Chronic Kidney Disease Has No Impact on Tear Film Substance P Concentration in Type 2 Diabetes

Overview

Journal Biomedicines

Specialty Biomedical Engineering

Date 2023 Sep 28

PMID 37760810

Authors

Kofi Asiedu

Sultan Alotaibi

Arun V Krishnan

Natalie Kwai

Ann Poynten

Maria Markoulli

Roshan Dhanapalaratnam

Affiliations

Soon will be listed here.

Abstract

Purpose: The study aimed to ascertain the potential effects of chronic kidney disease (CKD) on substance P concentration in the tear film of people with type 2 diabetes.

Methods: Participants were classified into two groups: type 2 diabetes with concurrent chronic kidney disease (T2DM-CKD (n = 25)) and type 2 diabetes without chronic kidney disease (T2DM-no CKD (n = 25)). Ocular surface discomfort assessment, flush tear collection, in-vivo corneal confocal microscopy, and peripheral neuropathy assessment were conducted. Enzyme-linked immunosorbent assays were utilized to ascertain the levels of tear film substance P in collected flush tears. Correlation analysis, hierarchical multiple linear regression analysis, and t-tests or Mann-Whitney U tests were used in the analysis of data for two-group comparisons.

Results: There was no substantial difference between the T2DM-CKD and T2DM-no CKD groups for tear film substance P concentration (4.4 (0.2-50.4) and 5.9 (0.2-47.2) ng/mL, respectively; p = 0.54). No difference was observed in tear film substance P concentration between the low-severity peripheral neuropathy and high-severity peripheral neuropathy groups (4.4 (0.2-50.4) and 3.3 (0.3-40.7) ng/mL, respectively; p = 0.80). Corneal nerve fiber length (9.8 ± 4.6 and 12.4 ± 3.8 mm/mm, respectively; p = 0.04) and corneal nerve fiber density (14.7 ± 8.5 and 21.1 ± 7.0 no/mm, respectively; p < 0.01) were reduced significantly in the T2DM-CKD group compared to the T2DM-no CKD group. There were significant differences in corneal nerve fiber density (21.0 ± 8.1 and 15.8 ± 7.7 no/mm, respectively; p = 0.04) and corneal nerve fiber length (12.9 ± 4.2 and 9.7 ± 3.8 mm/mm, respectively; p = 0.03) between the low- and high-severity peripheral neuropathy groups.

Conclusion: In conclusion, no significant difference in tear film substance P concentration was observed between type 2 diabetes with and without CKD. Corneal nerve loss, however, was more significant in type 2 diabetes with chronic kidney disease compared to type 2 diabetes alone, indicating that corneal nerve morphological measures could serve greater utility as a tool to detect neuropathy and nephropathy-related corneal nerve changes.

Citing Articles

Analysis of Clinical Characteristics and Neuropeptides in Patients with Dry Eye with and without Chronic Ocular Pain after FS-LASIK.

Zhao L, Zhou Y, Duan H, Zhang Y, Ma B, Yang T Ophthalmol Ther. 2024; 13(3):711-723.

PMID: 38190027 PMC: 10853104. DOI: 10.1007/s40123-023-00861-3.

References

Chao C, Golebiowski B, Zhao X, Chen S, Zhou S, Stapleton F . Long-term Effects of LASIK on Corneal Innervation and Tear Neuropeptides and the Associations With Dry Eye. J Refract Surg. 2016; 32(8):518-24. DOI: 10.3928/1081597X-20160603-01. View

Chaudhry V, Rowinsky E, Sartorius S, Donehower R, Cornblath D . Peripheral neuropathy from taxol and cisplatin combination chemotherapy: clinical and electrophysiological studies. Ann Neurol. 1994; 35(3):304-11. DOI: 10.1002/ana.410350310. View

Petropoulos I, Ponirakis G, Ferdousi M, Azmi S, Kalteniece A, Khan A . Corneal Confocal Microscopy: A Biomarker for Diabetic Peripheral Neuropathy. Clin Ther. 2021; 43(9):1457-1475. DOI: 10.1016/j.clinthera.2021.04.003. View

Krishnan A, Lin C, Kiernan M . Activity-dependent excitability changes suggest Na+/K+ pump dysfunction in diabetic neuropathy. Brain. 2008; 131(Pt 5):1209-16. DOI: 10.1093/brain/awn052. View

Dozio E, Vettoretti S, Lungarella G, Messa P, Corsi Romanelli M . Sarcopenia in Chronic Kidney Disease: Focus on Advanced Glycation End Products as Mediators and Markers of Oxidative Stress. Biomedicines. 2021; 9(4). PMC: 8068965. DOI: 10.3390/biomedicines9040405. View

Waddell P, Lawson S . Electrophysiological properties of subpopulations of rat dorsal root ganglion neurons in vitro. Neuroscience. 1990; 36(3):811-22. DOI: 10.1016/0306-4522(90)90024-x. View

Vagenas D, Pritchard N, Edwards K, Shahidi A, Sampson G, Russell A . Optimal image sample size for corneal nerve morphometry. Optom Vis Sci. 2012; 89(5):812-7. DOI: 10.1097/OPX.0b013e31824ee8c9. View

OConnor T, OConnell J, OBrien D, Goode T, Bredin C, Shanahan F . The role of substance P in inflammatory disease. J Cell Physiol. 2004; 201(2):167-80. DOI: 10.1002/jcp.20061. View

Singh R, Naderi A, Cho W, Ortiz G, Musayeva A, Dohlman T . Modulating the tachykinin: Role of substance P and neurokinin receptor expression in ocular surface disorders. Ocul Surf. 2022; 25:142-153. PMC: 10285737. DOI: 10.1016/j.jtos.2022.06.007. View

10.

Iyengar M, Soto L, Requena D, Ruiz-Alejos A, Huaylinos Y, Velasquez R . Tear biomarkers and corneal sensitivity as an indicator of neuropathy in type 2 diabetes. Diabetes Res Clin Pract. 2020; 163:108143. PMC: 8944933. DOI: 10.1016/j.diabres.2020.108143. View

11.

Arnold R, Pussell B, Howells J, Grinius V, Kiernan M, Lin C . Evidence for a causal relationship between hyperkalaemia and axonal dysfunction in end-stage kidney disease. Clin Neurophysiol. 2013; 125(1):179-85. DOI: 10.1016/j.clinph.2013.06.022. View

12.

Moulton E, Borsook D . C-Fiber Assays in the Cornea vs. Skin. Brain Sci. 2019; 9(11). PMC: 6896162. DOI: 10.3390/brainsci9110320. View

13.

Byun Y, Mok J, Chung S, Kim H, Joo C . Ocular surface inflammation induces de novo expression of substance P in the trigeminal primary afferents with large cell bodies. Sci Rep. 2020; 10(1):15210. PMC: 7494893. DOI: 10.1038/s41598-020-72295-x. View

14.

Belmonte C, Acosta M, Gallar J . Neural basis of sensation in intact and injured corneas. Exp Eye Res. 2004; 78(3):513-25. DOI: 10.1016/j.exer.2003.09.023. View

15.

Bae J, Kim J, Cho Y, Mah W, Bae Y . Quantitative analysis of afferents expressing substance P, calcitonin gene-related peptide, isolectin B4, neurofilament 200, and Peripherin in the sensory root of the rat trigeminal ganglion. J Comp Neurol. 2014; 523(1):126-38. DOI: 10.1002/cne.23672. View

16.

Yu M, Lee S, Lee H, Amouzegar A, Nakao T, Chen Y . Neurokinin-1 Receptor Antagonism Ameliorates Dry Eye Disease by Inhibiting Antigen-Presenting Cell Maturation and T Helper 17 Cell Activation. Am J Pathol. 2019; 190(1):125-133. PMC: 6943374. DOI: 10.1016/j.ajpath.2019.09.020. View

17.

Kramer H, Klingmuller D, Flachskampf F, Dusing R . Substance P-induced changes in kidney function in the conscious rat: relation to the renal prostaglandin system. Ren Physiol. 1983; 6(1):10-8. DOI: 10.1159/000172876. View

18.

Cornblath D, Chaudhry V, Carter K, Lee D, Seysedadr M, Miernicki M . Total neuropathy score: validation and reliability study. Neurology. 1999; 53(8):1660-4. DOI: 10.1212/wnl.53.8.1660. View

19.

Angus-Leppan H, Burke D . The function of large and small nerve fibers in renal failure. Muscle Nerve. 1992; 15(3):288-94. DOI: 10.1002/mus.880150306. View

20.

Markoulli M, You J, Kim J, Duong C, Tolentino J, Karras J . Corneal Nerve Morphology and Tear Film Substance P in Diabetes. Optom Vis Sci. 2017; 94(7):726-731. DOI: 10.1097/OPX.0000000000001096. View