Composite Renal Events Research Articles

Relationship Between Cardiac Structure and Function With Renal Function Trajectory and Outcomes in Patients With Heart Failure: Insights From the PARAGON-HF Trial.

Renal dysfunction is common and associated with a poor prognosis in patients with heart failure. However, the association of cardiac structure and function with decline in kidney function in this population is unknown. We aimed to assess the association between individual measures of cardiac structure and function with changes in renal function and renal outcomes in patients with heart failure with preserved ejection fraction. Patients enrolled in the PARAGON-HF (Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor With Angiotensin-Receptor Blockers Global Outcomes in Heart Failure With Preserved Ejection Fraction) echocardiographic substudy were included. The association between each echocardiographic parameter (expressed in standardized units) and changes over time in estimated glomerular filtration rate was calculated with repeated-measures mixed-effect models. Multivariable Cox proportional hazards models were used to identify individual cardiac parameters associated with the composite renal outcome (≥50% decline in estimated glomerular filtration rate relative to baseline, development of end-stage renal disease, or death attributable to renal causes), after adjusting for covariates. Among 1097 patients (mean age 74±8 years and 53% women), over a median follow-up of 2.9 years, 28 composite renal events (0.9 per 100 person-years) occurred. Higher left ventricular (LV) mass index and higher E/average e' ratio were associated with significantly more profound annual decline in estimated glomerular filtration rate (for both, -0.4 [95% CI, -0.7 to -0.1] mL/min/1.73 m2/y per 1 higher SD). Higher LV mass index, LV end-diastolic volume index, right ventricular end-diastolic area, and a lower right ventricular fractional area change were each associated with a significantly higher risk for the composite renal outcome. In the PARAGON-HF echocardiographic substudy, higher LV mass and filling pressures were independently associated with more profound kidney function decline, and higher LV mass and volume, as well as impaired right ventricular structure and function, were each associated with renal events. Assessing these parameters may help identify patients with heart failure with preserved ejection fraction at higher risk for adverse renal events and indicate potential therapeutic targets. URL: https://www.clinicaltrials.gov; Unique identifier: NCT01920711.

Nephrotoxicity of organophosphate flame retardants in patients with chronic kidney disease: A 2-year longitudinal study

Humans are extensively exposed to organophosphate flame retardants (OPFRs), an emerging group of organic contaminants with potential nephrotoxicity. Nevertheless, the estimated daily intake (EDI) and prognostic impacts of OPFRs have not been assessed in individuals with chronic kidney disease (CKD). In this 2-year longitudinal study of 169 patients with CKD, we calculated the EDIs of five OPFR triesters from urinary biomonitoring data of their degradation products and analyzed the effects of OPFR exposure on adverse renal outcomes and renal function deterioration. Our analysis demonstrated universal OPFR exposure in the CKD population, with a median EDIΣOPFR of 360.45 ng/kg body weight/day (interquartile range, 198.35–775.94). Additionally, our study revealed that high tris(2-chloroethyl) phosphate (TCEP) exposure independently correlated with composite adverse events and composite renal events (hazard ratio [95 % confidence interval; CI]: 4.616 [1.060–20.096], p = 0.042; 3.053 [1.075–8.674], p = 0.036) and served as an independent predictor for renal function deterioration throughout the study period, with a decline in estimated glomerular filtration rate of 4.127 mL/min/1.73 m2 (95 % CI, −8.127–−0.126; p = 0.043) per log ng/kg body weight/day of EDITCEP. Furthermore, the EDITCEP and EDIΣOPFR were positively associated with elevations in urinary 8-hydroxy-2’-deoxyguanosine and kidney injury molecule-1 during the study period, indicating the roles of oxidative damage and renal tubular injury in the nephrotoxicity of OPFR exposure. To conclude, our findings highlight the widespread OPFR exposure and its possible nephrotoxicity in the CKD population.

#1584 Development and validation of risk prediction models according to different clinical settings of IgA nephropathy: nationwide multicenter cohort study

Abstract Background and Aims IgA nephropathy (IgAN) is the most common glomerulonephritis with a high risk of progression to end-stage renal disease (ESRD). Because machine learning models developed for research have limited use in clinical settings, this study developed and validated prediction models for IgAN according to different clinical settings. Method In this study, we analyzed data from 1,174 patients in the Japanese Nationwide Retrospective Cohort Study in IgAN, focusing on a 10-year observation period. We defined the derivation data from January 2002 to April 2004, and temporal validation data from May 2004 to December 2004. The composite renal outcome was defined as a 1.5-fold increase in creatinine or progression to ESRD. We developed and evaluated the three prediction models according to the different clinical settings: the primary care model for general physicians in primary care settings, the tertiary care model for specialists in tertiary care hospitals, and the research institute model, a machine learning-based approach for academic research institute settings. Results After excluding 82 patients for missing data, 114 and 14 patients experienced the composite renal outcome in the derivation (n = 874) and validation (n = 218) cohorts, respectively. The primary care model identified three variables—eGFR <45 mL/min/1.73 m², proteinuria ≥0.5 g/day, and non-use of corticosteroids—as significant predictors (C-statistic: 0.796; 95% CI: 0.686-0.895). The tertiary care model composed of three variables including glomerular number, histological severity and tubular/interstitial severity showed a slightly higher C-statistic (0.807; 95% CI: 0.713-0.886). When stratifying patients into risk groups, the primary care model showed a higher incidence of composite renal events in high-risk patients, and the tertiary care model effectively discriminated outcomes in all groups. The research institute model, which included 38 variables including proteinuria level, hypertension, eGFR, and non-use of corticosteroids as key predictors, showed comparable performance (C-statistic: 0.808; 95% CI: 0.689-0.886). Conclusion The primary care and tertiary care models provide simple yet effective predictive tools, competitive with the machine learning-based research institution model. These models are critical for predicting renal outcomes in patients with IgA nephropathy and for patient management according to different clinical settings.

Effect of the dual sodium-glucose co-transporter-1 and -2 inhibitor sotagliflozin on renal outcomes in type 1 diabetes and type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials.

To investigate the renal safety profile of sotagliflozin, a novel sodium-glucose co-transporter-1 and -2 inhibitor, in patients with type 1 diabetes and type 2 diabetes, with or without renal impairment, as well as its efficacy in decreasing the risk of further renal events, with an emphasis on those with previous renal impairment. Embase, Medline, CENTRAL and Scopus were searched from their inception until 24 April 2023 for randomized controlled trials that reported estimated glomerular filtration rate (eGFR), urinary albumin excretion or composite renal events (CRE). The Cochrane risk of bias 2 tool was used. Mean difference, relative risk (RR) and 95% confidence intervals were estimated (PROSPERO: CRD42023425583). Fourteen studies were included in this review (n = 17 574 participants; intervention n = 9312, control n = 8262). The median follow-up was 24.5 (Q1 = 15.25, Q3 = 28) months. Four studies recruited participants with renal impairment; baseline eGFR ranged from 23.8 to 50.5 mL/min/1.73m2 . The change in eGFR for studies (n = 6) with a follow-up of 52 weeks or longer was -1.23 (-1.45, -1.01) mL/min/1.73m2 . Sotagliflozin did not significantly alter urinary albumin excretion. No change was observed in the risk of CRE (n = 6 studies; RR = 0.82 [0.61, 1.12]), including in participants with renal impairment. High risk of bias was a limitation of this review. Sotagliflozin did not adversely affect renal function or change the risk of key renal outcomes, including for participants with pre-existing renal impairment. Therefore, sotagliflozin was safe; however, further research is needed to determine its efficacy in reducing the risk of diabetic kidney disease.

Abstract 17602: Cardiac Structure and Function and Renal Outcomes in Patients With Heart Failure With Preserved Ejection Fraction: Insights From the PARAGON-HF Trial

Introduction: Chronic kidney disease is common and associated with a worse prognosis in patients with heart failure (HF). However, the association of cardiac structure and function with renal outcomes in patients with HF with preserved ejection fraction (HFpEF) is not known. Goal: Identify cardiac structural and functional correlates of renal outcomes in HFpEF. Methods: Patients enrolled in the echocardiographic sub-study of the PARAGON-HF trial were included. The endpoint of interest was a composite renal endpoint: a ≥50% decline in estimated glomerular filtration rate (eGFR) relative to baseline, development of end-stage renal disease, or death attributable to renal causes. Multivariable Cox proportional hazards models were used to identify measures of cardiac structural and functional parameters associated with the composite renal endpoint, adjusting for baseline eGFR, systolic blood pressure, NT-proBNP, treatment arm (sacubitril-valsartan or valsartan) and diabetes. Results: In 1,097 patients (53% women, mean age 74±8 years), over a median follow-up of 2.9 years (IQR 2.6-3.4 years) there were 28 composite renal events (0.9 per 100 patient-years). After multivariable adjustment, higher left ventricular (LV) posterior wall thickness and mass index, right ventricular (RV) end-diastolic and end-systolic areas as well as impaired RV function (lower fractional area change and lower absolute RV free wall longitudinal strain), but not LV systolic function (LVEF and global longitudinal strain) were each associated with a significantly higher risk for the composite renal endpoint ( Figure ). Conclusions: In the PARAGON-HF echocardiographic sub-study, evidence of cardiac biventricular remodeling and deterioration of RV function were associated with an increased risk of renal events. These results underscore the close relationship between the heart and kidneys in patients with HF even when LVEF is preserved.

#3788 PROGNOSTIC ROLE OF THE NEUTROPHIL-TO-LYMPHOCYTE RATIO IN PATIENTS WITH CHRONIC KIDNEY DISEASE

Abstract Background and Aims The neutrophil-to-lymphocyte ratio (NLR) has been demonstrated to have prognostic value in cardiovascular disease, infection, inflammatory disease, and several types of cancer. Therefore, it is expected that NLR has predictive value in patients with chronic kidney disease (CKD) but it has not been validated. Here, I aimed to investigate the possibility of NLR as a predictor of progression of CKD. Method This retrospective observational study included 141 patients with non-dialysis CKD. Subjects were divided into terciles (T1, T2, and T3) according to NLR. The primary outcome of interest was defined as a composite renal event, which included a decline in the estimated glomerular filtration rate (eGFR) of at least 50% or onset of end-stage renal disease (ESRD) during the follow-up period. Results The median follow-up duration was 5.45 ± 2.11 years. The median NLR for each group was 1.35 ± 0.05 in T1 (n=47), 2.16 ± 0.04 in T2 (n=47) and 4.29 ± 0.73 in T3 (n=47). The group with the highest NLR (T3) had higher baseline CKD and serum creatinine and lower eGFR levels than the group with the lowest NLR (T1). The cumulative incidence of composite renal events was significantly increased in T3, compared to T1 (p < 0.001, log-rank test). Cox regression analysis revealed that high NLR was independently associated with the risk of composite renal events (adjusted hazard ratio 2.85, 95% confidence interval 1.18-6.93). Conclusion A higher NLR reflects the more advanced stage of CKD and suggests that a role for NLR as a biomarker for predicting CKD progression.

Serum triglycerides level is independently associated with renal outcomes in patients with non-dialysis chronic kidney disease: Results from KNOW-CKD study.

To investigate whether high serum triglycerides (TG) level is associated with adverse renal outcomes in patients with non-dialysis chronic kidney disease (CKD), a total of 2,158 subjects from a prospective cohort study (Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease) were divided into the quartile by serum TG level. The primary outcomes were composite renal events, which is defined as a composite of decline of kidney function (the first occurrence of > 50% decline of estimated glomerular filtration rate or doubling of serum creatinine from the baseline) or onset of end-stage renal disease (initiation of dialysis or kidney transplantation). During the median follow-up of 6.940 years, the cumulative incidence of composite renal event was significantly differed by serum TG level in Kaplan-Meier curve analysis (P < 0.001, by Log-rank test). Cox regression analysis demonstrated that, compared to that of the 1st quartile, the risk of composite renal event was significantly higher in the 4th quartile (adjusted hazard ratio 1.433, 95% confidence interval 1.046 to 1.964). The association between high serum TG level and adverse renal outcome remained consistent in the cause-specific hazard model. Subgroup analyses revealed that the association is modified by age, estimated glomerular filtration rate, and spot urine albumin-to-creatinine ratio. In conclusion, high serum TG level is independently associated with adverse renal outcomes in patients with non-dialysis CKD. Interventional studies are warranted to determine whether lowering serum TG levels may alter the natural course of CKD.

Efficacy and safety of urate-lowering agents in asymptomatic hyperuricemia: systematic review and network meta-analysis of randomized controlled trials

BackgroundAsymptomatic hyperuricemia was found to be associated with increased cardiovascular disease risk but the potential benefits of urate-lowering therapy (ULT) remain controversial. We conducted a systematic review and network meta-analysis (NMA) with frequentist model to estimate the efficacy and safety of ULT in asymptomatic hyperuricemia.MethodsMEDLINE, Embase, and Scopus were searched without language restrictions. Randomized controlled trials (RCT) of adults with asymptomatic hyperuricemia were eligible if they compared any pair of ULTs (i.e., allopurinol, febuxostat, probenecid, benzbromarone, sulfinpyrazone, rasburicase, lesinurad, and topiroxostat) and placebo or no ULT, and had outcomes of interest, including composite renal events, major adverse cardiovascular events, serum urate levels, estimated glomerular filtration rate (eGFR), systolic blood pressure, and adverse events.ResultsNMA with frequentist approach was applied to estimate relative treatment effects, i.e., risk ratio (RR) and mean difference (MD). A total of 23 RCTs were eligible. NMA identified beneficial effects of ULT on composite renal events and eGFR but not for other outcomes. Allopurinol and febuxostat had significantly lower composite renal events than placebo (RR 0.39, 95% confidence interval [CI] 0.23 to 0.66, and RR 0.68, 95% CI 0.46 to 0.99, respectively). Both treatments also resulted in significantly higher eGFR than placebo (MD 3.69 ml/min/1.73 m2, 95% CI 1.31 to 6.08, and MD 2.89 ml/min/1.73 m2, 95% CI 0.69 to 5.09, respectively). No evidence of inconsistency was identified.ConclusionsEvidence suggests that allopurinol and febuxostat are the ULTs of choice in reducing composite renal events and improving renal function.Trial registration.This study was registered with PROSPERO: CRD42019145908. The date of the first registration was 12th November 2019.

Association Between Left Ventricular Geometry and Renal Outcomes in Patients With Chronic Kidney Disease: Findings From Korean Cohort Study for Outcomes in Patients With Chronic Kidney Disease Study.

BackgroundThe impact of left ventricular (LV) geometry on the renal outcomes in patients with chronic kidney disease (CKD) has not been established yet. We aimed to investigate the association of LV geometry with renal outcomes and all-cause mortality in patients with pre-dialysis CKD.MethodsA total of 2,144 subjects from the Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD) were categorized by LV geometry, which was defined by LV mass index and relative wall thickness [normal geometry, concentric remodeling, eccentric hypertrophy (eLVH), and concentric hypertrophy (cLVH)]. Study outcomes were composite renal events [decline of kidney function (the first occurrence of > 50% decline of eGFR or doubling of serum creatinine from the baseline) and onset of ESRD (initiation of dialysis or kidney transplantation) during follow-up periods)] and all-cause mortality.ResultsCox regression analysis revealed that eLVH [adjusted hazard ratio (HR) 1.498, 95% confidence interval (CI) 1.197–1.873] and cLVH (adjusted HR 1.289, 95% CI 1.011–1.643) were associated with increased risk of composite renal events, whereas concentric remodeling (adjusted HR 1.881, 95% CI 1.135–3.118) and cLVH (adjusted HR 2.216, 95% CI 1.341–3.664) were associated with increased risk of all-cause mortality. Sensitivity analyses confirmed that concentric remodeling (adjusted HR 1.993, 95% CI 1.197–3.368) and eLVH (adjusted HR 1.588, 95% CI 1.261–2.001) are independently associated with all-cause mortality and composite renal events, respectively.ConclusionIn conclusion, we report that LV geometry is significantly associated with adverse renal outcomes and all-cause mortality in patients with pre-dialysis CKD. Echocardiographic determination of LV geometry may help the early identification for the patients with high risk of CKD progression.

Association between use of sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 agonists, and dipeptidyl peptidase 4 inhibitors with kidney outcomes in patients with type 2 diabetes: A systematic review and network meta-analysis.

BackgroundThis study aimed to compare the efficacies of sodium-glucose cotransporter 2 (SGLT-2) inhibitors, glucagon-like peptide 1 (GLP-1) agonists, and dipeptidyl peptidase 4 (DPP-4) inhibitors on kidney outcomes in patients with type 2 diabetes using network meta-analysis.MethodsPubMed, EMBASE, and CENTRAL were searched for studies published up to September 28, 2020. Randomized clinical trials enrolling participants with type 2 diabetes were included, for which SGLT-2 inhibitors, GLP-1 agonists, and DPP-4 inhibitors were compared with either each other, or placebo or no treatment. A network meta-analysis using a Bayesian approach was performed. The primary outcome was composite renal events, and the secondary outcome was acute kidney injury (AKI) events. All research was conducted according to a protocol registered in the PROSPERO database (CRD42020208090).ResultsIn total, we retrieved 17 445 studies, of which 98 articles enrolling 186 335 participants were included for the network meta-analysis. For our primary outcome, the network meta-analysis revealed no significant difference between drug classes regardless of baseline factors. However, GLP-1 receptor agonists were most likely ranked best among the three drugs in reducing composite renal events (80%, moderate-quality evidence). Compared with the control groups (OR 0.74, 95% CI 0.62 to 0.87, low-quality evidence), GLP-1 receptor agonists (OR 0.76, 95% CI 0.59 to 0.96, moderate-quality evidence) and with DPP-4 inhibitors (OR 0.67, 95% CI 0.50 to 0.86, low-quality evidence), SGLT-2 inhibitors were associated with a lower risk of AKI events.ConclusionsIn this network meta-analysis, although none of the three new antidiabetic drug classes reduced the composite renal events in participants with type 2 diabetes, GLP-1 receptor agonists may be more effective. The use of SGLT-2 inhibitors was associated with a lower AKI event risk than DPP-4 inhibitors, GLP-1 agonists, placebo, or no treatment.

Low plasma renin activity is independently associated with kidney disease progression in patients with type 2 diabetes and overt nephropathy, including those with impaired kidney function: a 2-year prospective study.

Plasma renin activity (PRA) is lower in patients with diabetic nephropathy (DN) than in healthy individuals. However, the association, if any, between PRA and renal outcomes in patients with DN remains uncertain. In a 2-year prospective observational study, we aimed to investigate the association of PRA with the decline in kidney function in patients with DN. We studied 97 patients with DN who were categorized according to tertile (T1-T3) of PRA. The annual changes in estimated glomerular filtration rate (eGFR) (mL/min/1.73 m2/year) were determined from the slope of the linear regression curve for eGFR. The secondary endpoint was defined as a composite of the doubling of serum creatinine or end-stage renal disease. Results showed that kidney function rapidly declined with lower tertiles of PRA (median value [interquartile range] of the annual eGFR changes: -8.8 [-18.5 to -4.2] for T1, -8.0 [-14.3 to -3.2] for T2, and -3.1 [-6.3 to -2.0] for T3; p for trend <0.01). Multivariable linear regression analyses showed that, compared with T3, T1 was associated with a larger annual change in eGFR (coefficient, -4.410; 95% confidence interval [CI], -7.910 to -0.909 for T1). Composite renal events occurred in 46 participants. In multivariable Cox analysis, the lower tertiles of PRA (T1 and T2) were associated with higher incidences of the composite renal outcome (T2: hazard ratio [HR], 4.78; 95% CI, 1.64-13.89; T1: HR, 4.85; 95% CI 1.61-14.65) than T3. In conclusion, low PRA is independently associated with poor renal outcomes in patients with DN.

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.

Insulin-Like Growth Factor Binding Protein 7 Predicts Renal and Cardiovascular Outcomes in the Canagliflozin Cardiovascular Assessment Study.

To analyze the association between concentrations of plasma insulin-like growth factor binding protein 7 (IGFBP7) with renal and cardiac outcomes among participants with type 2 diabetes and high cardiovascular risk. Associations between IGFBP7 levels and clinical outcomes were assessed among participants in the Canagliflozin Cardiovascular Assessment Study (CANVAS) with type 2 diabetes and high cardiovascular risk. Among CANVAS participants, 3,577 and 2,898 had IGFBP7 measured at baseline and 1 year, respectively. Per log-unit higher concentration, baseline IGFBP7 was significantly associated with the composite renal end point of sustained 40% reduction in estimated glomerular filtration rate, need for renal replacement therapy, or renal death (hazard ratio [HR] 3.51; P < 0.001) and the composite renal end point plus cardiovascular death (HR 4.90; P < 0.001). Other outcomes, including development or progression of albuminuria, were also predicted by baseline IGFBP7. Most outcomes were improved by canagliflozin regardless of baseline IGFBP7; however, those with baseline concentrations ≥96.5 ng/mL appeared to benefit more from canagliflozin relative to the first progression of albuminuria compared with those with lower baseline IGFBP7 (HR 0.64 vs. 0.95; P interaction = 0.003). Canagliflozin did not lower IGFBP7 concentrations by 1 year; however, at 1 year, higher IGFBP7 concentrations more strongly predicted the composite renal end point (HR 15.7; P < 0.001). Patients with rising IGFBP7 between baseline and 1 year had the highest number of composite renal events. Plasma IGFBP7 concentrations predicted renal and cardiac events among participants with type 2 diabetes and high cardiovascular risk. More data are needed regarding circulating IGFBP7 and progression of diabetic kidney disease and its complications.

Echocardiographic parameters and renal outcomes in patients with preserved renal function, and mild- moderate CKD

BackgroundEchocardiographic characteristics across the spectrum of chronic kidney disease (CKD) have not been well described. We assessed the echocardiographic characteristics of patients with preserved renal function and mild or moderate CKD referred for echocardiography and determined whether echocardiographic parameters of left ventricular (LV) and right ventricular (RV) structure and function were associated with changes in renal function and mortality.MethodsThis retrospective cohort study enrolled all adult patients who had at least one trans-thoracic echocardiography between 2004 and 2014 in our institution. The composite outcome of doubling of serum creatinine or initiation of maintenance dialysis or kidney transplantation was the primary outcome. Mortality was the secondary outcome.Results29,219 patients were included. Patients with worse renal function had higher prevalence of structural and functional LV and RV abnormalities. Higher estimated glomerular filtration rate (eGFR) was independently associated with preserved LV ejection fraction, preserved RV systolic function, and lower LV mass, left atrial diameter, pulmonary artery pressure, and right atrial pressure, as well as normal RV structure. 1041 composite renal events were observed. 8780 patients died during the follow-up. Pulmonary artery pressure and the RV, but not the LV, echocardiographic parameters were independently associated with the composite renal outcome. In contrast, RV systolic function, RV dilation or hypertrophy, LV ejection fraction group, LV diameter quartile, and pulmonary artery pressure quartile were independently associated with all-cause mortality.ConclusionsEchocardiographic abnormalities are frequent even in early CKD. Echocardiographic assessment particularly of the RV may provide useful information for the care of patients with CKD.

Sodium-glucose co-transporter-2 inhibitors and risk of adverse renal outcomes among patients with type 2 diabetes: A network and cumulative meta-analysis of randomized controlled trials.

To compare the associations of individual sodium-glucose co-transporter-2 (SGLT2) inhibitors with adverse renal outcomes in patients with type 2 diabetes mellitus (T2DM). PubMed, EMBASE, CENTRAL and ClinicalTrials.gov were searched for studies published up to May 24, 2016, without language or date restrictions. Randomized trials that reported at least 1 renal-related adverse outcome in patients with T2DM treated with SGLT2 inhibitors were included. Pairwise and network meta-analyses were carried out to calculate the odds ratios (ORs) with 95% confidence intervals (CIs), and a cumulative meta-analysis was performed to assess the robustness of evidence. In total, we extracted 1334 composite renal events among 39 741 patients from 58 trials, and 511 acute renal impairment/failure events among 36 716 patients from 53 trials. Dapagliflozin was significantly associated with a greater risk of composite renal events than placebo (OR 1.64, 95% CI 1.26-2.13). Empagliflozin seemed to confer a lower risk than placebo (OR 0.63, 95% CI 0.54-0.72), canagliflozin (OR 0.48, 95% CI 0.29-0.82) and dapagliflozin (OR 0.38, 95% CI 0.28-0.51). With regard to acute renal impairment/failure, only empagliflozin was significantly associated with a lower risk than placebo (OR 0.72, 95% CI 0.60-0.86). The cumulative meta-analysis indicated the robustness of our significant findings. The present meta-analysis indicated that dapagliflozin may increase the risk of adverse renal events, while empagliflozin may have a protective effect among patients with T2DM. Further data from large well-conducted randomized controlled trials and a real-world setting are warranted.

Comparison of efficacy and safety between benidipine and hydrochlorothiazide in fosinopril-treated hypertensive patients with chronic kidney disease: protocol for a randomised controlled trial

IntroductionCo-administration of a diuretic or calcium channel blocker with an ACE inhibitor are both preferred combinations in patients with hypertensive chronic kidney disease (CKD). According to the available evidence, it...

Net endogenous acid production is associated with a faster decline in GFR in African Americans

Increased acid excretion may promote renal injury. To evaluate this in African Americans with hypertensive nephrosclerosis, we studied the association between the net endogenous acid production and progression of kidney disease in 632 patients in the AASK trial. Protein and potassium intakes were estimated from 24-hour urea nitrogen and potassium excretion, and used to estimate net endogenous acid production, averaged over 2 years, approximating routine intake. The link between net endogenous acid production and the I125iothalamate glomerular filtration rate (iGFR) and time to end stage renal disease or doubling of serum creatinine was analyzed using mixed models and Cox proportional hazards regressions. The trend in higher net endogenous acid production was significantly associated with a faster decline in iGFR over a median of 3.2 years. After adjustment for age, body mass index, baseline iGFR, urine protein to creatinine ratio and randomized treatment group, the trend in higher net endogenous acid production remained significantly associated with a faster decline in iGFR at a rate 1.01 mL/min/1.73 m2 per year faster in the highest to the lowest quartile. However, in time to event analyses over a median of 7.7 years, the adjusted hazard ratio (1.10) for composite renal events per 25 mEq/day higher net endogenous acid production was not significant. Hence, our findings implicate endogenous acid production as a potential modifiable risk factor for progressive kidney disease.

Adverse Effects of Cyclooxygenase 2 Inhibitors on Renal and Arrhythmia Events

Adverse effects of selective cyclooxygenase 2 (COX-2) inhibitors on renal events and arrhythmia have been controversial, with suggestions of a class effect. To quantitatively evaluate adverse risks of renal events (renal dysfunction, hypertension, and peripheral edema) and arrhythmia events and to explore drug class effects and temporal trends of apparent effects of the COX-2 inhibitors: rofecoxib, celecoxib, valdecoxib, parecoxib, etoricoxib, and lumiracoxib. A systematic search of EMBASE and MEDLINE (through June 2006), bibliographies, US Food and Drug Administration reports, and pharmaceutical industry clinical trial databases. From relevant reports, 114 randomized double-blind clinical trials were included. Information on publication year, participant characteristics, trial duration, drug, control, dose, and events were extracted using a standardized protocol. Results were pooled via random-effects models and meta-regressions. Of 116 094 participants from 114 trial reports including 127 trial populations (40 rofecoxib, 37 celecoxib, 29 valdecoxib + parecoxib, 15 etoricoxib, and 6 lumiracoxib), there were a total of 6394 composite renal events (2670 peripheral edema, 3489 hypertension, 235 renal dysfunction) and 286 arrhythmia events. Results indicated significant heterogeneity of renal effects across agents (P for interaction = .02), indicating no class effect. Compared with controls, rofecoxib was associated with increased risk of arrhythmia (relative risk [RR], 2.90; 95% confidence interval [CI], 1.07-7.88) and composite renal events (RR, 1.53; 95% CI, 1.33-1.76); adverse renal effects increased with greater dose and duration (both P< or =.05). For all individual renal end points, rofecoxib was associated with increased risk of peripheral edema (RR, 1.43; 95% CI, 1.23-1.66), hypertension (RR, 1.55; 95% CI, 1.29-1.85), and renal dysfunction (RR, 2.31; 95% CI, 1.05-5.07). In contrast, celecoxib was associated with lower risk of both renal dysfunction (RR, 0.61; 95% CI, 0.40-0.94) and hypertension (RR, 0.83; 95% CI, 0.71-0.97) compared with controls. Other agents were not significantly associated with risk. Time-cumulative analyses indicated that for rofecoxib the adverse risks for peripheral edema and hypertension were evident by the end of year 2000 and for risk of arrhythmia by 2004. In this comprehensive analysis of 114 randomized trials with 116,094 participants, rofecoxib was associated with increased renal and arrhythmia risks. A COX-2 inhibitor class effect was not evident. Future safety monitoring is warranted and may benefit from an active and continuous cumulative surveillance system.