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Dyslipidemia may be a risk factor for progression in children with IgA nephropathy

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Abstract

Background

IgA nephropathy (IgAN) is often chronically progressive and commonly accompanied by dyslipidemia. However, the intrinsic relationship between dyslipidemia and IgAN remains to be elucidated. This study aimed to investigate the impact of different types of dyslipidemia on clinical and pathological characteristics in children with IgAN.

Methods

In our retrospective cohort study from January 2006 to January 2021, 276 children with IgAN were ultimately included in the baseline analysis, and 169 were included in the follow-up analysis. The clinical and pathological features of different types of dyslipidemia and their effect on kidney prognosis were analyzed.

Results

Children in the dyslipidemia group had more severe clinical characteristics (higher blood urea nitrogen, serum uric acid, and 24-h proteinuria; higher proportion of hypertension; and lower serum albumin and estimated glomerular filtration rate) and pathological changes (higher proportion of Lee grades IV–V and E1, S1, and C2 in MEST-C). Furthermore, the clinical and pathological characteristics were worse in the mixed hyperlipidemia group. Multivariate logistic analysis showed that hypertension, steroid treatment, lower serum albumin, severe proteinuria, and segmental glomerulosclerosis were independent risk factors for dyslipidemia in children with IgAN. The Kaplan–Meier analysis revealed that the probability of kidney survival in children with dyslipidemia was lower than that in those without dyslipidemia, with a median follow-up of 5.9 years.

Conclusions

Children with IgAN and dyslipidemia, especially mixed hyperlipidemia, are prone to more severe clinical and pathological changes. Our study provides further insight into dyslipidemia as a potential risk factor in children with IgAN.

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Data availability

The data are available from the corresponding author upon reasonable request.

Code availability

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References

  1. Xu X, Wang G, Chen N, Lu T, Nie S, Xu G, Zhang P, Luo Y, Wang Y, Wang X, Schwartz J, Geng J, Hou FF (2016) Long-term exposure to air pollution and increased risk of membranous nephropathy in China. J Am Soc Nephrol 27:3739–3746. https://doi.org/10.1681/ASN.2016010093

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Yang Y, Zhang Z, Zhuo L, Chen DP, Li WG (2018) The spectrum of biopsy-proven glomerular disease in China: a systematic review. Chin Med J (Engl) 131:731–735. https://doi.org/10.4103/0366-6999.226906

    Article  Google Scholar 

  3. Magistroni R, D’Agati VD, Appel GB, Kiryluk K (2015) New developments in the genetics, pathogenesis, and therapy of IgA nephropathy. Kidney Int 88:974–989. https://doi.org/10.1038/ki.2015.252

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Coppo R, Robert T (2020) IgA nephropathy in children and in adults: two separate entities or the same disease? J Nephrol 33:1219–1229. https://doi.org/10.1007/s40620-020-00725-0

    Article  PubMed  Google Scholar 

  5. Editorial Board of Chinese Journal of Pediatrics (2009) Expert consensus for prevention and treatment of dyslipidemia in children and adolescents. Chin J Pediatr 47:426–428

  6. Ashoor IF, Mansfield SA, O’Shaughnessy MM, Parekh RS, Zee J, Vasylyeva TL, Kogon AJ, Sethna CB, Glenn DA, Chishti AS, Weaver DJ, Helmuth ME, Fernandez HE, Rheault MN; CureGN Consortium (2019) Prevalence of cardiovascular disease risk factors in childhood glomerular diseases. J Am Heart Assoc 8:012143. https://doi.org/10.1161/JAHA.119.012143

  7. Gai Z, Wang T, Visentin M, Kullak-Ublick GA, Fu X, Wang Z (2019) Lipid accumulation and chronic kidney disease. Nutrients 11:722. https://doi.org/10.3390/nu11040722

    Article  CAS  PubMed Central  Google Scholar 

  8. Hager MR, Narla AD, Tannock LR (2017) Dyslipidemia in patients with chronic kidney disease. Rev Endocr Metab Disord 18:29–40. https://doi.org/10.1007/s11154-016-9402-z

    Article  CAS  PubMed  Google Scholar 

  9. Pan L, Liao YH, Mo MQ, Zhang QH, Yin RX (2020) CMIP SNPs and their haplotypes are associated with dyslipidaemia and clinicopathologic features of IgA nephropathy. Biosci Rep 40:BSR20202628. https://doi.org/10.1042/BSR20202628

  10. Syrjanen J, Mustonen J, Pasternack A (2000) Hypertriglyceridaemia and hyperuricaemia are risk factors for progression of IgA nephropathy. Nephrol Dial Transplant 15:34–42. https://doi.org/10.1093/ndt/15.1.34

    Article  CAS  PubMed  Google Scholar 

  11. Deng Y, Wu Q, Chen W, Zhu L, Liu W, Xia F, Sun L, Lin X, Zeng R (2021) Lipidomics reveals association of circulating lipids with body mass index and outcomes in IgA nephropathy patients. J Mol Cell Biol 13:565–575. https://doi.org/10.1093/jmcb/mjab040

    Article  CAS  PubMed Central  Google Scholar 

  12. Zhao Y-Y, Vaziri ND, Lin R-C (2015) Lipidomics: new insight into kidney disease. Adv Clin Chem 68:153–175. https://doi.org/10.1016/bs.acc.2014.11.002

    Article  CAS  PubMed  Google Scholar 

  13. Schwartz GJ, Muñoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, Furth SL (2009) New equations to estimate GFR in children with CKD. J Am Soc Nephrol 20:629–637. https://doi.org/10.1681/ASN.2008030287

    Article  PubMed  PubMed Central  Google Scholar 

  14. Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150:604–612. https://doi.org/10.7326/0003-4819-150-9-200905050-00006

    Article  PubMed  PubMed Central  Google Scholar 

  15. Levin A, Stevens PE (2014) Summary of KDIGO 2012 CKD Guideline: behind the scenes, need for guidance, and a framework for moving forward. Kidney Int 85:49–61. https://doi.org/10.1038/ki.2013.444

    Article  PubMed  Google Scholar 

  16. Flynn JT, Kaelber DC, Baker-Smith CM, Blowey D, Carroll AE, Daniels SR, de Ferranti SD, Dionne JM, Falkner B, Flinn SK, Gidding SS, Goodwin C, Leu MG, Powers ME, Rea C, Samuels J, Simasek M, Thaker VV, Urbina EM (2017) Clinical practice guideline for screening and management of high blood pressure in children and adolescents. Pediatrics 140:e20171904. https://doi.org/10.1542/peds.2017-1904

    Article  PubMed  Google Scholar 

  17. Hogan MC, Reich HN, Nelson PJ, Adler SG, Cattran DC, Appel GB, Gipson DS, Kretzler M, Troost JP, Lieske JC (2016) The relatively poor correlation between random and 24-hour urine protein excretion in patients with biopsy-proven glomerular diseases. Kidney Int 90:1080–1089. https://doi.org/10.1016/j.kint.2016.06.020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Du Bois D, Du Bois EF (1989) A formula to estimate the approximate surface area if height and weight be known. 1916. Nutrition 5:303–313

    PubMed  Google Scholar 

  19. Knoppova B, Reily C, Maillard N, Rizk DV, Moldoveanu Z, Mestecky J, Raska M, Renfrow MB, Julian BA, Novak J (2016) The origin and activities of IgA1-containing immune complexes in IgA nephropathy. Front Immunol 7:117. https://doi.org/10.3389/fimmu.2016.00117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Lee SM, Rao VM, Franklin WA, Schiffer MS, Aronson AJ, Spargo BH, Katz AI (1982) IgA nephropathy: morphologic predictors of progressive renal disease. Hum Pathol 13:314–322. https://doi.org/10.1016/s0046-8177(82)80221-9

    Article  CAS  PubMed  Google Scholar 

  21. Trimarchi H, Barratt J, Cattran DC, Cook HT, Coppo R, Haas M, Liu Z-H, Roberts ISD, Yuzawa Y, Zhang H, Feehally J (2017) Oxford classification of IgA nephropathy 2016: an update from the IgA nephropathy classification working group. Kidney Int 91:1014–1021. https://doi.org/10.1016/j.kint.2017.02.003

    Article  PubMed  Google Scholar 

  22. (1992) National Cholesterol Education Program (NCEP): highlights of the report of the expert panel on blood cholesterol levels in children and adolescents. Pediatrics 89:495–501

  23. Pan L, Yang Z, Wu Y, Yin R-X, Liao Y, Wang J, Gao B, Zhang L (2016) The prevalence, awareness, treatment and control of dyslipidemia among adults in China. Atherosclerosis 248:2–9. https://doi.org/10.1016/j.atherosclerosis.2016.02.006

    Article  CAS  PubMed  Google Scholar 

  24. Le W, Liang S, Hu Y, Deng K, Bao H, Zeng C, Liu Z (2012) Long-term renal survival and related risk factors in patients with IgA nephropathy: results from a cohort of 1155 cases in a Chinese adult population. Nephrol Dial Transplant 27:1479–1485. https://doi.org/10.1093/ndt/gfr527

    Article  CAS  PubMed  Google Scholar 

  25. Wang J, He L, Yan W, Peng X, He L, Yang D, Liu H, Peng Y (2020) The role of hypertriglyceridemia and treatment patterns in the progression of IgA nephropathy with a high proportion of global glomerulosclerosis. Int Urol Nephrol 52:325–335. https://doi.org/10.1007/s11255-019-02371-3

    Article  CAS  PubMed  Google Scholar 

  26. Gyebi L, Soltani Z, Reisin E (2012) Lipid nephrotoxicity: new concept for an old disease. Curr Hypertens Rep 14:177–181. https://doi.org/10.1007/s11906-012-0250-2

    Article  CAS  PubMed  Google Scholar 

  27. Moorhead JF, Chan MK, El-Nahas M, Varghese Z (1982) Lipid nephrotoxicity in chronic progressive glomerular and tubulo-interstitial disease. Lancet 2:1309–1311. https://doi.org/10.1016/s0140-6736(82)91513-6

    Article  CAS  PubMed  Google Scholar 

  28. Wu H, Xia Z, Gao C, Zhang P, Yang X, Wang R, Wang M, Peng Y (2020) The correlation analysis between the Oxford classification of Chinese IgA nephropathy children and renal outcome - a retrospective cohort study. BMC Nephrol 21:247. https://doi.org/10.1186/s12882-020-01913-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Opazo-Ríos L, Mas S, Marín-Royo G, Mezzano S, Gómez-Guerrero C, Moreno JA, Egido J (2020) Lipotoxicity and diabetic nephropathy: novel mechanistic insights and therapeutic opportunities. Int J Mol Sci 21:2632. https://doi.org/10.3390/ijms21072632

    Article  CAS  PubMed Central  Google Scholar 

  30. Bellur SS, Lepeytre F, Vorobyeva O, Troyanov S, Cook HT, Roberts ISD (2017) Evidence from the Oxford Classification cohort supports the clinical value of subclassification of focal segmental glomerulosclerosis in IgA nephropathy. Kidney Int 91:235–243. https://doi.org/10.1016/j.kint.2016.09.029

    Article  PubMed  Google Scholar 

  31. Trimarchi H, Coppo R (2020) The implications of focal segmental glomerulosclerosis in children with IgA nephropathy. Pediatr Nephrol 35:2043–2047. https://doi.org/10.1007/s00467-019-04414-4

    Article  PubMed  Google Scholar 

  32. Maixnerova D, Reily C, Bian Q, Neprasova M, Novak J, Tesar V (2016) Markers for the progression of IgA nephropathy. J Nephrol 29:535–541. https://doi.org/10.1007/s40620-016-0299-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Moran SM, Cattran DC (2019) Recent advances in risk prediction, therapeutics and pathogenesis of IgA nephropathy. Minerva Med 110:439–449. https://doi.org/10.23736/S0026-4806.19.06165-2

  34. Berthoux F, Mohey H, Laurent B, Mariat C, Afiani A, Thibaudin L (2011) Predicting the risk for dialysis or death in IgA nephropathy. J Am Soc Nephrol 22:752–761. https://doi.org/10.1681/ASN.2010040355

    Article  PubMed  PubMed Central  Google Scholar 

  35. Fu Q-Y, Ma L, Li C-C, He Z-J, Wang W-H, Luo K-F, Liu Y, Zhang Z-H, Yang Z-B, Tang H-L, Yan J-H (2020) Hypertension/prehypertension and its determinants in pediatric IgA nephropathy. Medicine (Baltimore) 99:e22310. https://doi.org/10.1097/MD.0000000000022310

    Article  CAS  Google Scholar 

  36. Ivanovic B, Tadic M (2015) Hypercholesterolemia and hypertension: two sides of the same coin. Am J Cardiovasc Drugs 15:403–414. https://doi.org/10.1007/s40256-015-0128-1

    Article  CAS  PubMed  Google Scholar 

  37. Hurtubise J, McLellan K, Durr K, Onasanya O, Nwabuko D, Ndisang JF (2016) The different facets of dyslipidemia and hypertension in atherosclerosis. Curr Atheroscler Rep 18:82. https://doi.org/10.1007/s11883-016-0632-z

    Article  CAS  PubMed  Google Scholar 

  38. Sarnak MJ, Bloom R, Muntner P, Rahman M, Saland JM, Wilson PWF, Fried L (2015) KDOQI US commentary on the 2013 KDIGO Clinical Practice Guideline for Lipid Management in CKD. Am J Kidney Dis 65:354–366. https://doi.org/10.1053/j.ajkd.2014.10.005

    Article  PubMed  Google Scholar 

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Acknowledgements

The authors thank all physicians who processed medical work and all children and their families who participated in this study.

Funding

This study received financial support from the National Natural Science Foundation of China (NSFC No. 81970611), and Guangdong Basic and Applied Basic Research Foundation (No. 2019A1515011546 and No. 2019A1515010694), and College Student Innovation and Entrepreneurship Program of Sun Yat-sen University (grant number: 202210651).

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Authors and Affiliations

  1. Department of Pediatric Nephrology and Rheumatology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China

    Hongjie Zhuang, Zhilang Lin, Shuhan Zeng, Mengjie Jiang, Lizhi Chen, Xiaoyun Jiang & Yuanyuan Xu

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  1. Hongjie Zhuang
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  2. Zhilang Lin
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  3. Shuhan Zeng
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  5. Lizhi Chen
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  6. Xiaoyun Jiang
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  7. Yuanyuan Xu
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Contributions

Yuanyuan Xu and Xiaoyun Jiang designed the study. Hongjie Zhuang and Shuhan Zeng collected the clinical data from the patients. Hongjie Zhuang, Zhilang Lin, and Mengjie Jiang performed the data analyses and wrote the manuscript. Yuanyuan Xu, Lizhi Chen, and Xiaoyun Jiang were the treating physicians of the patients and conducted a discussion. All the authors revised and approved the final version.

Corresponding authors

Correspondence to Xiaoyun Jiang or Yuanyuan Xu.

Ethics declarations

Ethics approval

This study was in accordance with the Declaration of Helsinki and approved by the ethics committee of the First Affiliated Hospital, Sun Yat-sen University (No. (2016) 040).

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Informed consent was obtained from legal guardians.

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The participants consented to the submission of the report for publication.

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The authors declare no competing interests.

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Hongjie Zhuang and Zhilang Lin contributed equally to this work.

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Zhuang, H., Lin, Z., Zeng, S. et al. Dyslipidemia may be a risk factor for progression in children with IgA nephropathy. Pediatr Nephrol 37, 3147–3156 (2022). https://doi.org/10.1007/s00467-022-05480-x

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