Tryptophan metabolites suppress the Wnt pathway and promote adverse limb events in chronic kidney disease.

Chronic kidney disease (CKD) imposes a strong and independent risk for peripheral artery disease (PAD). While solutes retained in CKD patients (uremic solutes) inflict vascular damage, their role in PAD remains elusive. Here, we show that the dietary tryptophan-derived uremic solutes including indoxyl sulfate (IS) and kynurenine (Kyn) at concentrations corresponding to those in CKD patients suppress ß-catenin in several cell types, including microvascular endothelial cells (ECs), inhibiting Wnt activity and proangiogenic Wnt targets in ECs. Mechanistic probing revealed that these uremic solutes downregulated ß-catenin in a manner dependent on serine 33 in its degron motif and through the aryl hydrocarbon receptor (AHR). Hindlimb ischemia in adenine-induced CKD and IS solute-specific mouse models showed diminished ß-catenin and VEGF-A in the capillaries and reduced capillary density, which correlated inversely with blood levels of IS and Kyn and AHR activity in ECs. An AHR inhibitor treatment normalized postischemic angiogenic response in CKD mice to a non-CKD level. In a prospective cohort of PAD patients, plasma levels of tryptophan metabolites and plasma's AHR-inducing activity in ECs significantly increased the risk of future adverse limb events. This work uncovers the tryptophan metabolite/AHR/ß-catenin axis as a mediator of microvascular rarefaction in CKD patients and demonstrates its targetability for PAD in CKD models.

Periprocedural Outcomes in Patients on Chronic Anticoagulation Undergoing Fistulograms.

BACKGROUND: Management of antithrombotic therapy with warfarin in patients undergoing fistulograms and possible interventions is controversial and difficult because of lack of adequate outpatient bridging options. Our goal was to assess periprocedural outcomes in patients managed using different anticoagulation strategies. METHODS: A retrospective, single-institution analysis of all patients on chronic anticoagulation with warfarin undergoing fistulograms from 2011 to 2017 was performed. Anticoagulation management strategies were classified as suspended warfarin (SW), continued warfarin (CW), and a heparin bridge with suspended warfarin (HB). Periprocedural outcomes were analyzed. RESULTS: There were 87 patients on chronic anticoagulation with warfarin who underwent 175 fistulograms. Median age was 63 years, and 43.4% were women. Indications for warfarin included atrial fibrillation (53%), prior pulmonary embolism/deep vein thrombosis (29%), and hypercoagulable state (14%). Distribution was SW (60%), CW (26%), and HB (14%). Approximately half (53%) were same-day procedures, 30% occurred during access-related admissions, and 14% were performed during nonaccess-related admissions. Common indications for a fistulogram included difficulty with dialysis (63.4%), access thrombosis (20.6%), and poor maturation (10.3%). Interventions included angioplasty (82.9%), thrombectomy/embolectomy (20.6%), and stenting (8.6%). Thirty-day outcomes for SW versus CW versus HB were similar for bleeding complications (5.7%, 6.5%, 8.3%; P = 0.89), systemic thrombotic complications (3.8%, 2.2%, 0%; P = 0.569), access rethrombosis (7.6%, 13%, 12.5%; P = 0.517), and tunneled dialysis catheter placement (11.4%, 13%, 12.5%; P = 0.958). After excluding procedures performed during a nonaccess-related admission, length of stay (LOS) was highest among HB (9.6 ± 7.8 days) compared with SW (2.6 ± 5.9 days) and CW (1 ± 2.8 days), (P < 0.0001). CONCLUSIONS: CW therapy in patients undergoing fistulograms was not associated with increased morbidity and was associated with shorter LOS. Bridging with heparin is not associated with improved outcomes, warranting a thorough consideration of continuing warfarin is safe and may streamline preservation of dialysis accesses without significantly increasing resource utilization.

Unique aspects of peripheral artery disease in patients with chronic kidney disease.

Peripheral artery disease (PAD) represents a major health care burden. Despite the advent of screening and interventional procedures, the long-term clinical outcomes remain suboptimal, especially in patients with chronic kidney disease (CKD). While CKD and PAD share common predisposing factors, emerging studies indicate that their co-existence is not merely an association; instead, CKD represents a strong, independent risk factor for PAD. These findings implicate CKD-specific mediators of PAD that remain incompletely understood. Moreover, there is a need to understand the mechanisms underlying poor outcomes after interventions for PAD in CKD. This review discusses unique clinical aspects of PAD in patients with CKD, including high prevalence and worse outcomes after vascular interventions and the influence of renal allograft transplantation. In doing so, it also highlights underappreciated aspects of PAD in patients with CKD, such as disparities in revascularization and higher peri-procedural mortality. While previous reviews have discussed general mechanisms of PAD pathogenesis, focusing on PAD in CKD, this review underscores a need to probe for CKD-specific pathogenic pathways that may unravel novel biomarkers and therapeutic targets in PAD and ultimately improve the risk stratification and management of patients with CKD and PAD.

Snuffbox arteriovenous fistulas have similar outcomes and patency as wrist arteriovenous fistulas.

OBJECTIVE: Radial artery-based wrist arteriovenous fistulas (AVFs) are commonly created as an initial upper extremity arteriovenous access. A more distal access site, such as the anatomic snuffbox AVF, can also be created. Although much has been written about wrist AVFs, outcomes of snuffbox AVFs are unclear. Our goal was to compare perioperative and midterm outcomes between these two types of distal access. METHODS: The Vascular Quality Initiative database was queried for all patients undergoing snuffbox AVFs and wrist AVFs from 2011 to 2017. Unmatched and matched analyses were performed for baseline characteristics and outcomes at 6 months for ischemic steal, wound infection, and arm swelling. Multivariable analysis was performed for unmatched and matched analyses for primary patency, surgical or endovascular repair, and patient survival. Kaplan-Meier matched analysis was performed for primary patency, freedom from surgical or endovascular intervention, and survival. RESULTS: We identified 4525 distal forearm fistulas: 179 (4%) snuffbox AVFs and 4346 (96%) wrist AVFs. The average age was 59 ± 14.7 years, and 72.3% of patients were male. There were no significant differences in baseline demographics or comorbidities of patients with snuffbox AVFs and wrist AVFs except that patients with snuffbox AVFs had fewer tunneled lines at access creation (70.2% vs 65.2%; P = .046) and had a lower American Society of Anesthesiologists class. There were no significant differences in unmatched outcomes at 6 months for ischemic steal (0.8% vs 1.9%; P = .336), wound infection (0% vs 0.2%; P = .649), and arm swelling (0.8% vs 1.3%; P = .592). Matched analysis showed no significant differences in baseline characteristics and outcomes at 6 months for ischemic steal (0% vs 1.8%; P = .146), wound infection (0% vs 0%), and arm swelling (0.9% vs 1.2%; P = .789). Kaplan-Meier matched analysis showed no significant differences between snuffbox AVFs and wrist AVFs at 6 months for primary patency (51% vs 48%; P = .61), freedom from endovascular intervention (84.5% vs 82.5%; P = .98), freedom from surgical intervention (90% vs 86%; P = .08), and survival (92% vs 96%; P = .1). In multivariable analysis of unmatched data, snuffbox AVFs and wrist AVFs had similar primary patency (hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.75-1.26; P = .83), likelihood of surgical intervention (HR, 0.61; 95% CI, 0.35-1.05; P = .074) and endovascular intervention (HR, 0.96; 95% CI, 0.65-1.42; P = .83), and survival (HR, 1.47; 95% CI, 0.9-2.4; P = .128). CONCLUSIONS: Snuffbox AVFs have midterm results similar to those of wrist AVFs.

Evaluating Provider Advice and Women's Beliefs on Total Weight Gain During Pregnancy.

Excessive gestational weight gain (GWG) is associated with complications for both mother and child. Minority women are at increased risk for excessive GWG, yet are underrepresented in published weight control interventions. To inform future interventions, we examined the prevalence and accuracy of provider advice and its association with personal beliefs about necessary maternal weight gain among predominantly Latina pregnant women. Secondary analysis examining baseline data (N = 123) from a healthy lifestyle randomized controlled trial conducted in and urban area of the South East. Only 23.6 % of women reported being told how much weight to gain during pregnancy; although 58.6 % received advice that met Institute of Medicine recommendations. Concordance of mothers' personal weight gain target with clinical recommendations varied by mothers' pre-pregnancy weight status [χ (4) (2)  = 9.781, p = 0.044]. Findings suggest the need for prenatal providers of low-income, minority women to engage patients in shaping healthy weight gain targets as a precursor to preventing excessive GWG and its complications.