Growth factors in progressive renal disease

Abstract

SUMMARY: Numerous studies of clinical and experimental renal disease have identified potentially pathogenetic roles for a large number of individual polypeptide growth factors, including transforming growth factor‐β, insulin‐like growth factor‐I and ‐II, platelet‐derived growth factor, angiotensin II, nitric oxide, connective tissue growth factor, hepatocyte growth factor, vascular endothelial growth factor, fibroblast growth factor, heparin‐binding epidermal growth factor‐like growth factor, epidermal growth factor and endothelins. Activation of renal growth factor pathways may be initially triggered by glomerular hyperfiltration injury and/or tubular hyper‐resorption injury. The production and actions of these growth factors are contextually influenced by the ambient cytokine milieu and perturbations of the extracellular matrix. Their overall balance, intensity and duration determine whether the net outcome is ultimately a co‐ordinated repair of tissue or a pernicious, fibrotic destruction of renal parenchyma. Specific growth factor blockade has been shown to ameliorate various experimental models of progressive renal disease. Moreover, current treatments proven to retard the progression of human renal disease (such as angiotensin converting enzyme inhibition, hydroxymethylglutaryl coenzyme A reductase inhibition, calcium channel blockade and low‐protein dietary intake), have also been found to antagonize numerous growth factor pathways. The clinical development of more specific growth factor therapies for progressive renal disease has been significantly limited to date by difficulties with selectively targeting and timing cytokine interventions, applying treatments in the setting of heterogeneous renal injury, modulating growth factors with opposing beneficial and deleterious actions, and overcoming growth factor network redundancies. Nevertheless promising new growth factor intervention strategies are being developed and clinical trials are already underway to assess the renoprotective efficacy of several novel pharmacological agents which manipulate renal growth factor activity (including endothelin antagonists, L‐arginine, trapidil and somatostatin analogues). Such strategies will hopefully strengthen our presently limited and relatively ineffective therapeutic armamentarium for progressive renal insufficiency.

Detection and analysis of urinary peptides by on-line liquid chromatography and mass spectrometry: application to patients with renal Fanconi syndrome

“…Peptides present in the glomerular filtrate may contribute to the progression of renal disease and dysfunction associated with proteinuria [1,2]. Analysis of urinary polypeptides has generally used immunochemical methods [3][4][5] for quantitative analysis of specific and known biomolecules.…”