scholarly journals Hemodialysis exacerbates proteolytic imbalance and pro-fibrotic platelet dysfunction

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Aaron J. Velasquez-Mao ◽  
Mark A. Velasquez ◽  
Zhengxiong Hui ◽  
Denise Armas-Ayon ◽  
Jingshen Wang ◽  
...  

AbstractMulti-organ fibrosis among end stage renal disease (ESRD) patients cannot be explained by uremia alone. Despite mitigation of thrombosis during hemodialysis (HD), subsequent platelet dysfunction and tissue dysregulation are less understood. We comprehensively profiled plasma and platelets from ESRD patients before and after HD to examine HD-modulation of platelets beyond thrombotic activation. Basal plasma levels of proteolytic regulators and fibrotic factors were elevated in ESRD patients compared to healthy controls, with isoform-specific changes during HD. Platelet lysate (PL) RNA transcripts for growth and coagulative factors were elevated post-HD, with upregulation correlated to HD vintage. Platelet secretome correlations to plasma factors reveal acutely induced pro-fibrotic platelet phenotypes in ESRD patients during HD characterized by preferentially enhanced proteolytic enzyme translation and secretion, platelet contribution to inflammatory response, and increasing platelet dysfunction with blood flow rate (BFR) and Vintage. Compensatory mechanisms of increased platelet growth factor synthesis with acute plasma matrix metalloproteinase (MMP) and tissue inhibitor of MMPs (TIMP) increases show short-term mode-switching between dialysis sessions leading to long-term pro-fibrotic bias. Chronic pro-fibrotic adaptation of platelet synthesis were observed through changes in differential secretory kinetics of heterogenous granule subtypes. We conclude that chronic and acute platelet responses to HD contribute to a pro-fibrotic milieu in ESRD.

2021 ◽  
Author(s):  
Aaron Velasquez-Mao ◽  
Mark Velasquez ◽  
Zhengxiong Hui ◽  
Denise Armas-Ayon ◽  
Jingshen Wang ◽  
...  

Abstract Multi-organ fibrosis among end stage renal disease (ESRD) patients cannot be explained by uremia alone. Despite mitigation of thrombosis during hemodialysis (HD), subsequent platelet dysfunction and tissue dysregulation are less understood. We comprehensively profiled plasma and platelets from ESRD patients before and after HD to examine HD-modulation of platelets beyond thrombotic activation. Basal plasma levels of proteolytic regulators and fibrotic factors were elevated in ESRD patients compared to healthy controls, with isoform-specific changes during HD. Platelet lysate (PL) RNA transcripts for growth and coagulative factors were elevated post-HD, with upregulation correlated to HD vintage. Platelet secretome correlations to plasma factors reveal acutely induced pro-fibrotic platelet phenotypes in ESRD patients during HD characterized by preferentially enhanced proteolytic enzyme translation and secretion, platelet contribution to inflammatory response, and increasing platelet dysfunction with blood flow rate (BFR) and Vintage. Compensatory mechanisms of increased platelet growth factor synthesis with acute plasma matrix metalloproteinase (MMP) and tissue inhibitor of MMPs (TIMP) increases show short-term mode-switching between dialysis sessions leading to long-term pro-fibrotic bias. Chronic pro-fibrotic adaptation of platelet synthesis were observed through changes in alpha-granule- and lysosome-filling behaviors. We conclude that chronic and acute platelet responses to HD contribute to a pro-fibrotic milieu in ESRD.


2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Muhittin Taskapili ◽  
Kubra Serefoglu Cabuk ◽  
Rukiye Aydin ◽  
Kursat Atalay ◽  
Ahmet Kirgiz ◽  
...  

Aim. To determine the effects of hemodialysis (HD) on tear osmolarity and to define the blood biochemical tests correlating with tear osmolarity among patients with end stage renal disease (ESRD).Material-Method. Tear osmolarity of ESRD patients before and after the hemodialysis program was determined as well as the blood biochemical data including glucose, sodium, potassium, calcium, urea, and creatinine levels.Results. Totally 43 eyes of 43 patients (20 females and 23 males) with a mean age of53.98±18.06years were included in the study. Tear osmolarity of patients was statistically significantly decreased after hemodialysis (314.06±17.77versus301.88±15.22 mOsm/L,p=0.0001). In correlation analysis, pre-HD tear osmolarity was negatively correlated with pre-HD blood creatinine level (r=-0.366,  p=0.016). Post-HD tear osmolarity was statistically significantly correlated with the post-HD glucose levels (r=0.305  p=0.047). Tear osmolarity alteration by HD was negatively correlated with creatinine alteration, body weight alteration, and ultrafiltration (r=-0.426,  p=0.004;r=-0.365,  p=0.016; andr=-0.320,p=0.036, resp.). There was no correlation between tear osmolarity and Kt/V and URR values.Conclusion. HD effectively decreases tear osmolarity to normal values and corrects the volume and composition of the ocular fluid transiently. Tear osmolarity alteration induced by HD is correlated with body weight changes, creatinine alterations, and ultrafiltration.


2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Nur Azem ◽  
Oriel Spierer ◽  
Meital Shaked ◽  
Meira Neudorfer

Background.Effects of hemodialysis (HD) treatment on retinal thickness and macular edema are unclear.Objective.To evaluate changes in retinal thickness using optical coherence tomography (OCT) in end stage renal disease (ESRD) patients with diabetic retinopathy (DR), with and without diabetic macular edema (DME), undergoing HD.Methods.Nonrandomized prospective study. Forty eyes of DR patients with ESRD treated with HD were divided into two groups: patients with macular edema and patients without macular edema. Both eyes were analyzed. Patients underwent an ophthalmic examination including OCT measurements of retinal thickness, blood albumin and hemoglobin A1C levels, blood pressure, and body weight, 30 minutes before and after HD.Results.We found no significant effects of HD on retinal thickness among patients both with and without DME. The former showed a trend towards reduction in retinal thickness in foveal area following HD, while the latter showed an increase. There was no correlation between retinal thickness and mean blood pressure, weight, kinetic model value—Kt/V, glycemic hemoglobin, or albumin levels before and after HD.Conclusions.HD has no significant effect on retinal thickness among patients with or without DME. Further studies on larger cohorts and repeated OCT examinations are needed to confirm the preliminary findings in this study.


2020 ◽  
pp. 988-994
Author(s):  
Toru Sanai ◽  
Ken Okamura ◽  
Tomoaki Onoue ◽  
Takashi Ono ◽  
Kenichi Motomura ◽  
...  

<b><i>Background:</i></b> To elucidate the role of hemodilution in the alteration of thyroid hormone levels in end-stage renal disease (ESRD), we compared thyroid function before and after hemodialysis (HD). <b><i>Methods:</i></b> Twenty-three male ESRD patients (age &#x3c;65 years) with either chronic glomerulonephritis (CGN) or diabetic nephropathy (DN), who were enrolled between June 2019 and August 2019, were included in the study. The free thyroxine (fT<sub>4</sub>), free tri-iodothyronine (fT<sub>3</sub>), and thyroid-stimulating hormone (TSH), thyroxine-binding globulin (TBG), and thyroglobulin (Tg), measured before and after HD in 12 patients with CGN (48.7 ± 11.8 years [mean ± standard deviation]) and 11 patients with DN (57.6 ± 6.5 years), were compared with 45 healthy controls (52.5 ± 11.9 years). <b><i>Results:</i></b> The fT<sub>4</sub>, fT<sub>3</sub>, and TBG were significantly low before HD and increased in parallel with an increase in hematocrit and albumin after HD in both ESRD subgroups. The TSH was high before HD and decreased significantly after HD, while Tg remained almost unchanged. In DN, the fT<sub>4</sub> levels were nearly identical, while fT<sub>3</sub> was lower with slightly higher TSH, compared with CGN. The TSH/fT<sub>4</sub> ratios before HD were significantly higher in both subgroups, and the fT<sub>3</sub>/fT<sub>4</sub> ratios after HD were significantly lower in DN than the control. <b><i>Conclusions:</i></b> Our findings suggest that the low fT<sub>4</sub> and fT<sub>3</sub> levels found in ESRD are due to hemodilution before HD, resulting in a slightly higher TSH level but almost unchanged Tg level, and that DN is associated with decreased T<sub>4</sub>-to-T<sub>3</sub> conversion.


Metabolites ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 34
Author(s):  
Tong Liu ◽  
Inci Dogan ◽  
Michael Rothe ◽  
Julius V. Kunz ◽  
Felix Knauf ◽  
...  

(1) Background: Factors causing the increased cardiovascular morbidity and mortality in hemodialysis (HD) patients are largely unknown. Oxylipins are a superclass of lipid mediators with potent bioactivities produced from oxygenation of polyunsaturated fatty acids. We previously assessed the impact of HD on oxylipins in arterial blood plasma and found that HD increases several oxylipins. To study the phenomenon further, we now evaluated the differences in arterial and venous blood oxylipins from patients undergoing HD. (2) Methods: We collected arterial and venous blood samples in upper extremities from 12 end-stage renal disease (ESRD) patients before and after HD and measured oxylipins in plasma by LC-MS/MS tandem mass spectrometry. (3) Results: Comparison between cytochrome P450 (CYP), lipoxygenase (LOX), and LOX/CYP ω/(ω-1)-hydroxylase metabolites levels from arterial and venous blood showed no arteriovenous differences before HD but revealed arteriovenous differences in several CYP metabolites immediately after HD. These changes were explained by metabolites in the venous blood stream of the upper limb. Decreased soluble epoxide hydrolase (sEH) activity contributed to the release and accumulation of the CYP metabolites. However, HD did not affect arteriovenous differences of the majority of LOX and LOX/CYP ω/(ω-1)-hydroxylase metabolites. (4) Conclusions: The HD treatment itself causes changes in CYP epoxy metabolites that could have deleterious effects in the circulation.


Author(s):  
Dan Luo ◽  
Wenbo Zhao ◽  
Zhiming Lin ◽  
Jianhao Wu ◽  
Hongchun Lin ◽  
...  

Gut microbiota alterations occur in end-stage renal disease (ESRD) patients with or without dialysis. However, it remains unclear whether changes in gut microbiota of dialysis ESRD patients result from dialysis or ESRD, or both. Similarly, there is a dearth of information on the relationship between gut microbiota and ESRD prognoses. We collected fecal samples and tracked clinical outcomes from 73 ESRD patients, including 33 pre-dialysis ESRD patients, 19 peritoneal dialysis (PD) patients, and 21 hemodialysis (HD) patients. 16S rRNA sequencing and bioinformatics tools were used to analyze the gut microbiota of ESRD patients and healthy controls. Gut microbiota diversity was different before and after dialysis. Bacteroidetes were significantly deceased in HD patients. Twelve bacterial genera exhibited statistically significant differences, due to dialysis (all P &lt; 0.05, FDR corrected). HD reversed abnormal changes in Oscillospira and SMB53 in pre-dialysis patients. Functional predictions of microbial communities showed that PD and HD altered signal transduction and metabolic pathways in ESRD patients. Furthermore, Bacteroides and Phascolarctobacterium were associated with cardiovascular mortality. Dorea, Clostridium, and SMB53 were related to peritonitis in PD patients. This study not only demonstrated differences in gut microbiota between pre-dialysis and dialysis ESRD patients, but also firstly proposed gut bacteria may exert an impact on patient prognosis.


2020 ◽  
Author(s):  
Ray-E Chang ◽  
Shih-Pi Lin ◽  
Feng-Jung Yang ◽  
Robert C. Myrtle

Abstract Background: Except for renal transplantation, peritoneal dialysis (PD) is considered to be relatively cost-effective option for end-stage renal disease (ESRD) patients. Less than 7% of ESRD patients receiving PD in Taiwan, and the promising benefits of PD treatment influenced health policy makers to seek ways to encourage PD utilization. The purpose of this study is to evaluate the effect of their policy initiatives.Methods: An observational longitudinal study using a before-and-after analysis was conducted. The propensity score matching technique was employed to match PD patients before and after the introduction of Taiwan’s efforts to encourage PD utilization in ESRD patients, and the change in PD technical failure was analyzed. HD patients were also matched as the control group to assess the impact of Taiwan’s PD utilization encouraging policies on mortality in PD patients. The competing risk regression approach for survival analysis was adopted in our study.Results: The results showed that while the PD encouraging policies had increased the PD utilization, the increase in PD utilization was accompanied by an increase in technique failure and an increase in mortality.Conclusions: The adoption of new treatments which may benefit patients and incentives to change physician practice behaviors require more disciplined and carefully managed implementation efforts. Care providers need to be equipped by adequate training and sufficient manpower as part of the policy package.


2017 ◽  
Vol 44 (3) ◽  
pp. 236-243 ◽  
Author(s):  
Diego Castini ◽  
Simone Persampieri ◽  
Riccardo Floreani ◽  
Andrea Galassi ◽  
Maria Luisa Biondi ◽  
...  

Background: End-stage renal disease (ESRD) represents a situation in which persistently elevated levels of cardiac troponins I (cTnI) are frequently found in the absence of clinically evident cardiac disease. Moreover, the effect of hemodialysis (HD) on cTnI levels is not definitively elucidated. The aim of this study was to investigate the effects of HD on cTnI levels in ESRD patients. Methods: We enrolled 30 asymptomatic ESRD patients on maintenance HD. All the patients were dialyzed thrice weekly. We compared each other's cTnI levels obtained before HD sessions (pre-HD) and cTnI levels obtained before and after HD sessions (post-HD). Results: The median value of baseline cTnI, measured before the first dialysis session of the week, was 0.018 ng/mL (interquartile range 0.012-0.051) and elevated levels (>0.034 ng/mL) were found in 9 (30%) patients. Pre-HD cTnI levels showed a statistically significant decrease between the first and the second weekly HD sessions (from 0.018 to 0.016 ng/mL; p = 0.002), while no difference was observed between the second and the third sessions over the week. Finally, no statistically significant differences were found between pre-HD and post-HD cTnI levels, considering each HD session and the averaged cTnI values. Conclusions: Our results indicate that HD does not significantly affect cTnI levels. Even when statistically significant, the observed changes were without clinical relevance indicating that HD does not affect by itself the diagnostic accuracy of cTnI assay in ESRD patients.


2011 ◽  
Vol 31 (2) ◽  
pp. 168-172 ◽  
Author(s):  
Mustafa Keles ◽  
Ummuhan Tozoglu ◽  
Abdullah Uyanik ◽  
Abubekir Eltas ◽  
Yusuf Ziya Bayindir ◽  
...  

Objective There are various causes of halitosis, one of which is chronic renal failure. The objective of this study was to investigate halitosis levels in end-stage renal disease (ESRD) patients before and after peritoneal dialysis (PD) therapy. Methods 42 subjects with ESRD were included in this study. The presence of halitosis was assessed using an organoleptic measurement and compared with blood urea nitrogen (BUN) levels and salivary flow rates. Decayed, missing, and filled teeth (DMFT) index and Community Periodontal Index (CPI) were calculated. All measurements were done before and after patients had received 3 months of PD therapy. Results Mean serum BUN level was found to be lower (46.05 ± 13.30 vs 91.24 ± 31.28 mg/dL), salivary flow rate higher (0.34 ± 0.07 vs 0.26 ± 0.04 mL/minute), and halitosis level lower (2.39 ± 0.60 vs 3.90 ± 0.37) at the end of 3 months of PD therapy than at the beginning of PD therapy. There was no significant difference in CPI or DMFT index before and after PD therapy (p > 0.05). There was statistically significant positive correlation between the presence of halitosis and BUN levels ( r = 0.702, p = 0.001 before PD; r = 0.45, p = 0.002 after PD) and a negative correlation between the presence of halitosis and salivary flow rates ( r = -0.69, p = 0.000 before PD; r = -0.37, p = 0.01 after PD). Conclusion High BUN levels and low salivary flow rates were found to be associated with halitosis. PD may play an important role in decreasing the level of halitosis in ESRD patients.


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