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 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)

Reduced Glomerular Filtration and Elevated Urinary Protein Excretion in Diabetic Ketoacidosis

1990 ◽  
Vol 79 (4) ◽  
pp. 444-447 ◽  
Author(s):  
M. MILTÉNYI ◽  
A. SZABÓ ◽  
T. TULASSAY ◽  
A. KÖRNER ◽  
E. KENESEI ◽  
...  
Keyword(s):  
Glomerular Filtration ◽  
Diabetic Ketoacidosis ◽  
Urinary Protein Excretion ◽  
Urinary Protein ◽  
Protein Excretion

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 Association of angiotensin I-converting enzyme gene polymorphism with susceptibility to antiproteinuric effect of angiotensin I-converting enzyme inhibitors in patients with proteinuria.

1995 ◽  
Vol 6 (6) ◽  
pp. 1676-1678
Author(s):  
T Moriyama ◽  
H Kitamura ◽  
S Ochi ◽  
M Izumi ◽  
K Yokoyama ◽  
...  
Keyword(s):  
Ace Inhibitors ◽  
Urinary Protein ◽  
Converting Enzyme ◽  
Angiotensin I ◽  
Ace Gene ◽  
Protein Excretion ◽  
Angiotensin I Converting Enzyme ◽  
Antiproteinuric Effect ◽  
The Difference ◽  
Effective Group

The antiproteinuric effect of angiotensin I-converting enzyme (ACE) inhibitors in patients with renal diseases of various origins has been well recognized. However, individual responses regarding the degree of decrease in urinary protein excretion appear to vary considerably. The mechanism underlying this variable response to ACE inhibitors has not been clarified yet. A possible role of ACE gene insertion/deletion (I/D) polymorphism in the responsiveness to antiproteinuric effect of ACE inhibitors is examined. Thirty-six patients with proteinuria (23 men and 13 woman; mean age, 47 +/- 13 yr) were studied. These patients were classified into two groups on the basis of the percent decrease in their urinary protein excretion: the effective group, those with a decrease in proteinuria (18 patients, -64 +/- 19%) and the noneffective group (18 patients, +13 +/- 40%). A 287-base pair (bp) I/D polymorphism in the ACE gene was examined by polymerase chain reaction. The allelic frequencies of the ACE gene were I/D = 0.53/0.47 in the effective group and I/D = 0.81/0.19 in the noneffective group. The difference in the allelic frequencies between the two groups was significant (chi 2 = 6.25, P = 0.0114 < 0.05). Furthermore, the difference in the responsiveness of proteinuria to ACE inhibition between genotype II versus genotype ID + DD was statistically significant (chi 2 = 4.05, P = 0.0442 < 0.05). There was no significant difference between the two groups with regard to initial urinary protein level, blood pressure, renal function, and daily sodium intake. The genetic susceptibility to the antihypertensive effect of ACE inhibitors was also studied, but no significant relation was observed. This study suggests the association of ACE gene I/D polymorphism with the antiproteinuric efficacy of ACE inhibitors in patients with proteinuria.

scholarly journals Effect of angiotensin-converting enzyme inhibition in HIV-associated nephropathy.

1997 ◽  
Vol 8 (7) ◽  
pp. 1140-1146
Author(s):  
G C Burns ◽  
S K Paul ◽  
I R Toth ◽  
S L Sivak
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Serum Creatinine ◽  
Enzyme Inhibition ◽  
Angiotensin Converting Enzyme Inhibition ◽  
Converting Enzyme ◽  
Protein Excretion ◽  
Baseline Creatinine ◽  
Converting Enzyme Inhibition ◽  
Nephrotic Range Proteinuria ◽  
H Protein

Angiotensin-converting enzyme inhibition (ACEI) delays progression of diabetic and nondiabetic renal disease. This study examined the effect of fosinopril, 10 mg by mouth daily, in HIV-associated nephropathy (HIV-AN). Twenty patients with HIV-AN were studied. Of 11 patients with non-nephrotic-range proteinuria, 7 received treatment and 4 did not. Average baseline creatinine (mg/dl) for treated and nontreated patients was 1.3 +/- 0.24 and 1.0 +/- 0.25, respectively (P = 0.07). At 24 wk, creatinine of treated and nontreated patients was 1.5 +/- 0.34 and 4.9 +/- 2.4 (P = 0.006). Average baseline 24-h urine protein excretion (g/d) for treated and nontreated patients was 1.6 +/- 0.68 and 0.78 +/- 0.39, respectively (P = 0.02). At 24 wk, 24-h protein excretion of treated and non-treated patients was 1.25 +/- 0.86 and 8.5 +/- 1.4 (P = 0.006). Of nine patients with nephrotic-range proteinuria, five were treated and four were not. Average baseline creatinine for treated and nontreated patients was 1.7 +/- 0.46 and 1.9 +/- 0.42, respectively (P = 0.4). At 12 wk, creatinine for treated and nontreated patients was 2.0 +/- 1.0 and 9.2 +/- 2.0 (P = 0.02). The baseline 24-h protein excretion for treated and nontreated patients was 5.4 +/- 1.6 and 5.2 +/- 0.97 (P = 0.9). At 12 wk, 24-h protein excretion for treated and nontreated was 2.8 +/- 1.0 and 10.5 +/- 3.5 (P = 0.008). These preliminary data suggest that treatment with ACEI may stabilize serum creatinine and 24-h protein excretion for up to 24 wk in patients with non-nephrotic-range proteinuria and for up to 12 wk in patients with nephrotic-range proteinuria when initial serum creatinine is < or = 2.0 mg/dl. Furthermore, the renin-angiotensin system may play a role in HIV-AN, and early treatment with ACEI may be beneficial in HIV-AN.

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