RENAL TUBULE CELL REPAIR FOLLOWING ACUTE RENAL INJURY

Experimental data suggests the recovery of renal function after ischem ic or nephrotoxic acute renal failure is due to a replicative repair p rocess dependent upon prepominately paracrine release of growth factor s. These growth factors promote renal proximal tubule cell proliferati on and a differentiation phase dependent on the interaction between tu bule cells and basement membrane. These insights identify the molecula r basis of renal repair and ischemic and nephrotoxic acute renal failu re, and may lead to potential therapeutic modalities that accelerate r enal repair and lessen the morbidity and mortality associated with the se renal disease processes. In this regard, there is a prominent vasoc onstrictor response of the renal vasculature during the postischemic p eriod of developing acute renal failure. The intravenous administratio n of pharmacologic doses of atrial natriuretic factor (ANF) in the pos tischemic period have proven efficacious by altering renal vascular re sistance, so that renal blood flow and glomerular filtration rate impr ove. ANF also appears to protect renal tubular epithelial integrity an d holds significant promise as a therapeutic agent in acute renal fail ure. Of equal or greater promise are the therapeutic interventions tar geting the proliferative reparative zone during the postischemic perio d. The exogenous administration of epidermal growth factor or insulin- like growth factor-1 in the postischemic period have effectively decre ased the degree of renal insufficiency as measured by the peak serum c reatinine and has hastened renal recovery as measured by the duration of time required to return the baseline serum creatinine values. A sim ilarly efficacious role for hepatocyte growth factor has also been rec ently demonstrated.