Doubling Of Serum Creatinine Level Research Articles

Blood pressure targets for hypertension in people with chronic renal disease.

Chronic kidney disease (CKD) is an independent risk factor for cardiovascular disease, development of end-stage renal disease, and all-cause mortality. It affects around 10% of the population worldwide. The prevalence of hypertension in people with CKD ranges from 22% in stage 1 to 80% in stage 4. Elevated arterial blood pressure is one of the major independent risk factors for adverse cardiovascular events. Thereby, reducing blood pressure to below standard targets may be beneficial but could also increase the risk of adverse events. The optimal blood pressure target in people with hypertension and CKD remains unknown. Primary: to compare the effects of standard and lower-than-standard blood pressure targets for hypertension in people with chronic kidney disease on mortality and morbidity outcomes. Secondary: to assess the magnitude of reductions in systolic and diastolic blood pressure, the proportion of participants reaching blood pressure targets, and the number of drugs necessary to achieve the assigned target. We used standard, extensive Cochrane search methods. We searched the Cochrane Hypertension Specialized Register, CENTRAL, MEDLINE, Embase, one other database, and two trial registers up to 8 February 2023. We also contacted authors of relevant papers regarding further published and unpublished work. We applied no language restrictions. We included randomized controlled trials (RCTs) in people with hypertension and CKD that provided at least twelve months' follow-up. Eligible interventions compared lower targets for systolic/diastolic blood pressure (130/80 mmHg or lower) to standard targets for blood pressure (140 to 160/90 to 100 mmHg or lower). Participants were adults with CKD and elevated blood pressure documented in a standard way on at least two occasions, or already receiving treatment for elevated blood pressure. We used standard Cochrane methods. Our critical outcomes were: total mortality, total serious adverse events, total cardiovascular events, cardiovascular mortality, and progression to end-stage renal disease. Important outcomes were: participant withdrawals due to adverse effects, and number of participants with a doubling of serum creatinine level or at least a 50% reduction in the glomerular filtration rate (GFR) at the end of the study. We used GRADE to assess the certainty of the evidence for the critical outcomes. This review received no funding. We included six RCTs that contributed data for meta-analysis, involving 7348 participants overall (range 840 to 4733 people per study). The mean follow-up was 3.6 years (range 1.0 to 8.0 years). Three studies were publicly funded, two were privately funded, and one had both public and private funding. All RCTs provided individual participant data. None of the included studies blinded participants or clinicians because of the need to titrate antihypertensive drugs to reach a specific blood pressure target. However, an independent committee blinded to group allocation assessed clinical events in all studies. Critical outcomes. Compared with standard blood pressure targets, lower targets likely result in little to no difference in total mortality (risk ratio (RR) 0.90, 95% confidence interval (CI) 0.76 to 1.06; 6 studies, 7348 participants), total serious adverse events (RR 1.01, 95% CI 0.94 to 1.08; 6 studies, 7348 participants), and total cardiovascular events (RR 1.00, 95% CI 0.87 to 1.15; 5 studies, 6508 participants), all with moderate-certainty evidence. Compared with standard blood pressure targets, lower targets may result in little to no difference in cardiovascular mortality (RR 0.90, 95% CI 0.70 to 1.16; 6 studies, 7348 participants) and progression to end-stage renal disease (RR 0.94, 95% CI 0.80 to 1.11; 4 studies, 4788 participants), both with low-certainty evidence. Important outcomes. We found little to no differences in: participant withdrawals due to adverse effects; and the number of participants with a doubling of serum creatinine level, or at least a 50% reduction in GFR at the end of the study. Exploratory outcomes. Compared to the standard blood pressure target groups, participants in the lower target groups achieved lower systolic and diastolic blood pressure values after one year, and required a higher number of antihypertensive drugs at the end of the studies. A higher proportion of participants in the standard blood pressure target groups achieved the targets they were assigned than did participants in the intensive target groups. Compared to a standard blood pressure target, lower blood pressure targets probably result in little to no difference in total mortality, total serious adverse events, and total cardiovascular events, and may result in little to no difference in total cardiovascular mortality or in the progression to end-stage renal disease in people with hypertension and CKD. However, the evidence underpinning these conclusions has several limitations. All studies were open design, blood pressure measurement was performed at a medical office, and there was scant information about adverse events. Future research should include high-quality adverse event data, report results for people with different levels of proteinuria, and consider out-of-office blood pressure monitoring. Several studies are ongoing, and may provide new evidence for this topic in the near future.

An overview of the CANVAS Program and CREDENCE trial: The primary outcomes and key clinical implications for those managing patients with type 2 diabetes.

To provide an overview of the primary outcomes and key clinical implications of the CANVAS Program and CREDENCE trial, which were event-driven, double-blind randomized controlled trials that established the efficacy and safety of canagliflozin in those with type 2 diabetes (T2D) and high cardiovascular risk (CV) or albuminuric chronic kidney disease (CKD). The CANVAS programme (CANVAS and CANVAS-R trials) randomized 10 142 people with T2D and high CV risk to canagliflozin or placebo and followed them for a median of 126 weeks. The primary efficacy outcome was met, with canagliflozin treatment associated with a 14% reduction in major adverse CV events (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.75 to 0.97; p < 0.001) as compared to placebo. The CREDENCE trial randomized 4401 individuals with T2D and albuminuric CKD to canagliflozin or placebo and followed them for 109 weeks. The CREDENCE trial also met its primary endpoint; canagliflozin treatment was associated with a 30% reduction in the composite of kidney failure, sustained doubling of serum creatinine level, or death from kidney or CV causes (HR 0.70, 95% CI 0.59 to 0.82; p < 0.001). Substantial reductions in hospitalization for heart failure (CANVAS: HR 0.67, 95% CI 0.52 to 0.87; CREDENCE: HR 0.61, 95% CI 0.47 to 0.80) and other key CV and kidney outcomes were also identified. Relative clinical benefits were consistent across subgroups defined by baseline age, sex, kidney function and history of CV disease but absolute benefits were greatest in those at highest baseline risk. Total serious adverse events were less common with canagliflozin treatment. Concerns about amputation and fracture risk observed in the CANVAS Program were not seen in CREDENCE and appear to have been spurious chance findings. Canagliflozin reduced important CV, kidney and mortality outcomes in those with T2D and high CV risk or CKD across diverse patient groups, with a good safety profile. Taken together with the other sodium-glucose cotransporter-2 inhibitor CV and renal outcomes trials, these landmark findings have changed the treatment landscape for patients worldwide.

Association Between Trimethylamine N-oxide and Adverse Kidney Outcomes and Overall Mortality in Type 2 Diabetes Mellitus.

Type 2 diabetes (T2D) is the major contributor to chronic kidney disease and end-stage kidney disease (ESKD). The influence of trimethylamine N-oxide (TMAO) on kidney outcomes in T2D remains unclear. To examine the association between fasting serum TMAO levels and adverse kidney outcomes in patients with T2D. Between October 2016 and June 2020, patients with T2D were recruited and monitored every 3 months until December 2021. Serum TMAO levels were assessed using liquid chromatography-mass spectrometry. The primary kidney outcomes were doubling of serum creatinine levels or progression to ESKD necessitating dialysis; the secondary kidney outcome was a rapid 30% decline in estimated glomerular filtration rate within 2 years. All-cause mortality was also evaluated. Among the 440 enrolled patients with T2D, those in the highest serum TMAO tertile (≥0.88 μM) were older, had a longer diabetes duration, elevated blood urea nitrogen, and lower estimated glomerular filtration rate. Over a median follow-up period of 4 years, 26 patients (5.9%) had a doubling of serum creatinine level or progression to ESKD. After propensity score weighting, the patients in the highest serum TMAO tertile had a 6.45-fold increase in the risk of doubling of serum creatinine levels or progression to ESKD and 5.86-fold elevated risk of rapid decline in kidney function compared with those in the lowest tertile. Additionally, the stepwise increase in serum TMAO was associated with all-cause mortality. Patients with T2D with elevated circulating TMAO levels are at higher risk of doubling serum creatinine, progressing to ESKD, and mortality. TMAO is a potential biomarker for kidney function progression and mortality in patients with T2D.

#3447 ENVIRONMENTAL MELAMINE EXPOSURE AND ADVERSE KIDNEY OUTCOMES IN PATIENTS WITH TYPE 2 DIABETES MELLITUS

Abstract Background and Aims The impact of environmental melamine exposure on kidney outcomes in type 2 diabetes (T2D) remains unclear. The aim of this study is to evaluate the relationship between melamine and adverse kidney progression in T2D population. Method This longitudinal study enrolled 561 T2D patients during October 2016 and June 2020 and followed until December 2021. Baseline urinary melamine levels were measured by LC-MS/MS, and average daily intake (ADI) of melamine was estimated. Primary kidney outcomes were defined as doubling of serum creatinine levels or end stage kidney disease (ESKD), and secondary kidney outcomes included rapid decline in kidney function as estimated glomerular filtration rate (eGFR) decline &amp;gt; 5 ml/min/1.73m2/year. Results Baseline median urinary corrected melamine levels and estimated DI of melamine were 0.8 μg/mmol and 0.3 µg/kg/day in 561 T2D patients. During 3.7 years of follow-up, urinary corrected melamine level was positively correlated with reaching composite outcomes of either doubling of serum creation levels or ESKD and rapid decline in kidney function. Those with the highest quartile of urinary corrected melamine had 2.96-fold risk of composite outcomes of either doubling of serum creation levels or ESKD and 2.47-fold risk of eGFR decline &amp;gt; 5 ml/min/1.73m2/year. Estimated ADI of melamine also had significant correlation with adverse kidney outcomes. Furthermore, the positive relationship between melamine exposure and rapid decline in kidney function was only found in T2D patients with male, baseline eGFR ≥ 60 ml/min/1.73m2 or glycated hemoglobin ≤ 7%. Conclusion Melamine exposure is significantly associated with kidney outcomes in T2D patients, especially in those with male, well sugar control or preserved baseline kidney function.

Urinary Metabolite Profile Predicting the Progression of CKD.

Key Points As a biomarker, urinary metabolites could bridge the gap between genetic abnormalities and phenotypes of diseases.We found that levels of betaine, choline, fumarate, citrate, and glucose were significantly correlated with kidney function and could predict kidney outcomes, providing prognostic biomarkers in CKD. Background Because CKD is caused by genetic and environmental factors, biomarker development through metabolomic analysis, which reflects gene-derived downstream effects and host adaptation to the environment, is warranted. Methods We measured the metabolites in urine samples collected from 789 patients at the time of kidney biopsy and from urine samples from 147 healthy participants using nuclear magnetic resonance. The composite outcome was defined as a 30% decline in eGFR, doubling of serum creatinine levels, or end-stage kidney disease. Results Among the 28 candidate metabolites, we identified seven metabolites showing (1) good discrimination between healthy controls and patients with stage 1 CKD and (2) a consistent change in pattern from controls to patients with advanced-stage CKD. Among the seven metabolites, betaine, choline, glucose, fumarate, and citrate showed significant associations with the composite outcome after adjustment for age, sex, eGFR, the urine protein–creatinine ratio, and diabetes. Furthermore, adding choline, glucose, or fumarate to traditional biomarkers, including eGFR and proteinuria, significantly improved the ability of the net reclassification improvement (P &lt; 0.05) and integrated discrimination improvement (P &lt; 0.05) to predict the composite outcome. Conclusion Urinary metabolites, including betaine, choline, fumarate, citrate, and glucose, were found to be significant predictors of the progression of CKD. As a signature of kidney injury–related metabolites, it would be warranted to monitor to predict the renal outcome.

Renal protection and safety of sodium-glucose cotransporter-2 inhibitors in chronic kidney disease.

Chronic kidney disease (CKD) has a clinical characteristic of progressive loss of kidney function and becomes a serious health and social concern. SGLT2i (sodium-glucose cotransporter 2 inhibitors), a class of anti-diabetic medications, is shown to reduce cardiovascular and renal events. This systematic review and meta-analysis aimed to assess whether SGLT2i could become a new treatment strategy for CKD for its renal protection and safety. Based on predetermined criteria, a bibliographical search was performed on May 31, 2022, by searching the following databases: ISI Web of Science, Embase, PubMed, and the Cochrane Library. Statistical analysis was conducted to assess renal protection and safety of SGLT2i by using Cochrane Review Manager Version 5.3. Thirty randomised controlled trials fulfilled the inclusion criteria and were eligible for this meta-analysis. Our study found that the SGLT2i can sustainably reduce the urine albumin/creatinine ratio (UACR) at different time points and prevent the progression to macroalbuminuria. Before 24 weeks, SGLT2i can decrease the estimated glomerular filtration rate (eGFR) compared to the control group. Interestingly, after 24 weeks, SGLT2i can continuously maintain the increase in eGFR when compared with the control group. Furthermore, SGLT2i can reduce the event rates of incident or worsening nephropathy, a decline in estimated eGFR of ≥ 50%, doubling of serum creatinine level, acute renal failure and renal failure. Interestingly, the renoprotective effects of SGLT2i are independent of its glycemic effects. SGLT2i can reduce the morbidity rate of any related adverse events, any related severe adverse events and SGLT2i have not increased the event rates of urinary tract infection, bone fractures, amputation, and acute pancreatitis when compared with the control group. SGLT2i can protect renal function and are safe drug for CKD. SGLT2i are promising therapeutic agents for CKD patients.

Environmental melamine exposure and adverse kidney outcomes in patients with type 2 diabetes mellitus

The impact of melamine exposure on kidney outcomes in type 2 diabetes mellitus (T2D) patients remains unclear. In this prospective cohort study, 561 T2D patients during October 2016 and June 2020 were enrolled and followed until December 2021. Baseline one-spot urinary corrected melamine levels were measured by LC-MS/MS. Average daily intake (ADI) of melamine represented environmental melamine exposure in daily life, and was estimated using urinary corrected melamine level by creatinine excretion (CE)-based model. Primary kidney outcomes were defined as doubling of serum creatinine levels or end stage kidney disease (ESKD), and secondary kidney outcomes included rapid decline in kidney function as estimated glomerular filtration rate (eGFR) decline >5 ml/min/1.73 m2/year. Baseline median urinary corrected melamine levels and estimated DI of melamine were 0.8 μg/mmol and 0.3 μg/kg/day in 561 T2D patients. During 3.7 years of follow-up, urinary corrected melamine level was positively correlated with reaching composite outcomes of either doubling of serum creation levels or ESKD and rapid decline in kidney function. Those with the highest quartile of urinary corrected melamine had 2.96-fold risk of composite outcomes of either doubling of serum creation levels or ESKD and 2.47-fold risk of eGFR decline >5 ml/min/1.73 m2/year. Estimated ADI of melamine also had significant correlation with adverse kidney outcomes. Furthermore, the positive relationship between melamine exposure and rapid decline in kidney function was only found in T2D patients with male, baseline eGFR ≥60 ml/min/1.73 m2 or glycated hemoglobin ≤7%. In conclusion, melamine exposure is significantly associated with adverse kidney outcomes in T2D patients, especially in those with male, well sugar control or good baseline kidney function.

Renal outcomes of rivaroxaban compared with warfarin in Asian patients with nonvalvular atrial fibrillation: A nationwide population-based cohort study.

Further studies are needed to expand the evidence for the association of rivaroxaban with a lower risk of adverse renal outcomes in patients with atrial fibrillation (AF) as compared with warfarin, especially in Asians. To determine whether there are differences in adverse renal outcomes between rivaroxaban and warfarin-treated AF patients. Using the Korean nationwide claims database partly linked to laboratory results, patients with AF who initiated warfarin or rivaroxaban from 1 January 2014 to 31 December 2017 were identified. Inverse probability of treatment weighting (IPTW) was used to balance the baseline characteristics of the two groups. The primary outcome (kidney failure) was defined as the need for maintenance dialysis or having kidney transplantation. For the exploratory analysis in a subset of patients with baseline and follow-up laboratory results, the composite of renal outcomes, including estimated glomerular filtration rate (eGFR) lower than 15 ml/min/1.73 m2 at follow-up measurement, starting dialysis, or having kidney transplantation, ≥ 30% decline in eGFR, doubling of serum creatinine level, and acute kidney injury (AKI) were evaluated. The two groups were compared using Cox proportional hazards regression in the weighted population. We identified 30,933 warfarin users and 17,013 rivaroxaban users (51% of low dose rivaroxaban). After IPTW, the mean age was 70 years, and the mean CHA2DS2-VASc score was 3.9 in both groups. During a median follow-up of 0.93 (interquartile ranges 0.23-2.10) years, weighted incidence rates of kidney failure for warfarin and rivaroxaban were 0.83 and 0.32 per 100 person-years, respectively. Compared with the warfarin group, the rivaroxaban group was associated with a lower risk of kidney failure (hazard ratio [HR] 0.389, 95% confidence interval [CI] 0.300-0.499, p < 0.001). In patients with preexisting chronic kidney disease or eGFR ≤ 60 ml/min/1.73 m2, rivaroxaban was more beneficial than warfarin in reducing the risk of kidney failure. For the composite of five renal outcomes in the exploratory analysis, the rivaroxaban group showed a lower risk than warfarin (HR 0.798, 95% CI 0.713-0.892, p < 0.001). Rivaroxaban was associated with lower risks of renal adverse outcomes than warfarin in Korean patients with AF.

Impact of SGLT2 inhibitors treatment on the chronic kidney disease in people with type 2 diabetes

Diabetes is the most common cause of CKD (chronic kidney disease). CKD is also one of the most important diabetic complication. SGLT2 (sodium glucose co‐transporter‐2) inhibitors are new class of medication used to lower high blood glucose level in people with type 2 diabetes. In new researches SGLT2 inhibitors demonstrated a significant and clinically relevant reduction in the risks of albuminuria and progression of nephropathy, doubling of serum creatinine levels, and initiation of renal replacement therapy. This review focuses on the therapeutic effectiveness of using SGLT2 inhibitors for the treatment of CKD in type 2 diabetes.

A Narrative Review of Diabetic Kidney Disease: Previous and Current Evidence-Based Therapeutic Approaches.

Diabetic kidney disease (DKD) is one of the most important diabetic complications. DKD is also the most common cause of chronic kidney disease (CKD) and end-stage renal disease. This review focused on potential therapeutic drugs for which there is established evidence of treatment for DKD. The earliest evidence for DKD treatment was established with renin-angiotensin system (RAS) inhibitors; however, their efficacy was partial. Recently, the sodium-glucose co-transporter2 (SGLT2) inhibitors, including empagliflozin (EMPA-REG Outcome), canagliflozin (CREDENCE trial), and dapagliflozin (DAPA-CKD), demonstrated a significant and clinically relevant reduction in the risks of albuminuria and progression of nephropathy, doubling of serum creatinine levels, and initiation of renal replacement therapy. Additionally, incretin-based therapeutic agents, such as glucagon-like peptide1, liraglutide (LEADER), and dipeptidyl peptidase4 inhibitors, linagliptin (CARMERINA) have elicited vasotropic actions, suggesting a potential for reducing the risk of DKD. Until recently, mineralocorticoid receptor antagonists (MRAs) have not been suitable for DKD treatment because of their adverse effect of hyperkalemia. In contrast, finerenone, a non-steroidal MRA, significantly reduced renal composite endpoint without severe hyperkalemia that would force its discontinuation (FIDELIO-DKD). Thus, the mainstay treatments of DKD are RAS inhibitors, SGLT2 inhibitors, incretin-based therapeutic agents, and non-steroidal MRA, or in other words, the DKD "fantastic four".

FC083: Finerenone and Canagliflozin in the Treatment of Chronic Kidney Disease and Type 2 Diabetes: Matching-Adjusted Indirect Treatment Comparison of Fidelio-DKD and Credence

Abstract BACKGROUND AND AIMS Finerenone (FIN: an oral, nonsteroidal mineralocorticoid receptor antagonist) and canagliflozin (CAN: a sodium-glucose cotransporter 2 inhibitor) demonstrated cardiorenal efficacy in patients with chronic kidney disease and type 2 diabetes on top of renin–angiotensin system blockade in phase III placebo-controlled studies (FIDELIO-DKD [NCT02540993] for FIN; CREDENCE [NCT02065791] for CAN) [3,2]. In the absence of head-to-head studies, we assessed FIN and CAN in this patient population while appropriately accounting for meaningful differences between the trials. METHOD We performed an anchored matching-adjusted indirect comparison (MAIC), with placebo (PBO) as a common comparator, to generate measures of efficacy and safety while accounting for differences between the two study populations [3]. Individual patient-level data from FIDELIO-DKD and published data from CREDENCE were used [1,[2]. Weights were calculated and assigned to each patient in FIDELIO-DKD so the weighted population of FIDELIO-DKD matched that of CREDENCE for selected baseline characteristics, e.g. mean estimated glomerular filtration rate (eGFR; 44.3 and 56.2 mL/min/1.73 m2 in FIDELIO-DKD and CREDENCE, respectively). Weights were obtained from a logistic regression model of the odds of enrolment in CREDENCE and FIDELIO-DKD for baseline characteristics believed to be effect modifiers. Hazard ratios (HRs) with 95% confidence intervals (CIs) comparing FIN and PBO for time-to-event endpoints were estimated based on the weighted population of FIDELIO-DKD. HRs with 95% CIs comparing FIN and CAN were then calculated from results of the previous step and published data from CREDENCE [2]. This analysis evaluated the cardiorenal composite endpoint from CREDENCE (kidney failure [dialysis, transplantation or sustained eGFR &amp;lt; 15 mL/min/1.73 m2), a doubling of serum creatinine level or death from kidney or cardiovascular disease) [2] and hyperkalaemia. A sensitivity analysis that matched patients based on their history of heart failure was performed. RESULTS Calculation of the weights for the FIDELIO-DKD population (N = 5674) resulted in an effective sample size of 1288 for the pseudo-population formed by the weighting to compare with the CREDENCE population (N = 4401). For the cardiorenal composite endpoint, the HR (95% CI) for FIN and PBO based on reweighted FIDELIO-DKD data was 0.72 (0.59–0.90) and the MAIC-based HR (95% CI) for FIN and CAN was 1.03 (0.79–1.35) (P = 0.802). For hyperkalaemia, the MAIC-based HR (95% CI) for FIN and CAN was 2.25 (1.67–3.03) (P &amp;lt; 0.001). Similar efficacy and safety results were demonstrated in the sensitivity analysis. CONCLUSION The MAIC for FIDELIO-DKD and CREDENCE enabled more robust assessment of FIN and CAN when a similar patient population was considered. There was no evidence of a significant difference between FIN and CAN in the cardiorenal composite endpoint as assessed in CREDENCE. These results are consistent with a recent analysis using a different payer-accepted method that also accounted for differences between the FIDELIO-DKD and CREDENCE inclusion criteria and endpoints [3,4].

The effect of renin\u2013angiotensin\u2013aldosterone system inhibitors on continuous and binary kidney outcomes in subgroups of patients with diabetes: a meta-analysis of randomized clinical trials

IntroductionDiabetic nephropathy is the leading cause of kidney failure. Clinical practice guidelines recommend prescribing renin–angiotensin aldosterone system inhibitors (RAASi) to prevent diabetic nephropathy at any stage. We conducted this systematic review and meta-analysis to compare the effects of RAASi with placebo and other antihypertensive agents in adults with diabetes on continuous and binary kidney outcomes to provide a comprehensive review of the class effect of RAASi on several subgroups.MethodsA systematic electronic search to identify randomized clinical trials of a duration of ≥ 12 months that recruited ≥ 50 adult participants with type 1 or 2 diabetes with any stage of chronic kidney disease and proteinuria was conducted in MEDLINE, CINAHL, EMBASE, and Cochrane library with no language restriction. Studies were screened against the inclusion and exclusion criteria by two reviewers independently.ResultsIn this meta-analysis, evidence was drawn from 26,551 patients with diabetes from 46 studies. Our analysis shows that RAASi were better than placebo in reducing SrCr (the raw mean difference [RMD] = -13.4 μmol/L; 95%CI: -16.78; -10.01) and albuminuria levels (standardized mean difference [SMD] = -1; 95%CI: -1.57, -0.44, I2 = 96%). When compared to other active treatments, RAASi did not reduce SrCr (RMD = 0.03 μmol/L; 95%CI: -6.4, 6.10, I2 = 76%), caused a non-significant reduction of GFR levels (RMD = -1.21 mL/min; 95%CI: -4.52, 2.09, I2 = 86%), and resulted in modest reduction of albuminuria levels (SMD = -0.55; 95%CI: -0.95, -0.16, I2 = 90%). RAASi were superior to placebo in reducing the risks of kidney failure (OR = 0.74; 95%CI: 0.56, 0.97) and doubling of serum creatinine levels (SrCr; OR = 0.71; 95%CI: 0.55, 0.91), but not in promoting the regression of albuminuria (OR = 3.00; 95%CI: 0.96, 9.37). RAASi, however, were not superior to other antihypertensives in reducing the risks of these outcomes. Patients with type 2 diabetes, macroalbuminuria and longer duration of diabetes had less risk of developing kidney failure in placebo-controlled trials, while longer duration of diabetes, normal kidney function, and hypertension increased the probability of achieving regression of albuminuria in active-controlled trials.ConclusionWhile our findings revealed the non-superiority of RAASi over other antihypertensives and portrayed a class effect on several subgroups of study participants, it raised a challenging question on whether RAASi deserve their place as first-line therapy in managing diabetic nephropathy.

Mycophenolate mofetil or tacrolimus compared with azathioprine in long-term maintenance treatment for active lupus nephritis.

This study aimed to evaluate the efficacy and safety of mycophenolate mofetil (MMF) or tacrolimus (TAC) compared with azathioprine (AZA) as maintenance therapy for active lupus nephritis (ALN). Patients with ALN who responded to 24 weeks of induction treatment were enrolled. Patients who received MMF or TAC as induction therapy continued MMF or TAC treatment during the maintenance period, whereas those who received intravenous cyclophosphamide were subjected to AZA treatment. The primary endpoint was the incidence of renal relapse. Secondary endpoints included extrarenal flares and composite endpoints (deaths, end-stage renal disease, or doubling of serum creatinine levels). A total of 123 ALN patients (47 in the MMF group, 37 in the TAC group, and 39 in the AZA group) were enrolled. The median follow-up time was 60 months. Ten MMF-treated patients, ten TAC-treated patients, and eight AZA-treated patients experienced renal relapses (P = 0.844). The cumulative renal relapse rates in the MMF group (P = 0.934) and TAC group (P = 0.673) were similar to the renal relapse rate in the AZA group. No significant difference in the incidence of severe adverse event was observed among the groups. Long-term maintenance therapies with MMF or TAC might have similarly low rates of renal relapse and similar safety profiles compared with AZA.

Self-management program for patients with chronic kidney disease (SMP-CKD) in Southern China: protocol for an ambispective cohort study

BackgroundChronic kidney disease (CKD) is a major global health problem. Short-term self-management has been considered to effect some renal and psychological endpoints. However, there are currently very few studies about self-management for CKD that a) have been scientifically designed by a theory-based framework and b) that evaluate the long-term effects and working mechanism. This study presents the rationale and design of a theory-based cohort study to explore how this self-management intervention works and its effectiveness on the Chinese CKD population.MethodsIn this ambispective intervention cohort study,1,200 patients with CKD stages 1–5 will be recruited from July 2015 to July 2024 in 3 branches of Guangdong Provincial Hospital of Chinese Medicine (GPHCM) in Guangdong province, China. The patients in the self-management cohort will choose to receive an intervention that consists of education, nutrition/diet modification, lifestyle change recommendation, medication review, and psychology support based on Social Cognition Theory (SCT). The patients in the control cohort will do regular follow-ups based on the clinic rules. All the patients will be followed up for 5 years, or until the occurrence of a primary outcome. Detailed clinical, laboratory markers, nutritional status, psychological exposures and outcome questionaries will be collected semiannually in CKD stage 1–2 and trimonthly in stage 3–5 patients. The primary outcome is the occurrence of composite clinical endpoints (doubling of serum creatinine level, ESKD, loss of renal function (≥ 40% decline in GFR from baseline), death, major cardiovascular or cerebrovascular events). The main secondary outcomes include the absolute change and slope of eGFR, absolute changes of urinary protein creatinine ratio, 24-h urine proteinuria, intact parathyroid hormone level, and self-management adherence rate and quality of life from baseline to end of the study. The effectiveness of self-management will be analyzed and the association between longitudinal trajectories of self-management and renal outcomes will be evaluated.DiscussionThis study aims to provide further evidence for the effectiveness of theory-based self-management in CKD patients and to improve the lives of patients with CKD by slowing progression, improving psychological well-being and overall quality of life.Trial registrationChinese Clinical Trial Register (ChiCTR1900024633). 19 July, 2019. http://www.chictr.org.cn/showproj.aspx?proj=38378

Lower bicarbonate level is associated with CKD progression and all-cause mortality: a propensity score matching analysis

BackgroundAlthough metabolic acidosis is known as a potential complication of chronic kidney disease (CKD), there is limited information concerning the association between metabolic acidosis and clinical outcomes.MethodsFive hundred fifty-two patients referred to renal division of Iwata City Hospital from 2015 to 2017 were included as a retrospective CKD cohort, and finally 178 patients with CKD stage III or IV and 20 to 80 years of age were analyzed. We examined the association between serum bicarbonate (HCO3−) levels and clinical outcomes using Kaplan-Meier methods after the matching of baseline characteristics by propensity scores.ResultsOf 178 patients with CKD, patients with lower HCO3− levels (N = 94), as compared with patients with higher HCO3− levels (N = 84), were more likely to be male (P < 0.05), had more severe CKD stages (P < 0.05), more frequent use of renin-angiotensin system inhibitor (P < 0.05) or uric acid lowering agent (P < 0.001), heavier body weight (P < 0.001) and lower estimated glomerular filtration rate (P < 0.05). In Kaplan-Meier analysis after propensity score matching, the incidence of composite outcome as the doubling of serum creatinine level from baseline, end-stage kidney disease requiring the initiation of dialysis, or death from any causes was significantly fewer in the higher HCO3− group than the lower HCO3− group (N = 57 each group, P = 0.016).ConclusionsLower HCO3− level is significantly associated with the doubling of serum creatinine level, end-stage kidney disease or all-cause mortality in patients with CKD.Trial registrationThis study was registered with the Clinical Trial Registry of the University Hospital Medical Information Network (http://www.umin.ac.jp/, study number: UMIN000044861).

Renal, cardiovascular and safety outcomes of canagliflozin in patients with type 2 diabetes and nephropathy in East and South-East Asian countries: Results from the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation Trial.

ABSTRACTAims/IntroductionThe sodium–glucose cotransporter 2 inhibitor, canagliflozin, reduced kidney failure and cardiovascular events in the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial. We carried out a post‐hoc analysis to evaluate the efficacy and safety of canagliflozin in a subgroup of participants in East and South‐East Asian (EA) countries who are at high risk of renal complications.Materials and MethodsParticipants with an estimated glomerular filtration rate of 30 to <90 mL/min/1.73 m2 and urinary albumin‐to‐creatinine ratio of >300–5,000 mg/g were randomized to 100 mg of canagliflozin or a placebo. The effects of canagliflozin treatment on pre‐specified efficacy and safety outcomes were examined using Cox proportional hazards regression between participants from EA countries (China, Japan, Malaysia, the Philippines, South Korea and Taiwan) and the remaining participants.ResultsOf 4,401 participants, 604 (13.7%) were from EA countries; 301 and 303 were assigned to the canagliflozin and placebo groups, respectively. Canagliflozin lowered the risk of primary outcome (composite of end‐stage kidney disease, doubling of serum creatinine level, or renal or cardiovascular death) in EA participants (hazard ratio 0.54, 95% confidence interval 0.35–0.84). The effects of canagliflozin on renal and cardiovascular outcomes in EA participants were generally similar to those of the remaining participants. Safety outcomes were similar between the EA and non‐EA participants.ConclusionsIn the CREDENCE trial, the risk of renal and cardiovascular events was safely reduced in participants from EA countries at high risk of renal events.

Bolus Versus Prolonged Infusion of Broad-Spectrum Beta-Lactams for Patients with Hematologic Malignancies and High Risk Febrile Neutropenia - a Single Center Prospective Unblinded Randomized Trial

▪Background: Neutropenic fever is a life-threatening condition which is common in patients with hematologic malignancies, and prompt initiation of appropriate antibiotics is of great importance.Empirical treatment includes monotherapy with a beta-lactam containing anti-pseudomonal activity. Theoretically, time-dependent antibiotics are most active when administered as a continuous infusion, but evidence is lacking in cases of febrile neutropenia. This study examines the optimal dosing regimen (bolus infusion vs. prolonged 4 hour-infusion) for high risk patients undergoing hematopoietic cell transplantation or patients with acute leukemia and febrile neutropenia.Methods: This was a single center, prospective, unblinded randomized study, of 123 hospitalized hematologic patients enrolled between July 2015 and March 2017. The primary outcome was a successful response to treatment, defined as the combination of- defervescence at 96 hours after initiation of broad spectrum beta-lactams (pipracillin/tazobactam or ceftazidime) or before, sterile cultures after 72-96 hours, and no requirement of additional aminoglycoside therapy after 48 hours. Secondary outcomes included breakthrough fever or additional infection after 5 days from initiation of treatment, death within 30 days of study enrollment, duration of hospitalization, duration of neutropenia, occurrence of renal failure (doubling of serum creatinine levels) within 5 days, and requirement for noradrenaline due to hypotension. Patients were randomized using a computerized random number program and allocation was concealed by sequentially numbered sealed and opaque envelopes. All patients signed informed consent and the study was approved by the Tel Aviv Medical Center Institutional Review Board.Results: 123 patients were randomized to bolus infusion (n=63) and prolonged infusion (n=60). Febrile neutropenia occurred in 87% of the patients, and these patients were eligible for the intention-to-treat analysis (ITT). 73% of the patients were given at least one dose of antibiotic according to the allocation arm and were eligible for the per-protocol analysis, Figure. The patients' baseline characteristics were well-balanced between the 2 groups, Table 1. In the ITT analysis (Table 2), there was a higher success rate in patients allocated to the prolonged infusion arm, compared to those allocated to the bolus infusion arm (76% vs. 55%, p= .03). This was also true for the subgroups of patients with microbiologically documented infections (MDI) - (55.6% vs. 7.7%, p=.013) and blood stream infections, (BSI) - (67% vs. 8.3%, p=.009). Similarly, in the per-protocol analysis, the success rate was higher in patients allocated to the prolonged infusion arm who had MDI (62.5% vs. 12.5%, p=.039) or BSI (80% vs. 14.3%, p=.023). There was no difference in the secondary endpoint outcomes between the 2 groups. 30-day death rate was similarly low in both groups. Prolonged beta-lactam infusion was associated with significantly higher treatment success in a logistic regression model that included either BSI (odds ratio of 2.4, 95% CI 0.97-6.1, p=.058) or MDI (OR 2.8, 95% CI 1.1-7.4, p=.032) .Conclusions: This is the first randomized study showing superior treatment outcomes in patients with high-risk febrile neutropenia treated with prolonged versus bolus beta-lactam infusion. Optimization of beta-lactam dosing is a widely available and cost-effective strategy to improve treatment outcomes in patients with high risk febrile neutropenia. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Nephrosclerosis impacts time trajectory of renal function and outcomes in elderly individuals with chronic kidney disease

Despite hypertension ranks among the leading causes of chronic kidney disease (CKD), the impact of chronic hypertensive nephropathy, the so-called ‘nephrosclerosis’ (NS), on CKD progression is often unpredictable, particularly in...

Bupi Yishen Formula Versus Losartan for Non-Diabetic Stage 4 Chronic Kidney Disease: A Randomized Controlled Trial.

Chinese herbal medicine (CHM) might have benefits in patients with non-diabetic chronic kidney disease (CKD), but there is a lack of high-quality evidence, especially in CKD4. This study aimed to assess the efficacy and safety of Bupi Yishen Formula (BYF) vs. losartan in patients with non-diabetic CKD4. This trial was a multicenter, double-blind, double-dummy, randomized controlled trial that was carried out from 11-08-2011 to 07-20-2015. Patients were assigned (1:1) to receive either BYF or losartan for 48 weeks. The primary outcome was the change in the slope of the estimated glomerular filtration rate (eGFR) over 48 weeks. The secondary outcomes were the composite of end-stage kidney disease, death, doubling of serum creatinine, stroke, and cardiovascular events. A total of 567 patients were randomized to BYF (n = 283) or losartan (n = 284); of these, 549 (97%) patients were included in the final analysis. The BYF group had a slower renal function decline particularly prior to 12 weeks over the 48-week duration (between-group mean difference of eGFR slopes: −2.25 ml/min/1.73 m2/year, 95% confidence interval [CI]: −4.03,−0.47), and a lower risk of composite outcome of death from any cause, doubling of serum creatinine level, end-stage kidney disease (ESKD), stroke, or cardiovascular events (adjusted hazard ratio = 0.61, 95%CI: 0.44,0.85). No significant between-group differences were observed in the incidence of adverse events. We conclude that BYF might have renoprotective effects among non-diabetic patients with CKD4 in the first 12 weeks and over 48 weeks, but longer follow-up is required to evaluate the long-term effects. Clinical Trial Registration: http://www.chictr.org.cn, identifier ChiCTR-TRC-10001518.

Effects of intensive blood pressure control on mortality and cardiorenal function in chronic kidney disease patients

Background Blood pressure (BP) variability is highly correlated with cardiovascular and kidney outcomes in patients with chronic kidney disease (CKD). However, appropriate BP targets in patients with CKD remain uncertain. Methods We searched PubMed, Embase, and the Cochrane Library for randomized controlled trials (RCTs) of CKD patients who underwent intensive BP management. Kappa score was used to assess inter-rater agreement. A good agreement between the authors was observed to inter-rater reliability of RCTs selection (kappa = 0.77; P = 0.005). Results Ten relevant studies involving 20 059 patients were included in the meta-analysis. Overall, intensive BP management may reduce the incidence of cardiovascular disease mortality (RR: 0.69, 95% CI: 0.53 to 0.90, P: 0.01), all-cause mortality (RR: 0.77, 95% CI: 0.67 to 0.88, P < 0.01) and composite cardiovascular events (RR: 0.84 95% CI: 0.75 to 0.95, P < 0.01) in patients with CKD. However, reducing BP has no significant effect on the incidence of doubling of serum creatinine level or 50% reduction in GFR (RR: 1.26, 95% CI: 0.66 to 2.40, P = 0.48), composite renal events (RR 1.07, 95% CI: 0.81 to 1.41, P = 0.64) or SAEs (RR: 0.97, 95% CI: 0.90 to 1.05, P = 0.48). Conclusion In patients with CKD, enhanced BP management is associated with reduced all-cause mortality, cardiovascular mortality, and incidence of composite cardiovascular events.