Moderate Renal Function Research Articles

Recommendation of pharmacokinetics/pharmacodynamics target of ethambutol to suppress tuberculosis resistance: A population pharmacokinetics study on a large prospective cohort

The ability of ethambutol (EMB) to suppress bacterial resistance has been demonstrated in a time-dependent manner. Through the development of a population pharmacokinetics (PK) model, this study aimed to suggest the PK/pharmacodynamics (PD) target and identify the significant covariates that influence interindividual variability (IIV) in the PK of EMB. In total, 837 patients from 20 medical centres across Korea were enrolled in this study. The non-linear mixed-effect method was used to establish and validate the population PK model. A two-compartment model with transit compartment absorption was sufficient to describe the PK of EMB. Body weight and renal function were identified as significant covariates that affect IIV of the apparent clearance (CL/F) of EMB. Patients with moderate renal function showed 35% and 55% lower CL/F (CL/F 89.9 L/h) compared with those with mild and normal renal function, respectively. All the renal function groups with simulated doses ranging from 800 to 1200 mg achieved area under the curve over minimum inhibitory concentration (MIC) >119, and maintained T>MIC for >23 h for MIC of 0.5 µg/mL. Based on our simulation result, it is suggested that doses of 800, 1000, and 1200 mg should obtain the T>MIC target of 4, 6, and 8 h, respectively. This model was validated internally and externally. This study provides insight into the PK/PD indexes of EMB for three different renal function groups and T>MIC targets for different doses. The results could be used to provide optimal-dose suggestions for EMB.

Population Pharmacokinetic Model for Unbound Concentrations of Daptomycin in Patients with MRSA Including Patients Undergoing Hemodialysis.

Unbound daptomycin concentrations are responsible for pharmacologically beneficial and adverse effects, although most previous reports have been limited to the use of total concentrations. We developed a population pharmacokinetic model to predict both total and unbound daptomycin concentrations. Clinical data were collected from 58 patients with methicillin-resistant Staphylococcusaureus including patients undergoing hemodialysis. A total of 339 serum total and 329 unbound daptomycin concentrations were used for model construction. Total and unbound daptomycin concentration was explained by a model that assumed first-order distribution with two compartments, and first-order elimination. Normal fat body mass was identified as covariates. Renal function was incorporated as a linear function of renal clearance and independent non-renal clearance. The unbound fraction was estimated to be 0.066 with a standard albumin of 45g/L and standard creatinine clearance of 100mL/min. Simulated unbound daptomycin concentration was compared with minimum inhibitory concentration as a measure of clinical effectiveness and exposure-level-related induction of creatine phosphokinase elevation. The recommended doses were 4mg/kg for patients with severe renal function [creatinine clearance (CLcr) ≤30mL/min] and 6mg/kg for patients with mild to moderate renal function (CLcr>30 and ≤60mL/min). A simulation indicated that dose adjusted by body weight and renal function improved target attainment. This population pharmacokinetics model for unbound daptomycin could help clinicians to select the appropriate dose regimen for patients undergoing daptomycin treatment and reduce associated adverse effects.

Pharmacokinetic and dose-finding study of osimertinib in patients with impaired renal function and low body weight.

The safety of osimertinib is limited in patients with severe or moderate renal impairment, or low body weight. This study aimed to investigate the safety, pharmacokinetics (PK) and recommended dose (RD) of osimertinib in patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) with impaired renal function and low body weight. Thirty-one eligible patients were enrolled and allocated into four cohorts: A, normal renal function (estimated glomerular filtration rate [eGFR] ≥ 50 mL/min/1.73 m2 ) and normal body weight (≥45 kg); B, moderate renal impairment (eGFR=30-50 mL/min/1.73 m2 ); C, low body weight (<45 kg); and D, severe renal impairment (eGFR <30 mL/min/1.73 m2 or undergoing dialysis). PK parameters and safety were evaluated with a starting dose of 80 mg osimertinib administered orally once daily in cohorts A, B, and C and 40 mg once daily in cohort D. The PK parameters in cohorts A, B, and C were found to be similar. No dose-limiting toxicity was observed, and the RD was determined to be 80 mg once daily in patients with moderate renal function and low body weight. Four serious adverse events, acneiform rash, diarrhea, QTc prolongation, and interstitial lung disease, were noted. Although the PK parameters of osimertinib were similar across all cohorts, toxicity occurred more frequently in patients with impaired renal function and low body weight. Clinicians should prescribe osimertinib with caution in NSCLC patients with impaired renal function and low body weight.

Clinical Characteristics and Prognosis of Diabetic Foot Ulcers Patients of Different Renal Function Statuses

To explore the clinical characteristics and the prognosis of diabetic foot ulcers (DFU) inpatients of different renal function statuses. A retrospective analysis of 962 inpatients with DFU was conducted. The patients were divided into three groups according to their renal function statuses, and the clinical characteristics of the three groups were compared to identify differences. In addition, the patients were followed up in outpatient clinics or by telephone and their prognostic status and risk factors for death were analyzed. Analysis of the clinical characteristics showed that, compared with diabetic patients with normal renal function or mild renal function impairment, diabetic patients with moderate and severe renal function impairment had a longer course of disease ( P<0.001). Patients with foot ulcers of Wagner grade 4 predominates the moderate and severe renal function impairment groups ( P<0.05). Patients in the moderate and severe renal function impairment groups had a relatively higher proportion of comorbidities, including hypertension, coronary heart disease, and peripheral arterial disease ( P<0.05). These patients had relatively lower levels of glycosylated hemoglobin and hemoglobin (all P<0.05) and relatively higher levels of neutrophil ratio and procalcitonin (all P<0.05). Of the two groups, patients in the moderate renal function impairment group were older ( P<0.001) and had lower ankle-brachial index ( P<0.001). The severe renal function impairment group had a higher proportion of patients with foot ulcers of Wagner grades 3 and 5 (all P<0.05). For the purpose of conducting prognostic analysis, 748 patients were followed up in outpatient clinics or by telephone for a median length of 41 months. Among them, 239 died. The all-cause mortality was 31.9%, and the mortality in the three groups was 25.8%, 46.2% ( P<0.001), and 59.4% ( P<0.001), respectively. The survival rate of patients in the moderate and severe renal function impairment groups was significantly lower than those in the normal renal function and mild renal function impairment groups ( P<0.001). Univariate Cox regression analysis showed that age, concomitant coronary heart disease and peripheral arterial disease, degree of renal function impairment, and foot ulcers of Wagner grade 4 and 5 were associated with all-cause deaths. Furthermore, multivariate Cox regression analysis showed that moderate and severe renal function impairment was an independent risk factor for all-cause deaths in DFU patients ( P<0.001). As renal function impairment worsens, patients with DFU present clinical characteristics of greater complexity, higher risks of cardiovascular events, and higher mortality. It is essential to prevent kidney damage and foot ulcers, to pay attention to the cardiovascular risks of DFU patients with moderate and severe renal function impairment, and to reduce mortality.

Association between physical activity and mortality in the Japanese general population with mild to moderate impaired renal function: the Jichi Medical School (JMS) cohort study.

The association between physical activity volume or intensity and mortality in general population with impaired renal function is unclear. We assessed these relationships among Japanese residents with impaired renal function. We analyzed 638 individuals with estimated creatinine clearance below 60ml/min in the Jichi Medical School cohort study. Exposures included the daily amount of physical activity converted to the physical activity index (PAI) used in the Framingham study and the activity time for each intensity. Physical activity intensity was classified into sedentary and nonsedentary. Nonsedentary activity was further divided into light-intensity and moderate-to-vigorous physical activity (MVPA). The outcome was all-cause mortality. Quartiles of the exposures were created, and hazard ratios (HRs) were calculated using the Cox proportional hazards model. The mean age of the subjects was 63.3years, and 72.4% were female. In total, 172 deaths were registered during 11,567 person-years. No significant association was found between PAI and mortality. A significant association was found between long sedentary time and increased mortality (p = 0.042). Regarding nonsedentary activity, the HRs [95% confidence intervals (CIs)] for Q2, Q3, and Q4 versus Q1 were 0.85 (0.55-1.31), 0.67 (0.41-1.08), and 0.90 (0.54-1.45), respectively. In the subdivided analysis for light-intensity activity, the HRs (95% CIs) of Q2, Q3, and Q4 versus Q1 were 0.53 (0.33-0.84), 0.51 (0.34-0.82), and 0.57 (0.34-0.96), respectively. No significant association was found between MVPA and mortality. Nonsedentary activity, especially light-intensity activity, significantly reduced mortality among residents with impaired renal function.

Population Pharmacokinetic Analysis Proves Superiority of Continuous Infusion in PK/PD Target Attainment with Oxacillin in Staphylococcal Infections.

Considering its very short elimination half-life, the approved oxacillin dosage might not be sufficient to maintain the pharmacokinetic/pharmacodynamics (PK/PD) target of time-dependent antibiotics. This study aimed to describe the population pharmacokinetics of oxacillin and to explore the probability of PK/PD target attainment by using various dosing regimens with oxacillin in staphylococcal infections. Both total and unbound oxacillin plasma concentrations retrieved as a part of routine therapeutic drug-monitoring practice were analyzed using nonlinear mixed-effects modeling. Monte Carlo simulations were used to generate the theoretical distribution of unbound oxacillin plasma concentration-time profiles at various dosage regimens. Data from 24 patients treated with oxacillin for staphylococcal infection have been included into the analysis. The volume of distribution of oxacillin in the population was 11.2 L, while the elimination rate constant baseline of 0.73 h-1 increased by 0.3 h-1 with each 1 mL/s/1.73 m2 of the estimated glomerular filtration rate (eGFR). The median value of oxacillin binding to plasma proteins was 86%. The superiority of continuous infusion in achieving target PK/PD values was demonstrated and dosing according to eGFR was proposed. Daily oxacillin doses of 9.5 g, 11 g, or 12.5 g administered by continuous infusion have been shown to be optimal for achieving target PK/PD values in patients with moderate, mild, or normal renal function, respectively.

The Urinary Glucose Excretion by Sodium–Glucose Cotransporter 2 Inhibitor in Patients With Different Levels of Renal Function: A Systematic Review and Meta-Analysis

ObjectivePrevious evidence suggested that sodium–glucose cotransporter 2 inhibitor (SGLT2i)-mediated urinary glucose excretion (UGE) appeared to be reduced with a decrease in glomerular filtration rate. Thus, we conducted a systematic review and meta‐analysis to compare SGLT2i-mediated UGE among individuals with different levels of renal function.MethodsWe conducted systematic searches in PubMed, Medline, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrial.gov from inception to May 2021. Clinical studies of SGLT2i with reports of UGE changes in predefined different levels of renal function were included. The results were expressed as pooled effect sizes with 95% confidence interval (CI). A random-effects model was used to calculate the pooled effect sizes.ResultsIn total, eight eligible studies were included. Significant differences were observed in the post-treatment UGE level among subgroups stratified by renal function (P <0.001 for subgroup difference), which were gradually decreased along with the severity of impaired renal function. Consistently, changes in UGE before and after SGLT2i treatment were also decreased along with the severity of impaired renal function [67.52 g/day (95%CI: 55.58 to 79.47 g/day) for individuals with normal renal function, 52.41 g/day (95%CI: 38.83 to 65.99 g/day) for individuals with mild renal function impairment, 35.11 g/day (95%CI: 19.79 to 50.43 g/day) for individuals with moderate renal function impairment, and 13.53 g/day (95%CI: 7.20 to 19.86 g/day) for individuals with severe renal function impairment; P <0.001 for subgroup differences].ConclusionsSGLT2i-mediated UGE was renal function dependent, which was decreased with the extent of renal function impairment.

Benefit and risk of adding rivaroxaban in patients with coronary artery disease: A systematic review and meta-analysis.

BackgroundAlthough the European Medicines Agency and the US Food and Drug Administration have, respectively, approved rivaroxaban for the prevention of recurrent major adverse cardiovascular events in patients with myocardial infarction and stable coronary artery disease, its efficacy and safety is unclear. This meta‐analysis aimed to evaluate the benefit and risk of adding rivaroxaban in coronary artery disease (CAD) patients, focusing on treatment effects stratified by different baseline clinical presentations.HypothesisThere are differences in treatment effects of adding rivaroxaban among CAD patients with different baseline clinical presentations.MethodsMedline, EMBASE, and Cochrane Databases were systematically searched from inception to 21 July 2020 for randomized controlled trials (RCTs) comparing rivaroxaban in CAD patients. The primary efficacy endpoint and safety endpoint were assessed by using Mantel–Haenszel pooled risk ratios (RRs) and 95% confidence intervals (CIs).ResultsFive RCTs that included 43 650 patients were identified. Patients receiving rivaroxaban had a significantly lower risk of the primary efficacy endpoint (RR, 0.86; 95% CI, 0.76–0.97, p = .01) accompanied by increased risk of the primary safety endpoint (RR, 1.83; 95% CI, 1.10–3.05, p = .02). Subgroup analyses showed that in males the risk–benefit appears to be more favorable while in patients ≥65 years, in females, in patients with diabetes, those with mild to moderate impaired renal function, and region of Asia/other seems unfavorable.ConclusionRivaroxaban may provide an additional choice for secondary prevention in CAD patients. However, careful estimation of the risk of ischemic and bleeding events using patient characteristics are critical to achieving net benefit.

Oseltamivir-Current Dosing Recommendations Reduce the Therapeutic Benefit in Patients With Mild to Moderate Renal Function and/or Large Body Mass: A Review of the Literature With Recommendations to Optimize Dosing, Including the Use of Therapeutic Drug Monitoring.

Oseltamivir is indicated for the treatment and prophylaxis of influenza infections. Achieving therapeutic concentrations EARLY in the course of the infection impacts greatly on the magnitude of benefit. Oseltamivir is renally cleared and dose reductions are advised for patients with renal impairment. The purpose of this review was to determine whether these dose reductions facilitate the early attainment of therapeutic concentrations. The review also examined the effect of body mass on the same outcome. Oseltamivir is administered as a prodrug and converted to the active carboxylate moiety in the liver. Published articles that included oseltamivir carboxylate (OC) pharmacokinetics in patients with renal impairment and those with large body mass were reviewed. Concentrations of OC achieved in the first 24 hours were compared with those from patients with normal renal function and body mass. Studies that informed dosage regimens for patients with mild to moderately impaired renal function focused on attaining steady-state concentrations similar to those observed in patients with normal renal function. They overlooked the importance of achieving therapeutic concentrations EARLY in the course of the infection. As a result, many patients will not attain therapeutic concentrations until too late in the infection. This is also true for patients with a large body mass. Current dosing advice for oseltamivir in patients with mild to moderate renal impairment and those with a larger body mass are likely to reduce (or even negate) its efficacy. The first dose should be 75 mg for patients with normal body mass and proportionately larger when body mass is larger. Subsequent doses should be reduced in proportion to the degree of renal impairment. Timely therapeutic drug monitoring can provide invaluable dosing (and other) information to the clinician treating patients with influenza and could improve patient outcomes.

Does Renal Function Remain Stable after Puberty in Children who underwent Ureteral Reimplantation due to Ureterovesical Junction Obstruction?

Ureteric reimplantation due to ureterovesical junction (UVJ) obstruction enjoys high success in the short term. However, renal function after reimplantation must accommodate the numerous changes in the pediatric urinary tract that occur along with child development that may theoretically cause an occult loss of renal function. The purpose of this study was to evaluate whether improved renal function after ureter reimplantation for antenatal diagnosed UVJ obstruction remains stable after puberty. Twenty-one children who underwent open reimplantation using Politano-Leadbetter technique were followed until they completed puberty. Mean age at surgery was 14.3 months (range: 3-60 months). Five (23.8%) of 21 children had right hydronephrosis, 13 (61.9%) had left hydronephrosis, and 3 (14.3%) had bilateral hydronephrosis. The Society for Fetal Urology (SFU) level of the hydronephrosis was 3 (47.6%) in 10 children and 4 (52.4%) in remaining 11. Fourteen (66.6%) patients had poor renal function upon surgery and the remaining seven (33.4%) patients had moderate renal function. The mean renal function upon operation was 28 ± 4.3 (mean ± standard deviation [SD]). Reimplantation led to the increase in the RRF in the short-term period from 28 ± 4.3% prior to the surgery to 36.4 ± 5% (p < 0.001) in all patients and remains stable 35 ± 5% after puberty in all the reviewed patients. Our data demonstrate for the first time that successful ureteral reimplantation following antenatal diagnosis of UVJ obstruction is associated with an improvement in renal function, not only during short- and midterm follow-up but also allows preserving the renal function throughout the puberty period.

Concomitant management of renal calculi and recurrent ureteropelvic junction obstruction with percutaneous nephrolithotomy and antegrade balloon dilation.

ObjectiveThis study aimed to present our experience of concomitant management of renal calculi and recurrent ureteropelvic junction obstruction (UPJO) with percutaneous nephrolithotomy (PCNL) and antegrade balloon dilation.MethodsWe retrospectively reviewed 31 patients who underwent PCNL and antegrade balloon dilation for treatment of renal calculi and recurrent UPJO. The inclusion criterion was the presence of UPJO after failed pyeloplasty with ipsilateral renal calculi. Success was defined as achievement of both symptomatic and radiographic resolution of any stones and obstruction.ResultsAll operations were successful without grade III or higher postoperative complications. A stone-free status was observed in all patients and the overall success rate of the procedure was 87.1% (27/31). The success rate of the procedure was significantly higher in patients with mild or moderate preoperative hydronephrosis (96%) than in those with high-grade preoperative hydronephrosis (50%). Moreover, the success rate of the procedure was lower in patients with poor preoperative renal function (0%) than in those with good or moderate renal function (93.1%).ConclusionCombined PCNL and antegrade balloon dilation management represents a safe and effective approach for patients with renal calculi and recurrent UPJO after failed pyeloplasty.

Efficacy and Safety of Non-Vitamin K Anticoagulants for Atrial Fibrillation in Relation to Different Renal Function Levels: A Network Meta-Analysis.

Background We performed a network meta-analysis (NMA) comparing the efficacy (stroke or systemic embolism) and safety (major bleeding) among different non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation (AF) and renal impairment, with the aim of recommending the proper drug and the dose based on renal function. Methods We searched PubMed, EMBASE, Web of Science, and Cochrane Library with the items “dabigatran, edoxaban, apixaban, rivaroxaban, warfarin, and atrial fibrillation” through August 2019. NMA was analyzed with R (version 3.5.1, R Foundation for Statistical Computing) with the packages gemtc recalling JAGS (version 4.3.0) for the efficacy and safety of each drug with regard to different levels of renal function. NetMetaXL (version 1.6.1) and winBUGS (version 1.4.3) were used to obtain the cumulative ranking curve (SUCRA) of each drug. Result In patients with normal renal function, dabigatran150 was ranked as the most effective drug (SUCRA 0.90), followed by dabigatran110 (SUCRA 0.68), apixaban (SUCRA 0.66), and rivaroxaban (SUCRA 0.59). With regard to the safety for preventing major bleeding, there was high probability that edoxaban30 (SUCRA 0.99) ranked first, compared to dabigatran110 (SUCRA 0.78) and edoxaban60 (SUCRA 0.66). For patients with mild renal impairment, with respect to the most effective drug for preventing stroke or systemic embolism, edoxaban60 ranked first (SUCRA 0.98), in comparison with dabigatran150 (SUCRA 0.74) and apixaban (SUCRA 0.64). Possibility of ranking first for the safest drug was edoxaban30 (SUCRA 0.99), followed by dabigatran110 (SUCRA 0.70) and apixaban (SUCRA 0.69). In patients with moderate renal function, dabigatran150 (SUCRA 0.95) ranked as the most effective drug in comparison with apixaban (SUCRA 0.66). Dabigatran110 (SUCRA 0.53), rivaroxaban (SUCRA 0.51), and edoxaban60 (SUCRA 0.50) had the similar probability of ranking third. When referred to the safest drug, probability of ranking first for preventing major bleeding was edoxaban30 (SUCRA 0.98), followed by apixaban (SUCRA 0.85) and edoxaban60 (SUCRA 0.64). Conclusion In patients with AF and renal impairment and for patients with normal renal function, dabigatran 110 mg (bid) might have a better effect on the clinical results. And it does not coincide with patients taking dabigatran 110 mg with dose reduction for other factors including aged ≥75 years, renal impairment (CrCL 30–50 mL/min), gastritis, esophagitis, or gastroesophageal reflux, receiving concomitant verapamil, and so on. For patients with mild renal impairment, apixaban 5 mg (bid) would be a better choice for preventing stroke or systemic embolism and major bleeding, while apixaban 5 mg (bid) and edoxaban 60 mg (qd) were recommended for patients with moderate renal impairment. However, considering the fact of no RCTs for the head-to-head comparison, caution should be exercised over selecting each of NOACs for patients.

Effect of Dipeptidyl Peptidase 4 Inhibitors on Cardiovascular Events in Type-2 Diabetes Patients with Renal Impairment: A Systematic Review and Meta-analysis.

Background:Recent studies suggested that the increased risk of heart failure by DPP-4 inhibitors may have an interconnection with patients' baseline eGFR. We decided to investigate the effect of DPP-4 inhibitors and the degree of renal function on cardiovascular (CV) safety in type 2 diabetes (T2D) patients.Materials and Methods:Systemic search of literature that examined the DPP-4 inhibitors and reported cardiovascular outcomes in diabetes patients with renal impairment were performed. Studies were examined for inclusion criteria: Randomized controlled trials with reduced renal function taking DPP-4 inhibitors alone or in combination with other anti-diabetes agents reporting evaluable CV events for at least 24 weeks.Result:Analysis of four CV outcome studies (11,789 patients with eGFR ≤60 ml/min/1.73m2) did not find any increase in primary composite endpoints with DPP-4 inhibitors in patients stratified by baseline renal function. Rate of hospitalization due to heart failure (hHF) is found to be non-inferior to placebo group in patients with renal insufficiency (RR 1.07; 95% CI, 0.96-1.20 P = 0.26). In moderate renal dysfunction, there is a significant increase in heart failure risk compared to placebo. (RR 1.27; 95% CI, 1.033 -1.5 8; P = 0.024).Conclusion:Treatment with DPP-4 inhibitors did not affect the risk of cardiovascular events regardless of baseline renal function, however, an increase in the risk of hHF in moderate renal function in T2D patients with high CV risk merits careful consideration. Further research would be necessitated to reach definitive conclusion to understand the effect of declining renal function on CV safety of DPP-4 inhibitors.

Correlation of Serum 1,5-AG with Uric Acid in Type 2 Diabetes Mellitus with Different Renal Functions.

Aim Recent studies found that levels of serum uric acid (SUA) were positively associated with serum 1,5-anhydroglucitol (1,5-AG) in subjects with type 2 diabetes mellitus (T2DM). In the current study, we investigated the association between 1,5-AG and UA in T2DM patients with different renal functions. Methods A total of 405 T2DM patients, 213 men and 192 women, participated in the study. Patients' clinical information was collected, and serum 1,5-AG, SUA, and other clinical characteristics were measured. Correlation analyses were carried out to analyze their correlation with serum 1,5-AG and SUA. Results The male group showed higher levels of SUA than the female group (282.1 ± 91.2 and 244.7 ± 71.89 μmol/L, respectively, P < 0.01). Pearson's correlation coefficients determine that SUA was positively associated with 1,5-AG in both men (r = 0.213, P < 0.05) and women (r = 0.223, P < 0.05), and such relationship can be influenced by the renal function. The positive association still existed with moderate impaired renal function. Moreover, 1,5-AG had a negative association with haemoglobin A1c (HbA1c) in T2DM subjects with eGFR ≥ 30 mL/min/1.73 m2 (P < 0.01). Conclusion The positive association between SUA and 1,5-AG still exists in T2DM with moderate renal failure. 1,5-AG can still reflect the glucose levels in patients with CKD stages 1-3.

Mediterranean Diet Score: Associations with Metabolic Products of the Intestinal Microbiome, Carotid Plaque Burden, and Renal Function.

Metabolic products of the intestinal microbiome such as trimethylamine N-oxide (TMAO) that accumulate in renal failure (gut-derived uremic toxins, GDUTs) affect atherosclerosis and increase cardiovascular risk. We hypothesized that patients on a Mediterranean diet and those consuming lower amounts of dietary precursors would have lower levels of GDUTs. Patients attending vascular prevention clinics completed a Harvard Food Frequency Questionnaire (FFQ) and had plasma levels of TMAO, p-cresylsulfate, hippuric acid, indoxyl sulfate, p-cresyl glucuronide, phenyl acetyl glutamine, and phenyl sulfate measured by ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. Carotid plaque burden was measured by ultrasound; CKD-Epi equations were used to estimate the glomerular filtration rate. In total, 276 patients completed the study. Even moderate renal function significantly increased plasma GDUTs, which were significantly associated with higher carotid plaque burden. There was no significant difference in plasma levels of any GDUT associated with a Mediterranean diet score or with intake of dietary precursors. In omnivorous patients with vascular disease, the intake of dietary precursors of intestinal metabolites or adherence to a Mediterranean diet did not change plasma GDUT. Approaches other than diet, such as probiotics and repopulation of the intestinal microbiome, may be required to mitigate the adverse effects of GDUTs.

Efficacy and safety of sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes and moderate renal function impairment: A systematic review and meta-analysis

AimsA systematic review and meta-analysis was conducted to evaluate the clinical efficacy and safety of sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with type 2 diabetes (T2D) and moderate renal function impairment. MethodsEmbase, Medline, and Cochrane Central were searched, and randomized controlled trials comparing SGLT2 inhibitors to placebos and other drugs for T2D were collected. ResultsSeven RCTs with a total of 3307 participants were included, and the overall bias was low. In the patients with T2D and moderate renal function impairment (30 ml/min/1.73 m2 ≤ estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2) compared with the placebo, SGLT2 inhibitors improved HbA1c significantly (WMD, −0.23%; 95% CI: −0.38 to −0.08), presented a lower incidence of hypoglycemia (30.1% vs. 34.6%; RR, 0.85; 95% CI: 0.76 to 0.96), led to the reduction of eGFR (WMD, −1.74 ml/min/1.73 m2; 95% CI: −3.45 to −0.03), resulted in an obvious reduction in body weight (WMD, −1.45 kg; 95% CI: −2.01 to −0.89), and presented a similar risk of urinary tract infection and genital infection. ConclusionsSGLT2 inhibitors are safe, but mildly reduce the HbA1c level. The clinical significance of SGLT2 inhibitors in the target population was limited.

Differential Impact of Chronic Kidney Disease on Coronary Calcification and Atherosclerosis in Asymptomatic Individuals with or without Diabetes: Analysis from a Coronary Computed Tomographic Angiography Registry

Aim: The aim of this study was to assess the combined effects of chronic kidney disease (CKD) and diabetes on the extent and developmental pattern of coronary artery disease (CAD). Methods: A total of 3,017 self-referred asymptomatic individuals without known CAD who underwent 64-channel dual-source coronary computed tomography angiography between 2006 and 2010 were enrolled. The patients were divided into six groups based on their diabetes status (nondiabetic or diabetic) and estimated glomerular filtration rate (eGFR) (eGFR > 90 mL/min/1.73 m², normal renal function; eGFR 60–89, mild CKD; or eGFR 30–59, moderate CKD). We compared the coronary artery calcium score (CACS), segment stenosis score (SSS), and ≥50% obstructive CAD among the groups. Results: In nondiabetics, whereas SSS and ≥50% obstructive CAD were not different as renal function deteriorated, after adjusting for cardiovascular risk factors, CACS showed a unique developmental pattern: no CACS increase until mild CKD, but abrupt increase from the stage of moderate CKD (moderate vs. normal renal function, adjusted OR 5.118, 95% CI 1.293–20.262, p = 0.020). In diabetics, patients from the stage of mild CKD were more likely to have ≥50% obstructive CAD (p = 0.004), higher CACS (p = 0.020), and SSS (p = 0.001) in multivariable analysis. Conclusions: The presence of CKD did not have a significant impact on the development of coronary atherosclerosis, but affected the progression of coronary calcification more markedly from the stage of moderate CKD in nondiabetics. However, in diabetics, the deterioration of renal function was significantly associated with the development of coronary atherosclerosis and calcification from the stage of mild CKD.

Meta-analysis of safety and efficacy for direct oral anticoagulation treatment of non-valvular atrial fibrillation in relation to renal function

IntroductionWe performed a meta-analysis of the safety and efficacy of anticoagulation treatment for atrial fibrillation (AF) in relation to renal function. We also examined the change in estimated glomerular filtration rate (eGFR) from baseline and compared the outcomes for patients with stable and worsening renal function. Materials and methodsWe selected studies that used randomized controlled trials in which outcomes for direct oral anticoagulants (DOACs) (dabigatran, rivaroxaban, apixaban, or edoxaban) were compared with those for warfarin in AF patients with normal, mild or moderate renal function, except the severe one (creatinine clearance<30). ResultsWe assessed five clinical trials, involving 72,608 patients. Pooled analysis indicated that the risk of stroke was lower for DOACs than for warfarin among patients with mild renal impairment (Risk ratio, 0.79; 95% confidence interval, 0.68–0.91) and moderate renal impairment (0.80, 0.69–0.92). No major differences were found in patients with normal renal function. Additionally, DOACs were associated with fewer major bleeds among patients with normal (0.77, 0.70–0.84), mild (0.86, 0.77–0.95), and moderate renal impairment (0.73, 0.65–0.82). Among those treated with DOACs, a lower dosage was associated with lower risk of major bleeding (0.75, 0.68–0.83) and higher risk of stroke or systemic embolism (1.28, 1.12–1.47). Further, DOACs tended to be associated with a lower estimated glomerular filtration rate (eGFR) than warfarin even after 30months. Finally, we found significant differences in the risk of stroke (2.09, 1.64–2.68) and major bleeding (2.01, 1.66–2.42) between patients with stable and worsening renal function. ConclusionsDOACs have a greater clinical benefit than warfarin with respect to renal function. They are associated with a comparatively lower risk of stroke and major bleeding, as well lower eGFR. This suggests these agents are a better choice in patients with renal disease.

Association of serumγ-glutamyl transpeptidase level with kidney function in essential hypertension patients

Objective To analyze the association of serumγ-glutamyl transpeptidase (GGT) level with kidney function in essential hypertension patients. Methods 500 patients with essential hypertension were selected.They were divided into high glomerular filtration rate (GFR) group, normal renal function group, mild renal function decline group, and moderate or severe renal function decline group based on GFR.The fasting blood glucose, serum lipid, routine laboratory tests, hepatic and renal function were detected by routine methods.The one way ANOVA test was used to show differences among groups, and the relationship of serum GGT with GFR was assessed by using the Pearson correlation coefficient and multiple linear regressions. Results There were 500 hypertension patients[(56.03±7.38)years old, 240 males and 260 females] enrolled in this study.Among them, 43(23/20) cases were in the high GFR group, 161(82/79) cases were in the normal renal function group, 219(105/114) cases were in the mild renal function decline group, and 77(30/47) cases were in the moderate or severe renal function decline group.The sex, blood pressure, heart rate, body mass index, fasting blood glucose, blood lipid level had no statistically significant differences among the groups (all P>0.05), but the age, aspartate transaminase(AST), alanine transaminase(ALT) and GGT had statistically significant differences among the groups (all P<0.05). Pearson correlation analysis showed: age(r=0.278, P=0.002) was negatively associated with GFR, while AST(r=0.159, P=0.003), ALT(r=0.352, P<0.001) and GGT(r=0.237, P<0.001) were positively correlated with GFR.Multiple linear regression analysis showed that the serum GGT (β=0.146, 95%CI 0.099, 0.282, P<0.001) was also positively correlated with GFR. Conclusion Our study demonstrated that the level of GGT was positively correlated with GFR in essential hypertension patients, and monitoring the changes of serum GGT may have significant effect on kidney function. Key words: Hypertension; Serumγ-glutamyl transpeptidase; Glomerular filtration rate

Néphrectomie partielle pour tumeur de Wilms unilatérale chez l’enfant : est-ce pertinent ?

Wilms tumors (WTs) are the most frequent renal tumors in children. Radical nephrectomy (RN) remains the gold-standard surgical treatment for this type of cancer. Excellent results in overall survival (>90%) make it possible to consider nephronic preservation. The objective of this systematic review is to evaluate the relevance of nephron-sparing surgery (NSS) for the treatment of nonsyndromic unilateral Wilms tumor (UWT) in children. Articles in English related to "unilateral Wilms tumor, unilateral nephroblastoma, partial nephrectomy, nephron-sparing surgery, renal function" identified in the Medline library were screened and data were extracted to perform a qualitative systematic review. We identified 377articles, 14 of which were integrated into the analysis. Data on 4288children were included, 3994 (93.1%) underwent RN, whereas 294 (6.8%) underwent NSS. StageI anatomopathology resulted in 55.1% RN and 79% NSS. Overall survival and event-free survival were similar: respectively 95.7% and 92.8% after RN and 96 and 90.5% after NSS. Positive margin status was higher after NSS (8.5% vs 0.5%), but tumor rupture and local tumor recurrences were similar. The rate of mild to moderate renal function was higher after RN (42% vs 10% after NSS). NSS is regularly performed for WT in case of bilateral or syndromic tumors, but the literature considering UWT does not show consensus. The superiority of NSS for renal outcomes has now been fully evaluated, but the main problem of this surgery in case of UWT is to ensure oncologic outcomes as good as outcomes after RN. WTs are usually massive tumors for which partial nephrectomy is contraindicated, but studies showed that chemotherapy before surgery could reduce tumor volume and make NSS possible. This review shows that NSS results seem to be as good as RN results and that preoperative chemotherapy should be highlighted for its participation in the reduction of the positive margin status. Although radiotherapy is used with caution because of its side effects, some studies showed that it gave excellent results for oncologic salvage after local recurrence. Constant progress in medical imaging and detection systems has led to the emergence of a new type of assistance for surgeons such as image reconstruction and vessel or urinary tract system segmentation. Virtual simulation of the operation based on a real case should help evaluate the feasibility of complex procedures in the near future. NSS for UWT seems to be a credible therapeutic alternative. New technologies such as 3Dreconstruction should help surgeons define the best parameters to select ideal tumors for this surgery in the near future. For the moment, small tumors (<4cm), distant from the renal hilum (ideally on the upper pole) that respect at least 50% of the renal parenchyma (ideally superficial with exophytic development) seem to be the perfect indication for NSS.