Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022672 (acute tubular necrosis)
 2,175 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transforming growth factor (TGF)-beta1 is important in fibrogenesis and has been involved in the pathogenesis of chronic allograft nephropathy (CAN). The angiotensinogen (AGT) gene encodes the only glycoprotein known to be a precursor of the vasopressor angiotensin II. Angiotensin II is also a growth factor and a profibrogenic cytokine. It mediates the induction of TGF-beta1. We studied the relationship among the intragraft expression of AGT, TGF-beta1, and CAN in stable renal transplant patients (RTP). We used a competitive quantitative reverse transcriptase-polymerase chain reaction (RT-PCR)-ELISA assay to identify intragraft amounts of AGT expression in RTP and correlated it with TGF-beta1 mRNA expression. We studied and performed kidney biopsies on 12 RTP with long-functioning grafts and 6 RTP in the immediate posttransplantation period (7 days) who had acute tubular necrosis as control. Histology was based on Banff working classification criteria. Total RNA was isolated from biopsy specimens. For RT-PCR-ELISA, we created heterologous RNA competitors that coamplified with the same primers as AGT and TGF-beta1. Six of 12 long RTP had proteinuria >1000 mg/24 hr and 6 had proteinuria <1000 mg/24 hr. The differences between Banff grades (P =0.03), AGT, and TGF-beta1 levels by RT-PCR-ELISA were statistically significant between both groups (106.2+/-60.7 vs. 34.1+/-11.9 pg/microg total RNA [P =0.01] and 5954+/-5612 vs. 436+/-517 transcripts/microg total RNA [P =0.01], respectively). The control group showed AGT levels of 25+/-12.2 pg/microg total RNA and TGF-beta1 levels of 228+/-111 transcripts/microg total RNA, significant only for the higher proteinuria group (P=0.01 and P=0.04, respectively). There was a correlation between AGT and TGF-beta1 in both groups (r=0.96, P=0.001). We showed a relationship between mRNA expression of AGT and TGF-beta1 in kidney transplant patients with different grades of CAN and proteinuria.
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PMID:Intragraft messenger RNA expression of angiotensinogen: relationship with transforming growth factor beta-1 and chronic allograft nephropathy in kidney transplant patients. 1235 92

Contrast-induced nephropathy (CIN) is regarded as acute tubular necrosis resulting from the cytotoxicity of contrast media and the medullary hypoxia linking to the interplay of vasoconstriction and vasodilatation. Saline infusion may prevent CIN by inhibiting renin release and thus production of angiotensin II (ANG II), a vasoconstrictor, from angiotensin I (ANG I). Yet the use of angiotensin converting enzyme inhibitor (ACEI) yields conflicting results in the prevention of CIN. We hypothesise that ACEI will be useful for CIN prevention when the saline infusion is insufficient, useless when the saline infusion is sufficient, and counterproductive when the saline infusion is excessive, respectively. When the production of ANG I and thus ANG II is insufficiently inhibited by insufficient saline infusion, ACEI may help prevent CIN by conferring extra inhibition on the production of ANG II from ANG I. The counterproductive effect may result from ACEI blocking the generation of angiotensin 1-7, a potent vasodilator, from angiotensin 1-9 whose precursor, ANG I, is excessively diminished by excessive saline infusion. Clinical data suggest that normal saline infusion at a rate of 1 ml/kg/h for 12 h, 1 ml/kg/h for 6 h, and 2 ml/kg/h for 6 h before and after contrast injection provide sufficient, insufficient, and excessive hydration in the prevention of CIN, respectively. The mainstream guideline is to stop ACEI and provide sufficient hydration for CIN prevention. Alternatively one may continue to have ACEI but the use of normal saline infusion must be limited to 1 ml/kg/h for 6 h before and after contrast injection.
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PMID:A hypothesis on the conflicting results of angiotensin converting enzyme inhibitor in the prevention of contrast-induced nephropathy. 2643 30