Cell proliferation is increased during tissue repair and remodeling. Interestingly, this increased turnover and increased extracellular matrix mRNA persist at the same high levels even in late stage glomerulosclerosis, indicating that ongoing remodeling can occur45. Growth factors affect cell cycle events other than those related to hypertrophy or proliferation. TGF- may directly cause apoptosis, an active form of cell death that does not elicit an inflammatory response. Angiotensin mediates apoptosis via the AT2 receptor. Withdrawal of some growth factors, including PDGF or IGF-1, may activate apoptosis18. Increased cell growth was accompanied by increased apoptosis both in proliferative and sclerotic human glomerular diseases. In experimental mesangial proliferative glomerulonephritis, apoptosis of the mesangial cells was associated with healing and return of structure to normal46. Apoptosis may serve as a healing mechanism, eliminating injured cells with minimal stimulation of immune/inflammatory mechanisms and cytokines.

Topof page


The importance of controlling blood pressure is well recognized as a goal of primary importance in treating progressive renal diseases. However, recent data point to beneficial effects that can be potentially achieved with interventions aimed at nonhemodynamic mechanisms of progressive sclerosis. These mechanisms include increased growth factors, which may be induced in response to various stimuli. The final result of these processes is increased matrix accumulation, the root cause of sclerosis. The particular growth factors and the roles they play may differ at the various stages of injury. The contribution of angiotensin II is particularly relevant since it can be inhibited by currently clinically available agents. The potential regression of glomerular sclerosis has now been shown in human diabetic nephropathy. Animal studies point to PAI-1 as a key target in achieving this remodeling of matrix, however, the specific factors that could optimize regeneration of open capillary loops have not been identified. Further study is necessary to determine the specific role each of these factors plays in varying settings of renal growth to maximize beneficial growth responses and inhibit those deleterious to kidney function and structure.

Topof page



1. Hostetter TH, Olson JL, Rennke HG, Venkatachalam MA & Brenner BM. Hyperfiltration in remnant nephrons: a potentially adverse response to renal ablation. Am J Physiol 1981;241: F85–F93. | PubMed | ISI | ChemPort |
2. Fogo A & Ichikawa I. Glomerular growth promoter—the common channel to glomerular sclerosis. inContemporary Issues in Nephrology: The Progressive Nature of Renal Disease1992; vol. 26 edited by Mitch WE New York, Churchill Livingstone, Inc. pp: 23–54.
3. Neuringer JR, Anderson S & Brenner BM. The role of systemic and intraglomerular hypertension. inContemporary Issues in Nephrology: The Progressive Nature of Renal Disease 1992; vol. 26 edited by Mitch WE New York, Churchill Livingstone pp: 1–21.
4. Anderson S, Meyer TW, Rennke HG & Brenner BM. Control of glomerular hypertension limits glomerular injury in rats with reduced renal mass. J Clin Invest 1985; 76: 612–619. | PubMed | ISI | ChemPort |
5. Fogo A, Yoshida Y, Glick AD, Homma T & Ichikawa I. Serial micropuncture analysis of glomerular function in two rat models of glomerular sclerosis. J Clin Invest 1988; 82: 322–330. | PubMed | ISI | ChemPort |