Pathophysiology

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The driving force for glomerular filtration is the pressure gradient from the glomerulus to Bowman space of the proximal tubule. Glomerular pressure depends on renal blood flow (RBF) and is controlled by the combined resistances of the renal afferent and efferent arterioles.

Regardless of the cause of ARF, reductions in RBF represent a common pathologic pathway for decreasing GFR.1 This relationship is most clear in prerenal failure, defined by conditions with normal tubular and glomerular function, where GFR is depressed by compromised renal perfusion. Intrinsic renal failure occurs with diseases of the glomerulus, interstitium, or tubule, associated with the release of renal vasoconstrictors. 2 Postobstructive renal failure initially produces an increase in tubular pressure decreasing the filtration driving force. This pressure gradient soon equalizes, and the maintenance of depressed GFR depends on vasoconstrictors. 3

Depressed RBF and nephrotoxins result in ischemia and renal cell death. This initial injury triggers the production of oxygen free radicals and release of leukotrienes that continue to cause cell injury. Tubular cellular damage results in disruption of tight junctions between cells, allowing backleak of glomerular filtrate, further depressing effective GFR. In addition, dying cells slough off into the tubules, forming obstructing casts further decreasing GFR and leading to oliguria.

During this period of depressed RBF, the kidneys are especially vulnerable to further insults. 4 Exposure to known nephrotoxins such as radiocontrast agents, aminoglycosides, and nonsteroidal anti-inflammatory drugs (NSAIDs) at this time explains the high rate of iatrogenic causes of ARF 5 (Table. .88:2).

Recovery from ARF is first dependent on restoration of RBF. In prerenal failure, restoration of circulating blood volume is usually sufficient. Rapid relief of urinary obstruction in postrenal failure results in a prompt decrease of vasoconstrictors. Clearance of tubular toxins and initiation of therapy for glomerular diseases decrease vasoconstriction and restore RBF in patients with intrinsic renal failure.

Once RBF is restored, the remaining functional nephrons will increase their filtration and eventually hypertrophy. Depending on the size of this remnant nephron pool, GFR will proportionately recover. If the number of remaining nephrons is below a critical value, continued hyperfiltration results in progressive glomerular sclerosis eventually leading to nephron loss. A vicious cycle then ensues where continued nephron loss causes more hyperfiltration until complete renal failure occurs. Hyperfiltration of remnant nephrons explains the commonly observed scenario where progressive renal failure is frequently observed after recovery from ARF. 6

The differential diagnosis of ARF is classified according to the prerenal, intrinsic renal, and postrenal etiologies of ARF.

Prerenal failure is the most common cause of ARF, accounting for 40 to 80 percent of all cases. 7 Prerenal failure is produced by conditions that decrease renal perfusion (Tabie 88.z3.). Besides being an independent cause of ARF, prerenal failure is a common precursor to ischemic and nephrotoxic causes of intrinsic renal failure.8

The etiologies of intrinsic renal failure are subdivided anatomically into diseases of the tubules, interstitium, glomeruli, and vessels ( Table.BB-^.). Intrinsic renal failure accounts for approximately 11 to 45 percent of all cases, depending on the population studied. For adults in a community hospital, prerenal failure accounted for 70 percent of ARF cases as compared with only 11 percent from intrinsic renal etiologies. 9 ARF has a different spectrum in the pediatric population: a higher incidence of intrinsic renal causes for ARF (45 percent) secondary to diseases such as glomerulonephritis and hemolytic-uremic syndrome. 10

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