Biomarkers - Renal Function

Renal Function

This section documents TILDA biomarkers of renal function and filtration, including creatinine and cystatin C.

Renal Function Biomarkers

Click each heading to expand details of this biomarker.

Overview

What is it? Creatinine is a waste product generated from the normal breakdown of creatine in skeletal muscle. It is removed from the blood primarily by filtration in the kidneys, and circulating concentrations are influenced by kidney function as well as factors including muscle mass.

Research relevance: Can be used to investigate kidney function and renal health, including the estimation of glomerular filtration rate (eGFR) and the study of chronic kidney disease and its associations with other health outcomes.

Sample type: Frozen K2EDTA blood plasma

Sample Collection / Handling

Plasma isolated from 10 mL of fresh whole blood, maintained at 2–4°C for 24–48 hours after blood collection and subsequently frozen at −80°C.

Assay / Measurement

Method: Enzymatic colorimetric assay. Creatinine is converted through reactions involving creatininase, creatinase and sarcosine oxidase, producing hydrogen peroxide that forms a coloured quinone-imine product. Colour intensity is proportional to the creatinine concentration.

Equipment / analyser: Waves 1 and 3: Roche Hitachi Cobas c 701 analyser with Roche Cobas Creatinine plus ver.2 kits.

Laboratory: Waves 1 and 3: Biochemistry Department, Laboratory Medicine (LabMed), St James’s Hospital, Dublin.

Measurement Characteristics

Characteristic Value
Units µmol/L
Measurement range 5‑2700 µmol/L
Lower detection limit 5 µmol/L
Assay CoV 0.026

Collection Waves

Biomarker Wave 1 Wave 2 Wave 3 Wave 4 Wave 5 Wave 6
Creatinine X X X

Reference

  • National Institute of Diabetes and Digestive and Kidney Diseases (2019) Your Kidney Test Results. Available at: https://www.niddk.nih.gov/health-information/diagnostic-tests/kidney-test-results

Example TILDA Papers

  • Canney, M, Sexton, DJ, O’Leary, N, Healy, M, Kenny, RA, Little, MA, O’Seaghdha, CM. Examining the utility of cystatin C as a confirmatory test of chronic kidney disease across the age range in middle-aged and older community-dwelling adults. Journal of Epidemiology and Community Health. 72(4):287-293. https://doi.org/10.1136/jech-2017-209864
  • Canney, M, Sexton, E, Tobin, K, Kenny, RA, Little, MA, O’Seaghdha, CM. The relationship between kidney function and quality of life among community-dwelling adults varies by age and filtration marker. Clinical Kidney Journal. 11(2):259-264. https://doi.org/10.1093/ckj/sfx084

Overview

What is it? Cystatin C is a low-molecular-weight protein produced by nucleated cells and removed from the circulation primarily through glomerular filtration by the kidneys. Its blood concentration is therefore related to glomerular filtration rate (GFR) and is less influenced by muscle mass than creatinine.

Research relevance: Can be used to investigate kidney function and renal health, including estimation of GFR and the study of chronic kidney disease. It can provide a complementary measure to creatinine, particularly where differences in muscle mass may affect creatinine-based estimates of kidney function.

Sample type: Frozen K2EDTA blood plasma

Sample Collection / Handling

Plasma isolated from 10 mL of fresh whole blood, maintained at 2–4°C for 24–48 hours after blood collection and subsequently frozen at −80°C.

Assay / Measurement

Method: Particle-enhanced immunoturbidimetric assay. Cystatin C in the sample agglutinates with latex particles coated with anti-cystatin C antibodies, and the resulting aggregates are measured turbidimetrically.

Equipment / analyser: Waves 1 and 3: Roche Hitachi Cobas c 701 analyser with Roche Cobas Tina-quant Cystatin C Gen.2 kits.

Laboratory: Waves 1 and 3: Biochemistry Department, Laboratory Medicine (LabMed), St James’s Hospital, Dublin.

Measurement Characteristics

Characteristic Value
Units mg/L
Measurement range 0.40-6.80 mg/L
Lower detection limit 0.40 mg/L
Assay CoV 0.022

Collection Waves

Biomarker Wave 1 Wave 2 Wave 3 Wave 4 Wave 5 Wave 6
Cystatin C X X X

Reference

  • Inker, L.A., Eneanya, N.D., Coresh, J., Tighiouart, H., Wang, D., Sang, Y., Crews, D.C., Doria, A., Estrella, M.M., Froissart, M., Grams, M.E., Greene, T., Grubb, A., Gudnason, V., Gutiérrez, O.M., Kalil, R., Karger, A.B., Mauer, M., Navis, G., Nelson, R.G., Poggio, E.D., Rodby, R., Rossing, P., Rule, A.D., Selvin, E., Seegmiller, J.C., Shlipak, M.G., Torres, V.E., Yang, W., Ballew, S.H., Couture, S.J., Powe, N.R. and Levey, A.S. (2021) ‘New creatinine- and cystatin C-based equations to estimate GFR without race’, New England Journal of Medicine, 385(19), pp. 1737–1749. doi:10.1056/NEJMoa2102953.

Example TILDA Papers

  • Canney, M, Sexton, DJ, O’Leary, N, Healy, M, Kenny, RA, Little, MA, O’Seaghdha, CM. Examining the utility of cystatin C as a confirmatory test of chronic kidney disease across the age range in middle-aged and older community-dwelling adults. Journal of Epidemiology and Community Health. 72(4):287-293. https://doi.org/10.1136/jech-2017-209864
  • Canney, M, Sexton, E, Tobin, K, Kenny, RA, Little, MA, O’Seaghdha, CM. The relationship between kidney function and quality of life among community-dwelling adults varies by age and filtration marker. Clinical Kidney Journal. 11(2):259-264. https://doi.org/10.1093/ckj/sfx084