•In patients ≥65 years, GLP-1 RAs reduced atherosclerotic oucomes.•In patients ≥65 years, SGLT2 inhibitors reduced heart failure and renal outcomes.•Some benefits were more pronounced in older ...patients compared to those <65 years.•Results for patients ≥75 years were based on limited data from primary studies.
To assess the cardiovascular effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose co-transporter-2 (SGLT2) inhibitors in older people with type 2 diabetes.
PubMed, Embase, and Cochrane library were searched up to November 2020 for cardiovascular outcomes trials with GLP-1 RAs or SGLT2 inhibitors that reported results for older patients with type 2 diabetes. Random-effects meta-analyses were conducted for different age subgroup categories.
A total of 11 studies (93,502 patients) were included. Consistent with their effect in the overall population, in patients ≥65 years, GLP-1 RAs reduced major adverse cardiovascular events (MACE) (hazard ratio HR, 0.86; 95% confidence interval CI, 0.80–0.92), cardiovascular death, stroke, and myocardial infarction. In the same age subgroup, SGLT2 inhibitors reduced MACE (HR, 0.90; 95% CI, 0.83–0.98) but had a neutral effect on its components. They also reduced heart failure hospitalization (HR, 0.62; 95% CI, 0.51–0.76), an effect that was not evident in patients <65 years, and the composite renal endpoint (HR, 0.57; 95% CI, 0.43–0.77). Meta-analyses for patients ≥75 years yielded similar results.
In older adults with diabetes, GLP-1 RAs reduced MACE and its components. SGLT2 inhibitors reduced MACE, and heart failure and renal outcomes.
This study sought to evaluate the efficacy and safety of sacubitril/valsartan in patients with heart failure with preserved ejection fraction (HFpEF) according to background mineralocorticoid ...receptor antagonist (MRA) therapy.
Current guidelines recommend consideration of MRAs in selected patients with HFpEF. This study assessed cardiovascular outcomes, renal outcomes, and safety of sacubitril/valsartan compared with valsartan in patients with HFpEF according to background MRA treatment.
PARAGON-HF (Prospective Comparison of ARNI angiotensin receptor-neprilysin inhibitor with ARB angiotensin-receptor blockers Global Outcomes in HF with Preserved Ejection Fraction) randomized 4,796 patients with HFpEF to sacubitril/valsartan or valsartan. In a pre-specified subgroup analysis, the effect of sacubitril/valsartan versus valsartan was evaluated according to baseline MRA use on the primary study composite of total heart failure hospitalizations and cardiovascular death using semiparametric proportional rates methods, as well as the renal composite of ≥50% decrease in estimated glomerular filtration rate, development of end-stage renal disease, or death from renal causes using Cox proportional hazards regression models. Annual decline in estimated glomerular filtration rate was analyzed with repeated-measures mixed-effect models. Key safety outcomes included incidence of hypotension, hyperkalemia, and elevations in serum creatinine above predefined thresholds.
Patients treated with MRAs at baseline (n = 1,239, 26%), compared with MRA nonusers (n = 3,557, 74%), were younger (72 vs. 73 years), more often male (52% vs. 47%), had lower left ventricular ejection fraction (57% vs. 58%), and a higher proportion of prior HF hospitalization (59% vs. 44%) (all p < 0.001). Efficacy of sacubitril/valsartan compared with valsartan with regard to the primary cardiovascular (for MRA users: rate ratio: 0.73; 95% confidence interval CI: 0.56 to 0.95; vs. for MRA nonusers: rate ratio: 0.94; 95% CI: 0.79 to 1.11; pinteraction = 0.11) and renal endpoints (for MRA users: hazard ratio: 0.31; 95% CI: 0.13 to 0.76; vs. for MRA non-users: HR: 0.59; 95% CI: 0.36 to 0.95; pinteraction = 0.21) did not significantly vary by baseline MRA use. The incidence of key safety outcomes including hypotension and severe hyperkalemia (K > 6.0 mmol/l) did not vary by baseline MRA use. However, annual decline in estimated glomerular filtration rate was less with the combination of MRA and sacubitril/valsartan (for MRA users: absolute difference favoring sacubitril/valsartan: +1.2 ml/min/1.73 m2 per year; 95% CI: 0.6 to 1.7; vs. for MRA nonusers: +0.4; 95% CI: 0.1 to 0.7; pinteraction = 0.01).
Clinical efficacy of sacubitril/valsartan compared with valsartan with regard to predefined cardiorenal composite outcomes in PARAGON-HF was consistent in patients treated and not treated with MRA at baseline. Addition of sacubitril/valsartan rather than valsartan alone to MRA appears to be associated with a lesser decline in renal function and no increase in severe hyperkalemia. These data support possible added value of combination treatment with sacubitril/valsartan and MRA in patients with HFpEF. (Prospective Comparison of ARNI angiotensin receptor -neprilysin inhibitor with ARB angiotensin-receptor blockers Global Outcomes in HF with Preserved Ejection Fraction PARAGON-HF; NCT01920711)
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Background: People with diabetes and kidney disease have a high risk of cardiovascular events and progression of kidney disease. Sodium glucose co-transporter 2 inhibitors lower plasma glucose by ...reducing the uptake of filtered glucose in the kidney tubule, leading to increased urinary glucose excretion. They have been repeatedly shown to induce modest natriuresis and reduce HbA1c, blood pressure, weight, and albuminuria in patients with type 2 diabetes. However, the effects of these agents on kidney and cardiovascular events have not been extensively studied in patients with type 2 diabetes and established kidney disease. Methods: The Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial aims to compare the efficacy and safety of canagliflozin versus placebo at preventing clinically important kidney and cardiovascular outcomes in patients with diabetes and established kidney disease. CREDENCE is a randomized, double-blind, event-driven, placebo-controlled trial set in in 34 countries with a projected duration of ∼5.5 years and enrolling 4,401 adults with type 2 diabetes, estimated glomerular filtration rate ≥30 to <90 mL/min/1.73 m2, and albuminuria (urinary albumin:creatinine ratio >300 to ≤5,000 mg/g). The study has 90% power to detect a 20% reduction in the risk of the primary outcome (α = 0.05), the composite of end-stage kidney disease, doubling of serum creatinine, and renal or cardiovascular death. Conclusion: CREDENCE will provide definitive evidence about the effects of canagliflozin on renal (and cardiovascular) outcomes in patients with type 2 diabetes and established kidney disease. Trial Registration: EudraCT number: 2013-004494-28; ClinicalTrials.gov identifier: NCT02065791.
Some medications have effects that depend on the time of day they are given. Current knowledge of the time-of-day effects of specific medications in hospitalized patients with cardiovascular disease ...is very limited. In hospitalized patients, increased medication efficiency might reduce dose (and associated side effects) and/or the length of time in the Intensive Care Unit (ICU) or hospital-potentially improving patient outcomes and patient and family quality of life and reducing financial costs. We studied whether the time of day or night patients in Cardiac or Intensive Care Units receive a diuretic affects urine volume.
In this observational study, data were collected from 7,685 patients (63% male, 18 to 98 years old) admitted to one hospital's Acute Care Cardiac units, Cardiac ICUs, Cardiac Surgery ICUs, and/or Non-cardiac ICUs who received intravenous furosemide (a diuretic), had measurements of urine volume, were hospitalized for ≥3 days between January 2016 to July 2021 and were older than 18 years. The outcomes of interest were urine volume normalized by the most recent (not older than 24 h) weight or body mass index (BMI), (i) in the hour after the time of diuretic administration, and (ii) when no diuretics were administered for the previous 3 h.
We identified diuretic medication administration time 23:00-04:59 as a predictor of higher urine volume response. For patients without recent diuretic medication, higher urine volume was predicted 11:00-16:59 and 17:00-22:59. Other factors that affected urine volume response to the diuretic were sex, age, medication dose, creatinine concentration, diagnoses, and hospital unit.
Time-of-day of medication administration may be a factor associated with increased medication efficiency. Randomized controlled trials should be conducted to quantify the relative effect of modifiable factors, such as time of medication administration, that may affect short- and longer-term outcomes.
•Glomerular C3 and C1q deposits emerged as independent risk factors for renal outcomes in IgAN patients.•Predictive models were compared for renal survival probability in patients with IgAN.•The ...predictive ability of C3 was slightly better than that of C1q in IgAN patients.
Immunoglobulin A nephropathy (IgAN) is regarded as the most common type of glomerulonephritis around the world and has the potential to result in renal failure. Complement activation has been addressed by a great body of evidence in the pathogenesis of IgAN. We aimed to evaluate the predictive value of C3 and C1q deposition for disease progression in IgAN patients in this retrospective study.
We recruited 1191 biopsy-diagnosed IgAN patients, and they were divided into different groups according to their glomerular immunofluorescence examination of renal biopsy tissues: 1) C3 deposits ≥ 2 + group (N = 518) and C3 deposits < 2 + group (N = 673). 2) C1q deposit-positive group (N = 109) and C1q deposit-negative group (N = 1082). The renal outcomes were end-stage renal disease (ESRD) and/or an estimated glomerular filtration rate (eGFR) decrease greater than 50% from the baseline value. Kaplan–Meier analyses were performed to evaluate renal survival. Univariate and multivariate Cox proportional hazard regression models were used to evaluate the effect of C3 and C1q deposition on renal outcome in IgAN patients. In addition, we compared the predictive value of mesangial C3 and C1q deposition in IgAN patients.
The median follow-up period was 53 months (interquartile range 36–75 months). During follow-up, 7% (84) of patients progressed to ESRD, and 9% (111) of patients had an eGFR decline ≥ 50%. IgAN patients complicated with C3 deposits ≥ 2 + were associated with more severe renal dysfunction and pathologic lesions at the time of renal biopsy. The crude incidence rates for the endpoint were 12.5% (84 out of 673) and 17.2% (89 out of 518) in the C3 < 2 + and C3 ≥ 2 + groups, respectively (P = 0.022). Of C1q deposit-positive and C1q deposit-negative patients, 22.9% (25 out of 109) and 13.7% (148 out of 1082) reached the composite endpoint, respectively (P = 0.009). Adding C3 deposition to clinical and pathologic models had better predictability of renal disease progression than C1q.
Glomerular C3 and C1q deposits affected the clinicopathologic features of IgAN patients and emerged as independent predictors and risk factors for renal outcomes. In particular, the predictive ability of C3 was slightly better than that of C1q.
The differential benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1RA) in cardiovascular or renal outcomes have not been fully ...investigated.
Patients with diabetes prescribed SGLT2i or GLP1RA were retrospectively identified. Patients treated with antihyperglycemic medications other than SGLT2i or GLP1RA were used as a control group. Primary outcomes were composite ischemic events (acute coronary syndrome, coronary revascularization, and stroke) and a composite of heart failure and renal events (hospitalization for heart failure, renal death, initiation of renal replacement therapy, and renal admission).
During a median 38.7 months of follow-up, the incidence of composite ischemic events tended to be lower in the GLP1RA group (annualized rate 0.82% per person-year) than in the other groups (1.68% per person-year in the SGLT2i group and 1.36% per person-year in the control group). The risk of a composite of heart failure and renal outcomes was significantly lower in the SGLT2i group than in the GLP1RA and control groups (0.86% per person-year, 2.33% per person-year, and 1.48% per person-year, respectively). The SGLT2i group had a slower decline in renal function over time compared to that in other groups.
SGLT2i showed more benefits in heart failure and renal outcomes, whereas GLP1RA tended to have more favorable ischemic outcomes.
•Recent guidelines recommend SGLT2i and GLP1RA for diabetic patients at higher risk.•Direct comparison of SGLT2i and GLP1RA for clinical outcomes are not yet available.•We compared the differential benefits of SGLT2i and GLP1RA on CV and renal outcomes.•SGLT2i showed more benefits in HF and renal outcomes across various subgroups.•GLP1RA tended to have more favorable ischemic outcomes (coronary events and stroke).
Renal Disorders in Pregnancy: Core Curriculum 2019 Gonzalez Suarez, Maria L.; Kattah, Andrea; Grande, Joseph P. ...
American journal of kidney diseases,
01/2019, Letnik:
73, Številka:
1
Journal Article
Recenzirano
Odprti dostop
As the incidence of chronic kidney disease increases and women pursue pregnancy at more advanced ages, the management of kidney disease in pregnancy has become increasingly relevant to the practicing ...nephrologist. Women with kidney disorders face several challenges in pregnancy due to increased physiologic demands on the kidney and risk for disease progression, the potential teratogenicity of medications, and the increased risk for complications such as preeclampsia and preterm delivery. Challenges posed by an underlying disease process in pregnancy, such as autoimmune disease or diabetes mellitus, necessitate an interdisciplinary team to ensure good maternal and fetal outcomes. Rates of acute kidney injury in pregnancy are generally declining worldwide, but remain a significant public health concern in developing countries. Pregnancy may also be the first time that a woman has kidney disease or hypertension diagnosed. An understanding of what constitutes normal physiologic changes in pregnancy is critical in a diagnostic evaluation. In this review, we review physiologic changes in pregnancy, causes and management of acute kidney injury in pregnancy, hypertensive disorders of pregnancy, and how to care for women with chronic kidney disease of various causes, including the use of antihypertensives and immunosuppressants.
The purpose of this study was to explore potential mediators of the effects of canagliflozin on heart failure in the CANVAS Program (CANagliflozin cardioVascular Assessment Study; NCT01032629 and ...CANagliflozin cardioVascular Assessment Study–Renal; NCT01989754).
Canagliflozin reduced the risk of heart failure among patients with type 2 diabetes in the CANVAS Program. The mechanism of protection is uncertain.
The percentages of mediating effects of 19 biomarkers were determined by comparing the hazard ratios for the effect of randomized treatment from an unadjusted model and from a model adjusting for the biomarker of interest. Multivariable analyses were used to assess the joint effects of biomarkers that mediated most strongly in univariable analyses.
Early changes after randomization in levels of 3 biomarkers (urinary albumin:creatinine ratio, serum bicarbonate, and serum urate) were identified as mediating the effect of canagliflozin on heart failure. Average post-randomization levels of 14 biomarkers (systolic blood pressure, low-density lipoprotein and high-density lipoprotein cholesterol, total cholesterol, urinary albumin:creatinine ratio, weight, body mass index, gamma glutamyltransferase, hematocrit, hemoglobin concentration, serum albumin, erythrocyte concentration, serum bicarbonate, and serum urate) were identified as significant mediators. Individually, the 3 biomarkers with the largest mediating effect were erythrocyte concentration (45%), hemoglobin concentration (43%), and serum urate (40%). In a parsimonious multivariable model, erythrocyte concentration, serum urate, and urinary albumin:creatinine ratio were the 3 biomarkers that maximized cumulative mediation (102%).
A diverse set of potential mediators of the effect of canagliflozin on heart failure were identified. Some mediating effects were anticipated, whereas others were not. The mediators that were identified support existing and novel hypothesized mechanisms for the prevention of heart failure with sodium glucose cotransporter 2 inhibitors.
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We sought to compare the risk of end-stage renal disease (ESRD), ischemic heart event (IHE), congestive heart failure (CHF), cerebrovascular accident (CVA), and all-cause mortality among 470,386 ...individuals with resistant and nonresistant hypertension (non-RH). Resistant hypertension (60,327 individuals) was subcategorized into two groups: 23,104 patients with cRH (controlled on four or more medicines) and 37,223 patients with uRH (uncontrolled on three or more medicines) in a 5-year retrospective cohort study. Cox proportional hazard modeling was used to estimate hazard ratios adjusting for age, gender, race, body mass index, chronic kidney disease (CKD), and comorbidities. Resistant hypertension (cRH and uRH), compared with non-RH, had multivariable adjusted hazard ratios (95% confidence intervals) of 1.32 (1.27–1.37), 1.24 (1.20–1.28), 1.46 (1.40–1.52), 1.14 (1.10–1.19), and 1.06 (1.03–1.08) for ESRD, IHE, CHF, CVA, and mortality, respectively. Comparison of uRH with cRH had hazard ratios of 1.25 (1.18–1.33), 1.04 (0.99–1.10), 0.94 (0.89–1.01), 1.23 (1.14–1.31), and 1.01 (0.97–1.05) for ESRD, IHE, CHF, CVA, and mortality, respectively. Men and Hispanics had a greater risk for ESRD within all three cohorts. Individuals with resistant hypertension had a greater risk for ESRD, IHE, CHF, CVA, and mortality. The risk of ESRD and CVA were 25% and 23% greater, respectively, in uRH compared with cRH, supporting the linkage between blood pressure and both outcomes.
Background: Previous meta-analyses demonstrated the benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i) primarily on patients with established atherosclerotic cardiovascular disease ...(ASCVD), but with questionable efficacy on patients at risk of ASCVD. Additionally, evidence of beneficial cardiorenal outcomes in patients with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m 2 with the CV outcomes trials remains unclear. Canagliflozin, one of the SGLT2i, has recently been studied in a large randomized controlled trial in diabetic patients with chronic kidney disease. Thus, there is a need to understand the combined outcomes on the population targeted for treatment with SGLT2i as a whole, regardless of ASCVD status. This meta-analysis will therefore assess the efficacy of SGLT2i in cardiovascular and renal outcomes in general, and in patients with eGFR under 60 mL/min/1.73 m 2 in particular. Methods: We searched PubMed and Cochrane databases for randomized, placebo-controlled studies involving SGLT2i. We examined composite cardiovascular outcomes of death from cardiovascular causes, nonfatal myocardial infarctions, nonfatal stroke, and heart failure hospitalizations. Renal composite outcomes and progression of albuminuria were also analyzed. Pooled relative risks (RR) and their 95% confidence intervals (CI) were calculated using a fixed-effects model. Results: The search yielded a total of 252 articles. Four studies were ultimately included in the meta-analysis after exclusion of other irrelevant studies. The pooled RR (95% CI) for the composite cardiovascular outcome was 0.93 (0.87–0.99) with a number needed to treat (NNT) of 167 in the general study population and 0.89 (0.77–1.02) in patients with eGFR <60 mL/min/1.73 m 2 . The pooled RR for all-cause mortality was 0.9 (0.84–0.97) with NNT = 143. The pooled RR for death from cardiovascular causes alone was 0.89 (0.81–0.99) in the general population and 0.82 (0.62–1.07) in patients with eGFR <60 mL/min/1.73 m 2 . The pooled RR for heart failure hospitalizations was 0.71 (0.63–0.79) with NNT = 91. With respect to renal outcomes, the pooled RR for the composite renal outcome was 0.63 (0.56–0.71) with NNT = 67; this was true even in patients with eGFR <60 mL/min/1.73 m 2 0.67 (0.59–0.76). Lastly, the pooled RR for progression of albuminuria was 0.80 (0.76–0.84). Conclusion: SGLT2i are associated with significantly lower major adverse cardiovascular events, heart failure hospitalizations, and all-cause mortality. The evidence is strongest in reducing heart failure hospitalizations. However, the evidence is weaker when it comes to the population subset with eGFR <60 mL/min/1.73 m 2 . SGLT2i are also associated with significantly lower adverse renal events, with these effects apparent even in the population with eGFR <60 mL/min/1.73 m 2 .
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