Antiproteinuric Effect of Naproxen and Indomethacin

Vriesendorp, R.; Donker, A. J. M.; Zeeuw, Dick de; Jong, Paul E. de; Hem, G. K. van der

doi:10.1159/000166941

Cited by 31 publications

(19 citation statements)

References 6 publications

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“…While this action has been noted previously by ourselves [7,8,13,14] and others [6,[9][10][11]15] with various NSAIDs. this is the first double-blind study against placebo to be reported.…”

Section: Discussionsupporting

confidence: 74%

“…For some authors, it is associated with a decrease in glomerular filtration [10], for others, the antiproteinuric effect and the effect on glomerular filtra tion are dissociated [15,16], A small decrease in filtra tion can be observed at the beginning of treatment. Fil tration however returns to normal in spite of continued treatment and when the antiproteinuric effect persists.…”

Section: Discussionmentioning

confidence: 99%

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Diclofenac, a Nonsteroidal Anti-Inflammatory Drug, Decreases Proteinuria in Some Glomerular Diseases: A Controlled Study

et al. 1987

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Treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) was first used in glomerulonephritis (GN) in 1966 but its efficiency is still debated. We studied the antiproteinuric effect of such a treatment in a double-blind study. 29 GN patients with normal renal function (17 membranoproliferative GN, 12 IgA GN) were randomly assigned to receive 100 mg/day of diclofenac or placebo for at least 2 months. There was a significant antiproteinuric effect of diclofenac versus placebo with a fall of 70% in the diclofenac group versus 6 % in the placebo group (p < 0.001 with the Mann-Whitney test). The median was 3 mg/min at onset and 2.45 mg/min after 2 months treatment with the placebo. In the diclofenac group, it was 2.2 and 0.95 mg/min, respectively (p < 0.01). Diclofenac did not significantly increase creatinine levels. Gastric irritation was noted only once. This study establishes the short-term antiproteinuric ation of diclofenac. Whether this action affets the final outcome is not yet determined.

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“…While this action has been noted previously by ourselves [7,8,13,14] and others [6,[9][10][11]15] with various NSAIDs. this is the first double-blind study against placebo to be reported.…”

Section: Discussionsupporting

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Diclofenac, a Nonsteroidal Anti-Inflammatory Drug, Decreases Proteinuria in Some Glomerular Diseases: A Controlled Study

et al. 1987

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“…Evidence for this is derived from studies using nonsteroidal anti-inflammatory drugs (NSAIDs), which block the production of prostaglandins. Interestingly, proteinuria can be reduced by pharmacological treatments with NSAIDs both in experimental models of glomerular injury and in clinical practice (13,23,35,(37)(38)(39). The mechanism of action of NSAIDs in this context is currently unknown.…”

mentioning

confidence: 99%

PGE₂ reduces arachidonic acid release in murine podocytes: evidence for an autocrine feedback loop

Lemieux

Rahal

Kennedy

2003

American Journal of Physiology-Cell Physiology

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Lemieux, Lyne I., Sherine S. Rahal, and Chris R. J. Kennedy. PGE2 reduces arachidonic acid release in murine podocytes: evidence for an autocrine feedback loop. Am J Physiol Cell Physiol 284: C302-C309, 2003. First published September 25, 2002 10.1152/ajpcell.00024.2002 production is associated with the progression of diseases such as membranous nephropathy, nephrotic syndrome, and anti-Thy1 nephritis. We investigated the signaling pathways that regulate the synthesis and actions of PGE2 in glomerular podocytes. To study its actions, we assessed the ability of PGE2 to regulate the production of its own precursor, arachidonic acid (AA), in a mouse podocyte cell line. PGE2 dose-dependently reduced phorbol ester (PMA)-mediated AA release. Inhibition of PMA-stimulated AA release by PGE2 was found to be cAMP/ PKA-dependent, because PGE2 significantly increased levels of this second messenger, whereas the inhibitory actions of PGE2 were reversed by PKA inhibition and reproduced by the cAMP-elevating agents forskolin and IBMX. PGE2 synthesis in this podocyte cell line increased fourfold at 60 min in response to PMA, coinciding with upregulation of cyclooxygenase (COX)-2 but not COX-1 levels. However, PGE2 synthesis was significantly reduced by COX-1-selective inhibition, yet to a lesser extent by COX-2-selective inhibition. Our findings suggest that PMA-stimulated PGE2 synthesis in mouse podocytes requires both basal COX-1 activity and induced COX-2 expression, and that PGE2 reduces PMAstimulated AA release in a cAMP/PKA-dependent manner. Such an autocrine regulatory loop might have important consequences for podocyte and glomerular function in the context of renal diseases involving PGE2 synthesis. adenosine 3Ј,5Ј-cyclic monophosphate; cyclooxygenase; E-prostanoid receptors PROSTAGLANDIN E 2 (PGE 2 ) is synthesized by the metabolism of phospholipase A 2 (PLA 2 )-derived arachidonic acid (AA) to prostaglandin G/H 2 via cyclooxygenase (COX) isoforms (COX-1 or COX-2), followed by the activity of prostaglandin E synthase (17). Thus, as in many other cell types, phospholipid-derived AA liberated in glomerular podocytes could serve as a substrate for PGE 2 synthesis depending on the available complement of COX isoforms. Interestingly, increased podocyte expression of COX-2 has been documented in both a diabetic rat model (20) as well as in a rat subtotal renal ablation model (41). This increased COX-2 expression might therefore translate into elevated PGE 2 levels acting on neighboring cells or the podocytes themselves. In such a scenario, COX-2-derived PGE 2 might therefore function as an autacoid in podocytes, interacting with one or more of its cell surface receptors.PGE 2 can interact with at least four G proteincoupled E-prostanoid (EP) receptor subtypes that have been cloned and characterized from a variety of species, including human, rabbit, rat, and mouse (1,2,5,12,16,28,32,42,44), and are designated EP 1 , EP 2 , EP 3 , and EP 4 . Several studies have confirmed the presence of both EP 1 and EP 4 receptor subtype...

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“…First, it is clearly dependent on the dose of the drugs. For indomethacin, naproxen, and flurbiprofen, the maximal allowed chronic dose had to be used for achieving an optimal antiproteinuric effect (46,40). Second, not only the dose of the NSAID, but also the specific NSAID determined the degree of response.…”

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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Antiproteinuric Effect of Naproxen and Indomethacin

Cited by 31 publications

References 6 publications

Diclofenac, a Nonsteroidal Anti-Inflammatory Drug, Decreases Proteinuria in Some Glomerular Diseases: A Controlled Study

Diclofenac, a Nonsteroidal Anti-Inflammatory Drug, Decreases Proteinuria in Some Glomerular Diseases: A Controlled Study

PGE₂ reduces arachidonic acid release in murine podocytes: evidence for an autocrine feedback loop

Renoprotection

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