Mild Renal Function Impairment Research Articles

Efficacy and safety of enavogliflozin vs. dapagliflozin as add-on therapy in patients with type 2 diabetes mellitus based on renal function: a pooled analysis of two randomized controlled trials

BackgroundWe assessed the efficacy and safety of enavogliflozin (0.3 mg), a newly developed SGLT-2 inhibitor, in patients with type 2 diabetes mellitus based on kidney function via pooled analysis of two 24-week, randomized, double-blind phase III trials.MethodsData from 470 patients were included (enavogliflozin: 0.3 mg/day, n = 235; dapagliflozin: 10 mg/day, n = 235). The subjects were classified by mildly reduced (60 ≤ eGFR < 90 mL/min/1.73 m², n = 247) or normal eGFR (≥ 90 mL/min/1.73 m², n = 223).ResultsIn the mildly reduced eGFR group, enavogliflozin significantly reduced the adjusted mean change of HbA1c and fasting plasma glucose levels at week 24 compared to dapagliflozin (− 0.94% vs. −0.77%, P = 0.0196). Enavogliflozin exhibited a more pronounced glucose-lowering effect by HbA1c when combined with dipeptidyl peptidase-4 inhibitors than that observed in their absence. Enavogliflozin showed potent blood glucose-lowering effects regardless of renal function. Conversely, dapagliflozin showed a significant decrease in the glucose-lowering efficacy as the renal function decreased. Enavogliflozin showed a higher urinary glucose excretion rate in both groups. The homeostatic model assessment showed that enavogliflozin markedly decreased the insulin resistance. The blood pressure, weight loss, or homeostasis model assessment of beta-cell function values did not differ significantly between enavogliflozin and dapagliflozin. Adverse events were similar between both drugs.ConclusionsThe glucose-lowering efficacy of enavogliflozin is superior to that of dapagliflozin in patients with type 2 diabetes mellitus with mild renal function impairment; this is attributed to its potent urinary glucose excretion-promoting ability. The emergence of new and potent SGLT-2 inhibitors is considered an attractive option for patients with inadequate glycemic control and decreased renal function.Trial registrationNot applicable (pooled analysis).

TCTAP A-038 Mild Renal Function Impairment and Long-Term Outcomes in Patients With Three-Vessel Coronary Artery Disease: A Cohort Study

TCTAP A-038 Mild Renal Function Impairment and Long-Term Outcomes in Patients With Three-Vessel Coronary Artery Disease: A Cohort Study

Mild Renal Function Impairment and Long-Term Outcomes in Patients with Three-Vessel Coronary Artery Disease: A Cohort Study

Introduction: Limited data are available on the long-term impact of mild renal dysfunction (estimated glomerular filtration rate [eGFR] 60–89 mL/min/1.73 m²) in patients with three-vessel coronary disease (3VD). Methods: A total of 5,272 patients with 3VD undergoing revascularization were included and were categorized into 3 groups: normal renal function (eGFR ≥90 mL/min/1.73 m², n = 2,352), mild renal dysfunction (eGFR 60–89, n = 2,501), and moderate renal dysfunction (eGFR 30–59, n = 419). Primary endpoint was all-cause death. Secondary endpoints included cardiac death and major adverse cardiac and cerebrovascular events (MACCE), a composite of death, myocardial infarction, and stroke. Results: During the median 7.6-year follow-up period, 555 (10.5%) deaths occurred. After multivariable adjustment, patients with mild and moderate renal dysfunction had significantly higher risks of all-cause death (adjusted hazard ratio [HR]: 1.36, 95% confidence interval [CI]: 1.07–1.70; adjusted HR: 2.06, 95% CI: 1.53–2.78, respectively) compared with patients with normal renal function. Patients after coronary artery bypass grafting (CABG) had a lower rate of all-cause death and MACCE than those undergoing percutaneous coronary intervention (PCI) in the normal and mild renal dysfunction group but not in the moderate renal dysfunction group. Results were similar after propensity score matching. Conclusions: In patients with 3VD, even mild renal impairment was significantly associated with a higher risk of all-cause death. The superiority of CABG over PCI diminished in those with moderate renal dysfunction. Our study alerts clinicians to the early screening of mild renal impairment in patients with 3VD and provides real-world evidence on the optimal revascularization strategy in patients with renal impairment.

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.

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.

Impact of Renal Insufficiency on Prognosis of Patients with Acute Coronary Syndrome.

PurposeChronic kidney disease (CKD) is common in patients admitted with acute coronary syndrome (ACS), and it is associated with poor outcomes. However, data are limited. Hence, we examined the long-term prognostic significance of estimated glomerular filtration rate (eGFR) among Chinese patients hospitalized with ACS.Patients and MethodsThis is a multicenter, observational study that included 1860 ACS patients enrolled between March 2014 and June 2019 from 11 hospitals in Chengdu. CKD-EPI equation was used to calculate the baseline eGFR. Patients were divided into three groups: eGFR ≥ 90 mL/min (normal renal function), eGFR 60 to <90 mL/min (mild impaired renal function), and eGFR < 60 mL/min (moderate or severe renal dysfunction). The endpoint was all-cause death during follow-up.ResultsAt baseline, 714 patients had normal renal function, while 746 patients had mild impaired renal function, and 400 patients had moderate or severe renal dysfunction. In the follow-up of 15 months (10 months, 22 months), 261 (14.0%) patients died;, 139 (34.8%) in the moderate or severe renal dysfunction group, 94 (12.6%) in the mild impaired renal function group, and 28 (3.9%) in the normal renal function group (log-rank p-value from Kaplan–Meier analysis <0.001). In multivariable Cox Proportional hazard analysis, age, systolic blood pressure (SBP), heart rate, eGFR, ST-elevation myocardial infarction (STEMI), and percutaneous coronary intervention (PCI) were independent predictors of all-cause death.ConclusionIn this study, among Chinese patients with ACS, renal insufficiency was associated with unfavorable long-term prognosis. Age, SBP, heart rate, eGFR, STEMI, and PCI could identify those at risk.

Assessment of renal function using magnetic resonance quantitative histogram analysis based on spatial labeling with multiple inversion pulses.

BackgroundThe incidence of chronic kidney disease (CKD) is high, and is easy to develop into end-stage renal disease (ESRD), which requires kidney dialysis or kidney transplantation. Therefore, we want to explore the clinical value of magnetic resonance quantitative histogram analysis based on spatial labeling with multiple inversion pulses (SLEEK) in assessing renal function in the early stage.MethodsOne hundred and twenty-nine patients underwent abdominal MRI examination, including a coronal SLEEK sequence. The patients were divided into the control group [CG, 47 cases, estimated glomerular filtration rate (eGFR) >90], the mild renal function impairment (mRI) group (48 cases, eGFR =60–90), and the moderate to severe renal function impairment (m-sRI) group (34 cases, eGFR <60). Two experienced radiologists delineated cortex and medulla regions of interest (ROIs) on SLEEK images to obtain cortex and medulla quantitative histogram parameters [Mean, Median, Percentiles (5th, 10th, 25th, 75th, and 90th), Skewness, Kurtosis, and Entropy] using FireVoxel. These histogram parameters were compared by proper statistical methods such as one-way analysis of variance, the χ2 test, and receiver operating characteristic (ROC) curve analysis.ResultsFour histogram parameters (Inhomogeneitycortex, Skewnesscortex, Kurtosismedulla, and Entropymedulla) differed significantly between the CG and the mRI group. One medulla (Entropymedulla) and nine cortex (Meancortex, Mediancortex, Kurtosiscortex, Entropycortex, and 5th, 10th, 25th, 75th, and 90th Percentilecortex) histogram parameters were significantly different between the m-RI and m-sRI groups. The most relevant parameter to eGFR was Inhomogenitycortex (r=−0.450, P<0.001). Inhomogeneitycortex had the largest area under the curve (AUC) for differentiating the mRI group from the CG (AUC =0.718; 95% CI: 0.616–0.806), while 25th Percentilecortex generated the largest AUC (AUC =0.786; 95% CI: 0.681–0.869) for differentiating the mRI and m-sRI groups.ConclusionsQuantitative histogram parameters based on a SLEEK sequence can be used to supplement renal dysfunction assessment. Cortex histogram parameters are more valuable for evaluating renal function than medulla histogram parameters.

Accelerated lipid peroxidation in a rat model of gentamicin nephrotoxicity.

Kidney disease represents a burden for the health care system worldwide. As the prevalence continues to rise, discovering new biomarkers of early kidney damage has become crucial. Oxidative stress (OS) represents one of the main factors involved in the early stages of many syndromes leading to kidney damage. Therefore, it must be studied in detail. To date, many studies have focused on OS in advanced stages of acute kidney injury (AKI), with great success. The aim of the present study was to ascertain whether even mild renal function impairment can be linked to specific systemic markers of OS and systemic antioxidants in order to pinpoint certain biomarkers for early kidney damage. We used male rats (Rattus norvegicus) in which we induced kidney damage by injecting gentamicin for 7 days. Blood was collected 24 h after the last dose of gentamicin. Urea, creatinine, 3-nitrotyrosine (3-NT), nitric oxide (NO), malondialdehyde (MDA), thiols (TS), total oxidative stress (TOS), and interferon-γ (IFN-γ) were determined. In addition, for the antioxidant status we measured total antioxidant capacity (TAC) and interleukin-10 (IL-10). Our results demonstrated that the rats had mild renal impairment consistent with a pre-AKI stage due to the nephrotoxic effect of gentamicin. However, TOS, MDA and NO were significantly higher in the gentamicin group compared to the control group. In addition, TAC was higher in the control group. Hence, OS markers reach higher levels and may potentially be used as markers of kidney damage even in cases of mild renal function impairment.

COVID-19 and the kidney: time to take a closer look.

Although coronavirus disease (COVID-19) is primarily a respiratory disease, the kidney may be among the target organs of infection with severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). Independently of baseline kidney function, acute kidney injury (AKI) is a common complication of COVID-19, associated with increased mortality and morbidity. Most frequently, COVID-19 causes acute tubular necrosis; however, in some cases, collapsing focal segmental glomerulosclerosis and direct viral tropism of the kidneys have also been documented. AKI secondary to COVID-19 has a multi-factorial origin. Even mild impairment of renal function is an independent risk factor for COVID-19 infection, hospitalisation and mortality. Dialysis patients also carry an increased risk of other severe COVID-related complications, including arrhythmias, shock, acute respiratory distress syndrome and acute heart failure. In such patients, COVID-19 may even present with atypical clinical symptoms, including gastrointestinal disorders and deterioration of mental status. More research is needed on the exact effects of SARS-CoV-2 on the kidneys. Finally, it remains to be proven whether the outcome of patients with kidney disease may be improved with anticipated vaccination programmes.

Increased risk of a first-ever myocardial infarction for women with mild impairment of renal glomerular function

Background and Aims: A new syndrome called "Shrunken Pore Syndrome" has been suggested, as the estimated glomerular filtration rate for cystatin C (eGFRcystatin C) is affected earlier due to differences in molecular size compared to eGFRcreatinine. The aim was to investigate if a lower eGFRcystatin C/eGFRcreatinine ratio in a prospective setting increases the risk of later developing a first-ever myocardial infarction (MI) independently of other cardiovascular risk factors.

Renal and metabolic effects of SGLT-2i and DPP-4i according to basal estimated glomerular filtration rate: Analysis from GIOIA, an observational prospective study

In the GIOIA study, users of both SGLT-2i and DPP-4i improved glycometabolic control, after 12 months, independently from baseline eGFR levels. Moreover, both classes led to a significant decrease in eGFR in participants with eGFR ≥ 90 ml/min/1.73 m2 and no deterioration in case of mild impairment of renal function.

Mild impairment of renal function (shrunken pore syndrome) is associated with increased risk of a future first-ever myocardial infarction in women

Impaired renal function is associated both with the development of cardiovascular disease and its prognosis. A new syndrome called ′Shrunken Pore Syndrome′ has been suggested, as the estimated glomerular filtration rate for cystatin C (eGFRcystatin C) is affected earlier due to differences in molecular size compared to eGFRcreatinine. The aim was to investigate if a lower eGFRcystatin C/eGFRcreatinine ratio in a prospective setting increases the risk of later developing a first-ever myocardial infarction (MI) independently of other cardiovascular risk factors. We used a nested case-referent study design within the Northern Sweden Health and Disease Study, and 545 subjects (29.0% women) were identified who prospectively developed a first-ever MI, and their 1054 matched referents. For women, but not for men, one standard deviation (SD) increase of ln z-scores of eGFRcystatin C/eGFRcreatinine ratio was associated with a lower risk of a future MI: odds ratio [95% confidence interval] 0.58 [0.34–0.99], adjusted for apolipoprotein B/A1 ratio, CRP, homocysteine, systolic blood pressure, body mass index, and diabetes. Furthermore, a high eGFRcreatinine associated independently with an increased risk of future MI in men only: OR 1.25 [1.05–1.48]. Thus, for women, a lower eGFRcystatin C/eGFRcreatinine ratio is associated with a higher risk of having a future first-ever MI, and it may be a valuable, easily implemented biomarker for risk of cardiovascular disease.

Post-transplant multimorbidity index and quality of life in patients with chronic graft-versus-host disease\u2014results from a joint evaluation of a prospective German multicenter validation trial and a cohort from the National Institutes of Health

Comorbidity after allogeneic hematopoietic stem cell transplantation (alloHSCT) impairs quality of life (QoL), physical functioning, and survival. We developed a new standardized measure to capture comorbidity after transplantation, the Post-transplant Multimorbidity Index (PTMI) in a cohort of 50 long term survivors. We subsequently evaluated the content validity and impact on survival and QoL within a multicenter trial, including 208 patients (pts) after alloHSCT, who were prospectively evaluated applying the FACT-BMT, the Human Activity Profile (HAP), the SF-36 v.2, PTMI and the Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI). The most prevalent comorbidities were compensated arterial hypertension (28.4%), ambulatory infections (25.5%), iron overload (23%), mild renal function impairment (20%), and osteoporosis (13%). Applying the PTMI 13% of patients had no comorbidity, while 37.1% had 1–3 comorbidities, 27.4% had 4–6 comorbidities, and 13.5% had > 6 comorbidities. Chronic graft-versus-host disease (cGvHD) was significantly associated with the PTMI, while age and prior acute GvHD were not. In contrast, the HCT-CI was not associated with the presence of cGvHD. cGvHD was significantly associated with depression (r = 0.16), neurological disease (r = 0.21), osteoporosis (r = 0.18) and nonmelanoma skin cancer (r = 0.26). The PTMI demonstrated strong measurement properties and compared to the HCT-CI captured a wider range of comorbidities associated with cGvHD.

P1795Impact of severe aortic stenosis treatment strategy in low-risk patients: a propensity matched analysis of surgical aortic valve replacement versus transcatheter aortic valve implantation

Abstract Introduction Recent studies suggest that transcatheter aortic valve implantation (TAVI) benefits might extend to lower risk patients. Our goal was to compare the impact of treatment strategy in mortality and peri-procedural complications in a low-risk severe aortic stenosis population. Methods Single-center retrospective study which screened patients undergoing intervention from June/2009 to July/2016 (682 isolated aortic valve replacement patients) and from June/2009 to July/2017 (400 TAVI patients). Low-risk was defined as EuroScore II &lt;4% for single non-CABG procedure. After excluding patients with EuroScore II ≥4%, previous cardiac surgery and/or undergoing pre-treatment PCI, 544 AVR and 119 TAVI patients were included. TAVI patients were propensity score paired in a 1:1 ratio with a group of AVR patients, matched by age, NYHA class, diabetes mellitus, COPD, atrial fibrillation, creatinine clearance and LVEF &lt;50% (mean standardized difference &lt;10% for matching variables). All patients completed at least 1 year of follow-up. Outcomes were adjudicated according to VARC2 criteria. Results A total of 158 patients (79 AVR and 79 TAVI) were matched (mean age 79±6 years, 79 men). Median EuroScore II was 2.3% (IQR 1.6–3.0%), 46% were in NYHA class ≥3 and 91% had preserved ejection fraction. Main comorbidities were hypertension (n=105, 67%), diabetes mellitus (n=48, 30%), COPD (n=35, 22%) and coronary artery disease (n=30, 19%). Most patients had at least mild renal function impairment and median creatinine clearance was 58 ml/min (IQR 43–62 ml/min). The 30-day mortality was 2.5% (n=2 in each group) and there were no differences in in-hospital complications. During a median follow-up of 3.8 years (IQR 2.1–6.1), 67 deaths occurred (39 on the AVR group and 28 on the TAVI group), and treatment strategy did not influence all-cause mortality (HR 0.97, 95% CI 0.60–1.60, log rank p=0.92) - figure 1. By multivariate analysis, need for dialysis during hospitalization remained the only independent predictor of all-cause mortality (adjusted HR 6.40, 95% CI 1.57–28.14, p=0.01). Figure 1 Conclusion In this low-risk matched population, treatment strategy did not influence mortality neither complications. Older age, higher NYHA class and renal impairment were the main contributors to the predicted surgical risk. These results suggest that both options are safe for low-risk patients, even though Heart Team remains essential to contemplate other variables that might alter patient management.

Mild impairment of renal function (shrunken pore syndrome) is associated with increased risk for future surgery for aortic stenosis

Recently, a new approach was proposed to detect mild impairment in renal function: a reduced ratio between estimated glomerular filtration rate (eGFR) calculated by cystatin C and eGFR calculated by creatinine. We aimed to evaluate if this ratio is associated with aortic stenosis (AS) requiring surgery. We identified 336 patients that first participated in population surveys and later underwent surgery for AS (median age [interquartile range] 59.8 [10.3] years at survey and 68.3 [12.7] at surgery, 48% females). For each patient, two matched referents were allocated. Cystatin C and creatinine were determined in stored plasma. eGFRcystatin C and eGFRcreatinine and their ratio were estimated. Conditional logistic regression analyses were used to estimate the risk (odds ratio (OR) with [95% confidence interval (CI)]) related to one (ln) standard deviation increase in the ratio between eGFRcystatin C and eGFRcreatinine. A high ratio was associated with lower risk for AS requiring surgery (OR [95% CI]) (OR 0.84 [0.73–0.97]), especially in women (0.74 [0.60–0.92] vs. 0.93 [0.76–1.13] in men). After further stratification for coronary artery disease (CAD), the association remained in women with CAD but not in women without CAD (0.60 [0.44–0.83] and 0.89 [0.65–1.23], respectively). In conclusion, a high ratio between eGFRcystatin C and eGFRcreatinine was associated with lower risk for surgery for AS, especially in women. Mild impairment of renal function is thus associated with future risk for AS requiring surgery.

Population pharmacokinetics of carboplatin, etoposide and melphalan in children: a re-evaluation of paediatric dosing formulas for carboplatin in patients with normal or mild impairment of renal function.

Carboplatin dosage is calculated by using the estimated glomerular filtration rate (GFR) to achieve a target plasma area under the plasma concentration-time curve (AUC). The aims of the present study were to investigate factors that influence the pharmacokinetics of carboplatin in children with high-risk neuroblastoma, and whether target exposures for carboplatin were achieved using current treatment protocols. Data on children receiving high-dose carboplatin, etoposide and melphalan for neuroblastoma were obtained from two study sites [European International Society for Paediatric Oncology (SIOP) Neuroblastoma study, Children's Hospital at Westmead; n = 51]. A population pharmacokinetic model was built for carboplatin to evaluate various dosing formulas. The pharmacokinetics of etoposide and melphalan was also investigated. The final model was used to simulate whether target carboplatin AUC (16.4mg ml-1 ·min) would be achieved using the paediatric Newell formula, modified Calvert formula and weight-based dosing. Allometric weight was the only significant, independent covariate for the pharmacokinetic parameters of carboplatin, etoposide and melphalan. The paediatric Newell formula and modified Calvert formula were suitable for achieving the target AUC of carboplatin for children with a GFR <100ml min-1 1.73m-2 but not for those with a GFR ≥100ml min-1 1.73m-2 . A weight-based dosing regimen of 50mg kg-1 achieved the target AUC more consistently than the other formulas, regardless of renal function. GFR did not appear to influence the pharmacokinetics of carboplatin after adjusting pharmacokinetic parameters for weight. This model-based approach validates the use of weight-based dosing as an appropriate alternative for carboplatin in children with either mild renal impairment or normal renal function.

Compare the effect of combined therapy between telbivudine plus adefovir dipivoxil and lamivudine plus adefovir dipivoxil corresponding to renal function in patients with hepatitis B virus infection

Objective: To compare the effect of combined therapy using lamivudine (LAM) plus adefovir (ADV) versus telbivudine (LdT) plus adefovir corresponding to the renal function of CHB patients. Methods: A total of 120 patients with chronic hepatitis B were enrolled. According to single daily dosing, they were divided into 4 groups: LdT + ADV group (n = 32), ADV+LdT group (n = 28), LAM + ADV group (n = 38) and ADV + LAM group (n = 22). Hepatorenal function, HBV serological markers, HBV DNA quantification, creatine kinase (CK) and other parameters were examined every 3 months. Serum alanine aminotransferase (ALT) normalization rate, undetectable HBV DNA rate, hepatitis B e antigen (HBeAg) seroconversion rate, level of serum creatinine (CR) and estimated glomerular filtration rate (eGFR) were analyzed at baseline time, and at weeks 24 and 52.Stastical data were analyzed by t- test and analysis of variance, count data using χ (2) test. Results: There was no statistically significant difference between the four groups in terms of ALT normalization rate, HBeAg seroconversion rate, undetectable HBV DNA rate at 24 and 52 weeks. Compared with baseline, at 24 weeks of treatment, there was no significant change in serum creatinine and eGFR in the 4 groups, but after 52 weeks of treatment, serum creatinine decreased in LdT + ADV and ADV + LdT groups and eGFR increased (P < 0.05); Serum creatinine in ADV and ADV + LAM increased, and eGFR was decreased than before (P < 0.05). After treatment, there was no significant difference in renal function between the four groups at 24 weeks, but at week 52, eGFR increased and serum creatinine decreased in LdT + ADV group compared with LAM + ADV group (P < 0.05); ADV + LdT Compared with ADV + LAM group, eGFR increased and serum creatinine decreased (P < 0.05). At 52 weeks of treatment, 5 patients with mildly impaired renal function in the ADV + LdT group [n = 10, eGFR 60-90 ml·min(-1) ·(1.73 m(2))(-1)] returned to normal, and none of the ADV + LAM group (n = 9) returned to normal. Conclusion: For patients with mild impaired renal function, adding LdT combined with ADV can improve renal function compared to that of LAM plus ADV.

Mineralocorticoid receptor antagonists in kidney transplantation: time to consider?

Although patient survival is significantly improved by kidney transplantation (KT) in comparison with dialysis, it remains significantly lower than that observed in the general population. Graft function is one of the major determinants of patient survival after KT. Mineralocorticoid receptor antagonists (MRAs) could be of particular interest in this population to improve graft function and treat or prevent cardiovascular (CV) complications. In KT, ischaemia/reperfusion injury is a major factor involved in delayed graft function, which is often associated with inferior long-term graft survival. Preclinical studies suggest that MRAs may prevent ischaemia/reperfusion-related lesions in addition to having a protective effect in preventing calcineurin inhibitor-induced nephrotoxicity. Clinical data also support the anti-proteinuric effect of MRAs in chronic kidney disease (CKD). Taken together, MRAs may hence be of particular benefit in improving short- and long-term graft function. Numerous randomized controlled trials (RCTs) have shown the efficacy of MRAs in both heart failure and resistant hypertension. As these comorbidities are frequent in kidney transplant recipients before transplantation or during follow-up, MRAs could represent a useful therapeutic option in those with mild renal function impairment. However, CKD patients are under-represented in RCTs and the CV effects of MRAs in kidney transplant recipients have yet to be specifically assessed in large-scale trials. Available evidence indicates a good safety profile for MRAs in patients with a glomerular filtration rate (GFR) >30 mL/min/1.73 m2. However, as for all patients prescribed an MRA, creatinine and potassium should also be closely monitored following MRA initiation in kidney transplant patients. Given the current evidence suggesting that MRAs prevent ischaemia/reperfusion-related lesions and calcineurin inhibitor-induced nephrotoxicity in kidney transplant recipients as well as CV events in patients at high risk of CV complications (such as those in kidney transplant recipients), trials are urgently needed to fully assess the clinical impact of MRA use in this population.

Renal function on admission affects both treatment strategy and long-term outcomes of patients with myocardial infarction (from the Polish Registry of Acute Coronary Syndromes).

Impairment of renal function (IRF) is an independent risk factor of myocardial infarction (MI). The aim of study was to determine if the presence of IRF affects the choice of treatment strategy in patients with MI, and if long-term mortality rates are influenced by the use of an invasive strategy in patients with MI according to the grade of IRF. Data from the PL-ACS Registry of 22,431 patients hospitalised for MI during 2007-2008 with an available estimated glomerular filtration rate (eGFR) with 2009 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula were included. Patients were stratified based on eGFR: ≥ 90 (normal); 60-89 (mild IRF); 30-59 (moderate IRF); 15-29 (severe IRF); and < 15 mL/min/1.73 m² (end-stage IRF). After adjustment, each increase in IRF grade reduced the likelihood of percutaneous coronary intervention by 19% (odds ratio [OR] 0.81; 95% confidence interval [CI] 0.78-0.85; p < 0.001). A higher IRF grade was independently associated with mortality (OR 2.01; 95% CI 1.86-2.18; p < 0.001) and major bleeding (OR 1.42; 95% CI 1.22-1.66; p < 0.001) during hospitalisation, and mortality at 12 (hazard ratio [HR] 1.55; 95% CI 1.49-1.62; p < 0.001) and 36 months (HR 1.50; 95% CI 1.45-1.55; p < 0.001). Invasive treatment was independently associated with improved 12-month prognosis in non-ST-segment elevation MI (NSTEMI) patients with mild-to-severe IRF and in ST-elevation MI (STEMI) patients at all IRF grades. Invasive procedures were less frequent with worsening renal dysfunction. Invasive treatment was associ-ated with improved 12-month prognosis in STEMI patients regardless of renal function and in NSTEMI patients with eGFR ≥ 15 mL/min/1.73 m².

Lucerastat, an iminosugar for substrate reduction therapy: pharmacokinetics, tolerability, and safety in subjects with mild, moderate, and severe renal function impairment

Lucerastat, an inhibitor of glucosylceramide synthase, has the potential for substrate reduction therapy in glycosphingolipid storage disorders such as Fabry disease. In pharmacokinetic studies in rats, dogs, and healthy subjects, the main route of elimination was renal. The pharmacokinetics, tolerability, and safety of lucerastat were evaluated in subjects with mild (group A), moderate (group B), and severe (group C) renal impairment. Group D included healthy subjects. Thirty-two subjects (8 per group) were included in this single-center, open-label study and received a single oral dose of 1000 mg lucerastat in groups A and B and 500 mg in groups C and D. The degree of renal impairment of the subjects was based on estimated glomerular filtration rate. Plasma lucerastat concentrations (dose-corrected) were higher in groups B and C compared to group D. The elimination phase half-life was slower in groups B (9.6 hours) and C (16.1 hours) compared to group D (7.0 hours). Increased exposure to lucerastat was observed in subjects from groups B and C with ratio of geometric means (90%CI) of 1.60 (1.29, 1.98) for group B vs D and 3.17 (2.76, 3.65) for group C vs D. There were no clinically relevant abnormalities in vital signs, 12-lead electrocardiograms, and clinical laboratory values. Four nonserious adverse events were reported by 4 subjects (1 in group A, 3 in group D). Lucerastat was well tolerated in all dose groups. Dose adjustment is warranted in subjects with moderate and severe renal impairment.