Faculty Bibliography

BACKGROUND:Acute kidney injury (AKI) requiring kidney replacement therapy (KRT) is associated with high mortality and utilization. We evaluated the use of an AKI-Standardized Clinical Assessment and Management Plan (SCAMP) on patient outcomes including mortality, hospital and ICU length of stay. METHODS:We conducted a 12-month controlled study in the ICUs of a large academic tertiary medical center. We alternated use of the AKI-SCAMP with use of a "sham" control form in 4-6-week blocks. The primary outcome was risk of inpatient mortality. Pre-specified secondary outcomes included 30-day mortality, 60-day mortality and hospital and ICU length of stay. Generalized estimating equations were used to estimate the impact of the AKI-SCAMP on mortality and length of stay. RESULTS:There were 122 patients in the AKI-SCAMP group and 102 patients in the control group. There was no significant difference in inpatient mortality associated with AKI-SCAMP use (41% vs 47% control). AKI-SCAMP use was associated with significantly reduced ICU length of stay (mean 8 (95% CI 8-9) vs 12 (95% CI 10-13) days; p = <0.0001) and hospital length of stay (mean 25 (95% CI 22-29) vs 30 (95% CI 27-34) days; p = 0.02). Patients in the AKI-SCAMP group less likely to receive KRT in the context of physician-perceived treatment futility than those in the control group (2% vs 7%, p=0.003). CONCLUSIONS:Use of the AKI-SCAMP tool for AKI-KRT was not significantly associated with inpatient mortality but was associated with reduced ICU and hospital length of stay and use of KRT in cases of physician-perceived treatment futility.

Hyperkalemia (serum K⁺ >5.0 mmol/L) is commonly observed among patients receiving maintenance hemodialysis and associated with increased risk of cardiac arrhythmias. Current international guidelines may not reflect the latest evidence on managing hyperkalemia in patients undergoing hemodialysis, and there is a lack of high-quality published studies in this area. This consensus guideline aims to provide recommendations in relation to clinical practice. Available published evidence was evaluated through a systematic literature review, and the nominal group technique was used to develop consensus recommendations from a panel of experienced nephrologists, covering monitoring, dietary restrictions, prescription of K⁺ binders, and concomitant prescription of renin-angiotensin-aldosterone system inhibitors. Recent studies have shown that K⁺ binders reduce the incidence of hyperkalemia, but further evidence is needed in areas including whether reduced-K⁺ diets or treatment with K⁺ binders improve patient-centered outcomes. Treatment of hyperkalemia in the hemodialysis setting is complex, and decisions need to be tailored for individual patients.

RATIONALE AND OBJECTIVE/OBJECTIVE:Canagliflozin reduced the risk of kidney failure and related outcomes in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) in the CREDENCE trial. This analysis of CREDENCE trial data examines the effect of canagliflozin on the incidence of kidney-related adverse events (AEs). STUDY DESIGN/METHODS:A randomized, double-blind, placebo-controlled, multicenter, international trial. SETTING AND PARTICIPANTS/METHODS:4,401 trial participants with T2DM, CKD, and urinary albumin:creatinine ratio >300-5000mg/g. INTERVENTIONS/METHODS:Participants were randomly assigned to receive canagliflozin 100mg/day or placebo. OUTCOMES/RESULTS:). RESULTS:, respectively; P-interaction=0.3), with similar results for AKI (P-interaction=0.9). Full recovery of kidney function within 30 days after an AKI event occurred more frequently with canagliflozin versus placebo (53.1% vs 35.4%; odds ratio: 2.2 [95% CI: 1.0, 4.7]; P=0.04). LIMITATIONS/CONCLUSIONS:Kidney-related AEs including AKI were investigator-reported and collected without central adjudication. Biomarkers of AKI and structural tubular damage were not measured and creatinine data after an AKI event were not available for all participants. CONCLUSION/CONCLUSIONS:Canagliflozin compared to placebo was associated with a reduced incidence of serious and non-serious kidney-related AEs in patients with T2DM and CKD. These results highlight the safety of canagliflozin with regard to adverse kidney disease events.

Background/UNASSIGNED:The intestinal microbiome is an appealing target for interventions in ESKD because of its likely contribution to uremic toxicity. Before conducting clinical trials of microbiome-altering treatments, it is necessary to understand the within-person and between-person variability in the composition and function of the gut microbiome in patients with ESKD. Methods/UNASSIGNED:We conducted a multicenter, nonrandomized, crossover feasibility study of patients on maintenance hemodialysis consisting of three phases: pretreatment (8 weeks); treatment, during which the prebiotic, p-inulin, was administered at a dosage of 8 g twice daily (12 weeks); and post-treatment (8 weeks). Stool samples were collected 1-2 times per week and blood was collected weekly for 28 weeks. The gut microbiome was characterized using 16S ribosomal-RNA sequencing and metabolomic profiling. Results/UNASSIGNED:=0.004) and a progressive decrease in prevalence of high intraclass correlations, indicating an increase in intraparticipant microbiome diversity during and after p-inulin treatment. An effect of p-inulin on the metabolomic profile was not evident. Conclusions/UNASSIGNED:The intraparticipant stability of the gut microbiome under no-treatment conditions, the tolerability of p-inulin, the signals of increased diversity of the microbiome with p-inulin treatment, and the willingness of participants to provide stool samples all support the feasibility of a larger trial to investigate interventions targeting the gut microbiome in patients with ESKD. Whether or not p-inulin has sufficient efficacy as an intervention requires evaluation in larger studies. Clinical Trial registry name and registration number/UNASSIGNED:Gut Microbiome and p-Inulin in Hemodialysis, NCT02572882.

Background/UNASSIGNED:Patients with CKD ha ve impaired immunity, increased risk of infection-related mortality, and worsened COVID-19 outcomes. However, data comparing nondialysis CKD and ESKD are sparse. Methods/UNASSIGNED:Patients with COVID-19 admitted to three hospitals in the New York area, between March 2 and August 27, 2020, were retrospectively studied using electronic health records. Patients were classified as those without CKD, those with nondialysis CKD, and those with ESKD, with outcomes including hospital mortality, ICU admission, and mortality rates. Results/UNASSIGNED:Of 3905 patients, 588 (15%) had nondialysis CKD and 128 (3%) had ESKD. The nondialysis CKD and ESKD groups had a greater prevalence of comorbidities and higher admission D-dimer levels, whereas patients with ESKD had lower C-reactive protein levels at admission. ICU admission rates were similar across all three groups (23%-25%). The overall, unadjusted hospital mortality was 25%, and the mortality was 24% for those without CKD, 34% for those with nondialysis CKD, and 27% for those with ESKD. Among patients in the ICU, mortality was 56%, 64%, and 56%, respectively. Although patients with nondialysis CKD had higher odds of overall mortality versus those without CKD in univariate analysis (OR, 1.58; 95% CI, 1.31 to 1.91), this was no longer significant in fully adjusted models (OR, 1.11; 95% CI, 0.88 to 1.40). Also, ESKD status did not associate with a higher risk of mortality compared with non-CKD in adjusted analyses, but did have reduced mortality when compared with nondialysis CKD (OR, 0.57; 95% CI, 0.33 to 0.95). Mortality rates declined precipitously after the first 2 months of the pandemic, from 26% to 14%, which was reflected in all three subgroups. Conclusions/UNASSIGNED:In a diverse cohort of patients with COVID-19, we observed higher crude mortality rates for patients with nondialysis CKD and, to a lesser extent, ESKD, which were not significant after risk adjustment. Moreover, patients with ESKD appear to have better outcom es than those with nondialysis CKD.

Background: Conservative kidney management (CKM) of kidney failure is an important treatment option for many patients. However, its availability in the United States (US) is not well described. We describe CKM resources and provider practice patterns in US Chronic Kidney Disease (CKD) clinics.
Method(s): Cross sectional analysis of provider surveys (n=22) from unique clinics in the US from the CKD Outcomes and Practice Patterns Study (CKDopps) collected between 2014-2017.
Result(s): Only eight (36%) providers reported involving palliative care in planning for and educating patients about kidney failure. A majority (59%) were extremely comfortable discussing CKM and nearly 100% typically discussed CKM as a treatment option. Nearly all (95%) reported their clinics had the ability to routinely deliver CKM, but only one had a CKM protocol or guideline, and none offered a specific CKM clinic. Most providers said their clinics used the word conservative to describe CKM, with 24% choosing palliative or supportive terminology. Regardless of involvement of PC, most providers estimated that 5% of their patients with or approaching kidney failure were managed with CKM. Patient preference, functional status, frailty, and comorbidities were the most important factors influencing provider decisions in contemplating the suitability of CKM for patients. (Figure 1)
Conclusion(s): Most providers report feeling comfortable discussing CKM, yet almost no clinics report resources or dedicated infrastructure for CKM delivery. Despite reported high frequency of discussing CKM, few patients were described as choosing this treatment pathway. Factors that influence consideration of CKM are consistent with elements that generally influence well-informed geriatric and end-of-life care. Efforts to improve assessment of those elements may allow for more informed recommendations of CKM

Background: Left ventricular (LV) systolic dysfunction is common in patients on maintenance hemodialysis (HD). Early identification of patients with depressed left ventricular ejection fraction (LVEF) can facilitate disease modifying treatment. Electrocardiograms (ECGs) are routinely performed in patients on HD, however they have not been used for estimating LVEF in this population.
Method(s): We analyzed data from five Mount Sinai facilities. Patients on HD with a transthoracic echocardiogram within 7 days of an ECG were identified using diagnostic and procedure codes. ECG data were preprocessed to remove recording artifacts, plotted to an image, and along with patient demographics were analyzed using a model comprised of a Multi-Layer Perceptron and a Convolutional Neural Network. We developed three models; 1) trained from scratch in only HD patients, 2) pre-trained on natural images (Imagenet), and 3) pre-trained on all LVEF:ECG pairs (n=696,890) excluding those for ESRD patients. Models 2 and 3 leverage transfer learning, which reuses knowledge gained from a task to perform a similar task. All models were trained/tested on LVEF:ECG pairs for ESRD patients within a Group Stratified K Fold (K=5) Cross Validation design, and performance was compared per Area Under Receiver Operating Characteristic curve (AUROC) for each category of LVEF, <=40%, 41 to <=50%, and >50%.
Result(s): We extracted 18,626 LVEF:ECG pairs for 2,168 ESRD patients. For detection of LVEF <=40%, models trained from scratch and pre-trained on Imagenet had AUROCs of 0.74 (95% CI: 0.67-0.80) and 0.71 (95% CI: 0.65-0.77) respectively. These were outperformed by the model pre-trained on ECG data [AUROC of 0.91 (95% CI: 0.88-0.93)]. Similar results were seen at detection of LVEF 41 to <=50% with the AUROC being 0.55 (95% CI: 0.49-0.6) for both the model trained from scratch and the Imagenet model, while the model pre-trained on ECG data achieved an AUROC of 0.82 (95% CI: 0.78-0.87).
Conclusion(s): A model pre-trained on non-HD LVEF:ECG pairs using transfer learning consistently outperformed models trained from scratch or pre-trained on Imagenet. This model can facilitate identification of LV systolic dysfunction in patients on HD. ROC curves

Background: Heart failure (HF) is an important contributor to the increased cardiovascular (CV) mortality incidence in ESKD. Therapies targeting HF's unique pathophysiology in ESKD are lacking. Hydralazine-isosorbide dinitrate (H-ISDN) targets reduced nitric oxide bioavailability and could improve CV mortality in ESKD Methods: Adult patients with HF on maintenance dialysis between January 2011 and December 31, 2016 were identified using the United States Renal Data System. There were 6306 patients with at least one prescription for H-ISDN and 75,851 non-users. The primary outcome was death from any cause. Secondary outcomes included cardiovascular death and sudden death. Treatment effects were estimated using stabilized inverse probability weights in Cox proportional hazards regression. Because H-ISDN has been shown to improve outcomes in Black HF patients, we investigated effect modification by race Results: Age was similar in H-ISDN users (66 +/- 13 years) and non-users (69 +/- 13 years) with 50% and 51% men, respectively. H-ISDN (51%) users were more likely to be of Black race than non-users (27%). Dialysis vintage was longer in H-ISDN (25 months) users compared with non-users (15 months). All characteristics were well balanced in weighted models. Risks of all-cause mortality, cardiovascular death, and sudden death were significantly reduced in H-ISDN users compared to non-users (Table). We did not identify significant effect modification by race (Figure)
Conclusion(s): To our knowledge, this is the first analysis of the impact of H-ISDN on mortality in ESKD. Our results suggest that combination H-ISDN improves survival in dialysis patients with HF

Background: Obesity is more prevalent among minorities, increasing the risk for cardio-renal morbidity. We explored interactions between race, body mass index (BMI), and the risk of hyperfiltration associated with Obesity Related Glomerulopathy (ORG).
Method(s): We created a cohort of women and girls ages 12-21 from the New York area using their longitudinal electronic health records (EHR). Glomerular filtration rate (GFR) was estimated in two ways: I) using the standard age recommended formulae, and II) eGFRr -without a race-specific coefficient. Multivariate logistic regression was used to analyze the relative contribution of risk factors for ORG associated hyperfiltration, defined by a threshold of >=135ml/min/1.73m2.
Result(s): 7315 Black and 15,102 non-Black women and girls were evaluated for kidney function in parallel to body measures. Hyperfiltration was more frequent in Black compared to non-Black individuals when using standard eGFR but was lower after eliminating the race-specific coefficient. Black race was independently associated with hyperfiltration with standard eGFR calculation (OR=3.43, 95% CI 2.95-3.99) but the association was reversed when estimated by eGFRr (OR=0.56, 95% CI 0.45-0.70). Risk of hyperfiltration was higher for Black individuals across all BMI strata with standard eGFR estimates, but when estimated as eGFRr hyperfiltration filtration risk was reduced for overweight (OR =0.70 95% CI 0.54-0.89) and obese (OR=0.47, 95% CI 0.37-0.60) participants.
Conclusion(s): Estimated CKD prevalence among Black adolescents and young adults increases following removal of the race coefficient while fewer have evidence of obesity associated hyperfiltration. In the CKD range of GFR we should consider a gradual increase in the race coefficient to avoid underestimation of obesity related glomerulopathy in the high normal range of GFR