Is chronic kidney disease comparable to diabetes as a coronary artery disease risk factor?

BACKGROUND: Chronic kidney disease (CKD) is one of the known risk factors for coronary heart disease (CHD). Though electrocardiograms (ECGs) have limited accuracy in determining the true prevalence of CHD, we wondered whether CKD and diabetes mellitus (DM) controlled for hypertension (HTN), had similar prevalences of ECG abnormalities that could reflect underlying coronary heart disease. METHOD: Data were collected for 5,942 men and women aged 30 to 69 years in the Tehran Lipid and Glucose Study (TLGS), a crosssectional phase of a large epidemiologic study first initiated in 1999. ECG findings of all subjects were coded according to Minnesota ECG coding criteria. The Whitehall criteria for abnormal ECG findings that could represent ischemia were utilized. Creatinine clearance (Crcl) was estimated using the Cockroft-Gault equation and diabetes was defined according to the American Diabetic Association (ADA) criteria. Subjects with moderate CKD and without DM were compared with the patients with DM without CKD. HTN prevalence was similar. The analysis was performed for all Whitehall ECG ischemia abnormalities combined, and separately for pathologic Q waves. RESULTS: In spite of an overall similar prevalence of smoking, and a lower incidence of dyslipidemia and HTN, moderate CKD patients had a higher prevalence of Whitehall criteria abnormal ECG findings compared with the patients with DM. Over 19% of patients with CKD had abnormal ECG findings while 14.7% of diabetic patients had abnormal ECGs (P = 0.02). The prevalence of Q waves was 11.5% in patients with CKD and 10.8% in patients with DM. In an age-matched subgroup of patients with DM and no CKD, the prevalence of ECG abnormalities was 19.3%, similar to the patients with moderate CKD and no DM (19.7%) (P = 0.9). The prevalence of pathologic Q waves in an age-matched group was 11.45%, compared with 11.5%, respectively. CONCLUSION: Moderate CKD is a major risk factor for the development of the Whitehall ECG criteria which have been associated with ischemic heart disease. The importance of CKD as a risk factor for ECG abnormalities is comparable with DM. Patients with moderate CKD probably are candidates for aggressive CHD risk modification.     

Cardiovascular risk in chronic kidney disease: what is new in the pathogenesis and treatment?

The prevalence of chronic kidney disease (CKD) has increased markedly over past decades due to the aging of the worldwide population. Despite the progress in the prevention and treatment, the cardiovascular (CV) morbidity and mortality remain high among patients with CKD. Although CKD is a progressive and irreversible condition, it is possible to slow decreasing kidney function, as well as the development and progression of associated with kidney disease comorbidities. Diabetes mellitus has become major cause of CKD worldwide. It is estimated that the prevalence of diabetes will increase from 425 million worldwide in 2017 to 629 million by 2045, substantially the percentage of diabetic nephropathy among CKD patients is set to rise markedly. The results of multicenter trials concerning novel antidiabetic drugs suggest that efficacy in reducing CV risk is independent of the improvement in glycemic control. This review discusses underlying causes of high CV risk and strategies reducing individual burden among CKD patients.     

Control of blood pressure in chronic kidney disease: how low to go?

Blood pressure (BP) lowering is an important therapeutic goal in patients with diabetic and non-diabetic chronic kidney disease (CKD) for slowing progression and preventing onset of cardiovascular disease. The guidelines for treatment of hypertension in patients with CKD recommend a target BP <130/80 mm Hg, with no clear threshold on the lower limit. However, results of recent randomized controlled trials on CKD indicate that aggressive lowering of BP may not provide additional benefit in the vast majority of patients. This paper will review the literature on the main trials examining the question concerning the optimal level of target BP in patients with CKD and also discuss reasonable target BP levels in light of the evidence, as well as future direction for research in such patients.     

Should eGFR and albuminuria be added to the Framingham risk score? Chronic kidney disease and cardiovascular disease risk prediction

Presence of chronic kidney disease (CKD) defined as decreased glomerular filtration rate (GFR) and/or increased urine albumin excretion is associated with heightened risk of cardiovascular disease (CVD) and all-cause as well as CVD mortality. Although CKD is strongly linked with CVD, it remains undetermined whether this strong association is simply due to shared CVD risk factors or unique traits consequential to CKD. The probability of future CVD events can be estimated with reasonable accuracy using the Framingham equation which was derived from the Framingham study, a community-based cohort of 5,209 white adults aged 30-62 years who were first examined in 1948. Efforts to capture excess CVD risk associated with CKD have been evaluated by adding estimated GFR, cystatin C, serum creatinine and measures of urinary albumin excretion to the Framingham equation which is based on traditional cardiovascular risk factors. Although decreased GFR and increased urine albumin excretion are consistently associated with cardiovascular outcomes, the addition of these factors to the Framingham equation has not been shown to substantially improve overall CVD risk prediction in populations not enriched with CKD. Moreover, the Framingham equation itself underpredicts cardiovascular events among adults with stage 3 and 4 CKD without clinical CVD. Given the poor performance of the Framingham equation in adults with CKD, future studies should explore risk equations which include traditional CVD risk factors and the unique comorbidities associated with CKD for prediction of cardiovascular events in adults with CKD.     

Idiopathic pediatric chronic kidney disease: can genomic technology crack the case?

In children, chronic kidney disease (CKD) that results from structural abnormalities and glomerular injury is readily diagnosed; however, most cases of pediatric CKD are of unknown etiology. In this issue of the JCI, Verbitsky and colleagues used chromosomal microarrays to evaluate genomic variation in children with CKD. Compared with control individuals, a substantial proportion of children with idiopathic CKD had clearly identifiable genomic imbalances. Moreover, in some cases, detailed analysis of these imbalances identified pathogenic alterations that were unsuspected based on clinical presentation. The results of this study support genome-wide evaluation for pediatric cases of CKD; however, more work will need to be done before such an approach is widely available in the clinic.     

Erythropoiesis and chronic kidney disease–related anemia: From physiology to new therapeutic advancements

Erythropoiesis is triggered by hypoxia and is strictly regulated by hormones, growth factors, cytokines, and vitamins to ensure an adequate oxygen delivery to all body cells. Abnormalities in one or more of these factors may induce different kinds of anemia requiring different treatments. A key player in red blood cell production is erythropoietin. It is a glycoprotein hormone, mainly produced by the kidneys, that promotes erythroid progenitor cell survival and differentiation in the bone marrow and regulates iron metabolism. A deficit in erythropoietin synthesis is the main cause of the normochromic normocytic anemia frequently observed in patients with progressive chronic kidney disease. The present review summarizes the most recent findings about each step of the erythropoietic process, going from the renal oxygen sensing system to the cascade of events induced by erythropoietin through its own receptor in the bone marrow. The paper also describes the new class of drugs designed to stabilize the hypoxia-inducible factor by inhibiting prolyl hydroxylase, with a discussion about their metabolism, disposition, efficacy, and safety. According to many trials, these drugs seem able to simulate tissue hypoxia and then stimulate erythropoiesis in patients affected by renal impairment. In conclusion, the in-depth investigation of all events involved in erythropoiesis is crucial to understand anemia pathophysiology and to identify new therapeutic strategies, in an attempt to overcome the potential side effects of the commonly used erythropoiesis-stimulating agents.     

Managing gout: how is it different in patients with chronic kidney disease?

Many patients with gout have comorbidities, including hypertension and chronic kidney disease (CKD). The goals when treating gout are no different in these patients, but the choice and dosage of drugs may need to be modified.     

Is “chronic kidney disease” a disease?

Several philosophers of medicine have attempted to answer the question “what is disease?” In current clinical practice, an umbrella term “chronic kidney disease” (CKD) encompasses a wide range of kidney health states from commonly prevalent subclinical, asymptomatic disease to rare end‐stage renal disease requiring transplant or dialysis to support life. Differences in severity are currently expressed using a “stage” system, whereby stage 1 is the least severe, and stage 5 the most. Early stage CKD in older patients is normal, of little concern, and does not require treatment. However, studies have shown that many patients find being informed of their CKD distressing, even in its early stages. Using existing analyses of disease in the philosophy literature, we argue that the most prevalent diagnoses of CKD are not, in fact, diseases. We conclude that, in many diagnosed cases of CKD, diagnosing a patient with a “disease” is not only redundant, but unhelpful.