Chronic kidney disease, prevalence of premature cardiovascular disease, and relationship to short-term mortality

doi:10.1016/j.ahj.2008.02.024

American Heart Journal

Volume 156, Issue 2, August 2008, Pages 277-283

https://doi.org/10.1016/j.ahj.2008.02.024 Get rights and content

Background

Chronic kidney disease (CKD) is recognized as an independent cardiovascular disease (CVD) risk state, particularly in the elderly, and has been defined by levels of estimated glomerular filtration rate (eGFR) and markers of kidney damage. The relationship between CKD and CVD in younger and middle-aged adults has not been fully explored.

Methods

Community volunteers completed surveys regarding past medical events and underwent blood pressure and laboratory testing. Chronic kidney disease was defined as an eGFR <60 mL·min⁻¹·1.73 m⁻² or urine albumin-creatinine ratio (ACR) ≥30 mg/g. Premature CVD was defined as self-reported myocardial infarction or stroke at <55 years of age in men and <65 years of age in women. Mortality was ascertained by linkage to national data systems.

Results

Of 31 417 participants, the mean age was 45.1 ± 11.2 years, 75.5% were female, 36.8% African American, and 21.6% had diabetes. A total of 20.6% were found to have CKD, with the ACR and eGFR being the dominant positive screening tests in the younger and older age deciles, respectively. The prevalences of premature myocardial infarction (MI), stroke, or death, and the composite were 5.3%, 4.7%, 0.8%, 9.2%, and 2.5%, 2.2%, 0.2%, 4.2% for those with and without CKD, respectively (P < .0001 for composite). Multivariable analysis found CKD (OR 1.44, 95% CI 1.27-1.63), age (OR 1.05 [per year], 95% CI 1.04-1.06), hypertension (OR 1.61, 95% CI 1.40-1.84), diabetes (OR 2.03, 95% CI 1.79-2.29), smoking (OR 1.91, 95% CI 1.66–2.21), and less than high school education (OR 1.59, 95% CI 1.37-1.85) as the most significantly associated factors for premature CVD or death (all P < .0001). Survival analysis found those with premature MI or stroke and CKD had the poorest short-term survival over the next 3 years after screening.

Conclusions

Chronic kidney disease is an independent predictor of MI, stroke, and death among men and women younger than age 55 and 65 years, respectively. These data suggest the biologic changes that occur with kidney failure promote CVD at an accelerated rate that cannot be fully explained by conventional risk factors or older age. Screening for CKD by using both the ACR and eGFR can identify younger and middle-aged individuals at high risk for premature CVD and near-term death.

Section snippets

Subjects

The National Kidney Foundation's Kidney Early Evaluation Program (KEEP) is a free, on-going community-based screening program designed to identify individuals at increased risk for kidney disease and encourage them to seek follow-up care.²³ From August 1, 2000, through December 31, 2005, participants from 48 National Kidney Foundation affiliates representing 50 states and 1,245 screening events were recruited. Eligible participants were men or women ≥18 years old; with DM or HTN; or with a

Results

Demographic characteristics of the population are given in Table I. The overall mean age of the sample was 45.1 ± 11.2 years. The proportions of men and women differed across the age groups because only women could populate cells with ages >55 years. In addition, women have been more prevalent in the KEEP screening program as a whole. There was a trend for older participants to be white and younger participants to be African American, Hispanic, or from another racial group. Of note, younger

Discussion

Among individuals who volunteered for this screening program, CKD, DM, and HTN were strongly related to increasing age. Among those who were found to have CKD at the screening event, the urine ACR was the dominant positive test in the younger age groups, whereas the eGFR was the test most likely to qualify and older individual for CKD. The prevalence of self-reported CVD also escalated according to age decile, but at a slightly higher relative rate for those with CKD. This held true after

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Cited by (157)

AWAREness of Diagnosis and Treatment of Chronic Kidney Disease in Adults With Type 2 Diabetes (AWARE-CKD in T2D)
2022, Canadian Journal of Diabetes
Diabetes remains the leading contributor to the development of chronic kidney disease (CKD) and end-stage kidney disease, emphasizing the urgency of identifying barriers to early diagnosis and intervention. The primary objective of this study was to describe the awareness, values and preferences of physicians and patients with respect to managing CKD among patients with type 2 diabetes (T2D).
A cross-sectional survey was conducted among physicians and adult patients with T2D and CKD based on estimated glomerular filtration rate and urine albumin-to-creatinine ratio (uACR) measured within 1 year. Physicians were recruited from email networks across Canada, excluding Alberta, and patients were recruited from LMC Diabetes and Endocrinology clinics in Ontario and Quebec. Two separate surveys were developed by a steering committee. Survey responses from 160 physicians (60 general practitioners, 50 endocrinologists and 50 nephrologists) and 169 patients were analyzed descriptively.
Gaps in physician care included insufficient use of uACR screening, limited knowledge or use of Kidney Disease Improving Global Outcomes (KDIGO) and KidneyWise resources and lower than expected prescription of recommended therapies. The patient data showed 51.5% of patients were unaware of a CKD diagnosis, and 75.6% of patients who received a prior CKD diagnosis would have preferred an earlier diagnosis.
The results highlight several opportunities for improving CKD in T2D management. More education and clarity are needed for physicians interpreting uACR levels that should prompt a referral to a nephrologist, and additional understanding of kidney risk progression is vital for patients.
Le fait que le diabète demeure la cause principale de l’apparition de l’insuffisance rénale chronique (IRC) et de l’insuffisance rénale terminale souligne l’urgence de déterminer les obstacles au diagnostic et aux interventions précoces. Le principal objectif de la présente étude était de décrire la conscientisation, les valeurs et les préférences des médecins et des patients quant à la prise en charge de l’IRC chez les patients atteints du diabète de type 2 (DT2).
Nous avons mené une enquête transversale auprès des médecins et des patients adultes atteints du DT2 et de l’IRC en fonction de la mesure du débit de filtration glomérulaire estimé et du calcul du rapport albuminurie:créatininurie (RAC) dans 1 année. Nous avons recruté les médecins à partir de réseaux de messagerie électronique du Canada, sauf de l’Alberta, et nous avons recruté les patients dans les cliniques LMC de l’Ontario et du Québec. Un comité directeur a élaboré 2 enquêtes distinctes. Les réponses de 160 médecins (60 omnipraticiens, 50 endocrinologues et 50 néphrologues) et de 169 patients aux enquêtes ont fait l’objet d’une analyse descriptive.
Les lacunes dans les soins des médecins ont notamment été le recours insuffisant à l’évaluation du RAC, les connaissances ou l’utilisation limitées des ressources de KDIGO et de KidneyWise, et le nombre de prescriptions de traitements recommandés moindre que prévu. Les données sur les patients ont montré que 51,5 % des patients ignoraient le diagnostic de MRC, et que 75,6 % des patients qui avaient déjà reçu un diagnostic de MRC auraient souhaité recevoir ce diagnostic plus précocement.
Les résultats font ressortir plusieurs possibilités pour améliorer la MRC dans la prise en charge du DT2. Les médecins doivent recevoir davantage de formation et de précisions pour interpréter les concentrations du RAC afin d’accélérer l’aiguillage vers un néphrologue, et les patients doivent avoir une meilleure compréhension de la progression du risque de maladie rénale.
Prevalence of Chronic Kidney Disease in Type 2 Diabetes: The Canadian REgistry of Chronic Kidney Disease in Diabetes Outcomes (CREDO) Study
2021, Clinical Therapeutics
Chronic kidney disease (CKD) in patients with type 2 diabetes (T2D) is associated with an elevated risk of end-stage kidney disease, cardiovascular disease (CVD), and death. As the breadth of treatment options for CKD in patients with T2D (CKD in T2D) continues to expand, an analysis of the current use of therapies and cardiovascular and kidney outcomes is necessary. The objectives of the study were to assess the prevalence of CKD in T2D among a contemporary cohort of patients, to describe patient characteristics and treatment patterns, and to examine health care practitioner rationale for initiating therapies.
The study was a retrospective, observational study (module A) with a prospective component (module B). For module A, sociodemographic data, medical history, prescription information, and laboratory investigations for patients seen by an endocrinologist in 2019 were retrieved from the LMC Diabetes Registry. Module B included a subset of patients for health care practitioner surveys to understand rationale for administering angiotensin-converting enzyme inhibitors (ACEis) or angiotensin receptor blockers (ARBs), steroidal mineralocorticoid receptor antagonists (MRAs), sodium-glucose cotransporter 2 inhibitors (SGLT2is), and glucagon-like peptide 1 receptor agonists (GLP-1RAs). Descriptive analyses were conducted.
The study included 14,873 patients (59% male). Mean patient age was 67 years, mean body mass index was 31 kg/m², and mean glycosylated hemoglobin was 7.6%. Mean diabetes duration was 16 years. The prevalence of CKD in patients with T2D was 47.9%. Common comorbidities were hypertension (76%), dyslipidemia (71%), and obesity (51%). CVD was reported in 22%. The proportion of kidney medications and emerging therapies varied, with 76% of patients using an ACEi or ARB, 48% using an SGLT2i, 30% using a GLP-1RA, and 3% using a steroidal MRA. In module B, physicians identified that ACEis/ARBs, SGLT2is, GLP-1RAs, or steroidal MRAs were administered to primarily treat CKD in 33%, 12%, 0%, and 4% of the patients (n = 500), respectively.
These findings improved our understanding of the current landscape and treatment patterns of CKD inT2D and highlighted the importance of considering treatments that will provide a comprehensive strategy for cardiovascular and kidney risk protection. Despite the high prevalence of CKD and comorbidities reported in a large, Canadian T2D specialist population, ACEis/ARBs, SGLT2is, and GLP-1RAs were underused, especially considering recent clinical trial reports. The relative use of steroidal MRAs was expectedly low. With an immense burden of CKD progression and among patients with T2D, the use of treatments that provide a comprehensive strategy for kidney protection will transform the landscape of CKD in T2D. ClinicalTrials.gov identifier: NCT04445181.
Implications of Kidney Disease in the Cardiac Patient
2020, Interventional Cardiology Clinics
Serum 8-hydroxydeoxyguanosine, a marker of oxidative DNA damage, is associated with mortality independent of inflammation in chronic kidney disease
2019, European Journal of Internal Medicine
Oxidative stress and low-grade systemic inflammation are common interrelated sequelae of chronic kidney disease (CKD) that associate with mortality. We investigated the association of serum 8-hydroxy-2′-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, with mortality in CKD individuals and analyzed whether inflammation modifies the association.
In 376 individuals with a wide range of estimated glomerular filtration rate (eGFR); >60 ml/min (n = 53), 15–60 ml/min (n = 60) and <15 ml/min (n = 263), cut-off values of serum 8-OHdG, high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and tumor necrosis factor (TNF) as predictors of mortality were determined by ROC curves. We analyzed associations of 8-OHdG with inflammation markers and the overlapping effect of hsCRP, IL-6 and TNF on the association between 8-OHdG and all-cause mortality by multivariate generalized linear models.
In separate individual exposure analyses, higher 8-OHdG, hsCRP, and IL-6 (but not TNF) were each independently associated with increased risk of death in multivariate models adjusted for age, sex, diabetes mellitus, cardiovascular disease, protein-energy wasting, cohort calendar year, blood sample storage time and eGFR. For 8-OHdG, the multivariate relative risk ratio, RR_8-OHdG (95% confidence interval) 1.17 (1.08–1.26), remained essentially unchanged when adjusting also for inflammation in three separate models including: hsCRP, RR_8-OHdG = 1.15 (1.06–1.25); IL-6, RR_8-OHdG = 1.15 (1.07–1.25); and TNF, RR_8-OHdG = 1.16 (1.07–1.26).
Serum 8-OHdG, a biomarker of oxidative DNA damage, is associated with increased all-cause mortality risk in individuals with a wide range of eGFR and this association is independent of inflammation.
Cardiovascular Disease and Chronic Kidney Disease
2019, Chronic Renal Disease
Cardiovascular disease (CVD) is a major cause of morbidity and mortality in patients with chronic kidney disease (CKD). The various phenotypes of cardiovascular disease including heart failure, ischemic heart disease, valvopathies, and arrhythmias are all represented with high disease burden in patients with CKD. Several traditional and nontraditional vascular risk factors are operational in the pathogenesis of cardiovascular disease in this population. Despite the well-known risk of cardiovascular disease, patients with CKD tend to be excluded from major cardiovascular outcome trials. Therefore there is less-robust available evidence on how to deliver optimal medical and procedural therapies for CVD in the CKD population. CKD patients also present with atypical symptom profiles and receive less aggressive goal–directed medical therapies for CVD compared to patients without CKD. Therapeutic effects of medical therapies as well as procedural interventions tend to be associated with higher complication rates related to the brittle bleeding–clotting paradigm in CKD, altered pharmacotherapeutics of drugs, and high vascular calcific burden. There is an urgent need to prioritize the inclusion of patients with CKD in cardiovascular trials, as well as to implement efforts to deliver cohesive care via multidisciplinary cardio-renal team models to achieve optimal long-term outcomes and CVD reduction in this vulnerable patient population.
Interventions to Improve Blood Pressure Control Among Socioeconomically Disadvantaged Patients With CKD: Kidney Awareness Registry and Education Pilot Randomized Controlled Trial
2019, Kidney Medicine
Sustainable interventions that enhance chronic kidney disease (CKD) management are not often studied in safety-net primary care, in which populations bear a disproportionate burden of disease and experience translational gaps between research and practice. We tested the feasibility of implementing and the impact of 2 technology-enhanced interventions designed to enhance CKD care delivery.
A 2×2 randomized controlled pilot trial.
Primary care provider teams (n = 6) and 137 patients with CKD aged 18 to 75 years from 2 safety-net primary care clinics, 2013 to 2015.
Primary care provider teams were randomly assigned to access a CKD registry with point-of-care notifications and quarterly feedback or a usual-care registry for 12 months. Patients within provider teams were randomly assigned to participate in a CKD self-management support program or usual care for 12 months.
We examined recruitment, randomization, and participation in each intervention. We also examined the impact of each intervention and their combination on change in systolic blood pressure (SBP), albuminuria, and patient self-reported behavioral measures after 12 months.
Among potentially eligible patients identified using the electronic health record, 24% were eligible for study participation, of whom 35% (n = 137) were enrolled. Mean age was 55 years, 41% were non–English speaking, and 93% were of racial/ethnic minority. Mean baseline estimated glomerular filtration rate was 70.5 (SD = 30.3) mL/min/1.73 m²; mean baseline SBP was 131 (SD = 21.8) mm Hg. Nearly 90% of clinicians reported that the CKD registry influenced their CKD management. More than 95% of patients randomly assigned to CKD self-management support engaged regularly with the intervention. Estimated changes in SBP over 1 year were nonstatistically different in each of the 3 intervention groups compared with usual care: (usual care: 0.5 [95% CI, −5.2 to 6.3] mm Hg; CKD registry only: −5.4 [95% CI, −12.2 to 1.4] mm Hg; CKD self-management support only: −6.4 [95% CI, −13.7 to 1.0] mm Hg; and CKD registry plus CKD self-management support: −0.5 [−5.5 to 4.5] mm Hg), though differences were larger among those with baseline SBPs > 140/90 mm Hg. Decreases in albuminuria were similarly nonstatistically different in each of the intervention groups compared with usual care. No differences were observed in patient self-reported behaviors.
Single health system.
Patient and provider interventions to improve CKD care are feasible to implement in low-income settings with promising results among those with uncontrolled blood pressure.
National Institute of Diabetes and Digestive and Kidney Diseases.
ClinicalTrials.gov, number: NCT01530958.

View all citing articles on Scopus

: Presented in part at the American Heart Association Scientific Sessions 2007, Orlando, Fla, November 7, 2007.

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Clinical InvestigationCoronary Artery DiseaseChronic kidney disease, prevalence of premature cardiovascular disease, and relationship to short-term mortality

Background

Methods

Results

Conclusions

Section snippets

Subjects

Results

Discussion

Kidney Int Suppl

Am J Kidney Dis

Kidney Int

J Am Coll Cardiol

Chest

Am J Kidney Dis

J Am Coll Cardiol

Renal insufficiency as a predictor of cardiovascular outcomes and the impact of ramipril: the HOPE randomized trial

Ann Intern Med

National Kidney Foundation Kidney Disease Outcomes Quality Initiative Guideline

Am J Kidney Dis

Low-grade albuminuria and incidence of cardiovascular disease events in nonhypertensive and nondiabetic individuals: the Framingham Heart Study

Circulation

Urinary albumin excretion predicts cardiovascular and noncardiovascular mortality in general population

Circulation

A prospective study of microalbuminuria and incident coronary heart disease and its prognostic significance in a British population: the EPIC-Norfolk study

Am J Epidemiol

Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in U.S. Adults. The Third National Health and Nutrition Examination Survey, 1988-1994

Diabetes Care

Chronic renal failure in non-insulin dependent diabetes mellitus: a population based study in Rochester, Minnesota

Ann Intern Med

Clinical Investigation
Coronary Artery Disease
Chronic kidney disease, prevalence of premature cardiovascular disease, and relationship to short-term mortality