Skip to main content
Top

Open Access 03-02-2025 | Review

Moving toward a better understanding of renal lymphatics: challenges and opportunities

Authors: Jianyong Zhong, Jing Liu, Ashley L. Mutchler, Haichun Yang, Annet Kirabo, Elaine L. Shelton, Valentina Kon

Published in: Pediatric Nephrology

Login to get access

Abstract

The development of lymphatic-specific markers has enabled detailed visualization of the lymphatic vascular network that has greatly enhanced our ability to explore this often-overlooked system. Lymphatics remove fluid, solutes, macromolecules, and cells from the interstitium and return them to circulation. The kidneys have lymphatics. As in other organs, the kidney lymphatic vessels are highly sensitive to changes in the local microenvironment. The sensitivity to its milieu may be especially relevant in kidneys because they are central in regulating fluid homeostasis and clearance of metabolites delivered into and eliminated from the renal interstitial compartment. Numerous physiologic conditions and diseases modify the renal interstitial volume, pressure, and composition that can, in turn, influence the growth and function of the renal lymphatics. The impact of the renal microenvironment is further heightened by the fact that kidneys are encapsulated. This review considers the development, structure, and function of the renal lymphatic vessels and explores how factors within the kidney interstitial compartment modify their structure and functionality. Moreover, although currently there are no pharmaceutical agents that specifically target the lymphatic network, we highlight several medications currently used in children with kidney disease and hypertension that have significant but underappreciated effects on lymphatics.

Graphical abstract

Appendix
Available only for authorised users
Literature
1.
go back to reference Donnan MD, Kenig-Kozlovsky Y, Quaggin SE (2021) The lymphatics in kidney health and disease. Nat Rev Nephrol 17:655–675PubMedCrossRef Donnan MD, Kenig-Kozlovsky Y, Quaggin SE (2021) The lymphatics in kidney health and disease. Nat Rev Nephrol 17:655–675PubMedCrossRef
3.
go back to reference Rossitto G, Bertoldi G, Rutkowski JM, Mitchell BM, Delles C (2024) Sodium, interstitium, lymphatics and hypertension-a tale of hydraulics. Hypertension 81:727–737PubMedCrossRef Rossitto G, Bertoldi G, Rutkowski JM, Mitchell BM, Delles C (2024) Sodium, interstitium, lymphatics and hypertension-a tale of hydraulics. Hypertension 81:727–737PubMedCrossRef
4.
go back to reference Russell PS, Itkin M, Windsor JA, Phillips ARJ (2023) Kidney lymphatics. Compr Physiol 13:4945–4984PubMedCrossRef Russell PS, Itkin M, Windsor JA, Phillips ARJ (2023) Kidney lymphatics. Compr Physiol 13:4945–4984PubMedCrossRef
6.
go back to reference Ishikawa Y, Akasaka Y, Kiguchi H, Akishima-Fukasawa Y, Hasegawa T, Ito K, Kimura-Matsumoto M, Ishiguro S, Morita H, Sato S (2006) The human renal lymphatics under normal and pathological conditions. Histopathology 49:265–273PubMedCrossRef Ishikawa Y, Akasaka Y, Kiguchi H, Akishima-Fukasawa Y, Hasegawa T, Ito K, Kimura-Matsumoto M, Ishiguro S, Morita H, Sato S (2006) The human renal lymphatics under normal and pathological conditions. Histopathology 49:265–273PubMedCrossRef
7.
go back to reference O’Morchoe CC, Omorchoe PJ, Donati EJ (1975) Comparison of hilar and capsular renal lymph. Am J Physiol 229:416–421PubMedCrossRef O’Morchoe CC, Omorchoe PJ, Donati EJ (1975) Comparison of hilar and capsular renal lymph. Am J Physiol 229:416–421PubMedCrossRef
8.
go back to reference Sakamoto I, Ito Y, Mizuno M, Suzuki Y, Sawai A, Tanaka A, Maruyama S, Takei Y, Yuzawa Y, Matsuo S (2009) Lymphatic vessels develop during tubulointerstitial fibrosis. Kidney Int 75:828–838PubMedCrossRef Sakamoto I, Ito Y, Mizuno M, Suzuki Y, Sawai A, Tanaka A, Maruyama S, Takei Y, Yuzawa Y, Matsuo S (2009) Lymphatic vessels develop during tubulointerstitial fibrosis. Kidney Int 75:828–838PubMedCrossRef
9.
go back to reference Creed HA, Kannan S, Tate BL, Godefroy D, Banerjee P, Mitchell BM, Brakenhielm E, Chakraborty S, Rutkowski JM (2024) Single-cell RNA sequencing identifies response of renal lymphatic endothelial cells to acute kidney injury. J Am Soc Nephrol 35:549–565PubMedCrossRef Creed HA, Kannan S, Tate BL, Godefroy D, Banerjee P, Mitchell BM, Brakenhielm E, Chakraborty S, Rutkowski JM (2024) Single-cell RNA sequencing identifies response of renal lymphatic endothelial cells to acute kidney injury. J Am Soc Nephrol 35:549–565PubMedCrossRef
10.
11.
go back to reference Albertine KH, O’Morchoe CC (1981) An ultrastructural study of the transport pathways across arcuate, interlobar, hilar, and capsular lymphatics in the dog kidney. Microvasc Res 21:351–361PubMedCrossRef Albertine KH, O’Morchoe CC (1981) An ultrastructural study of the transport pathways across arcuate, interlobar, hilar, and capsular lymphatics in the dog kidney. Microvasc Res 21:351–361PubMedCrossRef
12.
go back to reference Cuttino JT Jr, Clark RL, Jennette JC (1989) Microradiographic demonstration of human intrarenal microlymphatic pathways. Urol Radiol 11:83–87PubMedCrossRef Cuttino JT Jr, Clark RL, Jennette JC (1989) Microradiographic demonstration of human intrarenal microlymphatic pathways. Urol Radiol 11:83–87PubMedCrossRef
13.
go back to reference Kenig-Kozlovsky Y, Scott RP, Onay T, Carota IA, Thomson BR, Gil HJ, Ramirez V, Yamaguchi S, Tanna CE, Heinen S (2018) Ascending vasa recta are angiopoietin/Tie2-dependent lymphatic-like vessels. J Am Soc Nephrol 29:1097–1107PubMedCrossRef Kenig-Kozlovsky Y, Scott RP, Onay T, Carota IA, Thomson BR, Gil HJ, Ramirez V, Yamaguchi S, Tanna CE, Heinen S (2018) Ascending vasa recta are angiopoietin/Tie2-dependent lymphatic-like vessels. J Am Soc Nephrol 29:1097–1107PubMedCrossRef
14.
go back to reference Huang JL, Woolf AS, Kolatsi-Joannou M, Baluk P, Sandford RN, Peters DJ, McDonald DM, Price KL, Winyard PJ, Long DA (2016) Vascular endothelial growth factor C for polycystic kidney diseases. J Am Soc Nephrol 27:69–77PubMedCrossRef Huang JL, Woolf AS, Kolatsi-Joannou M, Baluk P, Sandford RN, Peters DJ, McDonald DM, Price KL, Winyard PJ, Long DA (2016) Vascular endothelial growth factor C for polycystic kidney diseases. J Am Soc Nephrol 27:69–77PubMedCrossRef
15.
go back to reference Donnan MD, Deb DK, Onay T, Scott RP, Ni E, Zhou Y, Quaggin SE (2023) Formation of the glomerular microvasculature is regulated by VEGFR-3. Am J Physiol Renal Physiol 324:F91–F105PubMedCrossRef Donnan MD, Deb DK, Onay T, Scott RP, Ni E, Zhou Y, Quaggin SE (2023) Formation of the glomerular microvasculature is regulated by VEGFR-3. Am J Physiol Renal Physiol 324:F91–F105PubMedCrossRef
16.
go back to reference Lee HW, Qin YX, Kim YM, Park EY, Hwang JS, Huo GH, Yang CW, Kim WY, Kim J (2011) Expression of lymphatic endothelium-specific hyaluronan receptor LYVE-1 in the developing mouse kidney. Cell Tissue Res 343:429–444PubMedCrossRef Lee HW, Qin YX, Kim YM, Park EY, Hwang JS, Huo GH, Yang CW, Kim WY, Kim J (2011) Expression of lymphatic endothelium-specific hyaluronan receptor LYVE-1 in the developing mouse kidney. Cell Tissue Res 343:429–444PubMedCrossRef
17.
go back to reference Jafree DJ, Moulding D, Kolatsi-Joannou M, Perretta Tejedor N, Price KL, Milmoe NJ, Walsh CL, Correra RM, Winyard PJ, Harris PC, Ruhrberg C, Walker-Samuel S, Riley PR, Woolf AS, Scambler PJ, Long DA (2019) Spatiotemporal dynamics and heterogeneity of renal lymphatics in mammalian development and cystic kidney disease. Elife 8:48183CrossRef Jafree DJ, Moulding D, Kolatsi-Joannou M, Perretta Tejedor N, Price KL, Milmoe NJ, Walsh CL, Correra RM, Winyard PJ, Harris PC, Ruhrberg C, Walker-Samuel S, Riley PR, Woolf AS, Scambler PJ, Long DA (2019) Spatiotemporal dynamics and heterogeneity of renal lymphatics in mammalian development and cystic kidney disease. Elife 8:48183CrossRef
18.
go back to reference Tanabe M, Shimizu A, Masuda Y, Kataoka M, Ishikawa A, Wakamatsu K, Mii A, Fujita E, Higo S, Kaneko T, Kawachi H, Fukuda Y (2012) Development of lymphatic vasculature and morphological characterization in rat kidney. Clin Exp Nephrol 16:833–842PubMedCrossRef Tanabe M, Shimizu A, Masuda Y, Kataoka M, Ishikawa A, Wakamatsu K, Mii A, Fujita E, Higo S, Kaneko T, Kawachi H, Fukuda Y (2012) Development of lymphatic vasculature and morphological characterization in rat kidney. Clin Exp Nephrol 16:833–842PubMedCrossRef
19.
go back to reference Lindström NO, McMahon JA, Guo J, Tran T, Guo Q, Rutledge E, Parvez RK, Saribekyan G, Schuler RE, Liao C, Kim AD, Abdelhalim A, Ruffins SW, Thornton ME, Baskin L, Grubbs B, Kesselman C, McMahon AP (2018) Conserved and divergent features of human and mouse kidney organogenesis. J Am Soc Nephrol 29:785–805PubMedPubMedCentralCrossRef Lindström NO, McMahon JA, Guo J, Tran T, Guo Q, Rutledge E, Parvez RK, Saribekyan G, Schuler RE, Liao C, Kim AD, Abdelhalim A, Ruffins SW, Thornton ME, Baskin L, Grubbs B, Kesselman C, McMahon AP (2018) Conserved and divergent features of human and mouse kidney organogenesis. J Am Soc Nephrol 29:785–805PubMedPubMedCentralCrossRef
20.
go back to reference Short KM, Combes AN, Lefevre J, Ju AL, Georgas KM, Lamberton T, Cairncross O, Rumballe BA, McMahon AP, Hamilton NA (2014) Global quantification of tissue dynamics in the developing mouse kidney. Develop Cell 29:188–202CrossRef Short KM, Combes AN, Lefevre J, Ju AL, Georgas KM, Lamberton T, Cairncross O, Rumballe BA, McMahon AP, Hamilton NA (2014) Global quantification of tissue dynamics in the developing mouse kidney. Develop Cell 29:188–202CrossRef
21.
go back to reference McMahon AP (2016) Development of the mammalian kidney. Curr Top Develop Biol 117:31–64CrossRef McMahon AP (2016) Development of the mammalian kidney. Curr Top Develop Biol 117:31–64CrossRef
22.
go back to reference Planas-Paz L, Strilić B, Goedecke A, Breier G, Fässler R, Lammert E (2012) Mechanoinduction of lymph vessel expansion. EMBO J 31:788–804PubMedCrossRef Planas-Paz L, Strilić B, Goedecke A, Breier G, Fässler R, Lammert E (2012) Mechanoinduction of lymph vessel expansion. EMBO J 31:788–804PubMedCrossRef
23.
go back to reference Witte MH, Dumont AE, Clauss RH, Rader B, Levine N, Breed ES (1969) Lymph circulation in congestive heart failure: effect of external thoracic duct drainage. Circulation 39:723–733PubMedCrossRef Witte MH, Dumont AE, Clauss RH, Rader B, Levine N, Breed ES (1969) Lymph circulation in congestive heart failure: effect of external thoracic duct drainage. Circulation 39:723–733PubMedCrossRef
24.
go back to reference Creed HA, Rutkowski JM (2021) Emerging roles for lymphatics in acute kidney injury: beneficial or maleficent? Exper Biol Med 246:845–850CrossRef Creed HA, Rutkowski JM (2021) Emerging roles for lymphatics in acute kidney injury: beneficial or maleficent? Exper Biol Med 246:845–850CrossRef
25.
go back to reference Pei G, Yao Y, Yang Q, Wang M, Wang Y, Wu J, Wang P, Li Y, Zhu F, Yang J, Zhang Y, Yang W, Deng X, Zhao Z, Zhu H, Ge S, Han M, Zeng R, Xu G (2019) Lymphangiogenesis in kidney and lymph node mediates renal inflammation and fibrosis. Sci Adv 5:eaaw5075PubMedPubMedCentralCrossRef Pei G, Yao Y, Yang Q, Wang M, Wang Y, Wu J, Wang P, Li Y, Zhu F, Yang J, Zhang Y, Yang W, Deng X, Zhao Z, Zhu H, Ge S, Han M, Zeng R, Xu G (2019) Lymphangiogenesis in kidney and lymph node mediates renal inflammation and fibrosis. Sci Adv 5:eaaw5075PubMedPubMedCentralCrossRef
26.
go back to reference Phillips S, Kapp M, Crowe D, Garces J, Fogo AB, Giannico GA (2016) Endothelial activation, lymphangiogenesis, and humoral rejection of kidney transplants. Human Pathol 51:86–95CrossRef Phillips S, Kapp M, Crowe D, Garces J, Fogo AB, Giannico GA (2016) Endothelial activation, lymphangiogenesis, and humoral rejection of kidney transplants. Human Pathol 51:86–95CrossRef
27.
go back to reference Rodas L, Barnadas E, Pereira A, Castrejon N, Saurina A, Calls J, Calzada Y, Madrid Á, Blasco M, Poch E (2022) The density of renal lymphatics correlates with clinical outcomes in IgA nephropathy. Kidney Int Rep 7:823–830PubMedPubMedCentralCrossRef Rodas L, Barnadas E, Pereira A, Castrejon N, Saurina A, Calls J, Calzada Y, Madrid Á, Blasco M, Poch E (2022) The density of renal lymphatics correlates with clinical outcomes in IgA nephropathy. Kidney Int Rep 7:823–830PubMedPubMedCentralCrossRef
28.
go back to reference Liu J, Liu Y, Zhou W, Liu Y, Zhu S, Yu Y, Huang J, Yu C (2023) Serum soluble LYVE1 is a promising non-invasive biomarker of renal fibrosis: a population-based retrospective cross-sectional study. Immunol Res 72:476–489PubMedPubMedCentralCrossRef Liu J, Liu Y, Zhou W, Liu Y, Zhu S, Yu Y, Huang J, Yu C (2023) Serum soluble LYVE1 is a promising non-invasive biomarker of renal fibrosis: a population-based retrospective cross-sectional study. Immunol Res 72:476–489PubMedPubMedCentralCrossRef
29.
go back to reference Zhong J, Yang HC, Shelton EL, Matsusaka T, Clark AJ, Yermalitsky V, Mashhadi Z, May-Zhang LS, Linton MF, Fogo AB, Kirabo A, Davies SS, Kon V (2022) Dicarbonyl-modified lipoproteins contribute to proteinuric kidney injury. JCI Insight 7:161878CrossRef Zhong J, Yang HC, Shelton EL, Matsusaka T, Clark AJ, Yermalitsky V, Mashhadi Z, May-Zhang LS, Linton MF, Fogo AB, Kirabo A, Davies SS, Kon V (2022) Dicarbonyl-modified lipoproteins contribute to proteinuric kidney injury. JCI Insight 7:161878CrossRef
30.
go back to reference Guo Y-C, Zhang M, Wang F-X, Pei G-C, Sun F, Zhang Y, He X, Wang Y, Song J, Zhu F-M (2017) Macrophages regulate unilateral ureteral obstruction-induced renal lymphangiogenesis through CC motif chemokine receptor 2–dependent phosphatidylinositol 3-kinase-AKT–mechanistic target of rapamycin signaling and hypoxia-inducible factor-1α/vascular endothelial growth factor-C expression. Am J Pathol 187:1736–1749PubMedCrossRef Guo Y-C, Zhang M, Wang F-X, Pei G-C, Sun F, Zhang Y, He X, Wang Y, Song J, Zhu F-M (2017) Macrophages regulate unilateral ureteral obstruction-induced renal lymphangiogenesis through CC motif chemokine receptor 2–dependent phosphatidylinositol 3-kinase-AKT–mechanistic target of rapamycin signaling and hypoxia-inducible factor-1α/vascular endothelial growth factor-C expression. Am J Pathol 187:1736–1749PubMedCrossRef
31.
go back to reference Liu J, Yu C (2022) Lymphangiogenesis and lymphatic barrier dysfunction in renal fibrosis. Int J Molec Sci 23:6970CrossRef Liu J, Yu C (2022) Lymphangiogenesis and lymphatic barrier dysfunction in renal fibrosis. Int J Molec Sci 23:6970CrossRef
32.
go back to reference Zawieja SD, Wang W, Chakraborty S, Zawieja DC, Muthuchamy M (2016) Macrophage alterations within the mesenteric lymphatic tissue are associated with impairment of lymphatic pump in metabolic syndrome. Microcirculation 23:558–570PubMedPubMedCentralCrossRef Zawieja SD, Wang W, Chakraborty S, Zawieja DC, Muthuchamy M (2016) Macrophage alterations within the mesenteric lymphatic tissue are associated with impairment of lymphatic pump in metabolic syndrome. Microcirculation 23:558–570PubMedPubMedCentralCrossRef
33.
go back to reference Baburaj K, Saeed A, Azam N, Durani S (1991) Exploring borate-activated electron-rich glyoxals as the arginine-reactivity probes. The reactivities of functionally critical arginines in some representative enzymes. Biochim Biophys Acta 1078:258–264PubMedCrossRef Baburaj K, Saeed A, Azam N, Durani S (1991) Exploring borate-activated electron-rich glyoxals as the arginine-reactivity probes. The reactivities of functionally critical arginines in some representative enzymes. Biochim Biophys Acta 1078:258–264PubMedCrossRef
34.
go back to reference Webb RL (1933) Observations on the propulsion of lymph through the mesenteric lymphatic vessels of the living rat. Anatom Rec 57:345–350CrossRef Webb RL (1933) Observations on the propulsion of lymph through the mesenteric lymphatic vessels of the living rat. Anatom Rec 57:345–350CrossRef
35.
go back to reference Dixon JB, Zawieja DC, Gashev AA, Coté GL (2005) Measuring microlymphatic flow using fast video microscopy. J Biomed Opt 10:064016PubMedCrossRef Dixon JB, Zawieja DC, Gashev AA, Coté GL (2005) Measuring microlymphatic flow using fast video microscopy. J Biomed Opt 10:064016PubMedCrossRef
36.
go back to reference Liao S, Cheng G, Conner DA, Huang Y, Kucherlapati RS, Munn LL, Ruddle NH, Jain RK, Fukumura D, Padera TP (2011) Impaired lymphatic contraction associated with immunosuppression. Proc Natl Acad Sci U S A 108:18784–18789PubMedPubMedCentralCrossRef Liao S, Cheng G, Conner DA, Huang Y, Kucherlapati RS, Munn LL, Ruddle NH, Jain RK, Fukumura D, Padera TP (2011) Impaired lymphatic contraction associated with immunosuppression. Proc Natl Acad Sci U S A 108:18784–18789PubMedPubMedCentralCrossRef
37.
go back to reference Zawieja SD, Castorena-Gonzalez JA, Dixon B, Davis MJ (2017) Experimental models used to assess lymphatic contractile function. Lymphat Res Biol 15:331–342PubMedPubMedCentralCrossRef Zawieja SD, Castorena-Gonzalez JA, Dixon B, Davis MJ (2017) Experimental models used to assess lymphatic contractile function. Lymphat Res Biol 15:331–342PubMedPubMedCentralCrossRef
38.
go back to reference Weiler M, Dixon JB (2013) Differential transport function of lymphatic vessels in the rat tail model and the long-term effects of Indocyanine Green as assessed with near-infrared imaging. Front Physiol 4:215PubMedPubMedCentralCrossRef Weiler M, Dixon JB (2013) Differential transport function of lymphatic vessels in the rat tail model and the long-term effects of Indocyanine Green as assessed with near-infrared imaging. Front Physiol 4:215PubMedPubMedCentralCrossRef
39.
42.
go back to reference Castorena-Gonzalez JA, Srinivasan RS, King PD, Simon AM, Davis MJ (2020) Simplified method to quantify valve back-leak uncovers severe mesenteric lymphatic valve dysfunction in mice deficient in connexins 43 and 37. J Physiol 598:2297–2310PubMedCrossRef Castorena-Gonzalez JA, Srinivasan RS, King PD, Simon AM, Davis MJ (2020) Simplified method to quantify valve back-leak uncovers severe mesenteric lymphatic valve dysfunction in mice deficient in connexins 43 and 37. J Physiol 598:2297–2310PubMedCrossRef
43.
go back to reference Liu J, Shelton EL, Crescenzi R, Colvin DC, Kirabo A, Zhong J, Delpire EJ, Yang HC, Kon V (2022) Kidney injury causes accumulation of renal sodium that modulates renal lymphatic dynamics. Int J Mol Sci 23:1428PubMedPubMedCentralCrossRef Liu J, Shelton EL, Crescenzi R, Colvin DC, Kirabo A, Zhong J, Delpire EJ, Yang HC, Kon V (2022) Kidney injury causes accumulation of renal sodium that modulates renal lymphatic dynamics. Int J Mol Sci 23:1428PubMedPubMedCentralCrossRef
44.
go back to reference Prowle JR, Echeverri JE, Ligabo EV, Ronco C, Bellomo R (2010) Fluid balance and acute kidney injury. Nat Rev Nephrol 6:107–115PubMedCrossRef Prowle JR, Echeverri JE, Ligabo EV, Ronco C, Bellomo R (2010) Fluid balance and acute kidney injury. Nat Rev Nephrol 6:107–115PubMedCrossRef
45.
go back to reference Wilcox CS, Sterzel RB, Dunckel PT, Mohrmann M, Perfetto M (1984) Renal interstitial pressure and sodium excretion during hilar lymphatic ligation. Am J Physiol Renal Physiol 247:F344–F351CrossRef Wilcox CS, Sterzel RB, Dunckel PT, Mohrmann M, Perfetto M (1984) Renal interstitial pressure and sodium excretion during hilar lymphatic ligation. Am J Physiol Renal Physiol 247:F344–F351CrossRef
46.
47.
go back to reference Rohn D, Stewart R, Elk J, Laine G, Drake R (1996) Renal lymphatic function following venous pressure elevation. Lymphology 29:67–75PubMed Rohn D, Stewart R, Elk J, Laine G, Drake R (1996) Renal lymphatic function following venous pressure elevation. Lymphology 29:67–75PubMed
48.
go back to reference Granger J (1992) Pressure natriuresis. Role of renal interstitial hydrostatic pressure. Hypertension 19:I9PubMedCrossRef Granger J (1992) Pressure natriuresis. Role of renal interstitial hydrostatic pressure. Hypertension 19:I9PubMedCrossRef
49.
go back to reference Khraibi A (1991) Direct renal interstitial volume expansion causes exaggerated natriuresis in SHR. Am J Physiol Renal Physiol 261:F567–F570CrossRef Khraibi A (1991) Direct renal interstitial volume expansion causes exaggerated natriuresis in SHR. Am J Physiol Renal Physiol 261:F567–F570CrossRef
50.
go back to reference Martino JA, Earley LE (1968) Relationship between intrarenal hydrostatic pressure and hemodynamically induced changes in sodium excretion. Circ Res 23:371–386PubMedCrossRef Martino JA, Earley LE (1968) Relationship between intrarenal hydrostatic pressure and hemodynamically induced changes in sodium excretion. Circ Res 23:371–386PubMedCrossRef
51.
go back to reference Skarlatos S, Brand PH, Metting PJ, Britton SL (1994) Spontaneous changes in arterial blood pressure and renal interstitial hydrostatic pressure in conscious rats. J Physiol 481:743–752PubMedPubMedCentralCrossRef Skarlatos S, Brand PH, Metting PJ, Britton SL (1994) Spontaneous changes in arterial blood pressure and renal interstitial hydrostatic pressure in conscious rats. J Physiol 481:743–752PubMedPubMedCentralCrossRef
52.
go back to reference Zhang T, Liu G, Sun M, Guan G, Chen B, Li X (2009) Functional, histological and biochemical consequences of renal lymph disorder in mononephrectomized rats. J Nephrol 22:109–116PubMed Zhang T, Liu G, Sun M, Guan G, Chen B, Li X (2009) Functional, histological and biochemical consequences of renal lymph disorder in mononephrectomized rats. J Nephrol 22:109–116PubMed
53.
go back to reference Balasubbramanian D, Baranwal G, Clark MC, Goodlett BL, Mitchell BM, Rutkowski JM (2020) Kidney-specific lymphangiogenesis increases sodium excretion and lowers blood pressure in mice. J Hypertens 38:874–885PubMedPubMedCentralCrossRef Balasubbramanian D, Baranwal G, Clark MC, Goodlett BL, Mitchell BM, Rutkowski JM (2020) Kidney-specific lymphangiogenesis increases sodium excretion and lowers blood pressure in mice. J Hypertens 38:874–885PubMedPubMedCentralCrossRef
54.
go back to reference Goodlett BL, Kang CS, Yoo E, Navaneethabalakrishnan S, Balasubbramanian D, Love SE, Sims BM, Avilez DL, Tate W, Chavez DR (2021) A kidney-targeted nanoparticle to augment renal lymphatic density decreases blood pressure in hypertensive mice. Pharmaceutics 14:84PubMedPubMedCentralCrossRef Goodlett BL, Kang CS, Yoo E, Navaneethabalakrishnan S, Balasubbramanian D, Love SE, Sims BM, Avilez DL, Tate W, Chavez DR (2021) A kidney-targeted nanoparticle to augment renal lymphatic density decreases blood pressure in hypertensive mice. Pharmaceutics 14:84PubMedPubMedCentralCrossRef
55.
go back to reference Lopez Gelston CA, Balasubbramanian D, Abouelkheir GR, Lopez AH, Hudson KR, Johnson ER, Muthuchamy M, Mitchell BM, Rutkowski JM (2018) Enhancing renal lymphatic expansion prevents hypertension in Mice. Circ Res 122:1094–1101PubMedCrossRef Lopez Gelston CA, Balasubbramanian D, Abouelkheir GR, Lopez AH, Hudson KR, Johnson ER, Muthuchamy M, Mitchell BM, Rutkowski JM (2018) Enhancing renal lymphatic expansion prevents hypertension in Mice. Circ Res 122:1094–1101PubMedCrossRef
56.
go back to reference Balasubbramanian D, Gelston CAL, Lopez AH, Iskander G, Tate W, Holderness H, Rutkowski JM, Mitchell BM (2020) Augmenting renal lymphatic density prevents angiotensin II-induced hypertension in male and female mice. Am J Hypertens 33:61–69PubMedCrossRef Balasubbramanian D, Gelston CAL, Lopez AH, Iskander G, Tate W, Holderness H, Rutkowski JM, Mitchell BM (2020) Augmenting renal lymphatic density prevents angiotensin II-induced hypertension in male and female mice. Am J Hypertens 33:61–69PubMedCrossRef
57.
go back to reference Machnik A, Neuhofer W, Jantsch J, Dahlmann A, Tammela T, Machura K, Park J-K, Beck F-X, Müller DN, Derer W (2009) Macrophages regulate salt-dependent volume and blood pressure by a vascular endothelial growth factor-C–dependent buffering mechanism. Nat Med 15:545–552PubMedCrossRef Machnik A, Neuhofer W, Jantsch J, Dahlmann A, Tammela T, Machura K, Park J-K, Beck F-X, Müller DN, Derer W (2009) Macrophages regulate salt-dependent volume and blood pressure by a vascular endothelial growth factor-C–dependent buffering mechanism. Nat Med 15:545–552PubMedCrossRef
58.
go back to reference Rossitto G, Mary S, Chen JY, Boder P, Chew KS, Neves KB, Alves RL, Montezano AC, Welsh P, Petrie MC, Graham D, Touyz RM, Delles C (2020) Tissue sodium excess is not hypertonic and reflects extracellular volume expansion. Nat Commun 11:4222PubMedPubMedCentralCrossRef Rossitto G, Mary S, Chen JY, Boder P, Chew KS, Neves KB, Alves RL, Montezano AC, Welsh P, Petrie MC, Graham D, Touyz RM, Delles C (2020) Tissue sodium excess is not hypertonic and reflects extracellular volume expansion. Nat Commun 11:4222PubMedPubMedCentralCrossRef
59.
go back to reference Heney N, O’Morchoe P, O’Morchoe C (1971) The renal lymphatic system during obstructed urine flow. J Urol 106:455–462PubMedCrossRef Heney N, O’Morchoe P, O’Morchoe C (1971) The renal lymphatic system during obstructed urine flow. J Urol 106:455–462PubMedCrossRef
60.
go back to reference O’Morchoe C, O’Morchoe P, Holmes M, Jarosz H (1978) Flow and composition of renal hilar lymph during volume expansion and saline diuresis. Lymphology 11:27–31PubMed O’Morchoe C, O’Morchoe P, Holmes M, Jarosz H (1978) Flow and composition of renal hilar lymph during volume expansion and saline diuresis. Lymphology 11:27–31PubMed
61.
go back to reference Wiig H, Schröder A, Neuhofer W, Jantsch J, Kopp C, Karlsen TV, Boschmann M, Goss J, Bry M, Rakova N (2013) Immune cells control skin lymphatic electrolyte homeostasis and blood pressure. J Clin Invest 123:2803–2815PubMedPubMedCentralCrossRef Wiig H, Schröder A, Neuhofer W, Jantsch J, Kopp C, Karlsen TV, Boschmann M, Goss J, Bry M, Rakova N (2013) Immune cells control skin lymphatic electrolyte homeostasis and blood pressure. J Clin Invest 123:2803–2815PubMedPubMedCentralCrossRef
62.
go back to reference Karlsen TV, Nikpey E, Han J, Reikvam T, Rakova N, Castorena-Gonzalez JA, Davis MJ, Titze JM, Tenstad O, Wiig H (2018) High-salt diet causes expansion of the lymphatic network and increased lymph flow in skin and muscle of rats. Arterioscler Thromb Vasc Biol 38:2054–2064PubMedCrossRef Karlsen TV, Nikpey E, Han J, Reikvam T, Rakova N, Castorena-Gonzalez JA, Davis MJ, Titze JM, Tenstad O, Wiig H (2018) High-salt diet causes expansion of the lymphatic network and increased lymph flow in skin and muscle of rats. Arterioscler Thromb Vasc Biol 38:2054–2064PubMedCrossRef
63.
go back to reference Inagami T, Kawamura M, Naruse K, Okamura T (1986) Localization of components of the renin-angiotensin system within the kidney. Fed Proc 45:1414–1419PubMed Inagami T, Kawamura M, Naruse K, Okamura T (1986) Localization of components of the renin-angiotensin system within the kidney. Fed Proc 45:1414–1419PubMed
64.
go back to reference O’Morchoe CC, O’Morchoe PJ, Albertine KH, Jarosz HM (1981) Concentration of renin in the renal interstitium, as reflected in lymph. Kidney Blood Press Res 4:199–206CrossRef O’Morchoe CC, O’Morchoe PJ, Albertine KH, Jarosz HM (1981) Concentration of renin in the renal interstitium, as reflected in lymph. Kidney Blood Press Res 4:199–206CrossRef
65.
go back to reference Dzau VJ, Wilcox CS, Sands K, Dunckel P (1986) Dog inactive renin: biochemical characterization and secretion into renal plasma and lymph. Am J Physiol Endocrinol Metab 250:E55–E61CrossRef Dzau VJ, Wilcox CS, Sands K, Dunckel P (1986) Dog inactive renin: biochemical characterization and secretion into renal plasma and lymph. Am J Physiol Endocrinol Metab 250:E55–E61CrossRef
66.
67.
go back to reference Cifarelli V, Eichmann A (2019) The intestinal lymphatic system: functions and metabolic implications. Cell Mol Gastroenterol Hepatol 7:503–513PubMedCrossRef Cifarelli V, Eichmann A (2019) The intestinal lymphatic system: functions and metabolic implications. Cell Mol Gastroenterol Hepatol 7:503–513PubMedCrossRef
68.
go back to reference Martel C, Li W, Fulp B, Platt AM, Gautier EL, Westerterp M, Bittman R, Tall AR, Chen S-H, Thomas MJ (2013) Lymphatic vasculature mediates macrophage reverse cholesterol transport in mice. J Clin Invest 123:1571–1579PubMedPubMedCentralCrossRef Martel C, Li W, Fulp B, Platt AM, Gautier EL, Westerterp M, Bittman R, Tall AR, Chen S-H, Thomas MJ (2013) Lymphatic vasculature mediates macrophage reverse cholesterol transport in mice. J Clin Invest 123:1571–1579PubMedPubMedCentralCrossRef
69.
go back to reference Mitrofanova A, Merscher S, Fornoni A (2023) Kidney lipid dysmetabolism and lipid droplet accumulation in chronic kidney disease. Nat Rev Nephrol 19:629–645PubMedCrossRef Mitrofanova A, Merscher S, Fornoni A (2023) Kidney lipid dysmetabolism and lipid droplet accumulation in chronic kidney disease. Nat Rev Nephrol 19:629–645PubMedCrossRef
70.
go back to reference Santambrogio L, Berendam SJ, Engelhard VH (2019) The antigen processing and presentation machinery in lymphatic endothelial cells. Front Immunol 10:1033PubMedPubMedCentralCrossRef Santambrogio L, Berendam SJ, Engelhard VH (2019) The antigen processing and presentation machinery in lymphatic endothelial cells. Front Immunol 10:1033PubMedPubMedCentralCrossRef
71.
go back to reference Zhang Y, Zhang C, Li L, Liang X, Cheng P, Li Q, Chang X, Wang K, Huang S, Li Y, Liu Y, Xu G (2021) Lymphangiogenesis in renal fibrosis arises from macrophages via VEGF-C/VEGFR3-dependent autophagy and polarization. Cell Death Dis 12:109PubMedPubMedCentralCrossRef Zhang Y, Zhang C, Li L, Liang X, Cheng P, Li Q, Chang X, Wang K, Huang S, Li Y, Liu Y, Xu G (2021) Lymphangiogenesis in renal fibrosis arises from macrophages via VEGF-C/VEGFR3-dependent autophagy and polarization. Cell Death Dis 12:109PubMedPubMedCentralCrossRef
72.
go back to reference Zhong J, Yang H-C, Yermalitsky V, Shelton EL, Otsuka T, Wiese CB, May-Zhang LS, Banan B, Abumrad N, Huang J (2021) Kidney injury-mediated disruption of intestinal lymphatics involves dicarbonyl-modified lipoproteins. Kidney Int 100:585–596PubMedPubMedCentralCrossRef Zhong J, Yang H-C, Yermalitsky V, Shelton EL, Otsuka T, Wiese CB, May-Zhang LS, Banan B, Abumrad N, Huang J (2021) Kidney injury-mediated disruption of intestinal lymphatics involves dicarbonyl-modified lipoproteins. Kidney Int 100:585–596PubMedPubMedCentralCrossRef
73.
74.
go back to reference Irrthum A, Devriendt K, Chitayat D, Matthijs G, Glade C, Steijlen PM, Fryns J-P, Van Steensel MA, Vikkula M (2003) Mutations in the transcription factor gene SOX18 underlie recessive and dominant forms of hypotrichosis-lymphedema-telangiectasia. Am J Hum Genet 72:1470–1478PubMedPubMedCentralCrossRef Irrthum A, Devriendt K, Chitayat D, Matthijs G, Glade C, Steijlen PM, Fryns J-P, Van Steensel MA, Vikkula M (2003) Mutations in the transcription factor gene SOX18 underlie recessive and dominant forms of hypotrichosis-lymphedema-telangiectasia. Am J Hum Genet 72:1470–1478PubMedPubMedCentralCrossRef
75.
go back to reference Mäkinen T, Jussila L, Veikkola T, Karpanen T, Kettunen MI, Pulkkanen KJ, Kauppinen R, Jackson DG, Kubo H, Nishikawa S-I (2001) Inhibition of lymphangiogenesis with resulting lymphedema in transgenic mice expressing soluble VEGF receptor-3. Nat Med 7:199–205PubMedCrossRef Mäkinen T, Jussila L, Veikkola T, Karpanen T, Kettunen MI, Pulkkanen KJ, Kauppinen R, Jackson DG, Kubo H, Nishikawa S-I (2001) Inhibition of lymphangiogenesis with resulting lymphedema in transgenic mice expressing soluble VEGF receptor-3. Nat Med 7:199–205PubMedCrossRef
76.
go back to reference Irrthum A, Karkkainen MJ, Devriendt K, Alitalo K, Vikkula M (2000) Congenital hereditary lymphedema caused by a mutation that inactivates VEGFR3 tyrosine kinase. Am J Hum Genet 67:295–301PubMedPubMedCentralCrossRef Irrthum A, Karkkainen MJ, Devriendt K, Alitalo K, Vikkula M (2000) Congenital hereditary lymphedema caused by a mutation that inactivates VEGFR3 tyrosine kinase. Am J Hum Genet 67:295–301PubMedPubMedCentralCrossRef
77.
go back to reference Fotiou E, Martin-Almedina S, Simpson MA, Lin S, Gordon K, Brice G, Atton G, Jeffery I, Rees DC, Mignot C, Vogt J, Homfray T, Snyder MP, Rockson SG, Jeffery S, Mortimer PS, Mansour S, Ostergaard P (2015) Novel mutations in PIEZO1 cause an autosomal recessive generalized lymphatic dysplasia with non-immune hydrops fetalis. Nat Commun 6:8085PubMedCrossRef Fotiou E, Martin-Almedina S, Simpson MA, Lin S, Gordon K, Brice G, Atton G, Jeffery I, Rees DC, Mignot C, Vogt J, Homfray T, Snyder MP, Rockson SG, Jeffery S, Mortimer PS, Mansour S, Ostergaard P (2015) Novel mutations in PIEZO1 cause an autosomal recessive generalized lymphatic dysplasia with non-immune hydrops fetalis. Nat Commun 6:8085PubMedCrossRef
78.
go back to reference Liu H, Hiremath C, Patterson Q, Vora S, Shang Z, Jamieson AR, Fiolka R, Dean KM, Dellinger MT, Marciano DK (2021) Heterozygous mutation of Vegfr3 reduces renal lymphatics without renal dysfunction. J Am Soc Nephrol 32:3099–3113PubMedPubMedCentralCrossRef Liu H, Hiremath C, Patterson Q, Vora S, Shang Z, Jamieson AR, Fiolka R, Dean KM, Dellinger MT, Marciano DK (2021) Heterozygous mutation of Vegfr3 reduces renal lymphatics without renal dysfunction. J Am Soc Nephrol 32:3099–3113PubMedPubMedCentralCrossRef
79.
go back to reference Bergmann C, Guay-Woodford LM, Harris PC, Horie S, Peters DJ, Torres VE (2018) Polycystic kidney disease. Nat Rev Dis Prim 4:50PubMedCrossRef Bergmann C, Guay-Woodford LM, Harris PC, Horie S, Peters DJ, Torres VE (2018) Polycystic kidney disease. Nat Rev Dis Prim 4:50PubMedCrossRef
80.
go back to reference Outeda P, Huso DL, Fisher SA, Halushka MK, Kim H, Qian F, Germino GG, Watnick T (2014) Polycystin signaling is required for directed endothelial cell migration and lymphatic development. Cell Rep 7:634–644PubMedPubMedCentralCrossRef Outeda P, Huso DL, Fisher SA, Halushka MK, Kim H, Qian F, Germino GG, Watnick T (2014) Polycystin signaling is required for directed endothelial cell migration and lymphatic development. Cell Rep 7:634–644PubMedPubMedCentralCrossRef
81.
go back to reference Coxam B, Sabine A, Bower NI, Smith KA, Pichol-Thievend C, Skoczylas R, Astin JW, Frampton E, Jaquet M, Crosier PS, Parton RG, Harvey NL, Petrova TV, Schulte-Merker S, Francois M, Hogan BM (2014) Pkd1 regulates lymphatic vascular morphogenesis during development. Cell Rep 7:623–633PubMedPubMedCentralCrossRef Coxam B, Sabine A, Bower NI, Smith KA, Pichol-Thievend C, Skoczylas R, Astin JW, Frampton E, Jaquet M, Crosier PS, Parton RG, Harvey NL, Petrova TV, Schulte-Merker S, Francois M, Hogan BM (2014) Pkd1 regulates lymphatic vascular morphogenesis during development. Cell Rep 7:623–633PubMedPubMedCentralCrossRef
82.
go back to reference Lilienfeld RM, Friedenberg RM, Herman JR (1967) The effect of renal lymphatic ligation on kidney and blood pressure. Radiology 88:1105–1109PubMedCrossRef Lilienfeld RM, Friedenberg RM, Herman JR (1967) The effect of renal lymphatic ligation on kidney and blood pressure. Radiology 88:1105–1109PubMedCrossRef
83.
go back to reference Beaini S, Saliba Y, Hajal J, Smayra V, Bakhos JJ, Joubran N, Chelala D, Fares N (2019) VEGF-C attenuates renal damage in salt-sensitive hypertension. J Cell Physiol 234:9616–9630PubMedCrossRef Beaini S, Saliba Y, Hajal J, Smayra V, Bakhos JJ, Joubran N, Chelala D, Fares N (2019) VEGF-C attenuates renal damage in salt-sensitive hypertension. J Cell Physiol 234:9616–9630PubMedCrossRef
85.
go back to reference Escudier B, Powles T, Motzer RJ, Olencki T, Arén Frontera O, Oudard S, Rolland F, Tomczak P, Castellano D, Appleman LJ (2018) Cabozantinib, a new standard of care for patients with advanced renal cell carcinoma and bone metastases? Subgroup analysis of the METEOR trial. J Clin Oncol 36:765–772PubMedPubMedCentralCrossRef Escudier B, Powles T, Motzer RJ, Olencki T, Arén Frontera O, Oudard S, Rolland F, Tomczak P, Castellano D, Appleman LJ (2018) Cabozantinib, a new standard of care for patients with advanced renal cell carcinoma and bone metastases? Subgroup analysis of the METEOR trial. J Clin Oncol 36:765–772PubMedPubMedCentralCrossRef
86.
go back to reference Matsui J, Funahashi Y, Uenaka T, Watanabe T, Tsuruoka A, Asada M (2008) Multi-kinase inhibitor E7080 suppresses lymph node and lung metastases of human mammary breast tumor MDA-MB-231 via inhibition of vascular endothelial growth factor-receptor (VEGF-R) 2 and VEGF-R3 kinase. Clin Cancer Res 14:5459–5465PubMedCrossRef Matsui J, Funahashi Y, Uenaka T, Watanabe T, Tsuruoka A, Asada M (2008) Multi-kinase inhibitor E7080 suppresses lymph node and lung metastases of human mammary breast tumor MDA-MB-231 via inhibition of vascular endothelial growth factor-receptor (VEGF-R) 2 and VEGF-R3 kinase. Clin Cancer Res 14:5459–5465PubMedCrossRef
87.
go back to reference Visuri MT, Honkonen KM, Hartiala P, Tervala TV, Halonen PJ, Junkkari H, Knuutinen N, Ylä-Herttuala S, Alitalo KK, Saarikko AM (2015) VEGF-C and VEGF-C156S in the pro-lymphangiogenic growth factor therapy of lymphedema: a large animal study. Angiogenesis 18:313–326PubMedCrossRef Visuri MT, Honkonen KM, Hartiala P, Tervala TV, Halonen PJ, Junkkari H, Knuutinen N, Ylä-Herttuala S, Alitalo KK, Saarikko AM (2015) VEGF-C and VEGF-C156S in the pro-lymphangiogenic growth factor therapy of lymphedema: a large animal study. Angiogenesis 18:313–326PubMedCrossRef
89.
go back to reference Russell PS, Hong J, Trevaskis NL, Windsor JA, Martin ND, Phillips ARJ (2022) Lymphatic contractile function: a comprehensive review of drug effects and potential clinical application. Cardiovasc Res 118:2437–2457PubMedCrossRef Russell PS, Hong J, Trevaskis NL, Windsor JA, Martin ND, Phillips ARJ (2022) Lymphatic contractile function: a comprehensive review of drug effects and potential clinical application. Cardiovasc Res 118:2437–2457PubMedCrossRef
90.
go back to reference Lee Y, Chakraborty S, Muthuchamy M (2020) Roles of sarcoplasmic reticulum Ca2+ ATPase pump in the impairments of lymphatic contractile activity in a metabolic syndrome rat model. Sci Rep 10:12320PubMedPubMedCentralCrossRef Lee Y, Chakraborty S, Muthuchamy M (2020) Roles of sarcoplasmic reticulum Ca2+ ATPase pump in the impairments of lymphatic contractile activity in a metabolic syndrome rat model. Sci Rep 10:12320PubMedPubMedCentralCrossRef
91.
go back to reference Telinius N, Mohanakumar S, Majgaard J, Kim S, Pilegaard H, Pahle E, Nielsen J, de Leval M, Aalkjaer C, Hjortdal V, Boedtkjer DB (2014) Human lymphatic vessel contractile activity is inhibited in vitro but not in vivo by the calcium channel blocker nifedipine. J Physiol 592:4697–4714PubMedPubMedCentralCrossRef Telinius N, Mohanakumar S, Majgaard J, Kim S, Pilegaard H, Pahle E, Nielsen J, de Leval M, Aalkjaer C, Hjortdal V, Boedtkjer DB (2014) Human lymphatic vessel contractile activity is inhibited in vitro but not in vivo by the calcium channel blocker nifedipine. J Physiol 592:4697–4714PubMedPubMedCentralCrossRef
92.
go back to reference Sangam K, Devireddy P, Konuru V (2016) Calcium channel blockers induced peripheral edema. Age 53(10):88 Sangam K, Devireddy P, Konuru V (2016) Calcium channel blockers induced peripheral edema. Age 53(10):88
93.
go back to reference Piscitani L, Reboldi G, Venanzi A, Timio F, D'Ostilio A, Sirolli V, Bonomini M (2023) Chyloperitoneum in peritoneal dialysis secondary to calcium channel blocker use: case series and literature review. J Clin Med 12:1930 Piscitani L, Reboldi G, Venanzi A, Timio F, D'Ostilio A, Sirolli V, Bonomini M (2023) Chyloperitoneum in peritoneal dialysis secondary to calcium channel blocker use: case series and literature review. J Clin Med 12:1930
94.
go back to reference Basualdo JE, Rosado IA, Morales MI, Fernández-Ros N, Huerta A, Alegre F, Landecho MF, Lucena JF (2017) Lercanidipine-induced chylous ascites: case report and literature review. J Clin Pharm Ther 42:638–641PubMedCrossRef Basualdo JE, Rosado IA, Morales MI, Fernández-Ros N, Huerta A, Alegre F, Landecho MF, Lucena JF (2017) Lercanidipine-induced chylous ascites: case report and literature review. J Clin Pharm Ther 42:638–641PubMedCrossRef
95.
96.
go back to reference Garner BR, Stolarz AJ, Stuckey D, Sarimollaoglu M, Liu Y, Palade PT, Rusch NJ, Mu S (2021) KATP channel openers inhibit lymphatic contractions and lymph flow as a possible mechanism of peripheral edema. J Pharmacol Exp Ther 376:40–50PubMedPubMedCentralCrossRef Garner BR, Stolarz AJ, Stuckey D, Sarimollaoglu M, Liu Y, Palade PT, Rusch NJ, Mu S (2021) KATP channel openers inhibit lymphatic contractions and lymph flow as a possible mechanism of peripheral edema. J Pharmacol Exp Ther 376:40–50PubMedPubMedCentralCrossRef
97.
go back to reference Shen B, Fu J, Guo J, Zhang J, Wang X, Pan X, Chen M, Zhou Y, Zhu M, Du J (2015) Role of Na+-K+-2Cl-cotransporter 1 in phenylephrine-induced rhythmic contraction in the mouse aorta: regulation of Na+-K+-2Cl-cotransporter 1 by Ca2+ sparks and KCa channels. Cell Physiol Biochem 37:747–758PubMedCrossRef Shen B, Fu J, Guo J, Zhang J, Wang X, Pan X, Chen M, Zhou Y, Zhu M, Du J (2015) Role of Na+-K+-2Cl-cotransporter 1 in phenylephrine-induced rhythmic contraction in the mouse aorta: regulation of Na+-K+-2Cl-cotransporter 1 by Ca2+ sparks and KCa channels. Cell Physiol Biochem 37:747–758PubMedCrossRef
98.
go back to reference Greenwood I, Hogg R, Large W (1995) Effect of frusemide, ethacrynic acid and indanyloxyacetic acid on spontaneous Ca-activated currents in rabbit portal vein smooth muscle cells. Brit J Pharmacol 115:733–738CrossRef Greenwood I, Hogg R, Large W (1995) Effect of frusemide, ethacrynic acid and indanyloxyacetic acid on spontaneous Ca-activated currents in rabbit portal vein smooth muscle cells. Brit J Pharmacol 115:733–738CrossRef
99.
go back to reference Yao L-C, Baluk P, Srinivasan RS, Oliver G, McDonald DM (2012) Plasticity of button-like junctions in the endothelium of airway lymphatics in development and inflammation. Am J Path 180:2561–2575PubMedPubMedCentralCrossRef Yao L-C, Baluk P, Srinivasan RS, Oliver G, McDonald DM (2012) Plasticity of button-like junctions in the endothelium of airway lymphatics in development and inflammation. Am J Path 180:2561–2575PubMedPubMedCentralCrossRef
100.
go back to reference Rockson SG, Tian W, Jiang X, Kuznetsova T, Haddad F, Zampell J, Mehrara B, Sampson JP, Roche L, Kim J, Nicolls MR (2018) Pilot studies demonstrate the potential benefits of antiinflammatory therapy in human lymphedema. JCI Insight 3:123775PubMedCrossRef Rockson SG, Tian W, Jiang X, Kuznetsova T, Haddad F, Zampell J, Mehrara B, Sampson JP, Roche L, Kim J, Nicolls MR (2018) Pilot studies demonstrate the potential benefits of antiinflammatory therapy in human lymphedema. JCI Insight 3:123775PubMedCrossRef
101.
go back to reference Makinen T (2019) Lymphatic vessels at the base of the mouse brain provide direct drainage to the periphery. Nature 572:34–35PubMedCrossRef Makinen T (2019) Lymphatic vessels at the base of the mouse brain provide direct drainage to the periphery. Nature 572:34–35PubMedCrossRef
102.
go back to reference Beckett EA, Hollywood MA, Thornbury KD, McHale NG (2007) Spontaneous electrical activity in sheep mesenteric lymphatics. Lymphat Res Biol 5:29–43PubMedCrossRef Beckett EA, Hollywood MA, Thornbury KD, McHale NG (2007) Spontaneous electrical activity in sheep mesenteric lymphatics. Lymphat Res Biol 5:29–43PubMedCrossRef
103.
go back to reference von der Weid PY, Rahman M, Imtiaz MS, van Helden DF (2008) Spontaneous transient depolarizations in lymphatic vessels of the guinea pig mesentery: pharmacology and implication for spontaneous contractility. Am J Physiol Heart Circ Physiol 295:H1989–H2000PubMedCrossRef von der Weid PY, Rahman M, Imtiaz MS, van Helden DF (2008) Spontaneous transient depolarizations in lymphatic vessels of the guinea pig mesentery: pharmacology and implication for spontaneous contractility. Am J Physiol Heart Circ Physiol 295:H1989–H2000PubMedCrossRef
104.
go back to reference Dossin T, Goffin E (2019) When the color of peritoneal dialysis effluent can be used as a diagnostic tool. Semin Dial 32:72–79PubMedCrossRef Dossin T, Goffin E (2019) When the color of peritoneal dialysis effluent can be used as a diagnostic tool. Semin Dial 32:72–79PubMedCrossRef
105.
go back to reference Davis MJ, Kim HJ, Zawieja SD, Castorena-Gonzalez JA, Gui P, Li M, Saunders BT, Zinselmeyer BH, Randolph GJ, Remedi MS, Nichols CG (2020) Kir6.1-dependent K(ATP) channels in lymphatic smooth muscle and vessel dysfunction in mice with Kir6.1 gain-of-function. J Physiol 598:3107–3127PubMedCrossRef Davis MJ, Kim HJ, Zawieja SD, Castorena-Gonzalez JA, Gui P, Li M, Saunders BT, Zinselmeyer BH, Randolph GJ, Remedi MS, Nichols CG (2020) Kir6.1-dependent K(ATP) channels in lymphatic smooth muscle and vessel dysfunction in mice with Kir6.1 gain-of-function. J Physiol 598:3107–3127PubMedCrossRef
106.
go back to reference Mizuno R, Ono N, Ohhashi T (1999) Involvement of ATP-sensitive K(+) channels in spontaneous activity of isolated lymph microvessels in rats. Am J Physiol 277:H1453–H1456PubMed Mizuno R, Ono N, Ohhashi T (1999) Involvement of ATP-sensitive K(+) channels in spontaneous activity of isolated lymph microvessels in rats. Am J Physiol 277:H1453–H1456PubMed
107.
go back to reference Telinius N, Kim S, Pilegaard H, Pahle E, Nielsen J, Hjortdal V, Aalkjaer C, Boedtkjer DB (2014) The contribution of K(+) channels to human thoracic duct contractility. Am J Physiol Heart Circ Physiol 307:H33–H43PubMedCrossRef Telinius N, Kim S, Pilegaard H, Pahle E, Nielsen J, Hjortdal V, Aalkjaer C, Boedtkjer DB (2014) The contribution of K(+) channels to human thoracic duct contractility. Am J Physiol Heart Circ Physiol 307:H33–H43PubMedCrossRef
108.
go back to reference Hashimoto S, Kawai Y, Ohhashi T (1994) Effects of vasoactive substances on the pig isolated hepatic lymph vessels. J Pharmacol Exp Ther 269:482–488PubMedCrossRef Hashimoto S, Kawai Y, Ohhashi T (1994) Effects of vasoactive substances on the pig isolated hepatic lymph vessels. J Pharmacol Exp Ther 269:482–488PubMedCrossRef
109.
go back to reference Ohhashi T, Azuma T (1986) Pre- and postjunctional alpha-adrenoceptors at sympathetic neuroeffector junction in bovine mesenteric lymphatics. Microvasc Res 31:31–40PubMedCrossRef Ohhashi T, Azuma T (1986) Pre- and postjunctional alpha-adrenoceptors at sympathetic neuroeffector junction in bovine mesenteric lymphatics. Microvasc Res 31:31–40PubMedCrossRef
110.
go back to reference Takahashi N, Kawai Y, Ohhashi T (1990) Effects of vasoconstrictive and vasodilative agents on lymphatic smooth muscles in isolated canine thoracic ducts. J Pharmacol Exp Ther 254:165–170PubMedCrossRef Takahashi N, Kawai Y, Ohhashi T (1990) Effects of vasoconstrictive and vasodilative agents on lymphatic smooth muscles in isolated canine thoracic ducts. J Pharmacol Exp Ther 254:165–170PubMedCrossRef
111.
go back to reference Ohhashi T, McHale NG, Roddie IC, Thornbury KD (1980) Electrical field stimulation as a method of stimulating nerve or smooth muscle in isolated bovine mesenteric lymphatics. Pflugers Arch 388:221–226PubMedCrossRef Ohhashi T, McHale NG, Roddie IC, Thornbury KD (1980) Electrical field stimulation as a method of stimulating nerve or smooth muscle in isolated bovine mesenteric lymphatics. Pflugers Arch 388:221–226PubMedCrossRef
112.
113.
go back to reference Takeshita T, Kawahara M, Fujii K, Kinoshita H, Morio M (1989) The effects of vasoactive drugs on halothane inhibition of contractions of rat mesenteric lymphatics. Lymphology 22:194–198PubMed Takeshita T, Kawahara M, Fujii K, Kinoshita H, Morio M (1989) The effects of vasoactive drugs on halothane inhibition of contractions of rat mesenteric lymphatics. Lymphology 22:194–198PubMed
114.
go back to reference Mohanakumar S, Majgaard J, Telinius N, Katballe N, Pahle E, Hjortdal V, Boedtkjer D (2018) Spontaneous and α-adrenoceptor-induced contractility in human collecting lymphatic vessels require chloride. Am J Physiol Heart Circ Physiol 315:H389–H401PubMedCrossRef Mohanakumar S, Majgaard J, Telinius N, Katballe N, Pahle E, Hjortdal V, Boedtkjer D (2018) Spontaneous and α-adrenoceptor-induced contractility in human collecting lymphatic vessels require chloride. Am J Physiol Heart Circ Physiol 315:H389–H401PubMedCrossRef
115.
go back to reference Lobov GI, Unt DV (2018) Protective effect of dexamethasone on lipopolysaccharide-induced inhibition of contractile function of isolated lymphatic vessels and nodes. Bull Exp Biol Med 165:602–605PubMedCrossRef Lobov GI, Unt DV (2018) Protective effect of dexamethasone on lipopolysaccharide-induced inhibition of contractile function of isolated lymphatic vessels and nodes. Bull Exp Biol Med 165:602–605PubMedCrossRef
116.
go back to reference Petunov SG, Orlov RS (1997) Effects of glucocorticoids on contractions and electric activity of lymphatic vessels. Ross Fiziol Zh Im I M Sechenova 83:59–66PubMed Petunov SG, Orlov RS (1997) Effects of glucocorticoids on contractions and electric activity of lymphatic vessels. Ross Fiziol Zh Im I M Sechenova 83:59–66PubMed
117.
go back to reference Wu TF, Carati CJ, Macnaughton WK, von der Weid PY (2006) Contractile activity of lymphatic vessels is altered in the TNBS model of guinea pig ileitis. Am J Physiol Gastrointest Liver Physiol 291:G566–G574PubMedCrossRef Wu TF, Carati CJ, Macnaughton WK, von der Weid PY (2006) Contractile activity of lymphatic vessels is altered in the TNBS model of guinea pig ileitis. Am J Physiol Gastrointest Liver Physiol 291:G566–G574PubMedCrossRef
Metadata
Title
Moving toward a better understanding of renal lymphatics: challenges and opportunities
Authors
Jianyong Zhong
Jing Liu
Ashley L. Mutchler
Haichun Yang
Annet Kirabo
Elaine L. Shelton
Valentina Kon
Publication date
03-02-2025
Publisher
Springer Berlin Heidelberg
Published in
Pediatric Nephrology
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-025-06692-7

Keynote webinar | Spotlight on adolescent vaping

Growing numbers of young people are using e-cigarettes, despite warnings of respiratory effects and addiction. How can doctors tackle the epidemic, and what health effects should you prepare to manage in your clinics?

Prof. Ann McNeill
Dr. Debbie Robson
Benji Horwell
Developed by: Springer Medicine
Watch now