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Background: We would like to present an unusual case of simultaneous stenosis of renal graft artery and vein diagnosed four months after transplantation. both treated by stent placement. Our aim is to point at the fact that renal graft venous stenosis is very rarely reported in the literature and - as it is not easy to diagnose by routine US - it could be overlooked. If early detected it can be treated by stent placement., Case Presentation: We present a case of 36-old-male with renal failure who received a kidney graft from deceased donor. The patient experienced delayed graft function. No rejection was found in the biopsy. Four months after transplantation the kidney function deteriorated to sCr 280 µmol/l. Graft artery stenosis together with graft vein stenosis was revealed. Both lesions were dilated with stent placement, the graft function returned to 230 µmol/l and became stable for 10 years. Ten years after stent placement graft function deteriorated to 300 µmol/l. An in stent restenosis of arterial stent was detected. It was successfully dilated by the balloon, the graft function returned to 230 µmol/l and stays stable for another 5 years., Conclusions: An unusual simultaneous transplanted kidney artery and vein stenosis treated by stent placement is presented. The patient had stable graft function for 15 years after the procedure with one re-intervention on arterial stent., (© 2024. The Author(s).)

Introduction: Monoallelic variants in the ALG5 gene encoding asparagine-linked glycosylation protein 5 homolog (ALG5) have been recently shown to disrupt polycystin-1 (PC1) maturation and trafficking via underglycosylation, causing an autosomal dominant polycystic kidney disease-like (ADPKD-like) phenotype and interstitial fibrosis. In this report, we present clinical, genetic, histopathologic, and protein structure and functional correlates of a new ALG5 variant, p.R79W, that we identified in 2 distant genetically related Irish families displaying an atypical late-onset ADPKD phenotype combined with tubulointerstitial damage., Methods: Whole exome and targeted sequencing were used for segregation analysis of available relatives. This was followed by immunohistochemistry examinations of kidney biopsies, and targeted (UMOD, MUC1) and untargeted plasma proteome and N-glycomic studies., Results: We identified a monoallelic ALG5 variant [GRCh37 (NM_013338.5): g.37569565G>A, c.235C>T; p.R79W] that cosegregates in 23 individuals, of whom 18 were clinically affected. We detected abnormal localization of ALG5 in the Golgi apparatus of renal tubular cells in patients' kidney specimens. Further, we detected the pathological accumulation of uromodulin, an N-glycosylated glycosylphosphatidylinositol (GPI)-anchored protein, in the endoplasmic reticulum (ER), but not mucin-1, an O- and N-glycosylated protein. Biochemical investigation revealed decreased plasma and urinary uromodulin levels in clinically affected individuals. Proteomic and glycoproteomic profiling revealed the dysregulation of chronic kidney disease (CKD)-associated proteins., Conclusion: ALG5 dysfunction adversely affects maturation and trafficking of N-glycosylated and GPI anchored protein uromodulin, leading to structural and functional changes in the kidney. Our findings confirm ALG5 as a cause of late-onset ADPKD and provide additional insight into the molecular mechanisms of ADPKD- ALG5 ., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

Although prolonged-release tacrolimus (PR-T) is widely approved for posttransplantation immunosuppression in kidney recipients, large-scale studies are required to assess long-term outcomes. We present follow-up data from the Advagraf-based Immunosuppression Regimen Examining New Onset Diabetes Mellitus in Kidney Transplant Recipients (ADVANCE) trial, in which kidney transplant patients (KTPs) received corticosteroid minimization with PR-T., Methods: ADVANCE was a 24-wk, randomized, open-label, phase-4 study. De novo KTPs received PR-T with basiliximab and mycophenolate mofetil and were randomized to receive an intraoperative corticosteroid bolus plus tapered corticosteroids until day 10 (arm 1) or an intraoperative corticosteroid bolus (arm 2). In this 5-y, noninterventional follow-up, patients received maintenance immunosuppression according to standard practice. The primary endpoint was graft survival (Kaplan-Meier). Secondary endpoints included patient survival, biopsy-confirmed acute rejection-free survival, and estimated glomerular filtration rate (4-variable modification of diet in renal disease)., Results: Follow-up study included 1125 patients. Overall graft survival at 1 and 5 y posttransplantation was 93.8% and 88.1%, respectively, and was similar between treatment arms. At 1 and 5 y, patient survival was 97.8% and 94.4%, respectively. Five-year graft and patient survival rates in KTPs who remained on PR-T were 91.5% and 98.2%, respectively. Cox proportional hazards analysis demonstrated similar risk of graft loss and death between treatment arms. Five-year biopsy-confirmed acute rejection-free survival was 84.1%. Mean ± standard deviation values of estimated glomerular filtration rate were 52.7 ± 19.5 and 51.1 ± 22.4 mL/min/1.73 m 2 at 1 and 5 y, respectively. Fifty adverse drug reactions were recorded, probably tacrolimus-related in 12 patients (1.5%)., Conclusions: Graft survival and patient survival (overall and for KTPs who remained on PR-T) were numerically high and similar between treatment arms at 5 y posttransplantation., Competing Interests: All authors report nonfinancial support from Astellas during the conduct of the study. O.W. has received research grants for clinical studies, speaker’s fees, honoraria, and travel expenses from Amgen, Astellas, Bristol-Myers Squibb, Chiesi, Janssen-Cilag, MSD, Novartis, Roche, Pfizer, and Sanofi. O.W. is also supported by an unrestricted grant of the Rudolf-Ackermann-Stiftung (Stiftung für Klinische Infektiologie). S.A., M.H., and N.U. are employed by Astellas. G.K. is a consultant statistician working on behalf of Astellas who has also received support for travel from Astellas. D.R.J.K. has received research grants, speaker’s fees, honoraria, and travel grants from Astellas., (Copyright © 2023 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Kidney transplant recipients are a very vulnerable population at risk of severe course and death from Covid-19. Several antiviral drugs are now available for the treatment of nonhospitalized individuals with mild to moderate Covid-19 and hospitalized patients with severe disease. The combination of monoclonal antibodies is also available to be used as pre-exposure prophylaxis in elderly patients. Previously used monoclonal antibodies for post-exposure prophylaxis are no longer effective because of the new mutations and are no longer recommended. Although the immune response to Covid-19 vaccines is impaired in kidney transplant recipients, the effectiveness of the Covid-19 vaccines was described even in this immunocompromised group. Therefore vaccination, together with anti-epidemic measures, remains the most important tool to prevent Covid-19.

Chronic kidney disease (CKD) affects 10% of the population of developed countries and significantly affects the population health. In addition to the well-known renoprotection tools slowing down the progression of CKD, SGLT2 inhibitors have been newly introduced into clinical practice based on the results of extensive studies, both in diabetics and non-diabetics. This expert opinion discusses the classification of CKD, current renoprotection options, and the recent role of SGLT2 inhibitors in the care of patients with CKD.

BK polyomavirus (BKPyV) often reactivates after kidney transplantation, causing BKPyV-associated nephropathy (BKPyVAN) in 1%-10% of cases with a potential detrimental effect on allograft survival. Kidney transplant recipients are regularly screened for BKPyV DNA in plasma. As this strategy may not always reduce the risk of BKPyVAN, other predictive markers are needed. To evaluate the role of pretransplant BKPyV-specific antibody, 210 kidney transplant recipients and 130 donors were screened for BKPyV DNA and BKPyV-specific antibodies. We found that the donor BKPyV immunoglobulin G (IgG) seroprevalence and antibody level were strongly associated with BKPyV-DNAemia and BKPyVAN, although multivariant analysis found the presence of anti-BKPyV-specific antibodies as a predictive factor only for BKPyV-DNAemia. The pretransplant recipient status had no effect on posttransplant BKPyV-DNAemia and BKVAN. BKPyV IgG levels remained stable in BKPyV-negative recipients during 1-year follow-up, while a considerable increase was observed in BKPyV-positive patients. The presence of anti-BKPyV-specific antibodies in kidney allograft donors is a good and reliable predictive marker for posttransplant BKPyV replication with relevance to risk stratification in transplant recipients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Saláková, Ludvíková, Hamšíková, Kolářová, Šroller, Viklický and Wohlfahrtová.)

In the era of COVID-19 pandemic, organ transplantation programs were facing serious challenges. The lung transplantation donor pool was extremely limited and SARS-CoV-2 viral load assessment has become a crucial part of selecting an optimal organ donor. Since COVID-19 is a respiratory disease, the viral load is thought to be more important in lung transplantations as compared to other solid organ transplantations. We present two challenging cases of potential lung donors with a questionable COVID-19 status. Based on these cases, we suggest that the cycle threshold (Ct) value should always be requested from the laboratory and the decision whether to proceed with transplantation should be made upon complex evaluation of diverse criteria, including the nasopharyngeal swab and bronchoalveolar lavage PCR results, the Ct value, imaging findings and the medical history. However, as the presence of viral RNA does not ensure infectivity, it is still to be clarified which Ct values are associated with the viral viability. Anti-SARS-CoV-2 IgA antibodies may support the diagnosis and moreover, novel methods, such as quantifying SARS-CoV-2 nucleocapsid antigen in serum may provide important answers in organ transplantations and donor selections.

Despite an increasing quality of life after renal transplantation, the number of recipients undertaking paid professional work remains relatively low. Employment after kidney transplantation became a new important marker of clinically significant health recovery. Furthermore, for social and economic reasons, returning to work and participation in social life may be considered as an objective parameter that demonstrate the effectiveness of transplantation. The objectives of the following study were to evaluate the factors that determine resuming paid work after renal transplantation, to assess a patient's decision about returning to professional activity by comparative analysis of renal transplant recipients from Poland, Czech Republic and Germany, and to identify groups of patients exposed to professional exclusion in those EU countries. Five hundred renal transplant recipients from three EU countries were included into the study. The two main research methods used in the study were the SF-36 questionnaire, constructed and validated to assess the quality of life after kidney transplantation and a questionnaire constructed for the purposes of this study. Multifactorial analysis identified several risk factors associated with professional exclusions after kidney transplantation, namely young or advanced age, female gender, lack of education, place of residence in rural areas, long period of illness, and lack of occupational activity before transplantation. Despite the high standards of social care and rehabilitation support, patients in Germany failed to take up professional activity after kidney transplantation in more cases than those in Poland and Czech Republic. Surprisingly, the objective function of the kidney (creatinine level) and the multidimensional assessment of quality of life (SF-36 survey) did not have a significant association with the employment status after renal transplantation.

Background: Kidney transplant recipients (KTRs) with "operational tolerance" (OT) maintain a functioning graft without immunosuppressive (IS) drugs, thus avoiding treatment complications. Nevertheless, IS drugs can influence gene-expression signatures aiming to identify OT among treated KTRs., Methods: We compared five published signatures of OT in peripheral blood samples from 18 tolerant, 183 stable, and 34 chronic rejector KTRs, using gene-expression levels with and without adjustment for IS drugs and regularised logistic regression., Findings: IS drugs explained up to 50% of the variability in gene-expression and 20-30% of the variability in the probability of OT predicted by signatures without drug adjustment. We present a parsimonious consensus gene-set to identify OT, derived from joint analysis of IS-drug-adjusted expression of five published signature gene-sets. This signature, including CD40, CTLA4, HSD11B1, IGKV4-1, MZB1, NR3C2, and RAB40C genes, showed an area under the curve 0⋅92 (95% confidence interval 0⋅88-0⋅94) in cross-validation and 0⋅97 (0⋅93-1⋅00) in six months follow-up samples., Interpretation: We advocate including adjustment for IS drug therapy in the development stage of gene-expression signatures of OT to reduce the risk of capturing features of treatment, which could be lost following IS drug minimisation or withdrawal. Our signature, however, would require further validation in an independent dataset and a biomarker-led trial., Funding: FP7-HEALTH-2012-INNOVATION-1 [305147:BIO-DrIM] (SC,IR-M,PM,DSt); MRC [G0801537/ID:88245] (MPH-F); MRC [MR/J006742/1] (IR-M); Guy's&StThomas' Charity [R080530]&[R090782]; CONICYT-Bicentennial-Becas-Chile (EN-L); EU:FP7/2007-2013 [HEALTH-F5-2010-260687: The ONE Study] (MPH-F); Czech Ministry of Health [NV19-06-00031] (OV); NIHR-BRC Guy's&StThomas' NHS Foundation Trust and KCL (SC); UK Clinical Research Networks [portfolio:7521]., Competing Interests: Declaration of Competing Interest Dr. Christakoudi reports grants from FP7-HEALTH-2012-INNOVATION-1 (project number 305147: BIO-DrIM), grants from National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London, during the conduct of the study. Mr. Runglall has nothing to disclose. Dr. Mobillo reports grants from FP7-HEALTH-2012-INNOVATION-1 (project number 305147: BIO-DrIM), during the conduct of the study. Dr. Rebollo-Mesa reports grants from [MR/J006742/1] to MRC Centre for Transplantation, grants from FP7-HEALTH-2012-INNOVATION-1 (project number 305147: BIO-DrIM), during the conduct of the study; other from UCB Pharma SRL, outside the submitted work. Mr. Tsui has nothing to disclose. Dr. Nova-Lamperti reports grants from CONICYT Bicentennial-Becas-Chile scholarship, during the conduct of the study. Dr. Taube has nothing to disclose. Dr. Norris has nothing to disclose. Mr. Kamra has nothing to disclose. Dr. Hilton reports personal fees from Chiesi Ltd, outside the submitted work. Dr. Augustine has nothing to disclose. Dr. Bhandari has nothing to disclose. Dr. Baker has nothing to disclose. Dr. Berglund has nothing to disclose. Dr. Carr has nothing to disclose. Dr. Game reports personal fees from Advisory board Chiesi pharmaceuticals, personal fees from Advisory board Recordati Rare Diseases, personal fees from Advisory board Syneos Health, outside the submitted work. Dr. Griffin has nothing to disclose. Dr. Kalra has nothing to disclose. Dr. Lewis has nothing to disclose. Dr. Mark reports personal fees and non-financial support from Vifor, personal fees from Astrazeneca, grants from Boehringer Ingelheim, personal fees and non-financial support from Pharmacosmos, personal fees from Janssen, personal fees from Novartis, personal fees from Pfizer, personal fees from Bristol Myers Squibb, personal fees and non-financial support from Napp, outside the submitted work. Dr. Marks has nothing to disclose. Dr. MacPhee reports other from AstraZeneca, other from AstraZeneca, grants and personal fees from Chiesi, personal fees from Astellas, personal fees from Sandoz, outside the submitted work. Dr. McKane has nothing to disclose. Dr. Mohaupt has nothing to disclose. Dr. Paz-Artal has nothing to disclose. Dr. Kon has nothing to disclose. Dr. Seron has nothing to disclose. Dr. Sinha has nothing to disclose. Dr. Tucker has nothing to disclose. Prof. Viklicky reports grants from CZECH MINISTRY OF HEALTH, during the conduct of the study. Dr. Stahl reports grants from FP7-HEALTH-2012-INNOVATION-1 (project number 305147: BIO-DrIM), during the conduct of the study. Dr. Lechler has nothing to disclose. Dr. Lord has nothing to disclose. Dr. Hernandez-Fuentes reports grants from FP7-HEALTH-2012-INNOVATION-1 (project number 305147: BIO-DrIM), grants from Medical Research Council MRC grants to Maria P. Hernandez-Fuentes [G0801537/ID: 88245], grants from Guy's and St Thomas’ Charity [grants R080530 and R090782], grants from EU; FP7/2007–2013], under grant agreement [No HEALTH-F5–2010–260687: The ONE Study], grants and non-financial support from National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London, non-financial support from Clinical Research Networks [study portfolio number 7521], during the conduct of the study; other from UCB Celltech., outside the submitted work; ., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Complement may contribute to donor-specific antibody (DSA)-triggered transplant injury. Here, we investigated whether the intrinsic strength of classical pathway and alternative pathway (AP) relates to the pathogenicity of DSA., Methods: Classical pathway and AP high-activity genotypes were defined according to C4 gene copy number and the presence of functional polymorphisms in C3 (C3 102G ), factor B (fB 32R ), and factor H (fH 62V ) genes. Associations of these genotypes with blood complement profiles and morphologic/molecular rejection features were evaluated in a cohort of 83 DSA-positive patients (antibody-mediated rejection [AMR], n = 47) identified upon cross-sectional screening of 741 kidney allograft recipients ≥180 days posttransplantation. Associations with long-term graft survival were evaluated in a larger kidney transplant cohort (n = 660) not enriched for a specific type of rejection., Results: In the cohort of DSA-positive subjects, the number of C4 gene copies was related to C4 protein levels in serum and capillary C4d staining, but not AMR activity. Patients with a high-activity AP complotype, which was associated with complement consumption in serum, showed enhanced microcirculation inflammation (median glomerulitis plus peritubular capillaritis score, 2 [interquartile range, 0-4 versus 1 0-2]; P = 0.037). In the larger transplant cohort, this complotype was associated with a slightly increased risk of graft loss (hazard ratio, 1.52; 95% confidence interval, 1.02-2.25; P = 0.038 and multivariable Cox model, 1.55; 1.04-2.32; P = 0.031)., Conclusions: Our study suggests a contribution of complement genetics to the phenotypic presentation of AMR. Future studies will have to clarify whether a possible association of AP strength with graft survival relates to enhanced antibody-triggered injury., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Active infection with BK polyomavirus (BKPyV) may cause serious complications in transplantation settings. Recently, the level of BKPyV IgG seroreactivity in graft donors has been shown to predict viremia and BKPyV-associated nephropathy in kidney transplant (KTx) recipients. Pretransplantation testing of the donor and recipient BKPyV serostatus could, therefore, identify patients at high risk. For the development of serological immunoassays, antibody response to the predominant BKPyV subtypes (BKPyV-I and BKPyV-IV) was studied using virus-like particle (VLP)-based enzyme-linked immunosorbent assay (ELISA). VLPs made from the capsid protein, VP1, derived from BKPyV-I and BKPyV-IV subtypes were produced using a baculovirus expression system and used as antigens. The tests were used for IgG antibody determination in 50 KTx recipients and 111 healthy blood donors. While 87% of samples reacted with mixed BKPyV-I and BKPyV-IV antigens, only 49% of samples were reactive in both ELISA tests when using BKPyV-I or BKPyV-IV antigens separately. Twenty-seven percent of healthy blood donors and 26% of KTx recipients were reactive only with BKPyV-I, while 9% and 20% were reactive only with BKPyV-IV, respectively. To determine the specificities of the antigens, selected seropositive samples were retested after preadsorption with soluble BKPyV-I, BKPyV-IV, or JC polyomavirus antigens. The experiments confirmed that recombinant VP1 VLP-based ELISAs predominantly detected BKPyV type-specific antibodies. The results imply that anti-BKPyV antibody ELISA tests should contain a mixture of subtype-specific VLP-based antigens instead of antigen derived from the most prevalent BKPyV-I subtype. The tests can be used for serological surveys of BKPyV infection and improved KTx patient management., (© 2019 Wiley Periodicals, Inc.)