyme inhibitor (ACEI) and angiotensin II receptor blocker (ARB) agents for preserving renal function in IgA nephropathy (IgAN) have yielded conflicting results. To evaluate systematically the effects of ACEI/ARB agents on IgAN, we conducted a meta analysis of published randomised controlled trials (RCTs). Methods: MEDLINE, EMBASE, the Cochrane Library and article reference lists were searched for RCTs that compared ACEI/ARB with placebo and any other antihypertensive agents or non-immunosuppressive agents for treating IgAN. The quality of the studies was evaluated with the method of intention to treat analysis and allocation concealment, as well as with the Jadad method. Meta analyses were performed on the outcomes of proteinuria and renal function in patients with IgAN. Results: Eleven RCTs involving 585 patients were included in the review. Seven trials used placebo/no treatment as controls. Four trials used other antihypertensive agents as controls. Overall, ACEI/ARB agents had statistically significant effects on protecting renal function(p < 0.00001) and reduction of proteinuria (p < 0.00001) when compared with control group. Tests for heterogeneity showed no difference in effect among the studies. Systolic and diastolic blood pressure, glomerular filtration rate (GFR), age, did not influence treatment response. ACEI/ARB agents were well tolerated. Conclusions: The current cumulative evidence suggests that ACEI/ARB agents had statistically significant effects on protecting renal function and reduction of proteinuria in patients with IgAN when compared with control groups. ACEI/ ARB agents are a promising medication and should be investigated further.
Dietary flavonoid-rich polyphenolic antioxidants from bamboo leaves may protect against internal exposure to acrylamide in humansviaaltering the mercapturic acid metabolites and hemoglobin adducts of acrylamide and glycidamide.
Abstract Objective The aim of this meta-analysis was to evaluate the therapeutic effects of mesenchymal stromal cells (MSCs) versus traditional regimens for induction therapy in kidney transplantation (KT), especially the safety of MSC infusion, practicability of MSCs as induction therapy agents, and posttransplant complications. Methods PubMed, Embase, EBSCO, Ovid, and the Cochrane Library were searched for prospective clinical trials that compared MSCs with traditional regimens for induction therapy in KT. Results Four trials were included, including a total of 197 patients. The pooled results revealed that MSC therapy had a lower 1-year infection rate than did the traditional therapies (RR = 0.65, 95% CI: 0.46–0.9, P = 0.01). There were no significant differences between the two protocols regarding the 1-year acute rejection (AR) rate (RR = 0.77, 95% CI: 0.41–1.45, P = 0.42), 1-year graft survival rate (RR = 0.99, 95% CI: 0.95–1.03, P = 0.74), delayed graft function (DGF) rate (RR = 0.54, 95% CI: 0.21–1.38, P = 0.2) and renal graft function at 1 month (MD = −1.56, 95% CI: − 14.2–11.08, p = 0.81), 3 months (MD = 0.15, 95% CI: − 5.63–5.93, p = 0.96), 6 months (MD = − 1.95, 95% CI: − 9.87–5.97, p = 0.63), and 12 months (MD = − 1.13, 95% CI: − 7.16–4.89, p = 0.71) postsurgery. Subgroup analysis demonstrated that the 1-year AR rate, 1-year graft survival rate, DGF rate, and renal graft function at 12 months postsurgery did not significantly differ between the low-dose calcineurin inhibitor (CNI) group and the standard-dose CNI group, indicating the potential benefits of successful CNI sparing in combination with MSC treatment. Moreover, when MSCs were applied as an alternative therapy rather than an additional therapy or allogeneic MSCs were utilized instead of autologous MSCs, all of the outcomes mentioned above were comparable. Conclusion Induction therapy with MSCs is safe and has similar immune response modulation effects to those of traditional regimens in the short term in KT recipients. However, regarding the long-term effects, as suggested by the 1-year infection rate and the potential of CNI sparing, MSC therapy has significant advantages. However, these advantages should be further verified in more well-designed, multicenter randomized controlled trials (RCTs) with large sample sizes and long follow-up periods.
Objective To evaluate the efficacy and safety of sirolimus and tacrolimus after renal transplantation.Method PubMed,Web of knowledge,Medline and the Cochrane Library were searched with the terms and Boolean operators as (kidney transplantation OR renal transplantation) AND (sirolimus OR rapamycin) AND (tacrclimus OR FKS06).Results retrieved were last updated on June 9,2014.Language limit of English and Chinese only was applied.Trials were excluded if enrolling recipients of organs other than kidneys,reporting none of the outcomes in point or combining sirolimus with tacrolimus.Patient and graft survival,acute rejection and adverse events were evaluated as primary outcomes and glomerular filtration rate (GFR) was an additional surrogate for renal function.Professional meta-analysis software RevMan 5.1 was employed to analyze the pooled risk ratio (RR) and mean difference (M D) followed by subgroup analysis and sensitivity analysis.Result Fifteen studies were included with 2480 patients.Patients in the sirolimus group showed an increased rate of acute rejection within one-year's follow-up 2.02 (95％ CI 1.37-2.99,P＜0.05) and also a higher risk of adverse events 1.31 (95％ CI 1.02-1.68,P＜0.05).The incidence of hyperlipidaemia was significantly higher with RR =1.75 (95％ CI 1.17-2.61,P＜ 0.01) in the sirolimus group.The other outcomes were insignificantly different between two groups.In subgroups with ATG as immunity induction and higher sirolimus concentration (＞4-8 μg/L),the difference was insignificant (P ＞ 0.05).Conclusion This meta-analysis concluded that sirolimus showed no advantage over tacrolimus when used early after transplantation.When used with higher concentrations,or with ATG as immunity induction,the disadvantages may be avoided.More clinical evidence is needed.
Key words:
Renal transplantation ; Immunosuppressin; Sirolimus ; Tacrolimus; Meta-analysis
The current study developed an ultrahigh-performance liquid chromatography tandem mass spectrometry method to simultaneously analyze cascade metabolites of acrylamide in urine of rats and humans, including acrylamide, glycidamide, N-acetyl-S-(2-carbamoylethyl)-l-cysteine (AAMA), N-acetyl-S-(2-carbamoylethyl)-l-cysteine-sulfoxide, N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-l-cysteine, and N-acetyl-S-(1-carbamoyl-2-hydroxyethyl)-l-cysteine. A tandem solid-phase extraction procedure was novelly used to purify all metabolites at once from human urine. The rapid analysis showed high sensitivity with LOD and LOQ ranges of 0.1–0.8 and 0.4–5.8 ng/mL, respectively, and achieved acceptable within-laboratory reproducibility (RSD < 12.0%) and spiking recovery (92.2%–117.3%) within 8 min per sample. Approximately 70.7 and 63.0% of ingested acrylamide were recovered during the toxicokinetics analysis from urine of male and female rats, respectively. For nonsmoking participants, the urinary levels of acrylamide and glycidamide were higher in men than women, whereas the urinary concentration of AAMA showed the opposite behavior. The current analysis provides methodological support of cascade metabolites of acrylamide for the dietary short-term internal exposure assessment of acrylamide.
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