Robert N. Foley MD
Chronic Disease Research Group, & School of Medicine, University of Minnesota Minneapolis, Minnesota USA

Summary: The public health importance of chronic kidney disease (CKD) has only become appreciated in the last decade.  While glomerular filtration rate (GFR) and urinary albumin creatinine levels are highly predictive of mortality, thresholds that may be useful for screening may be much closer to ‘normal’ than generally recognised. When optimising the balance between true negative and true positive mortality prediction, GFR from creatinine, from cystatin C and albumin creatinine ratios (ACR) all seem to perform similarly. Among the older population, mortality rates with creatinine based-GFR are lowest for those with levels between 60 and 90 mL/min/1.73 m2, unlike with GFR from cystatin C, where mortality rates climb monotonically with declining GFR. Thus, the validity of creatinine-based GFR in older community-dwelling individuals is questionable. Nationally-representative data suggest management of modifiable cardiovascular risk factors in adults with CKD is not optimal. This article explores the possibility that robust association between declining kidney function and cardiovascular outcomes could be caused by an unknown, confounding, shared-risk factor and extrapolates findings from renal transplant donor populations to support this hypothesis.

Key words: Epidemiology, Cardiovascular Disease, Chronic Kidney Disease

Ching-Yan Goh, MD^1,2 Claudio Ronco MD^1-3
1 Department of Nephrology, Ospedale San Bortolo, and
² Department of Nephrology, Selayang Hospital, Kuala Lumpur, Malaysia
³ International Renal Research Institute (IRRIV) Vicenza, Italy

Summary: “Cardio-Renal Syndromes” (CRS) are disorders of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other. The current definition has been expanded into five subtypes whose etymology reflects the primary and secondary pathology, the time-frame and simultaneous cardiac and renal co-dysfunction secondary to systemic disease: CRS type I: acute worsening of heart function (AHF-ACS) leading to kidney injury and/or dysfunction. CRS type II: chronic abnormalities in heart function (CHF-CHD) leading to kidney injury or dysfunction. CRS type III: acute worsening of kidney function (AKI) leading to heart injury and/or dysfunction. CRS type IV: chronic kidney disease (CKD) leading to heart injury, disease and/or dysfunction. CRS type V: systemic conditions leading to simultaneous injury and/or dysfunction of heart and kidney. These different subtypes may have a different pathophysiological mechanism and they may represent separate entities in terms of prevention and therapy.

Key words: acute kidney injury, acute heart failure, chronic kidney disease, cardio-renal syndrome, reno-cardiac syndrome, heart-kidney interaction, cardiovascular risk.

Kevin Damman1 MD, PhD, Paul R. Kalra2 MD, FRCP, Hans Hillege1 MD, PhD.
1 Department of Cardiology, University Medical Center, Groningen, University of Groningen,The Netherlands.
2 Department of Cardiology, Portsmouth Hospitals NHS Trust, Portsmouth. UK

Summary: Renal dysfunction is extremely common in patients with chronic heart failure (CHF). Although the pathogenesis of reduced glomerular filtration rate (GFR) may differ between patients and even over time within an individual, the result is the same:reduced GFR is strongly related to increased mortality and morbidity. Potential explanations for the renal impairment include shared aetiological risk factors, such as atherosclerosis, hypertension, endothelial dysfunction and inflammation. Furthermore, a complex series of pathophysiological interactions exists between these two organ systems; an abnormality in one system will in general adversely impact on the other, resulting in a vicious cycle of disease progression. Improved understanding of the aetiology of reduced GFR in patients with CHF is fundamental to identifying appropriate therapies. Whilst reduced cardiac output and thereby renal perfusion is undoubtedly important, other factors, such as increased central venous pressure and anaemia may be amenable to therapeutic intervention.

Key words Cardiorenal • Chronic kidney disease • Heart failure

David Lewis1,2   Richard Haynes1,2   Martin J Landray1
1Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford,
2Oxford Kidney Unit, Churchill Hospital, Oxford, UK

Summary: Patients with chronic kidney disease (CKD) develop premature cardiovascular disease. In the general population (without CKD) there are strong associations between cholesterol fractions and the risk of coronary disease and a weaker association with stroke. Randomised trials in the general population convincingly demonstrate that lowering blood cholesterol (chiefly with a “statin”) reduces the risk of vascular events.
Patients with CKD differ significantly from the general population: They have markedly disturbed lipid metabolism which manifests as elevated triglyceride concentrations, reduced HDL cholesterol concentrations and a preponderance of small, dense LDL particles which are potentially more atherogenic; the observational association between lipids and vascular disease is bizarre, and is confounded by comorbidity; and the nature of the vascular disease appears less strongly associated with classical atherosclerosis. Randomised trials are required to determine the relevance of blood lipids to the development of vascular disease in patients with CKD, but to date the results of such studies are inconclusive and an effect on atherosclerotic events cannot be excluded.
Patients with CKD are also at risk of end-stage renal disease. There is some evidence that lipids are involved in the progression of renal disease and modifying them may delay the progression of CKD. However, the current data is based on effects on markers of progression (e.g. proteinuria). The ongoing SHARP (Study of Heart and Renal Protection) trial should provide reliable information about both the effects of statins on vascular and renal risk.

Keywords: Chronic kidney disease, lipid, cholesterol, cardiovascular disease, statins

Irene M. van der Meer, MD, PhD,1,2  Piero Ruggenenti, MD,1,3 Giuseppe Remuzzi, MD, FRCP1,3
1Unit of Nephrology, Azienda Ospedaliera Ospedali Riuniti di Bergamo, Bergamo, Italy. 3Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
2Department of Internal Medicine, Division of Nephrology, University Hospital Maastricht, The Netherlands.

Summary: The diabetic patient with chronic kidney disease (CKD) is at very high risk of cardiovascular disease (CVD). Primary and secondary CVD prevention is of major importance and should be targeted at traditional cardiovascular risk factors and risk factors specific for patients with CKD. In patients on renal replacement therapy, the association between traditional CVD risk factors and the incidence of CVD may be reversed, and pharmaceutical interventions that benefit the general population may be ineffective or even harmful in this high-risk population.
The World Health Organisation has estimated that 366 million people will be affected worldwide in 2030.The major part is accounted for by diabetes mellitus type 2 (T2DM). The prevalence of diabetes mellitus type 1 (T1DM) is also increasing: for children. The prevalence of diabetic complications, such as cardiovascular disease (CVD), renal disease, retinopathy, and neuropathy will rise steeply. Because diabetic patients constitute a large proportion of patients requiring nephrological care, this review addresses the specific issues involved in the prevention and treatment of CVD and CVD risk factors in CKD patients with diabetes.

Key words: chronic kidney disease, cardiovascular, diabetic, haemodialysis, proteinuria

Aghogho Odudu1, MBChB, MRCP, Chris McIntyre1,2, MBBS, MRCP, DM
1Department of Renal Medicine, Royal Derby Hospital, Derby, UK
2School of Graduate Entry Medicine and Health, University of Nottingham, UK.

Summary: It is well recognised that dialysis patients suffer excess morbidity and mortality and that this is mainly due to cardiac failure and sudden cardiac death rather than conventional risk factors.  Dialysis patients are primed by a number of structural, functional, and microcirculatory abnormalities to experience demand myocardial ischaemia. We have shown that haemodialysis induces repetitive myocardial ischaemia in the majority of patients.  In this way, haemodialysis itself may contribute to the development of heart failure and the risk of sudden death. There is recent appreciation that peritoneal dialysis is also capable of exerting short term effects on cardiovascular performance through both mutual and exclusive mechanisms to haemodialysis.  The aim of this article is to give an appreciation of the possibility that modification of the dialysis procedure is capable of improving treatment tolerability and has the potential to reduce the excessive rates of cardiovascular morbidity and mortality.

Keywords: Baroreflex sensitivity · Cardiovascular complications ·  Chronic kidney disease · Haemodialysis · Heart failure · Myocardial stunning · Peritoneal dialysis.

Darren Green1 MRCP, Paul R Roberts 2 MD. FRCP.
1Clinical Research Fellow, Department of Renal Medicine, Salford Royal Hospital. Manchcester UK.
2Consultant Cardiologist, Southampton University Hospital, SO16 6YD

Summary: One in four dialysis patients will die suddenly. Most do not fall into the high risk categories that are associated with sudden death in the general population. The cause of sudden death in the dialysis population is unknown. It may be related to factors associated with chronic kidney disease itself e.g. inflammation, vascular stiffness, left ventricular hypertrophy, coronary artery disease, electrolyte/fluid abnormalities or autonomic dysfunction. Studies of patients with implantable cardioverter defibrillators (ICDs) have shown that patients with chronic kidney disease (CKD) are more likely to use their devices for ventricular arrhythmias but in spite of this still have a high associated mortality. Until a comprehensive risk stratification strategy is understood, minimising risk by good control of basic parameters such as fluid balance, electrolytes and blood pressure, along with careful assessment of all patients for evidence of coronary artery disease and heart failure is the mainstay of management of the CKD patient.

Keywords:  Sudden Cardiac Death, Chronic Kidney Disease, Dialysis, Arrhythmia

Helen Eddington MBChB. MRCP.   Prof Philip A Kalra MA. MB Bhir. FRCP. MD.
Salford Royal Foundation NHS Trust, Vascular research Group, Salford

Summary: Chronic Kidney Disease – Mineral Bone Disorder (CKD-MBD) is a multifaceted characterisation used to help describe the systemic derangement of mineral bone metabolism in renal disease, which was previously referred to, rather simplistically, as ‘renal osteodystrophy’ or ‘renal bone disease’. In this review we will try and show the evidence relating these factors to cardiovascular morbidity and mortality and give some evidence as to the mechanisms for this. The treatments used for this condition are also integral to the increased cardiovascular mortality seen in renal patients and a summary of these effects will also be covered.

Keywords: Chronic Kidney Disease, Bone Disease, Cardiovascular, Mineral metabolism

Dr Rajan Sharma BSC MD MRCP.
Department of Cardiology, Ealing Hospital NHS Trust, London, U.K.

Summary: Cardiovascular disease (CVD) remains the major cause of mortality and morbidity in patients with advanced chronic kidney disease (CKD) and after renal transplantation. The mechanisms for cardiotoxicity are multiple. Identifying high - risk patients remains a challenge. Given the poor long term outcome of dialysis patients who do not receive renal transplantation and the lower supply of donor kidneys relative to demand, optimal selection of renal transplantation candidates is crucial. This requires a clear understanding of the validity of cardiac tests in this patient group. This article explores the strengths and weaknesses of currently available diagnostic tools in patients with advanced CKD. Echocardiography is very useful for the detection of cardiomyopathy and prognosis. Stress echocardiography, myocardial perfusion imaging and coronary angiography are the best tools for the assessment of coronary artery disease. All predict outcome. No single gold standard investigation exists. At present, there is not an optimal technique for predicting sudden cardiac death in this patient group. Ultimately, the choice of cardiac test will always be determined by patient preference, local expertise and availability. 

Key words: End stage renal disease, cardiovascular disease, mortality, coronary artery disease, uraemic cardiomyopathy, renal transplantation

Debbie Sutton1, BSc RD. Fiona Symes2, BSc (Hons) RD
1Renal Research Dietitian Portsmouth Hosiptal, 2Derby City General Hospital

Summary: Increased collaboration between the vascular specialities is clearly leading to increased understanding of the inter-relationships between the different disease states and how each impacts and influences the others. This advantage will be reflected in improved patient care if the practical outworking of this growing knowledge is carefully implemented at service level.
This article outlines how the aspects of diet and lifestyle associated with vascular related disease, complement, contrast and in some cases contradict each other. It gives information and guidelines as to how the expertise of dietitians working in the different specialist areas might usefully be shared to be of maximum advantage to all patients.

Key words Chronic kidney disease • Education • Nutrition/malnutrition

Donald S. Silverberg1 MD FRCP,  Dov Wexler2 MD,  Adrian Iaina1 MD, Doron Schwartz1, MD.
1 Department of Nephrology, 2 Department of Cardiology and Heart Failure, Tel Aviv Medical Center, Tel Aviv, Israel.

Summary: Anaemia is common in Congestive Heart Failure and associated with increased mortality, morbidity and progressive renal failure. The common causes of anaemia are the associated renal failure and excessive cytokine production, both of which can cause depression of the erythropoietin production in kidney and depression of erythropoietin response in bone marrow. The cytokines induce iron deficiency by increasing hepcidin production from the liver, which reduces gastrointestinal iron absorption and iron release from iron stores located in the macrophages and hepatocytes. Attempts to control this anaemia have to consider the use of Erythropoiesis Stimulating Agents (ESA) also oral and, probably more importantly, intravenous (IV) iron.  Studies of anaemia with ESA and oral, or IV iron and with IV iron alone have shown a positive effect on hospitalisation, and other factors in cardiac and renal function, Quality of Life, and reduced Beta Natriuretic Peptide and have not demonstrated an increase in cardiovascular damage. Some studies and meta-analyses revealed improvement in these parameters others have not.  Adequately-powered long-term placebo-controlled studies of ESA and of IV iron in CHF are still needed.

Key words : Anaemia, Chronic Kidney Disease, Cardiovascular, Erythropoiesis-Stimulating Agents.

Charles J Ferro MD1.   David Benavente MD1,Colin D Chue MRCP2.
Departments of Nephrology1 and Cardiology2 University of Birmingham and University Hospital Birmingham. UK

Summary. The existence of the renin-angiotensin-aldosterone system was first postulated over 100 years ago. Following the identification of all the major components, came the discovery of their potential pathogenicity in cardiovascular and renal disease. The introduction of drugs that inhibit the synthesis or actions of this system has prompted a number of trials that have largely shaped how cardiovascular and renal disease is managed today. The continued discovery of yet more components of this system promises to further our understanding of its influence on disease processes and herald the development of more highly selective drugs, ensuring that the renin-angiotensin-aldosterone system will continue to be a key area of interest for many years to come.

Keywords: cardiovascular disease, kidney disease, renin-angiotensin-aldosterone system

Mike Seddon MRCP MD and Nick Curzen PhD FRCP
Wessex Cardiac Unit, Southampton University Hospitals, Southampton. UK

Summary: Chronic Kidney Disease (CKD) is associated with a high burden of coronary artery disease, myocardial infarction and cardiovascular death. Detection and treatment of coronary artery disease in CKD patients has been hampered by the limitations of screening tests, the lack of direct evidence for therapeutic interventions in this specific population, and concerns about therapy-related adverse effects. However, these patients potentially have much to gain from conventional strategies used in the general population. This review summarises the current evidence regarding the treatment of coronary artery disease in patients with CKD, with the focus on coronary revascularisation by percutaneous coronary intervention or coronary artery bypass grafting.

Key words: Coronary, revascularisation, chronic, kidney.

Mike Seddon MRCP MD and Nick Curzen PhD FRCP
Wessex Cardiac Unit, Southampton University Hospitals, Southampton. UK

Summary: Chronic Kidney Disease is associated with a high burden of coronary artery disease, myocardial infarction and cardiovascular death. Management of patients with CKD presenting with acute coronary syndromes is more complex than in the general population, due to greater diagnostic uncertainty and the lack of direct evidence for therapeutic interventions in this specific population, coupled with concerns about therapy-related adverse effects. However, these patients potentially have much to gain from conventional revascularisation strategies used in the general population. This review summarises the current evidence regarding the treatment of patients with CKD presenting with acute coronary syndromes, in particular with respect to coronary revascularisation strategies.

Key words: Coronary, revascularisation, chronic, kidney.

Karen Jenkins RN, PG Dip HE, MSc. Renal Nurse Consultant. Honorary Lecturer University of Kent. Kent Kidney Care Centre.
Mary Kirk, RN, MSc Cardiology. Cardiology Nurse Consultant .Honorary Lecturer University of Kent.

Summary: Renal impairment may be evident at any stage of heart failure (CHF). Up to 30% of patients with heart failure have abnormal renal function (Geisberg and Butler 2006). Chronic kidney disease (CKD) can be a complication of heart failure and chronic heart disease can be a consequence of CKD. Members of the multidisciplinary team such as nurses, dieticians and physiotherapists should be encouraged to maximise their knowledge and skills across disease areas to influence and improve outcomes of those with CKD and CHF. In particular management of fluid balance, blood pressure control/monitoring, discussion of blood results and reduction of cardiovascular risk factors. Close monitoring and effective management of modifiable cardiac risk factors such as diabetes and hypertension can reduce onset and slow progression of CKD. This can be done by applying the key principles of good practice such as communication between healthcare professionals, patient education and empowerment alongside early identification and management of symptoms of CKD and CHF.

Key words: Heart Failure, Chronic Kidney Disease, Cardio renal syndrome Risk Management.

Emily P McQuarrie1 BSc, MB, ChB, MRCP; Bengt C Fellström2 MD, PhD;
Hallvard Holdaas3 MD, PhD; Alan G Jardine1 BSc, MD, FRCP.
1Renal Research Group, University of Glasgow, UK, 2Dept. of Nephrology, University of Uppsala, Sweden.  3Dept. of Nephrology, University of Oslo, Norway.
 
Summary:  Renal transplant recipients have a marked increased risk of premature cardiovascular disease compared with the general population, although considerably lower than that of patients receiving maintenance haemodialysis. Currently, a successful renal transplant is the most effective way of reducing the incidence of cardiovascular disease and cardiovascular mortality in patients with end-stage renal disease. Cardiovascular disease in transplant recipients is poorly characterised and differs from the non-renal population. In this short review, we highlight three points: (1) how the natural history of Cardiovascular disease in renal transplant recipients differs from the general population; (2) that understanding the relationship between individual risk factors and specific cardiovascular events is vital to manage cardiovascular disease in Renal transplant recipients and (3) that transplant recipients carry with them multiple risk factors accumulated during progressive kidney disease and dialysis. Multiple risk factor intervention is required and much of the risk factor baggage may be irreversible. The time to address potential cardiovascular complications of renal transplantation is at the time the patient first presents with progressive renal disease.

Key words: Cardiovascular, Dialysis, Hypertension, Lipids, Mortality, Myocardial infarction, Transplant, Uraemic cardiomyopathy.

Constantina Chrysochou  MBChB. MRCP.  Philip A Kalra MA. MB Bhir. FRCP. MD.
Renal Department, Salford Royal Hospital. Salford UK

Summary: The detrimental link between cardiac and renal pathophysiology in atherosclerotic renovascular disease (ARVD) is well described. Patients with ARVD usually have significant atherosclerotic disease in other vascular beds including the coronary circulation, and structural and functional cardiac changes are highly prevalent. This excess cardiovascular burden likely contributes to the increased cardiac morbidity and mortality seen in these patients.
In this review we describe the associations of cardiovascular disease and ARVD and treatment thereof. The clinical debate of which patients are offered any additional advantage by revascularisation over medications alone remains to be answered. The close link between cardiac and renal pathophysiology in ARVD raises the possibility that renal revascularisation might confer a benefit to cardiac morphology and function. This is the subject of ongoing randomised controlled trials.

Key Words:  Atherosclerotic renovascular disease. Cardiovascular disease. Chronic Kidney Failure.  Cardiac Failure

Gobnait Byrne1 BSc RN  & Fiona Murphy2 BSc RN
1Trinity College Dublin –Lecturer. School of Nursing & Midwifery Studies
2PhD Candidate Trinity College, Senior lecturer, School of Nursing & Midwifery Studies.

Summary :Cardiac Rehabilitation programmes are an integrated part of the total care of the patient and are delivered by a multidisciplinary team. Cardiac Rehabilitation is usually organised in four phases and has shown to reduce the morbidly and mortality associated with cardiac disease.  Chronic Kidney Disease patients who are at risk of, or already have, Cardiovascular Disease should be monitored, educated and managed through close working relationships between the renal and cardiac multidisciplinary teams. One mechanism by which this may be achieved is through the use of cardiac rehabilitation programmes.

Key Words: Cardiac Rehabilitation, Cardiovascular Disease, Chronic Kidney Disease.

Daniel Teta, MD, PhD
Department of Nephrology, University Hospital (CHUV), Lausanne, Switzerland

Summary. Obesity has adverse consequences in the general population. In patients with chronic kidney disease (CKD), it is associated with increased inflammation, insulin resistance, hypertension, and dyslipidaemia, which are important risk factors CKD progression and death. In adults with CKD stages 1 to 4, weight loss should be encouraged since it reduces proteinuria and glomerular hyperfiltration, which are frequent in obese patients. Proposals for modifications of lifestyle, physical activity and calorie restriction are the first measures. Pharmacological treatments are generally unsafe in these patients, except orlistat, but that has modest efficacy. Bariatric surgery may be the only option in severe obesity, if all other measures fail.
For obese patients on dialysis treatment, eligible for kidney transplantation, weight loss is mandatory to prevent obesity-related surgical complications and improve patient and graft survival after transplantation. Interventions should emphasise exercise to increase muscle mass, and calorie but not protein restriction. Bariatric surgery must be carried out by experienced surgeons due to high risk of complications. For obese patients, not transplant candidates, loosing weight may be proposed since benefits of weight loss remain uncertain.

Key Words : Chronic Kidney Disease • Cardiovascular Risk • Obese • Weight Loss