Glomerular haematuria, renal interstitial haemorrhage and acute kidney injury

Cleary, Catalina Martín; Moreno, Juan Antonio; Fernández, Beatriz; Ortíz, Alberto; Parra, Emilio González; Gracia, Carolina; Blanco-Colio, Luís Miguel; Barat, A.; Egido, Jesús

doi:10.1093/ndt/gfq493

Cited by 40 publications

(42 citation statements)

References 9 publications

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“…Our findings indicate that glomerular hemorrhage in WRN is independent of oxidative stress. The possible beneficial effects of NAC treatment in WRN may be associated with reduction of oxidative stress in the kidney (3,25).…”

Section: Discussionmentioning

confidence: 99%

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N-acetylcysteine ameliorates acute kidney injury but not glomerular hemorrhage in an animal model of warfarin-related nephropathy

Ware

Qamri

Özcan

et al. 2013

American Journal of Physiology-Renal Physiology

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Ware K, Qamri Z, Ozcan A, Satoskar AA, Nadasdy G, Rovin BH, Hebert LA, Nadasdy T, Brodsky SV. N-acetylcysteine ameliorates acute kidney injury but not glomerular hemorrhage in an animal model of warfarin-related nephropathy. Am J Physiol Renal Physiol 304: F1421-F1427, 2013. First published April 10, 2013 doi:10.1152/ajprenal.00689.2012.-Warfarin-related nephropathy (WRN) occurs under conditions of overanticoagulation with warfarin. WRN is characterized by glomerular hemorrhage with occlusive tubular red blood cell (RBC) casts and acute kidney injury (AKI). Herein we test the hypothesis that oxidative stress plays a role in the AKI of WRN. 5/6 Nephrectomy rats were treated with either warfarin (0.04 mg·kg Ϫ1 ·day Ϫ1 ) alone or with four different doses of the antioxidant N-acetylcysteine (NAC). Also tested was the ability of our NAC regimen to mitigate AKI in a standard ischemia-reperfusion model in the rat. Warfarin resulted in a threefold or greater increase in prothrombin time in each experimental group. Serum creatinine (Scr) increased progressively in animals receiving only warfarin ϩ vehicle. However, in animals receiving warfarin ϩ NAC, the increase in Scr was lessened, starting at 40 mg·kg Ϫ1 ·day Ϫ1 NAC, and completely prevented at 80 mg·kg Ϫ1 ·day Ϫ1 NAC. NAC did not decrease hematuria or obstructive RBC casts, but mitigated acute tubular injury. Oxidative stress in the kidney was increased in animals with WRN and it was decreased by NAC. The NAC regimen used in the WRN model preserved kidney function in the ischemia-reperfusion model. Treatment with deferoxamine (iron chelator) did not affect WRN. No iron was detected in tubular epithelial cells. In conclusion, this work taken together with our previous works in WRN shows that glomerular hematuria is a necessary but not sufficient explanation for the AKI in WRN. The dominant mechanism of the AKI of WRN is tubular obstruction by RBC casts with increased oxidative stress in the kidney. oxidative stress; warfarin-related nephropathy; 5/6 nephrectomy WE SHOWED THAT WARFARIN coagulopathy induces acute kidney injury (AKI) that is associated with severe glomerular hematuria causing widespread tubular obstruction by red blood cell (RBC) casts (5-7). We documented this association in both humans (5-7) and animal models (31, 41). We named this condition warfarin-related nephropathy (WRN). WRN can have dire consequences, particularly in chronic kidney disease (CKD) patients, whose CKD progression can be accelerated (5, 6). In humans, WRN is not an uncommon complication of excessive anticoagulation with warfarin. Our retrospective studies show that when the international normalized ratio (INR) acutely exceeds 3.0, 16% of non-CKD patients (6) and 33-37% of CKD patients (5, 6) may develop AKI within ϳ1 wk of the INR Ͼ 3.0. Those at greatest risk of WRN have CKD or cardiovascular disease (5, 6).The most conspicuous feature of WRN is the presence of numerous renal tubules obstructed by RBC casts. On this basis, it has been assumed that the tubular obstruction was t...

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Section: Discussionmentioning

confidence: 99%

“…For example, CKD patients have reduced plasma antioxidant enzyme activities, such as glutathione peroxidase and catalase (12). Growing evidence indicates that glomerular hemorrhage may lead to tubular epithelial cell injury (3,25). The pathogenesis of tubular injury by RBC includes heme toxicity and iron-associated cellular damage (19,32,39).…”

mentioning

confidence: 99%

N-acetylcysteine ameliorates acute kidney injury but not glomerular hemorrhage in an animal model of warfarin-related nephropathy

Ware

Qamri

Özcan

et al. 2013

American Journal of Physiology-Renal Physiology

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“…Hb is a strong oxidant with potent pro-inflammatory properties that could lead to tubular cell injury and AKI [5]. To restrain these harmful effects, Hb is cleared by CD163, a scavenger receptor present on the surface of alternatively activated M2 macrophages [6,7]. CD163-mediated Hb uptake not only decreases Hb concentration but also induces anti-inflammatory pathways by increasing heme oxygenase-1 (HO-1) synthesis [8].…”

Section: Introductionmentioning

confidence: 99%

“…HO-1 catalyzes the conversion of heme to biliverdin, decreasing the production of reactive oxygen species (ROS) [9]. CD163 and HO-1 are expressed in several kidney diseases related with renal accumulation of Hb, such as IgAN and MH-AKI [7], paroxysmal nocturnal hemoglobinuria [10] and warm antibody hemolytic anaemia [11]. Moreover, recent data provide in vivo evidence that induction of HO-1 is a beneficial response from tissues exposed to heme-induced oxidative stress [12].…”

Section: Introductionmentioning

confidence: 99%

Oxidative Stress, Macrophage Infiltration and CD163 Expression Are Determinants of Long-Term Renal Outcome in Macrohematuria-Induced Acute Kidney Injury of IgA Nephropathy

Gutiérrez

Egido²,

Rubio‐Navarro³

et al. 2012

Nephron Clin Pract

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Background: Macroscopic hematuria (MH) may cause acute kidney injury (AKI) in IgA nephropathy. Up to 25% of patients with MH-associated AKI do not recover baseline renal function. Our objective was to identify subjects at high risk for an adverse renal function. Methods: We examined macrophages, oxidative stress markers (NADPH-p22 and HO-1) and the hemoglobin scavenger receptor (CD163) in renal biopsy specimens from 33 MH-AKI patients with complete recovery (CR, n = 17) or incomplete recovery (IR, n = 16) of renal function after 6.72 (range 0.5–21.5) years of follow-up. Results: CD163-expressing macrophages, HO-1 and NADPH-p22 expression were located in areas surrounding tubules with iron deposits and filled with erythrocyte casts. CD163-positive macrophages score and HO-1- and p22-positive staining correlated positively with percentage of tubules with erythrocyte casts and tubular necrosis. Macrophage infiltration, CD163-positive macrophage score, NADPH-p22- and HO-1-positive staining areas were significantly greater in IR patients when compared with CR patients. The CD163-positive macrophage score and oxidative stress markers (p22 and HO-1) were negatively correlated with renal function outcome, as determined by estimated glomerular filtration rate (eGFR) and proteinuria, at the end of the follow-up period. In multivariate analysis, the CD163-positive macrophage score remained significantly associated with final eGFR and proteinuria after adjustment by age, gender, duration of MH, initial eGFR and proteinuria. Conclusions: Increased macrophage infiltration, CD163 expression and oxidative stress are significant prognostic factors for an IR of renal function in patients with MH-associated AKI. These molecular pathways may be involved in the renal response to injury and could be useful to improve diagnosis and therapeutics.

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“…Superoxide dismutase (SOD) catalyses the conversion of superoxide anion ( -2 O ), a reactive oxygen species (ROS), to hydrogen peroxide (H 2 O 2 ) and molecular oxygen (O 2 ). Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase can also produce ROS, which leads to proteinuria and haematuria [60]. H 2 O 2 induces haem degradation in red blood cells, particularly when glutathione is deficient [61].…”

Section: Glyoxal Methylglyoxal and Glyoxylatementioning

confidence: 99%