Effect of indomethacin on proteinuria in rats with autologous immune complex nephropathy

Kirschenbaum, Michael A.; Liebross, Burt A.; Serros, Edward R.

doi:10.1016/0090-6980(85)90192-3

Cited by 13 publications

(3 citation statements)

References 14 publications

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“…cPLA 2 is an important mediator of C5b-9-dependent GEC injury. First, arachidonic acid (AA) released by cPLA 2 is metabolized in GEC via cyclooxygenases-1 and -2 to prostaglandin E 2 and thromboxane A 2 (20), and inhibition of prostanoid production reduces proteinuria in PHN (21)(22)(23)(24)(25) and in human membranous nephropathy (26). Second, cPLA 2 may mediate GEC injury more directly (16).…”

mentioning

confidence: 99%

Complement C5b-9 Membrane Attack Complex Increases Expression of Endoplasmic Reticulum Stress Proteins in Glomerular Epithelial Cells

Cybulsky¹,

Takano²,

Papillon³

et al. 2002

Journal of Biological Chemistry

110

148

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In the passive Heymann nephritis (PHN) model of membranous nephropathy, complement C5b-9 induces glomerular epithelial cell (GEC) injury, proteinuria, and activation of cytosolic phospholipase A 2 (cPLA 2 ). This study addresses the role of endoplasmic reticulum (ER) stress proteins (bip, grp94) in GEC injury. GEC that overexpress cPLA 2 (produced by transfection) and "neo" GEC (which expresses cPLA 2 at a lower level) were incubated with complement (40 min), and leakage of constitutively expressed bip and grp94 from ER into cytosol was measured to monitor ER injury. Greater leakage of bip and grp94 occurred in complement-treated GEC that overexpress cPLA 2 , as compared with neo, implying that cPLA 2 activation perturbed ER membrane integrity. After chronic incubation (4 -24 h), C5b-9 increased bip and grp94 mRNAs and proteins, and the increases were dependent on cPLA 2 . Expression of bip-antisense mRNA reduced stimulated bip protein expression and enhanced complement-dependent GEC injury. Glomerular bip and grp94 proteins were up-regulated in proteinuric rats with PHN, as compared with normal control. Pretreatment of rats with tunicamycin or adriamycin, which increase ER stress protein expression, reduced proteinuria in PHN. Thus, C5b-9 injures the ER and enhances ER stress protein expression, in part, via activation of cPLA 2 . ER stress protein induction is a novel mechanism of protection from complement attack.

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mentioning

confidence: 99%

Complement C5b-9 Membrane Attack Complex Increases Expression of Endoplasmic Reticulum Stress Proteins in Glomerular Epithelial Cells

Cybulsky¹,

Takano²,

Papillon³

et al. 2002

Journal of Biological Chemistry

110

148

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“…In diets rich in animal proteins, the inhibition of the tubuloglomerular feedback, the increase in glucagon secretion and the local production of vasodilatory prostacyclin have been called as explanations of hyperfiltration and increased glomerular permeability (52,53). Indomethacin, an old, nonspecific, antiproteinuric drug, reduces proteinuria in human and animal studies, supporting a major role of prostaglandins in the pathogenesis of hyperfiltration and proteinuria (54,55).…”

Section: Effect Of Dietary Proteins On Tubulo-glomerular Feedback Andmentioning

confidence: 99%

Nephroprotection by SGLT2i in CKD Patients: May It Be Modulated by Low-Protein Plant-Based Diets?

et al. 2020

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Sodium-glucose-transporter 2 inhibitors (SGLT2i) are a new class of anti-diabetic drugs that in large trials such as CREDENCE have shown also a reduction of glomerular hyperfiltration and albuminuria in type 2 diabetic patients. Hence, the interest toward SGLT2i is focused toward this potential nephroprotective effect, in order to reduce the progression to overt nephropathy, and it seems to be confirmed in the most recent DAPA-CKD trial. This is the reason why the indication for SGLT2i treatment has been extended to chronic kidney disease (CKD) patients with eGFR up to 30 ml/min, namely with CKD stage 1–3. In patients with CKD stage 3 to 5, the most recent KDIGO guidelines recommend low-protein diet and plant-based regimens to delay end-stage kidney disease (ESKD) and improve quality of life. Similarly to SGLT2i, low-protein diets exert renal-protective effects by reducing single nephron hyperfiltration and urinary protein excretion. Beyond the glomerular hemodynamic effects, both protein restriction and SGLT2i are able to restore autophagy and, through these mechanisms, they may exert protective effects on diabetic kidney disease. In this perspective, it is likely that diet may modulate the effect of SGLT2i in CKD patients. Unfortunately, no data are available on the outcomes of the association of SGLT2i and low-protein and/or vegan diets. It is therefore reasonable to investigate whether CKD patients receiving SGLT2i may have further advantages in terms of nephroprotection from the implementation of a low-protein and/or plant-based diet or whether this association does not result in an additive effect, especially in vascular nephropathies.

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“…This effect appeared without hemodynamic alterations, following a thromboxane synthe sis inhibitor. Proteinuria also improves when cyclooxygenase is inhibited in autologous models of immune complex glomerulone phritis [66] and after treatment with dietary fish oil, which reduces glomerular prostaglan din formation in mice with lupus nephritis [67], Other investigators, however, failed to demonstrate a role of eicosanoids in the mediation of proteinuria in glomerular im mune injury. Inhibition of stimulated TxB?…”

Section: Proteinuriamentioning

confidence: 99%

Eicosanoids: Biosynthesis and Function in the Glomerulus

Stahi¹,

Thaiss²

1987

Kidney Blood Press Res

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Effect of indomethacin on proteinuria in rats with autologous immune complex nephropathy

Cited by 13 publications

References 14 publications

Complement C5b-9 Membrane Attack Complex Increases Expression of Endoplasmic Reticulum Stress Proteins in Glomerular Epithelial Cells

Complement C5b-9 Membrane Attack Complex Increases Expression of Endoplasmic Reticulum Stress Proteins in Glomerular Epithelial Cells

Nephroprotection by SGLT2i in CKD Patients: May It Be Modulated by Low-Protein Plant-Based Diets?

Eicosanoids: Biosynthesis and Function in the Glomerulus

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