Skip to main content
Erschienen in: Clinical and Experimental Nephrology 4/2017

21.10.2016 | Original article

The potential role of perivascular lymphatic vessels in preservation of kidney allograft function

verfasst von: Akihiro Tsuchimoto, Toshiaki Nakano, Shoko Hasegawa, Kosuke Masutani, Yuta Matsukuma, Masahiro Eriguchi, Masaharu Nagata, Takehiro Nishiki, Hidehisa Kitada, Masao Tanaka, Takanari Kitazono, Kazuhiko Tsuruya

Erschienen in: Clinical and Experimental Nephrology | Ausgabe 4/2017

Einloggen, um Zugang zu erhalten

Abstract

Background

Lymphangiogenesis occurs in diseased native kidneys and kidney allografts, and correlates with histological injury; however, the clinical significance of lymphatic vessels in kidney allografts is unclear.

Methods

This study retrospectively reviewed 63 kidney transplant patients who underwent protocol biopsies. Lymphatic vessels were identified by immunohistochemical staining for podoplanin, and were classified according to their location as perivascular or interstitial lymphatic vessels. The associations between perivascular lymphatic density and kidney allograft function and pathological findings were analyzed.

Results

There were no significant differences in perivascular lymphatic densities in kidney allograft biopsy specimens obtained at 0 h, 3 months and 12 months. The groups with higher perivascular lymphatic density showed a lower proportion of progression of interstitial fibrosis/tubular atrophy grade from 3 to 12 months (P for trend = 0.039). Perivascular lymphatic density was significantly associated with annual decline of estimated glomerular filtration rate after 12 months (r = −0.31, P = 0.017), even after adjusting for multiple confounders (standardized β = −0.30, P = 0.019).

Conclusions

High perivascular lymphatic density is associated with favourable kidney allograft function. The perivascular lymphatic network may be involved in inhibition of allograft fibrosis and stabilization of graft function.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Howard RJ, Patton PR, Reed AI, Hemming AW, Van der Werf WJ, Pfaff WW, et al. The changing causes of graft loss and death after kidney transplantation. Transplantation. 2002;73:1923–8.CrossRefPubMed Howard RJ, Patton PR, Reed AI, Hemming AW, Van der Werf WJ, Pfaff WW, et al. The changing causes of graft loss and death after kidney transplantation. Transplantation. 2002;73:1923–8.CrossRefPubMed
2.
Zurück zum Zitat Teraoka S, Nomoto K, Kikuchi K, Hirano T, Satomi S, Hasegawa A, et al. Outcomes of kidney transplants from non-heart-beating deceased donors as reported to the Japan Organ Transplant Network from April 1995–December 2003: a multi-center report. Clin Transpl. 2004;91–102. Teraoka S, Nomoto K, Kikuchi K, Hirano T, Satomi S, Hasegawa A, et al. Outcomes of kidney transplants from non-heart-beating deceased donors as reported to the Japan Organ Transplant Network from April 1995–December 2003: a multi-center report. Clin Transpl. 2004;91–102.
3.
Zurück zum Zitat Nankivell BJ, Borrows RJ, Fung CL, O’Connell PJ, Allen RD, Chapman JR. The natural history of chronic allograft nephropathy. N Engl J Med. 2003;349:2326–33.CrossRefPubMed Nankivell BJ, Borrows RJ, Fung CL, O’Connell PJ, Allen RD, Chapman JR. The natural history of chronic allograft nephropathy. N Engl J Med. 2003;349:2326–33.CrossRefPubMed
4.
Zurück zum Zitat Chapman JR, O’Connell PJ, Nankivell BJ. Chronic renal allograft dysfunction. J Am Soc Nephrol. 2005;16:3015–26.CrossRefPubMed Chapman JR, O’Connell PJ, Nankivell BJ. Chronic renal allograft dysfunction. J Am Soc Nephrol. 2005;16:3015–26.CrossRefPubMed
5.
Zurück zum Zitat Joosten SA, Sijpkens YW, van Kooten C, Paul LC. Chronic renal allograft rejection: pathophysiologic considerations. Kidney Int. 2005;68:1–13.CrossRefPubMed Joosten SA, Sijpkens YW, van Kooten C, Paul LC. Chronic renal allograft rejection: pathophysiologic considerations. Kidney Int. 2005;68:1–13.CrossRefPubMed
6.
Zurück zum Zitat Adair A, Mitchell DR, Kipari T, Qi F, Bellamy CO, Robertson F, et al. Peritubular capillary rarefaction and lymphangiogenesis in chronic allograft failure. Transplantation. 2007;83:1542–50.CrossRefPubMed Adair A, Mitchell DR, Kipari T, Qi F, Bellamy CO, Robertson F, et al. Peritubular capillary rarefaction and lymphangiogenesis in chronic allograft failure. Transplantation. 2007;83:1542–50.CrossRefPubMed
7.
Zurück zum Zitat Kerjaschki D, Regele HM, Moosberger I, Nagy-Bojarski K, Watschinger B, Soleiman A, et al. Lymphatic neoangiogenesis in human kidney transplants is associated with immunologically active lymphocytic infiltrates. J Am Soc Nephrol. 2004;15:603–12.CrossRefPubMed Kerjaschki D, Regele HM, Moosberger I, Nagy-Bojarski K, Watschinger B, Soleiman A, et al. Lymphatic neoangiogenesis in human kidney transplants is associated with immunologically active lymphocytic infiltrates. J Am Soc Nephrol. 2004;15:603–12.CrossRefPubMed
8.
Zurück zum Zitat Saaristo A, Tammela T, Farkkila A, Karkkainen M, Suominen E, Yla-Herttuala S, et al. Vascular endothelial growth factor-C accelerates diabetic wound healing. Am J Pathol. 2006;169:1080–7.CrossRefPubMedPubMedCentral Saaristo A, Tammela T, Farkkila A, Karkkainen M, Suominen E, Yla-Herttuala S, et al. Vascular endothelial growth factor-C accelerates diabetic wound healing. Am J Pathol. 2006;169:1080–7.CrossRefPubMedPubMedCentral
9.
Zurück zum Zitat Baluk P, Tammela T, Ator E, Lyubynska N, Achen MG, Hicklin DJ, et al. Pathogenesis of persistent lymphatic vessel hyperplasia in chronic airway inflammation. J Clin Investig. 2005;115:247–57.CrossRefPubMedPubMedCentral Baluk P, Tammela T, Ator E, Lyubynska N, Achen MG, Hicklin DJ, et al. Pathogenesis of persistent lymphatic vessel hyperplasia in chronic airway inflammation. J Clin Investig. 2005;115:247–57.CrossRefPubMedPubMedCentral
10.
11.
Zurück zum Zitat Thaunat O, Patey N, Morelon E, Michel JB, Nicoletti A. Lymphoid neogenesis in chronic rejection: the murderer is in the house. Curr Opin Immunol. 2006;18:576–9.CrossRefPubMed Thaunat O, Patey N, Morelon E, Michel JB, Nicoletti A. Lymphoid neogenesis in chronic rejection: the murderer is in the house. Curr Opin Immunol. 2006;18:576–9.CrossRefPubMed
12.
Zurück zum Zitat Vass DG, Hughes J, Marson LP. Restorative and rejection-associated lymphangiogenesis after renal transplantation: friend or foe? Transplantation. 2009;88:1237–9.CrossRefPubMed Vass DG, Hughes J, Marson LP. Restorative and rejection-associated lymphangiogenesis after renal transplantation: friend or foe? Transplantation. 2009;88:1237–9.CrossRefPubMed
13.
Zurück zum Zitat Seeger H, Bonani M, Segerer S. The role of lymphatics in renal inflammation. Nephrol Dial Transplant. 2012;27:2634–41.CrossRefPubMed Seeger H, Bonani M, Segerer S. The role of lymphatics in renal inflammation. Nephrol Dial Transplant. 2012;27:2634–41.CrossRefPubMed
14.
Zurück zum Zitat Stuht S, Gwinner W, Franz I, Schwarz A, Jonigk D, Kreipe H, et al. Lymphatic neoangiogenesis in human renal allografts: results from sequential protocol biopsies. Am J Transplant. 2007;7:377–84.CrossRefPubMed Stuht S, Gwinner W, Franz I, Schwarz A, Jonigk D, Kreipe H, et al. Lymphatic neoangiogenesis in human renal allografts: results from sequential protocol biopsies. Am J Transplant. 2007;7:377–84.CrossRefPubMed
15.
Zurück zum Zitat Solez K, Colvin RB, Racusen LC, Haas M, Sis B, Mengel M, et al. Banff 07 classification of renal allograft pathology: updates and future directions. Am J Transplant. 2008;8:753–60.CrossRefPubMed Solez K, Colvin RB, Racusen LC, Haas M, Sis B, Mengel M, et al. Banff 07 classification of renal allograft pathology: updates and future directions. Am J Transplant. 2008;8:753–60.CrossRefPubMed
16.
Zurück zum Zitat Tsuchimoto A, Masutani K, Haruyama N, Nagata M, Noguchi H, Okabe Y, et al. Renal interstitial fibrosis in 0-hour biopsy as a predictor of post-transplant anemia. Am J Nephrol. 2013;38:267–74.CrossRefPubMed Tsuchimoto A, Masutani K, Haruyama N, Nagata M, Noguchi H, Okabe Y, et al. Renal interstitial fibrosis in 0-hour biopsy as a predictor of post-transplant anemia. Am J Nephrol. 2013;38:267–74.CrossRefPubMed
17.
Zurück zum Zitat Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, et al. Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis. 2009;53:982–92.CrossRefPubMed Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, et al. Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis. 2009;53:982–92.CrossRefPubMed
18.
Zurück zum Zitat Schwartz GJ, Brion LP, Spitzer A. The use of plasma creatinine concentration for estimating glomerular filtration rate in infants, children, and adolescents. Pediatr Clin North Am. 1987;34:571–90.CrossRefPubMed Schwartz GJ, Brion LP, Spitzer A. The use of plasma creatinine concentration for estimating glomerular filtration rate in infants, children, and adolescents. Pediatr Clin North Am. 1987;34:571–90.CrossRefPubMed
19.
Zurück zum Zitat Nakano T, Nakashima Y, Yonemitsu Y, Sumiyoshi S, Chen YX, Akishima Y, et al. Angiogenesis and lymphangiogenesis and expression of lymphangiogenic factors in the atherosclerotic intima of human coronary arteries. Hum Pathol. 2005;36:330–40.CrossRefPubMed Nakano T, Nakashima Y, Yonemitsu Y, Sumiyoshi S, Chen YX, Akishima Y, et al. Angiogenesis and lymphangiogenesis and expression of lymphangiogenic factors in the atherosclerotic intima of human coronary arteries. Hum Pathol. 2005;36:330–40.CrossRefPubMed
20.
Zurück zum Zitat Sakamoto I, Ito Y, Mizuno M, Suzuki Y, Sawai A, Tanaka A, et al. Lymphatic vessels develop during tubulointerstitial fibrosis. Kidney Int. 2009;75:828–38.CrossRefPubMed Sakamoto I, Ito Y, Mizuno M, Suzuki Y, Sawai A, Tanaka A, et al. Lymphatic vessels develop during tubulointerstitial fibrosis. Kidney Int. 2009;75:828–38.CrossRefPubMed
21.
Zurück zum Zitat Zimmer JK, Dahdal S, Muhlfeld C, Bergmann IP, Gugger M, Huynh-Do U. Lymphangiogenesis is upregulated in kidneys of patients with multiple myeloma. Anat Rec. 2010;293:1497–505.CrossRef Zimmer JK, Dahdal S, Muhlfeld C, Bergmann IP, Gugger M, Huynh-Do U. Lymphangiogenesis is upregulated in kidneys of patients with multiple myeloma. Anat Rec. 2010;293:1497–505.CrossRef
22.
Zurück zum Zitat Yamamoto I, Yamaguchi Y, Yamamoto H, Hosoya T, Horita S, Tanabe K, et al. A pathological analysis of lymphatic vessels in early renal allograft. Transplant Proc. 2006;38:3300–3.CrossRefPubMed Yamamoto I, Yamaguchi Y, Yamamoto H, Hosoya T, Horita S, Tanabe K, et al. A pathological analysis of lymphatic vessels in early renal allograft. Transplant Proc. 2006;38:3300–3.CrossRefPubMed
23.
Zurück zum Zitat Xu X, Han Y, Wang Q, Cai M, Qian Y, Wang X, et al. Characterisation of tertiary lymphoid organs in explanted rejected donor kidneys. Immunol Investig. 2016;45:38–51.CrossRef Xu X, Han Y, Wang Q, Cai M, Qian Y, Wang X, et al. Characterisation of tertiary lymphoid organs in explanted rejected donor kidneys. Immunol Investig. 2016;45:38–51.CrossRef
24.
Zurück zum Zitat Suzuki Y, Ito Y, Mizuno M, Kinashi H, Sawai A, Noda Y, et al. Transforming growth factor-beta induces vascular endothelial growth factor-C expression leading to lymphangiogenesis in rat unilateral ureteral obstruction. Kidney Int. 2012;81:865–79.CrossRefPubMed Suzuki Y, Ito Y, Mizuno M, Kinashi H, Sawai A, Noda Y, et al. Transforming growth factor-beta induces vascular endothelial growth factor-C expression leading to lymphangiogenesis in rat unilateral ureteral obstruction. Kidney Int. 2012;81:865–79.CrossRefPubMed
26.
Zurück zum Zitat Cursiefen C, Chen L, Borges LP, Jackson D, Cao J, Radziejewski C, et al. VEGF-A stimulates lymphangiogenesis and hemangiogenesis in inflammatory neovascularization via macrophage recruitment. J Clin Investig. 2004;113:1040–50.CrossRefPubMedPubMedCentral Cursiefen C, Chen L, Borges LP, Jackson D, Cao J, Radziejewski C, et al. VEGF-A stimulates lymphangiogenesis and hemangiogenesis in inflammatory neovascularization via macrophage recruitment. J Clin Investig. 2004;113:1040–50.CrossRefPubMedPubMedCentral
27.
Zurück zum Zitat Yao LC, Baluk P, Feng J, McDonald DM. Steroid-resistant lymphatic remodeling in chronically inflamed mouse airways. Am J Pathol. 2010;176:1525–41.CrossRefPubMedPubMedCentral Yao LC, Baluk P, Feng J, McDonald DM. Steroid-resistant lymphatic remodeling in chronically inflamed mouse airways. Am J Pathol. 2010;176:1525–41.CrossRefPubMedPubMedCentral
29.
Zurück zum Zitat Mackay CR, Marston WL, Dudler L. Naive and memory T cells show distinct pathways of lymphocyte recirculation. J Exp Med. 1990;171:801–17.CrossRefPubMed Mackay CR, Marston WL, Dudler L. Naive and memory T cells show distinct pathways of lymphocyte recirculation. J Exp Med. 1990;171:801–17.CrossRefPubMed
30.
Zurück zum Zitat Martinez de la Torre Y, Locati M, Buracchi C, Dupor J, Cook DN, Bonecchi R, et al. Increased inflammation in mice deficient for the chemokine decoy receptor D6. Eur J Immunol. 2005;35:1342–6.CrossRefPubMed Martinez de la Torre Y, Locati M, Buracchi C, Dupor J, Cook DN, Bonecchi R, et al. Increased inflammation in mice deficient for the chemokine decoy receptor D6. Eur J Immunol. 2005;35:1342–6.CrossRefPubMed
31.
Zurück zum Zitat Segerer S, Jedlicka J, Wuthrich RP. Atypical chemokine receptors in renal inflammation. Nephron Exp Nephrol. 2010;115:e89–95.CrossRefPubMed Segerer S, Jedlicka J, Wuthrich RP. Atypical chemokine receptors in renal inflammation. Nephron Exp Nephrol. 2010;115:e89–95.CrossRefPubMed
32.
Zurück zum Zitat Wilcox CS, Sterzel RB, Dunckel PT, Mohrmann M, Perfetto M. Renal interstitial pressure and sodium excretion during hilar lymphatic ligation. Am J Physiol. 1984;247:F344–51.PubMed Wilcox CS, Sterzel RB, Dunckel PT, Mohrmann M, Perfetto M. Renal interstitial pressure and sodium excretion during hilar lymphatic ligation. Am J Physiol. 1984;247:F344–51.PubMed
33.
Zurück zum Zitat Zhang T, Guan G, Liu G, Sun J, Chen B, Li X, et al. Disturbance of lymph circulation develops renal fibrosis in rats with or without contralateral nephrectomy. Nephrology (Carlton). 2008;13:128–38.CrossRef Zhang T, Guan G, Liu G, Sun J, Chen B, Li X, et al. Disturbance of lymph circulation develops renal fibrosis in rats with or without contralateral nephrectomy. Nephrology (Carlton). 2008;13:128–38.CrossRef
Metadaten
Titel
The potential role of perivascular lymphatic vessels in preservation of kidney allograft function
verfasst von
Akihiro Tsuchimoto
Toshiaki Nakano
Shoko Hasegawa
Kosuke Masutani
Yuta Matsukuma
Masahiro Eriguchi
Masaharu Nagata
Takehiro Nishiki
Hidehisa Kitada
Masao Tanaka
Takanari Kitazono
Kazuhiko Tsuruya
Publikationsdatum
21.10.2016
Verlag
Springer Japan
Erschienen in
Clinical and Experimental Nephrology / Ausgabe 4/2017
Print ISSN: 1342-1751
Elektronische ISSN: 1437-7799
DOI
https://doi.org/10.1007/s10157-016-1338-9

Weitere Artikel der Ausgabe 4/2017

Clinical and Experimental Nephrology 4/2017 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.