609 Prognostic role of renal function in patients with previous myocardial infarction. A study with cardiac magnetic resonance

Aims There is not strong evidence in literature about the impact of renal function on the prognosis of patients with ischaemic cardiomyopathy. Thus, the aim of the study was to investigate mild renal impairment [estimated glomerular filtration rate (eGFR): 60–89 ml/min] as an independent prognostic factor in patients with history of myocardial infarction (MI). Methods and results We studied 339 consecutive patients (65 ± 13 years old, female 13%) from 2001 and 2012 with previous MI. Patients with eGFR <60 ml/min were excluded. We performed cardiac magnetic resonance (CMR) in all patients to quantify left ventricular ejection fraction (LVEF), volumes, and wall motion score index (WMSI), and to measure the infarction extent by late gadolinium enhancement (LGE). Renal function was estimated by creatinine value with Cockcroft–Gault formula and patients were divided according to normal (≥90 ml/min) and reduced (60–89 ml/min) eGFR. Patients with normal eGFR were 106 (31%, 56.9 ± 10.5 years old), 233 (69%, 66.1 ± 9.9 years old) had renal impairment. During follow-up (median 3.5 years), cardiac events (cardiac death or appropriate intra-cardiac defibrillator shock) occurred in 28/233 (12%) of patients with eGFR <90 ml/min and in 4/106 (4%) of patients with eGFR ≥90 ml/min (P < 0.05). Furthermore, survival curve showed a significantly worst prognosis in patients with renal impairment (P < 0.03). In the group of patients with ejection fraction (EF) < 35% (121 patients), cardiac events were observed only in patients with eGFR <90 ml/min (23/99, 23%, P < 0.05). At multivariate stepwise analysis, age >65 years old, eGFR <90 ml/min and WMSI >1.7 turned out to be independent predictor of cardiac events (P < 0.05). Conclusions In patients with previous MI, a mild renal impairment (eGFR between 60 and 89 ml/min) was an independent predictor of prognosis, especially if combined with left ventricular disfunction.

Associations of a SHROOM3 variant with mild renal impairment and depressive symptoms in a Chinese Han population

Background: To explore the associations of several genetic variants identified in the genome-wide association studies (GWAS) of European ancestry with mild renal impairment glomerular filtration rate (GFR) in Chinese Han population.Methods: Data of 1788 community-dwelling elders from the baseline survey of the ageing arm of the Rugao Longevity and Ageing Study was used. Plasma creatinine based GFR was estimated using the eGFR-EPI equations.Results: Of the 10 common polymorphisms identified in GWAS of the European ancestry, rs17319721 located in the first intron of the SHROOM3, was associated with GFR. A allele was associated with both decreased GFR level and greater odds of mild renal impairment (OR 1.12, 95% CI 1.01-1.23, p=0.029) defined by GFR<90 mL/min/1.73 m2 after adjusting for multiple confounds of chronic kidney disease. In addition, compared with rs17319721-GG genotype, AA was associated with both higher depressive score and greater risk of depression prevalence, showing a pleiotropic effects of rs17319721. However, we did not found significant association of GFR levels with another 42 common polymorphisms that was previously reported to be associated with the traditional risk factors of kidney diseases.Conclusions: SHROOM3-rs17319721 is associated with GFR levels, kidney impairment, and depressive symptoms in a Chinese population.

Efficacy and Safety of Non-Vitamin K Anticoagulants for Atrial Fibrillation in Relation to Different Renal Function Levels: A Network Meta-Analysis

Background. We performed a network meta-analysis (NMA) comparing the efficacy (stroke or systemic embolism) and safety (major bleeding) among different non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation (AF) and renal impairment, with the aim of recommending the proper drug and the dose based on renal function. Methods. We searched PubMed, EMBASE, Web of Science, and Cochrane Library with the items “dabigatran, edoxaban, apixaban, rivaroxaban, warfarin, and atrial fibrillation” through August 2019. NMA was analyzed with R (version 3.5.1, R Foundation for Statistical Computing) with the packages gemtc recalling JAGS (version 4.3.0) for the efficacy and safety of each drug with regard to different levels of renal function. NetMetaXL (version 1.6.1) and winBUGS (version 1.4.3) were used to obtain the cumulative ranking curve (SUCRA) of each drug. Result. In patients with normal renal function, dabigatran150 was ranked as the most effective drug (SUCRA 0.90), followed by dabigatran110 (SUCRA 0.68), apixaban (SUCRA 0.66), and rivaroxaban (SUCRA 0.59). With regard to the safety for preventing major bleeding, there was high probability that edoxaban30 (SUCRA 0.99) ranked first, compared to dabigatran110 (SUCRA 0.78) and edoxaban60 (SUCRA 0.66). For patients with mild renal impairment, with respect to the most effective drug for preventing stroke or systemic embolism, edoxaban60 ranked first (SUCRA 0.98), in comparison with dabigatran150 (SUCRA 0.74) and apixaban (SUCRA 0.64). Possibility of ranking first for the safest drug was edoxaban30 (SUCRA 0.99), followed by dabigatran110 (SUCRA 0.70) and apixaban (SUCRA 0.69). In patients with moderate renal function, dabigatran150 (SUCRA 0.95) ranked as the most effective drug in comparison with apixaban (SUCRA 0.66). Dabigatran110 (SUCRA 0.53), rivaroxaban (SUCRA 0.51), and edoxaban60 (SUCRA 0.50) had the similar probability of ranking third. When referred to the safest drug, probability of ranking first for preventing major bleeding was edoxaban30 (SUCRA 0.98), followed by apixaban (SUCRA 0.85) and edoxaban60 (SUCRA 0.64). Conclusion. In patients with AF and renal impairment and for patients with normal renal function, dabigatran 110 mg (bid) might have a better effect on the clinical results. And it does not coincide with patients taking dabigatran 110 mg with dose reduction for other factors including aged ≥75 years, renal impairment (CrCL 30–50 mL/min), gastritis, esophagitis, or gastroesophageal reflux, receiving concomitant verapamil, and so on. For patients with mild renal impairment, apixaban 5 mg (bid) would be a better choice for preventing stroke or systemic embolism and major bleeding, while apixaban 5 mg (bid) and edoxaban 60 mg (qd) were recommended for patients with moderate renal impairment. However, considering the fact of no RCTs for the head-to-head comparison, caution should be exercised over selecting each of NOACs for patients.

Comparative Study between Fractional Excretion of Sodium and Fractional Excretion of Urea in Differentiating Prerenal From Renal Acute Kidney Injury in ICU Patients with Circulatory Shock

Background The incidence of acute renal injury (AKI) in ICU is 5%. The mortality rate increases up to 50% if AKI is a part of multiple organ dysfunction syndrome. Aim of the Work Comparison between FENa and FEurea in differentiating renal from prerenal acute kidney injury in circulatory shock, and the effect of diuretics on their handling. Patients and Methods This retrospective study was conducted on 45 Egyptian patients with AKI complicating circulatory shock admitted to the ICUs of AIN SHAMS University Hospital, from August 2018 to February 2019. Consents were taken from all of them according to the local ethics committee approval. Results The cutoff points of both FENa and FEurea as a predictor of mortality were not statistically justified. This is explained as all our patients had circulatory shock, and so patients with mild renal impairment may die from their severe shock state, and patients with severe renal affection may survive if their shock could be rapidly corrected. This cutoff point calculation is recommended only in patients with AKI without other organ affections or shock that may affect the mortality. Conclusion Although both fractional excretion of urea (FEurea) and fractional excretion of sodium (FENa) are feasible, reproducible, and inexpensive markers used in differentiating renal from prerenal azotemia, in our study FEurea showed higher sensitivity and specificity than FENa, not only in differentiating renal from prerenal azotemia in critically ill patients complicating circulatory shock, but also its values were not affected by the use of diuretics like FENa in the same group of patients.

Real-world safety of pemetrexed, carboplatin, and pembrolizumab in U.S. NSCLC patients.

50 Background: A Phase 3 KEYNOTE-189 clinical trial showed improved clinical benefit with acceptable toxicity of pemetrexed combined with pembrolizumab and platinum (Gandhi, 2018). However, the safety data with this combination has not been evaluated in a real-world setting with large number of patients with non-squamous non-small cell lung cancer (NSQ NSCLC). Methods: Flatiron Health’s electronic health record-derived data were used to identify advanced NSQ NSCLC patients (≥18 y) who received pemetrexed, pembrolizumab, and carboplatin (≤6 cycles; Pem+Pembro+Carb) as initial treatment from May 2017 to Oct 2018. Endpoints were overall occurrence of select laboratory adverse events (AEs; any Grade and Grade ≥3), which were described by treatment phase (Pem/Pembro cycles < 5 vs ≥5) and pre-specified subgroups. Results: The study included 1088 patients (median age = 68 y; male, 57%). In patients with maintenance (Pem/Pembro ≥5) cohort (N = 462), the median number of treatment cycles was 9 for Pembro and 6 for Pem. The occurrence rates of neutrophil count decrease and platelet count decrease were numerically higher in the induction phase, whereas those of chronic kidney disease (CKD) showed an opposite trend (Table). Grade ≥3 CKD occurrence rate was higher in patients with mild renal impairment (5.1% vs 2.6%) and elderly (≥75 y) patients (7.5% vs 3.3%). Conclusions: Considering the heterogeneity and vulnerability of real-world population, the laboratory AE occurrence rate with Pem+Pembro+Carb in this study was comparable with those reported in KEYNOTE-189. Various trends were observed for the respective AEs by treatment phase. [Table: see text]

Hypertensive urgencies and emergencies

Hypertensive urgencies and emergencies occur most commonly in patients with previous hypertension, especially if inadequately managed. About 40% of cases have an underlying cause, most commonly renovascular disease, primary renal diseases, phaeochromocytoma, and connective tissue disorders. Hypertensive emergencies occur when severely elevated or sudden marked increase in blood pressure is associated with acute end-organ damage. Malignant phase hypertension is a rare condition characterized by very high blood pressure, with bilateral retinal haemorrhages and/or exudates or cotton wool spots, with or without papilloedema. Presentation is typically with visual disturbance, with or without headaches. Urinalysis may demonstrate proteinuria and haematuria, even in the absence of primary renal disease. Some patients with mild renal impairment at first presentation may improve, or even regain normal renal function, but this is unlikely to occur in those with more severe renal impairment at presentation.

Diffuse alveolar haemorrhage associated with subsequent development of ANCA positivity and emphysema in three young adults

Background Diffuse alveolar haemorrhage (DAH) is characterized by the diffuse accumulation of red blood cells within the alveoli, presence of ground glass opacities and/or consolidation on computed tomography (CT). Aside from identifiable non-immune causes, DAH is classically subdivided into idiopathic (idiopathic pulmonary haemosiderosis, IPH) and autoimmune DAH. Here we describe three cases presenting with recurrent pulmonary haemorrhage, initially classified as IPH, who, several years after first presentation, develop anti myeloperoxidase antibodies (MPO) positivity, emphysema on CT and, in one case, renal involvement. Case presentation Patient 1 was diagnosed with IPH aged 14. Her disease remained poorly controlled despite immunosuppression, although ANCA remained negative over the years. Nineteen years from initial presentation, she developed MPO-ANCA positive antibodies and mild renal impairment. She was treated with Rituximab with good response. From first presentation, the chest CT was consistently characterized by diffuse ground-glass opacities and interlobular septal thickening. Ten years later, cystic opacities consistent with emphysema, with a striking peribronchovascular distribution, developed. Patient 2 was diagnosed with IPH aged 32. He was treated with corticosteroids and methotrexate, with fluctuating response. At 11 years from initial presentation, MPO-ANCA positivity was identified, and emphysema with a peribronchovascular distribution was observed on CT, with subsequent significant increase in extent. Patient 3 was diagnosed with IPH at the age of seven, and had recurrent episodes of haemoptysis of varying degree of severity, treated with intermittent courses of corticosteroids until age 11, when he was intubated due to severe DAH. Eight years after the diagnosis emphysematous changes were noted on CT and MPO-ANCA positivity developed for the first time 11 years after initial diagnosis. Conclusions We believe these three cases highlight: 1) the possibility of development of ANCA positivity several years down the line from first DAH presentation 2) the possibility that DAH may lead to cystic/emphysematous changes with peribronchovascular distribution on CT. Moreover, the need for ongoing immunosuppressive treatment and the development of emphysema, emphasize a possible role played by autoimmune phenomena, even when DAH is initially diagnosed as “idiopathic”. Further studies are required to better understand the relationship between DAH, ANCA positivity and development of emphysema.

Persistent Rivaroxaban Effect Due to Impaired Renal Clearance and Medication Effects

Rivaroxaban (Xarelto; Johnson & Johnson Services, Inc) is a direct oral anticoagulant (DOAC) that works by directly inhibiting the active site of factor Xa (FXa). Rivaroxaban is metabolized and cleared via the kidney and liver. The results of various studies have shown that patients with severe renal impairment should receive reduced dosages of rivaroxaban or another anticoagulant due to impaired clearance. Although it is not required, monitoring rivaroxaban is useful in some conditions; however, the assays required for such monitoring are not readily available. Herein, we present a case of a 68-year-old Caucasian male patient who was receiving rivaroxaban (20 mg/day) for atrial flutter and had mild renal impairment. The patient was found to have increased effect of rivaroxaban due to further impairment of renal clearance caused by several renally cleared medications. This case highlights the importance of closely examining the renal function of and medication list for a patient before starting DOACs such as rivaroxaban.

Severe Combined Dyslipidemia With a Complex Genetic Basis

Background. Familial dysbetalipoproteinemia (also known as type 3 hyperlipoproteinemia) is typically associated with homozygosity for the apolipoprotein E2 isoform, but also sometimes with dominant rare missense variants in the APOE gene. Patients present with roughly equimolar elevations of cholesterol and triglyceride (TG) due to pathologic accumulation of remnant lipoprotein particles. Clinical features include tuberoeruptive xanthomas, palmar xanthomas, and premature vascular disease. Case. A 48-year-old male presented with severe combined dyslipidemia: total cholesterol and TG were 11.5 and 21.4 mmol/L, respectively. He had dyslipidemia since his early 20s, with tuberous xanthomas on his elbows and knees. His body mass index was 42 kg/m2. He also had treated hypertension, mild renal impairment, and a history of gout. He had no history of cardiovascular disease, peripheral arterial disease, or pancreatitis. Multiple medications had been advised including rosuvastatin, ezetimibe, fenofibrate, and alirocumab, but his lipid levels were never adequately controlled. Genetic Analysis. Targeted next-generation sequencing identified (1) the APOE E2/E2 homozygous genotype classically described with familial dysbetalipoproteinemia; (2) in addition, one APOE E2 allele contained the rare heterozygous missense variant p.G145D, previously termed apo E-Bethesda; (3) a rare heterozygous APOC2 nonsense variant p.Q92X; and (4) a high polygenic risk score for TG levels (16 out of 28 TG-raising alleles) at the 82nd percentile for age and sex. Conclusion. The multiple genetic “hits” on top of the classical APOE E2/E2 genotype likely explain the more severe dyslipidemia and refractory clinical phenotype.