Porth's Essentials of Pathophysiology, 4e

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Kidney and Urinary Tract Function

U N I T 7

Focal segmental glomerulosclerosis can be viewed as a heterogeneous group of glomerular diseases with different causes, pathologies, and outcomes. The dis- order may be idiopathic (primary) or occur secondary to reduced oxygen in the blood (e.g., sickle cell disease and cyanotic congenital heart disease), human immu- nodeficiency virus (HIV) infection, or intravenous drug abuse. 4,5 It can also occur as a secondary event reflecting scarring from other glomerular disorders, such as IgA nephropathy. There is also evidence of a genetic basis for some cases of the disorder. Multiple factors probably lead to a common pathway of injury. Clinical presentations and outcomes vary among the different patterns of injury. Most people with the disor- der show persistent proteinuria and progressive decline in renal function. Many persons with the disorder prog- ress to kidney failure within 5 to 20 years. 5 The disorder usually is treated with corticosteroids. Although kidney transplantation is the preferred treatment for end-stage kidney disease, focal segmental glomerulonephritis occurs in half of these people. IgA Nephropathy IgA nephropathy (i.e., Berger disease) is a primary glo- merulonephritis characterized by the presence of glo- merular IgA immune complex deposits. It can occur at any age, but most commonly has its onset in the sec- ond and third decades of life. 4,5,10,16,17 The disease occurs more commonly in men than women and is the most common cause of glomerular nephritis in Asians. The disorder is characterized by the deposition of IgA-containing immune complexes in the mesangium of the glomerulus (Fig. 25-10). Once deposited in the kidney, the immune complexes are associated with glomerular inflammation. The cause of the disorder is unknown. Some people with the disorder have elevated serum IgA levels. Recent studies have focused on poten- tial abnormalities of the IgA molecule as a factor in the pathogenesis of the disorder. 16

Early in the disease, many people with the disorder have no obvious symptoms and the disorder is dis- covered during routine screening or examination for another condition. In others, the disorder presents with gross hematuria that is preceded by upper respiratory tract infection, gastrointestinal tract symptoms, or a flulike illness. The hematuria usually lasts 2 to 6 days. Approximately one half of those with gross hematuria have a single episode, whereas the remainder experience a gradual progression of the disease with recurrent epi- sodes of hematuria and mild proteinuria. Progression usually is slow, extending over several decades. Immunofluorescence microscopy, using a specimen obtained through renal biopsy, is essential for diagnosis of IgA nephropathy. 5 The diagnostic finding is mesangial staining for IgA that is more intense than staining for IgG or IgM. At present, there are no satisfactory treat- ment measures for IgA nephropathy. The role of immu- nosuppressive drugs such as steroids and cytotoxic drugs is not clear. Hereditary Nephritis (Alport Syndrome) Alport syndrome represents a hereditary defect of the glo- merular basement membrane that results in hematuria and may progress to chronic renal failure. 4,5 Approximately 85% of cases are inherited as an X-linked autosomal dominant trait, whereas others have autosomal dominant and recessive patterns of inheritance. 5 In X-linked pedi- grees, boys are usually affected more seriously than girls. Affected boys usually progress to renal failure as adults, but progression may occur during adolescence. Although many girls never have more than mild hematuria with or without mild proteinuria, some have more significant dis- ease and may even progress to kidney failure. Diagnosis of Alport syndrome is often made after examination of the urine of a child from a family with multiple cases of hereditary nephritis. Children may ini- tially present with heavy microscopic hematuria (large amount of blood on dipstick), followed by the devel- opment of proteinuria. Many, but not all, persons with Alport syndrome have sensorineural deafness and vari- ous eye disorders, including lens dislocation, posterior cataracts, and corneal dystrophy. The hearing loss is bilateral and often is first detected during adolescence. Chronic Glomerulonephritis Chronic glomerulonephritis represents the chronic phase of a number of specific types of glomerulonephritis. 4,5 Some forms of acute glomerulonephritis (e.g., poststrep- tococcal glomerulonephritis) undergo complete resolu- tion, whereas others progress at variable rates to chronic glomerulonephritis. Some persons who present with chronic glomerulonephritis have no history of glomeru- lar disease. These cases may represent the end result of relatively asymptomatic forms of glomerulonephritis. Histologically, the condition is characterized by small kidneys with sclerosed glomeruli. In most cases, chronic glomerulonephritis develops insidiously and slowly pro- gresses to chronic kidney disease over a period of years (see Chapter 26).

FIGURE 25-10. IgA nephropathy. An immunofluorescence micrograph shows deposits of IgA in the mesangial areas. (From Jennette JC.The kidney. In: Rubin R, Strayer D, eds. Rubin’s Pathology: Clinicopathologic Foundations of Medicine. 6th ed. Philadelphia, PA: Wolters Kluwer Health | Lippincott Williams &Wilkins; 2012:781.)