scholarly journals Carbamylated Proteins in Renal Disease: Aggravating Factors or Just Biomarkers?

2022 ◽  
Vol 23 (1) ◽  
pp. 574
Author(s):  
Laëtitia Gorisse ◽  
Stéphane Jaisson ◽  
Christine Piétrement ◽  
Philippe Gillery

Carbamylation is a nonenzymatic post-translational modification resulting from the reaction between cyanate, a urea by-product, and proteins. In vivo and in vitro studies have demonstrated that carbamylation modifies protein structures and functions, triggering unfavourable molecular and cellular responses. An enhanced formation of carbamylation-derived products (CDPs) is observed in pathological contexts, especially during chronic kidney disease (CKD), because of increased blood urea. Significantly, studies have reported a positive correlation between serum CDPs and the evolutive state of renal failure. Further, serum concentrations of carbamylated proteins are characterized as strong predictors of mortality in end-stage renal disease patients. Over time, it is likely that these modified compounds become aggravating factors and promote long-term complications, including cardiovascular disorders and inflammation or immune system dysfunctions. These poor clinical outcomes have led researchers to consider strategies to prevent or slow down CDP formation. Even if growing evidence suggests the involvement of carbamylation in the pathophysiology of CKD, the real relevance of carbamylation is still unclear: is it a causal phenomenon, a metabolic consequence or just a biological feature? In this review, we discuss how carbamylation, a consequence of renal function decline, may become a causal phenomenon of kidney disease progression and how CDPs may be used as biomarkers.

2020 ◽  
Vol 21 (12) ◽  
pp. 4537
Author(s):  
Svenja Koslowski ◽  
Camille Latapy ◽  
Pierrïck Auvray ◽  
Marc Blondel ◽  
Laurent Meijer

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inheritable cause of end stage renal disease and, as of today, only a single moderately effective treatment is available for patients. Even though ADPKD research has made huge progress over the last decades, the precise disease mechanisms remain elusive. However, a wide variety of cellular and animal models have been developed to decipher the pathophysiological mechanisms and related pathways underlying the disease. As none of these models perfectly recapitulates the complexity of the human disease, the aim of this review is to give an overview of the main tools currently available to ADPKD researchers, as well as their main advantages and limitations.


1992 ◽  
Vol 15 (8) ◽  
pp. 465-469 ◽  
Author(s):  
L.K. Saha ◽  
J.C. Van Stone

We retrospectively analyzed data from 3,863 dialysis treatments in 329 end-stage renal disease patients over a period of 33 months to evaluate the accuracy of in vitro KT/V estimated by manufacturer's urea clearance data in relation to in vivo measured KT/V. In 1,087 urea clearances measured, mean actual clearance was 87% of predicted. At all blood flows, actual clearances were significantly lower than predicted (8-16% lower than predicted). In 2,807 KT/V measurements, predicted KT/V was 1.238 ± 0.005 whereas the mean of actual measured KT/V was 16% lower or 1.024 ± 0.005 (P < 0.0001). At different blood flows and with different dialyzers, predicted KT/V overestimated actual values. With increasing numbers of reuse, actual/predicted clearance ratios and actual/predicted KT/V ratios progressively dropped. Prescribing dialysis treatments using manufacturer's in vitro generated clearance data can lead to marked underdialysis of patients.


2021 ◽  
Author(s):  
Maaike F.J. Fransen ◽  
Gabriele Addario ◽  
Carlijn V.C. Bouten ◽  
Franck Halary ◽  
Lorenzo Moroni ◽  
...  

Abstract The number of patients with end-stage renal disease is continuously increasing worldwide. The only therapies for these patients are dialysis and organ transplantation, but the latter is limited due to the insufficient number of donor kidneys available. Research in kidney disease and alternative therapies are therefore of outmost importance. In vitro models that mimic human kidney functions are essential to provide better insights in disease and ultimately novel therapies. Bioprinting techniques have been increasingly used to create models with some degree of function, but their true potential is yet to be achieved. Bioprinted renal tissues and kidney-like constructs presents challenges, for example, choosing suitable renal cells and biomaterials for the formulation of bioinks. In addition, the fabrication of complex renal biological structures is still a major bottleneck. Advances in pluripotent stem cell-derived renal progenitors has contributed to in vivo-like rudiment structures with multiple renal cells, and these started to make a great impact on the achieved models. Natural- or synthetic-based biomaterial inks, such as kidney-derived extracellular matrix and gelatin-fibrin hydrogels, which show the potential to partially replicate in vivo-like microenvironments, have been largely investigated for bioprinting. As the field progresses, technological, biological and biomaterial developments will be required to yield fully functional in vitro tissues that can contribute to a better understanding of renal disease, to improve predictability in vitro of novel therapeutics, and to facilitate the development of alternative regenerative or replacement treatments. In this review, we resume the main advances on kidney in vitro models reported so far.


Open Medicine ◽  
2013 ◽  
Vol 8 (3) ◽  
pp. 297-301 ◽  
Author(s):  
Felix Liebscher ◽  
Tobias Arnold ◽  
Ying Liang ◽  
Thomas Reiter ◽  
Georg Böhmig ◽  
...  

AbstractAnti-vimentin auto-antibodies contribute to chronic allograft nephropathy. They exist in sera of end-stage renal disease patients on hemodialysis (ESRD) already before renal transplantation. We found recently that a 49 kDa vimentin fragment is increased in lymphocytes of ESRD patients which is presented on the cell surface. In vitro studies showed that such a fragment is formed during apoptosis by active caspase-3. We hypothesized that vimentin degradation in leukocytes of ESRD patients correlates to caspase-3 activation in vivo. Lymphocytes and monocytes were isolated from ESRD patients and from healthy volunteers and analyzed for vimentin expression and caspase-3 activation. In addition, apoptosis was induced in vitro and quantified by flow cytometry. ESRD monocytes have shown only the full length 60 kDa vimentin isoform. ESRD lymphocytes, however, showed in addition a strongly increased expression of the 49 kDa vimentin in all samples. Caspase-3 activation was found in 60% of ESRD lymphocytes and 66% of ESRD monocytes but not in healthy volunteers. UV-mediated induction of apoptosis was not associated with vimentin degradation. These experiments could confirm increased vimentin degradation in ESRD lymphocytes. However, we could not validate any correlation to apoptosis.


Author(s):  
Chih-Chien Chiu ◽  
Ya-Chieh Chang ◽  
Ren-Yeong Huang ◽  
Jenq-Shyong Chan ◽  
Chi-Hsiang Chung ◽  
...  

Objectives Dental problems occur widely in patients with chronic kidney disease (CKD) and may increase comorbidities. Root canal therapy (RCT) is a common procedure for advanced decayed caries with pulp inflammation and root canals. However, end-stage renal disease (ESRD) patients are considered to have a higher risk of potentially life-threatening infections after treatment and might fail to receive satisfactory dental care such as RCT. We investigated whether appropriate intervention for dental problems had a potential impact among dialysis patients. Design Men and women who began maintenance dialysis (hemodialysis or peritoneal dialysis) between January 1, 2000, and December 31, 2015, in Taiwan (total 12,454 patients) were enrolled in this study. Participants were followed up from the first reported dialysis date to the date of death or end of dialysis by December 31, 2015. Setting Data collection was conducted in Taiwan. Results A total of 2633 and 9821 patients were classified into the RCT and non-RCT groups, respectively. From the data of Taiwan’s National Health Insurance, a total of 5,092,734 teeth received RCT from 2000 to 2015. Then, a total of 12,454 patients were followed within the 16 years, and 4030 patients passed away. The results showed that members of the non-RCT group (34.93%) had a higher mortality rate than those of the RCT group (22.79%; p = 0.001). The multivariate-adjusted hazard ratio for the risk of death was 0.69 (RCT vs. non-RCT; p = 0.001). Conclusions This study suggested that patients who had received RCT had a relatively lower risk of death among dialysis patients. Infectious diseases had a significant role in mortality among dialysis patients with non-RCT. Appropriate interventions for dental problems may increase survival among dialysis patients. Abbreviations: CKD = chronic kidney disease, ESRD = end-stage renal disease, RCT = root canal therapy.


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