bluuebunny/crossref_metadata_2025 huggingface dataset:
The patient with renal cell cancer
Authors: Eisen Tim
Published: November 2015

Renal cancer is the commonest malignancy of the kidney and worldwide, accounts for between 2% and 3% of the total cancer burden. The mainstay of curative treatment remains surgery. There have been significant advances in surgical technique, the most important ones being nephron-sparing surgery and laparoscopic nephrectomy. The medical treatment of advanced renal cell cancer has only improved markedly in the last decade with the development of antiangiogenic tyrosine-kinase inhibitors, inhibitors of mammalian target of rapamycin, and a diminished role for immunotherapy.

Tyrosine-kinase inhibitor therapy results in reduction of tumour volume in around three-quarters of patients and doubles progression-free survival, but treatment is not curative. The management of side effects in patients on maintenance tyrosine-kinase inhibitors has improved in the last 3 years, although still presents difficulties which have to be actively considered.

The molecular biology of renal cell carcinoma is better understood than for the majority of solid tumours. The commonest form of renal cancer, clear-cell carcinoma of the kidney, is strongly associated with mutations in the von Hippel–Lindau gene and more recently with chromatin-remodelling genes such as PBRM1. These genetic abnormalities lead to a loss of control of angiogenesis and uncontrolled proliferation of tumour cells. There is a very wide spectrum of tumour behaviour from the extremely indolent to the terribly aggressive. It is not currently known what accounts for this disparity in tumour behaviour.

A number of outstanding questions are being addressed in scientific and clinical studies such as a clearer understanding of prognostic and predictive molecular biomarkers, the role of adjuvant therapy, the role of surgery in the presence of metastatic disease, how best to use our existing agents, and investigation of novel targets and therapeutic agents, especially novel immunotherapies.
Complicated urinary tract infection
Authors: Ali Ased , Pickard Rob
Published: November 2015

‘Complicated’ urinary tract infection (UTI) indicates infection occurring in anatomically or functionally abnormal urinary tract. Infections are not only more likely in such circumstances, but they are more likely to lead to complications such as acute pyelonephritis, and are frequently more difficult to eradicate, requiring more prolonged antimicrobial therapy. Some causes may be associated with susceptibility to specific micro-organisms. There may occasionally be a limited place for prophylactic therapy.
Hepatitis C
Authors: Fabrizi Fabrizio
Published: November 2015

Hepatitis C virus (HCV) is associated with a large spectrum of histopathological lesions in both native and transplanted kidneys. The exact frequency of kidney damage in HCV-infected patients remains unknown, but the most frequent associated renal lesion is membranoproliferative glomerulonephritis (MPGN) with deposition of immunoglobulin and complement (MPGN type 1), usually in the context of type II mixed cryoglobulinaemia associated with a monoclonal IgM which binds IgG.

Various approaches have been tried for the treatment of HCV-related glomerulonephritis, including immunosuppressive therapy (corticosteroids and cytotoxic agents), plasma exchange, and antiviral agents. Use of antiviral drugs for treatment of HCV-associated glomerulonephritis has shown encouraging results. Immunosuppressive therapy is recommended for cryoglobulinaemic kidney disease. Two distinct approaches should be considered for the treatment of HCV-associated cryoglobulinaemic glomerulonephritis according to the level of proteinuria and kidney failure. Preliminary evidence on rituximab therapy for HCV-related cryoglobulinaemic glomerulonephritis exists but several questions related to its use remain unclear.
Syphilis
Authors: Burdmann Emmanuel A.
Published: November 2015

Syphilis is an infectious disease caused by the bacterium Treponema pallidum. The transmission route is usually sexual, but prenatal contamination (congenital syphilis) and transmission by infected blood can also occur. The most frequent presentation of syphilis nephropathy is proteinuria, and the most common form of associated glomerular disease is membranous glomerulopathy. Kidney disease usually reverts with antibiotic therapy. Syphilis must always be considered in proteinuric HIV-infected patients. Renal biopsy is necessary to differentiate between HIV-associated nephropathy and syphilis-induced glomerulopathies, since both kidney diseases have analogous clinical presentations, but syphilis-induced glomerulopathies may recover with syphilis successful treatment.
Rickettsiosis
Authors: Burdmann Emmanuel A. , Jha Vivekanad
Published: November 2015

Rickettsiae are obligate intracellular bacteria transmitted by arthropods to a vertebrate host. Clinically relevant rickettsioses have a similar clinical pattern, manifesting as an acute febrile disease accompanied by headache, articular and muscle pain, and malaise.

Epidemic typhus is a worldwide distributed disease caused by the Rickettsia prowazekii, with a human louse as a vector. Data on epidemic typhus-related renal injury is extremely scarce.

Murine typhus is caused by the Rickettsia typhi and has a rodent flea as the vector. It is one of the most frequent rickettsioses, and is usually a self-limited febrile illness. Proteinuria, haematuria, elevations in serum creatinine (SCr) and/or blood urea nitrogen (BUN) and AKI have been reported. The real frequency of renal involvement in murine typhus is unknown. Renal abnormalities recover after the infectious disease resolution.

Scrub typhus, caused by the Orientia tsutsugamushi, has the Leptotrombidium mite larva as vector. It is endemic in the Tsutsugamushi triangle delimited by Japan, Australia, India, and Siberia. It can manifest either as a self-limiting disease or as a severe, life-threatening multiorgan illness. Early administration of adequate antibiotics is essential to prevent adverse outcomes. Proteinuria, haematuria, and acute kidney injury (AKI) are frequent.

Tick-borne rickettsioses are caused by bacteria from the spotted fever group and have ticks as vectors. Rocky Mountain spotted fever (RMSF) is caused by Rickettsia rickettsii. It is the most severe of the spotted fever rickettsial diseases, causing significant morbidity and lethality. RMSF occurs in North, Central, and South America. Renal impairment is frequent in severe forms of RMSF. Mediterranean spotted fever is caused by Rickettsia conorii, and is endemic in the Mediterranean area. It is usually a benign disease, but may have a severe course, clinically similar to RMSF. Haematuria, proteinuria, increased serum creatinine, and AKI may occur. Japanese spotted fever is caused by Rickettsia japonica. Lethal cases are reported yearly and AKI has occurred in the context of multiple organ failure.
Epidemiology of nephrolithiasis
Authors: Taylor Eric N. , Curhan Gary C.
Published: November 2015

Nephrolithiasis is common, costly, and painful. The prevalence of nephrolithiasis, defined as a history of stone disease, varies by age, sex, race, and geography while the incidence of nephrolithiasis, defined as the first stone event, varies by age, sex, and race. Epidemiologic studies have quantified the burden of kidney stone disease and expand our understanding of risk factors. A variety of dietary, non-dietary, and urinary risk factors contribute to the risk of stone formation and the importance of these varies by age, sex, and body mass index.

Low fluid intake, high urinary oxalate or calcium or uric acid, and low urinary citrate are all associated with nephrolithiasis. These results from epidemiologic studies can be considered in the clinical setting when devising treatment plans to reduce stone recurrence.
Approach to the patient with kidney stones
Authors: Chopra Bhavna , Goldfarb Stanley
Published: November 2015

A detailed history can identify some risk factors and narrows down the potential causes of kidney stone formation. Radiological investigations confirm the diagnosis and give information on likely stone type. Urine and serum biochemistry is invaluable, but a more comprehensive investigation is reserved for recurrent stone formers. In that case at least two 24h collections, remote from any acute event are recommended, measuring volume, pH, calcium, oxalate, citrate, uric acid and phosphate. Urinary crystals can shed light on some stone types.

For single or recurrent stones, analysis of stones themselves is invaluable. Analysis may include X-ray diffraction, infrared spectroscopy and a number of other techniques. .

Dietary evaluation is valuable in recurrent stone formers.
Imaging and interventional treatment
Authors: Raynal Gauthier , Traxer Olivier
Published: November 2015

Abstract

Urolithiasis has a great importance in the urologist’s practice: it is a common disease which represent a great part of the urologist’s activity, and stone disease is linked to the beginning of urology as an individual medical specialty and to many technical improvements, from the beginning of endoscopy up to extracorporeal shockwave lithotripsy and modern endourology.

Imaging and diagnostic techniques and pain relief are described. Usually stones <5mm will pass spontaneously and are managed conservatively. At 5-10mm medical expulsive therapy with an alpha-adrenergic blocker will shorten symptoms. Stones larger than this are likely to need tailored treatment depending on stone type and location and history, choosing from endoscopy, shockwave lithotripsy, or percutaneous lithotripsy.
Regulation of vasomotor tone in the afferent and efferent arterioles
Authors: Endlich Karlhans , Loutzenhiser Rodger
Published: November 2015

Pre-glomerular vessels are regulated by membrane potential alterations affecting the activity of L-type voltage-activated Ca2+ channels; whereas voltage-independent mechanisms regulate the efferent arteriole, notably influenced by angiotensin II and therefore by angiotensin converting enzyme inhibitors, and by non-steroidal anti-inflammatory drugs.

These properties underlie the physiologic control of glomerular capillary pressure, for example, by prostaglandin E2, during conditions of reduced renal perfusion and the stabilization of glomerular capillary pressure when the kidney is exposed to pressure fluctuations. A wealth of hormones affects the tone of renal vessels. The chapter focuses on basic regulatory and signalling mechanisms, emphasizing the unique aspects of the renal vasculature and the underlying features that facilitate the independent regulation of pre-glomerular and post-glomerular tone.
Ischaemic nephropathy
Authors: Alderson Helen , Chrysochou Constantina , Ritchie James , Kalra Philip A.
Published: November 2015

Ischaemic nephropathy describes loss of renal function or renal parenchyma due to stenosis or occlusion of the renal artery or its branches. In the Western world, this is usually the result of atherosclerotic renovascular disease, but other aetiologies include arteritis, embolic disease, dissection, and fibromuscular disease.

Chronic kidney disease is the most common manifestation of ischaemic nephropathy, but hypertension, flash pulmonary oedema, sensitivity to angiotensin blockade, and sensitivity of glomerular filtration rate to blood pressure reduction are all possible manifestations of occlusive diseases of the renal artery or its branches. Proteinuria may also occur.

This chapter describes these clinical features and the outcomes of ischaemic nephropathy. It goes on to discuss the haemodynamics and mechanisms and what we understand of the pathophysiology of the condition.
Coagulation disturbances in acute kidney injury
Authors: Jörres Achim , Hasper Dietrich , Oppert Michael
Published: November 2015

Patients with acute kidney injury may suffer from disturbances of the coagulation systems, either as a consequence of uraemia, or on the basis of an underlying disease, or due to blood–membrane interaction and/or anticoagulation during renal replacement therapy. The implications of this for their management, and anticoagulation during renal replacement therapy, are discussed. Some specific circumstances, including thrombotic microangiopathy, are mentioned.
Peritoneal dialysis in acute kidney injury
Authors: Van Biesen Wim
Published: November 2015

The advent of intermittent and continuous haemodialysis meant that peritoneal dialysis was progressively neglected for treatment of acute kidney injury. However, peritoneal dialysis has some specific features making it a suitable treatment in certain indications, such as risk of bleeding, neurosurgery, or haemodynamically unstable patients. In view of its low cost and relatively simple technology, it is also a very suitable technique in locations where no haemodialysis is available. Some specific aspects of the patient with acute kidney injury, mostly the fact that these patients are fast transporters, should be taken into account in the prescription. Occurrence of peritonitis should be monitored, and antibiotic treatment should be tailored to the higher clearances obtained in acute peritoneal dialysis as compared to chronic peritoneal dialysis.
Acute kidney injury in children
Authors: Fichtner Alexander , Schaefer Franz
Published: November 2015

In the past few decades, the overall incidence of acute kidney injury (AKI) in paediatric patients has increased and the aetiological spectrum has shifted from infection-related and intrinsic renal causes towards secondary forms of AKI related to exposure to nephrotoxic drugs and complex surgical, oncological, and intensive care manoeuvres. In addition, neonatal kidney impairment and haemolytic uraemic syndrome continue to be important specific paediatric causes of AKI raising unique challenges regarding prevention, diagnosis, and treatment. The search for new biomarkers is a current focus of research in paediatric as in adult AKI research.

Pharmacological intervention studies to prevent or attenuate AKI have provided positive evidence only for the prophylactic use of theophylline in severely depressed neonates, whereas dopamine and loop diuretics did not demonstrate any efficacy. Preliminary findings support a dose-dependent renoprotective action of fenoldopam in infants undergoing cardiac surgery.

Critical issues in the management of AKI in children include fluid handling, maintenance of adequate nutrition, and the choice of renal replacement therapy modality. Observational studies have suggested an adverse impact of fluid overload and late start of renal replacement therapy, and a randomized clinical trial revealed detrimental effects of aggressive fluid bolus therapy in volume-depleted children.

Technological advances have made it possible to apply continuous replacement therapies in children of all ages, including preterm neonates, using appropriately sized catheters, filters, tubing, and flow settings adapted to paediatric needs. However, the majority of children with AKI worldwide are still treated with peritoneal dialysis, and comparative studies demonstrating superiority of extracorporeal techniques over peritoneal dialysis are lacking.

The outcomes of paediatric AKI are comparable to adult patients. In critically ill children, mortality risk increases with each stage of AKI; mortality rates typically range between 15% and 30% for all AKI stages and 30% to 60% in children requiring renal replacement therapy. Chronic kidney disease develops in approximately 10% of children surviving AKI.
Cardiovascular surgery and acute kidney injury
Authors: Brown Jeremiah R. , Parikh Chirag R.
Published: November 2015

Over the last decade, cardiac surgery-associated acute kidney injury (AKI) has been recognized as a frequent adverse event following cardiac surgery. In this clinical context and others, AKI has been strongly associated with increased morbidity, mortality, and length of hospitalization. These adverse events that accompany AKI have been shown to be directly proportional to the magnitude of the peak rise in serum creatinine and the duration of AKI making AKI a costly complication and a target for prevention in hospitalized patients around the world. This chapter discusses the subsequent healthcare costs, utilization, mortality, and morbidity that follow subtle changes in serum creatinine known as AKI in the perioperative setting of cardiac surgery.
Contrast-induced acute kidney injury
Authors: Stewart Douglas , Shah Gaurav , Brown Jeremiah R. , McCullough Peter A.
Published: November 2015

Contrast-induced acute kidney injury (CI-AKI) occurs because all forms of intravascular contrast contain iodine and their biochemical structures induce immediate changes in systemic and renal vasoreactivity. In the kidneys, contrast induces a transient decrease in renal blood flow. This is more pronounced in patients with chronic kidney disease and diabetes mellitus. The reduction in blood flow allows slowed transit of contrast and reabsorption by the proximal tubular cells where contrast is directly toxic resulting in tubular cell dysfunction and death. When there is considerable damage, a transient rise in serum creatinine and reduction in urine output will be observed in the hours to days after contrast exposure. Principles to reduce CI-AKI include limiting the amount of contrast used, intravascular volume expansion to maximize renal blood flow and speed transit of contrast, and possibly agents to reduce the oxidative damage caused by the contrast agents themselves.
Acute kidney injury in pulmonary diseases
Authors: Yoon Soo Young , Mehta Ravindra L.
Published: November 2015

Acute kidney injury (AKI) and acute lung injury often complicate the course of hospitalized patients particularly in the ICU setting. When this association is present it is associated with high mortality. While one disorder may precede the other, they are particularly problematic when they coexist. Patients with AKI are more likely to be ventilated than patients without AKI and they have impaired ability to wean from the ventilator. This chapter describes the alterations in renal function in lung diseases, the alterations in lung function in patients with kidney disease, the pathophysiology of lung–kidney interactions, and the application of these interactions for clinical care. In addition the early recognition of AKI in lung injury and interventions to attenuate injury are described.
Haemodialysis
Authors: Ronco Claudio , Clark William R.
Published: November 2015

End-stage renal disease (ESRD) is common clinical condition for which life-sustaining therapies fortunately exist. On a global basis, more than 2 million patients now receive chronic haemodialysis (HD) for treatment of ESRD. For the vast majority of these patients, treatment is provided in a dialysis unit on a thrice-weekly basis, although there is growing interest in alternative therapies which vary with respect to location or frequency. Based on the number of patients requiring chronic HD now and in the foreseeable future, it is imperative that nephrologists understand the basic principles underlying this treatment. The factors affecting the delivery of therapy in HD can substantially be divided into two groups: (a) factors affecting the performance of the dialytic technique, which are primarily related to the characteristics of the parameters involved in the dialytic technique; and (b) factors affecting the clinical results of a given technique, which are primarily related to the interaction between the water and solute removal capacity of the technique and the kinetics of water and solutes within the human body. In this group, factors including staff compliance with the orders, patient compliance with prescribed time, and the patient’s physical condition are also important.

The focus of this chapter is the technical aspects of chronic HD prescription and delivery. After a brief review of the major components of the HD system (machine and extracorporeal circuit), the principles underlying solute and water removal are reviewed. The concept of clearance is then assessed, with particular emphasis on the determinants of small solute clearance with respect both to the dialyser and the patient.
Dialysis withdrawal and palliative care
Authors: Pinkhasov Arkadiy , Germain Michael J. , Cohen Lewis M.
Published: November 2015

This chapter discusses why dialysis withdrawal is so common in the United States, when dialysis withdrawal and withholding is appropriate, and the role of palliative care in the renal patient. It discusses guidelines that were created to aid in dialysis withdrawal, dialysis initiation, and prognostic calculation. Factors contributing to the phenomenon of dialysis discontinuation include variability in the criteria for initiation of renal replacement therapy, increasing numbers of incident and prevalent geriatric patients, new emphasis on autonomy and quality of life, the development of improved prognostic instruments for prediction of survival, growing acceptance of medical decisions that accelerate dying, and a clearer appreciation of the quality of dying that ensues following the cessation of dialysis. There continues to be a need for further integration of palliative medicine in the clinical management of patients with chronic kidney disease, especially since hospice services are often unavailable unless a decision is made to stop dialysis treatment. The importance of communication between staff and patients and the documentation of the plan of care is critical.
Peritoneal dialysis
Authors: Stachowska-Pietka Joanna , Waniewski Jacek , Lindholm Bengt
Published: November 2015

The principles of peritoneal dialysis are based on the physiological processes and their driving forces which permit the exchange of water (by ultrafiltration and fluid absorption) and solutes (by diffusion and convective transport) between the peritoneal microvasculature and the dialysate. In peritoneal dialysis, the peritoneal transport system—mesenchymal cells, interstitium, microvasculature, and lymphatics—is repeatedly exposed to high concentrations of an osmotic agent, and a volume load, leading to increased intraperitoneal hydrostatic and osmotic pressure. This results in immediate as well as long-term structural and functional changes of the peritoneal transport system. Clinical tests supplemented with mathematical modelling have been developed to monitor the quantitative characteristics of the peritoneal transport system, allowing detection and diagnosis of various problems and guidance when predicting consequences of changes in prescription.
Peritoneal dialysis
Authors: Dunsmore Sara , Bargman Joanne M.
Published: November 2015

Many patients tolerate peritoneal dialysis well and experience little difficulty with the process. There are, however, a number of unique complications that can arise in a patient undergoing peritoneal dialysis. While infection remains a significant concern, there are also many non-infectious problems that can occur. Many mechanical complications occur as a result of the increased intra-abdominal pressure associated with the instillation of fluid into the peritoneal cavity. The dialysate solution itself may also play a role in some of the metabolic complications seen. An awareness of the potential problems that can occur will help the clinician in properly caring for a patient on this therapy and this chapter describes a range of non-infectious complications that may arise.
Cardiovascular complications in end-stage renal disease patients
Authors: London Gerard M.
Published: November 2015

Cardiovascular complications are the predominant cause of death in patients with end-stage renal disease (ESRD). The high incidence of cardiovascular complications results from pathology present before ESRD (generalized atherosclerosis, diabetes, hypertension) and an additive effect of multiple factors including haemodynamic overload and metabolic and endocrine abnormalities more or less specific to uraemia or its treatment modalities. These disorders are usually associated and can exacerbate each other. While ischaemic heart disease is a frequent cause of cardiac death, heart failure and sudden death are the most frequent causes of death in ESRD. Cardiomyopathy of overload with development of left ventricular hypertrophy and fibrosis are the most characteristic alterations and major determinants of prognosis. Left ventricular hypertrophy may result in systolic and/or diastolic dysfunction and is a risk factor for arrhythmias, sudden death, heart failure, and myocardial ischaemia. Arterial disease, whether due to atherosclerosis or arteriosclerosis (or both), represents a major contributory factor to the cardiovascular complications. Arterial disease may result in ischaemic complications (ischaemic heart disease, peripheral artery diseases) or arterial stiffening with direct consequences on left ventricular afterload, decreased coronary perfusion, and microvascular abnormalities (inward remodelling and microvessel rarefaction).
Bacterial and fungal infections in patients on peritoneal dialysis
Authors: Goffin Eric , Labriola Laura , Jadoul Michel
Published: November 2015

Infections specifically related to peritoneal dialysis include peritonitis on the one hand, and exit-site and tunnel infections on the other hand.

The diagnosis of peritonitis rests on the classical triad of cloudy dialysate, abdominal pain, and presence of < 100 white-cells (including < 50 % polymorphonuclear cells) within the dialysate effluent. Because peritonitis is associated with high mortality and morbidity rates, empiric antibiotics should be initiated without delay, covering both Gram-positive and Gram-negative organisms. Most regimens include vancomycin or a first-generation cephalosporin for the former, and a third-generation cephalosporin or an aminoglycoside for the latter. Antibiotics are usually administered via the intraperitoneal route. Prophylaxis with an anti-fungal agent has to be considered in diabetic patients and in those who just received prolonged antibiotic administration. Cure is obtained in up to 80 % of the cases ; treatment failure however may occur with refractory or relapsing peritonitis episodes. This is especially common in fungal or fecal associated peritonitis, and will require catheter withdrawal. The incidence of peritonitis has dramatically decreased in recent years with the advent of new connectology systems, and both adequate preventive measures and improved patients’ education. Still it is not clearly documented that new biocompatible dialysate fluids have a favorable effect on peritonitis incidence.

Exit-site and tunnel infections are defined by the presence of a purulent discharge around the catheter and by erythema, oedema and tenderness of the subcutaneous pathway of the catheter, respectively. Antibiotics are recommended in case of documented infection. Cuff shaving may sometimes be required, as well as catheter removal in case of unfavourable evolution.
Volume assessment and management in dialysis
Authors: Agarwal Rajiv
Published: November 2015

The assessment of volume among patients on dialysis is an art and a science that is evolving. The assessment of volume requires integration of multiple sources of information including the history, physical examination, and several inexact scientific methods of volume assessment. Poor assessment of volume greatly affects the well-being of dialysis patients. Both hypovolaemia and hypervolaemia are associated with uncomfortable symptoms. Hypovolaemia, for example, may be associated with intradialytic hypotension, cramping, dizziness, access thrombosis, and occult organ hypoperfusion. Hypervolaemia, on the other hand, may manifest as shortness of breath, fatigue, effort intolerance, and recurrent hospitalization for heart failure. The latter may masquerade as recurrent pneumonias. Heart failure hospitalizations requiring acute dialysis occur in 14% of patients in the United States every year and over 2.5 years are associated with $266 million in Medicare costs; at least some of these costs are avoidable. In this chapter, the assessment of volume and its management are discussed.
Nutritional screening and nutritional management in dialysis patients
Authors: Avesani Carla Maria , Carrero Juan Jesús , Lindholm Bengt , Stenvinkel Peter
Published: November 2015

Patients on dialysis are prone to nutritional disturbances, that is, protein-energy wasting, obesity, and imbalance in body fluids and in serum phosphorus and potassium equilibrium. Hence, specialized nutritional care is highly important and include (a) a carefully assessment of the nutritional status, (b) prescription of diet with adequate energy and nutrients to treat and prevent the development of nutritional disturbances often observed in these patients, and (c) periodic follow-up to check adherence of the prescribed diet as well as to evaluate the nutritional status and efficacy of the dietary intervention. This chapter discusses these three aspects in detail and will guide nephrologists and dieticians when treating dialysed patients.
Organ donation
Authors: Mone Thomas
Published: November 2015

Kidney transplantation has been and continues to be dependent on the apparently unscientific and decidedly personal act of organ donation. In the best-performing regions of the world, 75–95% of those who are medically suitable actually become donors upon their deaths, but because of increasing rates of organ failure, even in these high-performing areas, waiting lists continue to grow. Deceased organ donation performance is highly variable even among medically developed countries, and it is especially challenged in countries with cultural, legal, ethical or religious, economic, clinical, or organizational practices that limit donation. Recognizing these challenges, the transplantation community has collaborated to identify and promulgate international best practices and to foster innovation in the management of deceased donation. The goal of this effort is to clarify the organizational structures, social change interventions, and medical practices necessary to maximize both living and deceased donation. Although donation practice differs significantly across countries, successful organ donation programmes share certain traits and practices that can be modified to fit varied medical delivery reimbursement and social systems and structures. The world’s best-performing donation programmes have focused on increasing the public’s and healthcare professionals’ trust in the donation process, ensuring equitable access to transplantation, and they have built donation organizations that borrow from the theory and practice of business and healthcare management systems. The critical processes, essential functions, job roles, and foundational principles of successful donation programmes require the use of the tools that have been shown to improve donation and increase transplantation, thereby reducing (or, ideally, ending) deaths on the waiting lists. The wider adoption of these tools by countries with fledgling or struggling organ donation would increase organ availability and its exploitation of the poor who in many countries become organ ‘vendors’ rather than donors.
Recurrent renal disease
Authors: Clayton Philip , Chadban Steven
Published: November 2015

Although kidney transplantation restores kidney function, it does not cure the cause of kidney failure when it is glomerulonephritis or a systemic disease. These can recur in the allograft, causing graft dysfunction and ultimately graft failure. This is a challenge in the pre-transplant phase, perioperatively, and in a patient with renal allograft dysfunction. This chapter discusses the prophylaxis, diagnosis, and management of recurrent renal disease, including disease-specific information on focal and segmental glomerulosclerosis, membranous nephropathy, membranoproliferative glomerulonephritis, immunoglobulin A nephropathy, lupus nephritis, haemolytic uraemic syndrome, oxalosis, Goodpasture disease, oxalosis, and vasculitis, amongst others.
Paediatric renal transplantation
Authors: Sarwal Minnie M. , Shapiro Ron
Published: November 2015

Approximately 1 in 65,000 children develops end-stage renal disease (ESRD) each year with almost 1200 children (aged 0–19 years) in the United States developing ESRD annually. Kidney transplantation is the primary method of treating ESRD in the paediatric population. The special issues in children and adolescents with ESRD include achieving normal growth and cognitive development. This chapter discusses the advances in surgical techniques, patient selection, transplant evaluation/preparing for transplantation, postoperative management (including fluid management in infants and small children), and the evolution of immunosuppressive drugs that have resulted in improved quality of life and a reduction in the mortality rate of children with chronic renal failure.
The kidney in ageing
Authors: Glassock Richard J. , Rule Andrew D.
Published: November 2015

This chapter reviews the fundamental biology, anatomical alterations, and physiologic changes of the kidneys that accompany ageing of the human organism with particular emphasis on how these features contribute to loss of kidney function in ageing persons. The clinical relevance of these disturbances is discussed mainly through the lens of organ senescence. The diseases associated with or superimposed on the ageing kidney are discussed briefly as they are covered in more detail in other chapters of this book.
Management of intracranial aneurysms
Authors: Pirson Yves , Chauveau Dominique
Published: November 2015

An asymptomatic intracranial aneurysm (ICA) is found by screening in about 8% of patients with autosomal dominant polycystic kidney disease (ADPKD), with a trend to cluster in some families. Though most ICAs will remain asymptomatic, a minority of them may rupture, causing subarachnoid haemorrhage (SAH). Given the grave prognosis of ICA rupture, screening and prophylactic repair of unruptured ICAs have to be considered, with the aim to identify patients with a risk of ICA rupture that exceeds the risk of a prophylactic procedure, surgical or endovascular. Relying on a decision analysis model established in the general population, widespread screening in ADPKD patients is today not recommended. However, the chapter authors advise screening in ADPKD patients with a familial history of ICA or SAH. Additional acceptable indications are high-risk occupations and patient anxiety despite adequate information. Screening is preferably performed by high-resolution, three-dimensional, time-of-flight magnetic resonance imaging. When an asymptomatic ICA is found, a recommendation for whether to intervene depends on its size, site, morphology, patient life expectancy, and general health as well as the experience of the neuroradiologist–neurosurgeon team. Since the risk of new ICAs or enlargement of an existing one is very low in those with small (< 6 mm) ICAs, conservative management is usually recommended. Elimination of tobacco use and aggressive treatment of hypertension are strongly recommended.
Alport syndrome
Authors: Heidet Laurence , Knebelmann Bertrand , Claire Gubler Marie
Published: November 2015

The diagnosis of Alport syndrome is suspected from the clinical features and confirmed by identifying the almost pathognomonic ultrastructural changes to the basement membrane in a family member with early disease (so that glomeruli are not too sclerosed), or in modern times by identifying a causative mutation in one or more of the three implicated COL4 genes. Genetic testing is becoming simpler and cheaper, but is still out of the reach of many. Eighty-five per cent of cases are caused by COL4A5 mutations and 10–15% by autosomal recessive disease. A significant proportion of morbidity in X-linked disease occurs in female ‘carriers’ heterozygous for the disease. Changes by light microscopy are non-specific, and can be misleading unless accompanied by electron microscopy. Immunohistology can be helpful but may not be definitive as some causative mutations are not associated with absence of protein product. As COL4A5 is expressed in skin, skin studies are theoretically useful, but they are technically challenging and only a definite negative result is helpful. It is important to distinguish other disorders causing renal disease with deafness, and other causes of glomerular haematuria. Two rare syndromes are caused by extended deletions beyond the COL4A5 gene: X-linked Alport syndrome with diffuse oesophageal leiomyomatosis in which smooth muscle leoimyomas is transmitted in a dominant fashion, and X-linked Alport syndrome with mental retardation.
Molecular basis of renal tumour syndromes
Authors: Connor Thomas , Maxwell Patrick H.
Published: November 2015

Kidney cancer is among the most common adult malignancy. It accounts for over 3% of all new cases of cancer diagnosed in men and around 2% of all cancers in women in the United Kingdom. In the United States, 1 in 75 people will develop renal cancer in their lifetime and approximately one-third will have metastatic disease at presentation. Kidney cancer has a notoriously poor response to chemotherapy and radiotherapy, but treatment has evolved significantly in the past 10 years. Key to these recent developments in therapy has been a revolution in our understanding of the molecular basis of the renal tumour syndromes which are described in this chapter. Two to three per cent of cases of renal cancer are recognized as due to these syndromes, but they are likely to be recurrent, and to occur in other family members. Seven genes are currently implicated in these syndromes.
Hypoxia-inducible factor and renal disorders
Authors: Connor Thomas , Maxwell Patrick H.
Published: November 2015

Hypoxia-inducible factors (HIFs) are transcription factors that control the cellular response to changes in oxygen levels. This response is common to all cells in the body and is highly conserved in evolution. The kidney exhibits steep gradients in oxygenation which are important in the homeostatic response to anaemia. The cellular response to low levels of oxygen (hypoxia) also plays a role in such diverse processes as acute kidney injury, the progression of chronic kidney disease, and kidney cancer. There is now considerable interest in using drugs to manipulate the HIF response to treat these varied conditions.
Molecular basis of complement-mediated renal disease
Authors: Medjeral-Thomas Nicholas , Richards Anna , Pickering Matthew C.
Published: November 2015

Abnormal regulation of complement is intimately associated with C3 glomerulopathy and atypical haemolytic uraemic syndrome. Atypical haemolytic uraemic syndrome is characterized by renal thrombotic microangiopathy due to an inability to regulate complement activation along the renal endothelium. The development of thrombosis is critically dependent on the ability to activate C5. Eculizumab, a monoclonal anti-C5 antibody, is an effective therapy for this condition. C3 glomerulopathy refers to glomerular lesions characterized by accumulation of C3 in the absence of immunoglobulin. The prototypic example is dense deposit disease. This condition is associated with impaired regulation of the alternative pathway in plasma. In other subtypes of C3 glomerulopathy, familial studies have identified mutations within the complement factor H-related protein family. Polymorphic variation within this protein family also influences susceptibility to IgA nephropathy. The mechanism underlying these associations remains unknown and is the subject of ongoing research efforts.
Inherited metabolic diseases and the kidney
Authors: Lachmann Robin , Murphy Elaine
Published: November 2015

The kidney is affected in a number of inherited metabolic disorders. This chapter focuses on several in which renal disease is usually not the primary clinical manifestation, meaning that there are often other multisystem features and biochemical markers which aid diagnosis. They are rare, but important as early diagnosis and appropriate treatment can often improve outcome.
Fabry disease
Authors: Waldek Stephen
Published: November 2015

Fabry disease is a rare X-linked lysosomal storage disorder in which deficiency of alpha-galactosidase A leads to accumulation of substrate, mostly globotriaosylceramide, which causes a progressive, multiorgan disease affecting predominantly the kidneys, skin, heart, and nervous system. Painful peripheral (‘acral’) neuropathy is characteristic.

Key clinical signs are angiokeratoma found by close examination of skin; characteristic eye lesions may be seen; lipid deposits may be seen in urine. Renal biopsy appearances are characteristic and this is commonly where the diagnosis is first made. Increasingly, cardiologists are suspecting the condition in adults with echocardiographic appearances of left ventricular hypertrophy. Diagnosis in men is usually made by measurement of alpha-galactosidase in either white cells or plasma (or using blood spots). Unfortunately, many female patients can have normal enzyme levels so that genetic testing is the only way to confirm a diagnosis. Non-selective screening strategies (e.g. males on renal replacement therapy with uncertain renal diagnoses) have had low yields.
Kidney stem cells
Authors: Pleniceanu Oren , Dekel Benjamin
Published: November 2015

End-stage renal failure is a major cause of death with currently only dialysis and transplantation available as therapeutic options, each with its own limitations and drawbacks. To allow regenerative medicine-based kidney replacement therapies and due to the fact that neither haematopoietic stem cells nor mesenchymal stem cells, the most accessible human stem cells, can be used to derive genuine nephron progenitors, much attention has been given to finding adult renal stem cells. Several candidates for this have been described, but their true identity as stem or progenitor cells and their potential use in therapy has not yet been shown. However, the analysis of embryonic renal stem cells, specifically stem/progenitor cells that are induced into the nephrogenic pathway to form nephrons until the 34th week of gestation, has been much more conclusive.
Renal hypoplasia
Authors: Schreuder Michiel F.
Published: November 2015

In true renal hypoplasia, normal nephrons are formed but with a deficit in total numbers. As nephron number estimation is not possible in vivo, renal size is used as a marker. A widely used definition of renal hypoplasia is kidneys with a normal appearance on ultrasound but with a size less than two standard deviations below the mean for gender, age, and body size. A distinct and severe form of renal hypoplasia is called (congenital) oligomeganephronia, which is characterized by small but normal-shaped kidneys with a marked reduction in nephron numbers (to as low as 10–20% of normal), a distinct enlargement of glomeruli, and a reduced renal function. In many cases, the small kidney also shows signs of dysplasia on ultrasound, leading to the diagnosis of renal hypodysplasia. Based on the hyperfiltration hypothesis and clinical studies, glomerular hyperfiltration can be expected, resulting in hypertension, albuminuria, and renal injury, for which long-term follow-up of all patients with renal hypoplasia is desirable.
Normal variation in nephron numbers
Authors: Schreuder Michiel F.
Published: November 2015

Kidney development includes the formation of nephrons, which ceases around the 36th week of gestation. At that time, around 900,000 nephrons are formed, but with a 10-fold variation (from 200,000 to over 2 million). Many factors have been described to influence the number of nephrons per individual, such as genetic variations, intrauterine growth and prematurity, maternal diseases and (nutritional) deficiencies, and drugs used during nephrogenesis. Counting nephrons is currently only possible ex vivo, even though magnetic resonance imaging techniques are getting to the stage that in vivo estimations using stereology (the gold standard methodology) can be expected to become available in the next decade. In the meantime, renal size is often used as a marker for nephron endowment.
Pelviureteric junction obstruction and megaureter in children
Authors: Schreuder Michiel F.
Published: November 2015

Two main sites of urine flow obstruction in the upper urinary tract are located at the pelviureteric and vesicoureteric junctions, both of which result in urinary tract dilatation. With current antenatal ultrasound screening, most patients are identified before birth, and 10–30% of infants with antenatal hydronephrosis are found to have pelviureteric junction obstruction, and 5–10% vesicoureteric junction obstruction/megaureter. In addition, a megaureter can also be based on urine reflux, even in combination with obstruction, or be a non-refluxing non-obstructed megaureter. In case of obstruction, surgery may be indicated, but identifying cases that need to be operated on is challenging and no good marker to assist in this differentiation is available yet.
Posterior urethral valves
Authors: Schreuder Michiel F.
Published: November 2015

Posterior urethral valves is the most common congenital cause of lower urinary tract obstruction in males, and a common cause (15–17%) for end-stage renal disease in childhood. Most commonly, posterior urethral valves is suspected on basis of a screening antenatal ultrasound. Ultrasound will not detect posterior urethral valves itself, but recognizes the consequences of lower urinary tract obstruction with a dilated thick-walled bladder and dilation of the prostatic portion of the urethra. After birth, urine drainage has to be secured by placement of a bladder catheter, and imaging is needed to confirm the presence of the urethral valves and estimate the degree of damage to the kidney. Consequences of posterior urethral valves depend on the degree of renal dysplasia and bladder dysfunction. Prevention or minimization of such consequences by intrauterine urine drainage has not definitively shown a benefit of early vesico-amniotic shunting.
The patient with urinary tract obstruction
Authors: Yaqoob Muhammad M. , Bennett-Richards Katherine , Junaid Islam
Published: November 2015

Several terms usually describe obstruction of the urinary tract and its consequences such as hydronephrosis, obstructive uropathy, and obstructive nephropathy. Obstruction can be due to anatomical or functional abnormalities of the urethra, bladder, ureter, or renal pelvis. These abnormalities can be congenital or acquired. Obstructive uropathy also can occur during the course of diseases extrinsic to the urinary tract. This is a reversible cause of renal impairment and calls for urgent diagnosis and treatment to prevent chronic irreversible renal scarring and consequent progressive chronic renal disease.
Branchio-oto-renal syndrome
Authors: Vester Udo , Weber Stefanie
Published: November 2015

Branchio-oto-renal (BOR) syndrome involves branchial arch fistulas or cysts, ear malformations with hearing loss, and anomalies of the kidney. BOR syndrome is inherited in an autosomal dominant trait and is caused in most cases by mutations in the EYA1 gene. A few families with gene mutations in SIX1 or SIX5 have also been described. The variability of clinical symptoms is wide. Renal involvement is observed in the majority of cases ranging from mild anomalies (e.g. dilation or duplication of the urinary tract) to severe hypodysplasia of the kidneys which eventually lead to renal failure. Branchio-otic syndrome (BOS) is characterized by branchial arch and ear anomalies without detectable renal pathology. BOR and BOS can be seen within the same family.