BackgroundImmune checkpoint inhibitors (ICPi) are a novel and promising anti-cancer therapy. There are limited data on the incidence, risk factors and outcomes of acute kidney injury (AKI) in patients receiving ICPi.MethodsWe conducted a cohort study of patients receiving ICPi at our center between 2010 and 2017 via electronic health record. The primary outcome was AKI (increase of >50% from baseline serum creatinine (sCr)). Risk factors for AKI were assessed using logistic regression. Survival among those with and without AKI was compared using the Kaplan-Meier method.ResultsAmong 309 patients on ICPi, 51 (16.5%) developed AKI (Kidney Disease Improving Global Outcomes (KDIGO) stages 1: 53%, 2: 22%, 3: 25%). AKI was associated with other immune-related adverse events (IRAE) (OR 3.2, 95% CI 1.6 to 6; p<0.001), hypertension (OR 4.3, 95% CI 1.8 to 6.1; p<0.001) and cerebrovascular disease (OR 9.2; 95% CI 2.1 to 40; p<0.001). Baseline sCr, cancer, and ICPi type was not associated with AKI. Use of angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers (OR 2.9; 95% CI 1.5 to 5.7; p=0.002), diuretics (OR 4.3; 95% CI 1.9 to 9.8; p<0.001), and corticosteroid treatment (OR 1.9; 95% CI 1.1 to 3.6; p=0.03) were associated with AKI. In the multivariable analysis, AKI was associated only with other IRAE (OR 2.82; 95% CI 1.45 to 5.48; p=0.002) and hypertension (OR 2.96; 95% CI 1.33 to 6.59; p=0.008). AKI was not associated with increased risk of mortality (HR 1.1; 95% CI: 0.8 to 1.6; p=0.67). ICPi nephrotoxicity was attributed via biopsy or nephrologist assessment in 12 patients (six interstitial nephritis, two membranous nephropathy, two minimal change disease, and two thrombotic microangiopathy). Subsequent doses of ICPi were administered to 12 patients with prior AKI, with one (8.3%) having recurrent AKI.ConclusionAKI is a common complication in patients receiving ICPi treatment. The development of other IRAE and previous diagnosis of hypertension were associated with increased AKI risk. AKI was not associated with worse survival. Distinguishing kidney IRAE from other causes of AKI will present a frequent challenge to oncology and nephrology practitioners. Kidney biopsy should be considered to characterize kidney lesions and guide potential therapy.

Rationale and Objective Coronavirus disease 2019 (COVID-19) may be associated with high rates of AKI and kidney replacement therapy (KRT), potentially overwhelming healthcare resources. Our objective was to determine the pooled prevalence of AKI and KRT among hospitalized patients with COVID-19. Study Design Systematic Review and Meta-analysis Data sources Medline, Embase, the Cochrane Library, and a registry of preprinted studies, published up to 14 Oct 2020. Study Selection Eligible studies reported the prevalence of AKI in hospitalized patients with COVID-19 according to the Kidney Disease Improving Global Outcomes (KDIGO) definition. Data Extraction and Synthesis We extracted data on patient characteristics, the proportion of patients developing AKI and commencing KRT, important clinical outcomes (discharge from hospital, ongoing hospitalization and death), and risk of bias. Outcomes and Measures We calculated the pooled prevalence of AKI and receipt of KRT, along with 95% confidence intervals (CI) using a random effects model. We performed subgroup analysis based on admission to an intensive care unit (ICU). Results Of 2,711 records reviewed, we included 53 published and 1 preprint study in the analysis, which comprised 30,657 hospitalized patients with COVID-19. Data on AKI were available for 30,639 patients (n=54 studies), and the receipt of KRT for 27,525 patients (n=48 studies). The pooled prevalence of AKI was 28% (95% CI 22% to 34%; I 2 =99%), and the pooled prevalence of KRT was 9% (95% CI 7% to 11%; I 2 =97). The pooled prevalence of AKI among patients admitted to the ICU was 46% (95% CI 35% to 57%, I 2 =99%) and 19% of all ICU patients with COVID-19 (95% CI 15% to 22%; I 2 =88%) commenced KRT. Limitations There was significant heterogeneity among the included studies which remained unaccounted for in sub-group analysis. Conclusions AKI complicated the course of nearly 1 in 3 patients hospitalized with COVID-19. The risk of AKI was higher in critically ill patients with a substantial number receiving KRT at rates higher than the general ICU population. Since COVID-19 will be a public health threat for the foreseeable future, these estimates should help guide KRT resource planning.

Background and Objectives: Survivors of acute kidney injury (AKI) are at higher risk of chronic kidney disease and death, but few patients see a nephrologist following hospital discharge. Our objectives during this 2-year vanguard phase were to determine the feasibility of randomizing survivors of AKI to early follow-up with a nephrologist or usual care, as well as to collect data on care processes and outcomes. Design, Setting, Participants, and Measurements: We performed a randomized controlled trial in patients hospitalized with Kidney Disease Improving Global Outcomes (KDIGO) stage 2-3 AKI at 4 hospitals in Toronto, Canada. We randomized patients to early nephrologist follow-up (standardized basket of care that emphasized blood pressure control, cardiovascular risk reduction, and medication safety) or usual care from July 2015 to June 2017. Feasibility outcomes included the proportion of eligible patients enrolled, seen by a nephrologist, and followed to 1-year. The primary clinical outcome was a major adverse kidney event at 1-year, defined as death, maintenance dialysis, or incident/progressive chronic kidney disease. Results: We screened 3687 participants from July 2015 to June 2017, of whom 269 were eligible. We randomized 71 (26%) patients (34 to nephrology follow-up and 37 to usual care). The primary reason stated for declining enrollment included hospitalization-related fatigue (n=65), reluctance to add more doctors to the healthcare team (n=59), and long travel times (n=40). Nephrologist visits occurred in 24/34 (71%) intervention participants compared to 3/37 (8%) randomized to usual care. The primary clinical outcome occurred in 15/34 (44%) patients in the nephrologist follow-up arm and 16/37 (43%) patients in the usual care arm (relative risk=1.02, 95% CI 0.60-1.73). Conclusions: Major adverse kidney events are common in AKI survivors, but we found that the in-person model of follow-up posed a variety of barriers that was not acceptable to many patients. (ClinicalTrials.gov, NCT02483039).

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Background Transition from continuous renal replacement therapy (CRRT) to intermittent renal replacement therapy (IRRT) can be associated with intra-dialytic hypotension (IDH) although data to inform the definition of IDH, its incidence and clinical implications, are lacking. We aimed to describe the incidence and factors associated with IDH during the first IRRT session following transition from CRRT and its association with hospital mortality. This was a retrospective single-center cohort study in patients with acute kidney injury for whom at least one CRRT-to-IRRT transition occurred while in intensive care. We assessed associations between multiple candidate definitions of IDH and hospital mortality. We then evaluated the factors associated with IDH. Results We evaluated 231 CRRT-to-IRRT transitions in 213 critically ill patients with AKI. Hospital mortality was 43.7% (n = 93). We defined IDH during the first IRRT session as 1) discontinuation of IRRT for hemodynamic instability; 2) any initiation or increase in vasopressor/inotropic agents or 3) a nadir systolic blood pressure of < 90 mmHg. IDH during the first IRRT session occurred in 50.2% of CRRT-to-IRRT transitions and was independently associated with hospital mortality (adjusted odds ratio [OR]: 2.71; CI 1.51–4.84, p < 0.001). Clinical variables at the time of CRRT discontinuation associated with IDH included vasopressor use, higher cumulative fluid balance, and lower urine output. Conclusions IDH events during CRRT-to-IRRT transition occurred in nearly half of patients and were independently associated with hospital mortality. We identified several characteristics that anticipate the development of IDH following the initiation of IRRT.

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Phenomenon: Physician shortages in low-and middle-income countries (LMIC) have led to increased interest in using e-learning tools for training. Organic digital education (ODE)-digital scholarship largely created outside of formal medical curricula-has increased in popularity over the past decade. Medical podcasting has become one of the most prominent asynchronous ODE sources for learners in high-income (HI) countries; there have been no previous attempts to characterize their use in LMIC. Approach: Listener data from a 2-year period from three major internal medicine podcasts-Bedside Rounds, Core IM, and The Curbsiders-were aggregated, 188 episodes in total. These data were subdivided into country by top-level domain, normalized by population, and grouped together by World Bank income levels and English-speaking status. This methodology was also repeated to compare individual episodes on topics more versus less relevant to learners in LMIC. Findings: Over a 2-year period, the three podcasts had a total of 2.3 million unique downloads and were listened to in 192 of 207 countries worldwide. Overall, 91.5% of downloads were in HI countries, with 8.2% in LMIC. A total of 86.1% of listens were in countries with English as an official or unofficial listed language, whereas 13.8% were in countries without. Normalized for population, listeners in HI countries represented 970.5 listens per million population compared with 12.4 per million in LMIC. An analysis of individual episodes by topic showed that material more relevant to learners in LMIC had significantly more listeners from these countries. Insights: Compared with other forms of ODE, medical podcasting has much lower uptake in LMIC. However, there are considerable opportunities for growth. Medical podcasters in HI countries should be aware of a potential global audience and should take concrete steps to ensure a diversity of content and to periodically audit their data. Medical educators in LMIC should consider podcasting as a potentially powerful form of teaching. International medical educational organizations as well as podcasting organizations should provide resources for educators in these countries.