Porth's Essentials of Pathophysiology, 4e

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Disorders of Renal Function

C h a p t e r 2 5

Types of Glomerular Disease The clinical manifestations of glomerular disorders gener- ally fall into several categories: acute nephritic syndromes, rapidly progressive glomerulonephritis, nephrotic syn- drome, IgA nephropathy, hereditary nephritis (e.g., Alport syndrome), and chronic glomerulonephritis. 4,5,10–13 The nephritic syndromes produce a proliferative inflamma- tory response, whereas the nephrotic syndrome produces increased permeability of the glomerulus. Because most glomerular disorders can produce mixed nephritic and nephrotic syndromes, a definitive diagnosis often requires renal biopsy. Many cases of glomerular disease result in mild asymptomatic illness that is not recognized or is brought to the attention of a health care professional during routine screening or physical examination for another purpose. Disorders such as IgA nephropathy and Alport syndrome often present with asymptomatic hematuria and/or proteinuria. Acute Nephritic Syndrome Acute nephritic syndrome is an acute inflammatory process that occludes the glomerular capillary lumen and damages the capillary wall. It may occur as a renal-limited primary disorder, such as acute postinfectious glomerulonephritis, or as a secondary complicating dis- order in systemic diseases, such as SLE. In its most dra- matic form, acute nephritic syndrome is characterized by sudden onset of hematuria (either microscopic or grossly visible, with red cell casts), variable degrees of protein- uria, diminished glomerular filtration rate (GFR), oligu- ria, and signs of impaired renal function. Extracellular fluid accumulation, edema, and hypertension develop because of the decreased GFR and enhanced tubular reabsorption of salt and water. Acute Postinfectious Glomerulonephritis. Acute postinfectious glomerulonephritis usually occurs after infection with certain strains of group A β -hemolytic streptococci and is caused by deposition of immune complexes. 4,5,10,14 It also may occur after infections by other organisms, including staphylococci and a number of viral agents, such as those responsible for mumps, measles, and chickenpox. 4 This type of glomerular dis- ease is now rare in industrialized nations, but continues to be a common disorder in the underprivileged popula- tions of the world. 5 Although the disease is seen primar- ily in children, persons of any age can be affected. The acute phase of postinfectious glomerulonephri- tis is characterized by diffuse glomerular enlargement and hypercellularity. The hypercellularity is caused by infiltration of leukocytes, both neutrophils and mono- cytes; proliferation of endothelial and mesangial cells; and formation of electron-dense subepithelial depos- its, often having the appearance of “humps” (see Fig. 25-4B). There is also swelling of the endothelial cells, and the combination of proliferation, swelling, and leukocyte infiltration obliterates the glomerular capil- lary lumens. On immunofluorescence microscopy there are granular deposits of immunoglobulin G (IgG) and

the complement component C3 in the mesangium and along the basement membrane (Fig. 25-6). The classic case of poststreptococcal glomerulonephri- tis follows a streptococcal infection by approximately 7 to 12 days—the time needed for the development of antibodies. The primary infection usually involves the pharynx (pharyngitis), but can also result from a skin infection (impetigo). Oliguria, which develops as the GFR decreases, is one of the first symptoms. Proteinuria and hematuria follow because of increased glomeru- lar capillary wall permeability. The red blood cells are degraded by materials in the urine, and cola-colored urine may be the first sign of the disorder. Sodium and water retention gives rise to edema (particularly of the face and hands) and hypertension. Important laboratory findings include an elevated antistreptococcal antibody (ASO) titer, a decline in serum concentrations of C3 and other components of the complement cascade, and cryo- globulins (i.e., large immune complexes) in the serum. Treatment of acute poststreptococcal glomerulone- phritis includes eliminating the streptococcal infection with antibiotics and providing supportive care. The dis- order generally carries an excellent prognosis and rarely causes chronic kidney disease. In children, spontane- ous resolution of the glomerular lesion and nephritic syndrome is usually the norm and occurs within 6 to 8 weeks. Adults tend to recover more slowly, often with some degree of persistent azotemia that may, in some cases, progress to chronic kidney disease. Rapidly Progressive Glomerulonephritis Rapidly progressive glomerulonephritis is a clinical syn- drome characterized by signs of severe glomerular injury that does not have a specific cause. As its name indicates, this type of glomerulonephritis is rapidly progressive,

FIGURE 25-6. Acute postinfectious glomerulonephritis. An immunofluorescence micrograph demonstrates granular staining for complement C3 in capillary walls and the mesangium. (From Jennette JC.The kidney. In: Rubin R, Strayer DS, eds. Rubin’s Pathology: Clinicopathologic Foundations of Medicine. 6th ed. Philadelphia, PA: Wolters Kluwer Health | Lippincott Williams &Wilkins; 2012:776.)