121 results on '"L. Liefeldt"'
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2. Imlifidase – eine neue Strategie zur Desensibilisierung bei HLA-inkompatibler Lebendspende?
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E. von Hoerschelmann, F. Halleck, L. Liefeldt, E. Schrezenmeier, N. Lachmann, B. Osmanodja, M. Naik, C. Lücht, L. Gao, G. Eleftheriadis, and K. Budde
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Nephrology ,Internal Medicine - Published
- 2022
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3. Spenderrisiko – Vertrauen durch Evidenz
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L. Liefeldt and K.-U. Eckardt
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Nephrology ,Internal Medicine - Published
- 2018
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4. Nierentransplantation im Alter – eine Herausforderung
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Birgit Rudolph, R. Peters, Hans-H. Neumayer, K. Wu, A. Walter, Klemens Budde, Petra Glander, L. Liefeldt, and F. Friedersdorff
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Nephrology ,Internal Medicine - Published
- 2018
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5. Intensivierte vs. standardmäßige Dosierung von magensaftresistentem Mycophenolat- Natrium bei De-novo-Nierentransplantatempfängern: 1-Jahres-Ergebnisse einer randomisierten Studie
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R. Hackenberg, E.-M. Paulus, Martin Zeier, Martina Porstner, Claudia Sommerer, Petra Glander, Wolfgang Arns, S. Domhan, Christoph May, P. Schemmer, Klemens Budde, W. Fischer, M. Shipkova, L. Liefeldt, and T. Ariatabar
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Nephrology ,Internal Medicine - Published
- 2014
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6. Transplantation: clinical studies - A
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T. Yildirim, R. Yilmaz, M. Altindal, E. Turkmen, M. Arici, B. Altun, Y. Erdem, O. Guliyev, M. Erkmen Uyar, E. Tutal, Z. Bal, S. Sezer, U. Bal, B. Say n, B. Erdemir, A. O'Rourke-Potowki, N. Gauge, H. Penny, A. Cronin, S. Frame, D. J. Goldsmith, J. A. Yagan, A. Chandraker, R. M. Velickovic Radovanovic, A. Catic Djordjevic, B. Mitic, N. Stefanovic, T. Cvetkovic, N. Serpieri, F. Grosjean, G. Sileno, M. Torreggiani, V. Esposito, F. Mangione, M. Abelli, F. Castoldi, D. Catucci, C. Esposito, A. Dal Canton, A. V. Vatazin, A. B. Zulkarnaev, C. Borst, Y. Liu, J. Thoning, M. Tepel, C. Libetta, E. Margiotta, I. Borettaz, M. Canevari, C. Martinelli, E. Lainu, F. Meloni, V. Sepe, R. Miguel Costa, E. Vasquez Martul, J. Reboredo, C. Rivera, F. Simonato, G. Tognarelli, G. Daidola, E. Gallo, M. Burdese, V. Cantaluppi, L. Biancone, G. P. Segoloni, M. Priora, M. Messina, M. Tamagnone, A. Linsalata, A. Lavacca, G. Segoloni, W. Zuidema, R. Erdman, J. van de Wetering, F. Dor, J. Roodnat, E. Massey, L. Timmerman, J. IJzermans, W. Weimar, C. Sibley-Allen, R. Hilton, M. Moghul, L. Burnapp, G. Blake, T. Y. Koo, J.-S. Park, H. C. Park, G.-H. Kim, C. H. Lee, I. H. Oh, C. M. Kang, J. K. Hwang, S. C. Park, B. S. Choi, H. J. Chun, J. I. Kim, C. W. Yang, I. S. Moon, S. Van Laecke, W. Van Biesen, E. V. Nagler, Y. Taes, P. Peeters, R. Vanholder, R. Pruthi, R. Ravanan, A. Casula, M. Harber, P. Roderick, D. Fogarty, A. Cho, J.-h. Shin, H. R. Jang, J. E. Lee, W. Huh, D. J. K. Kim, H. Y. Oh, Y.-G. Kim, A. Sancho Calabuig, E. Gavela Martinez, J. Kanter Berga, S. Beltran Catalan, A. I. Avila Bernabeu, L. M. Pallardo Mateu, E. Gonzalez, N. Polanco, M. Molina, E. Gutierrez, L. Garcia Puente, A. Sevillano, E. Morales, M. Praga, A. Andres, M. Banasik, M. Boratynska, K. Koscielska-Kasprzak, D. Bartoszek, M. Myszka, S. Zmonarski, B. Nowakowska, E. Wawrzyniak, A. Halon, P. Chudoba, M. Klinger, J. Rojas-Rivera, J. M. Morales, J. Egido, C. M. Kopecky, M. Haidinger, C. Kaltenecker, M. Antlanger, G. Marsche, M. Holzer, J. Kovarik, J. Werzowa, M. Hecking, M. D. Saemann, J. M. Kim, E. S. Koh, B. H. Chung, Y. S. Kim, M. Krajewska, O. Mazanowska, D. Kaminska, M. Zabinska, B. Malkiewicz, D. Patrzalek, J. Sulowicz, S. Szostek, A. Wojas-Pelc, E. Ignacak, W. Sulowicz, V. Bellizzi, P. Calella, A. Cupisti, A. Capitanini, C. D'Alessandro, D. Giannese, A. Camocardi, G. Conte, M. Barsotti, G. Bilancio, R. Luciani, L. Locsey, I. Seres, D. Kovacs, L. Asztalos, G. Paragh, M. Wohlfahrtova, P. Balaz, S. Rokosny, P. Wohlfahrt, A. Bartonova, O. Viklicky, J. Kers, R. B. Geskus, L. J. Meijer, F. Bemelman, I. J. M. ten Berge, S. Florquin, J.-C. Hwang, M.-Y. Jiang, Y.-H. Lu, S.-F. Weng, A. Testa, G. Porto, M. Sanguedolce, B. Spoto, R. Parlongo, A. Pisano, G. Enia, G. Tripepi, C. Zoccali, N. Mamode, A. Lennerling, F. Citterio, K. Van Assche, S. Sterckx, M. Frunza, H. Jung, A. Pascalev, R. Johnson, C. Loven, T. Soleymanian, H. Keyvani, S. M. Jazayeri, Z. Fazeli, S. Ghamari, M. Mahabadi, V. Chegeni, I. Najafi, M. R. Ganji, K. M. E. Meys, J. W. Groothoff, K. Jager, F. Schaefer, B. Tonshoff, C. Mota, K. Cransberg, K. van Stralen, E. Gurluler, N. Gures, A. Alim, A. Gurkan, U. Cakir, I. Berber, R. Caluwe, E. Nagler, B. Van Vlem, A. Betkowska-Prokop, M. Kuzniewski, M. Krzanowski, I. Masson, M. Flamant, N. Maillard, E. Cavalier, O. Moranne, E. Alamartine, C. Mariat, P. Delanaye, L. L. Canas Sole, E. Iglesias Alvarez, M. C. M. C. Pastor, F. F. Moreno Flores, V. V. Abujder, F. F. Graterol, J. J. Bonet Sol, R. R. Lauzurica Valdemoros, M. Yoshikawa, K. Kitamura, K. Nakai, S. Goto, H. Fujii, T. Ishimura, M. Takeda, M. Fujisawa, S. Nishi, N. Prasad, D. Gurjer, D. Bhadauria, A. Gupta, R. Sharma, A. Kaul, M. Cybulla, M. West, K. Nicholls, J. Torras, G. Sunder-Plassmann, S. Feriozzi, S. Lo, P. Y. H. Wong, D. Ip, C. K. Wong, V. C. C. Chow, S. K. L. Mo, M. Molnar, A. Ujszaszi, M. E. Czira, M. Novak, I. Mucsi, J. M. Cruzado, S. Coelho, N. Porta, O. Bestard, E. Melilli, O. Taco, I. Rivas, J. Grinyo, L.-M. Pouteau, J.-M. N'Guyen, A. Hami, M. Hourmant, N. Ghahramani, Z. Karparvar, S. Shadrou, M. Ghahramani, J. P. Fauvel, A. Hadj-Aissa, F. Buron, E. Morelon, M. Ducher, C. Heine, P. Glander, H.-H. Neumayer, K. Budde, L. Liefeldt, N. Montero, A. C. Webster, A. Royuela, J. Zamora, M. Crespo, J. Pascual, A. Y. Adema, W. T. H. van Dorp, M. J. K. Mallat, H. W. de Fijter, Y. A. Hong, C. W. Park, Y.-S. Kim, G. Suleymanlar, Z. Uzundurukan, A. Kapuagas, I. Sencan, R. Akdag, A. Torio, V. Mas, M. J. Perez-Saez, M. Mir, A. Faura, O. Montes-Ares, M. D. Checa, D. Sawinski, J. Trofe-Clark, T. Sparkes, P. Patel, S. Goral, R. Bloom, H. J. Kim, S. J. Park, T. H. Kim, Y. W. Kim, Y. H. Kim, S. W. Kang, M. Abdel Halim, O. Gheith, T. Al-Otaibi, A. Mosaad, W. Awadeen, T. Said, P. Nair, and M. R. N. Nampoory
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Transplantation ,medicine.medical_specialty ,Nephrology ,business.industry ,Medicine ,business ,Intensive care medicine - Published
- 2013
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7. Aktuelle Aspekte der Immunsuppression nach Nierentransplantation
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L. Liefeldt, Manuela Schütz, Fritz Diekmann, Markus Giessing, Klemens Budde, Petra Glander, and Hans-H. Neumayer
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Nephrology ,Internal Medicine - Published
- 2008
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8. Lebendnierentransplantation
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Markus Giessing, Klemens Budde, C. Jung, H.-H. Neumayer, Harm Peters, Tom Florian Fuller, and L. Liefeldt
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Gynecology ,medicine.medical_specialty ,Nephrology ,business.industry ,Medicine ,business - Published
- 2006
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9. Contraindications to living donor kidney transplantation
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L. Liefeldt, Markus Giessing, Klemens Budde, and H.-H. Neumayer
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medicine.medical_specialty ,business.industry ,Contraindications ,MEDLINE ,General Medicine ,medicine.disease ,Kidney Transplantation ,Living donor ,Text mining ,Risk Factors ,Living Donors ,Humans ,Kidney Failure, Chronic ,Medicine ,business ,Intensive care medicine ,Kidney transplantation - Published
- 2005
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10. Nierenlebendspende
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M. Giessing, L. Liefeldt, B. Rehberg, and S. Deger
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- 2009
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11. [Modern immunosuppression following renal transplantation. Standard or tailor made?]
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K, Budde, M, Giessing, L, Liefeldt, H-H, Neumayer, and P, Glander
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Graft Rejection ,Treatment Outcome ,Graft Enhancement, Immunologic ,Chemotherapy, Adjuvant ,Graft Survival ,Practice Guidelines as Topic ,Humans ,Kidney Failure, Chronic ,Practice Patterns, Physicians' ,Kidney Transplantation ,Immunosuppressive Agents - Abstract
Renal transplantation is by far the best therapeutic option for end-stage kidney disease with respect to quality of life, psychosocial rehabilitation, and even patient survival. Optimal immunosuppressive therapy should provide effective prophylaxis of both acute rejection and chronic allograft dysfunction. Thus immunosuppressive therapy should help to maintain good renal function and could help to prevent premature death of the recipient. With the introduction of new immunosuppressants over the last decade a dramatic reduction of acute rejection rates from approximately 50% to 15-30% could be achieved. However, the search for novel immunosuppressive drugs continues, drugs which not only lead to effective prevention of acute rejection, but also have an impact on chronic allograft dysfunction and prevent further deterioration of this multifactorial process. Based on a short presentation of the "three signal model" of immunoactivation, the most important mechanisms and characteristics of the presently available immunosuppressants are described. Because the immunosuppressive objectives change over time, a phase-dependent adaptation is necessary. At present, most centers in Germany use an immunosuppressive combination therapy, consisting of a calcineurin inhibitor (CNI; cyclosporine or tacrolimus), a glucocorticoid (prednisolone or methylprednisolone), and mycophenolic acid (MPA), which is eventually combined with an antibody (e.g., IL-2R antibody) for induction. In contrast to the clear situation 10 years ago, highly specialized knowledge is required today with respect to mechanism of action, side effects, and potential interactions. This may enable the physician to adopt patient-oriented optimal immunosuppression. In the near future more individualized treatment options will be employed, which are adapted to the characteristics and side effects of the immunosuppressant, as well as to the characteristics of the donor, the recipient, and the transplanted organ such as immunology and ischemia. Another aspect is the reduction or elimination of some immunosuppressants at the earliest possible time. With new diagnostic and genetic markers the relationship between recipient and transplanted organ will be characterized better in the future and therapy will become more individualized. Altogether, these measures as well as optimized supportive therapy will help to further improve the longevity of the transplanted organ.
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- 2005
12. [Urological evaluation and follow-up of the kidney transplant patient]
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T F, Fuller, L, Liefeldt, D, Dragun, M, Tüllmann, S A, Loening, and M, Giessing
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Graft Rejection ,Postoperative Care ,Urologic Diseases ,Treatment Outcome ,Germany ,Practice Guidelines as Topic ,Preoperative Care ,Living Donors ,Humans ,Practice Patterns, Physicians' ,Kidney Transplantation - Abstract
Patients with end-stage renal disease awaiting kidney transplantation require regular urological evaluation. The urologist's main task is early diagnosis and treatment of genitourinary malignancies and evaluation of the lower urinary tract. Furthermore, urologists are often confronted with the question of whether or not to perform pretransplant urological surgery, i.e., native nephrectomy for polycystic kidney disease. Urological care after kidney transplantation involves diagnosis and treatment of ureteral complications, malignancies, lower urinary tract symptoms, and last but not least erectile dysfunction, which has a prevalence of 20-50% among kidney transplant recipients. For the evaluation and follow-up of the living kidney donor, international guidelines have been developed in recent years to also help the urologist to perform a correct evaluation and follow-up of the kidney donor.
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- 2005
13. Role of the cardiac renin-angiotensin system in human heart failure
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M, Paul, P, Stock, M, Langheinrich, L, Liefeldt, G, Schönfelder, and M, Böhm
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Heart Failure ,Renin-Angiotensin System ,Angiotensin II ,Humans ,Heart - Abstract
The local effects of angiotensin II (ANG II) on the heart may play an important role for the pathophysiology of cardiovascular disease. Numerous in vitro studies have demonstrated that angiotensin II has distinctive cellular effects in the cardiovascular system which are independent from its effects on blood pressure. These have led to the hypothesis that activation of the angiotensin system in the heart could be of functional relevance for the adaptive processes in several cardiovascular disorders such as cardiac hypertrophy heart failure. This concept has been further supported by clinical studies showing the beneficial effects of angiotensin-converting enzyme inhibitors in these circumstances. In order to study the gene regulation of renin-angiotensin system components in cardiac disorders we investigated the gene expression of angiotensin converting enzyme in human heart failure. Results showed that the enzyme is activated locally in this condition, supporting previous studies in animals. Taken together with recent evidence from genetic studies linking the enzyme to myocardial infarction and cardiac hypertrophy, our findings are in support of the notion that angiotensin converting enzyme plays a central role in cardiovascular physiology and pathophysiology.
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- 1995
14. Regulation of the endothelin system in transgenic rats expressing the human endothelin-2 gene
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L, Liefeldt, W, Böcker, G, Schönfelder, M, Zintz, and M, Paul
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Animals, Genetically Modified ,Base Sequence ,Receptors, Endothelin ,Endothelins ,Hypertension ,Molecular Sequence Data ,Animals ,Humans ,RNA, Messenger ,Polymerase Chain Reaction ,Rats - Abstract
We have established a transgenic rat model for the expression of the human endothelin-2 (ET-2). These animals exhibit overexpression of the transgene in tissues as well as in plasma. Despite these changes, blood pressure remains normal. To understand the regulatory mechanisms for normotension in the presence of increased ET-2 levels, we have investigated the ET system in more detail. We used competitive reverse transcription-polymerase chain reaction (RT-PCR) to evaluate possible overexpression or downregulation of endothelin A and B receptors at the mRNA level. PCR analyses revealed no significant differences of ETA and ETB receptor expression. In conclusion, the expression of human ET-2 in transgenic rats does not result in hypertension. Normotension in the transgenic animals is independent of ET receptor regulation. The reason for this may be counterregulation by other vasoactive systems, such as the NO system. Future studies will take this into account and will also concentrate on possible histomorphologic alterations caused by mitogenic properties of the endothelins.
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- 1995
15. Transplantation: clinical studies (2)
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R. Walker, I. Ruderman, R. Masterson, S. Cohney, M. Salvadori, P. Conti, E. Bertoni, A. Durrbach, F. Citterio, L. Mulloy, E. David-Neto, G. Russ, S. Vitko, R. Zhang, J. Xing, M. B. Harler, J. Grinyo, C. Rugiu, A. Trubian, P. Bernich, A. Lupo, A. Asbe-Vollkopf, A. Pannu, H. Hoefeld, S. Gauer, J. Gossmann, H. G. Kachel, S. Froese, S. Korom, H. Geiger, I. A. Hauser, L. Liefeldt, C. Kluener, P. Glander, M. Giessing, O. Gralla, H.-H. Neumayer, K. Budde, T. Kroencke, A. B. Liborio, R. M. Barros, R. M. Esmeraldo, M. L. M. B. Oliveira, F. J. V. Nogueira Paes, T. R. Mendoza, G. B. Silva Junior, E. F. Daher, M. Siekierka-Harreis, C. Bantis, N.-M. Kouri, C. Schwandt, L.-C. Rump, K. Ivens, J. Slatinska, E. Honsova, M. Burgelova, E. Slimackova, O. Viklicky, G. Tabernero, K. Rivero, G. Fernandez, J. Canueto, P. Garcia, P. Fraile, C. Lucas, J. M. Tabernero, A.-S. Bargnoux, N. Simon, V. Garrigue, A.-M. Dupuy, G. Mourad, J.-P. Cristol, U. Yapici, J. Kers, F. Bemelman, J. Roelofs, J. Groothoff, C. van der Loos, K. van Donselaar-van der Pant, M. Idu, N. Claessen, I. ten Berge, S. Florquin, B. Knap, Z. Dragonja, S. Dobnik, J. Buturovic Ponikvar, R. Ponikvar, A. Kandus, A. Bren, J. Kleemann, J. Engel, S. Winter, M. Brzoska, N. Obermueller, E. Schaeffeler, M. Oldak, J. Pazik, Z. Lewandowski, E. Sitarek, M. Dabrowski, R. Ploski, J. Malejczyk, M. Durlik, K. Slubowska, A. Urbanowicz, A. Sadowska, B. Lichodziejewska, K. Kurnicka, Z. Galazka, A. Chmura, J. Masin-Spasovska, G. Spasovski, G. Petrusevska, Z. Popov, N. Ivanovski, A. Di Napoli, M. F. Salvatori, F. Franco, D. Di Lallo, G. Guasticchi, A. Sancho, E. Gavela, S. Beltran, J. Kanter, B. Alemany, J. F. Crespo, L. M. Pallardo, A. Lionet, J.-B. Beuscart, D. Buob, A. BenHenda, F. Provot, M. Hazzan, C. Noel, F. Galan-Sanchez, P. Marin-Casanova, A. Mazuecos, T. Garcia-Alvarez, E. Aznar, M. Rodriguez-Iglesias, S. Ossareh, M. Salami, E. Mohammad, M. Hosseini, A. Pawlik, J. Chudek, A. Kolonko, J. Wilk, P. Jalowiecki, A. Wiecek, E. Zyablitskaya, E. Galkina, E. Yushina, C. Botelho, P. Aires, L. Santos, C. Romaozinho, F. Macario, R. Alves, P. Veiga, A. Mota, M. Yashi, T. Yagisawa, T. Kimura, A. Nukui, T. Fujiwara, Y. Sakuma, N. Ishikawa, T. Iwabuchi, O. Muraishi, P. Hambach, S. Esmen, K. Keven, S. Sengul, M. Ozcan, A. Ensari, A. Tuzuner, R. Calayoglu, G. Nergizoglu, T. Gullu Koca, N. Koca, A. Ersoy, B. Faria, M. Bustorff, F. Barros, I. Tavares, J. Santos, I. Ferreira, S. Sampaio, M. Pestana, B. Suvak, I. Kurultak, H. Tutkak, H. M. Choi, H. N. Yang, S.-K. Jo, W. Y. Cho, H.-K. Kim, A. Aybal Kutlugun, B. Altun, U. Akman, T. Aki, E. Turkmen, T. Yildirim, M. Altindal, R. Yilmaz, U. Yasavul, U. Thiem, G. Heinze, U. Gossler, T. Perkmann, F. Kainberger, F. Muhlbacher, W. Horl, K. Borchhardt, A. Sanchez-Escuredo, S. Holgado, C. Biosca, M. L. Granada, E. Barluenga, R. Lauzurica, R. Romero, A. Espinal, V. Torregrossa, B. Bayes, K. Tomida, T. Hamano, N. Fujii, N. Ichimaru, I. Matsui, Y. Isaka, H. Rakugi, S. Takahara, A. Avila, F. Dor, E. Massey, M. Frunza, R. Johnson, A. Lennerling, C. Loven, N. Mamode, A. Pascalev, S. Sterckx, K. Van Assche, W. Zuidema, W. Weimar, R. Allwin, null Roessel, S. Buettner, V. Belwe, J. Apaza, E. Gonzalez, N. Polanco, I. Bengoa, C. Cadenillas, A. Andres, J. M. Morales, S. Rocha, I. Fonseca, L. S. Martins, J. Vidinha, L. Dias, M. Almeida, S. Pedroso, A. Henriques, A. Cabrita, I. Neretljak, K. Mihovilovic, Z. Vidas, F. Jurenec, M. Knotek, S. Justa, R. Minz, M. Minz, S. Anand, A. Sharma, A. Lacquaniti, V. Donato, V. Chirico, G. Pettinato, M. Buemi, J. Galle, J. Addison, P. Perry, K. Claes, M. Farouk, A. Guerin, I. Kiss, C. Winearls, S. Di Giulio, N. Basic-Jukic, J. Slavicek, L. Bubic-Filipi, P. Kes, T. Scholbach, H.-K. Wang, A. H. Yang, C. C. Loong, T. H. Wu, I. Abboud, C. Antoine, T. Serrato, C. Lefaucheur, E. Pillebout, F. Gaudez, F. Fieux, M. Flamant, J. Verine, D. Viglietti, M.-N. Peraldi, and D. Glotz
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Transplantation ,Nephrology - Published
- 2011
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16. Continuous glucose monitoring for the prediction of posttransplant diabetes mellitus and impaired glucose tolerance on day 90 after kidney transplantation-A prospective proof-of-concept study.
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Eleftheriadis G, Naik MG, Osmanodja B, Liefeldt L, Choi M, Halleck F, Schrezenmeier E, Eckardt KU, Pigorsch M, Tura A, Kurnikowski A, Hecking M, and Budde K
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- Humans, Female, Male, Prospective Studies, Middle Aged, Prognosis, Follow-Up Studies, Diabetes Mellitus etiology, Risk Factors, Adult, Kidney Failure, Chronic surgery, Kidney Failure, Chronic complications, Blood Glucose Self-Monitoring, Proof of Concept Study, Graft Survival, Kidney Function Tests, Glomerular Filtration Rate, Biomarkers blood, Glycated Hemoglobin analysis, Graft Rejection etiology, Graft Rejection diagnosis, Monitoring, Physiologic methods, Aged, Continuous Glucose Monitoring, Kidney Transplantation adverse effects, Blood Glucose analysis, Glucose Intolerance etiology, Glucose Intolerance diagnosis, Glucose Intolerance blood, Postoperative Complications blood, Postoperative Complications etiology, Postoperative Complications diagnosis, Glucose Tolerance Test
- Abstract
Posttransplant diabetes mellitus (PTDM) and prediabetes represent serious complications after kidney transplantation and are associated with increased cardiovascular morbidity and mortality. We assessed the predictive performance of continuous glucose monitoring (CGM) compared with plasma glucose and hemoglobin A1c in 46 kidney transplant recipients (KTRs) without known preexisting diabetes mellitus. CGM (14-day recording duration) was performed on days 8, 30, 45, 60, 90, and 180 posttransplant. Eight patients (17%) developed PTDM and nine (20%) impaired glucose tolerance (IGT), as diagnosed by oral glucose tolerance test (oGTT)-derived 2-hour plasma glucose (2hPG) or glucose-lowering therapy on day 90. CGM-readouts percent of time >140 mg/dL (%TAR (140 mg/dL)) and percent of time >180 mg/dL (%TAR (180 mg/dL)) showed excellent in-sample test characteristics regarding PTDM from day 8 onward (days 8-90 receiver operating characteristic area under the curve: 0.88-0.99) and regarding PTDM/IGT with the commencement of maintenance immunosuppression from day 30 onward (days 30-90 receiver operating characteristic area under the curve: 0.88-0.91). Exploratory CGM-%TAR (140 mg/dL)-screening thresholds of 31.8% on day 8 and 13.2% on day 30 yielded sensitivities/specificities of 88%/83% for PTDM and 94%/78% for PTDM/IGT on day 90, respectively. Although our findings need to be replicated in studies with larger sample sizes, CGM bears promising potential to facilitate clinical practice and research regarding PTDM., Competing Interests: Declaration of competing interests The authors of this manuscript have conflicts of interest to disclose as described by the American Journal of Transplantation. G. Eleftheriadis reports travel support from Chiesi. M.G. Naik reports research funding from Berlin Institute of Health; travel support from Deutsche Gesellschaft für Nephrologie; and lecture honoraria from Novartis, Thermo Fisher Scientific, and Deutsche Gesellschaft für Nephrologie. B. Osmanodja reports travel support from Oncocyte. L. Liefeldt reports lecture honoraria from Universität Heidelberg and travel support from Deutsche Transplantationsgesellschaft. F. Halleck reports consulting fees from Orifarm; honoraria from Hansa, Chiesi, Novartis, and MSD; and travel support from Hansa Pharma; and is a member of the Advisory Board of TolerogenixX TOL-2 Study. E. Schrezenmeier reports grants from DFG, BMBF, and EKFS Exzellenzstipendium and honoraria from AstraZeneca, Medupdate Europe, and Berliner Dialyseseminar. K.-U. Eckardt reports grants from Amgen, Astra Zeneca, Bayer, Evotec, and Vifor and consulting fees from Akebia, Astra Zeneca, Bayer, Otsuka, and Retrophin and is a member of the Advisory Board of Astra Zeneca. K. Budde reports grants/contracts from Alexion, Astellas, AstraZeneca, Chiesi, CSL Behring, MSD, Otsuka, Stada, and Takeda; consulting fees from Alcuris, Alexion, Astellas, AstraZeneca, Bayer, Bristol-Myers Squibb, Carealytics, CareDx, Chiesi, CSL Behring, Fresenius, Hansa, HiBio, MSD, Natera, Neovii, Paladin, Pfizer, Pirche, Sanofi, Stada, Takeda, Veloxis, Vifor, and Xenothera; honoraria from Astellas, AstraZeneca, Chiesi, Fresenius, MSD, Paladin, Sanofi, and Takeda; and travel support from AstraZeneca, Chiesi, HiBio, MSD, Neovii, Paladin, Stada, Takeda, and Veloxis; is a member of the Advisory Board of Alcuris, Alexion, Astellas, AstraZeneca, Bristol-Myers Squibb, Carealytics, CareDx, Chiesi, CSL Behring, HiBio, MSD, Natera, Neovii, Paladin, Pfizer, Stada, Takeda, Veloxis, and Vifor; and reports leadership or fiduciary role in Deutsche Transplantationsgesellschaft and Eurotransplant. The other authors report no conflicts on interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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17. Continuous Glucose Monitoring for the Diagnosis of Post-Transplantation Diabetes Mellitus and Impaired Glucose Tolerance From Years One to Five After Kidney Transplantation-A Prospective Pilot Study.
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Eleftheriadis G, Naik MG, Osmanodja B, Liefeldt L, Halleck F, Choi M, Schrezenmeier E, Zukunft B, Tura A, and Budde K
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- Humans, Pilot Projects, Prospective Studies, Female, Male, Middle Aged, Cross-Sectional Studies, Adult, Aged, Postoperative Complications diagnosis, Postoperative Complications etiology, Postoperative Complications blood, Continuous Glucose Monitoring, Kidney Transplantation adverse effects, Glucose Tolerance Test, Blood Glucose analysis, Blood Glucose metabolism, Glycated Hemoglobin analysis, Glucose Intolerance diagnosis, Glucose Intolerance blood, Diabetes Mellitus blood, Diabetes Mellitus diagnosis, Diabetes Mellitus etiology
- Abstract
Post-transplantation diabetes mellitus (PTDM) and prediabetes are associated with increased cardiovascular morbidity and mortality in kidney transplant recipients (KTR), when diagnosed by an oral glucose tolerance test (oGTT). Hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) display low concordance with the oGTT in the early phase posttransplant. For this prospective cross-sectional pilot study, 41 KTR from years one to five after transplantation without known preexisting PTDM (defined by HbA1c ≥ 6.5% (NGSP) or 48 mmol/mol (IFCC) at last visit or glucose-lowering therapy) were recruited at the Charité Transplant Outpatient Clinic. For each study participant HbA1c, FPG and an oGTT were followed by CGM. 38 of the 41 patients recruited had sufficient CGM-recordings (≥10 days). PTDM and impaired glucose tolerance (IGT), as defined by the gold standard oral glucose tolerance test (oGTT)-derived 2-h plasma glucose (2hPG), were diagnosed in one (3%) and twelve (32%) patients, respectively. HbA1c exhibited good test characteristics regarding IGT (ROC-AUC: 0.87); sensitivity/specificity of HbA1c-threshold 5.7% (NGSP) or 39 mmol/mol (IFCC) were 1.0/0.64, respectively. Best performing CGM-readouts mean sensor glucose and percent of time >140 mg/dL (%TAR (140 mg/dL)) displayed acceptable diagnostic performance (ROC-AUC: 0.78 for both). Thus, HbA1c can aid in timely diagnosis of IGT in the stable phase after kidney transplantation., Competing Interests: GE received travel support from Chiesi. MN received research funding from Berlin Institute of Health; travel support from Deutsche Gesellschaft für Nephrologie; lecture honoraria from Novartis, Thermo Fisher Scientific, Deutsche Gesellschaft für Nephrologie. BO received travel support from Oncocyte. FH received grants from MSD, Hansa Pharma, Chiesi; consulting fees from Orifarm, Sanofi; honoraria from Hansa Pharma, Thermo Fischer, Aey Congresse; travel support from Hansa Pharma and is part of the advisory board of TolerogenixX TOL-2 Study. MC received grants from DFG, BMBF, EKFS Exzellenzstipendium; honoraria from Alexion, AstraZeneca, Berliner Dialyseseminar, Freunde der Berliner Charité, GSK, Novartis. KB received grants/contracts from Alexion, Astellas, AstraZeneca, Chiesi, CSL Behring, MSD, Otsuka, Stada, Takeda; consulting fees from Alcuris, Alexion, Astellas, AstraZeneca, Bayer, Bristol-Myers Squibb, Carealytics, CareDx, Chiesi, CSL Behring, Fresenius, Hansa, HiBio, MSD, Natera, Neovii, Paladin, Pfizer, Pirche, Sanofi, Stada, Takeda, Veloxis, Vifor, Xenothera; honoraria from Astellas, AstraZeneca, Chiesi, Fresenius, MSD, Paladin, Sanofi, Takeda; travel support from AstraZeneca, Chiesi, HiBio, MSD, Neovii, Paladin, Stada, Takeda, Veloxis; is part of the advisory board of Alcuris, Alexion, Astellas, AstraZeneca, Bristol-Myers Squibb, Carealytics, CareDx, Chiesi, CSL Behring, HiBio, MSD, Natera, Neovii, Paladin, Pfizer, Stada, Takeda, Veloxis, Vifor and has a leader or fiduciary role for Deutsche Transplantationsgesellschaft, Eurotransplant The remaining 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 © 2024 Eleftheriadis, Naik, Osmanodja, Liefeldt, Halleck, Choi, Schrezenmeier, Zukunft, Tura and Budde.)
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- 2024
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18. Office or home versus 24-h blood pressure measurement in stable kidney transplant recipients.
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Eleftheriadis G, Naik MG, Osmanodja B, Halleck F, Schrezenmeier E, Liefeldt L, Choi M, Bachmann F, Avaniadi DP, von Hoerschelmann E, Lücht C, Zaks M, Duettmann W, and Budde K
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- Humans, Female, Male, Middle Aged, Prospective Studies, Cross-Sectional Studies, Blood Pressure physiology, Transplant Recipients, Follow-Up Studies, Prognosis, Blood Pressure Determination methods, Adult, Aged, Kidney Failure, Chronic physiopathology, Kidney Failure, Chronic surgery, Kidney Transplantation, Blood Pressure Monitoring, Ambulatory methods, Hypertension diagnosis, Hypertension physiopathology, Hypertension etiology
- Abstract
Background: The aim of this study was to quantify hypertension control and evaluate concordance between all commonly available blood pressure (BP) modalities in kidney transplant recipients (KTRs)., Methods: For this prospective cross-sectional study, 89 stable KTRs were recruited at the Charité Transplant Outpatient Clinic. For each study participant office [manual office BP (MOBP) and automated office BP (AOBP)], 7-day home (HBPM) and 24-hour ambulatory BP (24h-ABPM) measurements were performed., Results: 80 of the 89 patients recruited had sufficient BP recordings. The mean BP for MOBP, AOBP, HBPM and 24h-ABPM was 129/73, 126/71, 131/85 and 130/81 mmHg, respectively. Uncontrolled hypertension, as defined by 24h-ABPM (mean ≥130/80 mmHg), was present in 53 (66%) patients. MOBP, AOBP and HBPM classified 19 (24%), 22 (28%) and 41 (51%) patients, respectively, as 'uncontrolled hypertensive'. The Bland-Altman plot showed good agreement between systolic MOBP, AOBP, HBPM and daytime-ABPM (mean bias: -1 ± 13 mmHg, -4 ± 13 mmHg, 1 ± 10 mmHg, respectively). Uncontrolled night-time hypertension was present in 74 (93%) KTRs, with 71 (89%) patients showing a non-physiological dipping pattern. Moderate positive correlation between daytime-ABPM/HBPM and night-time-ABPM (Pearson correlation coefficients: 0.62-0.73), followed by MOBP/AOBP (Pearson correlation coefficients: 0.49-0.59) was noted. Estimated eGFR and proteinuria displayed weak correlation with 24h-, daytime- and night-time-ABPM (absolute values of Pearson correlation coefficients: 0.04-0.41). No robust association with either 24h-, daytime- or night-time-ABPM was observed for volume status exams., Conclusions: Masked hypertension is highly prevalent in KTRs, especially due to high rates of uncontrolled night-time hypertension. HBPM shows the narrowest limits of agreement with daytime-ABPM. Daytime-ABPM and HBPM show the highest, albeit clinically insufficient, correlation with night-time-ABPM. Systematic integration of 24h-ABPM into clinical practice, as proposed by the 2023 ESH guidelines for the management of arterial hypertension, should not be withheld for the KTR population. Clinical trials evaluating the treatment of hypertension in KTRs are urgently needed., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)
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- 2024
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19. Kidney transplantation in patients with polycystic kidney disease: increased risk of infection does not compromise graft and patient survival.
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Waiser J, Klotsche J, Glander P, Schmidt D, Naik M, Liefeldt L, Budde K, Halbritter J, Halleck F, Zukunft B, Peters R, Friedersdorff F, Lachmann N, Eckardt KU, d'Anjou L, and Bachmann F
- Abstract
Background: Patients with autosomal dominant polycystic kidney disease (ADPKD) represent >10% of patients awaiting kidney transplantation. These patients are prone to potentially severe urinary tract (UTI) and liver cyst infections after transplantation. Whether such infections compromise outcome is unclear., Methods: Between 2000 and 2017 we performed 193 kidney transplantations in patients with ADPKD. In 189 patients, we assessed the occurrence, frequency, and severity of infection episodes requiring inpatient treatment and their impact on graft and patient outcomes compared with 189 matched controls. Risk factors were analyzed by uni- and multivariable analyses., Results: During a mean observation period of 77 months UTIs occurred more frequently in ADPKD patients (39.1% vs. 26.7%, P = .022; 0.8 ± 1.4 vs. 0.5 ± 1.1 episodes, P < .001). Eight ADPKD patients suffered from 19 episodes of liver cyst infection. Steroid medication (RR 3.04; P < .001) and recipient age (RR 1.05; P = .003) increased the risk for UTI/urosepsis, while nephrectomy reduced it (unilateral, RR 0.60; P = .088; bilateral, RR 0.45; P = .020). Patient survival was similar in both groups. The risk of graft failure was lower in ADPKD patients [hazard ratio (HR) 0.67; P = .047] due to a lower risk of death-censored graft loss (HR 0.47; P = .014). Donor age (HR 1.34; P = .002) and rejection (HR 8.47; P < .001) were risk factors for death-censored graft loss., Conclusions: ADPKD patients are at increased risk of UTI and liver cyst infection after transplantation. Steroid medication and recipient age seem to increase the risk of UTI/urosepsis, while nephrectomy seems to reduce it. Nevertheless, patient survival was similar compared to non-ADPKD patients and death-censored graft survival even better., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)
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- 2024
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20. Long-Term Outcome after Early Mammalian Target of Rapamycin Inhibitor-Based Immunosuppression in Kidney Transplant Recipients.
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Liefeldt L, Waiser J, Bachmann F, Budde K, Friedersdorff F, Halleck F, Lachmann N, Peters R, Rudolph B, Ünlü S, Wu K, and Glander P
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Background: The use of mammalian target of rapamycin inhibitors (mTORis) in kidney transplantation increases the risk of donor-specific human leukocyte antigen (HLA) antibody formation and rejection. Here, we investigated the long-term consequences of early mTORi treatment compared to calcineurin inhibitor (CNI) treatment. Methods: In this retrospective single-center analysis, key outcome parameters were compared between patients participating in randomized controlled immunosuppression trials between 1998 and 2011, with complete follow-up until 2018. The outcomes of eligible patients on a CNI-based regimen (n = 384) were compared with those of patients randomized to a CNI-free mTORi-based regimen (n = 81) and 76 patients randomized to a combination of CNI and mTORi treatments. All data were analyzed according to the intention-to-treat (ITT) principle. Results: Deviation from randomized immunosuppression for clinical reasons occurred significantly more often and much earlier in both mTORi-containing regimens than in the CNI treatment. Overall patient survival, graft survival, and death-censored graft survival did not differ between the treatment groups. Donor-specific HLA antibody formation and BPARs were significantly more common in both mTORi regimens than in the CNI-based immunosuppression. Conclusions: The tolerability and efficacy of the mTORi treatment in kidney graft recipients are inferior to those of CNI-based immunosuppression, while the long-term patient and graft survival rates were similar.
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- 2024
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21. [Outcome of ABO-incompatible living-donor kidney transplants : A plea for crossover living-donor kidney transplantation].
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Liefeldt L, Glander P, and Friedersdorff F
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- Humans, Retrospective Studies, Living Donors, ABO Blood-Group System, Kidney, Kidney Transplantation methods
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Background: The lack of postmortem donated organs is the background to varyingly high rates of living-donor kidney transplants worldwide. ABO blood group-incompatible living-donor kidney transplants have also been established for at least 20 years. The equivalence of the results of ABO-incompatible and ABO-compatible transplants has recently been questioned., Objective: In the sense of a critical reflection of our own kidney transplant program, we were interested in comparing ABO-incompatible with ABO-compatible living-donor kidney transplants., Materials and Methods: A retrospective analysis of the long-term outcomes of all living-donor kidney transplants performed at our center since the first ABO-incompatible transplants were performed in 2005 up to and including 2022 was performed., Results: Between 2005 and 2022, 1099 living kidney transplants were performed at the authors' center. Among them were 241 ABO-incompatible transplants. Transplant survival was significantly lower after ABO-incompatible donation than after ABO-compatible donation. This effect consisted of an increased mortality of the recipients, especially in the early phase, and a reduced longevity of the grafts., Conclusion: Including ABO-incompatible pairs for living-donor kidney transplants in crossover programs can improve medical outcomes and reduce costs., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)
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- 2024
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22. Retrospective analysis of the perioperative outcome in living donor kidney transplantation with multiple renal arteries: does accessory vessel ligation affect the outcome?
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Schmidt J, Peters R, Mang J, Ralla B, Moldovan DE, Dagnæs-Hansen J, Liefeldt L, Budde K, Lerchbaumer M, and Friedersdorff F
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- Humans, Renal Artery surgery, Living Donors, Retrospective Studies, Graft Survival, Kidney diagnostic imaging, Kidney surgery, Kidney blood supply, Treatment Outcome, Kidney Transplantation adverse effects
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Purpose: Accurate surgical reconstruction of arterial vascular supply is a crucial part of living kidney transplantation (LDKT). The presence of multiple renal arteries (MRA) in grafts can be challenging. In the present study, we investigated the impact of ligation versus anastomosis of small accessory graft arteries on the perioperative outcome., Methods: Clinical and radiological outcomes of 51 patients with MRA out of a total of 308 patients who underwent LDKT with MRA between 2011 and 2020 were stratified in two groups and analyzed. In group 1 (20 patients), ligation of accessory arteries (ARAs) and group 2 (31 patients) anastomosis of ARAs was performed., Results: Significant differences were observed in the anastomosis-, surgery-, and warm ischemia time (WIT) in favor of group 1. Students t-test showed comparable serum creatinine levels of 2.33 (± 1.75) to 1.68 (± 0.83) mg/dL in group 1 and 2.63 (± 2.47) to 1.50 (± 0.41) mg/dL in group 2, were seen from 1 week to 1 year after transplant. No increased rates of Delayed graft function (DGF), primary transplant dysfunction and transplant rejection were seen, but graft loss and revision rates were slightly higher when the ARAs were ligated. Analysis of Doppler sonography revealed that segmental perfusion deficits tend to regenerate during the clinical course., Conclusion: Ligation of smaller accessory renal arteries may not affect the outcome of living kidney transplantation, except for a minor increase in the reoperation rate. Segmental perfusion deficits of the graft seem to regenerate in most cases as seen in Doppler sonography., (© 2024. The Author(s).)
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- 2024
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23. Transplant nephrectomy: indication, surgical approach and complications-experiences from a single transplantation center.
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Mang J, Haag J, Liefeldt L, Budde K, Peters R, Hofbauer SL, Schulz M, Weinberger S, Dagnæs-Hansen J, Maxeiner A, Ralla B, and Friedersdorff F
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- Humans, Retrospective Studies, Transplantation, Homologous, Graft Survival, Nephrectomy adverse effects, Kidney
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Purpose: Management of a failed kidney allograft, and the question whether it should be removed is a challenging task for clinicians. The reported risks for transplant nephrectomy (TN) vary, and there is no clear recommendation on indications or surgical approach that should be used. This study gives an overview of indications, compares surgical techniques, and identifies risk factors for higher morbidity., Methods: Retrospective analysis was conducted on all transplant nephrectomies performed between 2005 and 2020 at Charité Hospital Berlin, Department of Urology. Patient demographics, laboratory parameters, graft survival data, indication for TN, and surgical complications were extracted from medical reports., Results: A total of 195 TN were performed, with graft intolerance syndrome being the most common indication in 52 patients (26.7%), acute rejection in 36 (18.5%), acute infection in 30 (15.4%), and other reasons to stop immunosuppression in 26 patients (13.3%). Rare indications were vascular complications in 16 (8.2%) and malignancies in the allograft in six (3.1%) cases. Extracapsular surgical approach was significantly more often used in cases of vascular complications and earlier allograft removal, but there was no difference in complication rates between extra- and intracapsular approach. Acute infection was identified as an independent risk factor for a complication grade IIIb or higher according to Clavien-Dindo classification, with a HR of 12.3 (CI 2.2-67.7; p = 0.004)., Conclusion: Transplant nephrectomy should only be performed when there is a good indication, and non-elective surgery should be avoided, when possible, as it increases morbidity., (© 2024. The Author(s).)
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- 2024
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24. COVID-19 Outcomes in Kidney Transplant Recipients in a German Transplant Center.
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Mikhailov M, Budde K, Halleck F, Eleftheriadis G, Naik MG, Schrezenmeier E, Bachmann F, Choi M, Duettmann W, von Hoerschelmann E, Koch N, Liefeldt L, Lücht C, Straub-Hohenbleicher H, Waiser J, Weber U, Zukunft B, and Osmanodja B
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Kidney transplant recipients (KTRs) show higher morbidity and mortality from COVID-19 than the general population and have an impaired response to vaccination. We analyzed COVID-19 incidence and clinical outcomes in a single-center cohort of approximately 2500 KTRs. Between 1 February 2020 and 1 July 2022, 578 KTRs were infected with SARS-CoV-2, with 25 (4%) recurrent infections. In total, 208 KTRs (36%) were hospitalized, and 39 (7%) died. Among vaccinated patients, infection with the Omicron variant had a mortality of 2%. Unvaccinated patients infected with the Omicron variant showed mortality (9% vs. 11%) and morbidity (hospitalization 52% vs. 54%, ICU admission 12% vs. 18%) comparable to the pre-Omicron era. Multivariable analysis revealed that being unvaccinated (OR = 2.15, 95% CI [1.38, 3.35]), infection in the pre-Omicron era (OR = 3.06, 95% CI [1.92, 4.87]), and higher patient age (OR = 1.04, 95% CI [1.03, 1.06]) are independent risk factors for COVID-19 hospitalization, whereas a steroid-free immunosuppressive regimen was found to reduce the risk of COVID-19 hospitalization (OR = 0.51, 95% CI [0.33, 0.79]). This suggests that both virological changes in the Omicron variant and vaccination reduce the risk for morbidity and mortality from COVID-19 in KTRs. Our data extend the knowledge from the general population to KTRs and provide important insights into outcomes during the Omicron era.
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- 2023
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25. A single centre in-depth analysis of death with a functioning kidney graft and reasons for overall graft failure.
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Mayrdorfer M, Liefeldt L, Osmanodja B, Naik MG, Schmidt D, Duettmann W, Hammett C, Schrezenmeier E, Friedersdorff F, Wu K, Halleck F, and Budde K
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- Adult, Humans, Immunosuppression Therapy, Kidney, Graft Survival, Graft Rejection etiology, Kidney Transplantation adverse effects, Cardiovascular Diseases
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Background: High numbers of unknown classifications and inconsistent methodologies in previous studies make the interpretation of causes leading to graft loss difficult. In addition, data on a holistic view looking at both death with a functioning graft (DWFG) and death-censored graft failure (DCGF) are sparse., Methods: In this single-centre study we included 1477 adult kidney transplants performed between 1997 and 2017, of which all 286 DWFGs until the end of observation were analysed and causes for death assigned. Additionally, the results were compared with the causes of 303 DCGFs of the same cohort to evaluate the impact of causes for overall graft loss., Results: The most frequent causes for DWFG were cardiovascular disease (CVD) in 30.8%, malignancy in 28.3% and infections in 21%. Only 9.4% of reasons for DWFG were unknown. Sudden death occurred in 40% (35/88) of patients classified as DWFG due to CVD. Overall graft loss was related to the effect of immunosuppression in 36.2% [infection 20.9% (123/589), malignancy 15.3% (90/589)] and CVD in 22.4% (132/589). In 27.4% (161/589), graft failure was associated with underimmunosuppression (rejection). For infections (60 DWFG, 63 DCGF) and CVD (88 DWFG, 44 DCGF), a considerable overlap was observed between DWFG and DCGF. For patients >70 years of age at transplantation, medical events accounted for 78% of overall graft losses and only 6.5% were associated with rejection., Conclusions: DWFG and DCGF share more causes for graft loss than previously reported and sudden death plays an underestimated role in death with a functioning graft., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)
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- 2023
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26. Temporary antimetabolite treatment hold boosts SARS-CoV-2 vaccination-specific humoral and cellular immunity in kidney transplant recipients.
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Schrezenmeier E, Rincon-Arevalo H, Jens A, Stefanski AL, Hammett C, Osmanodja B, Koch N, Zukunft B, Beck J, Oellerich M, Proß V, Stahl C, Choi M, Bachmann F, Liefeldt L, Glander P, Schütz E, Bornemann-Kolatzki K, López Del Moral C, Schrezenmeier H, Ludwig C, Jahrsdörfer B, Eckardt KU, Lachmann N, Kotsch K, Dörner T, Halleck F, Sattler A, and Budde K
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- Antibodies, Viral, Humans, Immunity, Cellular, Immunity, Humoral, Immunosuppressive Agents therapeutic use, SARS-CoV-2, Transplant Recipients, Vaccination, Antimetabolites therapeutic use, COVID-19 prevention & control, COVID-19 Vaccines immunology, Kidney Transplantation
- Abstract
Transplant recipients exhibit an impaired protective immunity after SARS-CoV-2 vaccination, potentially caused by mycophenolate (MPA) immunosuppression. Recent data from patients with autoimmune disorders suggest that temporary MPA hold might greatly improve booster vaccination outcomes. We applied a fourth dose of SARS-CoV-2 vaccine to 29 kidney transplant recipients during a temporary (5 weeks) MPA/azathioprine hold, who had not mounted a humoral immune response to previous vaccinations. Seroconversion until day 32 after vaccination was observed in 76% of patients, associated with acquisition of virus-neutralizing capacity. Interestingly, 21/25 (84%) calcineurin inhibitor-treated patients responded, but only 1/4 belatacept-treated patients responded. In line with humoral responses, counts and relative frequencies of spike receptor binding domain-specific (RBD-specific) B cells were markedly increased on day 7 after vaccination, with an increase in RBD-specific CD27++CD38+ plasmablasts. Whereas overall proportions of spike-reactive CD4+ T cells remained unaltered after the fourth dose, frequencies were positively correlated with specific IgG levels. Importantly, antigen-specific proliferating Ki67+ and in vivo-activated programmed cell death 1-positive T cells significantly increased after revaccination during MPA hold, whereas cytokine production and memory differentiation remained unaffected. In summary, antimetabolite hold augmented all arms of immunity during booster vaccination. These data suggest further studies of antimetabolite hold in kidney transplant recipients.
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- 2022
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27. Serological Response to Three, Four and Five Doses of SARS-CoV-2 Vaccine in Kidney Transplant Recipients.
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Osmanodja B, Ronicke S, Budde K, Jens A, Hammett C, Koch N, Seelow E, Waiser J, Zukunft B, Bachmann F, Choi M, Weber U, Eberspächer B, Hofmann J, Grunow F, Mikhailov M, Liefeldt L, Eckardt KU, Halleck F, and Schrezenmeier E
- Abstract
Mortality from COVID-19 among kidney transplant recipients (KTR) is high, and their response to three vaccinations against SARS-CoV-2 is strongly impaired. We retrospectively analyzed the serological response of up to five doses of the SARS-CoV-2 vaccine in KTR from 27 December 2020 until 31 December 2021. Particularly, the influence of the different dose adjustment regimens for mycophenolic acid (MPA) on serological response to fourth vaccination was analyzed. In total, 4277 vaccinations against SARS-CoV-2 in 1478 patients were analyzed. Serological response was 19.5% after 1203 basic immunizations, and increased to 29.4%, 55.6%, and 57.5% in response to 603 third, 250 fourth, and 40 fifth vaccinations, resulting in a cumulative response rate of 88.7%. In patients with calcineurin inhibitor and MPA maintenance immunosuppression, pausing MPA and adding 5 mg prednisolone equivalent before the fourth vaccination increased the serological response rate to 75% in comparison to the no dose adjustment (52%) or dose reduction (46%). Belatacept-treated patients had a response rate of 8.7% (4/46) after three vaccinations and 12.5% (3/25) after four vaccinations. Except for belatacept-treated patients, repeated SARS-CoV-2 vaccination of up to five times effectively induces serological response in kidney transplant recipients. It can be enhanced by pausing MPA at the time of vaccination.
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- 2022
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28. Predictors of Serological Response to SARS-CoV-2 Vaccination in Kidney Transplant Patients: Baseline Characteristics, Immunosuppression, and the Role of IMPDH Monitoring.
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Liefeldt L, Glander P, Klotsche J, Straub-Hohenbleicher H, Budde K, Eberspächer B, Friedersdorff F, Halleck F, Hambach P, Hofmann J, Koch N, Schmidt D, Schrezenmeier E, Seelow E, Weber U, Zukunft B, Eckardt KU, Choi M, Bachmann F, and Waiser J
- Abstract
Immunosuppression increases the risk of severe coronavirus disease 2019 (COVID-19). Morbidity and mortality of this disease in kidney transplant patients are higher than in the general population. As the vaccination response of transplant patients is weak, serological monitoring was performed. In this cohort study, we analyzed the determinants of vaccination response. All patients had no history of COVID-19. With anti-spike IgG monitoring, 148 responders and 415 non-responders were identified. We compared both groups using multivariate analyses of the cohort and a sub-cohort of mycophenolic-acid-treated patients. We investigated the influence of patient characteristics, immunosuppression, and erythrocyte inosine monophosphate dehydrogenase (IMPDH) activity. In responders, the time after transplantation was longer (13.5 vs. 8.5 years), the glomerular filtration rate was higher (56.9 vs. 47.8 mL/min/1.73 m2), and responders were younger (53.0 vs. 57.4 years). Heterologous vaccination was more effective than homologous vaccination. Calcineurin inhibitors plus mycophenolate reduced the seroconversion rate. No seroconversion was observed in belatacept patients. In mycophenolate-treated patients, IMPDH activity was a significantly better predictor of response than mycophenolate dose (AUC 0.84 vs. 0.62, p < 0.001). Immunosuppression strongly affects vaccine response. Modifications to immunosuppression should be considered in order to facilitate this response. Erythrocyte IMPDH activity can be used to guide mycophenolate treatment.
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- 2022
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29. Kidney Perfusion in Contrast-Enhanced Ultrasound (CEUS) Correlates with Renal Function in Living Kidney Donors.
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El-Bandar N, Lerchbaumer MH, Peters R, Maxeiner A, Kotsch K, Sattler A, Miller K, Schlomm T, Hamm B, Budde K, Liefeldt L, Fischer T, and Friedersdorff F
- Abstract
Contrast-enhanced ultrasound (CEUS) is a widely used diagnostic tool for analyzing perfusion and characterizing lesions in several organs. However, to date, it has not been sufficiently investigated whether there is an association between CEUS findings and kidney function. This study aimed at identifying the potential relationship between kidney function and the renal perfusion status determined by CEUS in living kidney donors. A total of 30 living kidney donors examined between April 2018 and March 2020 were included in the study. All patients underwent various diagnostic procedures for evaluation of renal function. CEUS was performed in all 30 donors one day before nephrectomy. Kidney perfusion was quantified using a postprocessing tool (VueBox, Bracco Imaging). Various perfusion parameters were subsequently analyzed and compared with the results of the other methods used to evaluate kidney function. Of all parameters, mean signal intensity (MeanLin) had the strongest correlation, showing significant correlations with eGFR (CG) (r = -0.345; p = 0.007) and total kidney volume (r = -0.409; p = 0.001). While there was no significant correlation between any perfusion parameter and diethylenetriaminepentaacetic acid (DTPA), we detected a significant correlation between MeanLin and DTPA (r = -0.502; p = 0.005) in the subgroup of normal-weight donors. The results indicate that signal intensity in CEUS is associated with kidney function in normal-weight individuals. Body mass index (BMI) may be a potential confounder of signal intensity in CEUS. Thus, more research is needed to confirm these results in larger study populations.
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- 2022
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30. Correction to: The underestimated burden of monogenic kidney disease in adults waitlisted for kidney transplantation.
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Schrezenmeier E, Kremerskothen E, Halleck F, Staeck O, Liefeldt L, Choi M, Schüler M, Weber U, Bachmann N, Grohmann M, Wagner T, Budde K, and Bergmann C
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- 2021
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31. Outcomes of Deceased Donor Kidney Transplantation in the Eurotransplant Senior Program with A Focus on Recipients ≥75 Years.
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Zompolas I, Peters R, Liefeldt L, Lehner LJ, Budde K, Ralla B, Goranova I, Maxeiner A, Lerchbaumer MH, Marticorena Garcia SR, Kanne M, Schlomm T, Schulz MRG, and Friedersdorff F
- Abstract
To evaluate the outcomes of kidney transplantations (KTs) in the Eurotransplant Senior Program (ESP) with a focus on the very old, defined as recipients ≥75 years. This retrospective clinical study included 85 patients, who under the ESP protocol underwent deceased donor kidney transplantation from January 2010 to July 2018 at the Charité-Universitätsmedizin Berlin in Germany. Recipients were divided in three age groups, i.e., Group 65-69, Group 70-74, Group ≥75, and compared. Prognostic risk factors for short and long-term outcomes of kidney transplantations were investigated. Graft survival at 1 and 5 years were respectively 90.7% and 68.0% for group 65-69, 88.9% and 76.2% for Group 70-74, and 100% and 71.4% for Group ≥75. Patient survival at 1 and 5 years were respectively 92.9% and 68.0% for Group 65-69, 85.7% and 61.5% for Group 70-74 and 100% and 62.5% for Group ≥75. Serum creatinine did not significantly differ between the three groups, with the exception of serum creatinine at 1 year. Increased recipient age and prolonged time on dialysis correlated with increased occurrence of postoperative complication. An increase in BMI, pretransplant diabetes mellitus and prolonged time on dialysis correlated with the occurrence of delayed graft function (DGF). History of smoking was identified as an independent risk factor for events of rejection. Increased human leukocyte antigen mismatches (HLA-MM) and prolonged cold ischemia time (CIT) correlated with higher rates of intensive care unit (ICU) treatment. This study supports kidney transplantations for the very old. End-stage renal disease (ESRD) patients ≥75 years of age who underwent kidney transplantation experienced comparable results to their younger counterparts. A comprehensive evaluation of ESRD patients with consideration of prognostic risk factor is the most suitable mean of identifying adequate kidney transplant candidates.
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- 2021
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32. Focal Segmental Glomerulosclerosis and Recurrence in Living Donor Recipients.
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Mang J, Hennig L, Liefeldt L, Duerr M, Lehner LJ, Bichmann A, Ralla B, Cash H, Kanne MC, Peters R, Maxeiner A, and Friedersdorff F
- Abstract
Purpose: Focal segmental glomerulosclerosis (FSGS) is a common cause for end-stage renal disease that can recur in the graft after kidney transplantation. The incidence of FSGS recurrence is reported in up to 47% of patients, predisposing those to possible poorer transplantation outcomes. Hence, we examined the incidence of FSGS recurrence and the effect on graft outcome in our patient cohort of living donor kidney transplantations (LDKT)., Patients and Methods: We analyzed 194 adult patients who received a LDKT between 2011 and 2017 of which 22 (11%) had FSGS as underlying disease. Demographic data and clinical outcomes, especially regarding recurrence of FSGS, were evaluated., Results: FSGS recurrence was identified in three (14%) patients within three months after transplantation, of whom two patients (9%) lost their graft. There was no significant difference in graft survival comparing FSGS to other reasons for end-stage renal disease., Conclusion: Incidence of FSGS recurrence in the present patient cohort was within the range reported in the literature and comparatively low. Our data support LDKT as a treatment option in patients with end-stage renal disease due to FSGS., Competing Interests: Dr Michael Duerr reports personal fees from Novartis Pharma GmbH and Takeda Pharmaceutical Company Limited, outside the submitted work. All authors declare that they have no other competing interests., (© 2021 Mang et al.)
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- 2021
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33. The underestimated burden of monogenic kidney disease in adults waitlisted for kidney transplantation.
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Schrezenmeier E, Kremerskothen E, Halleck F, Staeck O, Liefeldt L, Choi M, Schüler M, Weber U, Bachmann N, Grohmann M, Wagner T, Budde K, and Bergmann C
- Subjects
- Adult, Genetic Testing, Humans, Kidney, Glomerulosclerosis, Focal Segmental epidemiology, Glomerulosclerosis, Focal Segmental genetics, Kidney Transplantation, Polycystic Kidney, Autosomal Dominant, Renal Insufficiency, Chronic diagnosis, Renal Insufficiency, Chronic epidemiology, Renal Insufficiency, Chronic genetics
- Abstract
Purpose: Chronic kidney disease (CKD) is a major health-care burden. Increasing evidence suggests that a considerable proportion of patients are affected by a monogenic kidney disorder., Methods: In this study, the kidney transplantation waiting list at the Charité was screened for patients with undetermined cause of CKD. By next-generation sequencing (NGS) we targeted all 600 genes described and associated with kidney disease or allied disorders., Results: In total, 635 patients were investigated. Of these, 245 individuals had a known cause of CKD (38.5%) of which 119 had a proven genetic disease (e.g., ADPKD, Alport). The other 340 patients (53.5%) were classified as undetermined diagnosis, of whom 87 had kidney failure (KF) onset <40 years. To this latter group genetic testing was offered as well as to those patients (n = 29) with focal segmental glomerulosclerosis (FSGS) and all individuals (n = 21) suspicious for thrombotic microangiopathy (TMA) in kidney biopsy. We detected diagnostic variants in 26 of 126 patients (20.6%) of which 14 of 126 (11.1%) were pathogenic or likely pathogenic. In another 12 of 126 (9.5%) patients, variants of unknown significance (VUS) were detected., Conclusion: Our study demonstrates the diagnostic value of comprehensive genetic testing among patients with undetermined CKD.
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- 2021
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34. Exploring the Complexity of Death-Censored Kidney Allograft Failure.
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Mayrdorfer M, Liefeldt L, Wu K, Rudolph B, Zhang Q, Friedersdorff F, Lachmann N, Schmidt D, Osmanodja B, Naik MG, Duettmann W, Halleck F, Merkel M, Schrezenmeier E, Waiser J, Duerr M, and Budde K
- Subjects
- Adult, Aged, Allografts pathology, Allografts statistics & numerical data, Calcineurin Inhibitors adverse effects, Cardio-Renal Syndrome complications, Databases, Factual, Death, Female, Graft Rejection prevention & control, Humans, Immunity, Cellular, Immunity, Humoral, Immunosuppressive Agents therapeutic use, Male, Medication Adherence statistics & numerical data, Middle Aged, Polyomavirus Infections complications, Recurrence, Retrospective Studies, Survival Rate, T-Lymphocytes, Thrombosis complications, Time Factors, Tumor Virus Infections complications, Allografts physiopathology, Graft Rejection immunology, Graft Survival, Kidney Failure, Chronic surgery, Kidney Transplantation standards, Kidney Transplantation statistics & numerical data
- Abstract
Background: Few studies have thoroughly investigated the causes of kidney graft loss (GL), despite its importance., Methods: A novel approach assigns each persistent and relevant decline in renal function over the lifetime of a renal allograft to a standardized category, hypothesizing that singular or multiple events finally lead to GL. An adjudication committee of three physicians retrospectively evaluated indication biopsies, laboratory testing, and medical history of all 303 GLs among all 1642 recipients of transplants between January 1, 1997 and December 31, 2017 at a large university hospital to assign primary and/or secondary causes of GL., Results: In 51.2% of the patients, more than one cause contributed to GL. The most frequent primary or secondary causes leading to graft failure were intercurrent medical events in 36.3% of graft failures followed by T cell-mediated rejection (TCMR) in 34% and antibody-mediated rejection (ABMR) in 30.7%. In 77.9%, a primary cause could be attributed to GL, of which ABMR was most frequent (21.5%). Many causes for GL were identified, and predominant causes for GL varied over time., Conclusions: GL is often multifactorial and more complex than previously thought., (Copyright © 2021 by the American Society of Nephrology.)
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- 2021
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35. TBase - an Integrated Electronic Health Record and Research Database for Kidney Transplant Recipients.
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Schmidt D, Osmanodja B, Pfefferkorn M, Graf V, Raschke D, Duettmann W, Naik MG, Gethmann CJ, Mayrdorfer M, Halleck F, Liefeldt L, Glander P, Staeck O, Mallach M, Peuker M, and Budde K
- Subjects
- Humans, Software, Databases, Factual, Delivery of Health Care organization & administration, Electronic Health Records organization & administration, Electronic Health Records statistics & numerical data, Kidney Transplantation, Systems Integration, Telemedicine
- Abstract
TBase is an electronic health record (EHR) for kidney transplant recipients (KTR) combining automated data entry of key clinical data (e.g., laboratory values, medical reports, radiology and pathology data) via standardized interfaces with manual data entry during routine treatment (e.g., clinical notes, medication list, and transplantation data). By this means, a comprehensive database for KTR is created with benefits for routine clinical care and research. It enables both easy everyday clinical use and quick access for research questions with highest data quality. This is achieved by the concept of data validation in clinical routine in which clinical users and patients have to rely on correct data for treatment and medication plans and thereby validate and correct the clinical data in their daily practice. This EHR is tailored for the needs of transplant outpatient care and proved its clinical utility for more than 20 years at Charité - Universitätsmedizin Berlin. It facilitates efficient routine work with well-structured, comprehensive long-term data and allows their easy use for clinical research. To this point, its functionality covers automated transmission of routine data via standardized interfaces from different hospital information systems, availability of transplant-specific data, a medication list with an integrated check for drug-drug interactions, and semi-automated generation of medical reports among others. Key elements of the latest reengineering are a robust privacy-by-design concept, modularity, and hence portability into other clinical contexts as well as usability and platform independence enabled by HTML5 (Hypertext Markup Language) based responsive web design. This allows fast and easy scalability into other disease areas and other university hospitals. The comprehensive long-term datasets are the basis for the investigation of Machine Learning algorithms, and the modular structure allows to rapidly implement these into clinical care. Patient reported data and telemedicine services are integrated into TBase in order to meet future needs of the patients. These novel features aim to improve clinical care as well as to create new research options and therapeutic interventions.
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- 2021
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36. What happens after graft loss? A large, long-term, single-center observation.
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Schrezenmeier E, Lehner LJ, Merkel M, Mayrdorfer M, Duettmann W, Naik MG, Fröhlich F, Liefeldt L, Pigorsch M, Friedersdorff F, Schmidt D, Niemann M, Lachmann N, Budde K, and Halleck F
- Subjects
- Graft Rejection, Humans, Reoperation, Retrospective Studies, Risk Factors, Graft Survival, Kidney Transplantation adverse effects
- Abstract
The number of patients returning to dialysis after graft failure increases. Surprisingly, little is known about the clinical and immunological outcomes of this cohort. We retrospectively analyzed 254 patients after kidney allograft loss between 1997 and 2017 and report clinical outcomes such as mortality, relisting, retransplantations, transplant nephrectomies, and immunization status. Of the 254 patients, 49% had died 5 years after graft loss, while 27% were relisted, 14% were on dialysis and not relisted, and only 11% were retransplanted 5 years after graft loss. In the complete observational period, 111/254 (43.7%) patients were relisted. Of these, 72.1% of patients were under 55 years of age at time of graft loss and only 13.5% of patients were ≥65 years. Age at graft loss was associated with relisting in a logistic regression analysis. In the complete observational period, 42 patients (16.5%) were retransplanted. Only 4 of those (9.5%) were ≥65 years at time of graft loss. Nephrectomy had no impact on survival, relisting, or development of dnDSA. Patients after allograft loss have a high overall mortality. Immunization contributes to long waiting times. Only a very limited number of patients are retransplanted especially when ≥65 years at time of graft loss., (© 2021 The Authors. Transplant International published by John Wiley & Sons Ltd on behalf of Steunstichting ESOT.)
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- 2021
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37. Inosine 5'-Monophosphate Dehydrogenase Activity for the Longitudinal Monitoring of Mycophenolic Acid Treatment in Kidney Allograft Recipients.
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Glander P, Waiser J, Hambach P, Bachmann F, Budde K, Eckardt KU, Friedersdorff F, Gaedeke J, Kron S, Lorkowski C, Mai M, Neumayer HH, Peters R, Rudolph B, Schmidt D, Wu K, and Liefeldt L
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Biomarkers blood, Child, Child, Preschool, Chromatography, High Pressure Liquid, Female, Graft Rejection diagnosis, Graft Rejection immunology, Humans, Immunosuppressive Agents adverse effects, Male, Middle Aged, Mycophenolic Acid adverse effects, Predictive Value of Tests, Retrospective Studies, Time Factors, Treatment Outcome, Young Adult, Drug Monitoring, Erythrocytes enzymology, Graft Rejection prevention & control, IMP Dehydrogenase blood, Immunosuppressive Agents therapeutic use, Kidney Transplantation adverse effects, Mycophenolic Acid therapeutic use
- Abstract
Background: Mycophenolic acid (MPA) is a standard immunosuppressant in organ transplantation. A simple monitoring biomarker for MPA treatment has not been established so far. Here, we describe inosine 5'-monophosphate dehydrogenase (IMPDH) monitoring in erythrocytes and its application to kidney allograft recipients., Methods: IMPDH activity measurements were performed using a high-performance liquid chromatography assay. Based on 4203 IMPDH measurements from 1021 patients, we retrospectively explored the dynamics early after treatment start. In addition, we analyzed the influence of clinically relevant variables on IMPDH activity in a multivariate model using data from 711 stable patients. Associations between IMPDH activity and clinical events were evaluated in hospitalized patients., Results: We found that IMPDH activity reflects MPA exposure after 8 weeks of constant dosing. In addition to dosage, body mass index, renal function, and coimmunosuppression affected IMPDH activity. Significantly lower IMPDH activities were found in patients with biopsy-proven acute rejection as compared to patients without rejection (median [interquartile range]: 696 [358-1484] versus 1265 [867-1618] pmol xanthosine-5'-monophosphate/h/mg hemoglobin, P < 0.001). The highest IMPDH activities were observed in hospitalized patients with clinically evident MPA toxicity as compared to patients with hospitalization not related to MPA treatment (1548 [1021-2270] versus 1072 [707-1439] pmol xanthosine-5'-monophosphate/h/mg hemoglobin; P < 0.001). Receiver operating characteristic curve analyses underlined the usefulness of IMPDH to predict rejection episodes (area, 0.662; confidence interval, 0.584-0.740; P < 0.001) and MPA-associated adverse events (area, 0.632; confidence interval, 0.581-0.683; P < 0.001), respectively., Conclusions: IMPDH measurement in erythrocytes is a novel and useful strategy for the longitudinal monitoring of MPA treatment., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2021
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38. De novo HLA-alloimmunization to a kidney allograft incidentally without anastomoses.
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Friedersdorff F, Lachmann N, and Liefeldt L
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- Allografts, Graft Survival, HLA Antigens, Kidney, Tissue Donors, Graft Rejection, Isoantibodies
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- 2021
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39. Asymptomatic secondary hyperparathyroidism can mimic sacroiliitis on computed tomography.
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Kreutzinger V, Diekhoff T, Liefeldt L, Poddubnyy D, Hermann KGA, and Ziegeler K
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- Biomarkers, Case-Control Studies, Diagnosis, Differential, Disease Susceptibility, Humans, Hyperparathyroidism, Secondary etiology, Hyperparathyroidism, Secondary metabolism, Kidney Function Tests, Observer Variation, Retrospective Studies, Sacroiliitis metabolism, Severity of Illness Index, Asymptomatic Diseases, Hyperparathyroidism, Secondary diagnosis, Sacroiliitis diagnosis, Tomography, X-Ray Computed
- Abstract
Secondary hyperparathyroidism (sHPT) as a result of chronic kidney disease (CKD) is a common health problem and has been reported to manifest at the sacroiliac joints (SIJ). The aim of this investigation was to systematically assess sacroiliac joint changes in asymptomatic sHPT as detected by high-resolution CT. Included in this IRB-approved retrospective case-control study were 56 patients with asymptomatic sHPT as well as 259 matched controls without SIJ disease. Demographic data were retrieved from electronic patient records. High-resolution computed tomography datasets of all patients were subjected to a structured scoring, including erosions, sclerosis, osteophytes, joint space alterations and intraarticular calcifications. Chi
2 tests were used to compare frequencies of lesions. Erosions were significantly more prevalent in patients with sHPT, and were found mainly in the ventral (28.6% vs. 13.9%; p = 0.016) and middle (17.9% vs. 7.7%; p = 0.040) iliac portions of the SIJ. Partial ankylosis was rare in both cohorts (3.6% vs. 5.0%; p > 0.999); complete ankylosis was not observed. Neither extent not prevalence of sclerosis or calcifications differed significantly between groups. Joint lesions reminiscent of sacroiliitis can be found in a substantial portion of asymptomatic patients with secondary hyperparathyroidism. Further investigations into the clinical significance of these findings are warranted.- Published
- 2021
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40. Does the Side Matter? A Retrospective Cohort Study Comparing Left and Right Pure Laparoscopic Donor Nephrectomies.
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Zeuschner P, Stöckle M, Peters R, Miller K, Liefeldt L, Halleck F, Budde K, Hennig L, and Friedersdorff F
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- Adult, Aged, Female, Graft Survival, Humans, Male, Middle Aged, Postoperative Complications etiology, Retrospective Studies, Risk Assessment, Risk Factors, Time Factors, Treatment Outcome, Young Adult, Kidney Transplantation adverse effects, Laparoscopy adverse effects, Living Donors, Nephrectomy adverse effects
- Abstract
Objectives: Right laparoscopic donor nephrectomy (RLDN) is no longer regarded inferior to left LDN (LLDN). However, this knowledge is based on many studies suffering from inherent learning curves, center-specific imbalances, and different laparoscopic techniques., Methods: Pure LDNs at a high-volume referral center from 2011 to 2016 were retrospectively analyzed. Patient, graft characteristics, outcomes of LDNs, and corresponding open kidney transplantations were compared between LLDN and RLDN including a follow-up., Results: 160 (78.4%) LLDNs and 44 (21.6%) RLDNs only differed regarding graft characteristics, as more right grafts had multiple veins (34.1 vs. 6.9%, p < 0.001) and worse scintigraphic function (44 vs. 51%, p < 0.001). RLDNs were shorter (201 vs. 220 min, p = 0.032) with longer warm ischemia time (165 vs. 140 s, p < 0.001), but left grafts were transplanted faster (160 vs. 171 min, p = 0.048). Recipients of right kidneys had more postoperative complications (grade 3: 25.6 vs. 11.3%, p = 0.020). At a follow-up of 45 (range 6-79) months, neither the kidney function, nor death-censored graft (5-year: LLDN 89 vs. 92%, p = 0.969) and patient survival (5-year: LLDN 95 vs. 98%, p = 0.747) differed., Conclusions: Pure LLDN and RLDN can have different outcomes at high-volume centers, especially higher complications for recipients of right grafts. However, long-term function and graft survival are the same irrespective of the chosen side., (© 2021 The Author(s). Published by S. Karger AG, Basel.)
- Published
- 2021
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41. Pan-Genotype Pre-Exposure Prophylaxis (PrEP) Allows Transplantation of HCV-Positive Donor Kidneys to Negative Transplant Recipients.
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Duerr M, Liefeldt L, Friedersdorff F, Choi M, Öllinger R, Hofmann J, Budde K, Schrezenmeier E, and Halleck F
- Abstract
Transplant candidates are facing incremental mortality risks on the waiting list. Here, we report a novel strategy to expand the donor pool by including hepatitis C seropositive (HCV+) donors. We investigated a pre-exposure prophylactic (PrEP) treatment with direct-acting antivirals (DAA) to allow transplantation for HCV seronegative (HCV-) kidney transplant recipients (KTR) with the aim to prevent HCV infection post transplantation. In this prospective trial, a pan-genotypic PrEP with daclatasvir and sofosbuvir once daily for 12 week was administered at transplantation. The primary endpoint sustained virological negativity (SVN) 12 weeks after the end of PrEP. Seven patients received a transplantation from four HCV+ donors. Accumulated waiting time was 70 ± 31.3 months already. Of note, study subjects underwent transplantation 24.7 ± 16.1 days after given consent. All KTR developed excellent graft function without any rejection episodes. One patient died with a functioning graft due to sepsis 13 months after transplantation. PrEP demonstrated efficacy with no signs of HCV transmission with excellent tolerability. Two out of four HCV+ donors were viremic at the time of explantation. Interestingly, KTR developed HCV antibodies also from non viramic donors. The acceptance of HCV+ donor was safe and reduced waiting time under the protection of PrEP DAA in kidney transplantation.
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- 2020
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42. Low Seroprevalence of SARS-CoV-2 Antibodies during Systematic Antibody Screening and Serum Responses in Patients after COVID-19 in a German Transplant Center.
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Choi M, Bachmann F, Naik MG, Duettmann W, Duerr M, Zukunft B, Schwarz T, Corman VM, Liefeldt L, Budde K, and Halleck F
- Abstract
The coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 denotes a global health issue. Data regarding COVID-19 incidence in kidney transplant recipients (KTR) are sparse. From 19 March to 19 May 2020, we performed a systematic screening for COVID-19 in KTR. Tests included serum analysis for SARS-CoV-2 antibodies using S protein-based immunofluorescence, anti-SARS-CoV-2 S1 immunoglobulin G (IgG) and immunoglobulin A (IgA) enzyme-linked immunosorbent assays (ELISA), and/or quantitative reverse transcription polymerase chain reaction (qRT-PCR) from nasal-throat swabs. Outpatient serum samples from KTR with PCR confirmed COVID-19, and swab samples from recipients (+donors) undergoing kidney transplantation were analyzed. Out of 223 samples from outpatients, 13 patients were positive with solely anti-SARS-CoV-2-IgA and 3 with both anti-IgA and anti-IgG. In total, 53 patients were symptomatic in the past, but positive results could be found in both symptomatic and asymptomatic patients. After an in depth analysis using immunofluorescence and neutralization tests in 2 KTR, recent COVID-19 infection remained highly suspicious. Apart from outpatient visits, only 5 out of 2044 KTR were symptomatic and tested positive via PCR, of which 4 recovered and one died. All patients showed seroconversion during the course of the disease. This study demonstrated a low seroprevalence in a German KTR cohort, and seroconversion of IgA and IgG after COVID-19 could be demonstrated. Effective containment strategies enabled us to continue our transplant program.
- Published
- 2020
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43. Extended Criteria Donors in Living Kidney Transplantation Including Donor Age, Smoking, Hypertension and BMI.
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Plage H, Pielka P, Liefeldt L, Budde K, Ebbing J, Sugünes N, Miller K, Cash H, Bichmann A, Sattler A, Kotsch K, and Friedersdorff F
- Abstract
Purpose: An expansion of selection criteria for deceased organ transplantation already exists to manage the current donor shortage. Comparable evaluation of risk factors for living donors should be investigated to improve this issue., Patients and Methods: Our retrospective single-centre study analysed 158 patients with living kidney transplants performed between February 2006 and June 2012. We investigated the influence of donor risk factors (RF) including body mass index over 30 kg/m
2 , age >60 years, active nicotine abuse and arterial hypertension on postoperative kidney function with focus on the recipients. This was measured for long-term survival and glomerular filtration rate (GFR) in a 5-year follow-up., Results: Overall, out of 158 living donors, 84 donors were identified to have no risk factors, whereas 74 donors had at least one risk factor. We noted a significant higher delayed graft function (p=0.042) in the first 7 days after transplantation, as well as lower GFR of recipients of allografts with risk factors in the first-year after transplantation. In our long-term results, there was no significant difference in the functional outcome (graft function, recipient and graft survival) between recipients receiving kidneys from donors with no and at least one risk factors. In the adjusted analysis of subgroups of different risk factors, recipients of donors with "age over 60 years" at time of transplantation had a decreased transplant survival (p=0.014)., Conclusion: Thus, a careful expansion for selection criteria for living donors with critical evaluation could be possible, but especially the age of the donors could be a limited risk factor., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Plage et al.)- Published
- 2020
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44. Should We Perform Old-for-Old Kidney Transplantation during the COVID-19 Pandemic? The Risk for Post-Operative Intensive Stay.
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Zeuschner P, Sester U, Stöckle M, Saar M, Zompolas I, El-Bandar N, Liefeldt L, Budde K, Öllinger R, Ritschl P, Schlomm T, Mihm J, and Friedersdorff F
- Abstract
Health care systems worldwide have been facing major challenges since the outbreak of the SARS-CoV-2 pandemic. Kidney transplantation (KT) has been tremendously affected due to limited personal protective equipment (PPE) and intensive care unit (ICU) capacities. To provide valid information on risk factors for ICU admission in a high-risk cohort of old kidney recipients from old donors in the Eurotransplant Senior Program (ESP), we retrospectively conducted a bi-centric analysis. Overall, 17 (16.2%) patients out of 105 KTs were admitted to the ICU. They had a lower BMI, and both coronary artery disease (CAD) and hypertensive nephropathy were more frequent. A risk model combining BMI, CAD and hypertensive nephropathy gained a sensitivity of 94.1% and a negative predictive value of 97.8%, rendering it a valuable search test, but with low specificity (51.1%). ICU admission also proved to be an excellent parameter identifying patients at risk for short patient and graft survivals. Patients admitted to the ICU had shorter patient (1-year 57% vs. 90%) and graft (5-year 49% vs. 77%) survival. To conclude, potential kidney recipients with a low BMI, CAD and hypertensive nephropathy should only be transplanted in the ESP in times of SARS-CoV-2 pandemic if the local health situation can provide sufficient ICU capacities.
- Published
- 2020
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45. Robot-Assisted versus Laparoscopic Donor Nephrectomy: A Comparison of 250 Cases.
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Zeuschner P, Hennig L, Peters R, Saar M, Linxweiler J, Siemer S, Magheli A, Kramer J, Liefeldt L, Budde K, Schlomm T, Stöckle M, and Friedersdorff F
- Abstract
Living kidney donation is the best treatment for end-stage renal disease, however, the best surgical approach for minimally-invasive donor nephrectomy (DN) is still a matter of debate. This bi-centric study aimed to retrospectively compare perioperative outcomes and postoperative kidney function after 257 transperitoneal DNs including 52 robot-assisted (RDN) and 205 laparoscopic DNs (LDN). As primary outcomes, the intraoperative (operating time, warm ischemia time (WIT), major complications) and postoperative (length of stay, complications) results were compared. As secondary outcomes, postoperative kidney and graft function were analyzed including delayed graft function (DGF) rates, and the impact of the surgical approach was assessed. Overall, the type of minimally-invasive donor nephrectomy (RDN vs. LDN) did not affect primary outcomes, especially not operating time and WIT; and major complication and DGF rates were low in both groups. A history of smoking and preoperative kidney function, but not the surgical approach, were predictive for postoperative serum creatinine of the donor and recipient. To conclude, RDN and LDN have equivalent perioperative results in experienced centers. For this reason, not the surgical approach, but rather the graft- (preoperative kidney function) and patient-specific (history of smoking) aspects impacted postoperative kidney function.
- Published
- 2020
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46. Predictors of graft survival at diagnosis of antibody-mediated renal allograft rejection: a retrospective single-center cohort study.
- Author
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Waiser J, Klotsche J, Lachmann N, Wu K, Rudolph B, Halleck F, Liefeldt L, Bachmann F, Budde K, and Duerr M
- Subjects
- Allografts, Bortezomib therapeutic use, Cyclophosphamide therapeutic use, Glomerular Filtration Rate, Humans, Immunoglobulins, Intravenous therapeutic use, Retrospective Studies, Rituximab therapeutic use, Graft Rejection, Graft Survival, Kidney Transplantation adverse effects
- Abstract
Antibody-mediated rejection (ABMR) is a major cause of graft loss in renal transplantation. We assessed the predictive value of clinical, pathological, and immunological parameters at diagnosis for graft survival. We investigated 54 consecutive patients with biopsy-proven ABMR. Patients were treated according to our current standard regimen followed by triple maintenance immunosuppression. Patient characteristics, renal function, and HLA antibody status at diagnosis, baseline biopsy results, and immunosuppressive treatment were recorded. The risk of graft loss at 24 months after diagnosis and the eGFR slope were assessed. Multivariate analysis showed that eGFR at diagnosis and chronic glomerulopathy independently predict graft loss (HR 0.94; P = 0.018 and HR 1.57; P = 0.045) and eGFR slope (beta 0.46; P < 0.001 and beta -5.47; P < 0.001). Cyclophosphamide treatment (6× 15 mg/m
2 ) plus high-dose intravenous immunoglobulins (IVIG) (1.5 g/kg) was superior compared with single-dose rituximab (1× 500 mg) plus low-dose IVIG (30 g) (HR 0.10; P = 0.008 and beta 10.70; P = 0.017) and one cycle of bortezomib (4× 1.3 mg/m2 ) plus low-dose IVIG (HR 0.16; P = 0.049 and beta 11.21; P = 0.010) regarding the risk of graft loss and the eGFR slope. In conclusion, renal function at diagnosis and histopathological signs of chronic ABMR seem to predict graft survival independent of the applied treatment regimen. Stepwise modifications of the treatment regimen may help to improve outcome., (© 2019 Steunstichting ESOT.)- Published
- 2020
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47. Is a Retroaortic Vein a Risk Factor in Laparoscopic Living Donor Nephrectomy?
- Author
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Mang J, Hennig L, Biernath N, Liefeldt L, Bichmann A, Ralla B, Maxeiner A, Peters R, Cash H, Budde K, and Friedersdorff F
- Subjects
- Adolescent, Adult, Aorta, Abdominal, Female, Humans, Living Donors, Male, Middle Aged, Retrospective Studies, Risk Factors, Young Adult, Kidney Transplantation, Laparoscopy, Nephrectomy methods, Renal Veins abnormalities, Tissue and Organ Harvesting methods
- Abstract
Introduction: In living donor transplantation choosing the right donor and donor side for laparoscopic donor nephrectomy is a challenging task in clinical practice. Knowledge about anomalies in renal blood supply are crucial to evaluate the feasibility of the operative procedure. Few data so far exist whether the existence of a retroaortic left renal vein has an impact on living kidney transplantation outcome for donor and recipient., Materials and Methods: We retrospectively analyzed 221 patients who underwent laparoscopic living donor nephrectomy between 2011 and 2017 for existence of a retroaortic left renal vein. Clinical characteristics and operative outcomes for donors and recipients were analyzed., Results: 221 patients underwent donor nephrectomy between 2011 and 2017; 11 patients (4.98%) showed the feature of a retroaortic left renal vein, and in 8 patients (72.7%) out of those 11 the left kidney was chosen for transplantation. Mean preoperative serum creatinine was 0.77 (0.49-0.98) mg/dL and 1.28 (0.97-1.64) mg/dL at discharge. In recipients mean serum creatinine preoperatively, after 1 week, 1 month,1 year, 2 and 3 years of follow-up was 10.36 (6.09-20.77) mg/dL, 1.71 (0.67-2.72), 1.33 (0.70-1.89), 1.31 (0.95-2.13), 1.31 (0.98-2.13) and 1.33 (1.03-1.84), respectively. Neither donors nor recipients suffered from any operative complications., Conclusions: Laparoscopic living donor nephrectomy of a left kidney with retroaortic renal vein is safe for the donor, without limitation in the outcome for the recipient., (© 2020 The Author(s) Published by S. Karger AG, Basel.)
- Published
- 2020
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48. Native Nephrectomy before and after Renal Transplantation in Patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD).
- Author
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Maxeiner A, Bichmann A, Oberländer N, El-Bandar N, Sugünes N, Ralla B, Biernath N, Liefeldt L, Budde K, Giessing M, Schlomm T, and Friedersdorff F
- Abstract
The aim of this study was 1) to evaluate and compare pre-, peri-, and post-operative data of Autosomal Dominant Polycystic Kidney Disease (ADPKD) patients undergoing native nephrectomy (NN) either before or after renal transplantation and 2) to identify advantages of optimal surgical timing, postoperative outcomes, and economical aspects in a tertiary transplant centre. This retrospective analysis included 121 patients divided into two groups-group 1: patients who underwent NN prior to receiving a kidney transplant ( n = 89) and group 2: patients who underwent NN post-transplant ( n = 32). Data analysis was performed according to demographic patient details, surgical indication, laboratory parameters, perioperative complications, underlying pathology, and associated mortality. There was no significant difference in patient demographics between the groups, however right-sided nephrectomy was performed predominantly within group 1. The main indication in both groups undergoing a nephrectomy was pain. Patients among group 2 had no postoperative kidney failure and a significantly shorter hospital stay. Higher rates of more severe complications were observed in group 1, even though this was not statistically significant. Even though the differences between both groups were substantial, the time of NN prior or post-transplant does not seem to affect short-term and long-term transplantation outcomes. Retroperitoneal NN remains a low risk treatment option in patients with symptomatic ADPKD and can be performed either pre- or post-kidney transplantation depending on patients' symptom severity.
- Published
- 2019
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49. Analysis of the Effects of Day-Time vs. Night-Time Surgery on Renal Transplant Patient Outcomes.
- Author
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Sugünes N, Bichmann A, Biernath N, Peters R, Budde K, Liefeldt L, Schlomm T, and Friedersdorff F
- Abstract
Sleep deprivation and disruption of the circadian rhythms could impair individual surgical performance and decision making. For this purpose, this study identified potential confounding factors on surgical renal transplant patient outcomes during day and night. Our retrospective cohort study of 215 adult renal cadaver transplant recipients, of which 132 recipients were allocated in the "day-time" group and 83 recipients in the "night-time" group, primarily stratified the patients into two cohorts, depending on the start time. Within a 24 h operational system, "day-time" was considered as being from 8 a.m. to 8 p.m. and "night-time" from 8 p.m. to 8 a.m.. Primary outcomes examined patient and graft survival after three months and one year. Secondary outcomes included the presence of acute rejection (AR) and delayed graft function (DGF), as well as the rate of postoperative complications. In log-rank testing, "day-time" surgery was associated with a significantly higher risk of patient death ( p = 0.003), whereas long-term graft survival was unaffected by the operative time of day. The mean cold ischemia time (CIT), which was 12.4 ± 5.3 h in the "night-time" group, was significantly longer compared to 10.7 ± 3.6 for those during the day ( p = 0.01). We observed that "night-time" kidney recipients experienced more wound complications. From our single-centre data, we conclude that night-time kidney transplantation does not increase the risk of adverse events or predispose the patient to a worse outcome. Nevertheless, further research is required to explore the effect of fatigue on nocturnal surgical performance.
- Published
- 2019
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50. Perioperative antibiotic prophylaxis in renal transplantation: a single-center comparison between two regimens and a brief survey among the Eurotransplant renal transplantation centers.
- Author
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Bachmann F, Adam T, Friedersdorff F, Liefeldt L, Slowinski T, Budde K, and Waiser J
- Subjects
- Adult, Aged, Ampicillin therapeutic use, Cefazolin therapeutic use, Escherichia coli Infections epidemiology, Europe, Female, Floxacillin therapeutic use, Humans, Male, Middle Aged, Perioperative Care, Piperacillin therapeutic use, Postoperative Complications epidemiology, Retrospective Studies, Sepsis epidemiology, Sex Factors, Sulbactam therapeutic use, Surveys and Questionnaires, Urinary Tract Infections epidemiology, Anti-Bacterial Agents therapeutic use, Antibiotic Prophylaxis methods, Kidney Transplantation methods, Surgical Wound Infection prevention & control
- Abstract
Background: Perioperative antibiotic prophylaxis (PAP) is an integral part of kidney transplantation to prevent surgical site infections (SSI). In July 2015, we changed our standard from a multiple-dose to a single-dose (SD) prophylaxis. Here, we report on results with both regimens and a related survey among Eurotransplant renal transplantation centers., Methods: From July 2015, all kidney graft recipients of our center were scheduled to receive SD i.v. cefazolin (group SD, n = 107). They were compared to patients, transplanted since January 2014, receiving our previous standard (i.v. piperacillin/flucloxacillin) until postoperative day (POD) 7, plus oral sultamicillin until POD 10 (group MD, n = 105). The primary endpoint was the number of SSIs during a 3-month observational period., Results: The frequency of SSI episodes was generally low (group SD vs. MD: 2 vs. 4, p = 0.40). Of note, urinary tract infections occurred in 40 SD vs. 36 MD patients, respectively (p = 0.60). Urinary tract infections were caused by Escherichia coli in 36.8%. Female gender was the only independent risk factor on multivariate analysis (p = 0.002). In addition, 12 episodes of urosepsis in both groups occurred. All-cause infection with multi-resistant bacteria occurred less frequently in SD vs. MD patients (3.7% vs. 8.6%, p = 0.16). A majority of Eurotransplant centers used i.v. single-dose cephalosporins (36.9%), although substances and duration varied remarkably., Conclusion: Single-dose cefazolin was equally effective and less expensive compared to our previous MD regimen. Based on these findings, we conclude that future prospective studies should be designed to confirm the non-inferiority of single-dose antibiotic regimens.
- Published
- 2019
- Full Text
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