Prerenal kidney damage in patients with local cold injury

Introduction. Important links in the pathogenesis of cold alterations are vascular damage and powerful systemic alterations. The presence of premorbid pathology and the duration of the wound process negatively affects to the function of most organs and systems, including the kidneys. Renal insufficiency in patients with frostbite develops in the acute period of cold damage. This is indicated by a decrease in the amount of urine and an increase in creatinine levels in victims with frostbite. In this regard, the identification and analysis of the dynamics of new markers of renal dysfunction in patients with frostbite is promising both from a scientific and practical point of view.

The aim. To investigate the dynamics of changes in serum creatinine, NGAL and cystatin C levels in patients with local cold trauma.

Materials and methods. The study included 60 patients with frostbite of the III–IV degree of distal limb segments. The study was carried out depending on the volume of the lesion and the timing from the moment of cryoalteration.

The results of the study. In patients with grade III–IV frostbite, an increase in the level of lipocalin and serum creatinine was detected in the blood. The concentration of lipocalin and serum creatinine is directly proportional to the volume of cold-affected tissues. Indicators of lipocalin and serum creatinine decrease in the late stages of cryopreservation. The level of cystatin C significantly decreases during all periods of frostbite; the concentration of the latter does not depend on the severity of cryopreservation.

1. Mikhaylichenko MI, Shapovalov KG, Mudrov VA, Figursky SA, Emelianov RS. Pathogenetic significance of endothelial dysfunction in formation of vascular wall hypertonia in local cold trauma. Pathological Physiology and Experimental Therapy. 2020; 64(4): 54-61. (In Russ.). doi: 10.25557/0031-2991.2020.04.54-61

2. Sumin SA, Shapovalov KG. Emergency and urgent conditions: A textbook for the training of highly qualified personnel. Moscow: Meditsinskoe informatsionnoe agentstvo; 2019. (In Russ.).

3. Alekseev AA, Alekseev RZ, Bregadze AA, Konnov VA, Mikhailichenko AV, Semenova SV, et al. Diagnosis and treatment of frostbite (clinical recommendations). URL: http://combustiolog. ru/wp-content/uploads/2013/07/Diagnostika-i-lechenie-otmorozhenij-2017.pdf [date of access: 17.10.2021]. (In Russ.).

4. Vasina LV, Vlasov TD, Petrishchev NN. Functional heterogeneity of the endothelium (review). Arterial Hypertension. 2017; 23(2): 88-102. (In Russ.). doi: 10.18705/1607-419X-2017-23-2-88-102

5. Karyakina EV, Belova SV. Medium-weight molecules as an integral indicator of metabolic disorders (literature review). Russian Clinical Laboratory Diagnostics. 2004; 3: 3-8. (In Russ.).

6. Medical Encyclopedia. URL: https://znaiu.ru/art/400244900.php [date of access: 02.05.2018]. (In Russ.).

7. Potapnev MP. Immune mechanisms of sterile inflammation. Immunologiya. 2015; 36(5): 312-318. (In Russ.).

8. Mikhaylichenko MI, Shapovalov KG, Mudrov VA, Gruzdeva OS. The significance of matrix metalloproteinases and their inhibitors in the pathogenesis of local cold injury. Yakut Medical Journal. 2020; 2(70): 72-76. (In Russ.). doi: 10.25789/YMJ.2020.70.22

9. Mikhailichenko MI, Shapovalov KG. Microcirculatory disorders in the pathogenesis of local cold trauma. Regional Blood Circulation and Microcirculation. 2019; 18(2-70): 4-11. (In Russ.). doi: 10.24884/1682-6655-2019-18-2-4-11

10. Fried LF, Katz R, Sarnak MJ, Shlipak MG, Chaves PH, Jenny NS, et al. Kidney function as a predictor of noncardiovascular mortality. J Am Soc Nephrol. 2005; 16(12): 3728-3735. doi: 10.1681/ASN.2005040384

11. Grubb A, Björk J, Lindström V, Sterner G, Bondesson P, Nyman U. A cystatin C based formula without anthropometrics variables estimates glomerular filtration rate better than correlation clearance using the Cockroft – Gault formula. Scand J Clin Lab. 2005; 65(2): 153-162. doi: 10.1080/00365510510013596

12. Loew M, Hoffmann MM, Koenig W, Brenner H, Rothenbacher D. Genotype and plasma concentration of cystatin C in patients with coronary heart disease and risk for cardiovascular events. Atheroscler Thromb Vasc Biol. 2005; 25(7): 1470-1474. doi: 10.1161/01.ATV.0000168416.74206.62

13. Macisaak RJ, Tsalamandris C, Thomas MC, Premaratne E, Panagiotopoulos S, Smith TJ, et al. Estimation glomerular filtration rate in diabetes: A comparison of cystatin-C and creatinine-based methods. Diabetologia. 2006; 49(7): 1686-1689. doi: 10.1007/s00125-006-0275-7

14. Rule AD, Bregstraalh EJ, Slezak JM, Bergert J, Larson TS. Glomerular filtration rate estimates by cystatin C among different clinical presentations. Kidney Int. 2006. 69(2): 399-405. doi: 10.1038/sj.ki.5000073

15. Shlipak MG, Wassel Fyr CL, Chertow GM, Harris TB, Kritchevsky SB, Tylavsky FA, еt al. Cystatin C and mortality risk in the elderly: The health, aging, and body composition study. J Am Soc Nephrol. 2006; 17(1): 254-261. doi: 10.1681/ASN.2005050545

16. Sjöström P, Tidman M, Jones I. Determination of the production rate and non-renal clearance of cystatin C and estimation of the glomerular filtration rate from the serum concentration of cystatin C in humans. Scand J Clin Lab Invest. 2005; 65(2): 111124. doi: 10.1080/00365510510013523

17. Lattanzio MR, Nelson PK. Acute kidney injury: New concepts in definition, diagnosis, pathophysiology and treatment. J Am Osteopath Assoc. 2009; 109(1): 13-19.

18. Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P; Acute Dialysis Quality Initiative workgroup. Acute renal failure – definition, outcome measures, animal models, fluid therapy and information technology needs: The Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care. 2004; 8(4): R204-R212. doi: 10.1186/cc2872

19. Abosaif NY, Tolba YA, Heap M, Russell J, El Nahas AM. The outcome of acute renal failure in the intensive care unit according to RIFLE: Model application, sensitivity, and predictability. Am J Kidney Dis. 2005; 46(6): 1038-1048. doi: 10.1053/j.ajkd.2005.08.033

20. Leng X, Ding T, Lin H, Wang Y, Hu L, Hu J, et al. Inhibition of lipocalin 2 impairs breast tumorigenesis and metastasis. Cancer Res. 2009; 69(22): 8579-8584. doi: 10.1158/0008-5472.CAN-09-1934

21. Zhang XF, Zhang Y, Zhang XH, Zhou SM, Yang GG, Wang OC, et al. Clinical signifi e of Neutrophil gelatinaseassociated lipocalin (NGAL) expression in primary rectal cancer. BMC Cancer. 2009; 9: 134. doi: 10.1186/1471-2407-9-134

22. Tan BK, Adya R, Shan X, Syed F, Lewandowski KC, O’Hare JP, et al. Ex vivo and in vivo regulation of lipocalin-2, a novel adipokine, by insulin. Lipocalin-2 is upregulated by insulin via phosphatidylinositol 3-kinase and mitogen-activated protein kinase signaling pathways. Diabetes Care. 2009; 32(1): 129-131. doi: 10.2337/dc08-1236

23. Nishida M, Kawakatsu H, Okumura Y, Hamaoka K. Serum and urinary NGAL levels in children with chronic renal diseases. Pediatr Int. 2010; 52(4): 563-568. doi: 10.1111/j.1442200X.2010.03067.x

24. Malyszko J, Malyszko JS, Koc-Zorawska E, Kozminski P, Mysliwiec M. Neutrophil gelatinase-associated lipocalin in dialyzed patients is related to residual renal function, type of renal replacement therapy and infl tion. Kidney Blood Press Res. 2010; 32(6): 464-469. doi: 10.1159/000274048

25. Hinze CH, Suzuki M, Klein-Gitelman M, Passo MH, Olson J, Singer NG, et al. Neutrophil gelatinase-associated lipocalin is a predictor of the course of global and renal childhood-onset systemic lupus erythematosus disease activity. Arthritis Rheum. 2009; 60(9): 2772-2781. doi: 10.1002/art.24751

26. Gruzdeva OS, Mikhailichenko MI, Shapovalov KG. Morphological features of tissue changes during limb frostbite. The Transbaikalian Medical Bulletin. 2022; 1: 104-113. (In Russ.). doi: 10.52485/19986173_2022_1_104

27. Makris K, Markou N, Evodia E, Dimopoulou E, Drakopoulos I, Ntetsika K, et al. Urinary neutrophil gelatinase-associated lipocalin (NGAL) as an early marker of acute kidney injury in critically ill multiple trauma patients. Clin Chem Lab Med. 2009; 47(1): 79-82. doi: 10.1515/CCLM.2009.004

28. Yilmaz A, Sevketoglu E, Gedikbasi A, Karyagar S, Kiyak A, Mulazimoglu M, et al. Early prediction of urinary tract infection with urinary neutrophil gelatinase associated lipocalin. Pediatr Nephrol. 2009; 24(12): 2387-2392. doi: 10.1007/s00467-009-1279-6

29. Wasilewska A, Zoch-Zwierz W, Taranta-Janusz K, MichalukSkutnik J. Neutrophil gelatinase-associated lipocalin (NGAL): A new marker of cyclosporine nephrotoxicity? Pediatr Nephrol. 2010; 25(5): 889-897. doi: 10.1007/s00467-009-1397-1