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 | 2021 Mar
REPOSITORIES: biostudies-literature
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Remdesivir in Patients With Estimated GFR <30 ml/min per 1.73 m<sup>2</sup> or on Renal Replacement Therapy.
Estiverne Christopher C Strohbehn Ian A IA Mithani Zain Z Hirsch Jamie S JS Wanchoo Rimda R Goyal Pranisha Gautam PG Lee Dryden-Peterson Scott S Pearson Jeffrey C JC Kubiak David W DW Letourneau Alyssa R AR Bhattacharyya Roby R Jhaveri Kenar D KD Sise Meghan E ME
Kidney international reports 20201127 3
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Project description:IntroductionThere has been controversy about renin-angiotensin system (RAS) inhibition in IgAN patients with advanced (stage 4) chronic kidney disease (CKD). Therefore, we investigated the effect of RAS blockade in these patients.MethodsRenal specimens of 50 IgAN patients who underwent renal biopsy during stage 4 CKD between 2010 and 2020, were stained using immunohistochemistry to detect the expression of RAS receptors (AT1R, AT2R, MasR, and MrgD). The primary endpoint was a composite of end-stage renal disease (ESRD) and death. Main baseline information and the administration of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) were collected.ResultsDuring a median follow-up time of 25.5 months, 21 (42.0%) patients reached ESRD and none died. Six patients had a baseline eGFR of 15-20 ml/min/1.73m2, and reached ESRD with a median renal survival time of 7.0 (range 6.0-23.0) months. Among patients with a baseline eGFR of 20-30 ml/min/1.73m2, the percentage of patients using ACEI/ARB in progressive group was much lower than that in stable group (33.3% vs. 62.1%, P = 0.045), together with a shorter renal survival time in progressive group (26.0 vs. 30.5 months, P = 0.033). Macroproteinuria (24 h - UP ≥ 2.5 g) was also associated with a shorter renal survival time, as well as a significant decline in eGFR of stable group (24.4 vs. 26.4 ml/min/1.73 m2, P = 0.026). Lower eGFR [hazards ratio (HR), 0.829, 95% confidence interval (CI), 0.724-0.950; P = 0.007] and use of ACEI/ARB (HR, 0.356, 95% CI, 0.133-0.953; P = 0.040) were predictive of time to ESRD in this stage. No differences were found in the expression of AT1R, AT2R, MasR, and MrgD of renal tissues at the time of biopsy between stable and progressive groups.ConclusionContingent on monitoring serum creatinine and potassium levels, IgAN with macroproteinuria and a GFR of 20-30 ml/min/1.73m2 may still benefits from intrarenal RAS inhibition.
| S-EPMC9822756 | biostudies-literature
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:PurposeTo evaluate the associations between comorbidities and kidney function decline at 6-month and 1-year follow-up in outpatients with initial estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2.Materials and methodsOutpatients aged 18 and older with confirmed diagnosis, who had eGFR ≥ 30 mL/min/1.73 m2 measured between April 2017 and March 2019, were included in this retrospective observational study. Of them, 30,595 included outpatients had 6-month eGFR test and 27,698 included outpatients had 1-year eGFR test. The outpatients were further divided into two groups based on initial eGFR: between 30 and 59 and ≥ 60 mL/min/1.73 m2. Impaired renal function was defined as eGFR declined to below 30 mL/min/1.73 m2. The comorbidities with P values less than 0.1 identified in univariable logistic regression models were entered into the multivariable analysis with backward selection, thereby identifying comorbidities that increased the risk of eGFR decline at 6-month and 1-year follow-up.ResultsOutpatients with initial eGFR between 30 and 59 mL/min/1.73 m2 were 175.94 times more likely to have eGFR decline at 6 months, and were 94.10 times more likely to have eGFR decline at 1 year, compared with their corresponding initial eGFR ≥ 60 counterparts. Multivariable logistic regression analyses disclosed that chronic kidney disease, hypertension, and heart failure were independent risk factors for eGFR decline in outpatients with initial eGFR between 30 and 59 mL/min/1.73 m2.ConclusionsOutpatients with initial eGFR ≥ 60 mL/min/1.73 m2 might not need routine eGFR test prior to contrast-enhanced CT scan for 1 year. In addition, chronic kidney disease, hypertension, and heart failure increased the risk of declined renal function, particularly, in outpatients with initial eGFR between 30 and 59 mL/min/1.73 m2.
| S-EPMC10469099 | biostudies-literature
Project description:BackgroundAlthough the kidney failure risk equation (KFRE), a well-known predictive model for predicting dialysis dependency, is useful, it remains unclear whether the addition of biomarker changes to the KFRE model in patients with an estimated glomerular filtration rate (eGFR) <30 ml/min/1.73 m2 will improve its predictive value.MethodsWe retrospectively identified adults with eGFR <30 ml/min/1.73 m2 without dialysis dependency, and available health checkup data for two successive years using a large Japanese claims database (DeSC, Tokyo, Japan). We dichotomized the entire population into a training set (50%) and a validation set (the other half). To assess the incremental value in the predictive ability for dialysis dependency by the addition of changes in eGFR and proteinuria, we calculated the difference in the C-statistics and net reclassification index (NRI).ResultsWe identified 4499 individuals and observed 422 individuals (incidence of 45.2 per 1000 person-years) who developed dialysis dependency during the observation period (9343 person-years). Adding biomarker changes to the KFRE model improved C-statistics from 0.862 to 0.921, with an improvement of 0.060 (95% confidence intervals (CI) of 0.043-0.076, P < .001). The corresponding NRI was 0.773 (95% CI: 0.637-0.908), with an NRI for events of 0.544 (95% CI of 0.415-0.672) and NRI for non-events of 0.229 (95% CI of 0.186-0.272).ConclusionsThe KFRE model was improved by incorporating yearly changes in its components. The added information may help clinicians identify high-risk individuals and improve their care.
| S-EPMC11574387 | 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