Table 2 Clinical studies of microparticles in renal transplantation
From: Microparticles in kidney diseases: focus on kidney transplantation
Author/year | Design of study | Patients | Main outcomes | Conclusion |
|---|---|---|---|---|
Dimuccio V et al. 2014 [75] | prospective, randomized and monocentric trial | 25 transplanted patients 20 age-matched control 5 ESRD patients with residual diuresis | Urinary CD133 EVs significantly increased | 1. CD133 EVs may reflect activity of CD133 progenitor cells in renal homeostasis and may provide information on their regenerative potential after kidney injury |
Al-Massarani et al. 2009 [76] | Open, prospective, randomized and mono- | 52 patients 50 healthy control | At 12 months after Tx,↓ in MP and MP procoagulant was more pronounced in patients without CVD history | ↓ MP and MP procoagulant activity in renal graft even in patients without CVD history |
Quamri et al. 2014 [77] | Prospective, randomized and monocentric trial | 213 patients with KTx, 14 KTx and 60 healthy donors | No difference in the quantity of circulating EMP in the pre-KTx or after KTx recipient sera and healthy donor sera | ↓ in circulating EMP and Scr after kidney transplantation |
Al-Massarani et al. 2008 [66] | Open, prospective, randomized and mono | 52 patients 50 healthy control | Positive correlation between circulating endothelial cells (CEC) and history of CVD and between EMP and CMV infection at M12 (month of 12) | CEC usage in indexing vascular injury therapeutic options |
Wu et al. 2014 [78] | Randomized, double blind, placebo-controlled crossover trial | 84 patients with moderate risk of CVD (GG n = 40; GT/TT n = 44) | No significant effect of fish oil supplementation on BP plasma lipids or plasma glucose | GT/TT subjects tended to higher concentrations total cholesterol and LDL but vascular function not affected by Tx or eNOS genotype |
Schuerholz et al. 2007 [79] | Clinical controlled trial | 20 patients Group 1 with 10.4+/−6.1 h Group 2 with 23.7+/−3.8 h | Platelet-derived ex vivo microvesicle formation was higher in group 1 Platelet count was higher in short term ischemia | Lower platelet microvesicle formation after ex vivo stimulation with TRAP was associated with Cr that was lower in both groups longer graft ischemia |
Renner et al. 2013 [80] | Animal and human experimental study | Animal Cyclosporine injection (subcutaneously) for 8–12 weeks to old-man C57BL/6 mice Human EDTA-plasma from five patients before renal Tx and 14 days after initiation of treatment with tacrolimus | Cyclosporine-induced microparticles caused injury to bystander endothelial cells and complement mediated injury of the kidneys and vasculature in cyclosporine-treated mice Number of endothelial MPs in plasma of renal transplant patients increases 2 weeks after initiation of tacrolimus and it was associated with increased C3 deposition on endothelial MPs in some of patients | Injury-associated release of endothelial MPs is a mechanism for systemic insults trigger intravascular complement activation and complement-dependent renal diseases |
Kas-Deelen et al. 2000 [81] | Prospective clinical trial | 54 patients before HCMV infection at ~15 days after Tx weekly (40, 50, 60 days) in first antigenemia test until negative antigenemia 32 patients high antigenemia 12 patients mild antigenemia (<5 pp 65-positive granulocytes/50000 cells) 10 patients without HCMV infection | 1. Cytomegalic endothelial cells in moderate or high HCMV antigenemia 2. Uninfected endothelial cells in patients with or without HCMV antigenemia 3. Incidence of either CEC, EC or combination of both cells was with HCMV-related symptoms (p < 0.01) | Occurrence of rejection episodes before HCMV infection was an important risk for the occurrence of ECs in blood (ECs, CECs, or both) during HCMV infection (p < 0. 001) |
Werner et al. 2006 [48] | Prospective clinical trial | 50 patients with coronary artery disease underwent coronary angiography Circulating CD31+/annexin V+ apoptotic microparticles in peripheral blood was quantified by flow cytometry | Increased apoptotic microparticles counts positively correlated with impairment of coronary endothelial function | In patients with CAD endothelial-dependent vasodilatation closely relies on the degree of endothelial cell apoptosis. In patients with CAD, endothelial-dependent vasodilatation closely relies on the degree of endothelial cell apoptosis increased apoptotic MPs counts predict sever endothelial dysfunction independent of classical risk factors such as HTN, hypercholesterolemia, smoking, diabetes, age or sex |
Shahbazian et al. 2002 [55] | Prospective clinical trial | 173 renal transplant recipients were examined for VEGF promoter Polymorphism using sequence-specific primer-PCR | Acute rejection occurred in 38.7%; -1154*G and -2578*C alleles were associated with higher VEGF production VEGF-1154 GG and GA genotypes were significantly associated with acute rejection risk at 3Â months VEGF-2578 CC and CA genotypes were associated with increased rejection risk | -1154*G and -2578*C containing genotypes, encoding higher VEGF production as strongly associated with acute rejection and may be a useful marker for acute rejection |
Lorenzen et al. 2011 [53] | Prospective cohort study | 62 patients with acute rejection 19 control transplant patients without rejection 13 stable transplant patients with UTI by quantitative RT-PCR | The miR-10b and miR-210 were downregulated and miR-10a upregulated in patients with acute rejection compared to controls. Only miR-210 differed between patients with acute rejection when compared with UTI or transplant patients before/after rejection | Low miR-210 levels were associated with higher decline in GFR 1Â year after transplantation. Selected miRNA are strongly altered in urine of the patients with acute renal graft rejection. The miR-210 levels identify patients with acute rejection and predict long-term kidney function. Urinary miR-210 may thus serve as a novel biomarker of acute rejection |
Scian et al. 2011 [54] | Prospective study | 65 miRNA in samples with CAD with IF/TA vs. normal allografts by microarray Five miRNAs were selected and differential expression By RT-qPCR | Differential expression were detected for miR-142-3p, miR-204, miR-107, and miR-211 | Differential expression of miR-142-3p, miR-204, and miR-211 were observed between patient groups in urine samples. A characteristic miRNA signature for IF/TA that correlates with paired urine samples was identified. This study support the potential use of miRNAs as noninvasive markers of IF/TA and for monitoring graft function. |
Simmons et al. 2005 [60] | Prospective cohort study | 19 patients of living-donor kidney Txs were enrolled. CRP, IL-1, IL-6, IL-10, TNF-a, protein-associated carbonyl content, and F-2 isoprostanes at 1 week pretransplant and 1 week and 2 months posttransplant | ↑pretransplant levels of the pro-inflammatory proteins IL-6, TNF-a, CRP, oxidative markers (plasma protein carbonyls and F2-isoprostanes in ESRD patients vs. healthy control subjects ↓ posttransplant levels of pro-inflammatory proteins and oxidative markers on 2 months | Kidney Tx improves the chronic inflammation and ↑ oxidative stress due to uremia and may contribute to survival |
Jarmo et al. 1997 [59] | Prospective study | 20 pediatric renal allograft recipients 12 patients with chronic rejection and 8 with normal histology 9 pediatric liver allograft recipients 7 children with minimal change nephrotic syndrome Apoptotic cell death by apoptosis-induced oligonucleosomal DNA fragmentation in the biopsy using 3′ end labeling with terminal transferase gel fractionation and southern blotting specific cell types with ↑ DNA fragmentation using 3′ end labeling were determined | Specific DNA fragmentation in chronic rejection ↑apoptosis of both the proximal and distal tubular epithelial cells Mean number of apoptotic tubular cells was higher in the renal allografts than liver allograft recipients and patients with minimal change nephrotic syndrome | Increased apoptotic cell death of renal tubular epithelial cells in patients undergoing chronic renal allograft rejection |