Renal Pathophysiology

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Although the response to decreased renal perfusion has been described, there are some important pathophysiologic lessons to be learned by review ing three common causes of AKI where renal perfusion and GFR regulation are altered: the hepatorenal syndrome; bilateral renal artery stenosis, partic ularly after the administration of an ACE inhibitor; and the administration of

NSAIDs to susceptible subjects. Hepatorenal Syndrome

The hemodynamic changes occurring in hepatic cirrhosis are discussed in Chapter 4: marked splanchnic vasodilation, leading to reductions in systemic vascular resistance and blood pressure. As in other forms of effective volume depletion, the hypotension in hepatic cirrhosis is associated with progressive elevations in angiotensin II and norepinephrine release, resulting in an in creasing degree of renal ischemia. This is manifested by a gradual reduction in GFR as the hepatic disease becomes more severe. The decline in GFR in hepatic cirrhosis is often masked by reductions in the production of urea (due to the hepatic disease) and creatinine (due mostly to a loss of muscle mass). As a result, the plasma creatinine concen tration may remain within the “normal” range of 1.0 to 1.4 mg/dL in patients with a GFR as low as 20 mL/min. Measurement of cystatin c provides a non-creatinine-based estimate of GFR. Alternatively, measuring the creati nine clearance with a 24-hour urine collection will also provide a more accu rate assessment than the serum creatinine alone. The hepatorenal syndrome is defined as an otherwise unexplained and progressive elevation in the plasma creatinine concentration in a patient with advanced hepatic disease. The traditional classification of type I hepato renal syndrome is more severe and defined as a doubling of serum creatinine within 2 weeks and < 500 mL of urine per day now termed HRS-acute kidney injury (HRS-AKI). Type II is a more indolent process associated with resis tance to diuretics now termed non-AKI HRS or HRS-chronic kidney disease (CKD). Both types are associated with low FENa. The hepatorenal syndrome represents the end stage of a process that gradually lowers renal blood flow and GFR (see Fig. 11.6). Patient survival is extremely limited in hepatorenal syndrome (especially HRS-AKI) unless hepatic function can be improved (as with hepatic trans plantation). Mortality in this setting is due to hepatic encephalopathy or var iceal bleeding rather than due to renal injury. Treatment of hepatorenal syndrome with antidiuretic hormone ana logues (such as terlipressin) or with vasoconstrictors like norepinephrine re verses splanchnic vasodilation, which are often administered with albumin (see Chapter 4 and Fig. 4.6). Other treatment strategies include midodrine (oral α -1 adrenergic agonist and a systemic vasoconstrictor), along with oc treotide (an inhibitor of endogenous vasodilator release leading to splanch nic vasoconstriction); combined therapy theoretically improves renal and

CHAPTER 11 Acute Kidney Injury

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