bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inherited defects of connective tissue: Ehlers–Danlos syndrome, Marfan’s syndrome, and pseudoxanthoma elasticum
Authors: Burrows N.P. 
Published: February 2020

Abstract
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

Abstract
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 &lt;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 &gt;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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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 (&lt;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

Abstract
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

Abstract
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 (&gt;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 (&lt;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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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.