Restricted accessResearch articleFirst published online 2022-02-17
The effect of rheopheresis treatment on the cytokine profile in diabetic foot syndrome with hyperviscosity in the aspect of clinical changes: A preliminary study
Rheopheresis is a selective extracorporal double cascade filtration treatment, which can extract high molecular weight proteins being responsible for hyperviscosity. As the whole blood and plasma viscosity decrease microcirculation improves.
OBJECTIVE:
In this preliminary study we aimed to analyze additional beneficial effects of rheopheresis treatment with changes of pro-inflammantory cytokine levels in diabetic foot syndrome patients.
METHODS:
Two rheopheresis treatments were performed for 6 patients with diabetic foot ulcer and/or neuropathy on consecutive days. Before and after the treatments whole blood and plasma viscosity, as well as IL-6, IL-8, and TNF-alpha serum levels were determined, and complex angiological and ENG examinations were performed.
RESULTS:
Rheopheresis decreased the whole blood and plasma viscosity, and the serum levels of IL-6, IL-8, and TNF-alpha were markedly reduced. The life quality of the patients improved, the ulcers healed, the pain decreased. Daily dose of analgesics decreased in the follow-up period (6 months). The ENG showed improving amplitude and/or normalizing conduction speed.
CONCLUSION:
Application of rheopheresis in patients with diabetic foot syndrome has a beneficial effect, providing favorable rheological condition, normalizing cytokine profile and reducing the sensorineural symptoms.
MartiniR. Current opinion on the role of the foot perfusion in limbamputation risk assessment. Clin Hemorheol Microcirc. 2020;76(3):405–12. doi:10.3233/CH-200901.
2.
KrasulinaKA, GlazkovaPA, GlazkovAA, KulikovDA, RogatkinDA, KovalevaYA, BardeevaJN, DrevalAV. Reduced microvascular reactivity in patients with diabetic neuropathy. Clin Hemorheol Microcirc. 2021. doi: 10.3233/CH-211177. Online ahead of print.
3.
PendseySP. Understanding diabetic foot. Int J Diabetes Dev Ctries. 2010;30(2):75–9. doi:10.4103/0973-3930.62596.
4.
ChaoCY, CheingGL. Microvascular dysfunction in diabetic foot disease and ulceration. Diabetes Metab Res Rev. 2009;25(7):604–14. doi:10.1002/dmrr.1004.
5.
LatzaR, WolfS, KiesewetterH, JungF. Early rheological andmicrocirculatory changes in children with type I diabetes mellitus. Koscielny J, Clin Hemorheol Microcirc. 1998;19(2):139–50.
6.
McMillanDE. Plasma protein changes, blood viscosity, and diabetic microangiopathy. Diabetes.–64. PMID. 1976;25(Suppl 2):858–64. PMID: 971790.
7.
Schmid-SchönbeinH, VolgerE. Red-cell aggregation and red-cell deformability in diabetes. Diabetes. 1976;25(Suppl 2):897–902. PMID: 971793.
8.
VagueP, JuhanI. Red cell deformability, platelet aggregation, and insulin action. Diabetes. 1983;32(Suppl 2):88–91. doi:10.2337/diab.32.2.s88.
9.
Le DevehatC, KhodabandehlouT, VimeuxM. Impaired hemorheological properties in diabetic patients with lower limb arterial ischaemia. Clin Hemorheol Microcirc. 2001;25(2):43–8.
10.
BaskurtOK. Mechanism of blood rheology alterations. In: Handbook of Hemorheology and Hemodynamics. Baskurt OK, Hardeman MR, Rampling MW, Meiselman HJ, editors. Amsterdam: IOS Press; 2007. pp. 170–90.
AritaT, MaruyamaT, YokoyamaT, HiedaM, FukataM, FujinoT, MawatariS, AkashiK. Impaired deformability and association with density distribution of erythrocytes in patients with type 2 diabetes mellitus under treatment. Clin Hemorheol Microcirc. 2020;76(1):73–83. doi:10.3233/CH-200873.
13.
KlingelR, MummeC, FassbenderT, HimmelsbachF, AltesU, LotzJ, PohlmannT, BeyerJ, KüstnerE. Rheopheresis in patients with ischemic diabetic foot syndrome: results of an open label prospective pilot trial. Ther Apher Dial. 2003;7(4):444–55. doi:10.1046/j.1526-0968.2003.00082.
FerranniniM, VischiniG, StaffolaniE, ScacciaF, MianiN, ParravanoMC, LouisMM, SplendianiG, DiDaniele N. Rheopheresis in vascular diseases. Int J Artif Organs. 2007;30(10):923–9. doi:10.1177/039139880703001010.
16.
PadmanabhanA, Connelly-SmithL, AquiN, BalogunRA, KlingelR, MeyerE, PhamHP, SchneidermanJ, WittV, WuY, ZantekND, DunbarNM, SchwartzGEJ. Guidelines on the Use of Therapeutic Apheresis in Clinical Practice - Evidence-Based Approach from the Writing Committee of the American Society for Apheresis: The Eighth Special Issue. J Clin Apher. 2019;34(3):171–354. doi:10.1002/jca.21705.
CartyCL, HeagertyP, HeckbertSR, JarvikGP, LangeLA, CushmanM, TracyRP, ReinerAP. Interaction between fibrinogen and IL-6 genetic variants and associations with cardiovascular disease risk in the Cardiovascular Health Study. Ann Hum Genet. 2010;74(1):1–10. doi:10.1111/j.1469-1809.2009.00551.x.
19.
KorkmazP, KoçakH, OnbaşıK, BiçiciP, ÖzmenA, UyarC, ÖzatağDM. The role of serumprocalcitonin, interleukin-6, and fibrinogen levels in differentialdiagnosis of diabetic foot ulcer infection. J Diabetes Res. 2018;2018:7104352 doi:10.1155/2018/7104352.
20.
XuF, ZhangC, GravesDT. Abnormal cell responses and role of TNF-α in impaired diabetic wound healing. Biomed Res Int. 2013;2013:754802. doi:10.1155/2013/754802.
21.
PurwataTE. High TNF-alpha plasma levels and macrophages iNOS and TNF-alpha expression as risk factors for painful diabetic neuropathy. J Pain Res. 2011;4:169–75. doi:10.2147/JPR.S21751.
22.
MuZP, WangYG, LiCQ, LvWS, WangB, JingZH, SongXJ, LunY, QiuMY, MaXL. Association between tumor necrosis factor-α and diabetic peripheral neuropathy in patients with type 2 diabetes: a meta-analysis. Mol Neurobiol. 2017;54(2):983–96. doi:10.1007/s12035-016-9702-z.
23.
LainampetchJ, PanprathipP, PhosatC, ChumpathatN, PrangthipP, SoonthornworasiriN, PuduangS, WechjakwenN, KwanbunjanK. Association of Tumor Necrosis Factor Alpha, Interleukin 6, and C-Reactive Protein with the Risk of Developing Type 2 Diabetes: A Retrospective Cohort Study of Rural Thais. J Diabetes Res. 20198;2019:9051929. doi: 10.1155/2019/9051929.
24.
CiminiFA, BarchettaI, PorziaA, MainieroF, CostantinoC, BertocciniL, CeccarelliV, MoriniS, BaroniMG, LenziA, CavalloMG. Circulating IL-8 levels are increased in patients with type 2 diabetes and associated with worse inflammatory and cardiometabolic profile. Acta Diabetol. 2017;54(10):961–7. doi:10.1007/s00592-017-1039-1.
25.
HardemanMR, GoedhartPT, ShinS. Methods in hemorheology. In: Handbook of Hemorheology and Hemodynamics. Baskurt OK, Hardeman MR, Rampling MW, Meiselman HJ, editors. Amsterdam: IOS Press; 2007. pp. 242–266.
26.
NemethN, AlexyT, FurkaA, BaskurtOK, MeiselmanHJ, FurkaI, MikoI. Inter-species differences in hematocrit to blood viscosity ratio. Biorheology. 2009;46(2):155–65. doi:10.3233/BIR-2009-0533.
27.
NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in diabetes since a pooled analysis of 751 population-based studies with 4.4 million participants. Lancet. 2016;387(10027):1513–30. doi:10.1016/S0140-6736(16)00618-8.
28.
NavesCC. The Diabetic Foot: A Historical Overview and Gaps in Current Treatment. Adv Wound Care (New Rochelle). 2016;5(5):191–7. doi:10.1089/wound.2013.0518.
29.
FiorentinoTV, PriolettaA, ZuoP, FolliF. Hyperglycemia-induced oxidative stress and its role in diabetes mellitus related cardiovascular diseases. Curr Pharm Des. 2004;19(32):5695–703. doi:10.2174/1381612811319320005.
DinhT, VevesA. Microcirculation of the diabetic foot. Curr Pharm Des. 2005;11(18):2301–9. doi:10.2174/1381612054367328.
32.
DeClueCE, ShornickLP. The cytokine milieu of diabetic wounds. Diabetes Manag. 2015;5(6):525–37. doi:10.2217/dmt.15.44.
33.
StenkenJA, PoschenriederAJ. Bioanalytical chemistry of cytokines - a review. Anal Chim Acta. 2015;853:95–115. doi:10.1016/j.aca.2014.10.009.
34.
LaMarreJ, WollenbergGK, GoniasSL, HayesMA. Cytokine binding and clearance properties of proteinase-activated alpha 2-macroglobulins. Lab Invest. 1991;65(1):3–14. PMID: 1712874.
35.
MatsudaT, HiranoT, NagasawaS, KishimotoT. Identification of alpha 2-macroglobulin as a carrier protein for IL-6. J Immunol. 1989;142(1):148–52. PMID: 2462586
