bluuebunny/crossref_metadata_2025 huggingface dataset:
Nosocomial pneumonia
Authors: Lim Wei Shen
Published: February 2020

Nosocomial pneumonia is generally defined as a new pulmonary infiltrate on chest radiography, combined with evidence of infection expressed as fever, purulent respiratory secretions, and/or leucocytosis, with onset 48 hours or more after admission. It is the most frequent lethal nosocomial infection (overall mortality 7% in general ward inpatients to over 50% in critically ill patients). Most cases are caused by Gram-negative bacteria (50–70%) or Staphylococcus aureus (15–30%). Gram-negative bacteria reach the lung by aspiration of gastric contents or by microaspiration of upper airway secretions; throat cultures reveal that 60–75% of patients on intensive care units are colonized by these organisms (compared to 2–6% of healthy people).
Pulmonary complications of HIV infection
Authors: Choy Julia , Pozniak Anton
Published: February 2020

Most HIV-positive individuals will experience at least one significant episode of pulmonary disease during their lifetime. The immune status of the HIV-infected patient is the primary determinant of the risk of developing specific pulmonary diseases: those with advanced immunosuppression are predisposed to opportunistic infections and malignancies; those with mild or no immunosuppression are at greater risk of conditions including community-acquired pneumonia, chronic obstructive pulmonary disease, pulmonary hypertension, and interstitial lung disease. Pulmonary infections related to HIV infection with severe immunosuppression include Pneumocystis jirovecii pneumonia, tuberculosis, and fungal infections including aspergillosis and cryptococcosis. Lung malignancies related to HIV infection with severe immunosuppression include Kaposi’s sarcoma and lymphoma, which is typically non-Hodgkin’s B-cell lymphoma or primary effusion lymphoma (also caused by HHV-8).
Sleep-related breathing disorders
Authors: Morrell Mary J. , Kelly Julia , McMillan Alison , Hind Matthew
Published: February 2020

Obstructive sleep apnoea and other sleep-related breathing problems significantly impair the functioning of about 0.5–1% of the population. Obstructive sleep apnoea in adults is usually caused by obesity and fat deposits in the neck area (typically collar size of 17 inches (43 cm) or more), when the withdrawal of postural muscle tone during sleep allows the pharyngeal dilators to be overwhelmed, leading to excessive narrowing or collapse of the airway, with consequent apnoea and sleep fragmentation. Mild symptoms may resolve with lifestyle changes such as losing weight; learning to sleep on the side and avoiding sleeping on the back; no alcohol after 18.00 h; no sedatives; stopping smoking; keeping the nose as clear as possible. There is only one fully effective therapy for moderate to severe obstructive sleep apnoea—continuous positive airway pressure.

Vascular mortality is higher than average, although recent data have questioned this link.
Chronic obstructive pulmonary disease
Authors: Hopkinson Nicholas S.
Published: February 2020

Chronic obstructive pulmonary disease (COPD) is a lung condition caused by the inhalation of noxious materials, principally tobacco smoke, and characterized by airflow limitation that is not fully reversible. Key features are cough, sputum production, and breathlessness. There are chronic progressive symptoms and acute exacerbations. The term COPD incorporates several pathological processes, present to a variable extent in any given individual, involving both the airways (chronic bronchitis) and the lung parenchyma (emphysema). Most COPD patients will have one or more other long-term conditions. COPD is the third leading cause of death worldwide. COPD should be considered in those over the age of 35 who have (1) exposure to risk factors, usually, but not exclusively, tobacco smoke; (2) a history of chronic progressive respiratory symptoms; (3) airflow limitation that is not fully reversible.
Cystic fibrosis
Authors: Bush Andrew , Elston Caroline
Published: February 2020

Cystic fibrosis (CF) is a recessively inherited disease caused by mutations in the cystic fibrosis gene, located on the long arm of chromosome 7, which codes for a membrane protein—the cystic fibrosis transmembrane regulator protein—that is a chloride channel. More than 2,000 CF mutations have been identified, with the ΔF508 mutation being the most common of around 200 mutations that definitely cause disease (70% of CF chromosomes in the European population). Birth incidence varies with country of origin from 1 in 2,000 to 1 in 100,000. The most popular hypothesis is that mutant cystic fibrosis transmembrane regulator protein fails to transport chloride ions normally, and there is secondary impairment of sodium, bicarbonate, and water transport.
Idiopathic pulmonary fibrosis
Authors: Molyneaux P.L. , Nicholson A.G. , Hirani N. , Wells A.U.
Published: February 2020

The synonymous terms idiopathic pulmonary fibrosis and cryptogenic fibrosing alveolitis refer to a relentlessly progressive fibrotic lung disorder. Incidence is about 5–15 per 100,000, men are more often affected than women, and it most commonly presents in the seventh and eighth decades. Aetiology remains uncertain. Typical presentation is with progressive exertional dyspnoea without wheeze, a non-productive cough, digital clubbing, and very fine end-inspiratory crackles. Central cyanosis and clinical evidence of pulmonary hypertension are late features. Diagnosis depends on careful exclusion of known causes of interstitial lung disease, followed by demonstration by radiological imaging or biopsy of the pathognomonic lesion of usual interstitial pneumonia. Two antifibrotic compounds, pirfenidone and nintedanib, have been proven to slow functional decline in idiopathic pulmonary fibrosis. Lung transplantation is appropriate in selected cases. Supportive therapy is central to the management of advanced disease. Five-year survival is 10–15%.
The lung in vasculitis
Authors: Margaritopoulos G.A. , Wells A.U.
Published: February 2020

Lung involvement in vasculitic disease can manifest as diffuse alveolar haemorrhage or as other pulmonary vasculopathy. Presenting features of diffuse alveolar haemorrhage include fever, weight loss, and other systemic symptoms in association with cough, breathlessness, and clinical signs suggestive of pneumonia. Haemoptysis may be present but is not invariable. A fall in haemoglobin over a day or longer suggests the diagnosis, and bronchoalveolar lavage is usually diagnostic. Other pulmonary vasculopathies present with breathlessness on exertion. Limited disease is generally treated with oral corticosteroid, given as monotherapy or in combination with a second-line immunosuppressive agent. Oral corticosteroid with either cyclophosphamide or rituximab are typically used to induce remission of generalized disease. Azathioprine or methotrexate with low-dose oral prednisolone are used to maintain remission.
Diffuse alveolar haemorrhage
Authors: Bourke S. J. , Spickett G.P.
Published: February 2020

Diffuse alveolar haemorrhage is characterized by acute respiratory failure, diffuse air space shadowing on the chest radiograph, haemoptysis, and anaemia. There are many different causes including immune-mediated diseases (notably pulmonary vasculitis, connective tissue diseases, and Goodpasture’s syndrome) and non-immune-mediated disease (cardiac failure, infection, coagulation disorders, thrombolytic therapy, toxins, and barotrauma). Prompt identification of the underlying cause is important in directing specific treatments. Goodpasture’s syndrome is an autoimmune disorder characterized by alveolar haemorrhage and glomerulonephritis due to antibasement membrane antibodies. Renal failure is usually the dominant feature, but alveolar haemorrhage can precede renal involvement. Idiopathic pulmonary haemosiderosis is a rare disorder of unknown cause with recurrent alveolar bleeding, which may provoke pulmonary fibrosis, and anaemia.
Eosinophilic pneumonia
Authors: Bourke S. J. , Spickett G.P.
Published: February 2020

Eosinophilic pneumonia is characterized by eosinophilic inflammation of the alveoli, usually with an accompanying eosinophilia of peripheral blood. The diagnosis should be considered when infiltrates on a chest radiograph are associated with blood eosinophilia, and is confirmed by demonstrating an excess of eosinophils in bronchoalveolar lavage fluid. Before concluding that the cause is ‘idiopathic’, the following must be considered: parasitic infestation with blood-borne parasites such as (in tropical eosinophilia) filarial worms; adverse drug reaction; asthma; allergic bronchopulmonary mycosis; vasculitis, notably eosinophilic granulomatosis with polyangiitis (previously known as Churg–Strauss syndrome); hypereosinophilic syndrome, a rare haematological disorder; and other disorders known to be associated with eosinophilic pneumonia. Causal factors need to be treated, but eosinophilic pneumonia otherwise often responds well to corticosteroid medication.
Hypersensitivity pneumonitis
Authors: Bourke S. J. , Spickett G.P.
Published: February 2020

Hypersensitivity pneumonitis is an immune-mediated lung disease in which the repeated inhalation of certain antigens provokes a hypersensitivity response, with granulomatous inflammation in the distal bronchioles and alveoli of susceptible people. A diverse range of antigens including bacteria (Thermophilic actinomycetes), fungi (Trichosporon cutaneum), animal proteins (bird antigens), mycobacteria, and chemicals may cause the disease. The commonest forms are bird fancier’s lung, farmer’s lung, humidifier lung, and metal-working fluid pneumonitis. In some cases no antigen is identified. Acute disease is characterized by recurrent episodes of breathlessness, cough, fevers, malaise, and flu-like symptoms occurring 4–8 hours after antigen exposure. Fever and basal crackles are the main physical signs.

Chronic disease is characterized by the insidious development of dyspnoea and persistent pneumonitis, sometimes progressing to lung fibrosis. Clinical features are similar to those of other varieties of pulmonary fibrosis, but clubbing is uncommon.
Lymphangioleiomyomatosis
Authors: Bourke S. J.
Published: February 2020

Lymphangioleiomyomatosis is characterized by cystic destruction of the lungs due to abnormal proliferation of smooth muscle cells. It is caused by mutations of the genes encoding hamartin and tuberin, sometimes in association with tuberous sclerosis. CT imaging shows characteristic multiple thin-walled cysts. There is usually progressive airways obstruction and impaired gas diffusion, and two-thirds of patients suffer pneumothoraces. Sirolimus can stabilize lung function and improve symptoms. Patients should avoid exogenous oestrogens, including oestrogen contraceptives or hormonal replacement therapy. Pregnancy may be associated with an increased risk of pneumothorax and loss of lung function. Hormonal therapy with progesterone or tamoxifen appears to be ineffective: other antioestrogen therapies, such as letrozole, are being studied. Lung transplantation is the main option for advanced disease.
Pulmonary amyloidosis
Authors: Bourke S. J.
Published: February 2020

Pulmonary amyloidosis is characterized by the deposition of monoclonal immunoglobulin light chain (AL) amyloid protein locally or diffusely in lung tissue. Local amyloid deposits in the airways, produced by B-cell clones within local tissues, may cause stridor, wheeze, cough, and haemoptysis. Diffuse alveolar deposition can occur as a complication of systemic amyloidosis. Local deposits of amyloid in the larynx, trachea, or bronchi may require treatment by endoscopic interventions, with mechanical debulking by forceps resection or laser therapy. Stenting may also be used to maintain airway patency. Radiotherapy has also been deployed successfully, and in certain circumstances may be a better option with less risk of bleeding or recurrence. Systemic AL amyloidosis may be treated by chemotherapy, while diffuse alveolar amyloidosis has a poor prognosis, particularly because it is associated with cardiac and renal amyloidosis.
Drug-induced lung disease
Authors: Bourke S. J.
Published: February 2020

Drug-induced lung disease is common and needs to be considered in the differential diagnosis of many respiratory conditions. The nature and timing of events often provide important clues and are sometimes sufficiently characteristic for drug-induced lung disease to be diagnosed with confidence, with resolution of symptoms on drug cessation providing further supportive evidence. Direct drug effects may arise through toxic, pharmacological, allergic, or idiosyncratic mechanisms (there may also be indirect effects). From a clinical perspective, adverse effects may be classified according to the induced disorder and the site of involvement. Asthma is the most common airway disorder to be induced or exacerbated by drugs. Cough is a well-recognized side effect of treatment with angiotensin-converting enzyme inhibitors. Pulmonary vascular involvement includes venous thromboembolism (e.g. oral contraceptive pill), and pulmonary hypertension (e.g. aminorex, now withdrawn), dasatinib, and interferons. Pleural effusions and thickening may result from drugs (e.g. dantrolene, bromocriptine, methysergide, and dasatinib).
Lung cancer
Authors: Spiro S.G. , Navani N.
Published: February 2020

Lung cancer remains the commonest killing cancer in both men and women in the developed world, and is increasingly common in developing countries, although as a result of decreased tobacco consumption in Western countries there has been a considerable reduction in the incidence among men over the last 20 years, and a slowing down in incidence in women over the last few years. Nevertheless, lung cancer is a greater cause of mortality in women than breast cancer in Western countries. There are several important industrial associations with lung cancer, in particular asbestos, but tobacco remains by far the most important cause.

There are four main cell types of lung cancer, of which adeno-, squamous, and large-cell varieties comprise non-small cell lung cancer, with the more aggressive type—small cell—being regarded as a separate entity from the point of view of treatment.
Joints and connective tissue—structure and function
Authors: Pap Thomas , Korb-Pap Adelheid , Hartmann Christine , Bertrand Jessica
Published: February 2020

Synovial joints are complex functional elements of the vertebrate body that provide animals with motion capabilities and hence the ability for locomotion and direct physical interaction with their environment. They are composed of different connective tissues structures that are derived from the same developmental structures in the embryo but have distinct cellular and biochemical properties. Articular cartilage and synovial membrane are key components of synovial joints and show several peculiarities that makes them different from other tissues. An in-depth knowledge of these features is important not only for understanding key features of articular function, but also providing explanations for important characteristics of both degenerative and inflammatory joint diseases. This chapter reviews the structure, biochemical composition, and function of articular cartilage and synovium, and points to important links between physiology and pathologic conditions, particularly arthritis.
Clinical investigation
Authors: Doherty Michael , Lanyon Peter C.
Published: February 2020

Disease markers are pathological or physiological characteristics of an individual that assist in determining the diagnosis, the current activity of disease, or the expected prognosis of the condition in that individual. Some markers relate to just one of these elements; others may relate to two, or occasionally all three. Clinical markers are derived from enquiry and examination of the patient. For many common rheumatic disorders, clinical assessment alone gives sufficient information for patient diagnosis and management. In some situations, however, particularly with inflammatory, metabolic, or multisystem disease, a search for additional investigational markers may be warranted. It is important to emphasize that the requirement for and selection of investigations, as well as their subsequent interpretation, is principally determined by the clinical assessment. Investigations are an adjunct, never a substitute, for competent clinical assessment. There is no place for a battery of screening tests.
Back pain and regional disorders
Authors: Ammendolia Carlo , Southerst Danielle
Published: February 2020

Over 70% of people in industrialized countries suffer from low back pain at some time, and it is one of the main reasons for visits to physicians. Risk factors include heavy physical work, smoking, stress, depression, and job dissatisfaction. In more than 90% of cases the exact anatomical source of back pain cannot be determined, and the preferred diagnostic label is ‘non-specific low back pain’. Investigation should be restricted to patients with red flags and clinical suspicion of serious disease, with magnetic resonance imaging the best imaging modality for the diagnosis of lumbar disorders. In the absence of red flags, patients with acute low back pain should receive non pharmacological care as first treatment option including reassurance, advise to remain active, massage and spinal manipulation followed by non steroidal anti-inflammatory drugs and muscle relaxants if necessary.
Rheumatoid arthritis
Authors: Baker Kenneth F. , Isaacs John D.
Published: February 2020

Rheumatoid arthritis is a common autoimmune disease characterized by both synovial and systemic inflammation. Synovitis classically presents as a symmetrical destructive polyarthritis affecting the hands and feet typified by episodic pain, stiffness, and swelling. Systemic inflammation leads to a range of extra-articular manifestations including organ involvement (e.g. interstitial lung disease, scleritis), constitutional features (e.g. fatigue, depression) and other complications (e.g. accelerated atherosclerosis, nerve and spinal cord compression). Rheumatoid arthritis is a clinical diagnosis based largely upon history and examination, supported by a limited range of investigation findings including elevated acute-phase reactants, autoantibodies (rheumatoid factor and anti-citrullinated peptide antibody), and imaging (e.g. musculoskeletal ultrasound). If left untreated, patients can rapidly develop irreversible joint damage leading to chronic pain, deformity, disability, and premature mortality. However, with early initiation of disease-modifying anti-rheumatic drugs (DMARDs) in treat-to-target strategies, disease remission is now achievable for many patients. Conventional synthetic DMARDs are the anchor of rheumatoid arthritis therapy, with methotrexate the recommended first choice. Biological DMARDs (monoclonal antibodies and soluble receptors) and targeted synthetic DMARDs (Janus kinase inhibitors) are reserved as second-line agents. Glucocorticoids are helpful as bridging therapy, though their considerable side effect profile prohibits their use as maintenance therapy. Non-steroidal anti-inflammatory drugs (NSAIDs) are effective in relieving arthritis pain, but long-term use is limited by their potential cardiovascular, renal, and gastrointestinal toxicities. With optimal care from a multidisciplinary team, many patients achieve and retain disease remission with maintenance of employment and quality of life.
Reactive arthritis
Authors: Stober Carmel B. , Gaston Hill
Published: February 2020

The term ‘reactive arthritis’ is sometimes used rather loosely to cover any form of arthritis that follows infection, and then includes post-viral arthritides, rheumatic fever, Lyme disease, and other forms of arthritis that do not generally share clinical features. Reactive arthritis a subset of post-infectious arthritis, and causative organisms are usually localized to the gastrointestinal or genitourinary tracts. Following infection, organisms or their components find their way to joints, where they provoke inflammatory immune responses. Whether the responses cross-react with self antigens is unclear; arthritis may be maintained by persistent infection. The disease commonly has specific extra-articular features not seen in other forms of post-infectious arthritis, and is genetically and pathologically a form of spondyloarthritis.
Inflammatory myopathies
Authors: Lundberg Ingrid E. , Chinoy Hector , Cooper Robert
Published: February 2020

The idiopathic inflammatory myopathies are a heterogenous group of disorders characterized by muscle weakness, inflammation in muscle tissue, and with frequent extramuscular involvement. Autoantibodies are common, supporting the notion of these disorders being autoimmune. Typically, inflammatory cell infiltrates are found in muscle biopsies. Other organs are frequently involved such as skin, lungs, joints, gastrointestinal tract, and the heart. These heterogenous disorders can be subclassified based on clinical and histopathological features, or by autoantibody specificities. The idiopathic inflammatory myopathies have traditionally comprised polymyositis (PM), dermatomyositis (DM), juvenile DM, PM/DM overlapping with another connective tissue disease, and inclusion body myositis. More recently a subgroup with similar clinical features but with no or scarce inflammation and with pronounced muscle fibre necrosis has been identified and termed immune-mediated necrotizing myopathy.
Large vessel vasculitis
Authors: Luqmani Raashid , Ponte Cristina
Published: February 2020

Large vessel vasculitis describes a group of primary vasculitides predominantly affecting the aorta and its major branches. The two major subtypes of large vessel vasculitis are giant cell arteritis (GCA) and Takayasu arteritis (TA), which have distinctive features. GCA occurs predominantly in white European women aged above 50 years, while TA affects women below 40 years from the Middle East and Asia. However, there are many similarities between GCA and TA, particularly in pathogenic mechanisms, histopathology, and clinical manifestations related to large vessel involvement. It remains unclear whether GCA and TA are distinct entities or represent different phenotypes of the same disease.
Behçet’s syndrome
Authors: Yurdakul Sebahattin , Fresko Izzet , Yazici Hasan
Published: February 2020

Behçet’s syndrome is an inflammatory disorder of unknown aetiology that involves arteries and veins of all sizes. Most cases are from the countries around the Mediterranean basin, the Middle East, and East Asia, with the highest prevalence in Turkey. It typically presents in the second and third decades with recurrent oral ulcers (98% of cases), genital ulcers (85%), acneiform lesions (85%), pathergy reaction (60% in some countries), erythema nodosum (50%), uveitis (50%), arthritis (50%), thrombophlebitis (30%), and less commonly with arterial occlusion/aneurysm, central nervous system involvement, or gastrointestinal lesions. A relapsing/remitting course is usual. Disease is more severe and mortality is higher in men. The diagnosis is clinical, laboratory findings are non-specific, and there is no specific diagnostic test for Behçet’s syndrome.
Polymyalgia rheumatica
Authors: Dasgupta Bhaskar , Matteson Eric L.
Published: February 2020

Polymyalgia rheumatica is one of the common inflammatory rheumatic diseases of older people. It overlaps with inflammatory arthritis and large-vessel vasculitis, particularly giant cell arteritis. Pathogenesis is unclear and may involve recognition of an infectious agent by aberrantly activated dendritic cells. Polymyalgia rheumatica is characterized by abrupt-onset pain and morning stiffness of the shoulder and pelvic girdle muscles, with an acute phase response (elevated erythrocyte sedimentation rate and/or C-reactive protein). Evaluation can be challenging, as many clinical and laboratory features may also be present in other conditions, including other rheumatological diseases, infection, and neoplasia. The mainstay of therapy is glucocorticoids. Adjunctive therapy can be initiated early in the disease course in patients with high risk of glucocorticoid-related side effects, severe or relapsing disease, or poor or ill sustained response to glucocorticoids. The response to standardized therapy is heterogeneous, and a significant proportion of patients do not respond completely.
Inherited defects of connective tissue: Ehlers–Danlos syndrome, Marfan’s syndrome, and pseudoxanthoma elasticum
Authors: Burrows N.P.
Published: February 2020

The inherited disorders of connective tissue are all conditions in which structural defects in collagen or other extracellular matrix proteins lead to its fragility, with the commonest sites of involvement being the skin, ligaments, vasculature, and hollow organs. These include Ehlers–Danlos syndrome, Marfan’s syndrome, and pseudoxanthoma elasticum. This chapter first examines Ehlers–Danlos syndrome, which is a heterogeneous group of disorders resulting from abnormalities in collagen synthesis and processing, or of other extracellular matrix proteins. They can be classified on the basis of descriptive clinical phenotype and/or underlying molecular cause. Most cases are autosomal dominant, but 30–50% may be sporadic. It then looks in detail at other disorders of the connective tissues, such as Marfan’s syndrome and pseudoxanthoma elasticum, including their presentations, diagnosis, treatment, and possible outlook.
Disorders of water and sodium homeostasis
Authors: Moritz Michael L. , Ayus Juan Carlos
Published: February 2020

Water intake and the excretion of water are tightly regulated processes that are able to maintain a near-constant serum osmolality. Sodium disorders (dysnatraemias—hyponatraemia or hypernatraemia) are almost always due to an imbalance between water intake and water excretion. Understanding the aetiology of sodium disorders depends on understanding the concept of electrolyte-free water clearance—this is a conceptual amount of water that represents the volume that would need to be subtracted (if electrolyte-free water clearance is positive) or added (if negative) to the measured urinary volume to make the electrolytes contained within the urine have the same tonicity as the plasma electrolytes. It is the concentration of the electrolytes in the urine, not the osmolality of the urine, which ultimately determines the net excretion of water. Hyponatraemia (serum sodium concentration <135 mmol/litre) is a common electrolyte disorder. It is almost invariably due to impaired water excretion, often in states where antidiuretic hormone release is (1) a normal response to a physiological stimulus such as pain, nausea, volume depletion, postoperative state, or congestive heart failure; or (2) a pathophysiological response as occurs with thiazide diuretics, other types of medications, or in the syndrome of inappropriate diuresis; with both often exacerbated in hospital by (3) inappropriate iatrogenic administration of hypotonic fluids. Hypernatraemia (serum sodium concentration >145 mmol/litre) is a common electrolyte disorder that occurs when water intake is inadequate to keep up with water losses. Since the thirst mechanism is such a powerful stimulus, hypernatraemia almost invariably occurs in the context of an illness and care that restricts the patient’s access to water. This chapter discusses the clinical features, management, and prevention of hyponatraemia and hypernatraemia.
Clinical presentation of renal disease
Authors: Fielding Richard E. , Farrington Ken
Published: February 2020

Renal disease may present in many ways, including (1) the screening of asymptomatic individuals; (2) with symptoms and signs resulting from renal dysfunction; and (3) with symptoms and signs of an underlying disease, often systemic, which has resulted in renal dysfunction. History and clinical signs—in many cases these are nonspecific or not apparent, and detection of renal disease relies on a combination of clinical suspicion and simple investigations, including urinalysis and estimation of renal function. Asymptomatic renal disease—this is common and most often detected as chronic depression of eGFR (known as chronic kidney disease, CKD), proteinuria, or haematuria, either as isolated features or in combination. Symptomatic renal disease—may present in many ways, including (1) with features of severe chronic depression of glomerular filtration rate—‘uraemia’, manifesting with some or all of anorexia, nausea, vomiting, fatigue, weakness, pruritus, breathlessness, bleeding tendency, apathy and loss of mental concentration, and muscle twitching and cramps; (2) acute kidney injury (AKI); (3) with urinary symptoms—frequency, polyuria, nocturia, oliguria, anuria, and visible (macroscopic) haematuria; and (4) loin pain. Specific renal syndromes—these include (1) nephrotic syndrome—comprising oedema, proteinuria, and hypoalbuminaemia—caused by primary or secondary glomerular disease; and (2) rapidly progressive glomerulonephritis with AKI. Other conditions—renal disease may be associated with and present in the context of many underlying conditions, including (1) diabetes mellitus; (2) renovascular disease; (3) myeloma and other malignancies; (4) infectious diseases, either as a nonspecific manifestation of the sepsis syndrome or as a specific complication of the particular infection; (5) systemic inflammatory diseases; (6) drug-induced renal disease; and (7) pregnancy.
Acute kidney injury
Authors: Firth John D.
Published: February 2020

Definition—for practical clinical purposes, acute kidney injury (AKI) is defined as a significant decline in renal excretory function occurring over hours or days, detected by either a fall in urinary output or a rise in the serum concentration of creatinine. Oliguria—defined (arbitrarily) as a urinary volume of less than 400 ml/day—is usually present, but not always. Clinical approach: diagnosis—all patients admitted to hospital with acute illness, but particularly older people and those with pre-existing chronic kidney disease, should be considered at risk of developing AKI. The most common precipitant is volume depletion. Serum creatinine and electrolytes should be measured on admission in all acutely ill patients, and repeated daily or on alternate days in those who remain so. Assessment—after treatment of life-threatening complications, the initial assessment of a patient who appears to have AKI must answer three questions: (1) is the kidney injury really acute? (2) Is urinary obstruction a possibility? And (3) is there a renal inflammatory cause? General aspects of management—the immediate management of a patient with renal impairment is directed towards three goals: (1) recognition and treatment of any life-threatening complications of AKI, (2) prompt diagnosis and treatment of hypovolaemia, and (3) specific treatment of the underlying condition—if this persists untreated then renal function will not improve. Specific causes of acute kidney injury—there are many possible causes of AKI, but in any given clinical context few of these are likely to require consideration. By far the most frequent are prerenal failure and acute tubular necrosis, which together account for 80 to 90% of cases of AKI seen by physicians.
Chronic kidney disease
Authors: Hutchison Alastair
Published: February 2020

Chronic kidney disease (CKD) is defined as kidney damage lasting for more than 3 months characterized by structural or functional abnormalities of the kidney, with or without decreased glomerular filtration rate (GFR). CKD has been subdivided into six stages depending on the estimated GFR (eGFR) and degree of proteinuria: CKD stage 1 is eGFR greater than 90 ml/min (per 1.73 m2) with other evidence of renal disease; CKD stage 2 is eGFR 60 to 89 ml/min, with other evidence of renal disease; CKD stage 3a is eGFR 45 to 59 ml/min; CKD stage 3b is eGFR 30 to 44 ml/min; CKD stage 4 is eGFR 15 to 29 ml/min; and CKD stage 5 is eGFR less than 15 ml/min. At each stage the CKD is further categorized according to the degree of proteinuria based on the albumin:creatinine ratio (ACR), from A1 (no increase in protein excretion) to A3 (severe proteinuria). The eGFR is least accurate when the serum creatinine is within or near the normal range. Mild CKD is common, with about 10% of the population of the United States of America having CKD stage 1, 2, or 3 (combined), but advanced CKD is relatively rare (about 0.2% are receiving renal replacement therapy). Patients with CKD stage 1, 2, or 3 are at relatively low risk of progressing to require renal replacement therapy, but are at high risk of death from cardiovascular disease. This chapter discusses the definition, aetiology, and pathophysiology of CKD, followed by sections on the prevention of progression, medical management of the consequences of CKD (including diet, CKD mineral and bone disorders, advanced hyperparathyroidism, and anaemia), and preparation for renal replacement therapy or conservative management of uraemia.
Haemodialysis
Authors: Mactier Robert
Published: February 2020

Maintenance haemodialysis (HD) is a highly successful treatment for patients with established renal failure and is the default therapy when other renal replacement therapy options are not available. HD uses the countercurrent flow of blood and dialysate through a hollow fibre dialyser to maximize the concentration gradient for diffusive transport of solutes. A hydrostatic gradient across the dialyser membrane induces ultrafiltration (UF) of water and convective transport of solutes by solvent drag. High-flux membranes are standard in most HD centres and are needed to achieve significant removal of middle molecules, of which β2-microglobulin (the cause of dialysis-related amyloid) is the prime example. The technique of haemodiafiltration contributes additional convective removal of fluid and better clearance of middle molecules. The need to secure and maintain reliable vascular access is fundamental to achieving adequate dialysis and maintaining health. An arteriovenous fistula is the preferred option, with fewer complications and longer survival than other access options. For historical and pragmatic reasons, HD is normally provided three times per week. Working definitions of adequacy are based on small-solute—typically urea—removal. The optimal dialysis dose has not been well defined, but minimum targets of delivered dose measured by urea reduction ratio and normalized urea clearance (Kt/V) have been established. The main acute complication of HD is intradialytic hypotension, resulting from an imbalance between the UF rate and the rate of vascular refill. Underlying cardiovascular disease, antihypertensive drugs, autonomic dysfunction, shortened dialysis times, large interdialytic fluid gains, and inaccurate dry-weight assessment all predispose. In the longer term, dialysis-related amyloidosis is a disabling, progressive condition caused by the polymerization of β2-microglobulin within tendons, synovium, and other tissues.
Immunoglobulin A nephropathy and IgA vasculitis (HSP)
Authors: Barratt Jonathan , Feehally John
Published: February 2020

Immunoglobulin A nephropathy (IgAN) is the commonest pattern of glomerulonephritis identified in areas of the world where renal biopsy is widely practised. It is defined pathologically by IgA deposition in the glomerular mesangium accompanied by a mesangial proliferative glomerulonephritis which may vary greatly in severity. Aetiology is uncertain, but abnormalities of IgA1 hinge-region O-glycosylation are consistently found. Clinical features—IgAN can present with (1) visible haematuria, typically in children and young adults, developing within a day or two of upper respiratory tract infection (‘synpharyngitic’); (2) asymptomatic nonvisible haematuria/proteinuria; (3) nephrotic syndrome (<5% of cases); (4) acute kidney injury (uncommon); and (5) chronic renal failure with up to 25% of patients reaching endstage renal failure within 20 years of diagnosis. Henoch–Schönlein purpura (HSP) is a small vessel systemic vasculitis characterized by small blood vessel deposition of IgA that predominantly affects the skin, joints, gut, and kidney, with nephritis that may be histologically indistinguishable from IgA nephropathy. Management—there is no treatment known to modify mesangial deposition of IgA. Treatment options are mostly directed at controlling blood pressure and limiting proteinuria through blockade of the renin–angiotensin–aldosterone axis. In the rare patient presenting with acute kidney injury in whom biopsy shows crescentic IgA nephropathy, a regimen such as those used for renal vasculitis and other forms of crescentic glomerulonephritis should be considered, for example, oral prednisolone in combination with cyclophosphamide.
Thin membrane nephropathy
Authors: Topham Peter , Feehally John
Published: February 2020

Thin membrane nephropathy is a common autosomal dominant glomerular disorder that results in persistent nonvisible haematuria and is pathologically characterized by the presence of diffuse and uniform thinning of the glomerular basement membrane. Recent genetic studies have identified mutations in the COL4A3 and COL4A4 genes in 40% of affected families. There is no specific treatment. Prognosis is excellent for most people, but a few cases with progressive renal impairment have been described.
Diabetes mellitus and the kidney
Authors: Bilous Rudolf
Published: February 2020

Diabetic nephropathy is the commonest cause of endstage renal disease in the developed world. Aetiology and pathology—causation is related to glycaemic control, hypertension, inflammation, genetic factors, and dietary and other environmental factors. Pathological hallmarks in the glomerulus are thickening of the glomerular basement membrane and mesangial expansion, with or without nodule formation, secondary to an accumulation of extracellular matrix. Many patients have a varying severity of tubulointerstitial inflammation and fibrosis. Staging and natural history—is classically described in terms of urinary albumin excretion rate (UAER). Clinical features—most patients (>60%) will have a normal UAER throughout their diabetic life, but 1 to 2% of the remainder develop persistent moderately increased albuminuria each year. Once UAER exceeds 200 µg/min, there tends to be a relentless increase in proteinuria and glomerular filtration rate declines progressively at a rate that largely depends upon blood pressure control. Prevention—tight glycaemic control can prevent moderately increased albuminuria in both type 1 and type 2 diabetes. Whether intensive blood pressure control using angiotensin-converting enzyme (ACE) inhibitors can also prevent this remains controversial. In both type 1 and type 2 diabetes, intensive blood pressure control using ACE inhibitors or angiotensin II receptor blockers (ARBs) slows progression from moderately to severely increased albuminuria and also slows the rate of decline in glomerular filtration rate in those with severely increased albuminuria. Management—aims for (1) control of glycaemia, (2) control of hypertension (<130/80 mmHg) using an ACE inhibitor or an ARB as first line; and (3) other interventions, including some or all of serum lipid lowering, smoking cessation, and reduction of dietary protein and salt.
Renal involvement in plasma cell dyscrasias, immunoglobulin-based amyloidoses, and fibrillary glomerulopathies, lymphomas, and leukaemias
Authors: Ronco Pierre , Bridoux Frank , Jaccard Arnaud
Published: February 2020

Plasma cell dyscrasias are characterized by uncontrolled proliferation of a single clone of B cells which is responsible for the secretion of a monoclonal immunoglobulin (Ig) or Ig subunit that can deposit in tissues. They can cause a wide range of renal diseases. Light-chain amyloidosis—renal presentation is usually with proteinuria, often progressing to nephrotic syndrome. A progressive decline in renal function may occur, leading finally to endstage renal failure. Diagnosis is made by the detection of monoclonal gammopathy and free light-chain excess in the serum (90% of cases), in combination with biopsy evidence of amyloid-forming light-chain deposits. Myeloma—renal failure is found at presentation in 20% of patients, occurs in 50% at some time, and is most commonly caused by cast nephropathy, with renal biopsy typically showing ‘fractured’ casts. Chemotherapy should be introduced promptly. Light-chain, light- and heavy-chain, and heavy-chain deposition disease—collectively known as monoclonal Ig deposition diseases, present with proteinuria and renal failure. Diagnosis is by renal biopsy. Treatment strategy is based on chemotherapy (bortezomib-based regimens) followed by autologous stem cell transplantation in selected cases. Fibrillary glomerulonephritis and immunotactoid glomerulopathy—usual presentation is with nephrotic syndrome, microscopic haematuria, and hypertension. Immunotactoid glomerulopathy usually responds to chemotherapy. Cryoglobulinaemia—type II (‘essential mixed’) may present with proteinuria, haematuria, hypertension, and gradually declining renal function, or with an acute nephritic picture. Renal biopsy typically reveals membranoproliferative glomerulonephritis with massive subendothelial deposits. Treatment involves antiviral agents and/or immunosuppression. Tumour lysis syndrome—a life-threatening metabolic emergency that occurs in patients with haemopathies with high cell turnover, mostly at the onset of chemotherapy. Treatment is based on saline diuresis (if possible), rasburicase, and haemodialysis (if required).
Sickle cell disease and the kidney
Authors: Sharpe Claire C.
Published: February 2020

About 60% of patients with sickle cell disease have sickle cell nephropathy. Clinical symptoms reflect medullary compromise, with polyuria, troublesome nocturia, enuresis, and dehydration being typical early manifestations. Haematuria, nonvisible and visible, is common. The prevalence of albuminuria rises with age, and those in whom this progresses rapidly are at greatest risk of developing endstage kidney disease, which eventually affects 10 to 15% of patients with sickle cell nephropathy.

Management of chronic kidney disease due to sickle cell nephropathy is along standard lines: no specific treatment has been shown to prevent the condition or retard its progression.
Malignancy-associated renal disease
Authors: Turner A. Neil
Published: February 2020

Malignancies can affect the kidneys by direct invasion, metabolic and remote effects of tumour products, deposition of tumour products, triggering of immune reactions, and effects of treatment.

Particular malignancy-associated renal diseases include the following:

Thrombotic microangiopathy—particularly reported for malignancies of the stomach, pancreas, and prostate, and also with certain chemotherapeutic agents.

Minimal-change nephrotic syndrome—rarely caused by lymphoma.

Membranous nephropathy—associated with malignancy, usually of solid organs, in 5 to 11% of cases. Malignant disease is typically advanced and obvious when nephrotic syndrome or heavy proteinuria is recognized. Very few treatable and otherwise subclinical tumours are uncovered by investigation in routine clinical practice.

Focal necrotizing and crescentic nephritis—may rarely be associated with malignancy, when they are usually antineutrophil cytoplasmic antibody negative.

Proteinuria—may be caused by agents that modulate interferons or vascular endothelial growth factors.
Atherosclerotic renovascular disease
Authors: Kalra Philip A. , Vassallo Diana
Published: February 2020

Atherosclerotic renovascular disease (ARVD) refers to atheromatous narrowing of one or both renal arteries and frequently coexists with atherosclerotic disease in other vascular beds. Patients with this condition are at high risk of adverse cardiovascular events, with mortality around 8% per year. Many patients with ARVD have chronic kidney disease, but only a minority progress to endstage kidney disease, suggesting that pre-existing hypertensive and/or ischaemic renal parenchymal injury is the usual cause of renal dysfunction. Many patients with ARVD are asymptomatic, but there can be important complications such as uncontrolled hypertension, rapid decline in kidney function, and recurrent acute heart failure (flash pulmonary oedema).

Management—patients with ARVD should receive medical vascular protective therapy just like other patients with atheromatous disease. This involves antiplatelet agents such as aspirin, statins, antihypertensive agents (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers are the drugs of choice), optimization of glycaemic control in diabetic patients, and advice/help to stop smoking. On the basis of randomized controlled trial data, they should not be offered revascularization by angioplasty/stenting for the purpose of improving blood pressure control or stabilizing/improving renal function. However, there is evidence that a subgroup of patients with specific complications of ARVD (as previously mentioned) may benefit from revascularization.
Renal involvement in genetic disease
Authors: Joly D. , Grünfeld J.P.
Published: February 2020

There are more than 200 inherited disorders in which the kidney is affected and which display a wide range of renal features. Autosomal dominant polycystic kidney disease— affects about 1/1000 individuals and accounts for 7% of cases of endstage renal failure in Western countries. Inheritance is autosomal dominant, with mutations in polycystin 1 responsible for 75% of cases and mutations in polycystin 2 accounting for most of the remainder. May present with renal pain, haematuria, urinary tract infection, or hypertension, or be discovered incidentally on physical examination or abdominal imaging, or by family screening, or after routine measurement of renal function. Commonly progresses to endstage renal failure between 40 and 80 years of age. Main extrarenal manifestations are intracranial aneurysms, liver cysts, and mitral valve prolapse. Alport’s syndrome—X-linked dominant inheritance in 85% of kindreds, with molecular defects involving the gene encoding the α-5 chain of the type IV collagen molecule. Males typically present with visible haematuria in childhood, followed by permanent nonvisible haematuria, and later by proteinuria and renal failure. Extrarenal manifestations include perceptive deafness of variable severity and ocular abnormalities. Carrier women often have slight or intermittent urinary abnormalities, but may develop mild impairment of renal function late in life, and a few develop endstage renal disease. In the autosomal recessive form of Alport’s syndrome, renal disease progresses to endstage before 20 to 30 years of age at a similar rate in both affected men and women. Other disorders covered in this chapter include hereditary tubulointerstitial nephritis, hereditary tumours, glomerular structural diseases, metabolic diseases with glomerular involvement (Fabry’s disease), congenital anomalies of the kidney and urinary tract, and other genetic diseases with kidney involvement.