scholarly journals High Level of Aristolochic Acid Detected With a Unique Genomic Landscape Predicts Early UTUC Onset After Renal Transplantation in Taiwan

2022 ◽  
Vol 11 ◽  
Author(s):  
Hong-Yue Lai ◽  
Li-Ching Wu ◽  
Po-Hsin Kong ◽  
Hsin-Hwa Tsai ◽  
Yen-Ta Chen ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Renal Transplantation ◽  
Clinical Outcomes ◽  
Aristolochic Acid ◽  
De Novo ◽  
Mammalian Target Of Rapamycin ◽  
Growth Factor Receptor ◽  
Normal Tissues ◽  
Genomic Landscape ◽  
High Level

BackgroundThe unusual high dialysis prevalence and upper urinary tract urothelial carcinoma (UTUC) incidence in Taiwan may attribute to aristolochic acid (AA), which is nephrotoxic and carcinogenic, exposure. AA can cause a unique mutagenic pattern showing A:T to T:A transversions (mutational Signature 22) analyzed by whole exome sequencing (WES). However, a fast and cost-effective tool is still lacking for clinical practice. To address this issue, we developed an efficient and quantitative platform for the quantitation of AA and tried to link AA detection with clinical outcomes and decipher the genomic landscape of UTUC in Taiwan.Patients and MethodsWe recruited 61 patients with de novo onset of UTUC after kidney transplantation who underwent radical nephroureterectomy. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) platform was developed for the quantitation of AA. Pearson’s chi-square test, Kaplan–Meier method, and Cox proportional hazard model were utilized to assess the correlations among AA detection, clinicopathological characteristics, and clinical outcomes. Seven tumors and seven paired normal tissues were sequenced using WES (approximately 800x sequencing depth) and analyzed by bioinformatic tool.ResultsWe found that high level of 7-(deoxyadenosin-N6-yl)aristolactam I (dA-AL-I) detected in paired normal tissues was significantly correlated with fast UTUC initiation times after renal transplantation (p = 0.035) and with no use of sirolimus (p = 0.046). Using WES analysis, we further observed that all tumor samples were featured by Signature 22 mutations, apolipoprotein B mRNA-editing enzyme, catalytic polypeptide (APOBEC)-associated gene mutations, p53 mutations, no fibroblast growth factor receptor 3 (FGFR3) mutation, and high tumor mutation burden (TMB). Especially, mammalian target of rapamycin (mTOR) activation predominated in dA-AL-I-detected samples compared with those without dA-AL-I detection and might be associated with UTUC initiation through cell proliferation and suppression of UTUC progression via autophagy inhibition.ConclusionAccordingly, dA-AL-I detection can provide more direct evidence to AA exposure and serve as a more specific predictive and prognostic biomarker for patients with de novo onset of UTUC after kidney transplantation.

Growth factor receptor interplay and resistance in cancer

2006 ◽  
Vol 13 (Supplement_1) ◽  
pp. S45-S51 ◽  
Author(s):  
Helen E Jones ◽  
Julia M W Gee ◽  
Iain R Hutcheson ◽  
Janice M Knowlden ◽  
Denise Barrow ◽  
...  
Keyword(s):  
Growth Factor ◽  
Kinase Inhibitors ◽  
De Novo ◽  
Acquired Resistance ◽  
Growth Factor Receptor ◽  
New Agents ◽  
Anti Cancer ◽  
Cancer Types ◽  
Epidermal Growth ◽  
High Level

Aberrant signalling through the epidermal growth factor receptor (EGFR) plays a major role in the progression and maintenance of the malignant phenotype and the receptor is therefore a rational anti-cancer target. A variety of approaches have been developed to specifically target the EGFR which include monoclonal antibodies and small molecule tyrosine kinase inhibitors, such as gefitinib (Iressa). However, the recent clinical experience across a range of cancer types is revealing that despite the anti-EGFR agents demonstrating some anti-tumour activity, there is a high level of de novo and acquired resistance to such treatments and moreover, overexpression of the EGFR is clearly not the sole determinant of response to such therapies. Such adverse phenomena, which serve to limit the overall therapeutic impact of these new agents, implies the existence of a greater complexity involved in the regulation of EGFR signalling than was previously assumed. Indeed, evidence is accumulating which demonstrates that signalling interplay occurs between the EGFR, and the IGF-1 receptor (IGF-1R) and the review will focus on the emerging concept of growth factor pathway switching between these two receptors as a means of influencing the effectiveness of anti-EGFR agents such as gefitinib.

scholarly journals Encapsulating peritoneal sclerosis: from early diagnosis to successful kidney transplantation

2021 ◽  
Author(s):  
Marina Reis ◽  
Ana Marta Gomes ◽  
Clara Santos ◽  
Daniela Lopes ◽  
João Carlos Fernandes
Keyword(s):  
Peritoneal Dialysis ◽  
Kidney Transplantation ◽  
Early Diagnosis ◽  
De Novo ◽  
Oral Prednisolone ◽  
Ultrafiltration Failure ◽  
Advanced Stages ◽  
One Year ◽  
High Level ◽  
Dialysis Withdrawal

Abstract Encapsulating peritoneal sclerosis is an uncommon but serious complication of peritoneal dialysis. In most cases, the symptoms appear after peritoneal dialysis withdrawal, which hampers its diagnosis. We present the case of a 44-years-old Caucasian male who had been on peritoneal dialysis for 6 years and 3 months and was switched to hemodialysis due to ultrafiltration failure. During his last months on peritoneal dialysis, he developed anorexia and asthenia, which were initially attributed to dialysis inadequacy. After hemodialysis induction, the patient developed abdominal pain, increased abdominal volume, obstipation alternating with diarrhea, and weight loss. Computed tomography showed de novo ascites. A diagnosis of early encapsulating peritoneal sclerosis was considered, and treatment was promptly initiated with nutritional support, oral prednisolone, and tamoxifen for one year. The patient progressed with resolution of the symptoms. One month after the end of the treatment, he underwent a successful kidney transplant and remain without any major intercurrences. A high level of clinical suspicion is crucial for the early diagnosis of encapsulating peritoneal sclerosis as the disease can be fatal in advanced stages. This case highlights that with early treatment, kidney transplantation can be successfully performed after an episode of encapsulating peritoneal sclerosis.

De novo Urothelial Carcinoma in Kidney Transplantation Patients with End-Stage Aristolochic Acid Nephropathy in China

2009 ◽  
Vol 83 (2) ◽  
pp. 200-205 ◽  
Author(s):  
Ming Yuan ◽  
Bing-Yi Shi ◽  
Han-Zhong Li ◽  
Ming Xia ◽  
Yong Han ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Urothelial Carcinoma ◽  
Aristolochic Acid ◽  
De Novo ◽  
Aristolochic Acid Nephropathy ◽  
End Stage

1949: Six Month Randomized Study Comparing Cyclosporine Microemulsion with C2 Monitoring and Tacrolimus in De Novo Kidney Transplantation

2004 ◽  
Vol 171 (4S) ◽  
pp. 515-515
Author(s):  
Felipe G. Balbontin ◽  
Bryce Kiberd ◽  
Philip Belitsky ◽  
Dharm Singh ◽  
Albert Fraser ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
De Novo ◽  
Randomized Study ◽  
C2 Monitoring ◽  
Cyclosporine Microemulsion

scholarly journals Effects of renal transplantation on erectile dysfunction: a systematic review and meta-analysis

2021 ◽  
Author(s):  
Irham Arif Rahman ◽  
Nur Rasyid ◽  
Ponco Birowo ◽  
Widi Atmoko
Keyword(s):  
Systematic Review ◽  
Erectile Dysfunction ◽  
Kidney Transplantation ◽  
Renal Transplantation ◽  
End Stage Renal Disease ◽  
Erectile Function ◽  
Meta Analysis ◽  
Post Transplantation ◽  
Stage Renal Disease ◽  
End Stage

AbstractErectile dysfunction (ED) is a major global health burden commonly observed in patients with end-stage renal disease (ESRD). Although renal transplantation improves the problem in some patients, it persists in ≈20–50% of recipients. Studies regarding the effects of kidney transplantation on ED present contradictory findings. We performed a systematic review to summarise the effects of kidney transplantation on ED. A systematic literature search was performed across PubMed, Cochrane, and Scopus databases in April 2020. We included all prospective studies that investigated the pre and posttransplant international index of erectile function (IIEF-5) scores in recipients with ED. Data search in PubMed and Google Scholar produced 1326 articles; eight were systematically reviewed with a total of 448 subjects. Meta-analysis of IIEF-5 scores showed significant improvements between pre and post transplantation. Our findings confirm that renal transplantation improves erectile function. Furthermore, transplantation also increases testosterone level. However, the evidence is limited because of the small number of studies. Further studies are required to investigate the effects of renal transplantation on erectile function.

Everolimus Therapeutic Concentration Range Defined from a Prospective Trial with Reduced-Exposure Cyclosporine in De Novo Kidney Transplantation

2004 ◽  
Vol 26 (5) ◽  
pp. 499-505 ◽  
Author(s):  
John M. Kovarik ◽  
Helio Tedesco ◽  
Julio Pascual ◽  
Giovanni Civati ◽  
Marie-Noelle Bizot ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
De Novo ◽  
Prospective Trial ◽  
Therapeutic Concentration
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