Serpil ÇEÇEN, Dilek YAĞCI ÇAĞLAYIK, Can ILGIN

Enflamatuvar belirteç olarak HCRP ve Sistatin C’nin obezitede böbrek fonksiyonları izleminde kullanılması

Amaç: Obezitede böbrek fonksiyonlarının takibinde glomerüler filtrasyon hızı (GFR)’nın belirlenmesi önemlidir. GFR belirlenmesinde kreatinin ve sistatin C kullanılmaktadır. Sistatin C yağ dokusu artışıyla orantılı olarak artmakta olup bu çalışmada amacımız obez bireylerde GFR hesaplanırken sistatin C kullanımının uygunluğunu araştırmaktır. Yöntem: Çalışmaya obezite şikayeti ile başvuran kadın hastalar dahil edildi (n=113). Bireylerin düz bir zeminde çıplak ayakla ve sırtları duvara gelecek şekilde dururken boy uzunlukları ölçüldü. Daha sonra biyoimpedans cihazında tüm vücut analizi yapılarak toplam vücut ağırlığı, beden kütle indeksi (BMI), yağ yüzdesi, yağ ağırlığı ve yağsız ağırlıkları tespit edildi. Hastaların biyokimyasal verilerine geriye yönelik olarak ulaşılarak değerlendirme yapıldı. Sistatin C, kreatinin değerleri ölçülmüş olan hastaların CKD-EPİ-GFR (Chronic Kidney Disease- Epidemiology Collaboration equationglomerular filtration rate), GFR-epi-cr (kreatinin- GFR), GFR-epi-cysc (sistatin C-GFR) ve GFR-epi-cr-cysc (kombine-GFR) değerleri hesaplandı. Bulgular: GFR-epi-cr değerinin yaş ve BMI ile azaldığını, boy uzunluğu ile arttığını, GFR-epi–cysc değerinin yaş, BMI, yağ yüzdesi, yağ ağırlığı ile azaldığını, boy uzunluğu ile anlamlı olarak arttığını, GFR-epi-cr-cysc değerinin yaş, BMI, yağ yüzdesi, yağ ağırlığı ile azaldığını tespit ettik. GFR-epi-cr, GFR-epi–cysc, GFR-epi-cr-cysc değerlerinin HCRP (High-C-reactif protein) ile azaldığını tespit ettik. Kreatinin değerinin yaş ile arttığını, GFRepi- cr, GFR-epi–cysc, GFR-epi-cr-cysc ile azaldığını tesbit ettik. Cystatin C değerlerinin yaş, vücut ağırlığı, BMI, yağ yüzdesi, yağ ağırlığı ile arttığını, GFR-epi-cr, GFR-epi–cysc, GFR-epi-cr-cysc ile azaldığını tesbit ettik. Sonuç: Sistatin C böbrek glomerüllerinden rahatlıkla geçebilen bir madde olup GFR hesaplamasında kullanılırken, obez bireylerde yağ dokusuyla artışı ile orantılı olarak sistatin C’nin arttığını ve GFR-epi–cysc ve GFR-epi-cr-cysc azaldığını tesbit ettik. Aynı zamanda yağ yüzdesi ve yağ dokusu artışı ile daha belirgin olmak üzere HCRP’nin artığını tesbit ettik. Bu sonuçlar obez bireylerde yağ dokusu artışı ile belirginleşen enflamasyonun böbrek fonksiyonlarını etkilediğini düşündürmesi açısından önemlidir. Çalışmamızdan elde ettiğimiz veriler, obez bireylerde GFR hesaplama ve böbrek fonksiyonlarını takipte kullanılan parametrelerin kullanımı konusunda farkındalık oluşturması açısından önemli görünmektedir. Çalışmamız göstermiştir ki, sistatin C’nin obez bireylerde GFR hesaplama ve böbrek fonksiyonlarını takipte kullanımı yanlış sonuçlar verebilir.

Use of HCRP and Cystatin C as inflammation markers in the follow-up of kidney functions in obesity

Objective: Determination of glomerular filtration rate is essential for kidney functions in obesity. Creatinine and cystatin C are used to determine glomerular filtration rate. Cystatin-c increases with the increase of adipose tissue. The study investigates the use of cystatin C in calculating the glomerular filtration rate in obese individuals. Methods: One hundred thirteen obese women were used in the study. The height of the patients was measured barefoot on a flat surface. A whole-body analysis was performed by bioimpedance device (Tanita- BC418), and body weight, body mass index (BMI), fat percentage, fat mass, fat-free mass were detected. Biochemical data were evaluated retrospectively. CKD-EPI-GFR (Chronic Kidney Disease Epidemiology Collaboration equation glomerular filtration rate), GFRepi- cr (creatinine-GFR), GFR-epi-cysc (cystatin C-GFR) and GFR-epi-cr-cysc (combined-GFR) values were calculated from the measured cystatin-c and creatinine values. Results: We found that GFR-epi-cr decreased with age and BMI, increased with height, GFR-epi-cysc decreased with age, BMI, fat percentage, fat mass, increased significantly with height, GFR-epi-cr-cysc decreased with age, BMI, fat percentage, fat mass. GFR-epi-cr, GFR-epi-cysc, GFR-epi-cr-cysc decreased with HCRP (High-C-reactif protein). Creatinine increased with age and decreased with GFR-epi-cr, GFR-epi-cysc, GFR-epi-cr-cysc. Cystatin-c increased with age, body weight, BMI, fat percentage, fat mass, and decreased GFR-epi-cr, GFR-epi-cysc, GFR-epi-crcysc. Conclusion: Cystatin C can pass through kidney glomeruli easily and used in GFR calculation. We found that while cystatin-c increases with increased adipose tissue in obese individuals, GFR-epi–cysc ve GFRepi- cr-cysc decreased. As well, HCRP increased with the fat percentage and fat mass. These results are essential in terms of inflammation, which is evident with the increase in adipose tissue, affects kidney functions in obese individuals. Our study is essential in raising awareness about GFR calculation and parameters used in the follow-up of kidney functions in obese individuals.Our study shows that to use of cystatin Cmay give wrong results to calculate GFR and follow up of kidney functions in obese individuals.

PDF

___

1. Engin A. The Pathogenesis of Obesity-Associated Adipose Tissue Inflammation. Adv Exp Med Biol. 2017;960:221-45.
2. Bonauto DK, Lu D, Fan ZJ. Obesity prevalence by occupation in Washington State, Behavioral Risk Factor Surveillance System. Prev Chronic Dis. 2014;11:130219.
3. Kim HS, Lee J, Cho YK, Park JY, Lee WJ, Kim YJ, et al. Differential Effect of Metabolic Health and Obesity on Incident Heart Failure: A Nationwide Population-Based Cohort Study. Front Endocrinol (Lausanne). 2021;12:625083.
4. Hsu CY, McCulloch CE, Iribarren C, Darbinian J, Go AS. Body mass index and risk for end-stage renal disease. Ann Intern Med. 2006; 144:21-8.
5. Moreira AD, Velasquez-Melendez G, Ladeira RM, da Silva Junior GB, Fonseca MJ, Barreto SM. Association between Adiposity Indexes and Kidney Disease: Findings from the Longitudinal Study of Adult Health (Elsa-Brazil). J Am Coll Nutr. 2021;1- 7.
6. Goossens GH. The Metabolic Phenotype in Obesity: Fat Mass, Body Fat Distribution, and Adipose Tissue Function. Obes Facts. 2017;10(3):207-15.
7. Stolarczyk E. Adipose tissue inflammation in obesity: a metabolic or immune response? Curr Opin Pharmacol. 2017;37:35-40.
8. Wisse BE. The inflammatory syndrome: the role of adipose tissue cytokines in metabolic disorders linked to obesity. J Am Soc Nephrol. 2004;15(11):2792-800.
9. Kittiskulnam P, Tiskajornsiri K, Katavetin P, Chaiwatanarat T, Eiam-Ong S, Praditpornsilpa K. The failure of glomerular filtration rate estimating equations among obese population. PLoS One. 2020;15(11):1-13.
10. McMahon GM, Waikar SS. Biomarkers in nephrology: Core curriculum 2013. Am JKidney Dis. 2013;62(1):165-78.
11. Donahue RP, Stranges S, Rejman K, Rafalson LB, Dmochowski J, Trevisan M. Elevated cystatin C concentration and progression to pre-diabetes: the Western New York study. Diabetes Care. 2007;30(7):1724-9.
12. Gren ST, Janciauskiene S, Sandeep S, Jonigk D, Kvist PH, Gerwien JG, et al. The protease inhibitor cystatin C down-regulates the release of IL-beta and TNF-alpha in lipopolysaccharide activated monocytes. J Leukoc Biol. 2016;100(4):811-22.
13. Smith ER. Cystatin C - More than a filtrationmarker? Atherosclerosis 2013;230:173-5.
14. Muntner P, Winstan J, Uribarri J, Mann D, Fox CS. Overweight and obesity and elevated serum cystatin C levels in US adults.Am J Med. 2008;121(4):341348.
15. Naour N, Fellahi S, Renucci JF, Poitou C, Rouault C, Basdevant A, et al. Potential contribution of adipose tissue to elevated serum cystatin C in human obesity, Obesity (Silver Spring). 2009;17: 2121-6.
16. Iseki K, Ikemiya Y, Kinjo K, Inoue T, Iseki C, Takishita S. Body mass index and the risk ofdevelopment of end-stage renal disease in a screened cohort. Kidney Int. 2004; 65:1870-76.
17. Nguyen S, Hsu C . Excess weight as a risk factor for kidney failure. Curr Opin Nephrol Hypertens. 2007;16(2):71-6.
18. Mokdad AH, Ford ES, Bowman BA, Dietz WH, Vinicor F,Bales VS, et al. Prevalence of obesity, diabetes, andobesity-related health risk factors, 2001. JAMA 2003;289(1): 76 -9.
19. Ejerblad E, Fored CM, Lindblad P, FryzekJ, McLaughlin JK, Nyren O. Obesity and risk for chronic renal failure. J Am Soc Nephrol 2006;17:1695-702.
20. Nenov VD, Taal MW, Sakharova OV, Brenner BM. Multi-hitnature of chronic renal disease. Curr Opin Nephrol Hypertens 2000;9:85-97.
21. Amaral LSB, Silva JA, Trindade TM, Ribas WBD, Macedo CL, Coimbra TM, et al. Renal changes in the early stages of diet-induced obesity in ovariectomized rats. Physiol Res. 2014;63(6):723- 32.
22. Shabaka A, Cases-Corona C, Fernandez-Juarez G. Therapeutic Insights in Chronic Kidney Disease Progression. Front Med (Lausanne). 2021;8:645187.
23. Navarro JF, Milena FJ, Mora C, Leon C, Garcia J. Renal pro-inflammatory cytokine gene expression in diabetic nephropathy: effect of angiotensinconverting enzyme inhibition and pentoxifylline administration. Am J Nephrol 2006; 26: 562-70.
24. Martos-Rus C, Katz-Greenberg G, Lin Z, Serrano E, Whitaker-Menezes D, Domingo-Vidal M, et al. Macrophage and adipocyte interaction as a source of infammation in kidney disease. Sci Rep. 2021;11(1):1-14.
25. De Castro IC, Pequito DCT, Borghetti G, Yamaguchi AA, de Brito GAP, Yamazaki RK, et al. Obesitylike metabolic effects of high-carbohydrate or high-fat diets consumption in metabolic and renal functions. Arch Physiol Biochem. 2021:1-11.
26. Sucedaram Y, Johns EJ, Husain R, Abdul Sattar M, H Abdulla M, Nelli G. Exposure to High-Fat Style Diet Induced Renal and Liver Structural Changes, Lipid Accumulation and Inflammation in Intact and Ovariectomized Female Rats. J Inflamm Res. 2021;14: 689-710.
27. Ye L, Hu X, Hu X, Yin S, Chen J, He H, et al. Curcumin analogue C66 attenuates obesity-induced renal injury by inhibiting chronic inflammation. Biomed Pharmacother. 2021;137:111418.
28. Çağlayık DY, Arıkan H, Çeçen S. HIV ile enfekte obez bireylerde Sistatin-C. Turk Hij Den Biyol Derg, 2019;76(4): 461-68.
29. Hojs R, Bevc S, Ekart R, Gorenjak M, Puklavec L. Serum cystatin C as an endogenousmarker of renal function in patients with mild to moderate impairment of kidney function. Nephrol Dial Transplant. 2006;21:1855-62.
30. Lemoine S, Panaye M, Pelletier C, Bon C, Juillard L, Dubourg L, et al. Cystatin C-Creatinine Based Glomerular Filtration Rate Equation in Obese Chronic Kidney Disease Patients: Impact of Deindexation and Gender. Am J Nephrol. 2016;44(1):63-70.
31. Jhatta C, Girdhar J, Gupta S, Verma I. To Compare the Level of Cystatin C in Type 2 Diabetes Mellitus with Obesity. Indian J Endocrinol Metab. 2020 Jul- Aug;24(4):312-18.
32. López-Martínez M, Luis-Lima S, Morales E, Navarro-Díaz M, Negrín-Mena N, Folgueras T, et al. The estimation of GFR and the adjustment for BSA in overweight and obesity: a dreadful combination of two errors. Int J Obes (Lond). 2020;44(5):1129- 40.
33. Lemoine S, Guebre-Egziabher F, Sens F, Nguyen- Tu MS, Juillard L, Dubourg L, et al. Accuracy of GFR estimation in Obese Patients. Clin J Am Soc Nephrol. 2014;9:720-7.