scholarly journals Clinical Relevance of Corticosteroid Withdrawal on Graft Histological Lesions in Low-Immunological-Risk Kidney Transplant Patients

2021 ◽  
Vol 10 (9) ◽  
pp. 2005
Author(s):  
Domingo Hernández ◽  
Juana Alonso-Titos ◽  
Teresa Vázquez ◽  
Myriam León ◽  
Abelardo Caballero ◽  
...  

The impact of corticosteroid withdrawal on medium-term graft histological changes in kidney transplant (KT) recipients under standard immunosuppression is uncertain. As part of an open-label, multicenter, prospective, phase IV, 24-month clinical trial (ClinicalTrials.gov, NCT02284464) in low-immunological-risk KT recipients, 105 patients were randomized, after a protocol-biopsy at 3 months, to corticosteroid continuation (CSC, n = 52) or corticosteroid withdrawal (CSW, n = 53). Both groups received tacrolimus and MMF and had another protocol-biopsy at 24 months. The acute rejection rate, including subclinical inflammation (SCI), was comparable between groups (21.2 vs. 24.5%). No patients developed dnDSA. Inflammatory and chronicity scores increased from 3 to 24 months in patients with, at baseline, no inflammation (NI) or SCI, regardless of treatment. CSW patients with SCI at 3 months had a significantly increased chronicity score at 24 months. HbA1c levels were lower in CSW patients (6.4 ± 1.2 vs. 5.7 ± 0.6%; p = 0.013) at 24 months, as was systolic blood pressure (134.2 ± 14.9 vs. 125.7 ± 15.3 mmHg; p = 0.016). Allograft function was comparable between groups and no patients died or lost their graft. An increase in chronicity scores at 2-years post-transplantation was observed in low-immunological-risk KT recipients with initial NI or SCI, but CSW may accelerate chronicity changes, especially in patients with early SCI. This strategy did, however, improve the cardiovascular profiles of patients.

2019 ◽  
Author(s):  
Joey Junarta ◽  
Nina Hojs ◽  
Robin Ramphul ◽  
Racquel Lowe-Jones ◽  
Juan C Kaski ◽  
...  

Abstract Background Kidney transplant patients suffer from vascular abnormalities and high cardiovascular event rates, despite initial improvements post-transplantation. The nature of the progression of vascular abnormalities in the longer term is unknown. This pilot study investigated changes in vascular abnormalities over time in stable kidney transplant patients long after transplantation. Methods Brachial artery flow-mediated dilation (FMD), nitroglycerin-mediated dilation, carotid-femoral pulse wave velocity (cf-PWV), ankle-brachial pressure index, and common carotid artery intima-media thickness (CCA-IMT) were assessed in 18 kidney transplant patients and 17 controls at baseline and 3-6 months after. Results There was no difference in age (51±13 vs. 46±11; P=0.19), body mass index (26±5 vs. 25±3; P=0.49), serum cholesterol (4.54±0.96 vs. 5.14±1.13; P=0.10), systolic blood pressure (BP) (132±12 vs. 126±12; P=0.13), diastolic BP (82±9 vs. 77±8; P=0.10), or diabetes status (3 vs. 0; P=0.08) between transplant patients and controls. No difference existed in vascular markers between patients and controls at baseline. In transplant patients, FMD decreased (-1.52±2.74; P=0.03), cf-PWV increased (0.62±1.06; P=0.03), and CCA-IMT increased (0.35±0.53; P=0.02). No changes were observed in controls. Conclusions Markers of vascular structure and function worsen in the post-transplant period on long-term follow-up, which may explain the continued high cardiovascular event rates in this population.


2021 ◽  
Vol 2 (3) ◽  
pp. 291-293
Author(s):  
Ryan J. Winstead ◽  
Johanna Christensen ◽  
Sara Sterling ◽  
Megan Morales ◽  
Dhiren Kumar ◽  
...  

Information regarding Coronavirus disease 2019 in the transplant population is lacking. Recently it has been suggested that cycle threshold values obtained on polymerase chain reaction tests may serve as a marker of disease severity with lower values (i.e., higher viral load) being associated with higher mortality. This study was done to assess the impact of remdesivir use on the time to a negative COVID-19 PCR as well as the degree of change between two Ct’s based on treatment. A total of 30 kidney transplant patients with a new diagnosis of COVID-19 were assessed. Serial PCR results were followed from the time of diagnosis then every 2–4 weeks until negative. In patients who received remdesivir immediately after COVID-19 confirmation compared to no remdesivir, time to negative PCR was not statistically different with a median duration of 57 days in both groups (p = 0.369). The change in the Ct between the first and the second PCR test was also not statistically different between groups with a median change of 18.4 cycles in the remdesivir group and 15.7 cycles without remdesivir (p = 0.516). The results of this small single-center analysis suggest that remdesivir may not be beneficial in shortening time to a negative COVID-19 PCR.


2019 ◽  
Vol 96 (1) ◽  
pp. 231-244 ◽  
Author(s):  
Claudia Sommerer ◽  
Barbara Suwelack ◽  
Duska Dragun ◽  
Peter Schenker ◽  
Ingeborg A. Hauser ◽  
...  

1998 ◽  
Vol 66 (4) ◽  
pp. 471-476 ◽  
Author(s):  
Touru Hanafusa ◽  
Yasuji Ichikawa ◽  
Hidefumi Kishikawa ◽  
Masahiro Kyo ◽  
Takanobu Fukunishi ◽  
...  

2013 ◽  
Vol 59 (12) ◽  
pp. 1761-1769 ◽  
Author(s):  
Jean-Baptiste Woillard ◽  
Nassim Kamar ◽  
Sandra Coste ◽  
Lionel Rostaing ◽  
Pierre Marquet ◽  
...  

BACKGROUND Recent studies have identified new candidate polymorphisms in the genes related to CYP3A activity or calcineurin inhibitor dose requirements in kidney transplant recipients. These genes and polymorphisms are CYP3A4 (cytochrome P450, family 3, subfamily A, polypeptide 4) (rs35599367-C>T; *22); POR [P450 (cytochrome) oxidoreductase] (rs1057868-C>T; *28); and PPARA (peroxisome proliferator-activated receptor alpha) (rs4253728-G>A). We investigated the impact of these polymorphisms on sirolimus (SRL) in vitro hepatic metabolism, SRL trough concentrations (C0), and SRL adverse events in kidney transplant recipients. METHODS The clinical study included 113 stable kidney transplant patients switched from a calcineurin inhibitor to SRL (SRL C0 measured at 1, 3, and 6 months thereafter). We investigated SRL metabolism in vitro using human liver microsomes derived from individual donors (n = 31). Microsomes and patients were genotyped by use of Taqman® allelic discrimination assays. The effects of polymorphisms and covariates were studied using multilinear regression imbedded in linear mixed-effect models or logistic regressions. RESULTS In vitro, the CYP3A4*22 allele resulted in approximately 20% lower metabolic rates of SRL (P = 0.0411). No significant association was found between CYP3A4, CYP3A5, or PPARA genotypes and SRL dose, C0, or C0/dose in kidney transplant patients. POR*28 was associated with a minor but significant decrease in SRL log-transformed C0 [CT/TT vs CC, β = −0.15 (0.05); P = 0.0197] but this did not have any impact on the dose administered, which limited the relevance of the finding. After adjustment for nongenetic covariates and correction for false discovery finding, none of the single-nucleotide polymorphisms tested showed significant association with SRL adverse events. CONCLUSIONS These recently described polymorphisms do not seem to substantially influence the pharmacokinetics of SRL or the occurrence of SRL adverse events in kidney transplant recipients.


2014 ◽  
Vol 29 (8) ◽  
pp. 1587-1597 ◽  
Author(s):  
A. P. Bouvy ◽  
M. Klepper ◽  
M. M. L. Kho ◽  
K. Boer ◽  
M. G. H. Betjes ◽  
...  

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