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

Abstract Background Echocardiographic 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. Methods This 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. Results 29,219 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. Conclusions Echocardiographic abnormalities are frequent even in early CKD. Echocardiographic assessment particularly of the RV may provide useful information for the care of patients with CKD.https://deepblue.lib.umich.edu/bitstream/2027.42/144773/1/12882_2018_Article_975.pd

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

Abstract Background Echocardiographic 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. Methods This 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. Results 29,219 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. Conclusions Echocardiographic abnormalities are frequent even in early CKD. Echocardiographic assessment particularly of the RV may provide useful information for the care of patients with CKD.https://deepblue.lib.umich.edu/bitstream/2027.42/144773/1/12882_2018_Article_975.pd

The Effect of Bicarbonate Administration via Continuous Venovenous Hemofiltration on Acid-Base Parameters in Ventilated Patients

Background. Acute kidney injury (AKI) and metabolic acidosis are common in the intensive care unit. The effect of bicarbonate administration on acid-base parameters is unclear in those receiving continuous venovenous hemofiltration (CVVH) and mechanical ventilatory support. Methods. Metabolic and ventilatory parameters were prospectively examined in 19 ventilated subjects for up to 96 hours following CVVH initiation for AKI at an academic tertiary care center. Mixed linear regression modeling was performed to measure changes in pH, partial pressure of carbon dioxide (pCO2), serum bicarbonate, and base excess over time. Results. During the 96-hour study period, pCO2 levels remained stable overall (initial pCO2 42.0 ± 14.6 versus end-study pCO2 43.8 ± 16.1 mmHg; P=0.13 for interaction with time), for those with initial pCO2 ≤40 mmHg (31.3 ± 5.7 versus 35.0 ± 4.8; P=0.06) and for those with initial pCO2 >40 mmHg (52.7 ± 12.8 versus 53.4 ± 19.2; P=0.57). pCO2 decreased during the immediate hours following CVVH initiation (42.0 ± 14.6 versus 37.3 ± 12.6 mmHg), though this change was nonsignificant (P=0.052). Conclusions. We did not detect a significant increase in pCO2 in response to the administration of bicarbonate via CVVH in a ventilated population. Additional studies of larger populations are needed to confirm this finding

Location of acute coronary artery thromboses in patients with and without chronic kidney disease

Patients with chronic kidney disease have high rates of myocardial infarction and death following an initial attack. Proximal location of coronary atherosclerotic lesions has been linked to the risk of acute myocardial infarction and to infarction-associated mortality. To examine if the spatial distribution of lesions differs in patients with and without chronic kidney disease, we used quantitative coronary angiography to measure this in patients with acute coronary thromboses who were having angiography following acute myocardial infarction. Multivariable linear regression was used to adjust for differences in baseline characteristics. Among 82 patients with stage 3 or higher chronic kidney disease, 55.6% of lesions were located within 30 mm and 87.7% were within 50 mm of the coronary ostia. This compared to 34.7 and 71.8%, respectively, among 299 patients without significant kidney disease. Chronic kidney disease was independently and significantly associated with a 7.0 mm decrease in the distance from the coronary ostia to the problem lesion. Our study suggests that a causal link between a more proximal culprit lesion location in patients with chronic kidney disease and their high mortality rates after myocardial infarct is possible and may have important implications for interventions to prevent infarction

The Effect of Bicarbonate Administration via Continuous Venovenous Hemofiltration on Acid-Base Parameters in Ventilated Patients

Background. Acute kidney injury (AKI) and metabolic acidosis are common in the intensive care unit. The effect of bicarbonate administration on acid-base parameters is unclear in those receiving continuous venovenous hemofiltration (CVVH) and mechanical ventilatory support. Methods. Metabolic and ventilatory parameters were prospectively examined in 19 ventilated subjects for up to 96 hours following CVVH initiation for AKI at an academic tertiary care center. Mixed linear regression modeling was performed to measure changes in pH, partial pressure of carbon dioxide (pCO2), serum bicarbonate, and base excess over time. Results. During the 96-hour study period, pCO2 levels remained stable overall (initial pCO2 42.0 ± 14.6 versus end-study pCO2 43.8 ± 16.1 mmHg; for interaction with time), for those with initial pCO2 ≤40 mmHg (31.3 ± 5.7 versus 35.0 ± 4.8; ) and for those with initial pCO2 >40 mmHg (52.7 ± 12.8 versus 53.4 ± 19.2; ). pCO2 decreased during the immediate hours following CVVH initiation (42.0 ± 14.6 versus 37.3 ± 12.6 mmHg), though this change was nonsignificant (). Conclusions. We did not detect a significant increase in pCO2 in response to the administration of bicarbonate via CVVH in a ventilated population. Additional studies of larger populations are needed to confirm this finding

Canagliflozin Reduces Kidney-Related Adverse Events in Type 2 Diabetes and CKD:Findings From the Randomized CREDENCE Trial

RATIONALE AND OBJECTIVE: Canagliflozin reduced the risk of kidney failure and related outcomes in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) in the CREDENCE trial. This analysis of CREDENCE trial data examines the effect of canagliflozin on the incidence of kidney-related adverse events (AEs). STUDY DESIGN: A randomized, double-blind, placebo-controlled, multicenter, international trial. SETTING AND PARTICIPANTS: 4,401 trial participants with T2DM, CKD, and urinary albumin:creatinine ratio >300-5000mg/g. INTERVENTIONS: Participants were randomly assigned to receive canagliflozin 100mg/day or placebo. OUTCOMES: Rates of kidney-related AEs were analyzed using an on-treatment approach, overall and by screening estimated glomerular filtration rate (eGFR) strata (30-<45, 45-<60, and 60-<90 mL/min/1.73m2). RESULTS: Canagliflozin was associated with a reduction in the overall incidence rate of kidney-related AEs (60.2 vs 84.0 per 1,000 patient-years; hazard ratio [HR]: 0.71 [95% confidence interval (CI): 0.61, 0.82]; P<0.001), with consistent results for serious kidney-related AEs (HR: 0.72 [95% CI: 0.51, 1.00]; P=0.05) and acute kidney injury (AKI; HR: 0.85 [95% CI: 0.64, 1.13]; P=0.3). The rates of kidney-related AEs were lower with canagliflozin relative to placebo across the 3 eGFR strata (HRs of 0.73, 0.60, and 0.81 for eGFR 30-<45, 45-<60, and 60-<90 mL/min/1.73m2, respectively; P-interaction=0.3), with similar results for AKI (P-interaction=0.9). Full recovery of kidney function within 30 days after an AKI event occurred more frequently with canagliflozin versus placebo (53.1% vs 35.4%; odds ratio: 2.2 [95% CI: 1.0, 4.7]; P=0.04). LIMITATIONS: Kidney-related AEs including AKI were investigator-reported and collected without central adjudication. Biomarkers of AKI and structural tubular damage were not measured and creatinine data after an AKI event were not available for all participants. CONCLUSION: Canagliflozin compared to placebo was associated with a reduced incidence of serious and non-serious kidney-related AEs in patients with T2DM and CKD. These results highlight the safety of canagliflozin with regard to adverse kidney disease events

Early Change in Albuminuria with Canagliflozin Predicts Kidney and Cardiovascular Outcomes:A Post Hoc Analysis from the CREDENCE Trial

Background The association between early changes in albuminuria and kidney and cardiovascular events is primarily based on trials of renin-angiotensin system blockade. It is unclear whether this association occurs with sodium-glucose cotransporter 2 inhibition. Methods TheCanagliflozin and Renal Events inDiabeteswith EstablishedNephropathy Clinical Evaluation (CREDENCE) trial enrolled 4401 patients with type 2 diabetes and CKD (urinary albumin-creatinine ratio [UACR].300 mg/g). This post hoc analysis assessed canagliflozin's effect on albuminuria and how early change in albuminuria (baseline to week 26) is associated with the primary kidney outcome (ESKD, doubling of serum creatinine, or kidney death), major adverse cardiovascular events, and hospitalization for heart failure or cardiovascular death. Results Complete data for early change in albuminuria and other covariates were available for 3836 (87.2%) participants in the CREDENCE trial. Compared with placebo, canagliflozin lowered UACR by 31% (95% confidence interval [95% CI], 27% to 36%) at week 26, and significantly increased the likelihood of achieving a 30% reduction in UACR ( odds ratio, 2.69; 95% CI, 2.35 to 3.07). Each 30% decrease in UACR over the first 26 weeks was independently associated with a lower hazard for the primary kidney outcome (hazard ratio [HR], 0.71; 95% CI, 0.67 to 0.76; P,0.001), major adverse cardiovascular events (HR, 0.92; 95% CI, 0.88 to 0.96; P,0.001), and hospitalization for heart failure or cardiovascular death (HR, 0.86; 95% CI, 0.81 to 0.90; P,0.001). Residual albuminuria levels at week 26 remained a strong independent risk factor for kidney and cardiovascular events, overall and in each treatment arm. Conclusions In people with type 2 diabetes and CKD, use of canagliflozin results in early, sustained reductions in albuminuria, which were independently associated with long-term kidney and cardiovascular outcomes

Cardiorenal protective effects of canagliflozin in CREDENCE according to glucose lowering

INTRODUCTION: Relationships between glycemic-lowering effects of sodium glucose co-transporter 2 inhibitors and impact on kidney and cardiovascular outcomes are uncertain. RESEARCH DESIGN AND METHODS: We analyzed 4395 individuals with prebaseline and postbaseline hemoglobin A1c (HbA1c) randomized to canagliflozin (n=2193) or placebo (n=2202) in The Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation trial. Effects on HbA1c were assessed using mixed models. Mediation of treatment effects by achieved glycemic control was analyzed using proportional hazards regression with and without adjustment for achieved HbA1c. End points included combined kidney or cardiovascular death, end-stage kidney disease or doubling of serum creatinine (primary trial outcome), and individual end point components. RESULTS: HbA1c lowering was modified by baseline estimated glomerular filtration rate (eGFR). For baseline eGFR 60-90, 45-59, and 30-44 mL/min/1.73 m2, overall HbA1c (canagliflozin vs placebo) decreased by -0.24%, -0.14%, and -0.08% respectively and likelihood of >0.5% decrease in HbA1c decreased with ORs of 1.47 (95% CI 1.27 to 1.67), 1.12 (0.94 to 1.33) and 0.99 (0.83 to 1.18), respectively. Adjustment for postbaseline HbA1c marginally attenuated canagliflozin effects on primary and kidney composite outcomes: unadjusted HR 0.67 (95% CI 0.57 to 0.80) and 0.66 (95% CI 0.53 to 0.81); adjusted for week 13 HbA1c, HR 0.71 (95% CI 0.060 to 0.84) and 0.68 (95% CI 0.55 to 0.83). Results adjusted for time-varying HbA1c or HbA1c as a cubic spline were similar and consistent with preserved clinical benefits across a range of excellent and poor glycemic control. CONCLUSIONS: The glycemic effects of canagliflozin are attenuated at lower eGFR but effects on kidney and cardiac end points are preserved. Non-glycemic effects may be primarily responsible for the kidney and cardioprotective benefits of canagliflozin.22

Effects of Canagliflozin in Patients with Baseline eGFR:Subgroup Analysis of the Randomized CREDENCE Trial

BACKGROUND AND OBJECTIVES: The Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial demonstrated that the sodium glucose cotransporter 2 (SGLT2) inhibitor canagliflozin reduced the risk of kidney failure and cardiovascular events in participants with type 2 diabetes mellitus and CKD. Little is known about the use of SGLT2 inhibitors in patients with eGFR 300-5000 mg/g, and an eGFR of 30 to 0.20). The estimate for kidney failure in participants with eGFR 0.12). CONCLUSIONS: This post hoc analysis suggests canagliflozin slowed progression of kidney disease, without increasing AKI, even in participants with eGFR <30 ml/min per 1.73 m2