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Autosomal Dominant Polycystic Kidney Disease

Autosomal dominant polycystic kidney disease (ADPKD) (MIM 173900) is a systemic disorder characterized by age-dependent occurrence of bilateral, multiple renal cysts as well as a variety of extrarenal manifestations. The latter include cysts in the liver bile ducts, pancreatic ducts, seminal vesicles, and arachnoid membrane, as well as noncystic manifestations, such as intracranial aneurysms and dolichoectasias, aortic root dilatation and aneurysms, mitral valve prolapse, and abdominal…

Renal Failure in Cirrhosis

Renal failure is a common complication of patients with advanced cirrhosis. The most common causes of renal failure in cirrhosis are those related to bacterial infections (with or without septic shock) and hepatorenal syndrome. Other causes include renal failure due to the administration of non steroidal anti-inflammatory drugs (NSAIDs), that associated with gastrointestinal bleeding (with or without hypovolemic shock) and due to intrinsic renal disease. Because…

Pathophysiology and Pathogenesis of Diabetic Nephropathy

Diabetic nephropathy is the major cause of end-stage renal disease (ESRD) in the industrialized world. Although the incidence of nephropathy due to type 1 diabetes may not be increasing, type 2 diabetes mellitus, considered 30 years ago a rather benign condition invariably associated with the “normal” aging process, is now the most common single cause of chronic kidney disease in the United States, Japan, and Europe.…

Ischemic Renal Disease

The intrinsic ability of the kidney to regulate renal blood flow and glomerular filtration rate (GFR) over a wide range of perfusion pressures has fascinated physiologists for decades. These adaptive responses to physiologic and pathologic alterations in renal perfusion, known collectively as renal autoregulation, serve to maintain renal excretory function in settings of decreased renal blood flow, such as in states of volume depletion, hypotension, or…

Pathophysiology of Acute Kidney Injury

This chapter focuses on the pathophysiological principles of Acute Kidney Injury (AKI), with special emphasis on the structural, cellular and molecular alterations occurring in ischemic, nephrotoxic and septic AKI. Changing concepts in the disease pathogenesis and approaches to treatment based on pathophysiological principles are also detailed. Keywords acute kidney injury, ischemia, acute tubular necrosis, sepsis, endothelial cell Clinical Overview Classifications and Definitions Acute Kidney Injury (AKI)…

Biomarkers for Assessment of Renal Function During Acute Kidney Injury

Acute kidney injury (AKI) is a common and serious condition, the diagnosis of which depends on serum creatinine measurements. Unfortunately, creatinine is a delayed and unreliable biomarker of AKI. The lack of reliable early biomarkers has crippled our ability to translate promising experimental therapies to human AKI. Fortunately, understanding the early stress response of the kidney to acute injuries has serendipitously revealed a number of potential…

Physiologic Principles in the Clinical Evaluation of Electrolyte, Water, and Acid–Base Disorders

The kidneys play a fundamental role in the regulation of water and electrolyte excretion as well as in the maintenance of acid base balance. Water and electrolyte homeostasis is accomplished almost exclusively through changes in the volume and composition of urine. Routes of external loss other than from the kidneys play a limited role in regulation, even though they may display some response to the needs…

Renal Filtration, Transport, and Metabolism of Albumin and Albuminuria

Albuminuria is a sensitive marker of kidney dysfunction and associated with increased mortality and risk of cardiovascular disease. Urinary excretion of albumin is regulated by balance between glomerular filtration and tubular reabsorption. Our knowledge of the molecular mechanisms regulating the glomerular albumin permeability and proximal tubule, endocytic reabsorption of albumin has greatly expanded and animal models as well as genetic analyses in human diseases have established…

Organic Anion and Cation Transporters in Renal Elimination of Drugs

Renal proximal tubules efficiently secrete anionic and cationic drugs and toxins. Many of the involved transporters are members of the solute carrier family 22 ( SLC22 ) and exhibit a broad substrate specificity. Uptake of organic anions from blood into proximal tubule cells occurs through organic anion transporters 1 and 3 (OAT1/ SLC22A6 and OAT3/ SLC22A8 ), and the uptake of organic cations involves organic cation…

Kidney Transport of Amino Acids and Oligopeptides, and Aminoacidurias

Amino acids and small peptides are very efficiently reabsorbed at the level of the kidney proximal tubule by a series of specialized membrane proteins. In a first step, they are taken up into tubular epithelial cells via secondary active transporters localized at the luminal brush border membrane. Most of these amino acids as well as the amino acids generated by the intracellular hydrolysis of the di-/tripeptides…

Glucose Reabsorption in The Kidney

Glucose is the major fuel source to the body’s tissue and its plasma concentration is maintained within narrow limits, 4–10 mM, except in diabetes where it may rise to over 16 mM. In this chapter we review the role of the kidneys in glucose homeostasis. In particular, we discuss the molecular and genetic evidence for the importance of SGLTs and GLUTs in the proximal tubule in…

Clinical Disturbances of Phosphate Homeostasis

In the kidney, filtered inorganic phosphate ions are reabsorbed along the proximal tubules. This transepithelial process involves sodium-dependent phosphate transporters that are localized at the apical (brush border) membrane. Currently, three Na/Pi-cotransporters that belong to the SLC 20 (PiT-2) and SLC 34 (NaPi-lla and NaPi-llc) families have been assigned to proximal tubular phosphate reabsorption, whereby SLC34 proteins play the major role. The primary functional difference between…

Proximal Tubular Handling of Phosphate

In the kidney, filtered inorganic phosphate ions are reabsorbed along the proximal tubules. This transepithelial process involves sodium-dependent phosphate transporters that are localized at the apical (brush border) membrane. Currently, three Na/Pi-cotransporters that belong to the SLC 20 (Pit-2) and SLC 34 (NaPi-lla and NaPi-llc) families have been assigned to proximal tubular phosphate reabsorption, whereby SLC34 proteins play the major role. The primary functional difference between…

Pathogenesis and Treatment of Nephrolithiasis

Kidney Stones A majority of patients form stones containing calcium oxalate (CaOx) and calcium phosphate (CaP). Of these most form predominantly CaOx stones in the absence of systemic disease, so called ‘idiopathic CaOx stone formers’ (ICSF). These stones form outside the nephrons, on the papillary surfaces, attached to interstitial apatite (Randall’s) plaque (RP). The initial overgrowth is CaP in the form of apatite over which CaOx…

Disorders of Calcium Metabolism

Calcium plays critical roles in both the structure and function of the human body. As a result, the extracellular calcium level is meticulous regulated by a complex system of hormones, receptors and organ systems. Increases or decreases in the extracellular calcium concentration lead to multi-organ dysfunction and are associated with a large number of disease states. In this chapter, we review the individual components that contribute…

The Hormonal Regulation of Calcium Metabolism

Calcium plays a vital role in several biological processes including normal neuromuscular transmission, muscular contractility, cellular signaling, enzyme function, and blood coagulation. Hence, the appropriate control of calcium homeostasis is vital to the well-being of the organism. Severe calcium deficiency results in tetany and, in extreme cases, grand mal seizures. The deposition of excess calcium at ectopic sites occurs in several diseases such as nephrolithiasis, arteriosclerosis,…

Renal Calcium Metabolism

Although bone harbors almost all of the body stores of calcium, the kidneys serve as the regulator of calcium homeostasis. Calcium filtered at the glomerulus is extensively reabsorbed by proximal tubules. This recovery proceeds without hormonal regulation and is governed by driving forces established by sodium absorption. Physiological adjustment of calcium transport occurs in distal tubules, where parathyroid hormone (PTH) regulates absorption. PTH also acts on…

The Calcium-Sensing Receptor

Cell surface sensors for extracellular Ca 2+ and Mg 2+ provide an important mechanism for the regulation of diverse physiological processes by extracellular divalent mineral ions. These ion sensors function as “calciostats” for Ca 2+ and/or Mg 2+ that not only regulate divalent mineral metabolism at the level of the whole organism but also control a variety of other cellular processes (e.g., salt and water handing…

Calcium Channels

The SLC4 ( s o l ute c arrier 4) family is a group of a membrane proteins that share sequence homology and in general mediate the transport of bicarbonate. It should be noted that bicarbonate transport is not unique to the SLC4 family. The structurally unrelated SLC26 family has at least three proteins that mediate CI − HCO − 3 exchange. In this chapter, the…

Mechanisms and Disorders of Magnesium Metabolism

Magnesium plays a vital role in virtually all cellular processes as a cofactor of enzymes, a structural element of proteins and nucleic acids, and a modulator of receptors and ion channels. The control of magnesium homeostasis primarily resides in the kidney tubules. Nephron segments critical for renal magnesium conservation mainly comprise the thick ascending limb and the distal convoluted tubule where different control mechanisms act. Over…