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Membranous Nephropathy

## Membranous nephropathy (MN) is the most common cause of adult-onset nephrotic syndrome in the white population. It is characterized by deposition of immunoglobulin G and complement components in the glomerular capillary wall and attendant new basement membrane synthesis. This histologic pattern is more properly called nephropathy than nephritis because there is rarely any inflammatory response in the glomeruli or interstitium. Primary MN is a kidney-limited…

Focal Segmental Glomerulosclerosis

## Focal segmental glomerulosclerosis (FSGS) is neither a disease nor a syndrome, but rather a set of clinicopathologic syndromes. The shared histopathologic findings include segmental glomerular scars, often with global glomerular tubulointerstitial scarring, no immunostaining or staining for immunoglobulin M (IgM) and C3, and no or minimal inflammatory cells in glomeruli or blood vessels. FSGS accounts for approximately 20% of cases of idiopathic nephrotic syndrome in…

Minimal Change Disease

Terminology and Histopathology Minimal change disease (MCD) is a common cause of nephrotic syndrome (NS). Also known as lipoid nephrosis, nil disease, and minimal change nephropathy , the kidney histology on light microscopy in MCD is relatively normal and lacks the significant glomerular cell proliferation, infiltration by circulating immunoeffector cells, immune deposits, tubulointerstitial changes, or alterations in the glomerular basement membrane (GBM) that characterize other glomerular…

ANCA-Associated Kidney Disease and Vasculitis

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a predominantly small-vessel vasculitis with a predilection for the kidney and respiratory tract. In the majority of cases, the disease is associated with autoantibodies (i.e., ANCAs) directed against one of two proteins located within the azurophilic granules of neutrophils: proteinase 3 (PR3) or myeloperoxidase (MPO). ANCAs have a central role in the pathogenesis and diagnosis of AAV. AAV has…

Glomerular Clinicopathologic Syndromes

Introduction Glomerular disease is the third most common cause of end-stage kidney disease worldwide. Glomerulonephritis (GN) has diverse presentations and work-up requires serum chemistry, serology, urinalysis with microscopy, and quantification of proteinuria. Patients present with several clinicopathological syndromes that can have various etiologies. These syndromes share similar charac­teristics in terms of findings on urinalysis, degree of proteinuria, presence of reduced glomerular filtration rate, edema, and hypertension,…

Respiratory Acidosis and Alkalosis

Respiratory Acidosis Respiratory acidosis, or primary hypercapnia, is the acid-base disturbance initiated by an increase in the carbon dioxide tension of body fluids and in whole-body CO 2 stores. Hypercapnia acidifies body fluids and elicits an adaptive increment in the plasma bicarbonate concentration ([HCO 3 − ]) that should be viewed as an integral part of the respiratory acidosis. Arterial CO 2 tension (P co 2…

Metabolic Alkalosis

Pathogenesis The pathogenesis of metabolic alkalosis requires two processes: (1) generation and (2) maintenance. Generation occurs by net gain of bicarbonate ions (HCO3 − ) or net loss of nonvolatile acid (usually HCl by vomiting) from the extracellular fluid. Although the kidneys have an impressive capacity to excrete HCO3 – under normal circumstances, in the maintenance stage of metabolic alkalosis the kidneys fail to excrete HCO3…

Metabolic Acidosis

Metabolic acidosis describes a process in which nonvolatile acids accumulate in the body. For practical purposes, this can result from either the addition of protons or the loss of base. The consequence of this process is a decline in the major extracellular buffer, bicarbonate, and, if unopposed, a decrease in extracellular pH. Depending on the existence and the magnitude of other acid-base disturbances, however, the extracellular…

Approach to Acid-Base Disorders

Acid-base disorders can have major clinical and diagnostic implications. If they generate extreme acidemia or alkalemia, the abnormal pH itself may result in pathophysiologic consequences. For example, the tertiary structure of proteins is altered by extreme pH conditions, potentially affecting the activity of enzymes and ion transport systems. Consequently, every metabolic pathway may be impacted by acidemia or alkalemia. In addition, extreme acidemia can depress cardiac…

Disorders of Calcium, Phosphorus, and Magnesium Homeostasis

Disorders of mineral metabolism (calcium, phosphorus, magnesium) are common, especially in hospitalized patients. The extracellular concentrations of these ions are less than 1% of total body stores, and the principal site of storage is bone. Thus, serum levels may not always reflect underlying pathology. Knowledge of the complex homeostasis of these ions is critical in formulating the differential diagnosis of disorders affecting these ions and in…

Disorders of Potassium Metabolism

Introduction Dyskalemias (i.e., hypo- and hyperkalemia) are common abnormalities that occur frequently in patients with chronic kidney disease and are associated with increased morbidity and mortality. Due to their acute effects on cardiac arrhythmias, severe hypo- and hyperkalemia are medical emergencies that require immediate intervention. Because of their potential for recurrence, dyskalemias require long-term interventions to minimize their recurrence. The recent development of newer potassium binders…

Volume, Edema, and the Clinical Use of Diuretics

Edema represents expansion of the interstitial volume and is a common phenotypic presentation of multiple pathologic processes. The word diuretic is derived from the Greek roots dia “thoroughly” and ourein “urine.” Consequently, the term diuretic is defined by its ability to amplify urine output and treat edema. Historically, “dropsy” was coincidentally alleviated by various plant and mineral compounds, including mercurial agents such as calomel and novasurol.…

Hypernatremia and Hyperosmolar Disorders

## The serum sodium concentration ([Na + ]) is the ratio of sodium to water in the extracellular fluid (ECF) compartment. It is determined by the relationship among total body sodium, potassium, and water, the last of which typically is the main determinant. Dysnatremias, or derangements in serum [Na + ], include both hyponatremia and hypernatremia. This chapter focuses on the etiology and management of hypernatremia,…

Imaging of the Kidneys

Introduction Visualizing the genitourinary system was one of the first goals of the nascent radiological sciences at the turn of the 20th century. It was a fortuitous discovery that the sodium iodide patients were taking for syphilis made their bladder denser (“opacified”) on x-ray imaging. The development of organic iodine agents that could be administered intravenously and would be excreted in the urine advanced the field…

Hematuria and Proteinuria

## Kidney disease is defined by a reduction in the glomerular filtration rate (GFR), impairment of tubular function, or damage to kidney structure. This damage manifests as loss of the integrity of the filtration barrier, impairment of tubular function, or changes in other processes that interfere with normal kidney function. Urinalysis and urine sediment examination are useful tools to detect this damage, and both hematuria and…

Urinalysis and Urine Microscopy

## The relatively simple chemical tests performed during routine urinalysis rapidly provide important information about a number of primary kidney and systemic disorders. The microscopic examination of the urine sediment is an indispensable part of the evaluation of patients with reduced glomerular filtration, proteinuria, hematuria, urinary tract infection, or nephrolithiasis, and the urine sediment provides valuable clues about the kidney parenchyma. Urine dipstick tests can be…

Assessment of Kidney Function in Acute and Chronic Settings

## Excretory function of the kidney occurs by glomerular filtration of plasma followed by selective tubular reabsorption or secretion of water and solutes to maintain homeostasis. Because glomerular filtration rate (GFR) is generally considered the best overall assessment of kidney function, this chapter focuses on GFR and its assessment, with other functions of the kidney reviewed elsewhere in the Primer . Glomerular Filtration Rate GFR is…

Kidney Development

Development of the Mammalian Kidney Congenital anomalies of the kidney and urinary tract (CAKUT) are common birth defects that account for 40%-50% of pediatric end-stage kidney disease (ESKD) worldwide. These comprise a wide range of malformations that may be sporadic or inherited. Nephron number can vary up to 10-fold in humans and, although ~40% of variation in creatinine clearance (a proxy for functioning nephrons) is due…

Overview of Kidney Structure and Function

## The kidneys play an essential role in normal homeostasis. The key functions of the kidneys include: 1 Maintenance of normal body fluid composition . The kidney plays a primary role in the regulation of both the intracellular and extracellular compartments by retention or excretion of water and electrolytes. The concentration of water, sodium, potassium, calcium, phosphate, and hydrogen are tightly regulated within these body compartments…