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.

284 Worsening renal function as an outcome predictor in patients with new onset atrial fibrillation on direct oral anticoagulant

Aims In patients with atrial fibrillation (AF), baseline kidney function is used to guide oral anticoagulant (OA) selection and dosing, and chronic kidney disease (CKD) is a significant outcome predictor. However, the incidence of worsening renal function (WRF) and its prognostic role during treatment with direct oral anticoagulants (DOACS) has been poorly explored. To assess the prognostic role of WRF in terms of bleedings and major adverse cardiovascular events (MACEs) in a cohort of patients with newly diagnosed non-valvular AF (NVAF) treated with DOACs. Methods and results Between January 2017 and March 2019, we enrolled all the patients with newly diagnosed NVAF and OA indication, treated with DOACs. Renal function was assessed using the mean value of the estimated glomerular filtration rates (eGFR) calculated using Cockcroft–Gault (CG), modification of diet in renal disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulas. CHA2DS2-VASc and HAS-BLED scores were used at baseline to estimate the ischaemic and haemorrhagic risk, respectively. At follow-up, WRF was identified as a decrease in eGFR of at least 20% while bleedings were classified according to the international society of thrombosis and haemostasis (ISTH) criteria. Finally, we defined AF progression as the transition from paroxysmal to persistent or permanent AF or from persistent to permanent AF. 1009 patients with newly diagnosed NVAF started on DOAC were enrolled. They were followed-up for 21.6 ± 9.5 months. Overall, WRF was observed in 181 cases (18%). Patients with WRF had higher rates of progression of AF (18.5% vs. 11.8%, P = 0.02), MACEs (20.4% vs. 12.9%, P = 0.09) and major bleedings (MBs) (9.4% vs. 4.7%, P = 0.013). WRF did not correlate with all bleedings, stroke, or acute coronary syndrome (ACS). However, those who presented WRF using CKD-EPI formula had higher ACS incidence (6.1% vs. 2.5%, P = 0.015), and generally better-predicted MACEs. At multivariate analysis adjusted for age, hypertension, baseline HAS-BLED score and WRF, the latter emerged as an independent predictor of MB (OR: 1.9, 95% CI: 1.059–3.51). Conclusions In patients with newly diagnosed NVAF treated with DOACs, WRF is associated with AF progression and MACEs, and emerged as an independent predictor of major bleedings. WRF evaluated with CKD-EPI formula better predicted MACEs.

Low rate of worsening renal function after 2 years of treatment with edoxaban in patients from the ETNA-AF-Europe study

Background Use of vitamin K antagonists (VKAs) is associated with a crude event rate of 23% per year for worsening renal function (WRF). Although non-vitamin K antagonist oral anticoagulants (NOACs) have been associated with a lower risk of longitudinal decline in renal function compared with VKAs, available evidence on renal function decline in patients using NOACs is still limited. Furthermore, renal function is a dose reduction criterion for NOACs, which poses an important question about how physicians should treat patients whose renal function worsens over time. Purpose To evaluate the degree of renal function decline in AF patients treated with edoxaban after 2 years of follow-up, and to investigate clinical outcomes of patients with vs without WRF in the ETNA-AF-Europe study. Methods ETNA-AF-Europe is a multinational, multicentre, observational, post-authorisation safety study conducted in 825 sites in 10 European countries. Results are based on a data snapshot taken on 26th October 2020 which include data up to 2 years of follow-up. Patients were excluded from the analysis population if data to calculate estimated glomerular filtration rate [eGFR] were not available for at least one of the follow-up time-points of 1-year and 2-year. We categorised patients (n=9084) into two subgroups: 1) those with WRF (i.e. ≥25% decline in eGFR from baseline; n=918), and 2) those without WRF (n=8166). eGFR was estimated using the Cockcroft-Gault formula. Baseline characteristics and annualised event rates including 95% confidence intervals were analysed using descriptive analyses. Results Of the 13,417 patients in ETNA-AF-Europe who were included in the 2-year follow-up analysis, 9084 were included in this subgroup analysis, of whom 56.2% were male. Baseline eGFR were similar between patients with and without WRF when comparing across the different renal function categories (Table 1). The majority of the edoxaban-treated patients did not experience WRF (89.9%) during the 2 years of follow-up. The proportion of patients with WRF (10.1%) were older, more often frail and had higher rates of underlying comorbidities, such as diabetes, hypertension and heart failure (Table 1). Patients with WRF had higher annualised event rates of all-cause and cardiovascular death than those without (3.78% vs 1.90% and 2.06% vs 0.92%, respectively). Major bleeding and stroke rates were low, but numerically higher in patients with renal worsening compared to those without WRF (Figure 1). Intracranial haemorrhage rates remained low (0.17% vs 0.19%; Figure 1) in both subgroups. Conclusions This subgroup analysis provides real-world evidence for a low risk of WRF in AF patients treated with edoxaban over a 2-year period. Patients with WRF had higher mortality than those without, as well as numerically higher major bleeding and stroke rates. Importantly, intracranial haemorrhage rates remained low irrespective of WRF. FUNDunding Acknowledgement Type of funding sources: Private company. Main funding source(s): Daiichi Sankyo Europe GmbH /

BRASH syndrome: more than just syncope

The pentad of bradycardia, renal failure, atrioventricular nodal blockade, shock, and hyperkalemia describes the BRASH syndrome, a newly recognized phenomenon in which accumulation of potassium and renally excreted atrioventricular nodal blockers cause a cycle of bradycardia, hypoperfusion, and worsening renal function. Here, we describe a case of BRASH in an elderly woman whose medications had recently changed, and who presented with bradycardia, anuria, and hypotension. Resolution of symptoms occurred over hours after the right treatment was started. Furthermore, we review case reports written in recent years for common BRASH syndrome patient characteristics.

Renal outcomes of idiopathic and atypical membranous nephropathy in adult Chinese patients: a single center retrospective cohort study

Background Membranous nephropathy (MN) is mainly classified into idiopathic MN (iMN) and secondary MN in etiology. In recent years, a new kind of membranous nephropathy, atypical membranous nephropathy (aMN) which shows “full house” in immunofluorescence but without definite etiology was paid more attention. In a single center cohort, the renal outcomes of iMN and aMN were compared. Methods iMN and aMN patients were selected from renal pathology databank from January 2006 to December 2015. Patients’ demographics, laboratory values, induction regimens and patients’ responses were recorded. Specially, creatinine, eGFR, albumin and 24 h urinary protein excretion were recorded at 6th month after the induction of immunosuppressive (IS) treatment and at the end of follow up. Complete proteinuria remission was defined as urinary protein < 0.3 g/d, partial proteinuria remission was defined as urinary protein between 0.3 g/d ~ 3.5 g/d and decreased > 50 % from the baseline. The primary outcome was worsening renal function, defined as a 30 % or more decrease in eGFR or end-stage renal disease (eGFR < 15ml/min/1.73m2). COX proportional hazard models were used to test if aMN was a risk factor of worsening renal function compared with iMN. Results There were 298 patients diagnosed with MN and followed in our center for 1 year or more, including 145 iMN patients with an average follow-up time of 4.5 ± 2.6 years, and 153 aMN patients with 4.1 ± 2.0 years (p = 0.109). The average age of iMN patients was older than aMN patients (56.1 ± 12.2 versus 47.2 ± 16.2 years old, p < 0.001). There were 99 iMN patients and 105 aMN patients with nephrotic range proteinuria and without previous immunosuppressive treatment. 93 (93.9 %) and 95 (90.5 %) patients underwent immunosuppressive treatment in iMN and aMN group, and there was no significant difference of the overall proteinuria remission rates at 6th month (59.1 % vs. 52.0 %, p = 0.334) and endpoint (73.7 % vs. 69.5 %, p = 0.505) between the two groups. 25 (25.3 %) patients in iMN group and 21 (20.0 %) patients in aMN group reached primary endpoint (X2 = 0.056, p = 0.812). Multivariate COX regression showed that after demographics, baseline laboratory values and remission status at 6th month were adjusted, aMN group had similar renal outcome compared with iMN group, the HR of primary outcome was 0.735 (95 % CI 0.360 ~ 1.503, p = 0.399). Conclusions The proteinuria remission rates and renal outcomes were similar in iMN and aMN patients after covariables were adjusted.