Books on the topic 'End stage renal failure; cardiovascular imaging'

Cardiovascular complications are the predominant cause of death in patients with end-stage renal disease (ESRD). The high incidence of cardiovascular complications results from pathology present before ESRD (generalized atherosclerosis, diabetes, hypertension) and an additive effect of multiple factors including haemodynamic overload and metabolic and endocrine abnormalities more or less specific to uraemia or its treatment modalities. These disorders are usually associated and can exacerbate each other. While ischaemic heart disease is a frequent cause of cardiac death, heart failure and sudden death are the most frequent causes of death in ESRD. Cardiomyopathy of overload with development of left ventricular hypertrophy and fibrosis are the most characteristic alterations and major determinants of prognosis. Left ventricular hypertrophy may result in systolic and/or diastolic dysfunction and is a risk factor for arrhythmias, sudden death, heart failure, and myocardial ischaemia. Arterial disease, whether due to atherosclerosis or arteriosclerosis (or both), represents a major contributory factor to the cardiovascular complications. Arterial disease may result in ischaemic complications (ischaemic heart disease, peripheral artery diseases) or arterial stiffening with direct consequences on left ventricular afterload, decreased coronary perfusion, and microvascular abnormalities (inward remodelling and microvessel rarefaction).

The incidence of chronic kidney disease (CKD) and end-stage kidney disease (ESKD) is increasing, reflecting an increase in the incidence and prevalence of hypertension and type 2 diabetes. Patients with CKD and ESKD frequently experience episodes of critical illness and require treatment in an intensive care unit (ICU)setting. Management requires specific consideration of their renal disease status together with their acute illness. Mortality in critically-ill patients with ESKD is frequently related to their co-morbid conditions, rather than their ESKD status. Illness severity scoring systems allocate high points for renal variables and tend to overestimate actual mortality. Patients with ESKD and CKD requiring ICU admission have better ICU and in-hospital survival than patients with denovo acute kidney injury requiring renal replacement therapy. Appropriately selected patients benefit from ICU admission and full consideration for ICU care should be given to these patients if required, despite their renal disease status. Cardiovascular disease and sepsis account for the majority of ICU admissions in this population and the aetiology of these conditions differs from that in patients without kidney disease. Optimal critical care management of patients with ESKD and CKD requires that these differences are recognized.

Cardiovascular disease is highly prevalent in patients with chronic kidney disease (CKD) and is the biggest contributor of death in these patients. Myocardial perfusion imaging (MPI) is a validated tool for diagnosing coronary artery disease (CAD) and for predicting short and long term prognosis in this patient population. Non-invasive stress imaging, with MPI or other imaging modalities, is widely used for risk stratification in patients with end-stage renal disease (ESRD) being evaluated for kidney transplantation due to the paucity of donor organs and the high cardiovascular risk of patients on the transplant waiting list. In this Chapter we will review the data on diagnostic accuracy and risk stratification using MPI in patients with CKD and ESRD highlighting the special challenges that are unique to this population. We will also discuss novel indicators that have been used in these patients to improve risk stratification.

The goals of treatment in renal vasculitis are to stop vasculitic activity and recover renal function. Subsequent strategies are required to prevent vasculitis returning and to address longer-term co-morbidities caused by tissue damage, drug toxicity, and increased cardiovascular and malignancy risk.Cyclophosphamide and high-dose glucocorticoids remain the standard induction therapy with alternative immunosuppressives, such as azathioprine, to prevent relapse. Plasma exchange improves renal recovery in severe presentations. Refractory disease resulting from a failure of induction or remission maintenance therapy requires alternative agents and rituximab has been particularly effective. Replacement of cyclophosphamide by rituximab for remission induction is supported by recent evidence. Methotrexate is effective in non-renal vasculitis but difficult to use in patients with renal impairment. Mycophenolate mofetil seems to be effective but there is less long-term evidence.Drug toxicity contributes to co-morbidity and mortality and has led to newer regimens with reduced cyclophosphamide exposure. Glucocorticoid toxicity remains a major problem with controversy over the rapidity with which glucocorticoids can be reduced or withdrawn.Disease relapse occurs in about 50% of patients. Early detection is less likely to lead to an adverse affect on outcomes. Rates of cardiovascular disease and malignancy are higher than in control populations but strategies to reduce their risk, apart from cyclophosphamide-sparing regimens, have not been developed. Thromboembolic events occur in 10% and may be linked to the recently identified autoantibodies to plasminogen and tissue plasminogen activator.Renal impairment at diagnosis is a strong predictor of patient survival and renal outcome. Other predictors include patient age, antineutrophil cytoplasmic antibody subtype, disease extent and response to therapy. Chronic kidney disease can stabilize for many years but the risks of end-stage renal disease are increased by acute kidney injury at presentation or renal relapse. Renal transplantation is successful with similar outcomes to other causes of end-stage renal disease.

Management of hypertension is dependent on the underlying cause and the magnitude of the blood pressure abnormality. Healthy behavioural changes are the primary management tool for treating primary hypertension in adolescents and other cardiovascular risk factors and obesity. In children and adolescents with renal hypertension, high blood pressure requires pharmacological treatment. There is randomized controlled trial evidence to support a blood pressure target for those with proteinuria of not higher than the 50th centile for age. The use of angiotensin-converting enzyme inhibitors is safe in patients with proteinuria, and assumed to be equally beneficial. For those without proteinuria, less stringent targets may be acceptable. Often a combination of two or three drugs is required to lower arterial blood pressure to the target blood pressures. In children and adolescents at or near end-stage renal failure, fluid removal by dialysis may be necessary to control hypertension.

Ciliopathies encompass a genotypically complex and phenotypically variable and overlapping series of disorders that makes the general term ‘ciliopathies’ very useful. The genes behind these conditions encode parts of the machinery of the primary cilium. This is also true of the major cystic kidney disorders autosomal dominant polycystic kidney disease and autosomal recessive polycystic kidney disease, but the ‘long tails’ of other ciliopathies are characterized by variable nephropathy (often without cyst formation), retinopathy, and effects on brain and skeletal development. Not all have substantial renal phenotypes. Bardet–Biedl syndrome (BBS) is an autosomal dominant condition characterized by obesity, retinopathy, nephropathy, and learning difficulty, but renal abnormalities are varied and end-stage renal failure occurs in only a minority. Many BBS genes have been described. Alström syndrome is a rare recessive disorder again associated with obesity and retinopathy, but also deafness and dilated cardiomyopathy. Renal failure is a common but later feature. Joubert syndrome is an autosomal dominant condition but can arise from mutations in at least 10 genes. It has a wide phenotypic variation with a common link being hypodysplasia of the cerebellar vermis and other abnormalities giving rise to the ‘molar tooth sign’ on cerebral magnetic resonance imaging scanning, associated with hypotonia in infancy, central ataxia, ocular apraxia, developmental delay, and varying degrees of cognitive impairment. Jeune syndrome is a recessive condition characterized by osteochondrodysplasia which can give rise to hypodevelopment of the chest wall known as suffocating thoracic dystrophy, in addition to other manifestations.

Autosomal dominant polycystic kidney disease (ADPKD) is responsible for up to 10% of prevalent patients with end-stage renal disease (ESRD). It is characterized by the enlargement of multiple bilateral renal cysts, present in almost all patients by their fifth decade. Loin pain is a common symptom that may be caused by cyst growth, intracyst haemorrhage, nephrolithiasis, or infection. Gross haematuria is also a common feature, but usually settles spontaneously. Excretory impairment develops after extensive cystic change has occurred and progresses to ESRD in half of all affected patients by the age of 60. However, the onset of cystic change and rate of renal functional decline are highly variable between individuals. ADPKD associated with the PKD1 gene has an earlier average age of cyst development and ESRD than PKD2, but the two cannot be distinguished on clinical grounds. Polycystins 1 and 2 are expressed in various organs and extrarenal disease may be the presenting feature. Intracranial aneurysms are five times more common in patients with ADPKD, but rupture is infrequent. Liver cysts are present in most patients and may be complicated by haemorrhage or infection, though liver failure is very rare. Massive hepatic cystic disease is confined to women, reflecting stimulatory effects of oestrogen on hepatic cyst growth. Cardiovascular disease is the leading cause of death in ADPKD and vascular dysfunction is present in many patients even before the development of excretory impairment. However, despite the multisystem manifestations of ADPKD, survival from ESRD is better for patients with ADPKD than for other non-diabetic causes of kidney failure.

Malignant hypertension (MH) is recognized clinically by elevated blood pressure together with retinal haemorrhages or exudates with or without papilloedema (grades III or IV hypertensive retinopathy); and may constitute a hypertensive emergency or crisis when complicated by evidence of end-organ damage including microangiopathic haemolysis, encephalopathy, left ventricular failure, and renal failure. Though reversible, it remains a significant cause of end-stage renal failure, and of cardiovascular and cerebrovascular morbidity and mortality in developing countries.MH can complicate pre-existing hypertension arising from diverse aetiologies, but most commonly develops from essential hypertension. The absolute level of blood pressure appears not to be critical to the development of MH, but the rate of rise of blood pressure may well be relevant in the pathogenesis. The pathogenesis of this transformation remains unclear.The pathological hallmark of MH is the presence of fibrinoid necrosis (medial vascular smooth muscle cell necrosis and fibrin deposition within the intima) involving the resistance arterioles in many organs. Fibrinoid necrosis is not specific to MH and this appearance is seen in other conditions causing a thrombotic microangiopathy such as haemolytic uraemic syndrome, scleroderma renal crisis, antiphospholipid syndrome, and acute vascular rejection post transplant. MH can both cause a thrombotic microangiopathy (TMA) but can also complicate underlying conditions associated with TMA.The pathophysiological factors that interact to generate and sustain this condition remain poorly understood. Risk factors include Afro-Caribbean race, smoking history, younger age of onset of hypertension, previous pregnancy, and untreated hypertension associated with non-compliance or cessation of antihypertensive therapy.Evidence from clinical studies and animal models point to a central role for the intrarenal renin–angiotensin system (RAS) in MH; there is good evidence for renal vasoconstriction and activation of the renal paracrine RAS potentiating MH once established; however, there may also be a role in the predisposition of MH suggested by presence of increased risk conferred by an ACE gene polymorphism in humans and polymorphisms for both ACE and AT1 receptor in an animal model of spontaneous MH. Other vasoactive mediators such as the endothelin and the inflammatory response may be important contributing to and increasing endothelial damage. There have been no randomized controlled trials to define the best treatment approach, but progressive lowering of pressures over days is considered safest unless made more urgent by critical clinical state. It seems logical to introduce ACE inhibition cautiously and early, but in view of the risk of rapid pressure lowering some recommend delay.

The risk of developing cardiovascular (CV) disease is increased in patients with chronic kidney disease (CKD) and although dyslipidaemia is a major contributory factor to the development of premature CV disease, the relationship is complex. Changes in lipid fractions are related to glomerular filtration rate and the presence and severity of proteinuria, diabetes, and other confounding factors. The spectrum of CV disease changes from lipid-dependent, atheromatous coronary disease in early CKD to lipid-independent, non-coronary disease, manifesting as heart failure, and sudden cardiac death in advanced and end-stage renal disease. Statin-based lipid-lowering therapy is proven to reduce coronary events across the spectrum of CKD. The relative reduction in overall CV events, however, diminishes as CKD progresses and the proportion of lipid-dependent coronary events declines. There is nevertheless a strong argument for the use of statin-based therapy across the spectrum of CKD. The argument is particularly strong for those patients with progressive renal disease who will eventually require transplantation, in whom preventive therapy should start as early as possible. The SHARP study established the benefits and endorses the use of lipid-lowering therapy in CKD 3-4 but uncertainty about the value of initiation of statin therapy in CKD 5 remains. There is, however, no rationale for stopping agents started earlier in the course of the illness for compelling indications, particularly in those who will ultimately be transplanted. The place of high-density lipoprotein-cholesterol raising and triglyceride lowering therapy needs to be assessed in trials. Modifying dyslipidaemia in CKD has demonstrated that lipid-dependent atheromatous cardiovascular disease is only one component of the burden of CV disease in CKD patients, that this is proportionately less in advanced CKD, and that modification of lipid profiles is only one part of CV risk management.

Management of patients with autosomal dominant polycystic kidney disease (ADPKD) currently comprises non-specific measures including promotion of healthy lifestyle, optimization of blood pressure control, and modification of cardiovascular risk factors. A high water intake of 3–4 L per day in patients with glomerular filtration rate greater than 30 mL/min/1.73 m2 may decrease the risk of kidney stones, but its potential benefit in reducing renal cyst growth is presently unproven. Maintenance of a target blood pressure of 130/80 mmHg is recommended by expert clinical guidelines though this is unlikely to slow cyst growth. It is unclear whether pharmacological blockade of the renin–angiotensin axis confers an extrarenal protective effect. Recognition of the variable clinical presentations of cyst infection, cyst haemorrhage, or nephrolithiasis is important for early diagnosis and optimal management of these complications. Most patients with ADPKD do well on dialysis and after transplantation. Nephrectomy may be needed to make space for a donor kidney, or if kidney size or infection is an issue after end-stage renal failure is reached. Recent advances in ADPKD have led to the identification of multiple potential therapeutic targets with more than 10 clinical trials completed or currently in progress. Given the promising results of the TEMPO trial, tolvaptan may well be the first disease-modifying drug to be approved for clinical use. Several other classes of drugs (e.g. somatostatin analogues, triptolide, metformin, and glucosylceramide synthase inhibitors) with good long-term safety profiles are promising candidates which may be repurposed for this disease. In the future, identifying patients with different risks of renal disease progression by their genotype and/or kidney volume will likely assume an important role for the clinical management of ADPKD.

In less than two decades, AIDS has been transformed from a rapidly fatal, untreatable illness to a manageable chronic disease. Early in the AIDS epidemic, HIV care and palliative care were inseparable; over time, these two treatment paradigms diverged. In the developed world, and to a lesser but increasing extent in the developing world, decreasing mortality rates have resulted in growing numbers of HIV-infected patients living with the disease for many years. As this long-surviving population increases, the challenges of chronic disease management, an expanding range of co-morbidities, and a process that has been described as ‘accelerated ageing’, have all emerged to present new needs and opportunities for palliative care expertise. Earlier in the epidemic, palliative care for AIDS focused primarily on end-of-life care and pain and symptom management related to the manifestations of AIDS-specific opportunistic infections and malignancies. Currently, pain and symptoms may be related to these as well as other co-morbid chronic diseases which commonly occur in HIV-infected patients, including cardiovascular, pulmonary, renal, hepatic, metabolic, and neurocognitive complications. Attention to these symptoms, quality of life issues, and psychosocial problems in long-surviving patients over many years will be increasingly important to support engagement with care and effective adherence with antiretroviral therapy over time. End-of-life care, while less frequent, also remains important, as patients may still die from AIDS, or even more commonly, from end-organ failure, non-AIDS defining malignancies, and/or other complications of ageing and chronic co-morbid disease. All these converging factors have now resulted in a new need for the re-integration of HIV care and palliative care, both to help HIV-infected patients live better and longer, as well as manage late-stage and end-of-life issues when they emerge.