scholarly journals Pilot Analysis of Late Conversion to Belatacept in Kidney Transplant Recipients for Biopsy-Proven Chronic Tacrolimus Toxicity

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Shruti Gupta ◽  
Ivy Rosales ◽  
David Wojciechowski
Keyword(s):  
Interstitial Fibrosis ◽  
Calcineurin Inhibitors ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Tubular Atrophy ◽  
Transplant Patients ◽  
Number Of Patients ◽  
Allograft Function ◽  
The Mean ◽  
Arteriolar Hyalinosis

Background. Calcineurin inhibitors are associated with chronic nephrotoxicity, manifesting as interstitial fibrosis/tubular atrophy (IF/TA) and arteriolar hyalinosis. Conversion from tacrolimus to belatacept may be one strategy to preserve renal function. Methods. We conducted a retrospective review of renal transplant patients followed at our institution who were converted to belatacept and found to have chronic tacrolimus toxicity on biopsy. The primary outcome was eGFR at conversion as compared to eGFR at 3, 6, 12, and 24 months after conversion. We also assessed incidence of infection and rates of allograft survival at 1 year. Results. The average time between transplant and conversion was 11.9 years. There was no decrease in eGFR at any postconversion time point as compared with preconversion. The mean eGFR at time of preconversion was 32.9 mL/min, as compared with 35.6 mL/min at 3 months (p=0.09), 34.1 mL/min at 6 months (p=0.63), 34.9 mL/min at 12 months (p=0.57), and 39.6 mL/min at 24 months after conversion (p=0.92). Four of 7 patients had increases in their eGFR after conversion. All grafts were functioning at 1 year after conversion. Conclusion. While this study was limited by a small number of patients, belatacept conversion stabilized eGFR at all time points in patients with late allograft function due to chronic tacrolimus toxicity, with a trend towards increased eGFR at 3 months.

scholarly journals Urinary vitronectin identifies patients with high levels of fibrosis in kidney grafts

2020 ◽  
Author(s):  
Laura Carreras-Planella ◽  
David Cucchiari ◽  
Laura Cañas ◽  
Javier Juega ◽  
Marcella Franquesa ◽  
...  
Keyword(s):  
Differential Expression ◽  
Kidney Transplant ◽  
Interstitial Fibrosis ◽  
Calcineurin Inhibitors ◽  
Enzyme Linked Immunosorbent Assay ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Tubular Atrophy ◽  
Non Invasive ◽  
Noninvasive Biomarkers

Abstract Background In kidney transplantation, fibrosis represents the final and irreversible consequence of the pathogenic mechanisms that lead to graft failure, and in the late stages it irremediably precedes the loss of renal function. The invasiveness of kidney biopsy prevents this condition from being frequently monitored, while clinical data are rather unspecific. The objective of this study was to find noninvasive biomarkers of kidney rejection. Methods We carried out proteomic analysis of the urinary Extracellular Vesicles (uEVs) from a cohort of kidney transplant recipients (n = 23) classified according to their biopsy-based diagnosis and clinical parameters as interstitial fibrosis and tubular atrophy (IFTA), acute cellular rejection (ACR), calcineurin inhibitors toxicity (CNIT) and normal kidney function (NKF). Results Shotgun mass spectrometry of uEV-proteins identified differential expression of several proteins among these different groups. Up to 23 of these proteins were re-evaluated using targeted proteomics in a new independent cohort of patients (n = 41) classified in the same diagnostic groups. Among other results, we found a differential expression of vitronectin (VTN) in patients displaying chronic interstitial and tubular lesions (ci and ct mean > 2 according to Banff criteria). These results were further confirmed by a pilot study using enzyme-linked immunosorbent assay (ELISA). Conclusion Urinary vitronectin levels are a potential stand-alone biomarker to monitor fibrotic changes in kidney transplant recipients in a non-invasive fashion.

scholarly journals A Systematic Review of COVID-19 Infection in Kidney Transplant Recipients: A Universal Effort to Preserve Patients’ Lives and Allografts

2020 ◽  
Vol 9 (9) ◽  
pp. 2986 ◽  
Author(s):  
Smaragdi Marinaki ◽  
Stathis Tsiakas ◽  
Maria Korogiannou ◽  
Konstantinos Grigorakos ◽  
Vassilios Papalois ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Distress Syndrome ◽  
Kidney Injury ◽  
Deceased Donor ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Male Predominance ◽  
Transplant Patients ◽  
Kidney Transplant Patients ◽  
The Mean

The coronavirus disease 2019 (COVID-19) pandemic has posed a significant challenge to physicians and healthcare systems worldwide. Evidence about kidney transplant (KTx) recipients is still limited. A systematic literature review was performed. We included 63 articles published from 1 January until 7 July 2020, reporting on 420 adult KTx recipients with confirmed COVID-19. The mean age of patients was 55 ± 15 years. There was a male predominance (67%). The majority (74%) were deceased donor recipients, and 23% were recently transplanted (<1 year). Most patients (88%) had at least one comorbidity, 29% had two, and 18% three. Ninety-three percent of cases were hospitalized. Among them, 30% were admitted to the intensive care unit, 45% developed acute respiratory distress syndrome, and 44% had acute kidney injury with 23% needing renal replacement therapy. From the hospitalized patients a total of 22% died, 59% were discharged, and 19% were still in hospital at the time of publication. Immunosuppression was reduced in 27%, discontinued in 31%, and remained unchanged in 5%. Hydroxychloroquine was administered to 78% of patients, antibiotics to 73%, and antivirals to 30% while 25% received corticosteroid boluses, 28% received anti-interleukin agents, and 8% were given immunoglobulin. The main finding of our analysis was that the incidence of COVID-19 among kidney transplant patients is not particularly high, but when they do get infected, this is related to significant morbidity and mortality.

Infections after renal transplantation

2017 ◽  
Vol 41 (2) ◽  
Author(s):  
Süha Dasdelen ◽  
Scott-Oliver Grebe
Keyword(s):  
Renal Transplantation ◽  
Transplant Patient ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Time Intervals ◽  
Transplant Patients ◽  
Number Of Patients ◽  
The Common ◽  
Stage Renal Disease ◽  
End Stage

AbstractRenal transplantation is the treatment-of-choice for a significant number of patients with end-stage renal disease. Prophylaxis, diagnosis and treatment of infections are cornerstones in the management of transplant patients. There are a number of opportunistic and rare pathogens in the immunosuppressed transplant patient population, whose early detection is essential for an optimized and targeted treatment. As the immunosuppressive regimen is adopted after transplantation and due to a potentially delayed reactivation of latent diseases, certain infections can occur in defined time intervals following transplantation. The present review summarizes the common and some of the rare diseases caused by the broad microbiological spectrum in kidney transplant recipients and the respective therapeutic options.

scholarly journals Management of Immunosuppression in Kidney Transplant Recipients Who Develop Malignancy

2019 ◽  
Vol 8 (12) ◽  
pp. 2189 ◽  
Author(s):  
Danwen Yang ◽  
Natanong Thamcharoen ◽  
Francesca Cardarelli
Keyword(s):  
Kidney Transplant ◽  
Graft Survival ◽  
Graft Function ◽  
Calcineurin Inhibitors ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Mortality And Morbidity ◽  
Transplant Patients ◽  
Risk Of Cancer ◽  
The Impact

The risk of cancer increases after transplantation. However, the consensus on immunosuppression (IS) adjustment after diagnosis of malignancy is lacking. Our study aims to assess the impact of IS adjustment on mortality of post-kidney transplant patients and allograft outcomes. We retrospectively reviewed the data in our center of 110 subjects. Our results showed IS dose adjustment was not statistically associated with mortality risk (HR 1.94, 95%CI 0.85–4.41, p = 0.12), and chemotherapy was the only factor that was significantly related to mortality (HR 2.3, 95%CI 1.21–4.35, p = 0.01). IS reduction was not statistically associated with worsening graft function (OR 3.8, 95%CI 0.77–18.71, p = 0.10), nor with graft survival (SHR 4.46, 95%CI 0.58–34.48, p = 0.15) after variables adjustment. Creatinine at cancer diagnosis and history of rejection were both negatively associated with graft survival (SHR 1.72, 95%CI 1.28–2.30, p < 0.01 and SHR 3.44, 95%CI 1.25–9.49, p = 0.02). Reduction of both mycophenolate and calcineurin inhibitors was associated with worsening graft function and lower graft survival in subgroup analysis (OR 6.14, 95%CI 1.14–33.15, p = 0.04; HR 17.97, 95%CI 1.81–178.78, p = 0.01). In summary, cancer causes high mortality and morbidity in kidney transplant recipients; the importance of cancer screening should be emphasized.

scholarly journals P1687ASSOCIATION OF URINARY MICRORNA-21-5P WITH INTERSTITIAL FIBROSIS AND TUBULAR ATROPHY (IFTA) IN RENAL TRANSPLANT RECIPIENTS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Michal Gniewkiewicz ◽  
Izabela Paszkowska ◽  
Jolanta Gozdowska ◽  
Katarzyna Czerwinska ◽  
Anna Sadowska-Jakubowicz ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Renal Allograft ◽  
Interstitial Fibrosis ◽  
Clinicopathological Parameters ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Tubular Atrophy ◽  
Kidney Allograft ◽  
Expression Levels ◽  
Allograft Function

Abstract Background and Aims One of the most limiting factors of long-term graft survival is chronic renal allograft dysfunction (CAD). The major hallmarks of CAD are interstitial fibrosis and tubular atrophy (IFTA). MicroRNAs (miRNAs) are 19-25 nucleotides, small, noncoding molecules involved in the regulation of gene expression. MiRNAs have a role in various immunological processes, including inflammation and fibrosis. Particularly, microRNA-21-5p (miR-21) is reported to be strongly associated with pathogenesis regarding tubulointerstitium. The aim of this study was to analyse expression levels of urinary miR-21 in the renal transplant recipients and evaluate their application in the assessment of IFTA and kidney allograft function. Method The expression levels of urinary miR-21 were measured in 31 renal transplant recipients with biopsy-evaluated IFTA (IFTA 0+I: n=17; IFTA II+III: n=14) by quantitative PCR. Protocolar biopsies were performed 1 or 2 years after renal transplantation. Urine samples were collected at the time of biopsy procedure. MicroRNA-191-5p was used as reference gene. Correlations between the clinicopathological parameters and the level of expression of miR-21 were assessed. Results Relative expression level of miR-21 was significantly increased in IFTA II+III group compared to IFTA 0+I group. MiR-21 correlated positively with serum concentration of creatinine and negatively with eGFR. ROC analysis showed diagnostic value of miR-21 with an area under curve (AUC) of 0.80, high sensitivity and specificity. Conclusion MiR-21 is associated with IFTA and dysfunction of kidney allograft. It may be considered as potential non-invasive biomarker of renal allograft function.

scholarly journals Urinary MicroRNA-21-5p as Potential Biomarker of Interstitial Fibrosis and Tubular Atrophy (IFTA) in Kidney Transplant Recipients

Diagnostics ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 113 ◽  
Author(s):  
Michal S. Gniewkiewicz ◽  
Izabela Paszkowska ◽  
Jolanta Gozdowska ◽  
Katarzyna Czerwinska ◽  
Anna Sadowska-Jakubowicz ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Renal Allograft ◽  
Interstitial Fibrosis ◽  
Graft Function ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Tubular Atrophy ◽  
Expression Levels ◽  
Allograft Dysfunction ◽  
Potential Biomarker

Chronic renal allograft dysfunction (CAD) is a major limiting factor of long-term graft survival. The hallmarks of progressive CAD are interstitial fibrosis and tubular atrophy (IFTA). MicroRNAs are small, regulatory RNAs involved in many immunological processes. In particular, microRNA-21-5p (miR-21) is considered to be strongly associated with pathogenesis regarding tubulointerstitium. The aim of this study was to assess urinary miR-21 expression levels in the kidney transplant recipients and determine their application in the evaluation of IFTA and kidney allograft function. The expression levels of miR-21 were quantified in the urine of 31 kidney transplant recipients with biopsy-assessed IFTA (IFTA 0 + I: n = 17; IFTA II + III: n = 14) by real-time quantitative PCR. Urine samples were collected at the time of protocolar biopsies performed 1 or 2 years after kidney transplantation. MicroRNA-191-5p was used as reference gene. MiR-21 was significantly up-regulated in IFTA II + III group compared to IFTA 0 + I group (p = 0.003). MiR-21 correlated significantly with serum concentration of creatinine (r = 0.52, p = 0.003) and eGFR (r = −0.45; p = 0.01). ROC analysis determined the diagnostic value of miR-21 with an area under curve (AUC) of 0.80 (p = 0.0002), sensitivity of 0.86 and specificity of 0.71. miR-21 is associated with renal allograft dysfunction and IFTA. Therefore, it could be considered as a potential diagnostic, non-invasive biomarker for monitoring renal graft function.

Immune Checkpoint Inhibitor (ICPI) induced Nephrotoxicity – An Insight.

JMS SKIMS ◽  
2020 ◽  
Vol 23 (3) ◽  
Author(s):  
Mohmad Hussian Mir ◽  
Tariq Ahmad Bhat ◽  
Khalid Parvez Sofi ◽  
Imtiyaz Ahmad Wani ◽  
Muzafar Maqsood Wani
Keyword(s):  
Acute Kidney Injury ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Kidney Injury ◽  
Check Point ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
New Class ◽  
Transplant Patients ◽  
Check Point Inhibitors

Immune check point inhibitors (ICPIs) are a new class of anti-neoplastic agents being increasingly used by oncologists to treat various malignancies. These drugs have been associated with varied side effects and have a nephrotoxic potential. Many cases of ICPI induced acute kidney injury are increasingly being reported. Their use in CKD patients on dialysis as well as in kidney transplant recipients is associated with various challenges. This review discusses the use of ICPIs in CKD, dialysis and renal transplant patients and their nephrotoxic potential  

Immunosuppressive Management of Pediatric Kidney Transplant Recipients

2020 ◽  
Vol 26 (28) ◽  
pp. 3451-3459
Author(s):  
Tomáš Seeman
Keyword(s):  
Immunosuppressive Therapy ◽  
Kidney Transplant ◽  
Induction Therapy ◽  
Graft Loss ◽  
Calcineurin Inhibitors ◽  
Mtor Inhibitors ◽  
Therapeutic Drug ◽  
High Dose ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients

: Kidney transplantation is a preferable treatment of children with end-stage kidney disease. All kidney transplant recipients, including pediatric need immunosuppressive medications to prevent rejection episodes and graft loss. : Induction therapy is used temporarily only immediately following transplantation while maintenance immunosuppressive drugs are started and given long-term. There is currently no consensus regarding the use of induction therapy in children; its use should be decided based on the immunological risk of the child. : The recent progress shows that the recommended strategy is to use as maintenance immunosuppressive therapy a combination of a calcineurin inhibitor (preferably tacrolimus) with an antiproliferative drug (preferably mycophenolate mofetil) with steroids that can be withdrawn early or late in low-risk children. The mTOR-inhibitors (sirolimus, everolimus) are used rarely in pediatrics because of common side effects and no evidence of a benefit over calcineurin inhibitors. The use of calcineurin inhibitors, mycophenolate, and mTOR-inhibitors should be followed by therapeutic drug monitoring. : Immunosuppressive therapy of acute rejection consists of high-dose steroids and/or anti-lymphocyte antibodies (T-cell mediated rejection) or plasma exchange, intravenous immunoglobulines and/or rituximab (antibodymediated rejection). : The future strategies for research are mainly precise characterisation of children needing induction therapy, more specific indications for mTOR-inhibitors and for the far future, the possibility to reach the immuno tolerance.

scholarly journals Preservation of epoxyeicosatrienoic acid bioavailability prevents renal allograft dysfunction and cardiovascular alterations in kidney transplant recipients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Thomas Duflot ◽  
Charlotte Laurent ◽  
Anne Soudey ◽  
Xavier Fonrose ◽  
Mouad Hamzaoui ◽  
...  
Keyword(s):  
Endothelial Function ◽  
Kidney Transplant ◽  
Plasma Levels ◽  
Renal Allograft ◽  
Transplant Recipients ◽  
Loss Of Function ◽  
Kidney Transplant Recipients ◽  
Allograft Dysfunction ◽  
Allograft Function ◽  
The Impact

AbstractThis study addressed the hypothesis that epoxyeicosatrienoic acids (EETs) synthesized by CYP450 and catabolized by soluble epoxide hydrolase (sEH) are involved in the maintenance of renal allograft function, either directly or through modulation of cardiovascular function. The impact of single nucleotide polymorphisms (SNPs) in the sEH gene EPHX2 and CYP450 on renal and vascular function, plasma levels of EETs and peripheral blood monuclear cell sEH activity was assessed in 79 kidney transplant recipients explored at least one year after transplantation. Additional experiments in a mouse model mimicking the ischemia–reperfusion (I/R) injury suffered by the transplanted kidney evaluated the cardiovascular and renal effects of the sEH inhibitor t-AUCB administered in drinking water (10 mg/l) during 28 days after surgery. There was a long-term protective effect of the sEH SNP rs6558004, which increased EET plasma levels, on renal allograft function and a deleterious effect of K55R, which increased sEH activity. Surprisingly, the loss-of-function CYP2C9*3 was associated with a better renal function without affecting EET levels. R287Q SNP, which decreased sEH activity, was protective against vascular dysfunction while CYP2C8*3 and 2C9*2 loss-of-function SNP, altered endothelial function by reducing flow-induced EET release. In I/R mice, sEH inhibition reduced kidney lesions, prevented cardiac fibrosis and dysfunction as well as preserved endothelial function. The preservation of EET bioavailability may prevent allograft dysfunction and improve cardiovascular disease in kidney transplant recipients. Inhibition of sEH appears thus as a novel therapeutic option but its impact on other epoxyfatty acids should be carefully evaluated.

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