Role of Thigh Muscle Strength and Joint Kinematics in Dynamic Stability: Implications for Y-Balance Test Performance.

CONTEXT: The Y-Balance Test Lower Quarter (YBT-LQ) is a widely utilized tool for evaluating dynamic postural control, requiring a combination of mobility and strength. This study aimed to investigate the combined relationship between isometric thigh muscle strength and joint kinematics on YBT-LQ performance. DESIGN: Cross-sectional laboratory study. METHODS: Isometric quadriceps and hamstrings strength were measured before the YBT-LQ in 39 healthy participants (27 females and 12 males). The test was performed under 3-dimensional markerless motion capture, where joint kinematics were extracted from the maximum reach position from each direction. Three multivariable linear regression models were then used to determine the strongest combination of predictors for YBT-LQ performance. RESULTS: Greater hamstrings strength and increased knee flexion, ankle dorsiflexion, and trunk ipsilateral-flexion joint angles explained 56.8% (P < .001) of the variance in anterior reach. Hip flexion, knee flexion, and ankle dorsiflexion angles were the strongest predictors for posteromedial reach distance, explaining 73.0% of the variance (P < .001). Last, 43.3% (P < .001) of the variance in posterolateral reach distance was predicted by hamstring strength and knee-flexion angle. CONCLUSIONS: These results emphasize the importance of hamstring strength in YBT-LQ performance across different reach directions. Additionally, the kinematics illustrate a potential movement strategy for maximizing reach distance on the YBT-LQ in healthy individuals. Clinicians can utilize this information to guide interventions aimed at improving dynamic postural control, particularly by focusing on increasing hamstring strength and testing for impairments in specific movement patterns.

Mechanistic Differences between Torsemide and Furosemide.

BACKGROUND: Torsemide is proposed to have clinically important pharmacokinetic and pharmacodynamic advantages over furosemide. However, clinical outcomes did not differ in the Torsemide Comparison with Furosemide for Management of Heart Failure (TRANSFORM-HF) randomized trial. METHODS: We conducted a multicenter mechanistic substudy of patients with heart failure randomized to oral furosemide or torsemide (TRANSFORM-Mechanism). At baseline and 30 days, participants underwent detailed assessments of pharmacokinetic and pharmacodynamic parameters. RESULTS: TRANSFORM-Mechanism enrolled 88 participants. Kidney bioavailability, or the proportion of dose delivered to the tubular site of action, was significantly less with torsemide compared to furosemide [median 17.1%, (IQR 12.3, 23.5%) vs. 24.8% (16.6, 34.1%), p < 0.001]. Furosemide had a longer duration of kidney drug delivery and duration of natriuresis (p≤0.004 for both). Prescribed doses of furosemide and torsemide in TRANSFORM-Mechanism were similar to TRANSFORM-HF, with providers on average using a 2:1 dose equivalence conversion between drugs. However, these doses resulted in a substantially greater natriuresis with torsemide (p<0.001). A dose equivalence of ∼4:1 resulted in similar natriuresis. Higher diuretic doses in the torsemide group resulted in mild perturbations in kidney function and significant increases in renin, aldosterone, and norepinephrine (p<0.05 for all). Plasma volume (p=0.52) and body weight (p=0.89) did not improve with torsemide vs. furosemide. CONCLUSIONS: We observed no meaningful pharmacokinetic/pharmacodynamic advantages for torsemide vs. furosemide. The greater natriuresis from higher diuretic doses in the torsemide group was offset by greater neurohormonal activation and kidney dysfunction.

Identifying and training deep learning neural networks on biomedical-related datasets.

This manuscript describes the development of a resources module that is part of a learning platform named 'NIGMS Sandbox for Cloud-based Learning' https://github.com/NIGMS/NIGMS-Sandbox. The overall genesis of the Sandbox is described in the editorial NIGMS Sandbox at the beginning of this Supplement. This module delivers learning materials on implementing deep learning algorithms for biomedical image data in an interactive format that uses appropriate cloud resources for data access and analyses. Biomedical-related datasets are widely used in both research and clinical settings, but the ability for professionally trained clinicians and researchers to interpret datasets becomes difficult as the size and breadth of these datasets increases. Artificial intelligence, and specifically deep learning neural networks, have recently become an important tool in novel biomedical research. However, use is limited due to their computational requirements and confusion regarding different neural network architectures. The goal of this learning module is to introduce types of deep learning neural networks and cover practices that are commonly used in biomedical research. This module is subdivided into four submodules that cover classification, augmentation, segmentation and regression. Each complementary submodule was written on the Google Cloud Platform and contains detailed code and explanations, as well as quizzes and challenges to facilitate user training. Overall, the goal of this learning module is to enable users to identify and integrate the correct type of neural network with their data while highlighting the ease-of-use of cloud computing for implementing neural networks. This manuscript describes the development of a resource module that is part of a learning platform named ``NIGMS Sandbox for Cloud-based Learning'' https://github.com/NIGMS/NIGMS-Sandbox. The overall genesis of the Sandbox is described in the editorial NIGMS Sandbox [1] at the beginning of this Supplement. This module delivers learning materials on the analysis of bulk and single-cell ATAC-seq data in an interactive format that uses appropriate cloud resources for data access and analyses.

"It Made Me Feel Like a Person Again": Benefits of Meals on Wheels-Based Social Connection Programs.

Social isolation and loneliness are associated with negative health outcomes, and these outcomes are exacerbated among older adults who are homebound. To address this issue, Meals on Wheels programs increasingly provide social connection services to clients in addition to home-delivered meals. This descriptive qualitative study examines the impact of three types of social connection programs on the well-being of homebound older adult clients, as well as on the volunteers and staff members who deliver the programs. Thematic analysis of semi-structured interviews conducted with 117 clients, volunteers, and staff in six Meals on Wheels social connection programs across the United States indicated that program participation was associated with substantial benefits. Benefits included the development of supportive friendships, reduced feelings of loneliness, and an improved overall sense of well-being. Insights from this study may inform the development, expansion, and sustainability of social connection programs provided by community-based organizations.

Strength of the Uninvolved Limb Following Return to Activity After ACL Injury: Implications for Symmetry as a Marker of Sufficient Strength.

Background: Muscular strength deficits are common after ACL injury. While the Limb Symmetry Index (LSI), using the uninvolved limb as a reference, is widely used, negative strength adaptations may affect both limbs post-injury. It is uncertain how the strength of the uninvolved limb in those with an ACL injury compares to uninjured individuals, making it unclear whether it is appropriate as a benchmark for determining sufficient strength. Purpose: To compare the strength of key lower extremity muscles of the uninvolved limb in those with history of ACL injury (ACL-I) to the dominant limb in individuals with no history of ACL injury (control). Study Design: Cross-sectional study. Methods: A total of 5,727 military cadets were examined, with 82 females and 126 males in the ACL-I group and 2,146 females and 3,373 males in the control group. Maximum isometric strength was assessed for six muscle groups measured with a hand-held dynamometer. Separate two-way ANOVAs with limb and sex were performed for each muscle group. Results: Significant main effects for limb were observed with the uninvolved limb in the ACL-I group displaying greater strength compared to the dominant limb in the control group for the quadriceps, hamstrings, and gluteus medius, but effect sizes were small (Cohen's d <0.25). Significant main effects for sex were observed with greater male muscular strength in all six muscle groups with small to large effect sizes (Cohen's d 0.49-1.46). No limb-by-sex interactions were observed. Conclusions: There was no evidence of reduced strength in the uninvolved limb in those with a history of ACL injury compared to the dominant limb in those with no prior ACL injury. This finding suggests that, after clearance to return to activities, the uninvolved limb can be used as a standard for comparison of sufficient strength, including when using the LSI. Level of Evidence: Level 3.

Validation of OpenCap: A low-cost markerless motion capture system for lower-extremity kinematics during return-to-sport tasks.

Low-cost markerless motion capture systems offer the potential for 3D measurement of joint angles during human movement. This study aimed to validate a smartphone-based markerless motion capture system's (OpenCap) derived lower extremity kinematics during common return-to-sport tasks, comparing it to an established optoelectronic motion capture system. Athletes with prior anterior cruciate ligament reconstruction (12-18 months post-surgery) performed three movements: a jump-landing-rebound, single-leg hop, and lateral-vertical hop. Kinematics were recorded concurrently with two smartphones running OpenCap's software and with a 10-camera, marker-based motion capture system. Validity of lower extremity joint kinematics was assessed across 437 recorded trials using measures of agreement (coefficient of multiple correlation: CMC) and error (mean absolute error: MAE, root mean squared error: RMSE) across the time series of movement. Agreement was best in the sagittal plane for the knee and hip in all movements (CMC > 0.94), followed by the ankle (CMC = 0.84-0.93). Lower agreement was observed for frontal (CMC = 0.47-0.78) and transverse (CMC = 0.51-0.6) plane motion. OpenCap presented a grand mean error of 3.85° (MAE) and 4.34° (RMSE) across all joint angles and movements. These results were comparable to other available markerless systems. Most notably, OpenCap's user-friendly interface, free software, and small physical footprint have the potential to extend motion analysis applications beyond conventional biomechanics labs, thus enhancing the accessibility for a diverse range of users.

Parity in bacterial communities and resistomes: Microplastic and natural organic particles in the Tyrrhenian Sea.

Petroleum-based microplastic particles (MPs) are carriers of antimicrobial resistance genes (ARGs) in aquatic environments, influencing the selection and spread of antimicrobial resistance. This research characterized MP and natural organic particle (NOP) bacterial communities and resistomes in the Tyrrhenian Sea, a region impacted by plastic pollution and climate change. MP and NOP bacterial communities were similar but different from the free-living planktonic communities. Likewise, MP and NOP ARG abundances were similar but different (higher) from the planktonic communities. MP and NOP metagenome-assembled genomes contained ARGs associated with mobile genetic elements and exhibited co-occurrence with metal resistance genes. Overall, these findings show that MPs and NOPs harbor potential pathogenic and antimicrobial resistant bacteria, which can aid in the spread of antimicrobial resistance. Further, petroleum-based MPs do not represent novel ecological niches for allochthonous bacteria; rather, they synergize with NOPs, collectively facilitating the spread of antimicrobial resistance in marine ecosystems.

Serial direct sodium removal in patients with heart failure and diuretic resistance.

AIMS: Loop diuretics may exacerbate cardiorenal syndrome (CRS) in heart failure (HF). Direct sodium removal (DSR) using the peritoneal membrane, in conjunction with complete diuretic withdrawal, may improve CRS and diuretic resistance. METHODS AND RESULTS: Patients with HF requiring high-dose loop diuretics were enrolled in two prospective, single-arm studies: RED DESERT (n = 8 euvolaemic patients), and SAHARA (n = 10 hypervolaemic patients). Loop diuretics were withdrawn, and serial DSR was utilized to achieve and maintain euvolaemia. At baseline, participants required a median 240 mg (interquartile range [IQR] 200-400) oral furosemide equivalents/day, which was withdrawn in all participants during DSR (median time of DSR 4 weeks [IQR 4-6]). Diuretic response (queried by formal 40 mg intravenous furosemide challenge and 6 h urine sodium quantification) increased substantially from baseline (81 ± 37 mmol) to end of DSR (223 ± 71 mmol, p < 0.001). Median time to re-initiate diuretics was 87 days, and the median re-initiation dose was 8% (IQR 6-10%) of baseline. At 1 year, diuretic dose remained substantially below baseline (30 [IQR 7.5-40] mg furosemide equivalents/day). Multiple dimensions of kidney function such as filtration, uraemic toxin excretion, kidney injury, and electrolyte handling improved (p < 0.05 for all). HF-related biomarkers including N-terminal pro-B-type natriuretic peptide, carbohydrate antigen-125, soluble ST2, interleukin-6, and growth differentiation factor-15 (p < 0.003 for all) also improved. CONCLUSIONS: In patients with HF and diuretic resistance, serial DSR therapy with loop diuretic withdrawal was feasible and associated with substantial and persistent improvement in diuretic resistance and several cardiorenal parameters. If replicated in randomized controlled studies, DSR may represent a novel therapy for diuretic resistance and CRS. CLINICAL TRIAL REGISTRATION: RED DESERT (NCT04116034), SAHARA (NCT04882358).

Jump Landing Kinematics: Establishing Normative Ranges For Male And Female Athletes.

CONTEXT: Lower extremity joint (LE) kinematics during landing tasks are important predictors of injury risk and performance outcomes in athletes. OBJECTIVE: To establish sex-related differences and normative ranges for LE kinematics during the jump-landing task in a large cohort of healthy military service academy cadets. DESIGN: Cross-Sectional Study. SETTING: US Air Force, Naval, and Military Academies. PARTICIPANTS: 5308 cadets (2062 females [38.8%]). MAIN OUTCOME MEASURE(S): Sex-related differences in LE kinematics were analyzed using independent samples t-tests. Mean differences (MD) and effect sizes (d) were reported for interpretability. Normative ranges for hip and knee joint angles were established separately for males and females at initial contact (IC) and 50% of the stance phase. RESULTS: Compared to males, moderate effect sizes (d ≥ .5) were observed for knee external rotation (negative value) where females displayed greater motion at IC and at 50% stance (MD: - 3.9˚ and -5.0˚, respectively, p < .001). The following findings were of small effect size (.2 ≥ d > .5). Females exhibited less knee and hip flexion at IC (MD: -1.8˚ and -0.5˚, respectively, p < .001) and at 50% stance (MD: -4.1˚ and -4.6˚, respectfully, p < .001). This was accompanied by females having greater knee valgus (negative value) and hip adduction at IC (MD: -2.2˚ and 1.06˚, respectively, p < .001) and at 50% stance (MD: -3.2˚ and 1.8˚, respectfully, p < .001). CONCLUSION: This study establishes normative ranges for LE kinematics during the jump-landing task in a large cohort of healthy military service academy cadets entering their first year. Sex- related differences in LE kinematics were observed, highlighting the importance of considering sex as a factor in the evaluation of lower extremity movement quality and management of injury risk.

Endovascular treatment of renal vein thrombosis in a young patient with lung transplant.

Spontaneous renal vein thrombosis is a rare entity. A 28-year-old woman with a history of a double-lung transplant was admitted with flank pain and found to have acute kidney injury. A magnetic resonance venogram demonstrated isolated left renal vein thrombosis with extension into the inferior vena cava. Initial management with therapeutic anticoagulation and hydration was unsuccessful. Thus, pharmacochemical thrombectomy was performed. A temporary suprarenal inferior vena cava filter was placed for intraoperative pulmonary prophylaxis. The patient's renal function returned to baseline and remained normal 13 months later. Early incorporation of percutaneous pharmacomechanical thrombectomy can improve renal function when medical therapy alone is unsuccessful.

Insulin Requirement and Infrainguinal Bypass Outcomes in Patients with Peripheral Arterial Disease.

BACKGROUND: Diabetes mellitus (DM) is a major risk factor for peripheral artery disease. The association of DM with major adverse limb events (MALE) after lower extremity revascularization remains controversial, as patients with diabetes are typically analyzed as a single, homogenous group. Using a large national database, this study examines the impact of insulin use and glycemic control on the outcomes following infrainguinal bypass. The hypothesis is that prevalent insulin therapy and elevated hemoglobin A1c (HbA1c) are associated with an increased risk of MALEs after infrainguinal bypass in patients with DM and could therefore be used for risk stratification. METHODS: The Vascular Quality Initiative database files for infrainguinal bypass (2007-2021) were retrospectively reviewed. Patients with DM undergoing bypass for peripheral artery disease were included. Patients on dialysis or with prior kidney transplantation were excluded. The characteristics and outcomes of patients with insulin-requiring diabetes mellitus (IRDM) were compared to those of patients not requiring insulin (noninsulin-requiring diabetes mellitus [NIRDM]) prior to the bypass procedure. RESULTS: A total of 9,686 patients with DM (56% IRDM) underwent bypass. Patients with IRDM were significantly younger than patients with NIRDM, more likely to be female (P < 0.01), African American (P < 0.01), and Hispanic (P = 0.031), and more likely to have comorbidities and be categorized into American Society of Anesthesiologist classes IV-V. They were more likely to be treated for chronic limb-threatening ischemia (P < 0.001). Patients with IRDM had significantly higher perioperative complications with no difference in perioperative mortality between the 2 groups. Beyond the perioperative period, with a mean follow-up of 427 days, patients with IRDM had significantly lower crude rates of primary patency and higher crude rates of major amputation, MALE, and mortality compared to patients with NIRDM. Regression analyses demonstrated that insulin requirement, but not HbA1c, was independently associated with a higher risk of MALE (hazard ratio = 1.17 [1.06-1.29]) and mortality (hazard ratio = 1.28 [1.16-1.43]). CONCLUSIONS: Insulin requirement, but not HbA1c, is significantly associated with MALEs and survival after infrainguinal bypass in the Vascular Quality Initiative. Stratification of patients with DM based on their prevalent insulin use prior to infrainguinal bypass surgery could improve the prediction of outcomes of peripheral arterial bypass surgery in patients with diabetes.

In the "Plant-Based" Era, Patients With Chronic Kidney Disease Should Focus on Eating Healthy.

In the era of plant-based diets, it is important for Nephrology providers to know the evidence regarding their healthfulness in patients with chronic kidney disease (CKD). A whole food, plant-based diet, which emphasizes fresh, minimally processed or refined plant-based foods and limits animal products, has shown benefits for patients with CKD. These include reduced dietary acid load, lower bioavailability of potassium and phosphorus, increased dietary fiber intake, nutritional adequacy, and cardiovascular and mortality benefits. Potential drawbacks include the need for specific knowledge, skills, and cost involved in preparing varied, healthy, and appetizing plant-based meals, leading to lower acceptability and accessibility to certain populations. Liberalization of the standard CKD diet to include healthy, minimally processed foods such as fruits, vegetables, nuts, legumes, and whole grains is likely beneficial, though more research is needed to determine whether a plant-based-only diet is the optimal way to achieve healthier eating in patients with CKD.

Empagliflozin in Heart Failure: Regional Nephron Sodium Handling Effects.

SIGNIFICANCE STATEMENT: The effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on regional tubular sodium handling is poorly understood in humans. In this study, empagliflozin substantially decreased lithium reabsorption in the proximal tubule (PT) (a marker of proximal tubular sodium reabsorption), a magnitude out of proportion to that expected with only inhibition of sodium-glucose cotransporter-2. This finding was not driven by an "osmotic diuretic" effect; however, several parameters changed in a manner consistent with inhibition of the sodium-hydrogen exchanger 3. The large changes in proximal tubular handling were acutely buffered by increased reabsorption in both the loop of Henle and the distal nephron, resulting in the observed modest acute natriuresis with these agents. After 14 days of empagliflozin, natriuresis waned due to increased reabsorption in the PT and/or loop of Henle. These findings confirm in humans that SGLT2i have complex and important effects on renal tubular solute handling. BACKGROUND: The effect of SGLT2i on regional tubular sodium handling is poorly understood in humans but may be important for the cardiorenal benefits. METHODS: This study used a previously reported randomized, placebo-controlled crossover study of empagliflozin 10 mg daily in patients with diabetes and heart failure. Sodium handling in the PT, loop of Henle (loop), and distal nephron was assessed at baseline and day 14 using fractional excretion of lithium (FELi), capturing PT/loop sodium reabsorption. Assessments were made with and without antagonism of sodium reabsorption through the loop using bumetanide. RESULTS: Empagliflozin resulted in a large decrease in sodium reabsorption in the PT (increase in FELi=7.5%±10.6%, P = 0.001), with several observations suggesting inhibition of PT sodium hydrogen exchanger 3. In the absence of renal compensation, this would be expected to result in approximately 40 g of sodium excretion/24 hours with normal kidney function. However, rapid tubular compensation occurred with increased sodium reabsorption both in the loop ( P < 0.001) and distal nephron ( P < 0.001). Inhibition of sodium-glucose cotransporter-2 did not attenuate over 14 days of empagliflozin ( P = 0.14). However, there were significant reductions in FELi ( P = 0.009), fractional excretion of sodium ( P = 0.004), and absolute fractional distal sodium reabsorption ( P = 0.036), indicating that chronic adaptation to SGLT2i results primarily from increased reabsorption in the loop and/or PT. CONCLUSIONS: Empagliflozin caused substantial redistribution of intrarenal sodium delivery and reabsorption, providing mechanistic substrate to explain some of the benefits of this class. Importantly, the large increase in sodium exit from the PT was balanced by distal compensation, consistent with SGLT2i excellent safety profile. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: ClinicalTrials.gov ( NCT03027960 ).

Circular external fixation for revision of failed tibia internal fixation.

BACKGROUND: The management of failed tibial fracture fixation remains a challenge for orthopaedic surgeons. This study investigate the utility and outcomes of circular external fixation in the management of failed internal fixation of tibial fractures. METHODS: Retrospective review of a prospectively collected database of a complex limb reconstruction unit at a major trauma centre was done during December 2022. Patients with failed internal fixation of tibial fracture who underwent revision surgery with circular external fixation frame were included. RESULTS: 20 patients with a mean age of 47.8 ± 16.5 years (range: 15-69) were included. Fourteen (70.0%) patients had failed plate and screws fixations, and the remaining six (30.0%) failed intramedullary nail fixation. The most common indication for revision surgery was development of early postoperative surgical site infection (5 patients; 25.0%). The mean duration of frame treatment was 199.5 ± 80.1 days (range = 49-364), while the mean follow-up duration following frame removal was 3.2 ± 1.8 years (range = 2-8). The overall union rate in this series was 100%; and all infected cases had complete resolution from infection. The total number of complications was 11, however, only two complications required surgical intervention. The most common complications reported were pin site infection (6; 30.0%) and limb length discrepancy of 2 cm (2; 10.0%). CONCLUSIONS: Circular external fixation is a reliable surgical option in the treatment of failed internal fixation of tibia fractures. This technique can provide limb salvage in complex infected and noninfected cases with a high union rate and minimal major complications.

Current and Developing Technologies for BP Monitoring.

PURPOSE OF REVIEW: To discuss new and emerging technologies for blood pressure measurement and monitoring, including the limitations of current blood pressure measurement techniques, hopes for new device technologies, and the current barriers impeding change in this space. RECENT FINDINGS: A number of new cuffless devices are being developed and poised to emerge on the marketplace in coming years. There are several different types of technologies and sensors currently under study. New guidelines for validation of cuffless blood pressure devices have recently been developed in anticipation of this change. The current standards for blood pressure device validation are specific to cuff-based technology and are insufficient for validating devices with cuffless-based technologies. In anticipation of a number of new cuffless technologies coming to market in the coming years, three sets of standards have been developed and published in recent years to address this gap.

Hybrid Revision of Dysfunctional Aneurysmal Arteriovenous Fistulas.

Endovascular therapy has become the first-line treatment for failing hemodialysis arteriovenous fistulas (AVFs). However, open revision remains an important modality for vascular access maintenance and the recommended approach for AVF aneurysms. This case series describes a hybrid approach for aneurysmal access revision. Three patients were referred for second opinion after failure of endovascular therapy to establish a functioning access. The medical history is briefly described to highlight the limitations of endovascular therapy and the technical advantages of the hybrid approach in these clinical scenarios.

Secondary Hypertension Overview and Workup for the Primary Care Physician.

Secondary hypertension occurs in 5% to 10% of all patients with hypertension. Given the majority of patients with hypertension will not have a secondary cause, only select patients with specific characteristics should be screened. The causes include a range of abnormalities, some are quite rare, such as pheochromocytoma, while others are much more common, such as chronic kidney disease. When considering which disorders to test for, it is important to incorporate the clinical history, family history, and prevalence of each disease. Treatment is specific to the underlying cause and includes medications, procedures, surgery, and device therapies.

Drug-Coated Balloon and Drug-Eluting Stent Safety in Patients With Femoropopliteal and Severe Chronic Kidney Disease.

Background Patients with severe-stage chronic kidney disease (CKD) were excluded from femoropopliteal disease trials evaluating drug-coated balloons (DCBs) and drug-eluting stents (DESs) versus plain balloon angioplasty (POBA) and bare metal stents (BMSs). We examined the interaction between CKD status and device type for the association with 24-month all-cause mortality and major amputation risk. Methods and Results We studied patients undergoing femoropopliteal interventions (September 2016-December 2018) from Medicare-linked VQI (Vascular Quality Initiative) registry data. We compared outcomes for: (1) early-stage CKD (stages 1-3) receiving DCB/DES, (2) early-stage CKD receiving POBA/BMS, (3) severe-stage (4 and 5) CKD receiving DCB/DES, and (4) severe-stage CKD receiving POBA/BMS. We studied 8799 patients (early-stage CKD: 94%; severe-stage: 6%). DCB/DES use was 57% versus 51% in patients with early-stage versus severe-stage CKD. Twenty-four-month mortality risk for patients with early-stage CKD receiving DCB/DES (reference) was 21% versus 28% (hazard ratio [HR], 1.47 [95% CI, 1.31-1.65]) for those receiving POBA/BMS; patients with severe-stage CKD: those receiving DCB/DES had a 49% (HR, 2.61 [95% CI, 2.06-3.31]) mortality risk versus 52% (HR, 3.64 [95% CI, 2.91-4.55]) for those receiving POBA/BMS (interaction P<0.001). Adjusted analyses attenuated these results. For severe-stage CKD, DCB/DES versus POBA/BMS mortality risk was not significant at 24 months (post hoc comparison P=0.06) but was higher for the POBA/BMS group at 18 months (post hoc P<0.05). Patients with early-stage CKD receiving DCB/DES had the lowest 24-month amputation risk (6%), followed by 11% for early-stage CKD-POBA/BMS, 15% for severe-stage CKD-DCB/DES, and 16% for severe-stage CKD-POBA/BMS (interaction P<0.001). DCB/DES versus POBA/BMS amputation rates in patients with severe-stage CKD did not differ (post hoc P=0.820). Conclusions DCB/DES versus POBA/BMS use in patients with severe-stage CKD was associated with lower mortality and no difference in amputation outcomes.