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Published in: BMC Nephrology 1/2016

Open Access 01-12-2016 | Research article

Relation of peritubular capillary features to class of lupus nephritis

Authors: Sirirat Anutrakulchai, Tanin Titipungul, Thanyaluk Pattay, Putachart Mesung, Anucha Puapairoj, Dhavee Sirivongs, Cholatip Pongsakul, Prasit Futrakul, Bandit Thinkhamrop, Richard J. Johnson

Published in: BMC Nephrology | Issue 1/2016

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Abstract

Background

Experimental studies have linked peritubular capillary (PTC) loss with progression of chronic kidney disease. Minimal information on PTC in lupus nephritis (LN) has been reported. We therefore evaluated the PTC area in different classes of LN and determined if specific clinical characteristics correlated with PTC changes.

Methods

Renal biopsies of 253 subjects with LN (categorized using the ISN/RPS 2003 classification) and 13 normal renal donors (the controls) were retrospectively evaluated for PTC morphology by staining for CD31 with immunohistochemistry method. The percent positive area of PTC (% PTC) was correlated with serum and urinary measures of renal function and renal pathology.

Results

Significant PTC loss was observed in all classes of LN compared to controls. The % PTC area was highest in controls (7.64±1.48 %) with levels of 1.95±1.50, 4.16±3.85, 4.19±4.45, 5.02±1.79, and 4.45±3.75 in classes II, III, IV, IV combined with V and V, respectively (all p values < 0.05). The lowest PTC density was observed in class II LN, but this may be because some cases with worse classes of LN showed increased PTC density due to abnormally dilated capillaries associated with acute inflammation and angiogenesis. %PTC was increased in those with hematuria (5.8±5.2 vs. 3.6±3.4 %, red blood cells 3-10 vs. < 3 cells/high power field, p < 0.05) and was reduced in those with a moderately declined renal function (3.29±3.40 vs. 4.42±4.12, eGFR 15-59 vs. ≥ 60 ml/min/1.73 m2, p < 0.05). Nephrotic-range proteinuria also trended to be associated with lower PTC density although it did not reach statistical significance (3.1±2.6 vs. 4.9±4.5, p= 0.067).

Conclusions

LN is associated with PTC loss and the severity correlates with reduced renal function. Further studies are needed to investigate whether a loss of PTC can predict long term renal outcomes in LN.
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Literature
1.
go back to reference Arbuckle MR, McClain MT, Rubertone MV, Scofield RH, Dennis GJ, James JA, et al. Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N Engl J Med. 2003;349:1526–33.CrossRefPubMed Arbuckle MR, McClain MT, Rubertone MV, Scofield RH, Dennis GJ, James JA, et al. Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N Engl J Med. 2003;349:1526–33.CrossRefPubMed
2.
go back to reference Lorenz G, Desai J, Anders HJ. Lupus nephritis: update on mechanisms of systemic autoimmunity and kidney immunopathology. Curr Opin Nephrol Hypertens. 2014;23:211–7.CrossRefPubMed Lorenz G, Desai J, Anders HJ. Lupus nephritis: update on mechanisms of systemic autoimmunity and kidney immunopathology. Curr Opin Nephrol Hypertens. 2014;23:211–7.CrossRefPubMed
3.
go back to reference Markowitz GS, D’Agati VD. Classification of lupus nephritis. Curr Opin Nephrol Hypertens. 2009;18:220–5.CrossRefPubMed Markowitz GS, D’Agati VD. Classification of lupus nephritis. Curr Opin Nephrol Hypertens. 2009;18:220–5.CrossRefPubMed
4.
go back to reference Weening JJ, D’Agati VD, Schwartz MM, Seshan SV, Alpers CE, Appel GB, et al. Classification of glomerulonephritis in systemic lupus erythematosus revisited. Kidney Int. 2004;65:521–30.CrossRefPubMed Weening JJ, D’Agati VD, Schwartz MM, Seshan SV, Alpers CE, Appel GB, et al. Classification of glomerulonephritis in systemic lupus erythematosus revisited. Kidney Int. 2004;65:521–30.CrossRefPubMed
5.
go back to reference Weening JJ, D’Agati VD, Schwartz MM, Seshan SV, Alpers CE, Appel GB, et al. Classification of glomerulonephritis in systemic lupus erythematosus revisited. J Am Soc Nephrol. 2004;15:241–50.CrossRefPubMed Weening JJ, D’Agati VD, Schwartz MM, Seshan SV, Alpers CE, Appel GB, et al. Classification of glomerulonephritis in systemic lupus erythematosus revisited. J Am Soc Nephrol. 2004;15:241–50.CrossRefPubMed
6.
go back to reference Kiremitci S, Ensari A. Classifying lupus nephritis: an ongoing story. Scientific World Journal. 2014;2014:580620.CrossRefPubMed Kiremitci S, Ensari A. Classifying lupus nephritis: an ongoing story. Scientific World Journal. 2014;2014:580620.CrossRefPubMed
7.
go back to reference Wu LH, Yu F, Tan Y, Qu Z, Chen MH, Wang SX, et al. Inclusion of renal vascular lesions in the 2003 ISN/RPS system for classifying lupus nephritis improves renal outcome predictions. Kidney Int. 2013;83:715–23.CrossRefPubMed Wu LH, Yu F, Tan Y, Qu Z, Chen MH, Wang SX, et al. Inclusion of renal vascular lesions in the 2003 ISN/RPS system for classifying lupus nephritis improves renal outcome predictions. Kidney Int. 2013;83:715–23.CrossRefPubMed
8.
go back to reference Barber C, Herzenberg A, Aghdassi E, Su J, Lou W, Qian G, et al. Evaluation of clinical outcomes and renal vascular pathology among patients with lupus. Clin J Am Soc Nephrol. 2012;7:757–64.CrossRefPubMed Barber C, Herzenberg A, Aghdassi E, Su J, Lou W, Qian G, et al. Evaluation of clinical outcomes and renal vascular pathology among patients with lupus. Clin J Am Soc Nephrol. 2012;7:757–64.CrossRefPubMed
9.
go back to reference Banfi G, Bertani T, Boeri V, Faraggiana T, Mazzucco G, Monga G, et al. Renal vascular lesions as a marker of poor prognosis in patients with lupus nephritis. Am J Kidney Dis. 1991;18:240–8.CrossRefPubMed Banfi G, Bertani T, Boeri V, Faraggiana T, Mazzucco G, Monga G, et al. Renal vascular lesions as a marker of poor prognosis in patients with lupus nephritis. Am J Kidney Dis. 1991;18:240–8.CrossRefPubMed
10.
go back to reference Alsuwaida AO. Interstitial inflammation and long-termrenal outcomes in lupus nephritis. Lupus. 2013;22:1446–54.CrossRefPubMed Alsuwaida AO. Interstitial inflammation and long-termrenal outcomes in lupus nephritis. Lupus. 2013;22:1446–54.CrossRefPubMed
11.
go back to reference Yu F, Wu LH, Tan Y, Li LH, Wang CL, Wang WK, et al. Tubulointerstitial lesions of patients with lupus nephritis classified by the 2003 International Society of Nephrology and Renal Pathology Society system. Kidney Int. 2010;77:820–9.CrossRefPubMed Yu F, Wu LH, Tan Y, Li LH, Wang CL, Wang WK, et al. Tubulointerstitial lesions of patients with lupus nephritis classified by the 2003 International Society of Nephrology and Renal Pathology Society system. Kidney Int. 2010;77:820–9.CrossRefPubMed
12.
go back to reference Hsieh C, Chang A, Brandt D, Guttikonda R, Utset TO, Clark MR. Predicting outcomes of lupus nephritis with tubulointerstitial inflammation and scarring. Arthritis Care Res. 2011;63:865–74.CrossRef Hsieh C, Chang A, Brandt D, Guttikonda R, Utset TO, Clark MR. Predicting outcomes of lupus nephritis with tubulointerstitial inflammation and scarring. Arthritis Care Res. 2011;63:865–74.CrossRef
14.
go back to reference Bohle A, Mackensen-Haen S, Wehrmann M. Significance of postglomerular capillaries in the pathogenesis of chronic renal failure. Kidney Blood Press Res. 1996;19:191–5.CrossRefPubMed Bohle A, Mackensen-Haen S, Wehrmann M. Significance of postglomerular capillaries in the pathogenesis of chronic renal failure. Kidney Blood Press Res. 1996;19:191–5.CrossRefPubMed
15.
go back to reference Konda R, Sato H, Sakai K, Sato M, Orikasa S, Kimura N. Expression of platelet-derived endothelial cell growth factor and its potential role in up-regulation of angiogenesis in scarred kidneys secondary to urinary tract diseases. Am J Pathol. 1999;155:1587–97.CrossRefPubMedPubMedCentral Konda R, Sato H, Sakai K, Sato M, Orikasa S, Kimura N. Expression of platelet-derived endothelial cell growth factor and its potential role in up-regulation of angiogenesis in scarred kidneys secondary to urinary tract diseases. Am J Pathol. 1999;155:1587–97.CrossRefPubMedPubMedCentral
16.
go back to reference Pillebout E, Burtin M, Yuan HT, Briand P, Woolf AS, Friedlander G, et al. Proliferation and remodeling of the peritubular microcirculation after nephron reduction association with the progression of renal lesions. Am J Pathol. 2001;159:547–60.CrossRefPubMedPubMedCentral Pillebout E, Burtin M, Yuan HT, Briand P, Woolf AS, Friedlander G, et al. Proliferation and remodeling of the peritubular microcirculation after nephron reduction association with the progression of renal lesions. Am J Pathol. 2001;159:547–60.CrossRefPubMedPubMedCentral
17.
go back to reference Thacker SG, Berthier CC, Mattinzoli D, Rastaldi MP, Kretzler M, Kaplan MJ. The detrimental effects of IFN-α on vasculogenesis in lupus are mediated by repression of IL-1 pathways: potential role in atherogenesis and renal vascular rarefaction. J Immunol. 2010;185:4457–69.CrossRefPubMedPubMedCentral Thacker SG, Berthier CC, Mattinzoli D, Rastaldi MP, Kretzler M, Kaplan MJ. The detrimental effects of IFN-α on vasculogenesis in lupus are mediated by repression of IL-1 pathways: potential role in atherogenesis and renal vascular rarefaction. J Immunol. 2010;185:4457–69.CrossRefPubMedPubMedCentral
18.
go back to reference Hayakawa S, Nakabayashi K, Karube M, Arimura Y, Soejima A, Yamada A, et al. Tubulointerstitial immune complex nephritis in a patient with systemic lupus erythematosus : role of peritubular capillaritis with immune complex deposits in the pathogenesis of the tubulointerstitial nephritis. Clin Exp Nephrol. 2006;10:146–51.CrossRefPubMed Hayakawa S, Nakabayashi K, Karube M, Arimura Y, Soejima A, Yamada A, et al. Tubulointerstitial immune complex nephritis in a patient with systemic lupus erythematosus : role of peritubular capillaritis with immune complex deposits in the pathogenesis of the tubulointerstitial nephritis. Clin Exp Nephrol. 2006;10:146–51.CrossRefPubMed
19.
go back to reference Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro 3rd AF, Feldman HI, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150:604–12.CrossRefPubMedPubMedCentral Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro 3rd AF, Feldman HI, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150:604–12.CrossRefPubMedPubMedCentral
20.
go back to reference Pusztaszeri MP, Seelentag W, Bosman FT. Immunohistochemical Expression of Endothelial Markers CD31, CD34, von Willebrand Factor, and Fli-1 in Normal Human Tissues. J Histochem Cytochem. 2006;54:385–95.CrossRefPubMed Pusztaszeri MP, Seelentag W, Bosman FT. Immunohistochemical Expression of Endothelial Markers CD31, CD34, von Willebrand Factor, and Fli-1 in Normal Human Tissues. J Histochem Cytochem. 2006;54:385–95.CrossRefPubMed
21.
go back to reference Gluhovschi C, Gluhovschi G, Potencz E, Herman D, Trandafirescu V, Petrica L, et al. The endothelial cell markers von Willebrand Factor (vWF), CD31 and CD34 are lost in glomerulonephritis and no longer correlate with the morphological indices of glomerular sclerosis, interstitial fibrosis, activity and chronicity. Folia Histochem Cytobiol. 2010;48:230–6.CrossRefPubMed Gluhovschi C, Gluhovschi G, Potencz E, Herman D, Trandafirescu V, Petrica L, et al. The endothelial cell markers von Willebrand Factor (vWF), CD31 and CD34 are lost in glomerulonephritis and no longer correlate with the morphological indices of glomerular sclerosis, interstitial fibrosis, activity and chronicity. Folia Histochem Cytobiol. 2010;48:230–6.CrossRefPubMed
22.
go back to reference Sivridis E, Giatromanolaki A, Touloupidis S, Pasadakis P, Vargemezis V. Platelet endothelial cell adhesion molecule-1 and angiogenic factor expression in idiopathic membranous nephropathy. Am J Kidney Dis. 2003;41:360–5.CrossRefPubMed Sivridis E, Giatromanolaki A, Touloupidis S, Pasadakis P, Vargemezis V. Platelet endothelial cell adhesion molecule-1 and angiogenic factor expression in idiopathic membranous nephropathy. Am J Kidney Dis. 2003;41:360–5.CrossRefPubMed
23.
go back to reference Izmirly PM, Barisoni L, Buyon JP, Kim MY, Rivera TL, Schwartzman JS, et al. Expression of endothelial protein C receptor in cortical peritubular capillaries associates with a poor clinical response in lupus nephritis. Rheumatology (Oxford). 2009;48:513–9.CrossRef Izmirly PM, Barisoni L, Buyon JP, Kim MY, Rivera TL, Schwartzman JS, et al. Expression of endothelial protein C receptor in cortical peritubular capillaries associates with a poor clinical response in lupus nephritis. Rheumatology (Oxford). 2009;48:513–9.CrossRef
24.
go back to reference Ohashi R, Kitamura H, Yamanaka N. Peritubular capillary injury during the progression of experimental glomerulonephritis in rats. J Am Soc Nephrol. 2000;11:47–56.PubMed Ohashi R, Kitamura H, Yamanaka N. Peritubular capillary injury during the progression of experimental glomerulonephritis in rats. J Am Soc Nephrol. 2000;11:47–56.PubMed
25.
go back to reference Kang DH, Joly AH, Oh SW, Hugo C, Kerjaschki D, Gordon KL, et al. Impaired angiogenesis in the remnant kidney model: I. Potential role of vascular endothelial growth factor and thrombospondin-1. J Am Soc Nephrol. 2001;12:1434–47.PubMed Kang DH, Joly AH, Oh SW, Hugo C, Kerjaschki D, Gordon KL, et al. Impaired angiogenesis in the remnant kidney model: I. Potential role of vascular endothelial growth factor and thrombospondin-1. J Am Soc Nephrol. 2001;12:1434–47.PubMed
26.
go back to reference Ohashi R, Shimizu A, Masuda Y, Kitamura H, Ishizaki M, Sugisaki Y, et al. Peritubular capillary regression during the progression of experimental obstructive nephropathy. J Am Soc Nephrol. 2002;13:1795–805.CrossRefPubMed Ohashi R, Shimizu A, Masuda Y, Kitamura H, Ishizaki M, Sugisaki Y, et al. Peritubular capillary regression during the progression of experimental obstructive nephropathy. J Am Soc Nephrol. 2002;13:1795–805.CrossRefPubMed
27.
go back to reference Zhu XY, Chade AR, Rodriguez-Porcel M, Bentley MD, Ritman EL, Lerman A, et al. Cortical microvascular remodeling in the stenotic kidney: role of increased oxidative stress. Arterterioscl Thromb Vasc Biol. 2004;24:1854–9.CrossRef Zhu XY, Chade AR, Rodriguez-Porcel M, Bentley MD, Ritman EL, Lerman A, et al. Cortical microvascular remodeling in the stenotic kidney: role of increased oxidative stress. Arterterioscl Thromb Vasc Biol. 2004;24:1854–9.CrossRef
28.
go back to reference Futrakul N, Futrakul P. Renal microvascular disease in an aging population: a reversible process? Ren Fail. 2008;30:353–6.CrossRefPubMed Futrakul N, Futrakul P. Renal microvascular disease in an aging population: a reversible process? Ren Fail. 2008;30:353–6.CrossRefPubMed
29.
go back to reference Carmi Y, Voronov E, Dotan S, Lahat N, Rahat MA, Fogel M, et al. The role of macrophage-derived IL-1 in induction and maintenance of angiogenesis. J Immunol. 2009;183:4705–14.CrossRefPubMed Carmi Y, Voronov E, Dotan S, Lahat N, Rahat MA, Fogel M, et al. The role of macrophage-derived IL-1 in induction and maintenance of angiogenesis. J Immunol. 2009;183:4705–14.CrossRefPubMed
30.
go back to reference Ono M. Molecular links between tumor angiogenesis and inflammation: inflammatory stimuli of macrophages and cancer cells as targets for therapeutic strategy. Cancer Sci. 2008;99:1501–6.CrossRefPubMed Ono M. Molecular links between tumor angiogenesis and inflammation: inflammatory stimuli of macrophages and cancer cells as targets for therapeutic strategy. Cancer Sci. 2008;99:1501–6.CrossRefPubMed
31.
go back to reference Avihingsanon Y, Benjachat T, Tassanarong A, Sodsai P, Kittikovit V, Hirankarn N. Decreased renal expression of vascular endothelial growth factor in lupus nephritis is associated withworse prognosis. Kidney Int. 2009;75:1340–8.CrossRefPubMed Avihingsanon Y, Benjachat T, Tassanarong A, Sodsai P, Kittikovit V, Hirankarn N. Decreased renal expression of vascular endothelial growth factor in lupus nephritis is associated withworse prognosis. Kidney Int. 2009;75:1340–8.CrossRefPubMed
32.
go back to reference Shulman K, Rosen S, Tognazzi K, Manseau EJ, Brown LF. Expression of vascular permeability factor (VPF/VEGF) is altered in many glomerular diseases. J Am Soc Nephrol. 1996;7:661–6.PubMed Shulman K, Rosen S, Tognazzi K, Manseau EJ, Brown LF. Expression of vascular permeability factor (VPF/VEGF) is altered in many glomerular diseases. J Am Soc Nephrol. 1996;7:661–6.PubMed
33.
go back to reference Robak E, Sysa-Jedrzejewska A, Robak T. Vascular endothelial growth factor and its soluble receptors VEGFR-1 and VEGFR-2 in the serum of patients with systemic lupus erythematosus. Mediators Inflamm. 2003;12:293–8.CrossRefPubMedPubMedCentral Robak E, Sysa-Jedrzejewska A, Robak T. Vascular endothelial growth factor and its soluble receptors VEGFR-1 and VEGFR-2 in the serum of patients with systemic lupus erythematosus. Mediators Inflamm. 2003;12:293–8.CrossRefPubMedPubMedCentral
34.
go back to reference Heshmat NM, El-Kerdany TH. Serum levels of vascular endothelial growth factor in children and adolescents with systemic lupus erythematosus. Pediatr Allergy Immunol. 2007;18:346–53.CrossRefPubMed Heshmat NM, El-Kerdany TH. Serum levels of vascular endothelial growth factor in children and adolescents with systemic lupus erythematosus. Pediatr Allergy Immunol. 2007;18:346–53.CrossRefPubMed
35.
go back to reference Navarro C, Candia-Zuniga L, Silveira LH, Ruiz V, Gaxiola M, Avila MC, et al. Vascular endothelial growth factor plasma levels in patients with systemic lupus erythematosus and primary antiphospholipid syndrome. Lupus. 2002;11:21–4.CrossRefPubMed Navarro C, Candia-Zuniga L, Silveira LH, Ruiz V, Gaxiola M, Avila MC, et al. Vascular endothelial growth factor plasma levels in patients with systemic lupus erythematosus and primary antiphospholipid syndrome. Lupus. 2002;11:21–4.CrossRefPubMed
36.
go back to reference Frieri M, Samih MA, Dzhindzhikhashvili M, Liu H, Balsam L, Rubinstein S, Frieri M, Samih MA, Dzhindzhikhashvili M, Liu H, Balsam L, Rubinstein S. Toll-like receptor 9 and vascular endothelial growth factor levels in human kidneys from lupus nephritis patients. J Nephrol. 2012;25:1041–6.CrossRefPubMed Frieri M, Samih MA, Dzhindzhikhashvili M, Liu H, Balsam L, Rubinstein S, Frieri M, Samih MA, Dzhindzhikhashvili M, Liu H, Balsam L, Rubinstein S. Toll-like receptor 9 and vascular endothelial growth factor levels in human kidneys from lupus nephritis patients. J Nephrol. 2012;25:1041–6.CrossRefPubMed
37.
go back to reference Avihingsanon Y, Phumesin P, Benjachat T, Akkasilpa S, Kittikowit V, Praditpornsilpa K, et al. Measurement of urinary chemokine and growth factor messenger RNAs: a noninvasive monitoring in lupus nephritis. Kidney Int. 2006;69:747–53.CrossRefPubMed Avihingsanon Y, Phumesin P, Benjachat T, Akkasilpa S, Kittikowit V, Praditpornsilpa K, et al. Measurement of urinary chemokine and growth factor messenger RNAs: a noninvasive monitoring in lupus nephritis. Kidney Int. 2006;69:747–53.CrossRefPubMed
38.
go back to reference Sloan RP, Schwartz MM, Korbet SM, Borok RZ. Long-term outcome in systemic lupus erythematosus membranous glomerulonephritis. Lupus Nephritis Collaborative Study Group. J Am Soc Nephrol. 1996;7:299.PubMed Sloan RP, Schwartz MM, Korbet SM, Borok RZ. Long-term outcome in systemic lupus erythematosus membranous glomerulonephritis. Lupus Nephritis Collaborative Study Group. J Am Soc Nephrol. 1996;7:299.PubMed
39.
go back to reference Katavetin P, Inagi R, Miyata T, Tanaka T, Sassa R, Ingelfinger JR, et al. Albumin suppresses vascular endothelial growth factor via alteration of hypoxia-inducible factor/hypoxia-responsive element pathway. Biochem Biophys Res Com. 2008;367:305–10.CrossRefPubMed Katavetin P, Inagi R, Miyata T, Tanaka T, Sassa R, Ingelfinger JR, et al. Albumin suppresses vascular endothelial growth factor via alteration of hypoxia-inducible factor/hypoxia-responsive element pathway. Biochem Biophys Res Com. 2008;367:305–10.CrossRefPubMed
Metadata
Title
Relation of peritubular capillary features to class of lupus nephritis
Authors
Sirirat Anutrakulchai
Tanin Titipungul
Thanyaluk Pattay
Putachart Mesung
Anucha Puapairoj
Dhavee Sirivongs
Cholatip Pongsakul
Prasit Futrakul
Bandit Thinkhamrop
Richard J. Johnson
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Nephrology / Issue 1/2016
Electronic ISSN: 1471-2369
DOI
https://doi.org/10.1186/s12882-016-0388-2

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