Interaction of the endothelin system and calcineurin inhibitors after kidney transplantation

2002 ◽  
Vol 103 (s2002) ◽  
pp. 396S-398S ◽  
Author(s):  
Torsten SLOWINSKI ◽  
Thomas SUBKOWSKI ◽  
Petra DIEHR ◽  
Daniela BACHERT ◽  
Lutz FRITSCHE ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Calcineurin Inhibitors ◽  
Urinary Protein Excretion ◽  
Urinary Protein ◽  
Converting Enzyme ◽  
Protein Excretion ◽  
Endothelin System ◽  
Endothelin Converting Enzyme ◽  
Group Time ◽  
Morning Dosage

Plasma endothelin (ET)-1 concentrations have been shown to be elevated in patients receiving calcineurin-inhibitors (CI). We investigated urinary and plasma ET-1 (uET-1, pET-1), BigET-1 (uBigET-1, pBigET-1) concentrations, and plasma soluble endothelin-converting enzyme (ECE) concentrations in 381 adult caucasian kidney allograft recipients with graft survival of more than 2 years from the outpatients department of our clinic. Blood and urine probes were always drawn immediately before morning dosage of immunosuppressants. Mean of urinary protein excretion (meanProt) and mean of serum creatinine (meanCrea) were calculated from all available measurements in the most recent year. uET-1 and uBigET-1 were adjusted for urinary protein excretion by calculating uET-1/meanProt and uBigET-1/meanProt. Patients (n = 310) were on a cyclosporine A or FK506 (CI-group) based immunosuppression protocol, and 71 patients were immunosuppressed without use of CI (nonCI group). Time since transplantation was similar in both groups (mean±S.D.; CI-group: 7.55±2.50; nonCI-group: 7.74±3.06 years, P = 0.240) as well as meanCrea (mean±S.D.; CI-group: 1.97±1.34; nonCI-group: 1.77±1.29mg/dl, P = 0.326). pET-1 was significantly higher in the CI-group, compared with nonCI (mean±S.D.; 0.87±1.4 versus 0.56±0.76fmol/ml, P = 0.011). pBigET-1 was similar (mean±S.D.; 0.85±1.41 versus 0.70±1.21fmol/ml, P = 0.33). ECE concentrations were higher in the CI group (mean±S.D.; 14.30±18.02 versus 9.23±7.42ng/ml, P = 0.001). uET-1/meanProt and uBigET-1/meanProt concentration were similar in the CI-group compared with the nonCI-group (mean±S.D.; uET-1/meanProt: 15±24 versus 21±40pmol/g, P = 0.139; uBigET-1/meanProt: 34±55 versus 19±23pmol/g, P = 0.248). pET-1 elevation in patients receiving CI might be more likely to be due to elevated conversion of pBig-ET-1 by more ECE, and not to higher concentrations of pBigET-1.

scholarly journals Evidence that an angiotensin-converting enzyme inhibitor has a different effect on glomerular injury according to the different phase of the disease at which the treatment is started.

1994 ◽  
Vol 5 (4) ◽  
pp. 1139-1146
Author(s):  
N Perico ◽  
S C Amuchastegui ◽  
V Colosio ◽  
G Sonzogni ◽  
T Bertani ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Converting Enzyme ◽  
Systolic Blood Pressure ◽  
Ace Inhibitor ◽  
Diabetic Rats ◽  
Urinary Protein Excretion ◽  
Urinary Protein ◽  
Converting Enzyme ◽  
Glomerular Injury ◽  
Protein Excretion

In rats with streptozotocin-induced diabetes, the effect of an angiotensin-converting enzyme (ACE) inhibitor on the evolution of glomerular injury according to the time at which the treatment is started with respect to the onset of the disease was studied. Three groups of animals were used, a control Group 1 and two groups of diabetic rats treated with insulin (Groups 2 and 3). The latter were monitored until urinary protein excretion reached 40 to 50 mg/24 h (on average, 23 wk after the induction of the diabetes). At this time, Group 2 continued to receive insulin alone, whereas Group 3 was also given the ACE inhibitor moexipril for 8 more wk. Untreated diabetic rats showed a moderate increase in systolic blood pressure that was normalized by moexipril administration. Urinary protein excretion progressively increased during the 8-wk follow-up in untreated diabetics that, at the end of the study, developed moderate glomerular sclerosis. Moexipril treatment lowered urinary protein excretion to a normal range and completely prevented glomerular injury. Three other groups of rats were similarly treated, except that moexipril treatment was started later on (when proteinuria reached 100 to 200 mg/24 h, on average, 32 wk after the induction of diabetes), and were monitored for another 8 wk. Untreated and treated diabetics had comparable blood glucose levels throughout. Systolic blood pressure, significantly increased in untreated diabetic rats, was effectively controlled by moexipril administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Activity of the endothelin system in kidney allograft recipients is not associated with progression of chronic graft dysfunction

2002 ◽  
Vol 103 (s2002) ◽  
pp. 393S-395S ◽  
Author(s):  
Torsten SLOWINSKI ◽  
Thomas SUBKOWSKI ◽  
Petra DIEHR ◽  
Daniela BACHERT ◽  
Lutz FRITSCHE ◽  
...  
Keyword(s):  
Serum Creatinine ◽  
Graft Function ◽  
Urinary Protein ◽  
Graft Dysfunction ◽  
Kidney Allograft ◽  
Protein Excretion ◽  
Endothelin System ◽  
Chronic Graft Dysfunction ◽  
The Mean ◽  
Morning Dosage

Endothelin (ET) A receptor antagonists have been shown to be beneficial in rat models of chronic kidney allograft dysfunction. We investigated urinary and plasma ET-1 (uET-1, pET-1) and BigET-1 (uBigET-1, pBigET-1) concentrations, and plasma soluble ET-converting enzyme (ECE) concentration in 310 adult Caucasian kidney allograft recipients with graft survival of more than 2 years from the outpatients department of our clinic. All patients were on cyclosporine A- or FK506-based immunosuppression protocols. From all available measurements since transplantation, we calculated the slope of serum creatinine-1/year (slopeCrea) as a parameter for progression of chronic graft dysfunction, as well as the mean of serum creatinine (meanCrea) from most recent year before measurements as a parameter for actual graft function. The slope of urinary protein excretion/year (slopeProt) and mean of urinary protein concentration (meanProt) from most recent year was calculated analogue. uET-1 and uBigET-1 were adjusted for protein excretion by calculating uET-1/meanProt and uBigET-1/meanProt. Blood and urine probes for measurements were always drawn immediately before morning dosage of immunosuppressants. There was no significant correlation of any measured component of the ET system with slopeCrea or slopeProt. MeanCrea (mg/dl) was significantly correlated with pBigET-1 (fmol/ml) and pET-1 (fmol/ml) (pBigET-1: r = 0.179, P = 0.001; pET-1: r = 0.161, P = 0.009). The other measured components of the ET systems were not significant correlated with meanCrea. In conclusion, the actual graft function is associated with elevated pET-1 and BigET-1 concentrations as it is well known from other forms of impaired kidney function. However, the actual concentration of ET-1, soluble ECE, and BigET-1 in urine and plasma in our study is not associated with parameters for progression of chronic graft dysfunction.

Additive antiproteinuric effect of angiotensin-converting enzyme inhibition and non-steroidal anti-inflammatory drug therapy: A clue to the mechanism of action

1991 ◽  
Vol 81 (3) ◽  
pp. 367-372 ◽  
Author(s):  
Jan E. Heeg ◽  
Paul E. de Jong ◽  
Dick de Zeeuw
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Glomerular Filtration ◽  
Urinary Protein Excretion ◽  
Urinary Protein ◽  
Angiotensin Converting Enzyme Inhibition ◽  
Converting Enzyme ◽  
Inflammatory Drug ◽  
Protein Excretion ◽  
Antiproteinuric Effect ◽  
Anti Inflammatory

1. Both the angiotensin-converting enzyme inhibitor, lisinopril, and the non-steroidal anti-inflammatory drug, indomethacin, lower urinary protein excretion in renal disease and improve the selectivity of the residual proteinuria. Despite the clearly different renal haemodynamic profiles of the two drugs, we hypothesize that the antiproteinuric effect has a final common pathway that is a reduction in glomerular filtration pressure. 2. We studied the effects of lisinopril and indomethacin, separately and in combination, on urinary protein excretion, selectivity of proteinuria and renal haemodynamics in nine non-diabetic patients with overt proteinuria. 3. Urinary protein excretion was 5.4 ± 2.5 g/24 h in the control period. Lisinopril monotherapy lowered urinary protein excretion by 53 ± 26%. During indomethacin treatment urinary protein excretion was reduced by 63 ± 24%. After adding indomethacin to lisinopril, urinary protein excretion fell by a further 58 ± 23%, resulting in a 79 ± 17% decrease during combined therapy. 4. Although both lisinopril and indomethacin monotherapy appeared to result in an improvement in glomerular protein permselectivity, no further improvement was seen during the combination therapy. 5. The changes in proteinuria were associated with changes in glomerular filtration rate, which showed a pronounced fall with combination therapy. The renal haemodynamic profiles during the different therapies suggest a post-glomerular vasodilatation by lisinopril and a pre-glomerular vasoconstriction by indomethacin, and the combination of both during the combined treatment. 6. These data suggest a synchronous afterload and preload reduction of glomerular filtration pressure as the cause of the additive effect of the combination of angiotensin-converting enzyme inhibition and non-steroidal anti-inflammatory drug therapy in lowering glomerular filtration rate and proteinuria.

scholarly journals Progression of urinary protein excretion after kidney transplantation: A marker for poor long-term prognosis

2015 ◽  
Vol 35 (4) ◽  
pp. 374-384
Author(s):  
Josefa Borrego Hinojosa ◽  
Miguel Angel Gentil Govantes ◽  
Mercedes Cabello Díaz ◽  
Alberto Rodriguez Benot ◽  
Auxiliadora Mazuecos Blanca ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Urinary Protein Excretion ◽  
Urinary Protein ◽  
Protein Excretion ◽  
Long Term Prognosis

scholarly journals Progression of urinary protein excretion after kidney transplantation: A marker for poor long-term prognosis

Nefrología ◽  
2015 ◽  
Vol 35 (4) ◽  
pp. 374-384 ◽  
Author(s):  
Josefa Borrego Hinojosa ◽  
Miguel Angel Gentil Govantes ◽  
Mercedes Cabello Díaz ◽  
Alberto Rodriguez Benot ◽  
Auxiliadora Mazuecos Blanca ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Urinary Protein Excretion ◽  
Urinary Protein ◽  
Protein Excretion ◽  
Long Term Prognosis
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