Progression of chronic renal disease in the dog

Progressive loss of nephron function may be caused by persistence of factor s that initiated renal disease. However, newer studies suggest that nephron damage is self-perpetuating once renal mass is reduced to some critical le vel. Original theories on mechanisms of self-perpetuated nephron injury foc used on intraglomerular hypertension and glomerular hypertrophy, but severa l other factors have now been incriminated, including tubulointerstitial re sponses, proteinuria, and oxidative stress. Studies of dogs with surgically reduced renal mass (remnant kidney model of chronic renal disease) have al lowed investigation of the self-progression theory in this species. Use of this model eliminates pre-existing renal disease as a confounding factor. D ata from these studies indicate that self-perpetuated renal injury is initi ated when mild azotemia is induced (plasma creatinine concentration = 2 to 4 mg/dL). Thus, with naturally occurring renal disease(s). it is likely tha t self-perpetuated nephron damage is occurring before or at the time when m ost cases of chronic renal disease are diagnosed. In dogs with remnant kidn eys, loss of renal function often occurs at a linear rate over time, but no n-linear patterns are common as well. The reciprocal of plasma creatinine c oncentration, which has been used to monitor rate of progression, is only a fair marker of renal function when compared to GFR. Thus, clinical results from creatinine measurements on cases of naturally occurring disease shoul d not be interpreted too stringently. In remnant kidney dogs, the magnitude of proteinuria (UPC ratio) was not predictive of the rate in decline of GF R, casting doubt on importance of proteinuria in causing progression of ren al disease. However, progressive increases in UPC may be a marker of an acc elerated rate of renal injury. Self-perpetuation of renal injury in dogs co uld be the sole mechanism by which naturally occurring renal diseases progr ess. When more information is available on the rate of progression of natur ally occurring diseases, it may become apparent whether factors initially i nciting renal damage have an additive effect on rate of progression.