PMID- 11158856
OWN - NLM
STAT- MEDLINE
DCOM- 20010426
LR  - 20190815
IS  - 1523-6838 (Electronic)
IS  - 0272-6386 (Linking)
VI  - 37
IP  - 1 Suppl 2
DP  - 2001 Jan
TI  - How renal cytokines and growth factors contribute to renal disease progression.
PG  - S21-4
AB  - Terminal renal failure is the final common fate of chronic nephropathies 
      regardless of the type of original insult. After removal of a critical number of 
      nephrons, adaptive hemodynamic changes in the remaining nephrons ensure enough 
      filtration power to the kidney but are ultimately detrimental. Such changes are 
      largely mediated by the local formation of angiotensin II (AII) and prevented by 
      the use of angiotensin-converting enzyme inhibitors, which also limit the forced 
      opening of large unselective pores in the glomerular barrier, restoring size 
      selectivity. Recent studies suggested that proteins filtered through the 
      glomerular capillary, previously considered a marker of the severity of renal 
      lesions, might have intrinsic toxicity on the proximal tubular cells and a 
      contributory role in the progression of renal damage. Protein overload of 
      proximal tubular cells induced the secretion of endothelin-1 (ET-1), monocyte 
      chemoattractant protein-1 (MCP-1), and regulated on activation, normal T 
      expressed and secreted (RANTES) that was mainly directed toward the basolateral 
      compartment of the cell. Evidence available in rat models of proteinuric renal 
      disease shows that expression of genes encoding such vasoactive and 
      proinflammatory molecules as ET-1, MCP-1, and RANTES was consistently 
      upregulated, and synthesis of the corresponding peptides was enhanced in renal 
      tissue. Additional mechanisms of proximal tubular cell activation leading to 
      interstitial inflammation and matrix deposition are the filtration of 
      protein-bound metals and hormones and deposition and activation of filtered 
      complement. Limiting protein traffic and the biological effect of excessive 
      tubular protein reabsorption by drugs interfering with AII synthesis or 
      biological activity prevents renal disease progression.
FAU - Benigni, A
AU  - Benigni A
AD  - Mario Negri Institute for Pharmacological Research, Bergamo, Italy. 
      abenigni@irfmn.mnegri.it
FAU - Remuzzi, G
AU  - Remuzzi G
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Am J Kidney Dis
JT  - American journal of kidney diseases : the official journal of the National Kidney 
      Foundation
JID - 8110075
RN  - 0 (Angiotensin-Converting Enzyme Inhibitors)
RN  - 0 (Cytokines)
RN  - 0 (Growth Substances)
RN  - 11128-99-7 (Angiotensin II)
SB  - IM
MH  - Angiotensin II/metabolism
MH  - Angiotensin-Converting Enzyme Inhibitors/therapeutic use
MH  - Animals
MH  - Cytokines/*metabolism
MH  - Disease Progression
MH  - Glomerular Filtration Rate/drug effects
MH  - Growth Substances/*metabolism
MH  - Humans
MH  - Kidney/drug effects/*metabolism/pathology
MH  - Kidney Diseases/etiology/*metabolism/prevention & control
MH  - Kidney Tubules, Proximal/cytology/drug effects/metabolism
MH  - Proteinuria/complications/prevention & control
MH  - Rats
EDAT- 2001/02/13 11:00
MHDA- 2001/05/11 10:01
CRDT- 2001/02/13 11:00
PHST- 2001/02/13 11:00 [pubmed]
PHST- 2001/05/11 10:01 [medline]
PHST- 2001/02/13 11:00 [entrez]
AID - S0272-6386(01)29556-0 [pii]
AID - 10.1053/ajkd.2001.20734 [doi]
PST - ppublish
SO  - Am J Kidney Dis. 2001 Jan;37(1 Suppl 2):S21-4. doi: 10.1053/ajkd.2001.20734.