CONFERENCE UPDATE: ASN KIDNEY WEEK 2023
Early reduction of albuminuria facilitated by finerenone contributes to optimal kidney and CV outcomes in patients with T2D: Mediation analysis of the FIDELIO-DKD and FIGARO-DKD trials
In patients with type 2 diabetes (T2D), albuminuria is an early clinical marker of chronic kidney disease (CKD) and is associated with an increased risk of CKD progression and cardiovascular (CV) events.1 Finerenone, a non-steroidal mineralocorticoid receptor antagonist, has exhibited efficacy in significantly improving kidney and CV outcomes and reducing the urine albumin-to-creatinine ratio (UACR) by >30% compared to placebo in 2 prior phase 3 randomized controlled trials, FIDELIO-DKD and FIGARO-DKD.1 However, the relationship between an early finerenone-induced reduction in UACR and optimal kidney and CV outcomes remains unclear.1 As such, investigators from the FIDELIO-DKD and FIGARO-DKD trials performed a causal mediation analysis based on pooled data from both trials.1 During the ASN Kidney Week 2023, Professor Rajiv Agarwal from Indiana University, Indianapolis, the United States (US), presented results from the analysis.1
A total of 12,512 patients from FIDELITY (a prespecified pooled analysis of the FIGARO-DKD and FIDELIO-DKD trials) with CKD and T2D who had available UACR data were included in this causal mediation analysis.1 Patients had been randomly assigned 1:1 to receive either finerenone (n=6,273) or placebo (n=6,239).1 Baseline characteristics such as age, sex, systolic blood pressure (SBP), history of cardiovascular disease (CVD), estimated glomerular filtration rate (eGFR) levels, SGLT-2 inhibitor, and RAS inhibitor use were similar in both the finerenone and placebo groups.1 In particular, both groups possessed comparable median UACR at baseline (finerenone: 513.6mg/g; placebo: 514.5mg/g).1 The outcomes of this causal mediation analysis consisted of a composite of kidney outcomes (time to kidney failure, sustained ≥57% decrease in eGFR from baseline, or kidney-related death) and CV outcomes (time to CV death, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for heart failure), which were used to evaluate the benefits of finerenone-induced UACR reduction.1
At 4 months, the finerenone group experienced a 31% greater UACR reduction compared to the placebo group (33.6% vs. 2.6%), with 53% of patients (n=3,338) in the finerenone group experiencing ≥30% UACR reduction from baseline compared to only 27% of patients (n=1,684) in the placebo group.1 An early reduction in UACR of ≥30% also contributed to a reduced risk of composite kidney outcome events compared to those with <30% UACR reduction in both treatment groups over a 4-year period.1 In addition, patients who achieved an early reduction in UACR of ≥30% experienced fewer composite CV outcome events than those with <30% UACR reduction in the finerenone group.1
Subsequently, the reduction in UACR, when analyzed as a continuous variable, mediated 84% (95% CI: 49-100%) and 37% (95% CI: 8-65%) of the treatment effect of finerenone on the kidney and CV outcomes respectively.1 When UACR change was analyzed as a dichotomous variable using the guideline-recommended ≥30% reduction threshold, the treatment of finerenone mediated 64% and 26% of kidney and CV outcomes respectively.1
In summary, early albuminuria reduction facilitated by finerenone mediated a sizable proportion of the treatment effect against CKD progression and a modest proportion of the effect against CV outcomes in patients with CKD and T2D.1 The findings of this analysis highlight that achieving early albuminuria reduction with finerenone can induce durable benefits to both kidney and CV health, further emphasizing the importance of monitoring of UACR after treatment initiation in patients with T2D.1
Novel assessment tool for predicting CKD progression and identifying high-risk individuals in early-stage CKD: The Klinrisk model
Current chronic kidney disease (CKD) management strategies are dependent on the estimated glomerular filtration rate (eGFR) of patients, which gradually shapes them into a one-size-fits-all care model that lacks personalized treatments.1 In addition, despite the availability of risk assessment tools
The CopenFast trial: Discerning glycemic control and fetal outcomes between insulin aspart and faster aspart in pregnant diabetic women
Fetal overgrowth is associated with a lack of HbA1c control during pregnancy and is a common obstetric condition among women with type 1 (T1D) and type 2 (T2D) diabetes.1 Glycemic control is complicated among pregnant women with studies showing ≥45% of pregnant women with T1D experiencing ≥1 episode
Nirmatrelvir-ritonavir therapy demonstrated manageable tolerability among COVID-19 patients with CKD
Despite being an effective oral antiviral therapy for coronavirus 2019 (COVID-19), nirmatrelvir-ritonavir (NMV-r) was not approved for patients with an estimated glomerular filtration rate (eGFR) <30mL/min/1.75m2.1 This can be attributed to a phenomenon known as “renalism”, which is the frequent exc
Dapagliflozin reduces ESKD risk in geriatric CKD patients with comorbidities: A local case sharing
The prevalence of chronic kidney disease (CKD) among the elderly population is on the rise.1,2 The incidence of advanced-stageCKD increased sharply with advancing age.3 When compared with the younger counterparts, older patients with advanced CKD are more likely to be intolerable to conventional therapies, such as angiotensin-converting enzyme inhibitors (ACEis)or angiotensin receptor blockers (ARBs).2,3 In 2021, dapagliflozin was approved for the treatment of patients regardless of type 2 diabetes (T2D), providing an additional treatment option to address the medical gap in the local CKD management.4In an interview with Omnihealth Practice, Dr. Shea, Tat-Mingshared 2 clinical cases of patients aged >80 years with stage 3/4 CKD having multiple comorbidities, in whom dapagliflozin stabilized their estimated glomerular filtration rate (eGFR)and halted CKD progression. Dr. Shea also discussed the clinical data of dapagliflozin and provided practical tips to optimize treatment outcomes in the elderly CKD population.
A local case sharing: Dapagliflozin reduces proteinuria and slows disease progression in CKD patients
Dapagliflozin, a sodium-glucose co-transporter 2 (SGLT-2) inhibitor, has demonstrated improved renal outcomes in patients with chronic kidney disease (CKD), with or without type 2 diabetes (T2D), in the DAPA-CKD trial, providing an additional treatment option on top of angiotensin-converting enzyme inhibitors (ACEis) or angiotensin receptor blockers (ARBs) for better management of CKD patients.1 In an interview with Omnihealth Practice, Dr. Tam, Chun-Hay shared a clinical case of an 89-year-old patient with stage 3 CKD without T2D, in whom dapagliflozin reduced proteinuria and stabilized his renal function with good tolerability. He also discussed the clinical data of dapagliflozin and provided some practical tips on its use to optimize treatment outcomes.
Semaglutide gains FDA approval for treating obesity in adolescents aged ≥12 years
Semaglutide, a glucagon-like peptide-1 (GLP-1) analog that aids in weight loss by suppressing appetite, has recently gained approval from the United States (US) Food and Drug Administration (FDA) to treat obesity in children aged ≥12 years.1,2 The approval was based on the positive findings of a rec
New paradigms in hepatitis management to address treatment challenges and barriers to care
In a webinar organized by the Hong Kong Association for the Study of Liver Diseases (HKASLD), Professor Kim, Seung-Up and Dr. Wong, Yu-Jun Eugene introduced the new paradigms in viral hepatitis disease control. While Prof. Kim discussed some topics of hepatitis B virus (HBV) management, including the increased risk of kidney disease with long-term antiviral use and the appropriate first-line agents to mitigate this risk, Dr. Wong presented the challenges of hepatitis C virus (HCV) management and access to care, highlighting the efficacy and safety of the direct-acting antiviral (DAA) treatment of sofosbuvir/ velpatasvir (SOF/VEL) in HCV patients and the simplified treatment monitoring in reducing the healthcare burden.
Comparing the newly FDA-approved tirzepatide with insulin glargine in T2DM patients at high CV risk: The SURPASS-4 trial
Tirzepatide was approved by the U.S. Food and Drug Administration (FDA) on May 13, 2022 as the first and only dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) receptor agonist for type 2 diabetes mellitus (T2DM), given its potent glucose-lowering effects.1