A PILOT STUDY OF ANGIOTENSIN II AS PRIMARY VASOPRESSOR IN CRITICALLY ILL ADULTS WITH VASODILATORY HYPOTENSION: THE ARAMIS STUDY.

ABSTRACT: Objective: The aim of the study is to evaluate the efficacy and safety of using angiotensin II (Ang2) as primary vasopressor for vasodilatory hypotension. Methods: This was a prospective observational study of critically ill adults admitted to an academic intensive care unit (ICU) with vasodilatory hypotension. We treated 40 patients with Ang2 as primary vasopressor and compared them with 80 matched controls who received conventional vasopressors (norepinephrine, vasopressin, metaraminol, epinephrine, or combinations). Results : Mean age was 63 years and median Acute Physiology and Chronic Health Evaluation III score was 65. Ang2 patients had lower ICU mortality (10% vs 26%, P = 0.04); however, their 28- and 90-day mortality was not significantly different (18% vs 29%, P = 0.18; 22% vs 30%, P = 0.39). Peak serum creatinine levels were similar (128 vs 126 µmol/L, P = 0.81), as was the incidence and stage of acute kidney injury (70% vs 74%, P = 0.66), requirement for continuous renal replacement therapy (14% vs 13%, P = 0.84), and risk of major adverse kidney events at 7 days (20% vs 29%, P = 0.30). However, Ang2 patients with prior exposure to renin angiotensin aldosterone system inhibitors had a lower peak serum creatinine ( P = 0.03 for interaction) than conventional vasopressors patients, and serum troponin elevations were less common with Ang2 (8% vs 22%, P = 0.04). The incidence of thromboembolic complications was similar. Conclusions: Primary Ang2 administration in vasodilatory hypotension did not seem harmful compared with conventional vasopressors. Although Ang2 did not decrease peak serum creatinine levels or major adverse kidney events, its effects on intensive care unit survival, serum troponin, and renal function in patients on renin angiotensin aldosterone system inhibitors warrant further exploration in randomized trials (ACTRN12621000281897).

Risk factors for major adverse kidney events in the first year after acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) survivors are at increased risk of major adverse kidney events (MAKEs), including chronic kidney disease (CKD), end-stage kidney disease (ESKD) and death. High-risk AKI patients may benefit from specialist follow-up, but factors associated with increased risk have not been reported. METHODS: We conducted a retrospective study of AKI patients admitted to a single centre between 2012 and 2016 who had a baseline estimated glomerular filtration rate (eGFR) >30 mL/min/1.73 m2 and were alive and independent of renal replacement therapy (RRT) at 30 days following discharge. AKI was identified using International Classification of Diseases, Tenth Revision codes and staged according to the Kidney Disease: Improving Global Outcomes criteria. Patients were excluded if they were kidney transplant recipients or if AKI was attributed to intrinsic kidney disease. We performed Cox regression models to examine MAKEs in the first year, defined as the composite of CKD (sustained 25% drop in eGFR), ESKD (requirement for chronic RRT or sustained eGFR <15 mL/min/1.73 m2) or death. We examined secondary outcomes (CKD, ESKD and death) using Cox and competing risk regression analyses. RESULTS: We studied 2101 patients (mean ± SD age 69 ± 15 years, baseline eGFR 72 ± 23 mL/min/1.73 m2). Of these, 767 patients (37%) developed at least one MAKE (429 patients developed CKD, 21 patients developed ESKD, 375 patients died). MAKEs occurred more frequently with older age [hazard ratio (HR) 1.16 per decade, 95% confidence interval (CI) 1.10-1.24], greater severity of AKI (Stage 2 HR 1.38, 95% CI 1.16-1.64; Stage 3 HR 1.62, 95% CI 1.31-2.01), higher serum creatinine at discharge (HR 1.04 per 10 µmol/L, 95% CI 1.03-1.06), chronic heart failure (HR 1.41, 95% CI 1.19-1.67), liver disease (HR 1.68, 95% CI 1.39-2.03) and malignancy (non-metastatic HR 1.44, 95% CI 1.14-1.82; metastatic HR 2.26, 95% CI 1.80-2.83). Traditional risk factors (e.g. diabetes and cardiovascular disease) had limited predictive value. CONCLUSIONS: More than a third of AKI patients develop MAKEs within the first year. Clinical variables available at the time of discharge can help identify patients at increased risk of such events.

Clinical impact of genomic testing in patients with suspected monogenic kidney disease.

PURPOSE: To determine the diagnostic yield and clinical impact of exome sequencing (ES) in patients with suspected monogenic kidney disease. METHODS: We performed clinically accredited singleton ES in a prospectively ascertained cohort of 204 patients assessed in multidisciplinary renal genetics clinics at four tertiary hospitals in Melbourne, Australia. RESULTS: ES identified a molecular diagnosis in 80 (39%) patients, encompassing 35 distinct genetic disorders. Younger age at presentation was independently associated with an ES diagnosis (p < 0.001). Of those diagnosed, 31/80 (39%) had a change in their clinical diagnosis. ES diagnosis was considered to have contributed to management in 47/80 (59%), including negating the need for diagnostic renal biopsy in 10/80 (13%), changing surveillance in 35/80 (44%), and changing the treatment plan in 16/80 (20%). In cases with no change to management in the proband, the ES result had implications for the management of family members in 26/33 (79%). Cascade testing was subsequently offered to 40/80 families (50%). CONCLUSION: In this pragmatic pediatric and adult cohort with suspected monogenic kidney disease, ES had high diagnostic and clinical utility. Our findings, including predictors of positive diagnosis, can be used to guide clinical practice and health service design.

EARLY PERITONITIS AND ITS OUTCOME IN INCIDENT PERITONEAL DIALYSIS PATIENTS.

BACKGROUND: Early-onset peritonitis is a serious complication of peritoneal dialysis (PD) and is associated with heightened risks of technique failure and death. The risk factors for early peritonitis and its outcomes are unknown. METHODS: This registry study examined all incident Australian PD patients between 2003 and 2014. The primary outcome was early peritonitis, defined as onset within 12 months of starting therapy. Secondary outcomes were medical cure, relapse/recurrence, catheter removal, peritonitis-associated technique failure, and peritonitis-associated death. RESULTS: Of 9,845 patients, 2,615 experienced 3,827 early-peritonitis episodes (0.50 episodes per patient-year). Early peritonitis was more common in patients who were male, obese, had a history of cigarette smoking or cerebrovascular disease, used continuous ambulatory PD, and had received prior renal replacement therapy for > 90 days. Remoteness was a risk modifier for the association between race and early peritonitis; remote Aboriginal, Torres Strait Islander, Maori and Pacific Islander patients had the highest risk. Obese patients were more likely to achieve medical cure. Older patients were less likely to achieve cure and more likely to experience peritonitis-associated death. CONCLUSIONS: In summary, several factors predicted early peritonitis in incident PD patients. Modified approaches to patient selection, training techniques, and prevention strategies should be considered in high-risk individuals.