Renal Pathophysiology

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RENAL PATHOPHYSIOLOGY: THE ESSENTIALS

one study) rather than in three divided doses (1.33 mg/kg each). Once-daily therapy results in very high peak plasma and urinary concentrations; the lat ter exceeds the reabsorptive capacity of the proximal tubule, so that most of the drug is excreted, not taken up by the tubular cells. In contrast, reab sorption is not saturated with divided-dose therapy, and drug uptake by the proximal cells is much greater over the course of the day. Contrast Nephropathy This is a common and often preventable form of toxic tubular injury be cause it is the only clinical circumstance where the exact timing of exposure is known beforehand. The development of contrast nephropathy in hospi talized patients is associated with increased morbidity and mortality. Some experts debate the entity of contrast nephropathy, in patients with baseline normal renal function. Pathogenesis The mechanism of injury is thought to be a combination of direct vasocon strictive effects of the contrast agent with tubular toxicity mediated by gen eration of free radicals. Risk factors for developing contrast nephropathy include existing renal insufficiency, especially if a consequence of diabetic nephropathy, advanced heart failure or other cause of reduced renal perfu sion (such as hypovolemia), high total dose of contrast agent and the osmo lality of the agent used, and perhaps underlying multiple myeloma, especially if associated with hypercalcemia. Prevention The best treatment of contrast-induced renal injury is prevention. The risk can be lowered through the use of isotonic intravenous fluids (either sodium chloride or sodium bicarbonate), lower doses of contrast, the use of “isos molar” agents, the avoidance of repetitive studies that are closely spaced, and the avoidance of volume depletion and NSAID use. There is no evidence that withholding medications that affect autoregulation of GFR (renin-­ angiotensin inhibitors) reduces the risk. Clinical Course Postischemic or nephrotoxic ATN is associated with a progressive elevation in the plasma creatinine concentration, which may stabilize depending on the severity of the injury or continue to rise until dialysis is required. The renal injury typically begins on the day of the insult with hypotension or the administration of a radiocontrast agent; in comparison, the onset is delayed with aminoglycoside therapy. The rate of rise in the plasma creatinine concentration is generally > 0.5 mg/dL/day in patients with ATN. The maximum rate of creatinine rise in the setting of a GFR near zero is approximately from 2 to 2.5 mg/dL/day and would be associated with anuria.

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