bluuebunny/crossref_metadata_2025 huggingface dataset:
Renal radiology
Authors: Weston Michael J.
Published: November 2015

This chapter acts as an introduction to Chapters 10–16 and highlights the uses of plain radiography, fluoroscopy, ultrasound, computed tomography, positron emission tomography, magnetic resonance imaging, radionuclide studies, and image-guided intervention.
All imaging studies work best if a specific question is asked. This helps to choose both the best modality and protocol to answer the question. The clinical information given will often assist the interpretation of the findings. The more vague the indication for a scan, the less likely that useful information will be provided. Both the requesting clinician and the radiologist need to be clear how the scan result will alter management. Performing imaging procedures that will not alter the outcome is wasteful and unkind to the patient.
Plain radiography, excretion radiography, and contrast radiography
Authors: Kawashima Akira , LeRoy Andrew J.
Published: November 2015

Plain radiography is both a primary abdominal examination technique and an initial component of subsequent excretion and contrast radiographic studies. Excretion radiography is performed by means of antegrade opacification of the renal collecting systems, ureters, and bladder following intravenous contrast administration. Contrast radiography is obtained following direct injection of contrast media into the urinary tracts in an antegrade or retrograde fashion.
Although ultrasound, computed tomography, and magnetic resonance imaging are increasingly used to compensate for the limitations of excretion radiography, conventional urographic examinations remain important in the diagnosis of some urinary tract conditions.
Ultrasound
Authors: Wells Toby , Freeman Simon J.
Published: November 2015

Ultrasound assists nephrologists in many situations. It is essential in excluding obstruction as the cause of acute kidney injury, but it also helps to reach other diagnoses and guides interventions such as renal biopsy and placement of lines for dialysis and evaluating dialysis fistulae. It is the imaging technique of choice in assessing renal transplants. It has advantages: it does not involve ionizing radiation, allows rapid real-time imaging, is relatively inexpensive, and can be performed at the patient’s bedside. Ultrasound is the primary imaging modality in paediatric radiology for most conditions, largely because it does not involve ionizing radiation. The strengths and limitations of ultrasound need to be understood to ensure that the technique is applied appropriately.
Computed tomography
Authors: Teoh Eugene , Weston Michael J.
Published: November 2015

Computed tomography (CT) has increased in use exponentially for the assessment of patients with renal tract pathology. This has been promoted by the availability of multidetector thin-slice CT so that intravenous urography has been superseded by CT urography. The latter may be considered as a ‘one-stop’ imaging investigation for haematuria, with increased detection of both urinary tract cancers and urolithiasis. Multiplanar reformats are made possible with the use of thin slices, allowing clear delineation of other pathologies such as urinary tract injury. In the transplant recipient, protocols have been developed for the assessment of more immediate complications such as thrombotic and stenotic disease. During follow-up, CT continues to inform the management of post-transplant lymphoproliferative disorder and other immunosuppressant-related complications. Unenhanced CT of the urinary tract has established its role in assessment of patients with renal colic, with the ability to detect pathology outside of the urinary tract. Renal CT has been developed for the characterization of renal masses, accompanied by the now well-established Bosniak renal cyst classification system. As the usefulness of CT increases, clear awareness of safety issues has to be maintained. These include the administration of intravenous iodinated contrast medium in higher-risk patient groups, particularly those with renal impairment. The radiation burden that comes with CT poses an added risk to the patient that should not be ignored. This necessitates clear referral guidelines for its use, which should be applied in careful balance with the global assessment of the patient.
Radioisotopes in diagnostic imaging in nephrology
Authors: Dhandapani Ramya , Vinjamuri Sobhan
Published: November 2015

Radioisotopes play a key role in diagnostic imaging of the renal tract. Various functions of the kidneys can be assessed by different radiopharmaceuticals and the choice of a particular test depends on the clinical question. This chapter describes the routine functions of the kidneys that can be assessed by isotope renography and a clinical decision table is provided. The use of isotopes in imaging specific conditions such as infection, trauma, hypertension, and after renal transplant are included. Positron emission tomography and single-positron emission computed tomography of the kidneys offer the advantage of combining assessment of anatomy and physiological function.
Sodium transport and balance
Authors: Schild Laurent
Published: November 2015

The kidney maintains the extracellular fluid volume and blood pressure by regulating urinary sodium (Na+) excretion to precisely balance daily Na+ intake. Genetic and experimental evidence support a central role for the distal nephron in the fine tuning of urinary Na+ excretion. The cellular and molecular aspects of the transporters involved in Na+ reabsorption in the distal nephron, and their regulation linked to complex signaling pathways are discussed.
Na+ absorption can be viewed as a continuum in the activities of specific transport processes along the distal nephron. The crosstalk between these different and complex reabsorptive processes is important for the adaptation of Na+ excretion in various physiological, pathophysiological, and pharmacological conditions.
Potassium homeostasis
Authors: Doucet Alain , Crambert Gilles
Published: November 2015

The equilibrium between the concentration of K+ in the extracellular space (low) and the intracellular compartment (high) is crucial for maintaining the electrical properties of excitable and non-excitable cells, because it determines the membrane resting potential. The high intracellular concentration of K+ (120–140 mmol/L) also contributes to the intracellular osmolarity, a determinant of cell volume. It is therefore crucial to finely tune both extracellular and intracellular K+ concentrations.
There is a coordinated regulation between processes/mechanisms that store/release K+ from internal stores (internal balance) and those that retain/excrete K+ (external balance).
Renal acid–base homeostasis
Authors: Wagner Carsten A. , Devuyst Olivier
Published: November 2015

The kidney is central to acid–base homeostasis. Major processes are reabsorption of filtered bicarbonate, de novo synthesis of bicarbonate from ammoniagenesis, and net excretion of protons. The latter requires buffers such as ammonium, phosphate, citrate and other bases binding protons (so-called titratable acids).
The proximal tubule is the major site of bicarbonate reabsorption and only site of ammoniagenesis. The thick ascending limb and the distal convoluted tubule handle ammonia/ammonium and complete bicarbonate reabsorption. The collecting duct system excretes protons and ammonium, but may switch to net bicarbonate secretion. The kidney displays a great plasticity to adapt acid or bicarbonate excretion. Angiotensin II, aldosterone and endothelin are involved in regulating these processes, and they induce morphological changes along the nephron.
Inborn and acquired disorders of renal acid–base handling are caused by mutations in acid–base transport proteins or by dysregulation of adaptive mechanisms.
Phosphate homeostasis
Authors: Murer Heini , Biber Jürg , Wagner Carsten A.
Published: November 2015

Inorganic phosphate ions (H2PO4−/ HPO42−) (abbreviated as Pi) are involved in formation of bone and generation of high-energy bonds (e.g. ATP), metabolic pathways, and regulation of cellular functions. In addition, Pi is a component of biological membranes and nucleic acids. Only about 1% of total body Pi content is present in extracellular fluids, at a plasma concentration in adults within the range 0.8–1.4 mMol/L (at pH 7.4 mostly as HPO42−), with diurnal variations of approximately 0.2 mM. A small amount of plasma Pi is bound to proteins or forms complexes with calcium.
Under normal, balanced conditions, absorption of dietary Pi along the small intestine equals the output of Pi via kidney and faeces. Renal excretion of Pi represents the key determinant for the adjustment of normal Pi plasma concentrations. Renal reabsorption of Pi occurs along the proximal tubules by sodium-dependent Pi cotransporters that are strictly localized at the apical brush border membrane. Parathyroid hormone (PTH) and FGF23 are key regulators amongst a myriad of factors controlling excretion of Pi in urine, mostly by changes of the apical abundance of Na/Pi cotransporters.
Hypophosphataemia may result in osteomalacia, rickets, muscle weakness, and haemolysis. Hyperphosphataemia can lead to hyperparathyroidism and severe calcifications in different tissues.
Approach to the patient with polyuria
Authors: Bichet Daniel G.
Published: November 2015

In a polyuric patient, first exclude osmotic diuresis, then differentiate between primary polydipsia, central, and nephrogenic diabetes insipidus, with clinical characteristics, simple blood and urine tests, and hypothalamic magnetic resonance imaging. Mammals are osmoregulators and osmolality is perceived by central and peripheral osmotic receptors and influencing thirst perception and vasopressin secretion.
In congenital polyuric states it is useful to distinguish ‘pure’ polyuric states, that is, loss of water only but normal conservation of sodium, potassium, chloride, and calcium, from complex (water + sodium + calcium) polyuric states. For the latter, the triad polyuria/polyhydramnios/prematurity is a tell-tale sign of Bartter syndrome. We recommend sequencing of the nephrogenic diabetes insipidus and Bartter genes in all the affected congenital and hereditary polyuric patients. Acquired central and nephrogenic polyuric states are simpler to evaluate.
Approach to the patient with hypomagnesaemia
Authors: Konrad Martin , Schlingmann Karl P.
Published: November 2015

The kidneys play a central role in the maintenance of a normal magnesium balance. The distal renal tubule, especially the thick ascending limb of the loop of Henle, and the distal convoluted tubule mediate the regulation of a normal magnesium balance.
The clinical assessment of magnesium deficiency is described. Genetic causes are described in detail. Acquired causes are more common and often related to drug therapy or toxicity, or to metabolic acidosis or phosphate depletion.
Mechanisms of glomerular injury
Authors: Turner Neil
Published: November 2015

Proteinuric diseases, historically termed ‘nephrosis’, are characterized by subtle abnormalities in podocytes or by abnormal glomerular matrix, including the scarring laid down by inflammatory diseases. Angiotensin blockers, corticosteroids, calcineurin inhibitors, and a wide range of other drugs known or believed to be effective in different renal diseases, appear to have direct effects on podocytes that reduce proteinuria that may be important to their effectiveness. Several of these have previously been assumed to work via haemodynamic, immune or other modes.
Haematuric diseases are characterized by inflammatory disruption of the glomerular basement membrane (GBM) (‘nephritis’), or less commonly by fragile GBM without inflammation. The majority of haematuric conditions are slowly or rapidly destructive diseases associated with infiltration of inflammatory cells, and proliferation of endogenous cells of the glomerulus, probably in attempts at repair. With time, many haematuric diseases are associated with the development of proteinuria, possibly as a consequence of scarring and its effects on podocyte function.
Loin pain haematuria syndrome
Authors: Neary John
Published: November 2015

Loin pain haematuria syndrome is an uncommon but disabling condition which presents with recurrent severe loin pain and either microscopic or macroscopic haematuria. It predominantly affects young Caucasian females. The aetiology is unclear, but it seems to be most commonly initiated by glomerular bleeding. There are no defining features of the disorder on any investigation, and it is mostly termed a diagnosis of exclusion. A lack of a clear definition of the condition and uncertainty about the aetiology mean that this is still a poorly understood entity. A variety of medical and surgical treatments have been used with mixed results. The mainstays of treatment are effective analgesia management and involvement of a multidisciplinary team including psychological support.
Exercise-related pseudonephritis
Authors: Turner Neil
Published: November 2015

Vigorous and prolonged physical exercise can produce a range of urinary abnormalities which would normally be considered alarming. They include haematuria, haemoglobinuria, the appearance in urine of red cells in urine, some fragmented in a ‘glomerular’ manner, red cell cast formation, and proteinuria. A variety of names have been given to these syndromes, including march haematuria and march haemoglobinuria. Mostly these changes seem benign and self-limiting. Rarely they are associated with acute kidney injury but this is often in the context of other renal insults, extreme dehydration, or hyperpyrexic conditions. Vigorous exercise is also commonly associated with various electrolyte changes related to both over- and under-hydration. These can complicate assessment.
Transient proteinuria in the absence of haematuria appears to be a physiological response to even short-term exercise, its degree related to the intensity of the exercise.
Causation of these syndromes is mixed and not fully explained. There is good evidence for physical trauma to red cells being a significant part, but this cannot explain the appearance of glomerular red cells and red cell casts. Exercise-related changes mostly resolve within less than a day, and almost all by 72 hours.
Proteinuria
Authors: Turner Neil , Cameron Stewart
Published: November 2015

Excess protein in the urine almost always comes from the kidney. Proteinuria up to 150 mg/day in an adult (protein:creatinine ratio (PCR) up to 15 mg/mmol) is considered normal. Daily average excretion is 80 mg, of which about 30 mg is albumin that has been filtered and not reabsorbed. Other components comprise low-molecular-weight filtered proteins that have escaped reabsorption, and proteins secreted or lost into urine from cells of the nephron. Increased permeability of the glomerulus to high-molecular-weight proteins is the most common cause of the clinically detected proteinuria, and albumin is the major component of excess glomerular proteinuria.
Even small amounts of proteinuria are associated with increased cardiovascular risk and long-term renal risk. In patients with renal disease, regardless of type, proteinuria is a strong predictor of loss of glomerular filtration rate and proteinuria at levels higher than an equivalent of 1 g/24 hours can be considered high renal risk. This limit should be lowered in young patients, and if microscopic haematuria is also present.
For both cardiovascular and renal outcomes, risk is graded with severity of proteinuria. In routine clinical practice, ratios of albumin or total protein to creatinine level (ACR or PCR) in spot urine samples are usually more pragmatic and useful than 24-hour collections. ACR is more sensitive as a screening test (normal range up to 2.5 mg/mmol in men, 3.5 mg/mmol in women).
Pathophysiology of oedema in nephrotic syndrome
Authors: Turner Neil , Rajakrishna Premil
Published: November 2015

The mechanism by which loss of serum proteins into the urine causes expansion of extracellular fluid volume and oedema has become clearer. A key initiating abnormality is avid sodium retention by the kidney, leading to increased whole-body sodium and increased extracellular fluid volume. This appears to be driven primarily by overactivation of the amiloride-sensitive epithelial sodium channel (ENaC) in the collecting duct, activated proteolytically through abnormal filtration of plasminogen, and its activation to plasmin in the nephron.
Conventional explanations for nephrotic oedema focused on low colloid osmotic pressure as a consequence of loss of serum proteins, leading to egress of extracellular fluid from the intravascular compartment. It was hypothesized that this led to underfilling of the circulation and a drive to sodium retention. While low osmotic pressure may play a part in the clinical picture of nephrotic syndrome, a variety of observations suggest that underfilling is not a common feature except in the most severe nephrotic syndrome. Furthermore the gradient in colloid osmotic pressure between serum and interstitium tends to be preserved in nephrotic syndrome.
The distribution of excess extracellular fluid is markedly different in patients with nephrotic syndrome from that seen in patients who have reduced glomerular filtration rate as the cause of sodium retention. This is not fully understood but hypotheses centre on capillary permeability and colloid osmotic pressure effects.
Immunoglobulin A nephropathy
Authors: Lai Kar Neng , Tang Sydney C. W.
Published: November 2015

Immunoglobulin A (IgA) nephropathy is the most common primary glomerulonephritis. It runs a slow and sometimes relentless clinical course with consequent end-stage renal failure in 35–40% of patients 25–30 years after first clinical presentation. The pathology is characterized by deposition of macromolecular (polymeric) IgA1 in the glomerular mesangium, proliferation of mesangial cells, increased synthesis of extracellular matrix, and infiltration of macrophage, monocytes, and T cells.
Drug-induced and toxic glomerulopathies
Authors: Woywodt Alexander , Chiu Diana
Published: November 2015

Glomerulopathies induced by particular exogenous compounds or molecules include those attributable to toxicity, and those caused by inducing an immune or autoimmune response. Tubules are more commonly the target of toxicity as they absorb and concentrate components of filtrate. Damage to endothelial cells may account for thrombotic microangiopathy in response to calcineurin inhibitors. Endothelial cells are also likely to be the target in drug-induced small vessel vasculitis. Toxicity to podocytes accounts for focal segmental glomerulosclerosis caused by pamidronate and other agents. Chloroquine can cause a remarkable pseudo-storage disorder with inclusions in podocytes that resemble those seen in Fabry disease. The mechanism by which drugs cause minimal change disease, another podocyte disorder, is not known. Membranous nephropathy may be caused by exposure to gold, mercury, and some other drugs; this is antibody mediated and presumably the targets are altered podocyte surface molecules. Inhibitors of the mammalian target of rapamycin (mTOR) cause proteinuria, possibly through effects on vascular endothelial growth factor, inhibitors of which are associated with not only proteinuria (an expected podocyte effect) but also thrombotic microangiopathy (endothelial cell effect). This latter may be through disturbing podocyte-endothelium cross-signaling.
Heavy metal-induced tubulointerstitial nephritis
Authors: D’Haese Patrick C. , Vervaet Benjamin A. , Verhulst Anja
Published: November 2015

Environmental and occupational exposure to heavy metals should be considered an important health hazard, even more so since evidence has been provided in recent literature for toxic effects occurring even at low levels. The kidney is highly vulnerable to metal toxicity and the extent of renal damage depends on the nature, dose, route, and duration of exposure. Both acute and chronic intoxication have been demonstrated to cause kidney injury, with various levels of severity, ranging from tubular dysfunctions to severe chronic kidney disease.
The epidemiology of heavy metals poisoning, their renal handling, pathophysiological mechanisms of renal toxicity, diagnosis, and monitoring, as well as therapeutic aspects are dealt with. The metals discussed include lead, cadmium, mercury, uranium, arsenic, and chromium.
Recommendations for management of high renal risk chronic kidney disease
Authors: Ferro Charles J. , Ng Khai Ping
Published: November 2015

Poorer renal function is associated with increasing morbidity and mortality. In the wider population this is mainly as a consequence of cardiovascular disease. Renal patients are more likely to progress to end-stage renal disease, but also have high cardiovascular risk.
Aiming to reduce both progression of renal impairment and cardiovascular disease are not contradictory. Focusing on the management of high-risk patients with proteinuria and reduced glomerular filtration rates, it is recommended that blood pressure should be kept below 140/90, or 130/80 if proteinuria is > 1 g/24 h (protein:creatinine ratio (PCR) >100 mg/mmol or 0.9 g/g). These targets may be modified according to age and other factors. Angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor antagonists should form part of the therapy for patients with proteinuria > 0.5 g/24 h (PCR > 50 mg/mmol or 0.45 g/g). Use of ACEIs or angiotensin receptor blockers in patients with lower levels of proteinuria may be indicated in some patient groups even in the absence of hypertension, notably in diabetic nephropathy. Evidence that other agents that reduce proteinuria bring additional benefits is weak at present. The best studies of ‘dual-blockade’ with various combinations of ACEIs, ARBs, and renin inhibitors have shown additional hazard with little evidence of additional benefit.
Hyperlipidaemia—regardless of lipid levels, statin therapy is indicated in secondary cardiovascular prevention, and in primary prevention where cardiovascular risk is high, noting that current risk estimation tools do not adequately account for the increased risk of patients with CKD. There is not substantial evidence that lipid lowering therapy impacts on average rates of loss of GFR in progressive CKD. Non-drug lifestyle interventions to reduce cardiovascular risk, including stopping smoking, are important for all. Acidosis—in more advanced CKD it is justified to treat acidosis with oral sodium bicarbonate.
Diet—sodium restriction to < 100 mmol/day (6 g/day) and avoidance of excessive dietary protein are justified in early to moderate CKD. Recommendations to limit levels of protein to 0.8 g/kg body weight are suggested by some, but additional protective effects of this are likely to be slight in patients who are otherwise well managed. Low-protein diets may carry some risk. Lower-protein diets may however be used to prevent symptoms in advanced CKD not treated by dialysis.
Diet and the progression of chronic kidney disease
Authors: Carrero Juan Jesús , Xu Hong , Lindholm Bengt
Published: November 2015

The dietary management of non-dialysed CKD patients has focused on limiting the intake of substances which lead to accumulation of urea, potassium, phosphorus, and sodium. Recent advances in nutritional epidemiology have given us the opportunity to examine the relationships between diet and CKD. This chapter focuses on evidence relating to retarding progression of renal impairment in the early to mid stages of CKD. Limits may need to change if GFR falls.
The hypothesis that a high dietary protein intake leads to progressive CKD through a mechanism of glomerular hyperfiltration has been taught for decades, and it appears effective in animals. However, the evidence that low-protein diets (LPDs) halt CKD progression in patients is weak. Their management is of course likely to include other interventions such as blood pressure control. There is risk to low-protein diets. There is some evidence that high protein intakes are harmful. We therefore recommend moderate protein intake (not low; not high – no protein supplements; around 1g/kg/day).
Salt handling is impaired in most patients with CKD, probably even early stages, and hypertension is an early feature, except in salt-losing patients, to whom different rules apply. Salt intake tends to raise blood pressure, worsen proteinuria, and reduce the effects of angiotensin converting enzyme inhibitors on blood pressure and proteinuria. Very low salt intakes are difficult to comply with and limit diet. In early stages of CKD we therefore recommend restriction to moderately low levels (below 6g/day of salt; 100 mmol of sodium). Lower levels may have additional benefits, and these limits may need to be reduced as GFR declines.
Potassium is associated with healthy, desirable foods such as fruit and vegetables. It should only be restricted if high serum values make this necessary.
Smoking in chronic kidney disease
Authors: Orth Stephan R.
Published: November 2015

Smoking has been acknowledged as the number one preventable cause of death in most countries. The adverse effects of smoking on the kidney are less known.
Prospective, population-based, observational studies, and evidence from experimental work indicate that smoking (a) is a relevant risk factor for chronic kidney disease (CKD) in the general population and (b) is associated with an increased risk of deterioration in renal function in CKD patients. The latter is especially true for patients with diabetic nephropathy or hypertensive renal damage. The conclusion is that smoking is an important renal risk factor and nephrologists should make greater efforts to motivate patients to stop smoking, not least because smoking cessation improves the prognosis of CKD.
Iron metabolism in chronic kidney disease
Authors: Malyszko Jolanta , Macdougall Iain C.
Published: November 2015

While whole-body (‘absolute’) iron deficiency is common and probably increased in frequency in chronic kidney disease (CKD), functional iron deficiency is a particular problem in CKD. Absolute iron deficiency is likely to be present in advanced CKD when the ferritin falls below 100 ng/mL and the TSAT falls below 20%.
Functional iron deficiency is characterized by the presence of adequate iron stores (as defined by conventional criteria), but with an inability to mobilize this iron rapidly enough to adequately support erythropoiesis with the administration of erythropoietin. Among such patients, the serum ferritin level is either normal or elevated (usually between 100 and 800 ng/mL), with a TSAT typically ≤20%.
Hepcidin, a novel peptide discovered at the turn of the twenty-first century, is an iron gatekeeper that plays a key role in functional iron deficiency, and the ‘anaemia of chronic disease’. The main function of hepcidin is homeostatic regulation of iron metabolism and mediation of host defence and inflammation. Hepcidin is the predominant negative regulator of iron absorption in the small intestine, iron transport across the placenta, and iron release from the macrophages. Novel strategies that modulate hepcidin and its target ferroportin for the treatment of anaemia of chronic diseases are currently undergoing extensive research.
Pleiotropic effects of vitamin D
Authors: Khavandi Kaivan , Amer Halima , Withers Sarah , Afzali Behdad
Published: November 2015

Vitamin D is a fat-soluble steroid pro-hormone integral to physiological health, fulfilling a central role in skeletal mineralization, bone metabolism, and immune biology. Although vitamin D is synthesized photochemically in the skin and some is absorbed from dietary sources, vitamin D insufficiency and deficiency are very common. Epidemiological studies have demonstrated a strong association between vitamin D and kidney and heart disease, and some supplementation studies have suggested that repletion may prevent and/or ameliorate cardiorenal injury. This chapter focuses on vitamin D biology and discusses the many associations of vitamin D perturbation with diseases of humans.
Coagulopathies in chronic kidney disease
Authors: Shrivastava Seema , Hunt Beverley J. , Dorling Anthony
Published: November 2015

Coagulation abnormalities are common in chronic kidney disease (CKD). Both haemorrhage and thrombosis are more common than in the general population.
Haemorrhage, when it occurs, is associated with increased morbidity and mortality compared to that seen in non-uraemic patients. It is more likely spontaneously, but particularly in association with anti-platelet agents or anticoagulants.
The increased risk of both arterial and venous thrombosis occurs in part because of the increase prevalence of traditional risk factors for thrombosis in CKD, in part because of the specific problems associated with nephrotic syndrome, and also because of specific putative prothrombotic factors associated with CKD, such as increased levels of coagulation factors and altered platelet function associated with uraemia.
Two syndromes, both characterized by intravascular thrombosis can contribute to the development of CKD. The first is antiphospholipid syndrome, due to the presence of antibodies against negatively charged phospholipids, in which thrombosis of the renal vasculature is relatively common. The second is a group of conditions, the thrombotic microangiopathies, in which inherited or acquired deficiencies of ADAMTS13, antiphospholipid antibodies, or pathological endothelial cell activation in renal vessels, sometimes due to functional deficiencies of one or more proteins regulating coagulation or complement activation, leads to acute renal dysfunction associated with anaemia.
Modality selection for renal replacement therapy
Authors: Thuraisingham Raj , Breen Cormac
Published: November 2015

The choice of treatment for end-stage kidney disease is an important one for patients. Ideally this should happen as a coordinated process over a period of time, supported by education and individualized treatment planning discussions to assist the patient in making an informed choice about their treatment. In this setting, patients suitable for transplantation may select this treatment modality and potentially, especially if there is a living kidney donor, be transplanted before the need for dialysis. Other patients may choose between dialysis modalities, between home and in-centre treatment, or in some cases between active dialysis treatment and conservative kidney care. A smaller proportion of patients may present with the urgent need to start dialysis, the crash-lander pathway. In this situation initial treatment planning and choice is more limited, treatment is more often determined by institutional practice, and treatment choice and formation of definitive dialysis access are achieved at a later date.
Patient education and involvement in pre-dialysis management
Authors: Cox Sue , Thomas Nicola
Published: November 2015

A well-structured, patient-focused education programme is essential in the pre-dialysis setting. It is well recognized that patients with progressive chronic kidney disease stages 4 and 5 need to access appropriate levels of education to ensure patient choice, preparation, and timely commencement of renal replacement therapy. This education needs to be structured to suit different learning styles, individualized in approach and provided by healthcare professionals who have appropriate training and skills. There are many barriers to learning and individuals need information at different times, in different formats, and varying levels. Assessment and individualized planning is paramount prior to any information being provided to ensure maximum benefit. Education should be provided in many formats and tailored to meet the individual’s needs. Patient involvement in education (peer education) is recommended. All education programmes should be continuously evaluated and user involvement is a must when developing and evaluating any aspect of the education programme.
The patient with vasculitis
Authors: Jayne David
Published: November 2015

The definition of vasculitis syndromes relies on clinical, serological, and pathological descriptions. A number of primary syndromes are recognized, of presumed autoimmune aetiology, but vasculitis may also occur as a secondary disease process. The heterogeneity of clinical presentation, low specificity of many clinical features, and mimics of other diseases complicate vasculitis diagnosis. The kidney is the most common severe manifestation for small vessel vasculitis syndromes and the severity of renal involvement predicts end-stage renal failure risk and death. Suspicion of vasculitis is key to early diagnosis and improving outcomes of vasculitis patients.

The current understanding of the classification of vasculitis syndromes is presented in this chapter along with descriptions of clinical presentations, and approaches to diagnosis.
The patient with systemic lupus erythematosus
Authors: van der Vlag Johan , Berden Jo H. M.
Published: November 2015

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with various clinical manifestations. The hallmark of SLE is the presence of antibodies against nuclear constituents, such as double-stranded (ds)DNA, histones, and nucleosomes. Local deposition of antinuclear antibodies in complex with nuclear autoantigens induces serious inflammatory conditions that can affect several tissues and organs, including the kidney.

The levels of antinucleosome and anti-dsDNA antibodies seem to correlate with glomerulonephritis and these autoantibodies can often be detected years before the patient is diagnosed with SLE. Apoptotic debris is present in the extracellular matrix and circulation of patients with SLE due to an aberrant process of apoptosis and/or insufficient clearance of apoptotic cells and apoptotic debris. The non-cleared apoptotic debris in patients with SLE may lead to activation of both the innate (myeloid and plasmacytoid dendritic cells) and adaptive (T and B cells) immune system. In addition to the activation by apoptotic debris and immune complexes, the immune system in SLE may be deregulated at the level of (a) presentation of self-peptides by antigen-presenting cells, (b) selection processes for both B and T cells, and (c) regulatory processes of B- and T-cell responses. Lupus nephritis may be classified in different classes based on histological findings in renal biopsies. The chromatin-containing immune complexes deposit in the capillary filter, most likely due to the interaction of chromatin with the polysaccharide heparan sulphate. A decreased renal expression of the endonuclease DNaseI further contributes to the glomerular persistence of chromatin and the development of glomerulonephritis.

Current treatment of lupus nephritis is not specific and aims to reduce the inflammatory response with general immunosuppressive therapies. However, research has revealed novel potential therapeutic candidates at the level of dendritic cells, B cells, and T cells.
The patient with haemolytic uraemic syndrome/thrombotic thrombocytopenic purpura
Authors: Noris Marina , Goodship Tim
Published: November 2015

The patient who presents with microangiopathic haemolytic anaemia, thrombocytopenia, and evidence of acute kidney injury presents a diagnostic and management challenge. Haemolytic uraemic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) are two of the conditions that frequently present with this triad. They are characterized by low platelet count with normal or near-normal coagulation tests, anaemia, and signs of intravascular red cell fragmentation on blood films, and high LDH levels.

HUS associated with shiga-like toxins produced usually by E.coli (typically O157 strains) may occur in outbreaks or sporadically, with geographical variations in incidence. It is predominantly a disease of young children in which painful blood diarrhoea in a minority of infected patients is succeeded by microangiopathy and acute kidney injury. Management is supportive and recovery is usual, although permanent renal damage may lead to later deterioration. Older patients may be affected and tend to have worse outcomes. Neuraminidase-producing Streptococcus pneumoniae infections (usually pneumonia) very rarely cause a similar HUS.

Atypical HUS occurs sporadically and is increasingly associated with defects in the regulation of the complement pathway, either genetic or autoimmune-caused. It may respond to plasma exchange for fresh frozen plasma. Recurrences are common, including after transplantation.

TTP is associated with more neurological disease and less renal involvement, but HUS and TTP overlap substantially in their manifestations. The underlying problem is in von Willebrand factor (vWF) cleavage. The plasma metalloprotease ADAMTS13 is responsible for cleaving vWF multimers, a process that is important to prevent thrombosis in the microvasculature. Autoantibodies or rarely genetic deficiency may impair this process. Plasma exchange may remove antibodies and replenish the protease.
Urinary tract infection in the adult
Authors: Sheerin Neil
Published: November 2015

Infection of the urinary tract is one of the commonest human infections. It can vary in severity from asymptomatic colonization, through self-limiting but distressing lower tract infection, to life-threatening sepsis. Any site in the urinary tract can be affected. The site of infection determines the pattern of symptoms, but this is also influenced by the age at presentation. The age at presentation and the nature of symptoms will not only suggest a clinical diagnosis, but also guide investigation and treatment. This chapter acts as an introduction to others in this section which address the different presentations of infections of the lower and upper urinary tracts in adults.
Upper urinary tract infection
Authors: Harber Mark
Published: November 2015

Pyelonephritis is a suppurative infection of the kidney most commonly due to bacterial infection that may be either acute or chronic. Acute pyelonephritis is usefully subdivided into uncomplicated and complicated. The term complicated pyelonephritis is associated with an abnormal urinary tract, obstruction, stones, immunocompromise, diabetes, pregnancy, or in practical terms any pyelonephritis resulting in severe illness. The distinction is important principally in terms of type, duration, and place of treatment.

The clinical spectrum of acute pyelonephritis ranges from relatively mild illness to pyonephrosis and emphysematous pyelonephritis with a fulminant course and high mortality.

The term chronic pyelonephritis has been used to describe kidneys damaged from multiple, recurrent, or partially treated episodes of infection, but for many of these examples ‘reflux nephropathy’ is a better description as the role of infection is not always clear. However chronic or very recurrent infections may be associated with diabetes, abnormal urinary tracts, and any cause of obstructed drainage. Chronic pyelonephritis is also an accurate description for the progressive ongoing destruction of the kidney that occurs in xanthogranulomatous pyelonephritis or malakoplakia.
Calcium stones
Authors: Bushinsky David A. , Moe Orson
Published: November 2015

Key predisposing factors in calcium stone formation are idiopathic hypercalciuria, primary hyperparathyroidism, and hyperoxaluria (dietary, enteric, idiopathic, sometimes genetic). These are described in detail. Other predisposing conditions include renal tubular acidosis, and risk factors identified in epidemiological studies such as hypocitraturia, increased urinary urate. is defined as an excess of urine calcium excretion without a discernible metabolic cause.
Cell biology of nephrocalcinosis/nephrolithiasis
Authors: Vervaet Benjamin A. , De Broe Marc E.
Published: November 2015

A dozen conditions are regularly associated with nephrocalcinosis, and two dozen more less frequently. Mechanisms of intratubular and interstitial crystal formation, and propagation or removal, as well as inhibitors of crystal formation, are described.
The structure and function of renal blood vessels
Authors: Endlich Karlhans , Loutzenhiser Rodger
Published: November 2015

The unique structural and functional properties of the renal vasculature are essential in facilitating the massive filtration and reabsorptive processes required for normal renal function. The afferent and efferent arterioles have evolved distinct activation mechanisms that allow an independent regulation of the inflow and outflow resistances of the glomerular capillaries and physiologic control of glomerular capillary pressure and glomerular filtration rate.
The kidney and control of blood pressure
Authors: Gonzalez-Albarrán Olga , Ruilope Luis M.
Published: November 2015

The kidneys can be at the root of the development of arterial hypertension or they can participate in the maintenance of hypertension and its sequels. Renal alterations interfering with the regulation of sodium homeostasis or facilitating the generation of vasoconstrictors, particularly angiotensin II, are involved in the dysregulation of arterial blood pressure that underlies the development of arterial hypertension. The biology of angiotensin is described in detail.

The kidneys are also the mediator of hypertension in such examples as renal ischaemia and hyperaldosteronism. The role of renal nerves, and renal depressor substances, are also described.

Transplantation experiments in animals and observations in human transplantation, as well as some primary gene defects, show the importance of renal mechanisms in hypertension. Once kidneys have been damaged, they often contribute to an increase in arterial pressure. Salt sensitivity is probably a major part of the mechanism, but it is mediated by multiple pathways.
The effect of hypertension on renal vasculature and structure
Authors: Wenzel Ulrich , Wiech Thorsten , Helmchen Udo
Published: November 2015

The concept of hypertensive nephrosclerosis was introduced by Volhard and Fahr in 1914 and has been extensively used in the literature since then, but its existence is controversial. While it is indisputable that malignant hypertension is a cause of end-stage renal disease (ESRD), there remains controversy as to whether the so-called benign nephrosclerosis can also lead to ESRD.

Pressure, if it is great enough, will eventually disrupt any structure. Obviously, this is also true of blood pressure. It is therefore not surprising that an experimentally induced great increase in pressure disrupts the integrity of the blood-vessel wall. Such vascular lesions may be caused or at least influenced by several factors: humoral factors such as angiotensin II, catecholamines, mineralocorticoids, and vasopressin may increase vascular permeability, thereby damaging the vessel walls independently of, or superimposed upon, elevated blood pressure.

Nephrosclerosis (literally, hardening of the kidney, Greek derivation: nephros, kidney; sclerosis, hardening) refers to diseases with predominant pathological changes occurring in the pre-glomerular vasculature and secondary changes involving the glomeruli and interstitium. Therefore, it is appropriate to describe first those vascular lesions, which, at least under defined experimental conditions, are believed to be caused solely by the presence of hypertension.
Renal artery stenosis
Authors: Ritchie James , Green Darren , Chrysochou Constantina , Kalra Philip A.
Published: November 2015

Modern practice typically utilizes indirect angiography by computed tomography or magnetic resonance imaging as the first-line diagnostic tool for renal artery stenosis, with no established screening tool able to meaningfully impact the pre-test probability of a positive finding. Neither can any current imaging technique reliably predict patient, blood pressure, or renal outcome following renal artery revascularization, although promising developments have been made in recent years.

A major mechanism of hypertension in renovascular hypertension is overproduction of renin in response to hypoperfusion. While renin levels can be useful in investigating patients likely to have secondary hypertension, in the setting of renal impairment renin levels are not particularly useful in distinguishing treatable renal artery stenosis from other causes of renal disease.
Non-dialytic management of the patient with acute kidney injury
Authors: Jörres Achim , Hasper Dietrich , Oppert Michael
Published: November 2015

The main focus in the non-dialytic management of patients with acute kidney injury (AKI) is the prevention and treatment of complications.

Nutritional support is an important aspect as many patients tend to be hypercatabolic, thus requiring adequate caloric intake, yet without administration of excessive fluid volumes. Inadequate nutrition in AKI may lead to enhanced production of urea nitrogen and azotaemia. However, hyperglycaemia is a frequent complication in these patients, often requiring continuous insulin therapy to achieve the recommended blood glucose target range of 110–150 mg/dL (6.11–8.33 mmol/L).

Patients with AKI are prone to infections which are a common cause of death in this population. Careful search for and intensive treatment of infections is therefore of utmost importance, and antimicrobial chemotherapy must be initiated as early as possible, especially in patients with sepsis and AKI.

Drug dosing in patients with AKI is complex and difficult. Residual kidney function can be highly variable and drug disposition may be altered due to changes in distribution volume, protein binding, and metabolism. Moreover, many drugs can be removed by renal replacement therapy (RRT). Therefore, adequate dosing must take into account the patient’s individual clinical characteristics, the specific pharmacokinetic/pharmacodynamic properties of the drug, and the mode and intensity of renal replacement therapy.
Electrolyte and acid–base disorders in AKI
Authors: Jörres Achim , Hasper Dietrich , Oppert Michael
Published: November 2015

Electrolyte disturbances are common in patients with acute kidney injury (AKI) and should be corrected. In particular, hyperkalaemia above 6–6.5 mmol/L (especially with electrocardiogram changes) constitutes a medical emergency and warrants immediate intervention. Both hypo- and hypernatraemia may occur during AKI. Chronic changes in serum sodium need to be corrected bearing in mind the underlying pathology; however, when severe and evolving rapidly they should be corrected faster, irrespective of the cause. Acid–base disorders are also common in AKI and need to be treated in the context of underlying problems and physiological compensatory mechanisms. In metabolic acidosis, a bicarbonate deficit may be corrected by sodium bicarbonate administration. Of note, whilst patients with AKI tend to retain electrolytes such as potassium and phosphate, this might be reversed during renal replacement therapy and even substitution of these losses may be required.