Remdesivir in Patients With Estimated GFR <30 ml/min per 1.73 m2 or on Renal Replacement Therapy.
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ABSTRACT:
SUBMITTER: Estiverne C
PROVIDER: S-EPMC7694470 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background and objectivesThe 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 <30 ml/min per 1.73 m2. The participants in the CREDENCE study had type 2 diabetes mellitus, a urinary albumin-creatinine ratio >300-5000 mg/g, and an eGFR of 30 to <90 ml/min per 1.73 m2 at screening. This post hoc analysis evaluated participants with eGFR <30 ml/min per 1.73 m2 at randomization.Design, setting, participants, & measurementsEffects of eGFR slope through week 130 were analyzed using a piecewise, linear, mixed-effects model. Efficacy was analyzed in the intention-to-treat population, on the basis of Cox proportional hazard models, and safety was analyzed in the on-treatment population. At randomization (an average of 29 days after screening), 174 of 4401 (4%) participants had an eGFR <30 ml/min per 1.73 m2 (mean [SD] eGFR, 26 [3] ml/min per 1.73 m2).ResultsFrom weeks 3 to 130, there was a 66% difference in the mean rate of eGFR decline with canagliflozin versus placebo (mean slopes, -1.30 versus -3.83 ml/min per 1.73 m2 per year; difference, -2.54 ml/min per 1.73 m2 per year; 95% confidence interval [CI], 0.90 to 4.17). Effects of canagliflozin on kidney, cardiovascular, and mortality outcomes were consistent for those with eGFR <30 and ≥30 ml/min per 1.73 m2 (all P interaction >0.20). The estimate for kidney failure in participants with eGFR <30 ml/min per 1.73 m2 (hazard ratio, 0.67; 95% CI, 0.35 to 1.27) was similar to those with eGFR ≥30 ml/min per 1.73 m2 (hazard ratio, 0.70; 95% CI, 0.54 to 0.91; P interaction=0.80). There was no imbalance in the rate of kidney-related adverse events or AKI associated with canagliflozin between participants with eGFR <30 and ≥30 ml/min per 1.73 m2 (all P interaction >0.12).ConclusionsThis 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.
| S-EPMC7769025 | biostudies-literature
Project description:BackgroundEvidence regarding the nonlinear relationship between serum uric acid (SUA) and blood lipids in Chinese population with hypertension is limited. Therefore, the present study aimed to investigate whether there is a nonlinear association between SUA and lipids in Chinese hypertensive population with an estimated glomerular filtration rate (eGFR) ≥30 ml/min/1.73 m2.MethodsA total of 13,355 hypertensive participants with eGFR ≥30 ml/min/1.73 m2 were selected from the Chinese Hypertension Registry Study. Multivariate linear regression was used to examine the linear relationship between SUA and lipids. Smooth curve fitting (penalized spline method) and threshold saturation effects were used to analyze the nonlinear association between SUA and lipids.ResultsIn the fully adjusted model, the results showed a positive correlation between SUA and TG (β = 0.15; 95% CI: 0.14, 0.16) and LDL-C (β = 0.06; 95% CI: 0.05, 0.07), respectively. However, the relationship between SUA and HDL-C was nonlinear. The inflection point of SUA was 7.24 mg/dL. On the left side of the inflection point (<7.24 mg/dL), SUA was negatively associated with HDL-C (β = -0.02; 95% CI -0.02, -0.01). On the right side of the inflection point (≥7.24 mg/dL), SUA was not related to HDL-C (β = 0.01; 95% CI -0.01, 0.02).ConclusionAfter adjusting for all covariates, SUA was positively associated with TG and LDL-C. The relationship between SUA and HDL-C was nonlinear. The negative correlation between SUA and HDL-C only existed when the SUA was less than 7.24 mg/dL in a hypertensive population with eGFR ≥30 ml/min/1.73 m2.
| S-EPMC7519986 | biostudies-literature
Project description:BackgroundLow-grade albuminuria has been considered a predictor of cardiovascular mortality. We investigated the relationship between high-normal albuminuria and subclinical atherosclerosis in non-diabetic men with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2.MethodsIn this cross-sectional study, 1,756 men with eGFR ≥60 mL/min/1.73 m2 and urine albumin-to-creatinine ratio (UACR) <30 mg/g, who attended general health checkups between April 2012 and March 2015, underwent blood sampling, urinalysis, and carotid ultrasonography. We excluded the subjects who were diabetic and/or received an anti-hypertensive drug. Carotid intima-media thickness (IMT) and the number of focal atheromatous plaques were used as indicators of subclinical atherosclerosis. Multiple linear regression analysis was performed to identify clinical factors associated with carotid IMT. Poisson regression analysis was used to assess the determinants of the carotid plaque number.ResultsMedian UACR was 4.8 mg/g (interquartile range, 3.6-6.9 mg/g). Compared with subjects with low-normal UACR (<10.0 mg/g), subjects with high-normal UACR (10.0-29.8 mg/g) had greater IMT and higher carotid plaque number. High-normal UACR was independently associated with thickened IMT in the model adjusted for conventional cardiovascular disease risk factors. Moreover, participants with high-normal UACR were also more likely to be associated with increased plaque count (prevalence ratio: 1.06; 95% confidence interval: 1.01-1.14) after adjustment for conventional cardiovascular disease risk factors.ConclusionsOur results indicate that high-normal albuminuria is associated with both carotid IMT and plaque formation in the non-diabetic male population with eGFR ≥60 mL/min/1.73 m2.
| S-EPMC6675088 | biostudies-literature
Project description:AimTo better understand the healthcare burden of people with type 2 diabetes (T2D) and estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73 m2 in Ontario, Canada.Materials and methodsWe used administrative data to evaluate the prevalence of T2D, eGFR < 90 mL/min/1.73 m2 and adverse cardiovascular co-morbidities in individuals aged ≥ 30 years living in Ontario, Canada. We also examined incremental healthcare costs and healthcare resource utilization (HCRU) for these patients with specific incident cardiovascular and renal outcomes, in comparison with controls without these outcomes.ResultsWhile the prevalence of T2D in the general population aged ≥ 30 years in Ontario increased by 1.8% over a 5-year period (2011-2012 to 2015-2016), the prevalence of eGFR < 90 mL/min/1.73 m2 among people with T2D increased by 35%. In comparison with corresponding controls without these outcomes, the per patient average total costs (Canadian dollars) over a 2-year analysis period were higher for patients with cardiovascular disease/chronic kidney disease related death ($69 827; n = 32 407), doubling of serum creatinine ($52 260; n = 22 825), those who started dialysis ($150 627; n = 3499) or received a kidney transplant ($50 664; n = 651). Similarly, HCRU was significantly greater for patients with these incident outcomes.ConclusionsThis real-world retrospective study highlights an increasing prevalence of T2D, eGFR < 90 mL/min/1.73 m2 , and the substantially higher healthcare costs and HCRU when these patients have adverse cardiovascular and renal outcomes. The existence of such a large economic burden underpins the importance of preventing these diabetes-related complications.
| S-EPMC8049006 | biostudies-literature
Project description:BackgroundThe Modification of Diet in Renal Disease (MDRD) Study equation underestimates measured glomerular filtration rate (GFR) at levels>60 mL/min/1.73 m2, with variable accuracy among subgroups; consequently, estimated GFR (eGFR)>or=60 mL/min/1.73 m2 is not reported by clinical laboratories. Here, performance of a more accurate GFR-estimating equation, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, is reported by level of GFR and clinical characteristics.Study designTest of diagnostic accuracy.Setting & participantsPooled data set of 3,896 people from 16 studies with measured GFR (not used for the development of either equation). Subgroups were defined by eGFR, age, sex, race, diabetes, prior solid-organ transplant, and body mass index.Index testseGFR from the CKD-EPI and MDRD Study equations and standardized serum creatinine.Reference testMeasured GFR using urinary or plasma clearance of exogenous filtration markers.ResultsMean measured GFR was 68+/-36 (SD) mL/min/1.73 m2. For eGFR<30 mL/min/1.73 m2, both equations have similar bias (median difference compared with measured GFR). For eGFR of 30-59 mL/min/1.73 m2, bias was decreased from 4.9 to 2.1 mL/min/1.73 m2 (57% improvement). For eGFR of 60-89 mL/min/1.73 m2, bias was decreased from 11.9 to 4.2 mL/min/1.73 m2 (61% improvement). For eGFR of 90-119 mL/min/1.73 m2, bias was decreased from 10.0 to 1.9 mL/min/1.73 m2 (75% improvement). Similar or improved performance was noted for most subgroups with eGFR<90 mL/min/1.73 m2, other than body mass index<20 kg/m2, with greater variation noted for some subgroups with eGFR>or=90 mL/min/1.73 m2.LimitationsLimited number of elderly people and racial and ethnic minorities with measured GFR.ConclusionsThe CKD-EPI equation is more accurate than the MDRD Study equation overall and across most subgroups. In contrast to the MDRD Study equation, eGFR>or=60 mL/min/1.73 m2 can be reported using the CKD-EPI equation.
| S-EPMC2926290 | biostudies-literature
Project description:Large volume fluid resuscitation is currently viewed as the cornerstone of the treatment of septic shock. The surviving sepsis campaign (SSC) guidelines provide a strong recommendation to rapidly administer a minimum of 30 mL/kg crystalloid solution intravenously in all patients with septic shock and those with elevated blood lactate levels. However, there is no credible evidence to support this recommendation. In fact, recent findings from experimental, observational and randomized clinical trials demonstrate improved outcomes with a more restrictive approach to fluid resuscitation. Accumulating evidence suggests that aggressive fluid resuscitation is harmful. Paradoxically, excess fluid administration may worsen shock. In this review, we critically evaluate the scientific evidence for a weight-based fluid resuscitation approach. Furthermore, the potential mechanisms and consequences of harm associated with fluid resuscitation are discussed. Finally, we recommend an individualized, conservative and physiologic guided approach to fluid resuscitation.
| S-EPMC7024756 | biostudies-literature
Project description:UnlabelledCortical porosity is increasingly recognized as an important risk for fracture in DM patients. The present study demonstrated that decreased cortical thickness, assessed using a newly developed quantitative ultrasonic bone densitometry, is a significant risk factor for vertebral fractures in type 2 diabetes mellitus patients with stage 3 or higher chronic kidney disease, but not in those without.IntroductionCortical porosity is increasingly recognized as an important risk factor for fracture in type 2 diabetes mellitus (T2DM) patients as well as in stage 3 chronic kidney disease (CKD) patients in whom serum parathyroid hormone (PTH) starts to increase. The present study aimed to clarify whether the coexistence of CKD might affect the relationship of decreased cortical thickness (CoTh) in the development of vertebral fractures (VF) in T2DM patients.MethodsIn this cross-sectional study, trabecular bone mineral density (TrBMD), elastic modulus of trabecular bone (EMTb), and CoTh were estimated with a new quantitative ultrasound bone densitometry in 173 T2DM patients. VFs were identified radiographically.ResultsThirty-nine patients (22.5%) had VF. Those with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2) (low eGFR) showed a significantly higher VF rate (32.4%) than those with eGFR ≥60 mL/min/1.73 m(2) (high eGFR, 16.2%). Serum PTH was significantly higher with low eGFR than with high eGFR. In those with high eGFR, EMTb was significantly lower in VF(+) than VF(-). In those with low eGFR, TrBMD, EMTb, and CoTh were significantly lower in VF(+) than in VF(-). In a multivariate logistic regression analysis, EMTb was independently and significantly associated with VF in T2DM patients with a high eGFR, in contrast to those with only CoTh with VF in T2DM with low eGFR.ConclusionThis study demonstrated CoTh as a factor independently associated with VF in T2DM patients with low eGFR and increasing serum PTH levels.
| S-EPMC4286635 | biostudies-literature
Project description:Edoxaban 60 mg is approved for stroke prevention in patients with atrial fibrillation (AF) not fulfilling any dose-reduction criteria. As edoxaban is partially renally cleared (≈50%), this study compared pharmacokinetics (PK) and pharmacodynamics of edoxaban 60 mg once daily with edoxaban 75 mg once daily in patients with AF with high renal clearance (creatinine clearance > 100 mL/min) over 12 months. Primary PK and pharmacodynamics end points were plasma edoxaban exposure and anti-factor Xa (FXa) concentration. A population PK model estimated edoxaban exposure at steady state. Efficacy and safety outcomes included composites of stroke, transient ischemic attack, systemic embolism, and major and clinically relevant nonmajor bleeding. Of 607 patients, 303 and 304 were randomized to edoxaban 60 and 75 mg, respectively. Edoxaban 75 mg provided ≈25% higher exposure than 60 mg. This increase was accurately depicted in the population PK model; anti-factor Xa concentration correlated with edoxaban exposure. Rates of composite and individual outcomes were similarly low between doses. In conclusion, the 25% increase in edoxaban dose (60-75 mg) resulted in ≈25% exposure increase in the 75-mg group. Higher exposure was not associated with reduced stroke risk in patients with AF with high renal clearance.
| S-EPMC9299591 | biostudies-literature
Project description:BackgroundData regarding the association between 24h urinary sodium and potassium excretion with kidney outcomes in patients with diabetes mellitus is currently scarce.MethodsWe conducted a single-center, retrospective cohort study in which 1230 patients with diabetes who had undergone a 24h urinary sodium and potassium excretion test were analyzed. Patients with incomplete urine collection were excluded based on 24h urinary creatinine excretion. Outcomes were the composite of a 30% decline in eGFR or death. Multivariate cox regression analysis was used to investigate the association between urinary sodium and potassium excretion and outcomes.ResultsWith a mean follow up period of 5.47 years, 130 patients reached the outcomes (30% decline in eGFR: 124, death: 6). Mean (SD) eGFR and 24h urinary sodium and potassium excretion at baseline were 78.6 (19.5) ml/min/1.73m2, 4.50 (1.64) g/day, and 2.14 (0.77) g/day. Compared with sodium excretion < 3.0 g/day, no significant change in risk of outcomes was observed with increased increments of 1.0 g/day. Compared with potassium excretion of < 1.5 g/day, 2.0-2.5 g/day, and 2.5-3.0 g/day were significantly associated with a lower risk of outcomes (hazard ratio [HR], 0.49 and 0.44; 95% confidence interval [CI], 0.28 to 0.84 and 0.22 to 0.87).Conclusions24h urinary sodium excretion was not significantly associated with a risk of 30% decline in eGFR or death in patients with diabetes. However, an increased risk of 30% decline in eGFR or death was significantly associated with 24h urinary potassium excretion < 1.5 g/day than with 2.0-2.5 g/day and 2.5-3.0 g/day.
| S-EPMC4852934 | biostudies-literature
Project description:Despite cardiovascular disease (CVD) and chronic kidney disease sharing similar causes and interplay, it is unknown if a broader relationship between these diseases exists across generations. We investigated the association between parental CVD history and estimated glomerular filtration rate (eGFR) in the community.Cross-sectional and longitudinal analyses.13,241 community-based adults with serum creatinine measurement and follow-up visits (from 1-8 visits ~2 years apart) from the Aerobics Center Longitudinal Study.Premature parental CVD history (before age 50 years).eGFR, decreased eGFR (<60 mL/min/1.73 m(2)), and rate of eGFR decline.Information for parental history was collected by protocol-standardized questionnaires. eGFR was assessed with serum creatinine.3,339 (25.2%) participants reported a history of parental CVD. Individuals with parental CVD had significantly lower eGFRs compared with those without parental CVD (69.4 ± 12.9 vs 74.8 ± 14.2 mL/min/1.73 m(2); P<0.001). After multivariable adjustment, parental CVD was associated independently with higher odds of having decreased eGFR (adjusted OR, 1.68; 95% CI, 1.52-1.86). Random-coefficient models showed that individuals with parental CVD had a faster decline in eGFR compared with those without parental CVD (sex- and ethnicity-adjusted annual change of -0.47 vs -0.41 mL/min/1.73 m(2); P=0.06).~70% of participants did not attend a second examination.Parental history of CVD was associated with lower baseline eGFR, higher odds of decreased eGFR, and a nominally faster rate of eGFR decline in the offspring. Such findings may imply previously unrecognized cross-generational links between both diseases and be of support in community screening programs.
| S-EPMC4414720 | biostudies-literature