Renal Safety of Tenofovir Disoproxil Fumarate and Entecavir in Liver Transplant Patients: A Nationwide Korean Registry Study

Background and aims: Tenofovir disoproxil fumarate (TDF) and entecavir (ETV) have been recommended after liver transplantation to prevent recurrence of hepatitis B virus infection. Despite its proven efficacy, the renal safety of TDF has not been established in liver transplant recipients. We aimed to compare the effects of TDF and ETV on renal function in liver transplant recipients and to evaluate risk factors for renal dysfunction after liver transplantation. Methods: This is a retrospective, observational multicenter study of data from the Korean Organ Transplantation Registry. We included adults who underwent liver transplantation for hepatitis B virus-related complications from April 2014 to December 2017 and received TDF or ETV post-transplantation. Renal dysfunction was defined as an estimated glomerular filtration rate decline by at least 20% from baseline (1 month post-transplantation). Median duration of follow-up was 29 months (interquartile range 19–42).Results: A total of 804 liver transplant patients were included. The cumulative probability of renal dysfunction was significantly higher in the TDF group than in the ETV group. Multivariable analysis confirmed that TDF was independently associated with an increased risk of renal dysfunction (hazard ratio = 1.47, 95% confidence interval 1.12-1.92; P = 0.005). Independent risk factors for renal dysfunction included older age, worse baseline renal function, and low body mass index. Renal dysfunction after liver transplantation was independently associated with increased mortality.Conclusions: In this nationwide study, use of TDF was associated with an increased risk of renal dysfunction, when compared with ETV.

Insights of Worsening Renal Function in Type 1 Cardiorenal Syndrome: From the Pathogenesis, Biomarkers to Treatment

Type-1 cardiorenal syndrome refers to acute kidney injury induced by acute worsening cardiac function. Worsening renal function is a strong and independent predictive factor for poor prognosis. Currently, several problems of the type-1 cardiorenal syndrome have not been fully elucidated. The pathogenesis mechanism of renal dysfunction is unclear. Besides, the diagnostic efficiency, sensitivity, and specificity of the existing biomarkers are doubtful. Furthermore, the renal safety of the therapeutic strategies for acute heart failure (AHF) is still ambiguous. Based on these issues, we systematically summarized and depicted the research actualities and predicaments of the pathogenesis, diagnostic markers, and therapeutic strategies of worsening renal function in type-1 cardiorenal syndrome.

Efficacy And Renal Safety of Febuxostat In Management of Gout And Chronic Kidney Disease: A Retrospective Study

Background: Elevated serum urate levels are associated with renal deterioration of chronic kidney disease (CKD). Whether urate-lowering treatment with febuxostat can improve renal function or attenuate the decline of the estimated glomerular filtration rate (eGFR) is controversial. The current study sought to explore efficacy and renal safety of febuxostat in gout patients with CKD and explore factors correlated with target serum urate (sUA).Methods: The current study was a single-center retrospective study comprising male gout patients with CKD. sUA, the rate of sUA < 360 µmol/L and renal safety were analyzed in subjects who had been treated with febuxostat for more than 44 weeks. Factors correlated with target sUA were explored by logistic regression analysis. Results: A total of 87 patients who had been diagnosed with gout and CKD met the inclusion criteria for the study. Twenty-five (28.73%) patients presented with stage 2 CKD, 58 (66.67%) were diagnosed with stage 3 CKD and 4 (4.60%) were diagnosed with stage 4 CKD. Analysis of sUA level showed a significant reduction at week 44~ (598.22 ± 95.11 µmol/L vs. 429.76 ± 123.45 μmol/L; P < 0.05), and the RAT increased to 34.50%. eGFR level of all patients was 52.37 ± 11.74 ml/min/1.73cm2 at baseline and 56.51 ± 15.01 ml/min/1.73cm2 at week 44~ (P < 0.05). The findings showed improvement of eGFR level in different stages of CKD, mainly in stage 3 CKD patients (P < 0.05). After stratification based on risk factors of hypertension, diabetic mellitus, hyperlipidemia and the usage of Non-Steroidal Anti-inflammatory Drugs (NSAIDs), the findings showed that eGFR levels of patients with ≤ 1 risk factors showed significant improvement (P < 0.05). Logistic regression analysis indicated that baseline sUA level and acute arthritis were correlated with the RAT in gout and CKD patients treated with febuxostat.Conclusions: In this retrospective study, febuxostat demonstrated effective and renal safety in gout patients with CKD. Baseline sUA level and acute arthritis may affect achieving of target sUA.

Comparing the Efficacy and Safety of Low-Carbohydrate Diets with Low-Fat Diets for Type 2 Diabetes Mellitus Patients: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Introduction. To compare the efficacy of low-carbohydrate diets (LCDs) with low-fat diets (LFDs) in body weight and glycemic control for type 2 diabetes mellitus (T2DM) patients, and their cardiovascular and renal safety. Methods. We searched PubMed, Ovid, Embase databases, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov from inception to April, 2021. Randomized controlled trials (RCTs) which lasted more than 3 months were included. The primary outcomes are the mean change from baseline in glycated haemoglobin (HbA1c) and body weight loss. Secondary outcomes included mean difference in lipid parameters, blood pressures, and serum creatinine. Results. Totally, 12 RCTs met inclusion criteria representing 761 patients. Compared with LFDs, treatment with LCDs achieved significant reduced HbA1c by 0.35% (95% CI: −0.45, −0.24; P < 0.00001). LCDs appeared to be more beneficial in decreasing body weight than LFDs (WMD = −2.99 kg; 95% CI: −4.36, −1.63; P < 0.0001), especially in the subgroup that used VLCDs (WMD = −9.49 kg; 95% CI: −12.88, −6.09, P < 0.00001). For cardiovascular risk factors, the LCD interventions significantly reduced TG concentration (WMD: −0.20 mmol/l; 95% CI: −0.31, −0.10; P = 0.0001) and increased HDL-C concentration (WMD: 0.09 mmol/l; 95% CI: 0.05,0.13; P < 0.00001). Subgroup analyses demonstrated that the difference in HbA1c, TG, and HDL-C between two dietary restrictions respectively lasted up to 1.5 and 2 years, whereas the beneficial effects of body weight loss diminished over time and disappeared after 2 years. LCDs were not associated with decreased level of TC or LDL-C, neither SBP nor DBP in comparison with LFDs. Moreover, no significant difference in serum creatinine could be found among such two diet interventions. Conclusions. LCDs are superior to LFDs for T2DM patients in improving HbA1c and reducing body weight, with a rewarding effect of some cardiovascular risk factors in a longer-term diabetes management. However, available data are insufficient to evaluate the association between diet interventions and renal safety. Future larger longer-term follow-up clinical trials are needed to provide more evidence about the sustainable effects and safety of LCDs compared with LFDs.

Renal Safety Profile of EGFR Targeted Therapies: A Study from VigiBase® the WHO Global Database of Individual Case Safety Reports

Kidney EGFR expression together with reported cases of glomerular diseases in the context of anti-EGFR drug administration raise concerns about the renal safety profile of these drugs. This issue is addressed in a case/non-case study carried out on VigiBase®, the WHO global database of individual case safety reports (ICRS). Disproportionality analysis of renal adverse effects related to the selected anti-EGFR drugs, erlotinib, gefitinib, afatinib, osimertinib, cetuximab and panitumumab, was assessed using the reporting odds ratio (ROR). Nine hundred and eighty-nine ICRSs were included. A signal of disproportionate reporting (SDR) was found for afatinib (ROR = 2.70; 95% CI [2.22–3.29]) and erlotinib (ROR = 1.73; 95% CI [1.46–2.04]) with acute kidney injury, and for afatinib (ROR = 2.41; 95% CI [1.78–3.27]), cetuximab (ROR = 1.42; 95% CI [1.14–1.78]) and erlotinib (ROR = 2.23; 95% CI [1.80–2.77]) with renal failure. The preferred term “diarrhoea” was frequently reported in the included cases. An SDR was found for erlotinib with haemolytic and uremic syndrome (ROR = 4.01; 95% CI [1.80–8.94]) and thrombotic microangiopathy (ROR = 4.94; 95% CI [2.80–8.72]). No SDR was seen for glomerular or tubule-interstitial diseases. This study showed that the anti-EGFR drug renal toxicity is mainly related to renal failure in the context of digestive toxicity.

Long-Term Renal Safety Between Patients With Chronic Hepatitis B Receiving Tenofovir vs. Entecavir Therapy: A Multicenter Study

Background Renal safety is a critical issue in chronic hepatitis B (CHB) patients receiving long-term entecavir (ETV) or tenofovir disofuroxil fumarate (TDF) therapy. We investigated their effects on estimated glomerular filtration rate (eGFR). Methods Treatment-naïve CHB patients receiving ETV or TDF for ≥1 year were recruited. The eGFR was assessed using the Chronic Kidney Disease Epidemiology Collaboration equation. We calculated average annual percent change (AAPC) in eGFR using Joinpoint regression. Results At beginning of observation, ETV group had unfavorable conditions than TDF group: lower eGFR and higher FIB-4 and APRI than TDF group (all P<0.001). After 6 years antiviral therapy, the mean eGFR in ETV group (n=1,793) was maintained (96.0 at first year to 95.6 mL/min/1.73 m2 at sixth year; AAPC -0.09%; P=0.322), whereas that in TDF group (n=1,240) significantly decreased annually (101.9 at first year to 96.9 mL/min/1.73 m2 at sixth year; AAPC -0.88%; P<0.001). Notably, in TDF group, even patients without diabetes (AAPC -0.80%; P=0.001) or hypertension (AAPC -0.87%; P=0.001) experienced significant decrease in eGFR. Expectably, accompanying diabetes (AAPC -1.59%; p=0.011) or hypertension (AAPC -1.00%; p=0.002) tended to accelerate eGFR decrease. TDF treatment (odds ratio 1.66, P<0.001), along with eGFR<60 mL/min/1.73 m2, serum albumin<3.5 mg/dL, and hypertension, were independently associated with ongoing renal dysfunction, defined as a negative slope of the mean eGFR change. Conclusions Compared to ETV, long-term TDF treatment induced slow, but progressive renal dysfunction. Although the annual eGFR change by TDF was small, careful monitoring is necessary, especially in patients requiring life-long therapy.

Efficacy Assessment of High Dose Colistin against Carbapenem-Resistant Gram-Negative Bacteria (CR-GNB) in Critically Ill Patients: A Retrospective Non-Inferiority Trial

Background: Colistin is an effective treatment option, recommended for carbapenem resistant gram-negative bacilli (CR-GNB) in critically ill patients. Due to high nephrotoxicity, dose management of Colistin is a tough decision to make. At standard dosage the efficacy of Colistin is not well defined. Consequently, strategies involving higher dosages were suggested. Objective: To evaluate the high dose of Colistin as non-inferior to standard dose in the treatment of CR-GNB in critically ill patients. Study Design: Retrospective comparative study Place and Duration of Study: Intensive Care Unit, King Saud Medical City Riyadh, Saudi Arabia from 1st January 2015 to 31st December 2017. Methodology: One hundred and ninety two patients that met the inclusion criteria from all participants were further divided into two groups. Group H (High dose) given the high dose of Colistin (9 million units intravenously (IV) loading dose, and then 9 million units/day in 2 or three divided doses) whereas group S was administered with standard dose (no loading dose, 6 million units/day). The primary endpoint of the study was the assessment of nephrotoxicity after the start of Colistin and secondary endpoints were the mortality within 14 days of commencing Colistin along with clinical effects and microbial clearance upon completion of treatment. Results: The results of the study established the non-inferiority of high dose of Colistin for the renal safety and also showed significant improvement in microbial clearance and length of ICU stay as compared to the standard dose. The other secondary end points such as mortality (p = 0.99), length of hospital stay (p = 0.39), and global improvement (p value of 0.06) revealed no significant difference between the two groups. Conclusion: The high dose of Colistin for the treatment of carbapenem resistance gram negative bacilli (CRGNB) was as safe as the standard dose for renal safety. But we also found that it also accelerates microbial clearance and reduces the time spent in the intensive care unit. Key words: Colistin, Colestimethate sodium, Gram negative bacteraemia, Sepsis, Multi-drug resistant organisms, Acute kidney injury

An observational retrospective cohort study of the effect of direct antiviral agents (DAAs) on glomerular filtration rate (GFR)

Background Hepatitis C virus (HCV) infection is known to be associated with high rates of liver related morbidities and mortality in the whole world. The interest of Public in HCV is growing, as more than 180 million people, (2.8%) of the global population, are infected with HCV. Aim of the Study To evaluate the effect of direct antiviral agents on glomerular filtrating rate (GFR). Patients and Methods The study performed on 120 subjects from the Hepatology outpatient clinic at Sharque elmadinah Hospital in Alexandria. Results The current results showed that the mean decrease in GFR in patients who received SOF/DAC were 5.21 ± 15.57 and 6.18 ± 16.13 after full 12 week regimen and after 1 year respectively while the mean decrease in patients SOF/SIM were 4.35 ± 14.9 and 3.57 ± 13.08 respectively. The decrease was not statistically significant in both regimens. Moreover, the mean GFR decrease in the only patient received SOF/Ribavirin was 12.8 and 30.9 after 12 weeks regimen and after one year respectively while for the only patient who received PAR/OMB/Rito/Ribavirin the decrease was 5.5 and 53.4 respectively. unfortunately, due to lack of sufficient patients number, the decrease an not be expressed statistically. Conclusion The new direct antiviral agents (sofosbuvir, daclatasvir and simeprevir) are effective and safe regarding glomerular filtration rate in patients with normal renal function. However, a meticulous monitoring of kidney function is mandatory during the course of these medications to early detect any untoward side effects. Moreover, such studies will yield beneficial data about the renal safety of these drugs if it could be performed on a larger scale of patients.