Faculty Bibliography

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: 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

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

AIMS /UNASSIGNED:Hyperkalaemia is a common complication of type 2 diabetes mellitus (T2DM) and limits the optimal use of agents that block the renin-angiotensin-aldosterone system, particularly in patients with chronic kidney disease (CKD). In patients with CKD, sodium‒glucose cotransporter 2 (SGLT2) inhibitors provide cardiorenal protection, but whether they affect the risk of hyperkalaemia remains uncertain. METHODS AND RESULTS /UNASSIGNED:The CREDENCE trial randomized 4401 participants with T2DM and CKD to the SGLT2 inhibitor canagliflozin or matching placebo. In this post hoc analysis using an intention-to-treat approach, we assessed the effect of canagliflozin on a composite outcome of time to either investigator-reported hyperkalaemia or the initiation of potassium binders. We also analysed effects on central laboratory-determined hyper- and hypokalaemia (serum potassium ≥6.0 and <3.5 mmol/L, respectively) and change in serum potassium. At baseline, the mean serum potassium in canagliflozin and placebo arms was 4.5 mmol/L; 4395 (99.9%) participants were receiving renin-angiotensin system blockade. The incidence of investigator-reported hyperkalaemia or initiation of potassium binders was lower with canagliflozin than with placebo [occurring in 32.7 vs. 41.9 participants per 1000 patient-years; hazard ratio (HR) 0.78, 95% confidence interval (CI) 0.64-0.95, P = 0.014]. Canagliflozin similarly reduced the incidence of laboratory-determined hyperkalaemia (HR 0.77, 95% CI 0.61-0.98, P = 0.031), with no effect on the risk of hypokalaemia (HR 0.92, 95% CI 0.71-1.20, P = 0.53). The mean serum potassium over time with canagliflozin was similar to that of placebo. CONCLUSION /UNASSIGNED:Among patients treated with renin-angiotensin-aldosterone system inhibitors, SGLT2 inhibition with canagliflozin may reduce the risk of hyperkalaemia in people with T2DM and CKD without increasing the risk of hypokalaemia.

Background/UNASSIGNED:There is a paucity of contemporary data examining electrolyte changes during and immediately after hemodialysis (HD), and their relationship with dialysate prescriptions. The present study examines these relationships. Methods/UNASSIGNED:We analyzed patient- (n=66) and HD session-level pre- and post-dialysis laboratory data (n=1,713) over a six-month period from the Monitoring in Dialysis Study. We fit mixed effects regression models to analyze electrolyte, blood urea nitrogen, creatinine, and albumin levels immediately post-HD, accounting for pre-HD and dialysate prescriptions. In a subset of US patients (n=40), 15-minute post-HD and 30-minute post-HD values were available at one session. Predictive models were fit to estimate electrolyte levels immediately post-HD, accounting for pre-HD concentrations and dialysate prescriptions. Results/UNASSIGNED:Serum bicarbonate, calcium, and albumin increased (mean increase 4.9±0.3 mEq/L, 0.7±0.1 mEq/L, and 0.4±0.03 g/dL, respectively), whereas potassium, magnesium, and phosphorus decreased immediately post-HD (mean -1.2±0.1 mEq/L, -0.3±0.03 mEq/L, and -3.0±0.2 mg/dL, respectively). Hypokalemia and hypophosphatemia were present in 40% of and 67% of immediate post-HD samples, respectively. Dynamic changes were observed in electrolyte concentrations at 15- and 30-minutes post-HD, compared to immediately post-HD. Conclusion/UNASSIGNED:We describe the magnitude of post-dialytic changes in serum electrolytes with contemporary HD, reporting a high incidence of electrolyte abnormalities post-HD, and present predictive nomograms relating electrolyte changes immediately post-HD to dialysate prescriptions. Our results may be useful for clinical care and provide insights for future research on dialysate prescriptions.

Background: Hyperkalaemia is a common complication of type 2 diabetes mellitus (T2DM) and limits the optimal use of agents that block the renin-angiotensin aldosterone system (RAAS), particularly in patients with chronic kidney disease (CKD). In patients with CKD, sodium glucose cotransporter 2 (SGLT2) inhibitors provide cardiorenal protection, but whether they affect the risk of hyperkalaemia remains uncertain.
Purpose(s):We sought to assess the effect of canagliflozin on hyperkalaemia and other potassium-related outcomes in people with T2DM and CKD by conducting a post-hoc analysis of the CREDENCE trial.
Method(s): The CREDENCE trial randomized 4401 participants with T2DM and CKD to the SGLT2 inhibitor canagliflozin or matching placebo. In this post-hoc analysis using an intention-to-treat approach, we assessed the effect of canagliflozin on a composite outcome of time to either investigator-reported hyperkalaemia or the initiation of potassium binders. We also analysed effects on central laboratory-determined hyper- and hypokalaemia (serum potassium >=6.0 and <3.5 mmol/L, respectively) and change in serum potassium.
Result(s): At baseline the mean serum potassium in canagliflozin and placebo arms was 4.5 mmol/L; 4395 (99.9%) participants were receiving renin angiotensin system blockade. Canagliflozin reduced the risk of investigator-reported hyperkalaemia or initiation of potassium binders (HR 0.78, 95% CI 0.64-0.95, p=0.014; Figure 1). The incidence of laboratorydetermined hyperkalaemia was similarly reduced (HR 0.77, 95% CI 0.61- 0.98, p=0.031; Figure 2); the risk of hypokalaemia (HR 0.92, 95% CI 0.71- 1.20, p=0.53) was not increased. Mean serum potassium over time with canagliflozin was similar to that of placebo.
Conclusion(s): Among patients treated with RAAS inhibitors, SGLT2 inhibition with canagliflozin may reduce the risk of hyperkalaemia in people with T2DM and CKD without increasing the risk of hypokalaemia. (Figure Presented)

Introduction/UNASSIGNED:Relative impacts of coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) on mortality and end-stage kidney disease (ESKD) in chronic kidney disease (CKD) are uncertain. Methods/UNASSIGNED:Data from Massachusetts residents with CKD undergoing CABG or PCI from 2003 to 2012 were linked to the United States Renal Data System. Associations with death, ESKD, and combined death and ESKD were analyzed in propensity score-matched multivariable survival models. Results/UNASSIGNED:We identified 6805 CABG and 17,494 PCI patients. Among 3775 matched-pairs, multi-vessel disease was present in 97%, and stage 4 CKD was present in 11.9% of CABG and 12.2% of PCI patients. One-year mortality (CABG 7.7%, PCI 11.0%) was more frequent than ESKD (CABG 1.4%, PCI 1.7%). Overall survival was improved and ESKD risk decreased with CABG compared to PCI, but effects differed in the presence of left main disease and prior myocardial infarction (MI). Survival was worse following PCI than following CABG among patients with left main disease and without MI (hazard ratio = 3.7, 95% confidence interval = 1.3-10.5). ESKD risk was higher with PCI for individuals with left main disease and prior infarction (hazard ratio = 8.1, 95% confidence interval = 1.7-39.2). Conclusion/UNASSIGNED:Risks following CABG and PCI were modified by left main disease and prior MI. In individuals with CKD, survival was greater after CABG than after PCI in patients with left main disease but without MI, whereas ESKD risk was lower with CABG in those with left main and MI. Absolute risks of ESKD were markedly lower than for mortality, suggesting prioritizing mortality over ESKD in clinical decision making.

BACKGROUND:Approximately 30%-45% of patients with nondialysis CKD have iron deficiency. Iron therapy in CKD has focused primarily on supporting erythropoiesis. In patients with or without anemia, there has not been a comprehensive approach to estimating the association between serum biomarkers of iron stores, and mortality and cardiovascular event risks. METHODS:The study included 5145 patients from Brazil, France, the United States, and Germany enrolled in the Chronic Kidney Disease Outcomes and Practice Patterns Study, with first available transferrin saturation (TSAT) and ferritin levels as exposure variables. We used Cox models to estimate hazard ratios (HRs) for all-cause mortality and major adverse cardiovascular events (MACE), with progressive adjustment for potentially confounding variables. We also used linear spline models to further evaluate functional forms of the exposure-outcome associations. RESULTS:Compared with patients with a TSAT of 26%-35%, those with a TSAT ≤15% had the highest adjusted risks for all-cause mortality and MACE. Spline analysis found the lowest risk at TSAT 40% for all-cause mortality and MACE. Risk of all-cause mortality, but not MACE, was also elevated at TSAT ≥46%. Effect estimates were similar after adjustment for hemoglobin. For ferritin, no directional associations were apparent, except for elevated all-cause mortality at ferritin ≥300 ng/ml. CONCLUSIONS:Iron deficiency, as captured by TSAT, is associated with higher risk of all-cause mortality and MACE in patients with nondialysis CKD, with or without anemia. Interventional studies evaluating the effect on clinical outcomes of iron supplementation and therapies for alternative targets are needed to better inform strategies for administering exogenous iron.