Porth's Essentials of Pathophysiology, 4e

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Kidney and Urinary Tract Function

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ifosfamide, and radiocontrast agents. 3,5 Several factors contribute to aminoglycoside nephrotoxicity, including a decrease in the GFR, preexisting renal disease, hypo- volemia, and concurrent administration of other drugs that have a nephrotoxic effect. Cisplatin accumulates in proximal tubule cells, inducing mitochondrial injury and inhibition of adenosine triphosphatase (ATPase) activ- ity and solute transport. Radiocontrast media–induced nephrotoxicity is thought to result from direct tubular toxicity and renal ischemia. 11 The risk for renal dam- age caused by radiocontrast media is greatest in elderly persons and those with preexisting kidney disease, vol- ume depletion, diabetes mellitus, and recent exposure to other nephrotoxic agents. The presence of multiple myeloma light chains, excess uric acid, hemoglobin, or myoglobin in the urine is the most frequent cause of ATN due to intratubular obstruc- tion. Both myeloma cast nephropathy (Chapter 11) and acute urate nephropathy (Chapter 8) usually are seen in the setting of widespread malignancy or massive tumor destruction by therapeutic agents. 3 Hemoglobinuria results from blood transfusion reactions and other hemolytic crises. Skeletal and cardiac muscles contain myoglobin, which corresponds to hemoglobin in func- tion, serving as an oxygen reservoir in the muscle fibers. Myoglobin normally is not found in the serum or urine. It has a low molecular weight; if it escapes into the cir- culation, it is rapidly filtered in the glomerulus. A life- threatening condition known as rhabdomyolysis occurs when increasing myoglobinuria levels cause myoglobin to precipitate in the renal tubules, leading to obstruction and damage to surrounding tubular cells. Myoglobinuria most commonly results from muscle trauma, but may result from extreme exertion, hyperthermia, sepsis, pro- longed seizures, potassium or phosphate depletion, and alcoholism or drug abuse. Both myoglobin and hemo- globin discolor the urine, which may range from the color of tea to red, brown, or black. Clinical Manifestations of Acute Tubular Necrosis. The clinical course of ATN, which is highly variable, is often divided into an initiation, maintenance and recov- ery phase. The onset or initiating phase, which lasts hours or days, is the time from the onset of the precipi- tating event (e.g., ischemic phase of prerenal failure or toxin exposure) until tubular injury occurs. The maintenance phase can involve either an oligu- ric or nonoliguric phase. Nonoliguric ATN has a better outcome. Conversion from a nonoliguric to an oligu- ric state is characterized by a marked decrease in the GFR, accompanied by retention of metabolic wastes such creatinine, urea, and sulfate, which normally are cleared by the kidneys. The urine output usually is lowest at this point. Fluid retention gives rise to edema, water intoxication, and pulmonary congestion. If the period of oliguria is prolonged, hypertension develops and with it signs of uremia (accumulation of nitrogenous wastes in the blood). When untreated, the neurologic manifestations of uremia progress from neu- romuscular irritability to seizures, somnolence, coma, and death.

The recovery phase is the period during which repair of renal tissue takes place. Its onset usually is heralded by a gradual increase in urine output and a fall in serum creatinine, indicating that the nephrons have recovered to the point at which urine excretion is possible. Diuresis often occurs before renal function has fully returned to normal. Consequently, BUN and serum creatinine, potassium, and phosphate levels may remain elevated or continue to rise even though urine output is increased. In some cases, the diuresis may result from impaired nephron function and may cause excessive loss of water and electrolytes. Eventually, renal tubular function is restored with improvement in concentrating ability. At about the same time, the creatinine and BUN begin to return to normal. In some cases, mild to moderate kid- ney damage persists. Diagnosis andTreatment Given the high morbidity and mortality rates associated with AKI, attention should be focused on prevention and early diagnosis. This includes assessment measures to identify persons at risk for development of AKI, including those with preexisting renal insufficiency and diabetes. These persons are particularly at risk for devel- opment of AKI due to nephrotoxic drugs (e.g., amino- glycosides and radiocontrast agents) or drugs such as the NSAIDs that alter intrarenal hemodynamics. Elderly persons are susceptible to all forms of AKI because of the effects of aging on renal reserve. Careful observation of urine output is essential for persons at risk for development of AKI. Urine tests that measure urine osmolality, urinary sodium concentra- tion, and fractional excretion of sodium help differ- entiate prerenal azotemia, in which the reabsorptive capacity of the tubular cells is maintained, from tubular necrosis, in which these functions are lost. One of the earliest manifestations of tubular damage is the inability to concentrate the urine. Further diagnostic information that can be obtained from the urinalysis includes evi- dence of proteinuria, hemoglobinuria, myoglobinuria, and casts or crystals in the urine. Blood tests for BUN and creatinine provide information regarding the ability to remove nitrogenous wastes from the blood. A major concern in the treatment of AKI is identifying and correcting the cause (e.g., improving renal perfusion, discontinuing nephrotoxic drugs). Fluids are carefully regulated in an effort to maintain normal fluid volume and electrolyte concentrations. Adequate caloric intake is needed to prevent the breakdown of body proteins, which increases nitrogenous wastes. 5,8,10 Parenteral hyperalimen- tation may be used for this purpose. Because secondary infections are a major cause of death in persons with AKI, constant effort is needed to prevent and treat such infections. Either hemodialysis (to be discussed) or continuous renal replacement therapy (CRRT) may be indicated when nitrogenous wastes and the water and electrolyte balance cannot be kept under control by other means. 5,10 Venovenous or arteriovenous CRRT has emerged as a