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Vasopressin in the Kidney—Historical Aspects

1 Introduction A century ago it was well established that the infusion of pituitary extract into animals could cause antidiuresis and a concentrated urine. The structure of this neurohypophyseal hormone, mammalian vasopressin (AVP) or antidiuretic hormone (ADH) was discovered in 1954 by Acher and Chavet. In 1957, two patients were diagnosed with bronchogenic cancer and subsequently developed hyponatremia. Both patients were observed to have an elevated…

Renin–Angiotensin Blockade: Therapeutic Agents

Key Points The renin–angiotensin system (RAS) has emerged over the last several decades as a key mediator of hypertension as well as cardiorenal homeostasis and disease progression. Several drug classes including angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and direct renin inhibitors have been developed as means to interrupting activity in this system. Several ACE inhibitors and ARBs are available and for the most part…

The Renin–Angiotensin System and the Heart

1 Introduction For many years, the renin–angiotensin system (RAS) was thought to be mainly a traditional circulating hormonal system whereby renal renin-dependent production of angiotensin II (Ang II) occurred in response to a fall in macula densa sodium concentration, low arterial pressure, or a decrease in circulating blood volume. Renin could then act upon its circulating substrate, angiotensinogen—primarily produced in the liver—to produce the inactive precursor…

The Renin–Angiotensin–Aldosterone System and the Kidney

1 Introduction The relationship between the renin–angiotensin–aldosterone system (RAAS) and its modulation of kidney function has been present for almost a century. It dates back to when renin was first described in the late 1800s and integrated into renal physiology with the experiments of Harry Goldblatt. Studies over the past four decades have further crystallized our knowledge of the cellular and molecular role of this system…

Physiology and Regulation of the Renin–Angiotensin–Aldosterone System

The renin–angiotensin–aldosterone system (RAAS) is a major hormonal regulatory system in the control of blood pressure (BP) and hypertension (HT). Several new components and pathways of the RAAS have been described during the past decade. In this chapter, these new components and pathways will be described and their potential clinical significance will be discussed. 1 The Classical Circulating Renin–Angiotensin System The classical renin–angiotensin system (RAS) (…

Renal Disposition of Drugs and Translation to Dosing Strategies

Renal excretion is an important clearance pathway for many drugs and their metabolites. Impaired renal excretion, either as a result of kidney disease or the effects of co-administered drugs, can lead to accumulation of drugs and their metabolites. In many cases dosing adjustments are required to maintain optimal therapeutic effects and to avoid accumulation of drugs to toxic levels. In this chapter, the processes involved in…

Homeostasis of Solute and Water by the Transplanted Kidney

This chapter analyzes the capacity of the transplanted kidney to transport solute and water. The intrinsic capacity of the transplanted kidney to regulate glomerular filtration rate (GFR), to exhibit T-G feedback are described along with alterations that flow from retrieval ischemia and surgical engraftment. Water homeostasis with respect to osmotic diuresis, tubular transport and tubular responses to hormone are described. Pathologic alterations of tubular transport are…

Individualizing the Dialysate to Address Electrolyte Disturbances in the Dialysis Patient

Patients with end-stage renal disease (ESRD) depend on dialysis to maintain fluid and electrolyte balance. Dialysis allows for solutes to diffuse between blood and dialysate such that, over the course of the procedure, plasma composition is restored toward normal values. The makeup of the dialysate is of paramount importance in accomplishing this goal. In most out-patient settings patients receive hemodialysis using dialysate prepared in bulk and…

Hematopoiesis and the Kidney

By the production of erythropoietin (EPO) the kidneys participate in the regulation of red cell and platelet formation. This chapter reviews the present knowledge about the structure, the receptors, the functions and the regulation of production of these hormones. The two hormones show similarities with regard to structure and receptor function but strongly differ with regard to the regulation of their production. Whilst the production of…

Management of Calcium and Bone Disease in Renal Patients

We have made significant advances in understanding of the pathogenesis and treatment of secondary hyperparathyroidism in chronic kidney disease (CKD). These include: (1) the discovery of the calcium-sensing receptor CaSR and the development of calcimimetics to target this receptor to suppress PTH secretion and production; (2) the recognition that metabolic derangements in calcium and phosphate have a significant impact on morbidity and mortality, possibly through effects…

Chronic Kidney Disease: Pathophysiology and the Influence of Dietary Protein

The incidence of CKD is increasing in the United States primarily driven by the rising incidence of obesity-related disease, such as hypertension and diabetes, and shifts in age and racial demographics. The complications of CKD intensify as GFR declines, and therefore an understanding of the advantages and limitations of various methods of assessing and anticipating progression of kidney disease is important. Our discussion of the pathophysiology…

Catalytic (Labile) Iron in Kidney Disease

Introduction Despite advances in understanding the pathophysiology of acute kidney injury (AKI) and chronic kidney disease, treatment for kidney disease remains unsatisfactory. In this chapter, we briefly recount the importance of acute kidney injury and chronic kidney disease, then provide a brief description of labile iron, and, finally, summarize the role of labile iron in acute and chronic kidney disease. The availability of iron chelators provides…

The Inflammatory Response to Ischemic Acute Renal Injury

Acute ischemia reperfusion injury (IRI) is a major cause of acute kidney injury (AKI). A major conceptual insight is that the total amount of renal injury is the result of not only the initial ischemic insult, by the ensuing responses. This simple insight has profound clinical implications: it suggests that therapy after the initial insult has already occurred may ameliorate the course of AKI. Some of…

Role of Proteinuria in the Progression of Renal Disease

Introduction Chronic progressive nephropathies, independent of the type of the initial insult, have in common persistently high levels of urinary protein excretion, chronic tubulointerstitial lesions, and glomerular sclerosis. It has become clear that in otherwise comparable groups of patients, those with higher levels of proteinuria are at a greater risk of progression. It has been long known that the severity of tubular interstitial damage is highly…

Role of Glomerular Mechanical Stress in the Pathogenesis of Chronic Kidney Disease

Determinants of Glomerular Ultrafiltration and How They are Influenced by the Glomerular Arterioles The notion that derangements of glomerular dynamics may exert a deleterious effect and play a role in the pathogenesis of chronic kidney disease (CKD) is relatively recent, having been first postulated in a coherent way in the early 1980s. This formulation was made possible after the determinants of glomerular ultrafiltration were directly measured…

Cellular Mechanisms of Drug Nephrotoxicity

This review will trace the general mechanisms of renal cell injury before focusing on selected specific nephrotoxins that demonstrate the key principles of injury. Potentially, all of the cellular events involved in injury leave molecular footprints, which can be used as biomarkers in urine or plasma. Event specific biomarkers may allow mapping the time course of injury and the recruitment of secondary injury pathways. We will…

Genetic Abnormalities in Glomerular Function

This chapter discusses recent advances in the understanding of genetic kidney diseases that primarily involve the glomerulus. The chapter is organized according to the site or mechanism of the primary abnormality: abnormalities of extracellular matrix, storage diseases affecting the glomerulus, primary defects in the slit diaphragm, cytoskeletal defects and defective transcriptional regulation. Key words Alport syndrome, Thin Basement Membrane Nephropathy, HANAC Syndrome, Collagen IV Nephropathies, Pierson…

Immunologic Mechanisms of Vasculitis

The kidneys are among the organs most commonly affected by systemic vasculitis. This chapter reviews the etiology and pathogenesis of forms of vasculitis that most often affect the kidneys. The emphasis is on vasculitis that targets predominantly small vessels because this category of vasculitis most often involves the kidneys. A broad spectrum of cellular and humoral inflammatory mediator systems are involved in the pathophysiology of vasculitis.…

Immune and Inflammatory Glomerular Diseases

This chapter is mainly devoted to immune-mediated kidney disorders, and is primarily focused on glomerular diseases. Lupus nephritis and ANCA-associated vasculitis are addressed in separate chapters. The reader is reminded that the renal involvement may be the initial manifestation of systemic disease, and the results of renal pathology may provide the first clues to diagnosis. In this chapter, glomerular diseases have been divided into diseases that…

Renal Physiology and Disease in Pregnancy

The urinary system, volume homeostasis, osmoregulation, and composition of body fluids are all altered in normal pregnancy. There are also hemodynamic changes involving cardiac output and blood pressure. Knowledge of these changes permits earlier detection of dysfunction as well as better management of pregnant patients with kidney disease and/or hypertension. In the fourth revision of this chapter, besides an updated review of renal physiology during pregnancy,…