Skin Autofluorescence as a Risk Marker in People Receiving Dialysis.

NCT02878317 | Completed Results

• 1 other identifier: 16050
• Study Type: observational
• Target: 81
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the present study is to investigate the association between the accumulation of advanced glycation end-products (AGE) and adverse outcomes (e.g. death) in people receiving haemodialysis and peritoneal dialysis based in Royal Derby Hospital, as well as the impact of a dietetic intervention on AGE accumulation. AGE will be measured non-invasively in the skin using a technique called skin autofluorescence (SAF). The present study will be conducted in two parts: Study 1: this will be a prospective study where participants will be followed-up for up to five years. The research team will measure the accumulation of AGE in the skin using a quick (less than five minutes) and painless technique called SAF. This involves placing the forearm on a piece of equipment that shines a light on the skin and measures the amount of light that is reflected back. Participants will be asked to complete nutritional and quality of life questionnaires, measurements of weight, height, arm circumference and skinfold thickness (i.e. anthropometry), simple eyesight tests and blood tests. Study 2: observational non-randomized proof of principle study where malnourished dialysis participants will receive a dietitian supervised intensive nutritional support. Participants will be followed-up for 2 years and will receive precise oral and written instructions on how to comply with the intervention. Blood and eyesight tests, SAF measurements, anthropometry and nutritional and quality of life assessments will be conducted. In Studies 1 and 2, approximately two teaspoons of blood will be collected to measure AGE levels and do some additional blood tests to help us investigate the effects of AGEs on the body. If the participants agree, the investigators will also store some of the blood for future research.

Conditions

Chronic Kidney Disease

Keywords

Glycosylation End Products, Advanced; Skin autofluorescence; Renal Dialysis

Outcome Measures

Primary Outcomes (1)

• Skin Autofluorescence Levels at 6 Months

  Skin autolfuorescence (SAF) was measured after 6 months of intensive dietetic advice and nutritional support with a validated Autofluorescence Reader (AGE) Standard Unit (SU), version 2.4.3. The AGE Reader SU directs an ultraviolet excitation light through an illumination window of approximately 1 cm2 on a skin area of the volar surface of the forearm at approximately 10 cm below the elbow. The AGE Reader then measures the amount of emitted light that is reflected back from the skin using a spectrometer and a 200-µm glass fiber. SAF is calculated as the ratio between emission and excitation and is expressed as arbitrary units (AU). Three measurements were conducted and the mean value of these was used for statistical analysis. The reference value of SAF for the age group of 60-70 years is 2.5±0.6 AU.

  6 months

Secondary Outcomes (6)

• Energy Intake at 6 Months.

  6 months

• Nutritional Status at 6 Months

  6 months

• Dietary Advanced Glycation End-products (AGE) Intake at 6 Months

  6 months

• Protein Intake at 6 Months.

  6 months

• Serum Albumin Levels at 6 Months

  6 months

Other Outcomes (5)

• Health-related Quality of Life, Short Form-36 Physical Component Score

  6 months

• Health-related Quality of Life, Short Form-36 Mental Component Score

  6 months

• Health-related Quality of Life, European QoL-5 Dimensions (EQ5D) Health State Score (HSS)

  6 months

Study Arms (2)

Study 2 - Non randomised proof of principle study

Malnourished participants received individualized nutritional advice and support formulated and delivered by experienced dietitians consisting of food fortification recommendations and oral nutritional supplementation aiming to achieve estimated nutritional requirements (i.e. energy \[30-35 kcal/kg/day\] and protein intake \[1.1-1.2 g/kg/day\]). Food fortification involved enhancing the energy and protein content of meals and snacks without increasing the portion sizes of foods. Advice was individualized according to patient needs and food preferences. Oral nutritional supplements included Fortisip Compact (2.4 kcal/ml), Fortisip (1.5 kcal/ml) and Fortijuice (1.5 kcal/ml), as well as Renapro® shot and Fresubin® 5kcal Shot.

Historical control group from Study 1

Participants on dialysis with malnutrition taken from Study 1, who were seen by their usual dietitian once a month and received standard nutritional counselling.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Participants undergoing HD and PD treatment.

You may qualify if:

• Haemodialysis cohort:
• Three dialysis sessions per week for 4 hours.
• Dialysis with biocompatible membranes.
• Able to give informed consent.
• Peritoneal Dialysis cohort:
• Dialysis with lactate/bicarbonate-buffered solutions with different glucose concentrations as prescribed for routine clinical care.
• Able to give informed consent.

You may not qualify if:

• Does not wish to participate.
• Renal transplant.
• Pregnancy or breast feeding or intending pregnancy.
• Expected survival less than one year.

Sponsors & Collaborators

• University of Nottingham: lead
• University Hospitals of Derby and Burton NHS Foundation Trust: collaborator

Study Sites (1)

Derby Hospitals NHS Foundation Trust

Derby, Derbyshire, DE22 3NE, United Kingdom

Location

Related Publications (19)

• Arsov S, Graaff R, van Oeveren W, Stegmayr B, Sikole A, Rakhorst G, Smit AJ. Advanced glycation end-products and skin autofluorescence in end-stage renal disease: a review. Clin Chem Lab Med. 2014 Jan 1;52(1):11-20. doi: 10.1515/cclm-2012-0832.

  PMID: 23612551 BACKGROUND

• Darlene, A., Dartt Reza, D. and D'Amore, P. (2011) Immunology, inflammation and diseases of the eye. Elsevier Press: pp. 287-288.

  BACKGROUND

• Graaff R, Arsov S, Ramsauer B, Koetsier M, Sundvall N, Engels GE, Sikole A, Lundberg L, Rakhorst G, Stegmayr B. Skin and plasma autofluorescence during hemodialysis: a pilot study. Artif Organs. 2014 Jun;38(6):515-8. doi: 10.1111/aor.12205. Epub 2013 Oct 29.

  PMID: 24164288 BACKGROUND

• Hartog JW, Voors AA, Schalkwijk CG, Scheijen J, Smilde TD, Damman K, Bakker SJ, Smit AJ, van Veldhuisen DJ. Clinical and prognostic value of advanced glycation end-products in chronic heart failure. Eur Heart J. 2007 Dec;28(23):2879-85. doi: 10.1093/eurheartj/ehm486. Epub 2007 Nov 5.

  PMID: 17986469 BACKGROUND

• Ishibashi T, Murata T, Hangai M, Nagai R, Horiuchi S, Lopez PF, Hinton DR, Ryan SJ. Advanced glycation end products in age-related macular degeneration. Arch Ophthalmol. 1998 Dec;116(12):1629-32. doi: 10.1001/archopht.116.12.1629.

  PMID: 9869793 BACKGROUND

• Junaid Nazar CM, Kindratt TB, Ahmad SM, Ahmed M, Anderson J. Barriers to the successful practice of chronic kidney diseases at the primary health care level; a systematic review. J Renal Inj Prev. 2014 Jul 1;3(3):61-7. doi: 10.12861/jrip.2014.20. eCollection 2014.

  PMID: 25340171 BACKGROUND

• Kandarakis SA, Piperi C, Topouzis F, Papavassiliou AG. Emerging role of advanced glycation-end products (AGEs) in the pathobiology of eye diseases. Prog Retin Eye Res. 2014 Sep;42:85-102. doi: 10.1016/j.preteyeres.2014.05.002. Epub 2014 Jun 4.

  PMID: 24905859 BACKGROUND

• Kellow NJ, Savige GS. Dietary advanced glycation end-product restriction for the attenuation of insulin resistance, oxidative stress and endothelial dysfunction: a systematic review. Eur J Clin Nutr. 2013 Mar;67(3):239-48. doi: 10.1038/ejcn.2012.220. Epub 2013 Jan 30.

  PMID: 23361161 BACKGROUND

• Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group (2013). KDIGO 2012 Clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int 4(Suppl. 3): pp. 1-150.

  BACKGROUND

• Kimura H, Tanaka K, Kanno M, Watanabe K, Hayashi Y, Asahi K, Suzuki H, Sato K, Sakaue M, Terawaki H, Nakayama M, Miyata T, Watanabe T. Skin autofluorescence predicts cardiovascular mortality in patients on chronic hemodialysis. Ther Apher Dial. 2014 Oct;18(5):461-7. doi: 10.1111/1744-9987.12160. Epub 2014 Jan 24.

  PMID: 24456287 BACKGROUND

• McIntyre NJ, Chesterton LJ, John SG, Jefferies HJ, Burton JO, Taal MW, Fluck RJ, McIntyre CW. Tissue-advanced glycation end product concentration in dialysis patients. Clin J Am Soc Nephrol. 2010 Jan;5(1):51-5. doi: 10.2215/CJN.05350709. Epub 2009 Nov 5.

  PMID: 19965551 BACKGROUND

• Nongnuch A, Davenport A. The effect of vegetarian diet on skin autofluorescence measurements in haemodialysis patients. Br J Nutr. 2015 Apr 14;113(7):1040-3. doi: 10.1017/S0007114515000379. Epub 2015 Mar 12.

  PMID: 25761438 BACKGROUND

• Oleniuc M, Schiller A, Secara I, Onofriescu M, Hogas S, Apetrii M, Siriopol D, Covic A. Evaluation of advanced glycation end products accumulation, using skin autofluorescence, in CKD and dialysis patients. Int Urol Nephrol. 2012 Oct;44(5):1441-9. doi: 10.1007/s11255-011-0097-5. Epub 2011 Dec 10.

  PMID: 22160646 BACKGROUND

• Siriopol D, Hogas S, Veisa G, Mititiuc I, Volovat C, Apetrii M, Onofriescu M, Busila I, Oleniuc M, Covic A. Tissue advanced glycation end products (AGEs), measured by skin autofluorescence, predict mortality in peritoneal dialysis. Int Urol Nephrol. 2015 Mar;47(3):563-9. doi: 10.1007/s11255-014-0870-3. Epub 2014 Nov 26.

  PMID: 25425437 BACKGROUND

• Smit AJ, Gerrits EG. Skin autofluorescence as a measure of advanced glycation endproduct deposition: a novel risk marker in chronic kidney disease. Curr Opin Nephrol Hypertens. 2010 Nov;19(6):527-33. doi: 10.1097/MNH.0b013e32833e9259.

  PMID: 20844429 BACKGROUND

• Uribarri J, Woodruff S, Goodman S, Cai W, Chen X, Pyzik R, Yong A, Striker GE, Vlassara H. Advanced glycation end products in foods and a practical guide to their reduction in the diet. J Am Diet Assoc. 2010 Jun;110(6):911-16.e12. doi: 10.1016/j.jada.2010.03.018.

  PMID: 20497781 BACKGROUND

• Singh VP, Bali A, Singh N, Jaggi AS. Advanced glycation end products and diabetic complications. Korean J Physiol Pharmacol. 2014 Feb;18(1):1-14. doi: 10.4196/kjpp.2014.18.1.1. Epub 2014 Feb 13.

  PMID: 24634591 BACKGROUND

• Zhang QL, Rothenbacher D. Prevalence of chronic kidney disease in population-based studies: systematic review. BMC Public Health. 2008 Apr 11;8:117. doi: 10.1186/1471-2458-8-117.

  PMID: 18405348 BACKGROUND

• Wright M, Jones C. Renal Association Clinical Practice Guideline on nutrition in CKD. Nephron Clin Pract. 2011;118 Suppl 1:c153-64. doi: 10.1159/000328067. Epub 2011 May 6. No abstract available.

  PMID: 21555894 BACKGROUND

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

This was a single-centre proof of principle study. The number of participants was small and the follow-up period was relatively short. The results observed in this study may not be applicable to populations with dark skin colour (who were excluded from our study) because skin autofluorescence measurements cannot be performed in persons with darker skin colour because of the high absorption of the excitation light.

Results Point of Contact

• Title: Professor Maarten Taal
• Organization: University of Nottingham

m.taal@nottingham.ac.uk

01332 224618

Study Officials

• Maarten Taal, Doctor

  University Hospitals of Derby and Burton NHS Foundation Trust

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2016
• First Posted: August 25, 2016
• Study Start: September 21, 2016
• Primary Completion: March 31, 2022
• Study Completion: March 31, 2022
• Last Updated: December 10, 2024
• Results First Posted: December 10, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)