The renal cortical fibroblast in renal tubulointerstitial fibrosis

Renal cortical fibroblasts have key roles in mediating intercellular communication with neighboring/infiltrating cells and extracellular matrix (ECM) and maintenance of renal tissue architecture. They express a variety of cytokines, chemokines, growth factors and cell adhesion molecules, playing an active role in paracrine and autocrine interactions and regulating both fibrogenesis and the interstitial inflammatory response. They additionally have an endocrine function in the production of epoetin. Tubulointerstitial fibrosis, the common pathological consequence of renal injury, is characterized by the accumulation of extracellular matrix largely due to excessive production in parallel with reduced degradation, and activated fibroblasts characterized by a myofibroblastic phenotype. Fibroblasts in the kidney may derive from resident fibroblasts, from the circulating fibroblast population or from haemopoetic progenitor or stromal cells derived from the bone marrow. Cells exhibiting a myofibroblastic phenotype may derive from these sources and from tubular cells undergoing epithelial to mesenchymal transformation in response to renal injury. The number of interstitial myofibroblasts correlates closely with tubulointerstitial fibrosis and progressive renal failure. Hence inhibiting myofibroblast formation may be an effective strategy in attenuating the development of renal failure in kidney disease of diverse etiology. (c) 2005 Elsevier Ltd. All rights reserved.

Vitamin A is associated with the inflammatory marker CRP in cystic fibrosis

We have observed that vitamin A levels, deficient in patients with severe disease, returned to normal post lungtransplant independent of oral supplementation or pancreatic sufficiency. We hypothesised that vitamin A is associated with disease severity and the inflammatory marker C-related peptide (CRP). Data from RCH paediatric and TPCH adult CF clinic subjects (ns138 CF, 138 control, aged 5–56 yr), who had participated in a study of bone mineral density (BMD) in which vitamins A, E, D, and CRP, height, weight and lung function had been measured was used. Groups were compared using t- or Wilcoxon-tests, and predictors of vitamin A examined usingmultiple regression. Vitamin A was lower in CF subjects (1.23"0.5 vs. 1.80"0.6 mmolyl, P-0.0001), increasingwith age in paediatric subjects but to a lesser extent in the CF group (Ps0.0007). CRP was correlated with age (rs0.6, P-0.0001). FEV1% predicted (FEV) (57.93"23.0 vs. 70.63"21.8, Ps0.0014), weight z-score (WTZ) (y0.76"0.9 vs. y0.12"1.0, Ps0.0002), lumbar spine BMD z-score (y1.08"1.3 vs. y0.50"1.2, Ps0.009) were lower, and CRP higher (median 7.0, IQR 2–4 vs. median 1.0, IQR 1–3 mgy l, P-0.0001) in vitamin A insufficient CF subjects (61 insufficient vs. 71 sufficient). In all subjects, control status (P-0.0001), WTZ (Ps0.02), vitamin E (Ps 0.0003), CRP (Ps0.001), 1,25 dihydroxy vitamin D (1,25 vit. D) (Ps0.0007), and child, adolescent or adult grouping (all P-0.0001) were predictive of vitamin A. In the CF group, CRP (Ps0.01), Vitamin E (P-0.0001) and 1.25 vit. D (Ps 0.006), but not FEV, were predictive. The normal increase in vitamin A with age was not observed in CF subjects, who had lower levels at any age. This failure of normal increase in vitamin A had a consistent association with increasingCRP , supportingthe hypothesis that increased inflammation may result in increased vitamin A consumption.