The biology of renal hypertrophy

Abstract

From the vast amount of data available it is obviously impossible to construct a schema which describes the sequence of events that transforms a normal renal tubular cell into an enlarged cell with an increased transport capacity, and which is consistent with all of the existing information in the literature. The author has attempted to synthesize most of the available information into an intelligible schema which can act as the basis for further inquiry. The basic tenet which underlies this approach is that renal tubular hypertrophy is not under the control of a specific renal growth factor. Rather, a sequence of events, usually initiated by an increase in single nephron glomerular filtration rate (possibly under the control of circulating or local hormones), increases the sensitivity of the tubular cells to a permissive balance of circulating and local growth factors. This may be initiated by the mechanical effect of an increased tubular fluid flow rate, but such a mechanism has thus far not been established. In the heart, the mechanical effect of increased aortic pressure increases protein synthesis within one hour [240], indicating that a precedent for mechanical stimualtion of cell growth does exist. A central feature of this altered sensitivity appears to be an increase in the activity of the Na-H antiporter, but how this transport event is related to increased phospholipid and protein biosynthesis is unclear. It should be stressed that there is no evidence to indicate that increased Na+-H+ antiport acts as a specific initiating factor for hypertrophy and it is also uncertain whether early stimulation of this process occurs in all forms of hypertrophy. The increased sensitivity of the renal tubular cells to growth factors allows these factors to act as mitogens, but, rather than leading to cell proliferation, they induce hypertrophy owing to the elaboration of one or more endogenous growth inhibitors which transform the mitogenic stimulus into a hypertrophic stimulus. An alternative possibility is that certain local factors which do not possess mitogenic activity may lead to hypertrophy in sensitized cells by an, as yet, undetermined mechanism. This may be the case with angiotensin II. Since an increase in dietary protein intake leads to renal hypertrophy as well as to an increase in plasma renin activity, the role of this hormone in hypertrophy requires further study. The results of this process is a cell which is enlarged with an increased complement of all its normal component molecules and organelles, and which has the capacity to perform a greater amount of reabsorptive and secretory work.