NEWS & PERSPECTIVE
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 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 exclusion of patients with advanced chronic kidney disease (CKD) and patients receiving dialysis and kidney transplant recipients from clinical trials evaluating new drugs.2 Furthermore, pharmacokinetic data implied that nirmatrelvir would accumulate with decreasing kidney function.2 Nevertheless, nephrology experts from the Chinese University of Hong Kong (CUHK)’s Faculty of Medicine (CU Medicine) and the Prince of Wales Hospital (PWH) had suggested that a modified dosage of nirmatrelvir-ritonavir, administered after hemodialysis, can theoretically limit the extent of drug accumulation, allowing the use of this antiviral therapy in patients with CKD.2 As such, much remains to be explored on implementing nirmatrelvir-ritonavir therapy in patients with CKD.1
A prospective, single-arm interventional study was conducted to evaluate the safety and effectiveness of dose-adjusted nirmatrelvir-ritonavir treatment in patients with CKD and COVID-19.1 A total of 85 adult patients with CKD (eGFR <60mL/min/1.75m2) and COVID-19 infection were recruited.1 Patients with an eGFR <30mL/minute/1.73m2 were classified into the low-eGFR group (n=65), while patients with an eGFR between >30mL/minute/1.73m2 were classified into the high-eGFR group (n=10).1 Additionally, 10 COVID-19 patients with an eGFR >60mL/min/1.75m2 were also included as controls.1 A modified dosage of nirmatrelvir-ritonavir was calculated by the CKD Epidemiology collaboration (CKD-EPI) creatinine equation based on the eGFR of each patient cohort and administered for 5 days.1 The prevalence of adverse events (AEs) and drug-discontinuation events served as the primary endpoints of this study.1 Secondary endpoints focused on the virological outcomes, such as polymerase chain reaction (PCR) cycle threshold (Ct) value and virological rebound.1
The modified dose of combined nirmatrelvir-ritonavir therapy has proven to be well-tolerated among COVID-19 patients with CKD.1 The overall prevalence rates of AEs and serious AEs are 9.4% and 5.9%.1 A total of 5 patients discontinued the treatment due to severe COVID-19 pneumonia and 2 because of gastrointestinal symptoms.1 No significant difference in the prevalence of AEs was observed between low- and high-eGFR cohorts.1 Among the patient population, cough (21.2%) and fatigue (11.8%) were the 2 most frequent symptoms reported during treatment.1 These symptoms resolved in 18.3 ± 11.1 days with no significant difference in resolution time between the eGFR cohorts (19.4 ± 11.1 vs. 17.9 ± 11.2; p=0.7).1
In terms of virological outcomes, a negative rapid antigen test (RAT) result was achieved after a mean period of 5.4 ± 3.3 days of treatment.1 The overall mean PCR Ct value was significantly increased after the 5-day treatment when compared to the baseline (p<0.001), with 63.8% of patients having a PCR Ct value >30 by day 5.1 The mean Ct value further increased to 38.8 ± 7.9 at day 15, resulting a final PCR Ct value of 43.7 ± 4.0 at day 30, both of which were significant improvements from the baseline (p<0.001).1 No significant differences in the change in viral load were observed between the low- and high-eGFR cohorts.1 In addition, 11.8% of patients experienced viral rebound during the study period, with 5.9% of patients developed symptom rebound.1 Nevertheless, none of the symptom rebound was associated with viral rebound.1
To conclude, the results of this study provided further evidence supporting nirmatrelvir-ritonavir’s desirable safety profile across different eGFR levels in COVID-19 patients, particularly high-risk patients with CKD (eGFR <30mL/min/1.75m2).1 Additionally, the results also indicated nirmatrelvir-ritonavir’s remarkable efficacy regardless of the patient’s eGFR status.1 Hence, modified doses of nirmatrelvir-ritonavir according to eGFR can be considered for COVID-19 patients with CKD.1
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.
Update on COVID-19 infection and vaccination management in SLE
The prevalence of Coronavirus disease 2019 (COVID-19) in systemic lupus erythematosus (SLE) patient is higher than in the normal population and SLE patients being associated with higher risk of death from COVID-19.1 The COVID-19 Treatment Guidelines Panel (hereinafter referred to as “The Panel”) fro
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.
Insightful experience: SGLT2i to treat heart failure with reduced ejection fraction
Heart failure (HF) is global pandemic affecting at least 26 million people worldwide in 2017 and has been increasing in prevalence.1 In 2020, HF plus other heart diseases caused an age-standardized death rate of 34.0 per 100,000 standard population in Hong Kong.2 Previously, patients with HF with reduced ejection fraction (HFrEF) were treated with a foundational triple therapy including β-blockers, renin-angiotensin system inhibitors [including angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs)] or angiotensin receptor-neprilysin inhibitors (ARNIs), as well as mineralocorticoid receptor antagonists (MRAs).3 With reference to the recent data supporting the benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2is) in patients with chronic HFrEF regardless of the diabetes status, it is noted that comprehensive diseasemodifying quadruple therapy has now become the new standard of care for HFrEF patients.4,5 In a recent interview with Omnihealth Practice, Professor Siu, Chung-Wah David shared his insights on the application of SGLT2i in HFrEF treatment.
Managing difficult-to-treat infections in immunocompromised patients
Infections by multidrug-resistant organisms (MDROs), especially Gram-negative rods, are associated with higher mortality, higher morbidity, longer hospital stay and increased public healthcare costs.1 For patients infected with carbapenemase-producing Enterobacteriaceae (CPE), few effective antibiot
An early portrait of neuropathological features of COVID-19
An outbreak of atypical pneumonia caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was initially reported in December 2019 from Wuhan in China.1 Since then, over 44 million people worldwide have been affected by the novel coronavirus disease 2019 (COVID-19).2 Owing to a high proportion of cases being asymptomatic or mildly symptomatic, the complete denominator of COVID-19 remains unknown.1 While literature is replete with pulmonary manifestations of COVID-19, its neurological complications are being increasingly recognized.1
Beyond diabetes: FDA now approves dapagliflozin for the treatment of chronic kidney disease
Dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor that was initially approved in 2014 for the treatment of type 2 diabetes mellitus (T2DM) and subsequently for heart failure with reduced ejection fraction (HFrEF), has recently received yet another approved indication by the United St
A large register-based study from Sweden identified chronic kidney disease as a risk factor for dementia in older adults
Chronic kidney disease (CKD), defined as the persistent reduction in kidney function, is a growing health concern in the elderlies with an estimated global mean prevalence of 34.3% for populations over the age of 70-years-old.1 Associated with multiple comorbidities, reduced kidney function is a str
What not to ignore when diabetes interacts with acute and chronic kidney diseases: A local case sharing
While they may not necessarily have a causal relationship, both chronic kidney disease (CKD) and diabetes mellitus (DM) have become increasingly more prevalent worldwide.1 As these conditions could be risk factors for developing acute kidney injury (AKI),2 CKD and DM must be carefully managed to pre