Additive Antiproteinuric Effect of the NSAID Indomethacin and the ACE Inhibitor Lisinopril

Heeg, Je; Jong, de Paul; Vriesendorp, R.; Zeeuw, de Dick

doi:10.1159/000168201

Cited by 45 publications

(23 citation statements)

References 9 publications

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“…ACEI reduce intracapillary pressure, leading to a recovery in glomerular size-selective function, which may account for their antiproteinuric and potential renoprotective effect [21,22]. A selective decrease in intraglomerular transcapillary pressure has also been shown, not related to any change in systemic blood pressure, but mainly due to ACEI-induced efferent arteriolar dilation [23,24]. Table 2 Enalapril and prednisone in nephrotic-range proteinuria -serum and urine electrophoresis Fig.…”

Section: Discussionmentioning

confidence: 99%

Enalapril and prednisone in children with nephrotic-range proteinuria

Delucchi

Cano

Rodríguez

et al. 2000

Pediatric Nephrology

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The effect of enalapril and low prednisone doses on the urinary protein electrophoretic pattern was studied in 13 pediatric patients with glomerular diseases and steroid-resistant nephrotic syndrome. Enalapril was administered at doses of 0.2-0.6 mg/kg per day for 24-84 months, and prednisone was introduced 2 months later in 11 patients at doses of 30 mg/m2 on alternate days. The urine protein electrophoretic pattern showed a reduction of 80% and 70% in the total protein and albumin, respectively, after enalapril. Total urinary protein decreased from 5.46 to 1.1 g/m2 per day (P<0.001). A marked change from a pattern of non-selective urinary protein loss to an albumin-selective proteinuria was observed. Mean total plasma proteins increased from 4.7 to 5.43 g/dl (P<0.001). Four patients became free of proteinuria 24 months after enalapril was started, but only 2 remained free of proteinuria at 48 months of follow-up. The other 11 patients had persistent albuminuria of between 0.5 and 2.6 g/m2 per day with a selective urinary electrophoretic pattern. No additional decrease was observed after steroids were introduced. A clinical improvement in edema was observed in all children. Three patients developed transient acute renal failure, during the course of an infectious disease; 2 developed peritonitis and 1 pneumopathy. In these patients withdrawal of enalapril was necessary until a complete recovery of renal function was observed. Four patients were hypertensive on admission, achieving normal blood pressure 1 month after enalapril was started. No episodes of systemic arterial hypotension were seen. Creatinine clearance and serum potassium showed no statistically significant change.

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Section: Discussionmentioning

confidence: 99%

Enalapril and prednisone in children with nephrotic-range proteinuria

Delucchi

Cano

Rodríguez

et al. 2000

Pediatric Nephrology

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“…It would be interesting to explore other non-RAS intervening modes of therapy directed to maximization of reduction of residual proteinuria. First, different studies demonstrated that intervention in the synthesis of prostaglandins by using NSAID has antiproteinuric properties with equal effectiveness as ACEi therapy (23,24). Because of the well-known side effects of nonselective NSAID, it would be of great interest to explore whether the relative new selective COX-2 inhibitors, for which lower rates of side effects are reported, share the antiproteinuric properties of NSAID, as discussed previously (25).…”

Section: Discussionmentioning

confidence: 98%

Individual Titration for Maximal Blockade of the Renin-Angiotensin System in Proteinuric Patients

Vogt

Navis²,

Zeeuw

2005

Journal of the American Society of Nephrology

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Agents that interfere with the renin-angiotensin system (RAS) reduce proteinuria and afford renal protection. The combination of different measures that serve maximization of RAS blockade is thought to improve the antiproteinuric efficacy. The feasibility and the efficacy of such a combination strategy were studied in nondiabetic patients with residual proteinuria during previous RAS blockade by individual antiproteinuric titration. P roteinuria nowadays is looked upon as an important and independent risk factor for progression of renal disease (1,2). Moreover, evidence from large clinical trials has become available, showing that reduction of proteinuria is important for long-term renoprotection (3,4). In addition, it has been noted that both residual proteinuria and the amount of antiproteinuric response are predictive for renal outcome in individual patients (5,6), indicating that residual proteinuria during therapy is a predictor of the individual renal prognosis. Accordingly, maximum reduction of proteinuria has been advocated as a treatment target for individual renal patients, in addition to control of BP (7-9). For optimal renoprotection, therefore, recent data suggest that treatment target for proteinuria should be Ͻ1 g/d and likely near zero (7,8).Intervention in the renin-angiotensin system (RAS) is currently the most effective strategy that combines renoprotection with proteinuria lowering. Roughly, the average antiproteinuric response of RAS blocking agents is 50%-both for angiotensin-converting enzyme inhibitors (ACEi) and for angiotensin II antagonists (AIIA) (10,11). There are several strategies to optimize the response, including dose titration of the RAS intervening agents (12), combining RAS blockade with lowsodium diet or a diuretic (13), and combining the different RAS blocking strategies (14). Indeed, ACEi plus AIIA renders more antiproteinuric effect and also more renoprotection (15). Although each of these measures is studied widely on the group level, until now, no individual data of maximal RAS blockade on proteinuria are available (9). Moreover, it is unknown whether it is possible, in a prospective manner, to obtain the target level of proteinuria Ͻ1 g/d by titrating these measures in individual patients. In the present study, our aim was to investigate the antiproteinuric potential of additional up-titration with an ACEi to maximal tolerated dose against a background of a maximal dosed AIIA combined with diuretic therapy in a sodium-restricted setting. Materials and Methods Patients and ProtocolPatients were selected from our renal outpatient clinic. All patients gave informed consent and fulfilled the inclusion criterion of a stable proteinuria Ͼ1 g/d and Ͻ10 g/d while they were still on their previous (nonimmune suppressive) antiproteinuric treatment. Moreover, only patients with BP Ͻ140/Ͻ90 mmHg, creatinine clearance Ն30 ml/min per 1.73 m 2 , and age between 18 and 70 yr were included. Patients with cardiovascular disease or diabetes were excluded, as well as frequent users of non...

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“…The effect on proteinuria appears related to the degree of prostaglandin E-2 (PGE-2) inhibition in the urine (40,41). Moreover, when ACE inhibitors are compared with NSAID, it is reported that there is equal reduction in urinary protein excretion (42,43). A combination of both treatments resulted even in a more potent antiproteinuric effect (43,44).…”

Section: Antiproteinuric Properties Count: Another Strategy?mentioning

confidence: 99%

“…Moreover, when ACE inhibitors are compared with NSAID, it is reported that there is equal reduction in urinary protein excretion (42,43). A combination of both treatments resulted even in a more potent antiproteinuric effect (43,44). Interestingly, Vriesendorp et al (45) reported on the renoprotective effect of indomethacin when used as an antiproteinuric tool in patients with proteinuria.…”

Section: Antiproteinuric Properties Count: Another Strategy?mentioning

confidence: 99%

Renoprotection

Vogt

Navis²,

Zeeuw

2002

Journal of the American Society of Nephrology

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Abstract. Data from recent clinical trials show that lowering of BP reduces the rate of renal function loss in chronic renal disease. There is evidence supporting the assertion that BP lowering obtained by intervention in the renin-angiotensinaldosterone system (RAAS) has an additive renoprotective effect in both diabetic and nondiabetic renal diseases. However, to dissociate BP-dependent and non-BP-dependent action of RAAS blockade, the relevant trials are in many cases flawed by design, resulting in BP differences between the comparative antihypertensive strategies. This review discusses whether the relevant literature allows for the conclusion that RAAS intervention has renoprotective effects in addition to its effects on BP. In particular, the main evidence for a specific renoprotective action of RAAS blockade is provided by its consistent antiproteinuric action, which cannot completely be attributed to the reduction in BP. Indeed, other strategies that lower proteinuria without having an antihypertensive effect, such as lowering dietary protein intake or the use of nonsteroidal antiinflammatory drugs, appear to have a renoprotective effect as well. Interestingly, a consistent finding across different intervention studies is that the more proteinuria is reduced the better the kidney appears to be protected. Therefore, it is concluded that agent-characteristics of RAAS intervention (i.e., antiproteinuric properties) independently influence renal function loss in addition to its BP-lowering effect. Future studies should further explore the renoprotective benefit of non-antihypertensive intervention measures, alone and in combination with antihypertensive strategies.Antihypertensive therapy has always been the cornerstone of renoprotective intervention. Recent large trials particularly indicate that intervention in the renin-angiotensin-aldosterone system (RAAS) appears to be effective in retarding the decline of renal function loss in both diabetic and nondiabetic renal diseases. In nondiabetic patients, the AIPRI (1) and REIN (2) studies showed that angiotensin-converting enzyme (ACE) inhibitors delay the progression of renal function loss. Lewis et al. (3) showed a renoprotective effect of ACE inhibitors in type 1 diabetic patients. Moreover, two recent studies, RENAAL (4) and IDNT (5), demonstrated angiotensin-II (AngII)-receptor (type 1) antagonists to be renoprotective in type 2 diabetics.The above-mentioned trials, comprising thousands of patients, can be taken as impressive evidence for RAAS intervention to be superior to other treatment strategies. However, whether the effects of RAAS intervention are due to the specific pharmacologic RAAS blockade as such or due to their antihypertensive potency is a crucial question. This issue is still open, because in many of the above trials, the obtained BP levels were lower in the patients treated with an agent that intervenes in the RAAS compared with the control groups. The current review focuses on this particular question, that is, is renoprotection obtain...

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Additive Antiproteinuric Effect of the NSAID Indomethacin and the ACE Inhibitor Lisinopril

Cited by 45 publications

References 9 publications

Enalapril and prednisone in children with nephrotic-range proteinuria

Enalapril and prednisone in children with nephrotic-range proteinuria

Individual Titration for Maximal Blockade of the Renin-Angiotensin System in Proteinuric Patients

Renoprotection

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