Urothelial carcinoma of the graft kidney with molecular analyses: a rare case report

Abstract Background Malignancy after transplantation is a leading cause of death among kidney transplant recipients. However, donor-derived malignancies are rare. We report a case of a high grade papillary urothelial carcinoma arising in a transplanted kidney. Case presentation A 62-year-old female who received a kidney transplantation more than 30 years ago presented with urinary tract infection, acute renal failure, and hydronephrosis of the transplant kidney. Anterograde nephrostogram showed a large filling defect in the lower pole of the transplant kidney and in the proximal 3–4 cm of the ureter. A biopsy from the renal pelvic mass showed a high grade urothelial carcinoma. She underwent an anterior exenteration, resection of both transplant and native kidneys and bilateral pelvic lymph node dissection. Pathologic examination showed a high grade papillary urothelial carcinoma which appeared to arise in the pelvis of the graft kidney, involve the graft ureter and native urinary bladder. The tumor had metastasized to one left obturator lymph node but spared the two native kidneys and ureters. Short tandem repeat (STR) analysis confirmed the tumor to be of donor origin. Next-generation sequencing identified amplification of TERT and loss of CDKN2A/CDKN2B in the primary tumor. Conclusion While it is known that transplant recipients have an increased risk of urothelial carcinoma compared to the general population, the lack of the well-documented risk factors, such as older age at transplantation, BK polyomavirus infection, and prolonged post-transplantation history and dissemination of the tumor in this case shed light on the de novo tumorigenesis of the graft kidney within the host microenvironment. Amplification of Telomerase reverse transcriptase (TERT) and loss of cyclin dependent kinase inhibitor 2A/2B (CDKN2A/CDKN2B) detected in the tumor by next gene sequencing suggests that they may play an important role in this case.

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Urothelial Carcinoma of the Graft Kidney With Molecular Analyses: A Rare Case Report

10.21203/rs.3.rs-318637/v1 ◽

2021 ◽

Author(s):

Joyce Chen ◽

Kenneth Haines ◽

William Lam ◽

Asha Reddy ◽

Meenakshi Mehrotra ◽

...

Keyword(s):

Lymph Node ◽

Urinary Bladder ◽

Urothelial Carcinoma ◽

Filling Defect ◽

High Grade ◽

Transplant Recipients ◽

Increased Risk ◽

Transplant Kidney ◽

Obturator Lymph Node ◽

Papillary Urothelial Carcinoma

Abstract BACKGROUNDMalignancy after transplantation is a leading cause of death in kidney transplant recipients. However, donor-derived malignancies are rarely reported. We herein report a high grade papillary urothelial carcinoma of the graft kidney, involving the graft ureter and native urinary bladder, invading one left obturator lymph node, and sparing the two native kidneys and ureters.CASE PRESENTATION62-year-old female with history of kidney transplantation more than 30 years ago, who presented with urinary tract infection, acute renal failure, and hydronephrosis of the transplant kidney. Anterograde nephrostogram showed a large filling defect in the lower pole of the transplant kidney and a filling defect in the proximal 3-4 cm of ureter. Biopsy taken from the renal pelvic mass showed a high grade urothelial carcinoma. She underwent hysterectomy, bilateral salpingo-oophorectomy, nephrectomy of native kidneys and transplant kidney, cystectomy and bilateral pelvic lymph node dissections. Histology showed a high grade papillary urothelial carcinoma of the graft kidney, involving the graft ureter, native urinary bladder and one left obturator lymph node and sparing the two native kidneys and ureters. Short tandem repeat (STR) analysis confirmed the tumor was of donor origin. The next-generation sequencing identified amplification of TERT and loss of CDKN2A/CDKN2B in the primary tumor.CONCLUSIONWhile it is known that transplant recipients have an increased risk of urothelial carcinoma compared to the general population, the lack of the well-documented risk factors, such as older age at transplantation, BK polyomavirus infection, and prolonged post-transplantation history and dissemination of the tumor in this case shed light on the de novo tumorigenesis of the graft kidney within the host microenvironment. Amplification of Telomerase reverse transcriptase (TERT) and loss of cyclin dependent kinase inhibitor 2A/2B (CDKN2A/CDKN2B) detected in the tumor by next gene sequencing suggests that they may play an important role in this case.

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SLCO1B3 polymorphisms and clinical outcomes in kidney transplant recipients receiving mycophenolate

Pharmacogenomics ◽

10.2217/pgs-2021-0102 ◽

2021 ◽

Author(s):

Lauren Schumacher ◽

Fang Fang ◽

Kelley M Kidwell ◽

Faisal Shakeel ◽

Daniel L Hertz ◽

...

Keyword(s):

Adverse Effects ◽

Acute Rejection ◽

Kidney Transplant ◽

Patient Survival ◽

De Novo ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Primary Analysis ◽

Adult Kidney ◽

Increased Risk

Aim: Determine the influence of SLCO1B3 polymorphisms on outcomes in kidney transplant recipients. Materials & methods: We retrospectively evaluated 181 adult kidney transplant recipients receiving mycophenolate. Outcomes included treated biopsy-proven acute rejection (tBPAR), de novo donor specific antibody (dnDSA) formation, graft survival, patient survival and mycophenolate-related adverse effects among SLCO1B3 genotypes. Results: The presence of SLCO1B3 variants was not associated with increased risk of tBPAR (HR: 1.45, 95% CI: 0.76–2.74), dnDSA (HR: 0.46, 95% CI: 0.16–1.36) or composite of tBPAR or dnDSA (HR: 1.14, 95% CI: 0.64–2.03). Graft and patient survival were reduced among variant carriers; however, inconsistent findings with the primary analysis suggest these associations were not due to genotype. Adverse effects were similar between groups. Conclusion: Presence of SLCO1B3 polymorphisms were not predictive of rejection or dnDSA in kidney transplant recipients.

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Cardiovascular calcifications in kidney transplant recipients

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab053 ◽

2021 ◽

Author(s):

Manuel Alfredo Podestà ◽

David Cucchiari ◽

Paola Ciceri ◽

Piergiorgio Messa ◽

José-Vicente Torregrosa ◽

...

Keyword(s):

Kidney Transplantation ◽

Kidney Transplant ◽

De Novo ◽

Immunosuppressive Drugs ◽

Current Evidence ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Increased Risk ◽

Cardiovascular Calcifications

AbstractVascular and valvular calcifications are highly prevalent in kidney transplant recipients (KTRs) and are associated with an increased risk of cardiovascular events, which represent the leading cause of long-term mortality in these patients. However, cardiovascular calcification has been traditionally considered as a condition mostly associated with advanced chronic kidney disease stages and dialysis, and comparatively fewer studies have assessed its impact after kidney transplantation. Despite partial or complete resolution of uraemia-associated metabolic derangements, KTRs are still exposed to several pro-calcifying stimuli that favour the progression of pre-existing vascular calcifications or their de novo development. Traditional risk factors, bone mineral disorders, inflammation, immunosuppressive drugs and deficiency of calcification inhibitors may all play a role, and strategies to correct or minimize their effects are urgently needed. The aim of this work is to provide an overview of established and putative mediators involved in the pathogenesis of cardiovascular calcification in kidney transplantation, and to describe the clinical and radiological features of these forms. We also discuss current evidence on preventive strategies to delay the progression of cardiovascular calcifications in KTRs, as well as novel therapeutic candidates to potentially prevent their long-term deleterious effects.

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Metabolic Complications and Kidney Transplantation: Focus on Glycaemia and Dyslipidaemia

Current Vascular Pharmacology ◽

10.2174/1570161117666190619143005 ◽

2020 ◽

Vol 18 (3) ◽

pp. 273-281 ◽

Cited By ~ 2

Author(s):

Panagiotis Anagnostis ◽

Stavroula Α. Paschou ◽

Eleftherios Spartalis ◽

Gerardo Sarno ◽

Paride De Rosa ◽

...

Keyword(s):

Graft Function ◽

Current Data ◽

Optimal Management ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Cvd Risk ◽

Oral Hypoglycaemic Agents ◽

Metabolic Complications ◽

Increased Risk ◽

Regimen Modification

Post-transplant diabetes mellitus (PTDM) and dyslipidaemia are the most common metabolic complications in kidney transplant recipients (KTR). They are associated with a higher risk of lower graft function and survival, as well as an increased risk of cardiovascular disease (CVD). The aim of this review is to provide current data on the epidemiology, pathophysiology and optimal management of these two principal metabolic complications in KTR. Several risk factors in this metabolic milieu are either already present or emerge after renal transplantation, such as those due to immunosuppressive therapy. However, the exact pathogenic mechanisms have not been fully elucidated. Awareness of these disorders is crucial to estimate CVD risk in KTR and optimize screening and therapeutic strategies. These include lifestyle (preferably according to the Mediterranean pattern) and immunosuppressive regimen modification, as well as the best available anti-diabetic (insulin or oral hypoglycaemic agents) and hypolipidaemic (e.g. statins) regimen according to an individual’s metabolic profile and medical history.

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Urinary Carnosinase-1 Excretion is Associated with Urinary Carnosine Depletion and Risk of Graft Failure in Kidney Transplant Recipients: Results of the TransplantLines Cohort Study

Antioxidants ◽

10.3390/antiox10071102 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1102

Author(s):

Angelica Rodriguez-Niño ◽

Diego O. Pastene ◽

Adrian Post ◽

M. Yusof Said ◽

Antonio W. Gomes-Neto ◽

...

Keyword(s):

Kidney Transplant ◽

Graft Failure ◽

Cox Regression ◽

Carbonyl Stress ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Increased Risk ◽

High Concentrations ◽

Kidney Function Decline

Carnosine affords protection against oxidative and carbonyl stress, yet high concentrations of the carnosinase-1 enzyme may limit this. We recently reported that high urinary carnosinase-1 is associated with kidney function decline and albuminuria in patients with chronic kidney disease. We prospectively investigated whether urinary carnosinase-1 is associated with a high risk for development of late graft failure in kidney transplant recipients (KTRs). Carnosine and carnosinase-1 were measured in 24 h urine in a longitudinal cohort of 703 stable KTRs and 257 healthy controls. Cox regression was used to analyze the prospective data. Urinary carnosine excretions were significantly decreased in KTRs (26.5 [IQR 21.4–33.3] µmol/24 h versus 34.8 [IQR 25.6–46.8] µmol/24 h; p < 0.001). In KTRs, high urinary carnosinase-1 concentrations were associated with increased risk of undetectable urinary carnosine (OR 1.24, 95%CI [1.06–1.45]; p = 0.007). During median follow-up for 5.3 [4.5–6.0] years, 84 (12%) KTRs developed graft failure. In Cox regression analyses, high urinary carnosinase-1 excretions were associated with increased risk of graft failure (HR 1.73, 95%CI [1.44–2.08]; p < 0.001) independent of potential confounders. Since urinary carnosine is depleted and urinary carnosinase-1 imparts a higher risk for graft failure in KTRs, future studies determining the potential of carnosine supplementation in these patients are warranted.

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Exhaled Hydrogen as a Marker of Intestinal Fermentation Is Associated with Diarrhea in Kidney Transplant Recipients

Journal of Clinical Medicine ◽

10.3390/jcm10132854 ◽

2021 ◽

Vol 10 (13) ◽

pp. 2854

Author(s):

Fernanda Rodrigues ◽

J. Swarte ◽

Rianne Douwes ◽

Tim Knobbe ◽

Camilo Sotomayor ◽

...

Keyword(s):

Small Bowel ◽

Kidney Transplant ◽

Surrogate Marker ◽

Bacterial Overgrowth ◽

Dietary Factors ◽

Multivariable Logistic Regression Analysis ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Increased Risk ◽

The Relationship

Background: Diarrhea is common among kidney transplant recipients (KTR). Exhaled hydrogen (H2) is a surrogate marker of small bowel dysbiosis, which may drive diarrhea. We studied the relationship between exhaled H2 and diarrhea in KTR, and explored potential clinical and dietary determinants. Methods: Clinical, laboratory, and dietary data were analyzed from 424 KTR participating in the TransplantLines Biobank and Cohort Study (NCT03272841). Fasting exhaled H2 concentration was measured using a model DP Quintron Gas Chromatograph. Diarrhea was defined as fast transit time (types 6 and 7 according to the Bristol Stool Form Scale, BSFS) of 3 or more episodes per day. We studied the association between exhaled H2 and diarrhea with multivariable logistic regression analysis, and explored potential determinants using linear regression. Results: KTR (55.4 ± 13.2 years, 60.8% male, mean eGFR 49.8 ± 19.1 mL/min/1.73 m2) had a median exhaled H2 of 11 (5.0–25.0) ppm. Signs of small intestinal bacterial overgrowth (exhaled H2 ≥ 20 ppm) were present in 31.6% of the KTR, and 33.0% had diarrhea. Exhaled H2 was associated with an increased risk of diarrhea (odds ratio 1.51, 95% confidence interval 1.07–2.14 per log2 ppm, p = 0.02). Polysaccharide intake was independently associated with higher H2 (std. β 0.24, p = 0.01), and a trend for an association with proton-pump inhibitor use was observed (std. β 0.16 p = 0.05). Conclusion: Higher exhaled H2 is associated with an increased risk of diarrhea in KTR. Our findings set the stage for further studies investigating the relationship between dietary factors, small bowel dysbiosis, and diarrhea after kidney transplantation.

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Standard induction with basiliximab versus no induction in low immunological risk kidney transplant recipients: study protocol for a randomized controlled trial

Trials ◽

10.1186/s13063-021-05253-1 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Aziza Ajlan ◽

Hassan Aleid ◽

Tariq Zulfiquar Ali ◽

Hala Joharji ◽

Khalid Almeshari ◽

...

Keyword(s):

Kidney Transplant ◽

De Novo ◽

Controlled Trial ◽

Controlled Clinical Trial ◽

First Year ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Double Blind ◽

Donor Specific Antibodies

Abstract Background Induction therapy with IL-2 receptor antagonist (IL2-RA) is recommended as a first-line agent in low immunological risk kidney transplant recipients. However, the role of IL2-RA in the setting of tacrolimus-based immunosuppression has not been fully investigated. Aims To compare different induction therapeutic strategies with 2 doses of basiliximab vs. no induction in low immunologic risk kidney transplant recipients as per KFSHRC protocol. Methods Prospective, randomized, double blind, non-inferiority, controlled clinical trial Expected outcomes 1. Primary outcomes: Biopsy-proven acute rejection within first year following transplant 2. Secondary outcomes: a. Patient and graft survival at 1 year b. eGFR at 6 months and at 12 months c. Emergence of de novo donor-specific antibodies (DSAs) Trial registration The study has been prospectively registered at clinicaltrials.gov (NTC: 04404127). Registered on 27 May 2020.

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Carcinomas in the bladder with papillary and pseudopapillary morphology - not always urothelial

Surgical and Experimental Pathology ◽

10.1186/s42047-020-00078-9 ◽

2020 ◽

Vol 3 (1) ◽

Author(s):

Daniel Abensur Athanazio ◽

Maiara Ferreira de Souza ◽

Maria Estela Pompeu do Amaral

Keyword(s):

Urinary Tract ◽

Urothelial Carcinoma ◽

Final Diagnosis ◽

Prostate Adenocarcinoma ◽

High Grade ◽

Case Presentation ◽

Carcinoma Prostate ◽

Papillary Urothelial Carcinoma ◽

Primary Bladder ◽

Bladder Adenocarcinoma

Abstract Background Urothelial carcinoma shows wide plasticity and broad morphologic spectrum. In many instances, the presence of papillary morphology is reassuring of the urothelial histogenesis of a high-grade invasive lesion but is not pathognomonic. Case presentation We reported herein four cases of carcinomas in the bladder with papillary morphology that had a final diagnosis different from urothelial carcinoma (3% of cases in a 42-month period). In high-grade tumors involving the urinary tract, the presence of papillary/pseudopapillary morphology is not sufficient to render a diagnosis of papillary urothelial carcinoma. Prostate adenocarcinoma, primary bladder adenocarcinoma or metastasis must be excluded in selected case scenarios.

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