Patients with CKD frequently have anemia that results from iron-restricted erythropoiesis and inflammation. Anemia of CKD is currently managed with iron supplements and erythropoiesis-stimulating ...agents (ESAs) to promote erythropoiesis and with RBC transfusion in severe cases. Hyporesponse to ESAs, or the need for larger than usual doses to attain a given hemoglobin (Hb) level, is associated with increased morbidity and mortality and presents a pressing clinical challenge, particularly for patients on dialysis. This paper reviews ESA hyporesponse and potential new therapeutic options in the management of anemia of CKD.
The most common causes of ESA hyporesponse include iron deficiency and inflammation, and to a lesser degree, secondary hyperparathyroidism, inadequate dialysis, malnutrition, and concomitant medications. Management of ESA hyporesponse is multipronged and involves treating low level infections, ensuring adequate nutrition, and optimizing iron status and dialysis modality, although some patients can remain refractory. Inflammation directly increases production and secretion of hepcidin, contributes to an impaired response to hypoxia, and suppresses proliferation of erythroid progenitors. Coordination of renal and hepatic erythropoietin (EPO) production and iron metabolism is under the control of hypoxia-inducible factors (HIF), which are in turn regulated by HIF-prolyl hydroxylases (HIF-PHs). HIF-PHs and hepcidin are therefore attractive potential drug targets particularly in patients with ESA hyporesponse. Several oral HIF-PH inhibitors have been evaluated in patients with anemia of CKD and have been shown to increase Hb and reduce hepcidin regardless of inflammation, iron status, or dialysis modality. These sustained effects are achieved through more modest increases in endogenous EPO compared with ESAs. Key Messages: Treatments that address ESA hyporesponse remain a significant unmet clinical need in patients with anemia of CKD. New therapies such as HIF-PH inhibitors have the potential to address fundamental aspects of ESA hyporesponse and provide a new therapeutic option in these patients.
Hypertension in CKD: Core Curriculum 2019 Ku, Elaine; Lee, Benjamin J.; Wei, Jenny ...
American journal of kidney diseases,
July 2019, 2019-07-00, 20190701, Letnik:
74, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Hypertension and chronic kidney disease (CKD) are closely interlinked pathophysiologic states, such that sustained hypertension can lead to worsening kidney function and progressive decline in kidney ...function can conversely lead to worsening blood pressure (BP) control. The pathophysiology of hypertension in CKD is complex and is a sequela of multiple factors, including reduced nephron mass, increased sodium retention and extracellular volume expansion, sympathetic nervous system overactivity, activation of hormones including the renin-angiotensin-aldosterone system, and endothelial dysfunction. Currently, the treatment target for patients with CKD is a clinic systolic BP < 130mm Hg. The main approaches to the management of hypertension in CKD include dietary salt restriction, initiation of treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and diuretic therapy. Uncontrolled hypertension can lead to significant cardiovascular morbidity and mortality and accelerate progression to end-stage kidney disease. Although intensive BP control has not been shown in clinical trials to slow the progression of CKD, intensive BP control reduces the risk for adverse cardiovascular outcomes and mortality in the CKD population.
Abstract In the US, approximately 11% of the population have diagnosed diabetes and nearly 40% have prediabetes. In addition, chronic kidney disease (CKD) affects 14% of the US population including ...up to 40% of those with diabetes. Cardiovascular disease (CVD) remains the leading cause of death worldwide where it affects approximately half of adults. The presence of CKD or diabetes doubles the risk of cardiovascular events. When both CKD and diabetes occur in the same patient the risks are further increased. The clinical problems of hypertension, hyperglycemia, and hyperlipidemia are all closely related with obesity, metabolic syndrome, Type 2 diabetes, CKD, atherosclerotic cardiovascular disease, heart failure and non‐alcoholic fatty liver disease and metabolic dysfunction‐associated steatohepatitis. The increasing frequency of obesity has driven increases in all of these medical comorbidities. These conditions frequently cluster together in the same patient exacerbating the risk of morbidity and mortality. They are also associated with cognitive dysfunction/dementia, pulmonary diseases, cancers, gastrointestinal diseases, immune system abnormalities, and inflammatory disorders. Only 6.8% of adults in US meet all targets for cardiovascular risk management with significant disparities based on race and ethnicity. Given the complexity of these multisystem problems in people with diabetes and obesity, it would seem reasonable to attempt to diagnose and treat many of the comorbidities earlier in the course of disease rather than wait for substantial end organ dysfunction to occur. The American Diabetes Association (ADA) has recently published a consensus statement recommending early screening for the diagnosis of heart failure, CKD and diabetes, recognizing both the frequency and gravity of this combination. Likewise, there are recommendations in the guidelines to facilitate screening for microalbuminuria, blood pressure, glycemic control and lipids earlier in patients at risk rather than wait and treat as a secondary prevention program. Thus, the general principle is to facilitate earlier recognition and diagnosis and provide treatment before downstream target organ complications occur. This review will focus on CVD and risk management based on newest recommendations and standards of care in people with diabetes by the ADA. The main considerations in the treatment of people with diabetes are glycemic control, blood pressure, lipids, and the use of medications with proven cardiorenal disease progression capability to prevent or delay.
To reduce the burden of cardiovascular disease (CVD), management strategies are increasingly focusing on preventive measures following early detection of markers of atherosclerosis. This review ...focuses on microalbuminuria, which is gaining recognition as a simple marker of an atherogenic milieu. Prospective and epidemiologic studies have found that microalbuminuria is predictive, independently of traditional risk factors, of all-cause and cardiovascular mortality and CVD events within groups of patients with diabetes or hypertension, and in the general population. The pathophysiologic mechanism underlying the association between albumin excretion and CVD is not fully defined. One hypothesis is that microalbuminuria may be a marker of CVD risk because it reflects subclinical vascular damage in the kidneys and other vascular beds. It may also signify systemic endothelial dysfunction that predisposes to future cardiovascular events. Based on this theory, periodic screening for microalbuminuria could allow early identification of vascular disease and help stratify overall cardiovascular risk, especially in patients with risk factors such as hypertension or diabetes. A positive test for urinary albumin excretion could signify the need for an intensive multifactorial intervention strategy, including behavior modification and targeted pharmacotherapy, aimed at preventing further renal deterioration and improving the overall CVD risk factor profile. Data from intervention studies suggest that treatment with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, statins, and/or strict glycemic control (in diabetics) offer significant reductions in cardiovascular and/or renal morbidity in patients with albuminuria. Use of this (old) marker may allow improved use of medications and strategies for secondary prevention.
CONTINUING MEDICAL EDUCATION LEARNING OBJECTIVES At the end of the activity, participants will be able to: * Identify the risks of kidney disease and their consequences in patients with type 2 ...diabetes (T2D). * Appropriately screen for the presence of chronic kidney disease (CKD) in patients with T2D. * Initiate evidence-based therapy to slow the progression of kidney disease in patients with T2D and CKD. * Describe the benefits and limitations of the steroidal and nonsteroidal mineralocorticoid receptor antagonists in the treatment of patients with DKD. KEY TAKEAWAYS * Diabetes is second only to hypertension as a cause of chronic kidney disease (CKD). * Urine albumin-to-creatinine ratio (UACR) is an independent and better predictor of cardiovascular mortality than estimated glomerular filtration rate (eGFR) across the full range of kidney function. * In patients with diabetic kidney disease (DKD), comprehensive treatment that includes achieving blood pressure, blood glucose, blood lipid, and body weight goals, as well as smoking cessation, is critical. * Treatment with a sodium-glucose cotransporter-2 inhibitor (SGLT-2i) should not be initiated in patients with an eGFR <60 mL/min/1.73 m.sup.2 (ertugliflozin), <45 mL/min/1.73 m.sup.2 (dapagliflozin or empagliflozin), or <30 mlVmin/1.73 m.sup.2 (canagliflozin). * The addition of an SGLT-2i (ie, canagliflozin, dapagliflozin, or empagliflozin) is recommended for patients with DKD who have inadequate glycemic control with metformin. * Finerenone is an nonsteroidal mineralocorticoid receptor antagonist shown to further improve kidney outcomes in patients with albuminuric DKD treated with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. * New treatment options for cardiovascular and renal protection are becoming available for use in combination with traditional medications for blood pressure, blood glucose, and blood lipid control. TARGET AUDIENCE Family physicians and clinicians who wish to gain increased knowledge and greater competency regarding primary care management of diabetic kidney disease. DISCLOSURES As a continuing medical education provider accredited by the Accreditation Council for Continuing Medical Education (ACCME), Primary Care Education Consortium (PCEC) requires any individual in a position to influence educational content to disclose any financial interest or other personal relationship with any commercial interest. This includes any entity producing, marketing, reselling, or distributing health care goods or services consumed by, or used on, patients. Mechanisms are in place to identify and mitigate any potential conflict of interest prior to the start of the activity. All relevant financial relationships have been mitigated. In addition, any discussion of off-label, experimental, or investigational use of drugs or devices will be disclosed by the faculty. Matthew Weir, MD, discloses that he serves as an advisor for Merck, AstraZeneca, Bayer, Janssen, Novo Nordisk, Boehringer Ingelheim, and Visor. Stephen Brunton, MD, editor, serves on the advisory board and speakers bureau for AstraZeneca, Bayer, and Novo Nordisk. He serves on the speakers bureau for Lilly and on the advisory board for Abbott Diabetes, Acadia, Sanofi, and Xeris. Gregory Scott, PharmD, editorial support, reports no conflicts of interest. SPONSORSHIP This article is sponsored by Primary Care Education Consortium, in collaboration with the Primary Care Metabolic Group. ACCREDITATION The Primary Care Education Consortium is accredited by the ACCME to provide continuing medical education for physicians. CREDIT DESIGNATION Primary Care Education Consortium designates this enduring material for a maximum of 1.0 AMA PRA Category 1 credits)TM. Physicians should claim only the credit commensurate with the extent of their participation in the activity. CME is available from August 1, 2021 to July 31, 2022. To receive CME credit, visit PAs AND NURSE PRACTITIONERS: AANP, ANCC, and AAPA accept certificates of participation from educational activities certified for AMA PRA Category 1 CreditTM from organizations accredited by ACCME. Visit FACULTY Matthew R. Weir, MD, Director of the Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland. ACKNOWLEDGMENT Editorial support was provided by Gregory Scott, PharmD, RPh, of the Primary Care Education Consortium. SUPPORTER This article is supported by an educational grant from Bayer Healthcare Pharmaceuticals Inc.
After reading this review article on ADPKD, participants should be able to: Identify people at high risk for ADPKD. Conduct a diagnostic evaluation. Initiate evidence-based therapy to slow kidney ...progression and treat extra-renal manifestations.
Hypertension is common, difficult to diagnose, and poorly controlled among patients with ESRD. However, controversy surrounds the diagnosis and treatment of hypertension. Here, we describe the ...diagnosis, epidemiology, and management of hypertension in dialysis patients, and examine the data sparking debate over appropriate methods for diagnosing and treating hypertension. Furthermore, we consider the issues uniquely related to hypertension in pediatric dialysis patients. Future clinical trials designed to clarify the controversial results discussed here should lead to the implementation of diagnostic and therapeutic techniques that improve long-term cardiovascular outcomes in patients with ESRD.
Inhibition of the renin-angiotensin-aldosterone system (RAAS) is a key strategy in treating hypertension and cardiovascular and renal diseases. However, RAAS inhibitors (angiotensin-converting enzyme ...inhibitors, angiotensin receptor blockers, aldosterone receptor antagonists, and direct renin inhibitors) increase the risk of hyperkalemia (serum potassium >5.5 mmol/L). This review evaluates the effects on serum potassium levels of RAAS inhibitors. Using PubMed, we searched for clinical trials published up to December 2008 assessing the effects on serum potassium levels of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, aldosterone receptor antagonists, and direct renin inhibitors, alone and in combination, in patients with hypertension, heart failure (HF), or chronic kidney disease (CKD); 39 studies were identified. In patients with hypertension without risk factors for hyperkalemia, the incidence of hyperkalemia with RAAS inhibitor monotherapy is low (< or =2%), whereas rates are higher with dual RAAS inhibition ( approximately 5%). The incidence of hyperkalemia is also increased in patients with HF or CKD (5% to 10%). However, increases in serum potassium levels are small ( approximately 0.1 to 0.3 mmol/L), and rates of study discontinuation due to hyperkalemia are low, even in high-risk patient groups (1% to 5%). Patients with HF or CKD are at greater risk of hyperkalemia with RAAS inhibitors than those without these conditions. However, the absolute changes in serum potassium are generally small and unlikely to be clinically significant. Moreover, these patients are likely to derive benefit from RAAS inhibition. Rather than denying them an effective treatment, electrolyte levels should be closely monitored in these patients.
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