Kidney Disease Research Articles

Link between obstructive uropathy and acute kidney injury

Obstructive uropathy represents a major risk of acute kidney injury. From an epidemiological point of view, it is responsible for 5% to 10% of cases of acute renal failure and 4% of cases of end-stage kidney disease. Although obstructive uropathy is a recognized disease, there is a significant lack of detailed research on this topic from both a nephrological and urological perspective. The majority of published research focuses on the pathophysiology of the topic and neglects a comprehensive analysis of diagnostic and treatment approaches supported by current data. In this context, it is crucial to assess the overall hemodynamic status, especially in the presence of urosepsis. Once clinical stability is assured, it is important to focus on symptom management, usually by controlling pain. Ultimately, it is crucial to decide immediately whether the patient should receive a prompt urinary diversion. Urinary diversion is an essential part of the treatment of obstructive uropathy and should be initiated promptly and without unnecessary delay once the diagnosis has been confirmed. Functional recovery of the obstructed kidney after decompression of the urinary tract depends on the degree of obstruction, the duration of the obstruction and the presence of a concomitant urinary tract infection. The timing and proper treatment of this condition determines the recovery of kidney function after an obstruction and prevents the development of chronic kidney disease. In this editorial, we emphasized the pathophysiological role and clinical significance of obstructive uropathy in the context of acute kidney injury.

Progress and prospects of finerenone in the treatment of type 2 diabetes mellitus related chronic kidney disease

The number of patients with type 2 diabetes mellitus (T2DM)-related chronic kidney disease (CKD) is substantial, and the disease burden is severe. Despite current treatment options, even with standard therapy, patients still face a high risk of kidney disease progression and cardiovascular events. Finerenone, a novel, highly selective, non-steroidal mineralocorticoid receptor antagonist (nsMRA), can directly and effectively block kidney and cardiovascular damage caused by excessive activation of mineralocorticoid receptors, while maintaining good safety. This article provides a review of the mechanism of action, clinical application value, guideline recommendations, and future prospects of finerenone.

Renal triple therapy: treatment strategies for type 2 diabetes mellitus complicated with chronic kidney disease

Type 2 diabetes mellitus and chronic kidney disease (T2DM-CKD) is common in the Chinese population and seriously threatens human health. With the development and application of new drugs, the outcome of T2DM-CKD has been improved in recent years. However, how to combine those drugs effectively and reduce side effects deserves further attention. "Renal triple therapy " (RTT) refers to combined and sequential use of three key medications in treatment of T2DM-CKD, namely renin-angiotensin system inhibitor (RASi), sodium-glucose cotransporter 2 inhibitor (SGLT-2i) and non-steroidal mineralocorticoid receptor antagonist (finerenone), targeting various pathogenic factors in T2DM-CKD. Clinical studies have demonstrated that RTT is superior for protecting the kidney and heart compared with single or dual therapy, and thus improves outcomes of patients with T2DM-CKD. Moreover, RTT can reduce the risk of drug-induced hyperkalemia. Based on research progress at home and abroad and personal clinical experience, this article discusses the origin, theoretical basis, benefits and precautions of RTT in treating T2DM-CKD, aiming to provide a good treatment strategy for primary care physicians and improve the overall level of disease prevention and control.

Eplerenone, diabetes, and chronic kidney disease in patients hospitalized for acute heart failure: findings from the EARLIER trial

BackgroundMineralocorticoid receptor antagonists (MRAs) are often underutilized in patients with heart failure (HF), particularly those with diabetes and/or chronic kidney disease (CKD). However, the impact of concurrent diabetes and CKD on the efficacy and safety of eplerenone in acute HF remains uncertain.MethodsThe EARLIER trial enrolled patients with acute HF, who were randomized to receive eplerenone or placebo for 6 months. Patients were categorized based on the presence of diabetes and/or CKD (defined by eGFR < 45 ml/min/1.73 m2 or UACR ≥ 30 mg/g), and the associations between diabetes/CKD categories and cardiovascular outcomes were assessed. The effects of eplerenone on HF-related outcomes (i.e., cardiovascular death, HF hospitalization, worsening HF, or out-of-hospital diuretic intensification) and adverse events were also assessed across diabetes/CKD status.ResultsAmong 300 patients (mean age 67 ± 13 years; 73% male), 39% had diabetes, mean estimated glomerular filtration rate was 63 ± 18 ml/min/1.73 m2, median urine albumin-to-creatinine ratio was 34 mg/g (13–84 mg/g), and 58% had CKD. Patients with both diabetes and CKD (26%) had a higher risk of cardiovascular death and/or hospitalization compared to those without either disease (HR, 95% CI = 2.57, 1.29–5.12; P = 0.007, P-for-interaction = 0.049), and poor prognosis persisted after adjusting for covariates (i.e., natriuretic peptide) (adjusted-HR, 95% CI = 2.33, 1.12–4.84; P = 0.02). Furthermore, the effects of eplerenone on HF-related outcomes and adverse events were consistent regardless of diabetes/CKD categories (all-P-for interaction > 0.05).ConclusionsIn patients with acute HF, the combination of diabetes and CKD was associated with an increased risk of cardiovascular events. However, the efficacy and safety of eplerenone were not influenced by diabetes and CKD status.Graphical abstract

Knowledge, attitudes and practices among patients with end-stage kidney disease towards hyperkalaemia management in Shenzhen, China: a cross-sectional study

ObjectivesTo investigate the knowledge, attitudes and practices (KAP) among patients with end-stage kidney disease (ESKD) towards hyperkalaemia.DesignA cross-sectional study.SettingThis study was conducted between September and November 2023 at the Department...

Snare-Assisted Retrieval of an Embolized Broken Double Lumen from the Heart of a Female Patient Diagnosed with End Stage Kidney Disease: A Case Report

Snare-Assisted Retrieval of an Embolized Broken Double Lumen from the Heart of a Female Patient Diagnosed with End Stage Kidney Disease: A Case Report

Clinical characteristics and short term outcomes of childhood immune complex membranoproliferative glomerulonephritis and C3 glomerulopathy: a single centre retrospective study

BackgroundMembranoproliferative glomerulonephritis, with its immune complex variety and C3 glomerulopathy, is a rare glomerular disease in children. The objective of this study was to determine the clinical features and short-term outcomes in children.MethodsThis retrospective cohort study was conducted at the Department of Pediatric Nephrology, Sindh Institute of Urology and Transplantation, Karachi, from January 2020, to June 2022. All the children with membranoproliferative lesions identified via light microscopy and less than 18 years were included.ResultsA total of 35 children were diagnosed MPGN, 7 (20%) with C3 glomerulopathy and 28 (80%) idiopathic immune complex MPGN. In the IC-MPGN group, 14 patients (50%) had crescentic glomerulonephritis. Induction therapy consisted of cyclophosphamide and methylprednisolone followed by steroids, azathioprine was prescribed for maintenance phase. At the 18-month follow-up, 9 (64%) patients were in complete remission (CR), 3 (21%) were in partial remission (PR), and 2 (15%) progressed to chronic kidney disease. The remaining 14 (50%) had non-crescentic idiopathic IC-MPGN and were prescribed steroids only, cyclophosphamide with steroids and angiotensin converting enzyme inhibitors. The outcomes at 18 months were relatively poorer than those with the crescentic variety. Four (28%) patients achieved CR, 8 (56%) PR, and 2 (14%) did not respond. In the C3 glomerulopathy cohort, 3 (43%) had crescentic glomerulonephritis, one child was in CR, and two were in PR. The non-crescentic C3G were kept on ACEI 3 (43%) and Mycophenolate mofetil 1 (14%). One child treated with ACEIs achieved a PR, two were in CR, and one child treated with MMF did not respond.ConclusionsThe outcome of MPGN (immune complex and C3G) is quite variable, and aggressive therapy for crescentic glomerulonephritis may show a favourable response. Considering the similar clinical presentations and patient outcomes, C3G and IC-MPGN might represent two facets of the same disease.

Effects of chronic kidney disease on complications and mortality after fracture surgery

PurposeThe purpose of this meta-analysis was to evaluate the effects of CKD on postoperative complications and the survival of patients with fractures.MethodsThe PubMed, Embase, Cochrane Library, and CNKI databases were searched from inception to May 15, 2024. The search strategy focused on two keywords: dialysis and hip fracture. Pooled odds ratios and mean differences were analyzed. RevMan 5.4 was used for data analysis in this meta-analysis.ResultsThis meta-analysis included 19 studies involving 1,615,440 patients. The CKD group had higher proportions of males, smokers, and patients with preoperative comorbidities such as diabetes, hypertension, heart failure, chronic lung disease, coronary heart disease, peripheral vascular disease, dementia, and wound infection. The CKD group also had a greater likelihood of postoperative myocardial infarction (OR = 1.67, 95% CI = 1.54–1.81, P < 0.00001, I2 = 33%). There was no significant difference in cerebrovascular accidents, liver failure, sepsis, and overall complications between the two groups. Additionally, the CKD group had higher mortality rates at 30 days (OR = 2.71, 95% CI = 2.23–3.28, P < 0.00001, I2 = 84%), 1 year (OR = 3.17, 95% CI = 2.64–3.82, P < 0.00001, I2 = 85%), 2 years (OR = 3.06, 95% CI = 2.88–3.25, P < 0.00001, I2 = 8%), and 10 years (OR = 6.85, 95% CI = 5.84–8.03, P < 0.00001, I2 = 0%) post-surgery compared to the non-CKD group.ConclusionCompared with patients in the non-CKD group, patients in the CKD group did not significantly differ in the incidence of most postoperative complications after fracture surgery. However, the CKD group had a significantly greater incidence of myocardial infarction and markedly higher postoperative mortality rates at 30 days, 1 year, 2 years, and 10 years.Trial registrationPROSPERO CRD42025648208.

Continuous glucose monitoring improves detection of glycemic excursions in hemodialysis patients with type 2 diabetes.

Optimal glucose management in individuals with type 2 diabetes (T2D) and end-stage kidney disease (ESKD) on hemodialysis is challenging. We compared the detection of glycemic excursions with continuous glucose monitoring (CGM) and capillary glucose testing (CBG) in this population. In this prospective observational study, insulin-treated adults with T2D on hemodialysis for ≥90 days wore a Dexcom G6-Pro CGM. Participants were instructed to perform CBG up to 4 times daily. We compared differences in glucose metrics and described CGM patterns in relation to dialysis sessions. Among 59 participants (age 57. 7±9years, HbA1c 7.09%), mean glucose measured by CBG and CGM was 165.7 ± 41.8 and 188.9 ± 45.0, with a time-in-range (TIR) of 68%±23 and 51%±26, respectively (p < 0.001). CGM detected that all participants had hyperglycemic episodes of 180mg/dL, with time-above-range (TAR) 180mg/dL of 47.8%±27, and 90% had episodes of >250mg/dL, with TAR >250mg/dL of 20.9%±21.7. CGM detected higher rates of hypoglycemia <70mg/dL, (47% vs. 25%, p=0.005) and <54mg/dL, (25% vs. 12%, p=0.08) than CBG testing. Nocturnal and prolonged hypoglycemia <70mg/dL were only detected by CGM (29% and 12%, respectively). CGM showed a pattern of improved glucose levels on pre-dialysis days, lower glucose levels during hemodialysis, and a rapid rise during the post-dialysis period. In participants with T2D and ESKD on hemodialysis, CGM improved the detection of hyperglycemic and hypoglycemic events, particularly nocturnal and prolonged episodes. CGM revealed distinct glycemic patterns related to dialysis sessions, potentially enabling more personalized management.

An attention enhanced dilated bottleneck network for kidney disease classification

Computer-Aided Design (CAD) techniques have been developed to assist nephrologists by optimising clinical workflows, ensuring accurate results and effectively handling extensive datasets. The proposed work introduces a Dilated Bottleneck Attention-based Renal Network (DBAR-Net) to automate the diagnosis and classification of kidney diseases like cysts, stones, and tumour. To overcome the challenges caused by complex and overlapping features, the DBAR_Net model implements a multi-feature fusion technique. Two fold convolved layer normalization blocks & capture fine-grained detail and abstract patterns to achieve faster convergence and improved robustness. Spatially focused features and channel-wise refined features are generated through dual bottleneck attention modules to improve the representation of convolved features by highlighting channel and spatial regions resulting enhanced interpretability and feature generalisation. Additionally, adaptive contextual features are obtained from a dilated convolved layer normalisation block , which effectively captures contextual insights from semantic feature interpretation. The resulting features are fused additively and processed through a linear layer with global average pooling and layer normalization. This combination effectively reduces spatial dimensions, internal covariate shifts and improved generalization along with essential features. The proposed approach was evaluated using the CT KIDNEY DATASET that includes 8750 CT images classified into four categories: Normal, Cyst, Tumour, and Stone. Experimental results showed that improved feature detection ability enhanced the performance of DBAR_Net model attaining a F1 score as 0.98 with minimal computational complexity and optimum classification accuracy of 98.86%. The integration of these blocks resulted in precise multi-class kidney disease detection, thereby leading to the superior performance of DBAR_Net compared to other transfer learning models like VGG16, VGG19, ResNet50, EfficientNetB0, Inception V3, MobileNetV2, and Xception.

PPDPF preserves integrity of proximal tubule by modulating NMNAT activity in chronic kidney diseases.

Genome-wide association studies (GWAS) have identified loci associated with kidney diseases, but the causal variants, genes, and pathways involved remain elusive. Here, we identified a kidney disease gene called pancreatic progenitor cell differentiation and proliferation factor (PPDPF) through integrating GWAS on kidney function and multiomic analysis. PPDPF was predominantly expressed in healthy proximal tubules of human and mouse kidneys via single-cell analysis. Further investigations revealed that PPDPF functioned as a thiol-disulfide oxidoreductase to maintain cellular NAD+ levels. Deficiency in PPDPF disrupted NAD+ and mitochondrial homeostasis by impairing the activities of nicotinamide mononucleotide adenylyl transferases (NMNATs), thereby compromising the function of proximal tubules during injuries. Consequently, knockout of PPDPF notably accelerated the progression of chronic kidney disease (CKD) in mouse models induced by aging, chemical exposure, and obstruction. These findings strongly support targeting PPDPF as a potential therapy for kidney fibrosis, offering possibilities for future CKD interventions.

Acute kidney disease after radical cystectomy for bladder cancer: a new onco-nephrological view.

To assess the incidence of acute kidney injury (AKI) and acute kidney disease (AKD) following radical cystectomy (RC) in patients with muscle-invasive bladder cancer (BCa). A consecutive cohort of 840 patients undergoing RC for muscle-invasive BCa at a tertiary institution (2010-2022) was analysed. Clinical variables, comorbidities, surgical techniques and oncological regimens were recorded pre- and post-surgery. Serum creatinine and estimated glomerular filtration rate (eGFR) were assessed at baseline, at 24, 48 and 72 h, and 6 days post-surgery for AKI, and at multiple intervals up to 60 days for AKD. Chronic kidney disease (CKD) stages G1 G2 and ≥G3 were classified according to the Kidney Disease Improving Global Outcomes (KDIGO) guidelines. A multivariable logistic regression model was used to predict postoperative AKI or AKD risk. Of the patients included in the study, 33% developed AKI and 54% developed AKD. Independent predictors included advanced age (odds ratio [OR] 1.05, 95% confidence interval [CI] 1.03-1.08), chronic hypertension (OR 1.43, 95% CI 1.03-2.00) and Charlson Comorbidity Index ≥2 (OR 1.59, 95% CI 1.09-2.33). Surgical factors, including use of a robot-assisted approach (OR 2.28, 95% CI 1.50-3.49) and ileal neobladder diversion (OR 1.84, 95% CI 1.05-3.24) were significant, possibly due to the associated prolonged operating times and metabolic challenges. Baseline renal function (CKD ≥G3, OR 2.17, 95% CI 1.28-3.68) and lower preoperative eGFR strongly correlated with AKD risk; a baseline eGFR below 20 mL/min was associated with an AKD risk ≥80%. Our results showed that AKI and AKD are frequent complications of RC for muscle-invasive BCa. Personalised nephrological counselling pre- and post-surgery is essential to minimise morbidity and mortality.

Microvascular aberrations found in human polycystic kidneys are an early feature in a Pkd1 mutant mouse model.

Therapies targeting blood vessels hold promise for autosomal dominant polycystic kidney disease (ADPKD), the commonest inherited disorder causing kidney failure. However, the onset and nature of kidney vascular abnormalities in ADPKD are poorly defined. Accordingly, we employed a combination of single-cell transcriptomics, three-dimensional imaging with geometric, topological and fractal analyses, and multimodal magnetic resonance imaging with arterial spin labelling to investigate aberrant microvasculature in ADPKD kidneys. Within human ADPKD kidneys with advanced cystic pathology and excretory failure, we identified a molecularly distinct blood microvascular subpopulation, characterised by impaired angiogenic signalling and metabolic dysfunction, differing from endothelial injury profiles observed in non-cystic human kidney diseases. Next, Pkd1 mutant mouse kidneys were examined postnatally when cystic pathology is well-established, but before excretory failure. An aberrant endothelial subpopulation was also detected, concurrent with reduced cortical blood perfusion. Disorganised kidney cortical microvasculature was also present in Pkd1 mutant mouse fetal kidneys when tubular dilation begins. Thus, aberrant features of cystic kidney vasculature are harmonised between human and mouse ADPKD supporting early targeting of the vasculature as a strategy to ameliorate ADPKD progression.

Sudden cardiac death due to isolated right ventricle thromboembolism in a young male.

Sudden cardiac death due to an isolated right ventricular thromboembolism is an uncommon cause of death. In the reported case, a healthy, asymptomatic young male with no past medical history outside of obesity and his age was found unresponsive by a family member who suspected him to be sleeping. Examination of the heart at autopsy revealed a large serpiginous, organized and obstructive blood clot compromising most of the right ventricle with no other cardiac abnormalities and without any evidence of a pulmonary embolism. The patient was found to not have any history of substance abuse, genetic predispositions, kidney disease, or COVID-19 infection which has all been linked to ventricular thrombi.

The Type 1 Diabetes Genetics Consortium (T1DGC).

Type 1 diabetes results from the autoimmune destruction of the insulin-producing beta cells. Genetic factors account for ∼50% of the risk for type 1 diabetes but, by the late 1990's, the genetic basis was limited. The Type 1 Diabetes Genetics Consortium (T1DGC) was formed in 2002 to accelerate discovery of genes contributing to type 1 diabetes risk through a grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) to assemble existing data and samples from affected sib-pair families and to establish new collections. In recognition of the 75th anniversary of the NIDDK, this manuscript highlights the contributions made by the T1DGC to understanding the genetic basis of type 1 diabetes using both family (for linkage) and case-control (for genome-wide association) designs. The T1DGC conducted large-scale genetic research and used fine mapping to define risk regions. The T1DGC data, results, and samples have been made available to the scientific community, leading to the discovery of over 100 loci associated with type 1 diabetes risk, many with small effects and relevant to autoimmune pathways. The T1DGC not only expanded the list of genes contributing to disease risk but also identified non-coding genetic variation in disease-relevant cell types that contributed to the etiology of type 1 diabetes. The success of the T1DGC and the NIDDK investment in the global consortium is highlighted in its continuing impact on mapping genetic variants to their function and identifying pathways that provide new targets for prediction, prevention and treatment of type 1 diabetes.

Correlation linking fibroblast growth factor 23 in circulation (FGF-23) and serum aldosterone levels in different stages of chronic kidney disease

BackgroundChronic kidney disease (CKD) continues to pose a serious medical issue. To date, the detection of CKD relies on renal function estimate and radiology. Hence, new sensitive diagnostic and prognostic bioindicators are urgently needed for early diagnosis and surveillance of CKD. This study aimed to assess the correlation linking fibroblast growth factor 23 (FGF23) in circulation and serum aldosterone levels in cases with CKD of different stages and investigate the theory that aldosterone may directly cause elevated FGF23 secretion in these cases.MethodsOur observational cross-sectional research was performed on 140 patients divided into: group A: 70 cases with diverse stages of recently discovered CKD that had not yet begun treatment with renin–angiotensin–aldosterone system (RAAS) blockers (CKD stages 1–5) and group B: 70 normal control subjects.ResultsThe levels of serum aldosterone and circulating FGF-23 levels varied significantly among CKD cases. High levels of circulating FGF-23 and serum aldosterone each considerably raise the risk of CKD by 1.15 and 1.043 times, correspondingly. With a sensitivity of 91.4%, a specificity of 90%, a positive predictive value of 90.1%, a negative predictive value of 91.3%, and an overall accuracy of 90.7%. The optimal cutoff value for FGF-23 was a prediction of kidney damage at ≥ 59,735 (p < 0.001). Patients’ FGF-23 levels and their CKD stages showed a strong correlation. For renal damage prediction, the optimal cutoff value for aldosterone is ≥ 117.59, with an area under the curve of 0.978, a sensitivity of 92.9%, a specificity of 88.6%, a positive predictive value of 89%, a negative predictive value of 92.5%, and an overall accuracy of 90.7% (p < 0.001). Our study found that FGF-23, age, and estimated glomerular filtration rate (eGFR) were the sole factors strongly related to aldosterone in CKD patients.ConclusionThere was a significant correlation linking circulating FGF23 and serum aldosterone levels among CKD cases, suggesting their potential as independent predictors of CKD progression. Both circulating FGF23 and aldosterone levels were considerably elevated in CKD cases in comparison with normal controls, highlighting their predictive performance.

Management of Diabetes in Patients with Chronic Kidney Disease.

Patients with diabetes and chronic kidney disease (CKD) are at increased risk of kidney disease progression and cardiovascular events. In this article, we will summarize the 2022 consensus report by the ADA and KDIGO on diabetes management in CKD and include newly available evidence to assist health care professionals in providing optimal care to patients living with diabetes and CKD. Comprehensive care strategies include lifestyle interventions, optimal glycemic, blood pressure, weight, and lipid management, and preferential use of therapies with proven heart and kidney beneficial effects. This article offers a concise overview of the multiple strategies aimed at reducing cardiovascular and kidney risk among people with diabetes and CKD, as recommended by multiple societies.

Reliability and Validity of Self-Reported Risk Factors for Stroke and Dementia.

Stroke and dementia are leading causes of mortality and can be prevented through risk factor management. Risk factor assessment requires laboratory or physical measurements. We aimed to determine whether self-reported risk factors serve as reliable proxies and predict stroke- and dementia-related mortality. We used cross-sectional data from the NHANES (National Health and Nutrition Examination Survey) from 1999 to 2018 linked to National Death Index records. We included participants with available data on self-reported and measured hypertension, hypercholesterolemia, diabetes, kidney disease, hearing impairment and overweight. Reliability was assessed using F1 scores, and used survey-weighted Cox-proportional hazards models evaluated associations with stroke- or dementia-related mortality. Reliability of self-reported risk factors was highest in overweight (F1 score 0.81, sensitivity 76%, specificity 77%) and diabetes (F1 score 0.71, sensitivity 77%, specificity 97%) and lowest for kidney disease (F1 score 0.25, sensitivity 16%, specificity 98%). Self-reported hypertension (hazard ratio [HR], 1.49 [95% CI, 1.14-1.94]) and diabetes (HR, 1.58 [95% CI, 1.18-2.12]) were associated with stroke-related mortality, comparable to measured risk factors. For dementia-related mortality, only measured hearing impairment (all dementia cases had hearing impairment at baseline) and both self-reported (HR, 0.50 [95% CI, 0.37-0.68]) and measured overweight (HR, 0.70 [95% CI, 0.52-0.93]) were associated. In conclusion, the reliability and validity of self-reported risk factors for stroke and dementia differ between risk factors. Although self-reported measures vary in their reliability, they perform equally as well as objective metrics for evaluating the risk of stroke- and dementia-related mortality.

Editorial Comment to "The Effect of Chronic Kidney Disease on Adverse In-Hospital Outcomes at Radical Prostatectomy".

Editorial Comment to "The Effect of Chronic Kidney Disease on Adverse In-Hospital Outcomes at Radical Prostatectomy".

Long-Term Outcomes of Peripheral Artery Disease in Veterans: Analysis of the Peripheral Artery Disease Long-Term Survival Study (PEARLS).

Contemporary research in peripheral artery disease (PAD) remains limited due to lack of a national registry and low accuracy of diagnosis codes to identify patients with PAD. Leveraging a novel natural language processing system that identifies PAD with high accuracy using ankle-brachial index and toe-brachial index values, we created a registry of 103 748 patients with new-onset PAD in the Veterans Health Administration. Study end points include mortality, cardiovascular events (hospitalization for acute myocardial infarction or stroke) and limb events (hospitalization for critical limb ischemia or major amputation) and were identified using Veterans Affairs and non-Veterans Affairs encounters. The mean age was 70.6 years; 97.3% were male, and 18.5% self-identified as Black. The mean ankle-brachial index value was 0.78 (SD: 0.26) and the mean toe-brachial index value was 0.51 (SD: 0.19). A majority of patients were current (27.1%) or former (30.0%) smokers. Prevalence of hypertension (86.6%), heart failure (22.7%), diabetes (54.8%), chronic kidney disease (23.6%), and chronic obstructive pulmonary disease (35.4%) was high. At 1 year, 9.4% of patients had died. The 1-year incidence of cardiovascular events was 5.6 per 100 patient-years and limb events was 7.0 per 100 patient-years. We have successfully launched a registry of >100 000 patients with a new diagnosis of PAD in the Veterans Health Administration, the largest integrated health system in the United States. The incidence of death and clinical events in our cohort is high. Ongoing studies will yield important insights regarding improving care and outcomes in this high-risk group.