Glycated and carbamylated albumin are more “nephrotoxic” than unmodified albumin in the amphibian kidney

Groß, Marie-Luise; Piecha, Grzegorz; Bierhaus, Angelika; Hanke, W.; Henle, Thomas; Schirmacher, Peter; Ritz, Eberhard

doi:10.1152/ajprenal.00342.2010

Cited by 46 publications

(45 citation statements)

References 39 publications

(34 reference statements)

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“…For example, carbamylated proteins, such as LDL, can induce endothelial cell death, vascular smooth muscle proliferation, monocyte inflammatory signaling, and endothelial/monocyte cell adhesion-each potentially accelerating the biochemical events of atherosclerosis (8,9,14,39,40). Moreover, carbamylated albumin itself seems to be proinflammatory (41). Additional study will need to clarify the mechanisms linking carbamylation with ESRD mortality.…”

Section: Discussionmentioning

confidence: 99%

Carbamylation of Serum Albumin and Erythropoietin Resistance in End Stage Kidney Disease

Kalim

Tamez

Wenger

et al. 2013

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives The mechanisms underlying erythropoietin resistance are not fully understood. Carbamylation is a post-translational protein modification that can alter the function of proteins, such as erythropoietin. The hypothesis of this study is that carbamylation burden is independently associated with erythropoietin resistance.Design, setting, participants, & measurements In a nonconcurrent prospective cohort study of incident hemodialysis patients in the United States, carbamylated albumin, a surrogate of overall carbamylation burden, in 158 individuals at day 90 of dialysis initiation and erythropoietin resistance index (defined as average weekly erythropoietin dose [U] per kg body weight per hemoglobin [g/dl]) over the subsequent 90 days were measured. Linear regression was used to describe the relationship between carbamylated albumin and erythropoietin resistance index. Logistic regression characterized the relationship between erythropoietin resistance index, 1-year mortality, and carbamylation.Results The median percent carbamylated albumin was 0.77% (interquartile range=0.58%-0.93%). Median erythropoietin resistance index was 18.7 units/kg per gram per deciliter (interquartile range=8.1-35.6 units/kg per gram per deciliter). Multivariable adjusted analysis showed that the highest quartile of carbamylated albumin was associated with a 72% higher erythropoietin resistance index compared with the lowest carbamylation quartile (P=0.01). Increasing erythropoietin resistance index was associated with a higher risk of death (odds ratio per unit increase in log-erythropoietin resistance index, 1.69; 95% confidence interval, 1.06 to 2.70). However, the association between erythropoietin resistance index and mortality was no longer statistically significant when carbamylation was included in the analysis (odds ratio, 1.44; 95% confidence interval, 0.87 to 2.37), with carbamylation showing the dominant association with death (odds ratio for high versus low carbamylation quartile, 4.53; 95% confidence interval, 1.20 to 17.10).Conclusion Carbamylation was associated with higher erythropoietin resistance index in incident dialysis patients and a better predictor of mortality than erythropoietin resistance index.

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Section: Discussionmentioning

confidence: 99%

Carbamylation of Serum Albumin and Erythropoietin Resistance in End Stage Kidney Disease

Kalim

Tamez

Wenger

et al. 2013

Clinical Journal of the American Society of Nephrology

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“…In an amphibian model (axolotl or Mexican salamander), intraperitoneal injection of carbamylated albumin induces renal peritubular fibrosis via induction of NFkB, transforming growth factor-beta (TGF-β), epidermal growth factor (EGF) and endothelin-1 by tubular cells [91].…”

Section: Sh Amino Acid Protein Lysylmentioning

confidence: 99%

Urea, a true uremic toxin: the empire strikes back

Lau

Vaziri

2016

Clinical Science

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Blood levels of urea rise with progressive decline in kidney function. Older studies examining acute urea infusion suggested that urea was well-tolerated at levels 8-10× above normal values. More recent in vitro and in vivo work argue the opposite and demonstrate both direct and indirect toxicities of urea, which probably promote the premature aging phenotype that is pervasive in chronic kidney disease (CKD). Elevated urea at concentrations typically encountered in uremic patients induces disintegration of the gut epithelial barrier, leading to translocation of bacterial toxins into the bloodstream and systemic inflammation. Urea induces apoptosis of vascular smooth muscle cells as well as endothelial dysfunction, thus directly promoting cardiovascular disease. Further, urea stimulates oxidative stress and dysfunction in adipocytes, leading to insulin resistance. Finally, there are widespread indirect effects of elevated urea as a result of the carbamylation reaction, where isocyanic acid (a product of urea catabolism) alters the structure and function of proteins in the body. Carbamylation has been linked with renal fibrosis, atherosclerosis and anaemia. In summary, urea is a re-emerging Dark Force in CKD pathophysiology. Trials examining low protein diet to minimize accumulation of urea and other toxins suggest a clinical benefit in terms of slowing progression of CKD.

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“…Carbamylated erythropoietin (cEPO), by contrast to native EPO, does not induce hematopoietic effects in erythropoietic parameters, such as erythrocyte count, hemoglobin concentration and hematocrit rate, which could have a clinical relevance in CRF [12,13], but presents cytoprotective effects and confers neuroprotection against stroke or diabetic neuropathy [14]. Moreover, it has been described in an amphibian model that carbamylated albumin (cAlb) was nephrotoxic, gaining the capacity to cause tubular and peritubular damages [15].…”

Section: Introductionmentioning

confidence: 99%

Homocitrulline: a new marker for differentiating acute from chronic renal failure

Desmons¹,

Jaisson²,

Piètrement³

et al. 2016

Clinical Chemistry and Laboratory Medicine (CCLM)

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Glycated and carbamylated albumin are more “nephrotoxic” than unmodified albumin in the amphibian kidney

Abstract: Gross M, Piecha G, Bierhaus A, Hanke W, Henle T, Schirmacher P, Ritz E. Glycated and carbamylated albumin are more "nephrotoxic" than unmodified albumin in the amphibian kidney. Am

Cited by 46 publications

References 39 publications

Carbamylation of Serum Albumin and Erythropoietin Resistance in End Stage Kidney Disease

Carbamylation of Serum Albumin and Erythropoietin Resistance in End Stage Kidney Disease

Urea, a true uremic toxin: the empire strikes back

Homocitrulline: a new marker for differentiating acute from chronic renal failure

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