CHAPTER 22 Renal Disorders 549
are gas-excreting pathogens. This almost exclusively occurs in patients with preexisting DM. Pyelonephritis can also be complicated by abscess formation, which should be suspected if there is continual fever or bac- teremia despite antibacterial treatment. Xanthogran- ulomatous pyelonephritis is an aggressive, rare form of chronic pyelonephritis. Chronic renal insufficiency deteriorating to renal failure may develop in the patient with chronic pyelonephritis. It is estimated that 10% to 20% of ESRD is secondary to chronic pyelonephritis. Polycystic Kidney Disease Polycystic kidney disease (PKD) is a genetic disorder that affects the kidneys and other organs. Because of the development of cysts in the renal tissue, renal function is impaired. Typically discovered in affected subjects during young adulthood, the progressive for- mation of cysts can number in the hundreds to thou- sands by age 50. Kidney enlargement occurs due to cysts. Kidneys can increase to four times normal size and weigh up to 20 times normal weight. Cysts also develop in other organs of the body, such as the liver. Epidemiology PKD affects approximately 600,000 people in the United States. It is the fourth leading cause of renal failure. The most common type of PKD is autosomal- dominant polycystic kidney disease (ADPKD), one of the most common inherited disorders. It is the most common hereditary cause of renal disease in adults and accounts for 6% to 8% of patients on dialysis in the United States. It is the most common cause of ESRD in the United States. Almost all people who inherit the ADPKD gene develop renal cysts by the age of 30 years. The disease can also be inherited because of a reces- sive gene; this form is referred to as autosomal-recessive polycystic kidney disease (ARPKD). This is a much less common form because both parents must carry the gene in order for an individual to develop the disorder. There is a 5% to 10% incidence of ARPKD with no family his- tory, and this is attributed to a sporadic type of genetic mutation. ARPKD is generally diagnosed in utero or within the neonatal period. HTN and lack of complete formation of the biliary tract and liver are also involved. Pulmonary hypoplasia, characteristic facies, and spine and limb abnormalities can be present in severe neo- natal cases, with death from respiratory distress. About 30% of affected newborns die shortly after birth. Etiology ADPKD is categorized as either ADPKD 1 or ADPKD 2, depending on the mutation of either of two genes. The majority of cases are ADPKD 1 caused by the PKD1 genetic mutation located at 16p13.3, which encodes for a protein called polycystin 1. The less common type is ADPKD 2, which involves a mutation at 4q21-22 of the PKD2 gene, which encodes for a protein called polycystin 2.
Both polycystin 1 and 2 are involved in renal epithelial cell cycle regulation and intracellular transport of cal- cium. ADPKD 1 is a more severe disease than ADPKD 2. Pathophysiology ADPKD leads to formation of fluid-filled cysts in both kidneys. The renal epithelial cell cycle becomes dys- functional, leading to hyperplasia of renal epithelial cells. The hyperplastic cells cause an outpocketing of the nephron tubule walls, with the formation of cysts that fill with fluid derived from glomerular filtrate. The cystic structures have continual hyperplastic growth and proliferate within the kidney. Glomerular filtrate accumulates in the cysts, and the surrounding nor- mal renal tissue is compressed and damaged. As cysts increase in number and size, the kidneys enlarge. Fibrotic changes occur in the kidneys with time. The cystic structures also develop blood vessels. The blood vessels are extremely fragile and susceptible to rup- ture, which causes leakage of blood into the cysts. With the entry of blood, the cystic walls stretch, caus- ing excruciating pain. Cysts often rupture into the renal calyces, causing gross hematuria. Aside from cystic kidneys, patients with ADPKD are also susceptible to disorders of other organs. Cysts can form in the liver, pancreas, and spleen. Diverticula, which are saccular structures that form in the intes- tinal wall, often occur in the colon. Heart valve prob- lems such as mitral valve prolapse commonly develop, causing heart murmur. Cerebral aneurysms occur four to five times more frequently in ADPKD patients than the general population. Cerebral aneurysms are weak- ened areas of a cerebral artery that are prone to rup- ture, which can lead to hemorrhagic stroke. Thoracic aortic aneurysm is also a common problem in patients with ADPKD. ADPKD also increases susceptibility to renal carcinoma. Clinical Presentation Patients with ADPKD usually present with pain caused by the pressure associated with fluid accumulation in the cysts. Because of stagnation of fluid within the cysts, uric acid and calcium crystals can precipitate and renal calculi can develop, which cause obstruction. In these cases, the patient presents with the pain of renal colic and hematuria. The kidneys cannot concentrate the urine; therefore, urine concentration defects occur with polyuria. Proteinuria, the loss of proteins into the urine, is a prognostic indicator in ADPKD. Stagnation of fluid within the cysts also increases susceptibility to kidney infection. CVA tenderness, fever, and pyuria occur if pyelonephritis develops. In addition, cysts place pres- sure on kidney blood vessels, which activates the RAAS. If this occurs, the patient will present with hypervole- mia and HTN. The patient with ADPKD can demonstrate various symptoms, depending on the involvement of other organs, such as the heart, colon, cerebral arteries, thoracic aorta, liver, spleen, or pancreas. By age 60, 50% of persons with ADPKD develop renal failure.
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