PMID- 11245776
OWN - NLM
STAT- MEDLINE
DCOM- 20010614
LR  - 20220419
IS  - 0270-9295 (Print)
IS  - 0270-9295 (Linking)
VI  - 21
IP  - 2
DP  - 2001 Mar
TI  - Urinary tract obstruction.
PG  - 133-45
AB  - Angiotensin II plays a pivotal role in the progression of renal diseases, 
      including obstructive nephropathy. Increasing levels of angiotensin II in 
      obstructive nephropathy upregulate the expression of several factors: 
      transforming growth factor-beta1 (TGF-beta1), tumor necrosis factor-alpha 
      (TNF-alpha), platelet-derived growth factor (PDGF), insulin-like growth factor 
      (IGF-1), osteopontin, vascular cell adhesion molecule-1 (VCAM-1), nuclear 
      factor-kappaB (NF-kappaB), monocyte chemoattractant peptide-1 (MCP-1), 
      intercellular adhesion molecule-1 (ICAM-1), and CD14 among others. Local 
      production of TGF-beta, by intrinsic renal cells or by macrophages invading the 
      kidney, is a key mediator of renal fibrosis. Activation of TGF-beta stimulates 
      endothelin production. Endothelin, in turn, is a potent stimulus for 
      fibrogenesis. Oxidative stress, fueled in part by angiotensin II, upregulates the 
      expression of adhesion molecules, chemoattractant compounds and cytokines. 
      Sustained obstructive nephropathy leads to apoptosis of tubular epithelial cells. 
      Several factors and genes involved in apoptosis have been described. Nuclear 
      factor kappa-B is involved in the transcriptional regulation of genes present in 
      several organs, including the kidney. NF-kappaB is activated in the setting of 
      ureteral obstruction. Administration of angiotensin-converting enzyme (ACE) 
      inhibitors decreased significantly the activation of NF-kappaB in the obstructed 
      kidney. Studies in neonatal rats indicate that chronic ureteral obstruction 
      decreases the expression of epidermal growth factor (EGF). Replacement of this 
      factor decreased apoptosis and reduced the expression of vimentin, clusterin, and 
      TGF-beta. The administration of IGF-1 also lessened the tubular and interstitial 
      pathology in the setting of ureteral obstruction. A spectrum of urinary tract 
      malformations have been described. The utility of certain markers such as fetal 
      serum beta(2) microglobulin as a predictor of postnatal renal function in 
      bilateral uropathies has been described. A number of pharmacologic interventions 
      that ameliorate the increased expansion of the interstitial volume, decrease the 
      expression of TGF-beta, and down-regulate the production of extracellular matrix 
      and the infiltration of the interstitium by macrophages have been described. 
      Drugs used include ACE inhibitors, administration of arginine, administration of 
      osteogenic protein-1, Pirferidone, and so on. It is likely that in the next 
      decade advances in genetic manipulations and new drug therapies may forestall the 
      development of fibrosis in the setting of urinary tract obstruction.
CI  - Copyright 2001 by W.B. Saunders Company
FAU - Klahr, S
AU  - Klahr S
AD  - Department of Medicine, Barnes-Jewish Hospital at Washington University School of 
      Medicine, St. Louis, MO 63110-1092, USA. sklahr@imgate.wustl.edu
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Semin Nephrol
JT  - Seminars in nephrology
JID - 8110298
RN  - 0 (NF-kappa B)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 11128-99-7 (Angiotensin II)
SB  - IM
MH  - Angiotensin II/physiology
MH  - Animals
MH  - Apoptosis
MH  - Fibrosis
MH  - Humans
MH  - NF-kappa B/physiology
MH  - Oxidative Stress
MH  - Signal Transduction
MH  - Transforming Growth Factor beta/physiology
MH  - Tumor Necrosis Factor-alpha/physiology
MH  - Up-Regulation
MH  - Ureteral Obstruction/drug therapy/genetics/*physiopathology
RF  - 84
EDAT- 2001/03/14 10:00
MHDA- 2001/06/15 10:01
CRDT- 2001/03/14 10:00
PHST- 2001/03/14 10:00 [pubmed]
PHST- 2001/06/15 10:01 [medline]
PHST- 2001/03/14 10:00 [entrez]
AID - S0270-9295(01)70005-8 [pii]
AID - 10.1053/snep.2001.20942 [doi]
PST - ppublish
SO  - Semin Nephrol. 2001 Mar;21(2):133-45. doi: 10.1053/snep.2001.20942.