Growth Factors In Acute Renal Failure

EGF

HGF

Ischemic and toxic

Ischemic and toxic

IGF-I

Established ARF

Ischemic and toxic

Pretreatment and established ARF

ARF—acute renal failure; EGF—epidermal growth factor; HGF—hepatocyte growth factor; IGF-I—insulin-like growth factor

ARF—acute renal failure; EGF—epidermal growth factor; HGF—hepatocyte growth factor; IGF-I—insulin-like growth factor

FIGURE 17-3

At least three growth factors have now been demonstrated to be useful as therapeutic agents in animal models of acute renal failure (ARF). These include epidermal growth factor (EGF), insulin-like growth factor I (IGF-I) and hepatocyte growth factor (HGF). All have efficacy in ischemia models and in a variety of toxic models of ARF. In addition, both IGF-I and HGF are beneficial when therapy is delayed and ARF is "established" after an ischemic insult. IGF-I has the additional advantage in that it also ameliorates the course of renal failure when given prophylactically before an acute ischemic insult.

FIGURE 17-4

Expression of messenger RNA (mRNA) for prepro-epidermal growth factor (EGF) in kidney. This schematic depicts the localization of mRNA for prepro-EGF under basal states in kidney. Prepro-EGF mRNA is localized to the medullary thick ascending limbs (MTAL) and distal convoluted tubules (DCT). Immunohistochemical studies demonstrate that under basal conditions the peptide is located on the luminal membrane with the active peptide actually residing within the tubule lumen. It is speculated that, during pathologic states, preformed EGF is either transported or routed to the basolateral membrane or can enter the interstitium via backleak. After a toxic or ischemic insult, expression of EGF is rapidly suppressed and can remain low for a long time. Likewise, total renal content and renal excretion of EGF decreases. CTAL—cortical thick ascending limb; IMCD—inner medullary collecting duct; OMCD—outer medullary collecting duct; and PCT—proximal convoluted tubule.

EGF

IGF-I

Submandibular salivary glands

Liver

Kidney

Lung

Others

Kidney

HGF

Heart

Liver

Muscle

Spleen

Other organs

Kidney

Other organs

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