Top

Published in:

Open Access 01-12-2019 | Systemic Lupus Erythematosus | Research article

Urinary podocyte microparticles are associated with disease activity and renal injury in systemic lupus erythematosus

Authors: Jian Lu, Ze Bo Hu, Pei Pei Chen, Chen Chen Lu, Jia Xiu Zhang, Xue Qi Li, Ben Yin Yuan, Si Jia Huang, Kun Ling Ma

Published in: BMC Nephrology | Issue 1/2019

Abstract

Background

New non-invasive biomarkers are demanded to identify renal damage in various autoimmune-associated kidney diseases. Glomerular podocyte damage mediated by systemic lupus erythematosus (SLE) plays an important role in the pathogenesis and progression of lupus nephritis (LN). This study evaluated whether the podocyte-derived microparticles (MPs) were novel biomarkers of clinical and histological features in SLE patients with LN.

Methods

A cross-sectional study, including 34 SLE patients and 16 healthy controls, was designed. Urinary annexin V⁺ podocalyxin⁺ MPs of all participants were quantified by flow cytometry. The correlation of podocyte-derived MPs with clinical and histological parameters of SLE patients was analysed.

Results

The number of annexin V⁺ podocalyxin⁺ MPs from urine samples were markly increased in patients with SLE. Furthermore, the level of urinary podocyte-derived MPs was positively correlated with the SLE Disease Activity Index (SLEDAI) score, anti-dsDNA antibody titre, erythrocyte sedimentation rate, and proteinuria. Conversely, it was negatively correlated with the level of complement C3 and serum albumin. The number of urinary podocyte-derived MPs was significantly increased in SLE patients with high activity indices. Receiver operating characteristic (ROC) curves were calculated to assess the power for podocyte-derived MP levels in differentiating between SLE patients with and without LN. Podocyte-derived MP levels were able to differentiate between SLE patients with mild disease activity, as well as those with moderate and above disease activity. SLE patients showed increased podocyte-derived MP excretion into the urine.

Conclusions

These findings suggest that the change in urinary podocyte-derived MP levels could be useful for evaluating and monitoring SLE disease activity.

Martinez MC, Andriantsitohaina R. Extracellular vesicles in metabolic syndrome. Circ Res. 2017;120(10):1674–86. https://doi.org/10.1161/CIRCRESAHA.117.309419.CrossRefPubMed

Pomatto MAC, Gai C, Bussolati B, Camussi G. Extracellular vesicles in renal pathophysiology. Front Mol Biosci. 2017;4:37. https://doi.org/10.3389/fmolb.2017.00037.CrossRefPubMedPubMedCentral

Burger D, Thibodeau JF, Holterman CE, Burns KD, Touyz RM, Kennedy CR. Urinary podocyte microparticles identify prealbuminuric diabetic glomerular injury. J Am Soc Nephrol. 2014;25(7):1401–7. https://doi.org/10.1681/ASN.2013070763.CrossRefPubMedPubMedCentral

Gilani SI, Anderson UD, Jayachandran M, Weissgerber TL, Zand L, White WM, Milic N, Suarez MLG, Vallapureddy RR, Naav A, Erlandsson L, Lieske JC, Grande JP, Nath KA, Hansson SR, Garovic VD. Urinary extracellular vesicles of podocyte origin and renal injury in preeclampsia. J Am Soc Nephrol. 2017;28(11):3363–72. https://doi.org/10.1681/ASN.2016111202.CrossRefPubMedPubMedCentral

Kwon SH, Woollard JR, Saad A, Garovic VD, Zand L, Jordan KL, Textor SC, Lerman LO. Elevated urinary podocyte-derived extracellular microvesicles in renovascular hypertensive patients. Nephrol Dial Transplant. 2017;32(5):800–7. https://doi.org/10.1093/ndt/gfw077.CrossRefPubMed

Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang CH. Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE Arthritis Rheum. 1992;35(6):630–40.CrossRef

Weening JJ, D'Agati VD, Schwartz MM, Seshan SV, Alpers CE, Appel GB, Balow JE, Bruijn JA, Cook T, Ferrario F, Fogo AB, Ginzler EM, Hebert L, Hill G, Hill P, Jennette JC, Kong NC, Lesavre P, Lockshin M, Looi LM, Makino H, Moura LA, Nagata M. The classification of glomerulonephritis in systemic lupus erythematosus revisited. J Am So Nephrol. 2004;15(2):241–50.CrossRef

Zhou H, Yuen PS, Pisitkun T, Gonzales PA, Yasuda H, Dear JW, Gross P, Knepper MA, Star RA. Collection, storage, preservation, and normalization of human urinary exosomes for biomarker discovery. Kidney Int. 2006;69(8):1471–6. https://doi.org/10.1038/sj.ki.5000273.CrossRefPubMedPubMedCentral

Dos Santos M, Poletti PT, Milhoransa P, Monticielo OA, Veronese FV. Unraveling the podocyte injury in lupus nephritis: clinical and experimental approaches. Semin Arthritis Rheum. 2017;46(5):632–41. https://doi.org/10.1016/j.semarthrit.2016.10.005.CrossRefPubMed

10.

dos Santos M, Bringhenti RN, Rodrigues PG, do Nascimento JF, Pereira SV, Zancan R, Monticielo OA, Gasparin AA, de Castro WP, Veronese FV. Podocyte-associated mRNA profiles in kidney tissue and in urine of patients with active lupus nephritis. Int J Clin Exp Pathol. 2015;8(5):4600–13.PubMedPubMedCentral

11.

Rezende GM, Viana VS, Malheiros DM, Borba EF, Silva NA, Silva C, Leon EP, Noronha IL, Bonfa E. Podocyte injury in pure membranous and proliferative lupus nephritis: distinct underlying mechanisms of proteinuria? Lupus. 2014;23(3):255–62. https://doi.org/10.1177/0961203313517152.CrossRefPubMed

12.

Perysinaki GS, Moysiadis DK, Bertsias G, Giannopoulou I, Kyriacou K, Nakopoulou L, Boumpas DT, Daphnis E. Podocyte main slit diaphragm proteins, nephrin and podocin, are affected at early stages of lupus nephritis and correlate with disease histology. Lupus. 2011;20(8):781–91. https://doi.org/10.1177/0961203310397412.CrossRefPubMed

13.

Burger D, Schock S, Thompson CS, Montezano AC, Hakim AM, Touyz RM. Microparticles: biomarkers and beyond. Clin Sci (Lond). 2013;124(7):423–41. https://doi.org/10.1042/CS20120309.CrossRef

14.

Vinuela-Berni V, Doniz-Padilla L, Figueroa-Vega N, Portillo-Salazar H, Abud-Mendoza C, Baranda L, Gonzalez-Amaro R. Proportions of several types of plasma and urine microparticles are increased in patients with rheumatoid arthritis with active disease. Clin Exp Immunol. 2015;180(3):442–51. https://doi.org/10.1111/cei.12598.CrossRefPubMedPubMedCentral

15.

Ramezani A, Devaney JM, Cohen S, Wing MR, Scott R, Knoblach S, Singhal R, Howard L, Kopp JB, Raj DS. Circulating and urinary microRNA profile in focal segmental glomerulosclerosis: a pilot study. Eur J Clin Investig. 2015;45(4):394–404. https://doi.org/10.1111/eci.12420.CrossRef

16.

Delic D, Eisele C, Schmid R, Baum P, Wiech F, Gerl M, Zimdahl H, Pullen SS, Urquhart R. Urinary Exosomal miRNA signature in type II diabetic nephropathy patients. PLoS One. 2016;11(3):e0150154. https://doi.org/10.1371/journal.pone.0150154.CrossRefPubMedPubMedCentral

17.

Pisetsky D. The role of microparticles in the pathogenesis of SLE: a new look at an old paradigm. Lupus Sci Med. 2017;4(1):e000220. https://doi.org/10.1136/lupus-2017-000220.CrossRefPubMedPubMedCentral

18.

Merchant ML, Rood IM, Deegens JKJ, Klein JB. Isolation and characterization of urinary extracellular vesicles: implications for biomarker discovery. Nat Rev Nephrol. 2017;13(12):731–49. https://doi.org/10.1038/nrneph.2017.148.CrossRefPubMedPubMedCentral

19.

Barreiro K, Holthofer H. Urinary extracellular vesicles. A promising shortcut to novel biomarker discoveries. Cell Tissue Res. 2017;369(1):217–27. https://doi.org/10.1007/s00441-017-2621-0.CrossRefPubMedPubMedCentral

20.

Liu ML, Williams KJ, Werth VP. Microvesicles in autoimmune diseases. Adv Clin Chem. 2016;77:125–75. https://doi.org/10.1016/bs.acc.2016.06.005.CrossRefPubMed

21.

Nielsen JS, McNagny KM. The role of podocalyxin in health and disease. J Am Soc Nephrol. 2009;20(8):1669–76. https://doi.org/10.1681/ASN.2008070782.CrossRefPubMed

22.

Hara M, Yanagihara T, Kihara I, Higashi K, Fujimoto K, Kajita T. Apical cell membranes are shed into urine from injured podocytes: a novel phenomenon of podocyte injury. J Am Soc Nephrol. 2005;16(2):408–16. https://doi.org/10.1681/ASN.2004070564.CrossRefPubMed

23.

Lam GK, Petri M. Assessment of systemic lupus erythematosus. Clin Exp Rheumatol. 2005;23(5 Suppl 39):S120–32.PubMed

24.

Houssiau FA, D'Cruz D, Sangle S, Remy P, Vasconcelos C, Petrovic R, Fiehn C, de Ramon Garrido E, Gilboe IM, Tektonidou M, Blockmans D, Ravelingien I, le Guern V, Depresseux G, Guillevin L, Cervera R, Group MNT. Azathioprine versus mycophenolate mofetil for long-term immunosuppression in lupus nephritis: results from the MAINTAIN nephritis trial. Ann Rheum Dis. 2010;69(12):2083–9. https://doi.org/10.1136/ard.2010.131995.CrossRefPubMedPubMedCentral

25.

Zhao Z, Weinstein E, Tuzova M, Davidson A, Mundel P, Marambio P, Putterman C. Cross-reactivity of human lupus anti-DNA antibodies with alpha-actinin and nephritogenic potential. Arthritis Rheum. 2005;52(2):522–30. https://doi.org/10.1002/art.20862.CrossRefPubMed

26.

Arriens C, Wren JD, Munroe ME, Mohan C. Systemic lupus erythematosus biomarkers: the challenging quest. Rheumatology (Oxford). 2017;56(suppl_1):i32–45. https://doi.org/10.1093/rheumatology/kew407.CrossRef

27.

Parikh SV, Nagaraja HN, Hebert L, Rovin BH. Renal flare as a predictor of incident and progressive CKD in patients with lupus nephritis. Clin J Am Soc Nephrol. 2014;9(2):279–84. https://doi.org/10.2215/CJN.05040513.CrossRefPubMed

Title: Urinary podocyte microparticles are associated with disease activity and renal injury in systemic lupus erythematosus
Authors: Jian Lu
Ze Bo Hu
Pei Pei Chen
Chen Chen Lu
Jia Xiu Zhang
Xue Qi Li
Ben Yin Yuan
Si Jia Huang
Kun Ling Ma
Publication date: 01-12-2019
Publisher: BioMed Central
Keywords: Systemic Lupus Erythematosus
Lupus Nephritis
Published in: BMC Nephrology / Issue 1/2019
Electronic ISSN: 1471-2369
DOI: https://doi.org/10.1186/s12882-019-1482-z

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Urinary podocyte microparticles are associated with disease activity and renal injury in systemic lupus erythematosus

Abstract

Background

Methods

Results

Conclusions

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2019

Partial nephrogenic diabetes insipidus associated with Castleman’s disease

An exploration of symptom burden and its management, in Saudi Arabian patients receiving haemodialysis, and their caregivers: a mixed methods study protocol

Higher serum uric acid level is inversely associated with renal function assessed by cystatin C in a Japanese general population without chronic kidney disease: the KOBE study

Sleep disturbance among Malaysian patients with end-stage renal disease with pruritus

Comparison between three different equations for the estimation of glomerular filtration rate in predicting mortality after coronary artery bypass

A case report of recurrent membranoproliferative glomerulonephritis after kidney transplantation due to ventriculoatrial shunt infection

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page