Albumin overload induces adaptive responses in human proximal tubular cells through oxidative stress but not via angiotensin II type 1 receptor

Shalamanova, Liliana; McArdle, Francis; Amara, Alieu; Jackson, Malcolm J.; Rustom, Rana

doi:10.1152/ajprenal.00265.2006

Cited by 30 publications

(27 citation statements)

References 49 publications

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“…The role of ROS and RNS is considered a critical factor involved in initiation and progression of various mammalian kidney diseases and injuries, including diabetic nephropathy, hypertension-related kidney injury, ischemia-reperfusion injury (IRI), toxic-induced nephropathy, and several forms of inflammatory syndromes (29, 75,148,278,297). There is generation of ROS and RNS in both renal tubular and vascular cells during numerous tissue and cellular stresses.…”

Section: Renal Sources Of Oxidative Stressmentioning

confidence: 99%

Oxidant Mechanisms in Renal Injury and Disease

Ratliff

Abdulmahdi

Pawar

et al. 2016

Antioxidants & Redox Signaling

557

513

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Significance: A common link between all forms of acute and chronic kidney injuries, regardless of species, is enhanced generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) during injury/ disease progression. While low levels of ROS and RNS are required for prosurvival signaling, cell proliferation and growth, and vasoreactivity regulation, an imbalance of ROS and RNS generation and elimination leads to inflammation, cell death, tissue damage, and disease/injury progression. Recent Advances: Many aspects of renal oxidative stress still require investigation, including clarification of the mechanisms which prompt ROS/ RNS generation and subsequent renal damage. However, we currently have a basic understanding of the major features of oxidative stress pathology and its link to kidney injury/disease, which this review summarizes. Critical Issues: The review summarizes the critical sources of oxidative stress in the kidney during injury/ disease, including generation of ROS and RNS from mitochondria, NADPH oxidase, and inducible nitric oxide synthase. The review next summarizes the renal antioxidant systems that protect against oxidative stress, including superoxide dismutase and catalase, the glutathione and thioredoxin systems, and others. Next, we describe how oxidative stress affects kidney function and promotes damage in every nephron segment, including the renal vessels, glomeruli, and tubules. Future Directions: Despite the limited success associated with the application of antioxidants for treatment of kidney injury/disease thus far, preventing the generation and accumulation of ROS and RNS provides an ideal target for potential therapeutic treatments. The review discusses the shortcomings of antioxidant treatments previously used and the potential promise of new ones.

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Section: Renal Sources Of Oxidative Stressmentioning

confidence: 99%

Oxidant Mechanisms in Renal Injury and Disease

Ratliff

Abdulmahdi

Pawar

et al. 2016

Antioxidants & Redox Signaling

557

513

View full text Add to dashboard Cite

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“…11,12 In vitro studies in which albuminuria was modeled by culturing tubular cells in the presence of albumin have led to conflicting results. Whereas some groups demonstrated that albumin can cause oxidative stress 13 and programmed cell death, 14,15 other studies showed that albumin is one of the major serum survival factors for renal tubular cells and can serve to scavenge reactive oxygen species. 16,17 To induce selective podocyte loss via a nonimmune mechanism, we utilized mice that contained the transgene for diphtheria toxin receptor (DTR) downstream of a polyadenylation signal flanked by loxP sites (iDTR mouse 18 ).…”

mentioning

confidence: 99%

Increased Tubular Proliferation as an Adaptive Response to Glomerular Albuminuria

Guo

Marlier

Shi

et al. 2012

Journal of the American Society of Nephrology

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Renal tubular atrophy accompanies many proteinuric renal diseases, suggesting that glomerular proteinuria injures the tubules. However, local or systemic inflammation and filtration of abnormal proteins known to directly injure tubules are also present in many of these diseases and animal models; therefore, whether glomerular proteinuria directly causes tubular injury is unknown. Here, we examined the renal response to proteinuria induced by selective podocyte loss. We generated mice that express the diphtheria toxin receptor exclusively in podocytes, allowing reproducible dose-dependent, specific ablation of podocytes by administering diphtheria toxin. Ablation of ,20% of podocytes resulted in profound albuminuria that resolved over 1-2 weeks after the re-establishment of normal podocyte morphology. Immediately after the onset of albuminuria, proximal tubule cells underwent a transient burst of proliferation without evidence of tubular damage or increased apoptosis, resulting in an increase in total tubular cell numbers. The proliferative response coincided with detection of the growth factor Gas6 in the urine and phosphorylation of the Gas6 receptor Axl in the apical membrane of renal tubular cells. In contrast, ablation of .40% of podocytes led to progressive glomerulosclerosis, profound tubular injury, and renal failure. These data suggest that glomerular proteinuria in the absence of severe structural glomerular injury activates tubular proliferation, potentially as an adaptive response to minimize the loss of filtered proteins.

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“…There were lower urinary MCP-1 levels in the 12/19 renal transplant recipients taking ACE-i. This might be expected if there was a beneficial effect in terms of a reduction in proteinuria [4,7,19]. In the ACE-i-treated group 12 patients with <0.5g proteinuria had MCP-1 levels <300 pg/d vs >300-3000 in the 7 remaining patients with proteinuria >1-6.4 g/24h and MCP-1 levels increased in parallel with the rise in proteinuria.…”

Section: Discussionmentioning

confidence: 97%

Urinary Monocyte Chemoattractant Protein-1 (MCP-1) in Renal Transplant Recipients: Implications in Proteinuric Patients

Amara¹,

Shalamanova²,

Sharma³

et al. 2007

TOTRANSJ

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Abstract/Background: After the first year of transplantation chronic allograft nephropathy is the most important cause of renal graft loss and hypertension and proteinuria occur commonly. In native nephropathies, proteinuria and progression to renal failure are linked and renal tubulo-interstitial fibrosis determines prognosis. Monocyte chemoattractant protein-1 (MCP-1) is a powerful chemokine promoting tubulo-interstitial fibrosis but data are limited in a transplant context. Hence this observational cross-sectional study. Methods:The MAP, 24h urinary creatinine clearance, proteinuria and MCP-1 were measured in 81 renal transplant patients (43 with chronic allograft nephropathy). Most patients were on calcineurin-inhibitor based immunosuppression. Regression analysis was applied and comparisons made with 64 patients with native nephropathies and comparable function. Results:One fifth (18/81) of all renal transplant patients had less than optimally controlled hypertension. Proteinuria was heaviest in non-transplanted patients (average 3.0 g/24h, 0.1-12.2) and the ciclosporin-treated transplant patients (1.2 g/24h, 0.02-6.4). Proteinuria and MCP-1 were positively correlated in all patients (r 0.54, p<0.0001) and r 0.84, p<0.0001 in 19 transplant patients receiving angiotensin-converting enzyme inhibitors. MCP-1 levels were highest in non-transplant and ciclosporin-treated patients; geometric mean (SE), 412.4(1.16) and 314.5(1.21) pg/24h respectively. MCP-1 levels were unrelated to age, MAP, creatinine clearance, or blood ciclosporin or tacrolimus levels. Conclusions:Urinary MCP-1 may be a useful non-invasive marker of chronic graft dysfunction in transplant patients facilitating monitoring of progression and response to treatment even in proteinuric patients.

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Albumin overload induces adaptive responses in human proximal tubular cells through oxidative stress but not via angiotensin II type 1 receptor

Cited by 30 publications

References 49 publications

Oxidant Mechanisms in Renal Injury and Disease

Oxidant Mechanisms in Renal Injury and Disease

Increased Tubular Proliferation as an Adaptive Response to Glomerular Albuminuria

Urinary Monocyte Chemoattractant Protein-1 (MCP-1) in Renal Transplant Recipients: Implications in Proteinuric Patients

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