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Objective To evaluate the relative efficacy and safety of different oral anticoagulant agents (OACs) for patients with atrial fibrillation (AF) and chronic kidney disease (CKD). Study Design Systematic review and pairwise and Bayesian network meta-analysis. Setting & Study Populations Adult patients with AF and CKD stages 3-5D who received OACs. Selection Criteria for Studies Randomized controlled trials (RCTs) and observational studies that reported the efficacy and safety outcomes of subgroups with a glomerular filtration rate (GFR) Data Extraction Two reviewers independently abstracted data, assessed study quality, and rated the strength of evidence (SOE). Analytical Approach Random-effects models using restricted maximum-likelihood methods were fit for the pairwise meta-analyses as well as a network meta-analysis within a Bayesian framework. Results Pairwise meta-analysis including 8 RCTs and 46 observational studies showed that direct OACs (DOACs) were superior to warfarin in preventing thromboembolic events (hazard ratio [HR], 0.86 [95% CI, 0.78-0.95]), without heterogeneity (I2 = 10.5%), and in reducing the risk of bleeding events (HR, 0.81 [95% CI, 0.66-0.99]), with substantial heterogeneity (I2 = 69.8%), in patients with AF and a GFR of 15-60 mL/min. Bayesian network meta-analysis including 8 RCTs showed that dose-adjusted apixaban and a 15-mg dose of edoxaban were superior to the other OAC regimens in reducing bleeding events. Dose-adjusted apixaban was more effective than edoxaban in preventing thromboembolic events for patients with AF and GFR in the range of 25-50 or 30-50 mL/min. In dialysis recipients with AF, the use of OACs increased the risk of bleeding events by 28% (HR, 1.28 [95% CI, 1.03-1.60]) without significant beneficial effects versus not using anticoagulants. Limitations Low SOE and heterogeneity in most comparisons. Conclusions This study suggests that DOACs are superior to warfarin for the prevention of thromboembolic events and reduction in bleeding risk in patients with AF and mild to moderate kidney disease. However, the low SOE limits the conclusions that can be drawn about the preferred DOAC. Notably, the use of OACs may increase bleeding risk without significant benefits in dialysis recipients with AF. Registration Registered at PROSPERO with identification number CRD42018090896.

Hematuria is the most typical presentation of immunoglobulin A nephropathy (IgAN); however, its role in disease progression is still controversial. This study aimed to evaluate the association of hematuria and progression of IgAN.Retrospective cohort study.A cohort of 1,333 patients with IgAN treated at a Chinese referral hospital with a median follow-up of 45 months.Microhematuria was evaluated in fresh urine using a fully automated urine particle analyzer (automated method) and urine sediment examination by a skilled examiner (manual method). Hematuria was characterized as a time-varying attribute; namely, average hematuria level was calculated for every 6-month period for each patient during follow-up. Remission was defined as average red blood cell count ≤5/high-power field (manual method) or ≤28 red blood cells/μL (automated method) during the first 6 months of follow-up.Composite event of 50% decline in estimated glomerular filtration rate or development of kidney failure.Multivariable cause-specific hazards models to analyze the relationship between hematuria and the composite kidney disease progression event.Time-varying hematuria during follow-up was an independent risk factor for the composite kidney disease progression event (HR, 1.46; 95% CI, 1.13-1.87; P = 0.003). Hematuria remission during the 6 months after diagnosis was associated with a significantly lower rate of the composite kidney disease progression event (HR, 0.41; 95% CI, 0.28-0.61; P 0.001). A significant interaction was detected between remission of proteinuria and remission of hematuria during the first 6 months (P 0.001). The association between remission of hematuria and kidney disease progression was detectable (HR, 0.46; 95% CI, 0.32-0.68) within the subpopulation with persistent proteinuria (protein excretion1.0 g/d during the first 6 months), but not among patients whose proteinuria had remitted (HR, 0.64; 95% CI, 0.31-1.29; P = 0.2). The 2 techniques for hematuria evaluation were strongly and significantly linearly correlated (r = 0.948; P 0.001), and results using these 2 methods were consistent.A single-center retrospective study. Proportional hazards regression incorporating time-varying covariates may create time-varying confounding. The predictive value of reductions in hematuria was not directly evaluated.Level of hematuria was independently associated with kidney disease progression, whereas hematuria remission was associated with improved kidney outcomes in IgAN among patients with persistent proteinuria. Additionally, to monitor IgAN progression, automated methods to evaluate hematuria hold promise as a replacement for manual evaluation of urinary sediment.

Background The outcomes of pregnancy in immunoglobulin A nephropathy (IgAN) are controversial. This cohort study assessed the effects of pregnancy on kidney disease progression and risk factors for adverse pregnancy outcomes in patients with IgAN. Study Design A cohort study. Setting & Participants Women of child-bearing age with IgAN and minimum follow-up of 1 year after biopsy from December 2003 to September 2014. Predictors Pregnancy, treated as a time-dependent variable; baseline (at time of biopsy) estimated glomerular filtration rate (eGFR), proteinuria, blood pressure, and kidney pathology (Oxford MEST classification). Outcomes Kidney disease progression event, defined as 30% decline in eGFR or end-stage kidney disease; rate of eGFR decline; and adverse pregnancy outcomes, including severe preeclampsia and fetal loss. Results Of 413 patients enrolled, 266 (64.4%), 101 (24.5%), 40 (9.6%), and 6 (1.5%) had chronic kidney disease (CKD) stages 1, 2, 3, and 4, respectively. During follow-up, 104 had 116 pregnancies, of which 110 continued beyond week 20; 309 patients did not become pregnant. After adjustment for age, eGFR, mean arterial pressure, proteinuria, and pathology class at the time of biopsy, subsequent pregnancy among patients with CKD stages 3 to 4, but not CKD stages 1 to 2, was associated with faster eGFR decline (−7.44 vs −3.90mL/min/1.73m 2 per year; P =0.007) and increased incidence of kidney progression events (HR, 5.14; 95% CI, 1.16-22.74) compared with patients who did not become pregnant. Limitations Relatively small sample size and single-center experience. Conclusions Pregnancy accelerated kidney disease progression in women with IgAN and CKD stage 3, but not in those at stage 1 or 2.

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.

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.

Background Recent studies have indicated that phosphorus may play an independent pathogenic role in chronic kidney disease (CKD) progression, but some of those studies were underpowered and yielded inconsistent results. Study Design Systematic review and meta-analysis. Setting & Population Non–dialysis-dependent patients with CKD (transplant recipients were excluded). Selection Criteria for Studies Studies assessing the risk ratio of serum phosphorus level on kidney failure and mortality for non–dialysis-dependent patients with CKD published from January 1950 to June 2014 were included following systematic searching of MEDLINE, EMBASE, and the Cochrane Library. Predictor Serum phosphorus level. Outcome Kidney failure, defined as doubled serum creatinine level, 50% decline in estimated glomerular filtration rate, or end-stage kidney disease. Results In 12 cohort studies with 25,546 patients, 1,442 (8.8%) developed kidney failure and 3,089 (13.6%) died. Overall, every 1-mg/dL increase in serum phosphorus level was associated independently with increased risk of kidney failure (hazard ratio, 1.36; 95% CI, 1.20-1.55) and mortality (hazard ratio, 1.20; 95% CI, 1.05-1.37). Limitations Existence of potential residual confounding could not be excluded. Conclusions This meta-analysis suggests an independent association between serum phosphorus level and kidney failure and mortality among non–dialysis-dependent patients with CKD and suggests that large-scale randomized controlled trials should target disordered phosphorus homeostasis in CKD.

Background The outcomes of pregnancy in immunoglobulin A nephropathy (IgAN) are uncertain. This study assessed the effects of pregnancy on kidney disease progression and risk factors for adverse pregnancy outcomes in IgAN. Study Design A matched-cohort study. Setting & Participants Women with IgAN with at least one pregnancy, 1 year of follow-up, and kidney function and proteinuria measurement at baseline (time of biopsy) matched with nonpregnant women with IgAN from Peking University First Hospital. Predictors Pregnancy, treated as a time-dependent variable; proteinuria; hypertension; and estimated glomerular filtration rate (eGFR). Outcomes Kidney disease progression, defined as eGFR halving or end-stage kidney disease; rate of eGFR decline; and adverse pregnancy outcomes, including severe pre-eclampsia, intrauterine death, embryo damage, fetal malformation, and induced and spontaneous abortions. Results Of 239 female patients, 62 women had 69 pregnancies and 62 matched nonpregnant patients were selected as controls. Pregnant patients had median proteinuria at baseline with protein excretion of 1.27 (range, 0.06-7.25)g/d and mean eGFR of 102.3 (range, 40.0-139.0)mL/min/1.73m 2 . During a mean follow-up of 45.7 months, 4 patients in the pregnancy group and 6 in the nonpregnancy group had kidney disease progression events. Time-dependent Cox analysis showed that pregnancy was not an independent risk factor for kidney disease progression events (HR, 1.2; 95%CI, 0.3-5.7). There was no significant difference in the median rate of eGFR decline in the 2 groups (−2.5 vs −2.4mL/min/1.73m 2 per year; P =0.7). Adverse pregnancy outcomes were observed in 15 patients. Proteinuria during pregnancy (OR, 1.39; 95%CI, 0.96-2.01) was a borderline predictor of adverse pregnancy outcomes. Limitations Retrospective study, most patients had preserved kidney function, study underpowered to detect a difference in kidney failure events. Conclusions The study does not permit a definitive conclusion about the effect of pregnancy on kidney disease progression in IgAN.

Preparations of the herb Tripterygium wilfordii Hook F are used widely for the treatment of chronic kidney disease in China. The efficacy and safety of Tripterygium preparations still have not been fully identified.Systematic review and meta-analysis.Patients with chronic kidney disease.Randomized controlled trials.Tripterygium preparations (Tripterygium glycoside tablets, Tripterygium hypoglaucum Hutch tablets, and Tripterygium granules or extracts) versus placebo, standard care, or other immunosuppressive treatment.Weighted mean difference and summary estimates of relative risk (RR) reductions with 95% CIs were calculated with a random-effects model. Outcomes analyzed included change in proteinuria, serum creatinine level, and creatinine clearance rate, as well as remission and relapse rate and drug-related adverse events.We identified 75 trials that included 4,386 participants. Overall, Tripterygium therapy reduced proteinuria by protein excretion of 628 (95% CI, -736 to -521) mg/d and reduced serum creatinine level by 0.12 (95% CI, -0.17 to -0.06) mg/dL compared with controls (both P0.001) in a range of kidney conditions. Tripterygium preparations also increased the rate of complete remission by 56% (95% CI, 32%-85%; P0.001) and of complete or partial remission by 24% (95% CI, 17%-31%; P0.001) while reducing relapse by 58% (95% CI, 42%-69%; P0.001). Tripterygium preparations increased the rate of liver function test result abnormalities (RR, 4.03; 95% CI, 2.24-7.25; P0.001) and altered menstruation (RR, 5.29; 95% CI, 2.09-13.38; P0.001).Suboptimal study quality, significant heterogeneity in the primary outcome.Tripterygium preparations may have nephroprotective effects, but high-quality trials are required to reliably determine the balance of benefits and harms.

Background Vitamin D has shown efficacy in the reduction of proteinuria in patients with chronic kidney disease. This study aimed to determine the effect of calcitriol on urinary protein excretion in patients with immunoglobulin A (IgA) nephropathy. Study Design Open-label, non–placebo-controlled, randomized study. Setting & Participants 50 patients with IgA nephropathy were enrolled. The main criterion for inclusion was urinary protein excretion >0.8 g/d after renin-angiotensin system–inhibitor treatment for at least 3 months. Intervention Patients were randomly assigned (1:1) to receive 2 doses (0.5 μg) of calcitriol per week or no treatment for 48 weeks. Outcomes The primary end point was to compare change in 24-hour urinary protein excretion from baseline to last measurement during treatment. Measurements Every 8 weeks, there was measurement of 24-hour urinary protein excretion, serum calcium, serum phosphorus, serum creatinine, and intact parathyroid hormone. Results Measurement of the primary end point showed changes in urinary protein excretion of +21% (from 1.29 to 1.58 g/24 h; 95% CI, −9% to +52%) in the control group and −19% (from 1.60 to 1.30 g/24 h; 95% CI, −42% to +4%) in the calcitriol-treated group. There was a significant decrease in proteinuria in the calcitriol-treated group compared with the control group (difference between groups, 41%; 95% CI, 5%-79%; P = 0.03). The secondary end point of achieving at least a 15% decrease in proteinuria was attained by 7 of 24 (29%) controls and 17 of 26 (65%) of those treated with calcitriol ( P = 0.02). No significant differences were observed in decrease in estimated glomerular filtration rate and change in blood pressure between the 2 groups. The incidence of recorded adverse events was similar between the 2 groups. Limitations Small and non–placebo-controlled study. Conclusions The addition of calcitriol to a renin-angiotensin system inhibitor resulted in a safe decrease in proteinuria in patients with IgA nephropathy.