The association between serum Perilipin-2 and kidney disease progression of patients with autosomal dominant polycystic kidney disease

Yıl 2024, Cilt: 4 Sayı: 1, 7 - 16, 29.01.2024

Mustafa Çetin , Eray Eroğlu , Çiğdem Karakükçü , Gökmen Zararsız , Ayşenur Çırak Gürsoy , İsmail Koçyiğit

https://doi.org/10.56016/dahudermj.1357040

Öz

Objective: We aimed to evaluate the relationship between serum perilipin-2 / adipophilin (PLIN-2 / ADRP) levels and clinical course in patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD).
Methods: 80 ADPKD patients with Chronic Kidney Disease (CKD) G1-G4 status, among the patients who were regularly followed up in the nephrology outpatient clinic between 2012 and 2019, were included in the study. CKD-G5 patients were excluded from the study. Baseline PLIN-2/ADRP levels were measured. Patients were divided into 2 groups according to the median serum PLIN-2/ADRP level. During the follow-up period, data such as blood pressure, height-adjusted total kidney volume (HtTKV), proteinuria, complete blood count, and biochemical tests were recorded.
Results: In the patients with serum PLIN-2 / ADRP level above the median value (11.675 ng / mL), BMI was significantly higher than the other group (p<0.001). The female sex ratio was found to be significantly increased in patients with serum PLIN-2 /ADRP levels above the median value. Serum PLIN-2/ADRP levels were found to increase as eGFR decreased in ADPKD patients, but it was not statistically significant. In patients with high baseline mean PLIN-2/ADRP levels, the mean eGFR decline was found to be 20 ml/min/1.73 m2. However, the mean eGFR decrease in the other group with a low baseline PLIN-2/ADRP value was found to be 16 ml/min/1.73 m2 after 7 years of follow-up.
Conclusion: PLIN-2 / ADRP levels increased in female ADPKD patients, and it is positively associated with BMI increase. Increased serum PLIN-2 / ADRP levels may be a harbinger of faster kidney function decline.

Anahtar Kelimeler

Perilipin-2 (PLIN-2/ADRP), Autosomal Dominant Polycystic Kidney Disease (ADPKD), female sex, body mass index (BMI)

Kaynakça

• Cordido A, Besada-Cerecedo L, García-González MA. The Genetic and Cellular Basis of Autosomal Dominant Polycystic Kidney Disease-A Primer for Clinicians. Front Pediatr. 2017;5:279. Published 2017 Dec 18. doi:10.3389/fped.2017.00279
• Ecder T. Cardiovascular complications in autosomal dominant polycystic kidney disease. Curr Hypertens Rev. 2013;9(1):2-11. doi:10.2174/1573402111309010002
• Mao Z, Xie G, Ong AC. Metabolic abnormalities in autosomal dominant polycystic kidney disease. Nephrol Dial Transplant. 2015;30(2):197-203. doi:10.1093/ndt/gfu044
• Meijer E, Gansevoort RT, de Jong PE, et al. Therapeutic potential of vasopressin V2 receptor antagonist in a mouse model for autosomal dominant polycystic kidney disease: optimal timing and dosing of the drug. Nephrol Dial Transplant. 2011;26(8):2445-2453. doi:10.1093/ndt/gfr069
• Santoro D, Pellicanò V, Visconti L, Trifirò G, Buemi M, Cernaro V. An overview of experimental and early investigational therapies for the treatment of polycystic kidney disease. Expert Opin Investig Drugs. 2015;24(9):1199-1218. doi:10.1517/13543784.2015.1059421
• Itabe H, Yamaguchi T, Nimura S, Sasabe N. Perilipins: a diversity of intracellular lipid droplet proteins. Lipids Health Dis. 2017;16(1):83. Published 2017 Apr 28. doi:10.1186/s12944-017-0473-y
• Imamura M, Inoguchi T, Ikuyama S, et al. ADRP stimulates lipid accumulation and lipid droplet formation in murine fibroblasts. Am J Physiol Endocrinol Metab. 2002;283(4):E775-E783. doi:10.1152/ajpendo.00040.2002
• Magnusson B, Asp L, Boström P, et al. Adipocyte differentiation-related protein promotes fatty acid storage in cytosolic triglycerides and inhibits secretion of very low-density lipoproteins. Arterioscler Thromb Vasc Biol. 2006;26(7):1566-1571. doi:10.1161/01.ATV.0000223345.11820.da
• Morrissey JJ, Kharasch ED. The specificity of urinary aquaporin 1 and perilipin 2 to screen for renal cell carcinoma. J Urol. 2013;189(5):1913-1920. doi:10.1016/j.juro.2012.11.034
• Niccoli G, D'Amario D, Borovac JA, et al. Perilipin 2 levels are increased in patients with in-stent neoatherosclerosis: A clue to mechanisms of accelerated plaque formation after drug-eluting stent implantation. Int J Cardiol. 2018;258:55-58. doi:10.1016/j.ijcard.2018.01.074
• Morrissey J. J., Mobley J., Song J., et al. Urinary concentrations of aquaporin-1 and perilipin-2 in patients with renal cell carcinoma correlate with tumor size and stage but not grade. Urology. 2014;83(1):256.e9–256.e14. doi: 10.1016/j.urology.2013.09.026.
• Morrissey JJ, Mobley J, Figenshau RS, Vetter J, Bhayani S, Kharasch ED. Urine aquaporin 1 and perilipin 2 differentiate renal carcinomas from other imaged renal masses and bladder and prostate cancer. Mayo Clin Proc. 2015;90(1):35-42. doi:10.1016/j.mayocp.2014.10.005
• Xu S, Lee E, Sun Z, et al. Perilipin 2 Impacts Acute Kidney Injury via Regulation of PPARα. J Immunol Res. 2021;2021:9972704. Published 2021 Sep 9. doi:10.1155/2021/9972704
• Kocyigit I, Yilmaz MI, Gungor O, et al. Vasopressin-related copeptin is a novel predictor of early endothelial dysfunction in patients with adult polycystic kidney disease. BMC Nephrol. 2016;17(1):196. Published 2016 Nov 30. doi:10.1186/s12882-016-0406-4
• Levey AS, Eckardt KU, Dorman NM, et al. Nomenclature for Kidney Function and Disease: Executive Summary and Glossary From a Kidney Disease: Improving Global Outcomes (KDIGO) Consensus Conference. Perit Dial Int. 2021;41(1):5-14. doi:10.1177/0896860820934730
• Chebib FT, Perrone RD, Chapman AB, et al. A Practical Guide for Treatment of Rapidly Progressive ADPKD with Tolvaptan. J Am Soc Nephrol. 2018;29(10):2458-2470. doi:10.1681/ASN.2018060590
• Axelsson J, Aström G, Sjölin E, et al. Uraemic sera stimulate lipolysis in human adipocytes: role of perilipin. Nephrol Dial Transplant. 2011;26(8):2485-2491. doi:10.1093/ndt/gfq755
• Orlicky DJ, Libby AE, Bales ES, et al. Perilipin-2 promotes obesity and progressive fatty liver disease in mice through mechanistically distinct hepatocyte and extra-hepatocyte actions. J Physiol. 2019;597(6):1565-1584. doi:10.1113/JP277140
• Conte M, Santoro A, Collura S, et al. Circulating perilipin 2 levels are associated with fat mass, inflammatory and metabolic markers and are higher in women than men. Aging (Albany NY). 2021;13(6):7931-7942. doi:10.18632/aging.202840
• Nowak KL, You Z, Gitomer B, et al. Overweight and Obesity Are Predictors of Progression in Early Autosomal Dominant Polycystic Kidney Disease. J Am Soc Nephrol. 2018;29(2):571-578. doi:10.1681/ASN.2017070819
• Nowak KL, Steele C, Gitomer B, Wang W, Ouyang J, Chonchol MB. Overweight and Obesity and Progression of ADPKD. Clin J Am Soc Nephrol. 2021;16(6):908-915. doi:10.2215/CJN.16871020
• Kocyigit I, Ozturk F, Eroglu E, et al. Dysmetabolic markers predict outcomes in autosomal dominant polycystic kidney disease. Clin Exp Nephrol. 2019;23(9):1130-1140. doi:10.1007/s10157-019-01748-z
• Schrier RW, Brosnahan G, Cadnapaphornchai MA, et al. Predictors of autosomal dominant polycystic kidney disease progression. J Am Soc Nephrol. 2014;25(11):2399-2418. doi:10.1681/ASN.2013111184