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Published in: BMC Nephrology 1/2019

Open Access 01-12-2019 | Chronic Kidney Disease | Research article

Salivary creatinine as a diagnostic tool for evaluating patients with chronic kidney disease

Authors: Dada Oluwaseyi Temilola, Karla Bezuidenhout, Rajiv Timothy Erasmus, Lawrence Stephen, Mogamat Razeen Davids, Haly Holmes

Published in: BMC Nephrology | Issue 1/2019

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Abstract

Background

Preliminary studies have shown the potential use of salivary creatinine concentration in the diagnosis of chronic kidney disease (CKD). For saliva to replace serum as a diagnostic tool, studies must be done to determine its effectiveness in the diagnosis and staging of CKD. The aim of the present study was to evaluate the use of salivary creatinine as a safe and non-invasive alternative for identifying patients with CKD.

Methods

A cross-sectional study was conducted at Tygerberg Hospital in Cape Town, on 230 patients, across all stages of CKD. Ethical approval to conduct the study was obtained from the University of the Western Cape Biomedical Research Ethics Committee, and written informed consent was provided by each participant. Saliva and serum samples were collected for creatinine analysis and the correlation determined using Spearman’s correlation. Receiver operating characteristics (ROC) analysis was used to determine the diagnostic ability of salivary creatinine. A cut-off value for optimal sensitivity and specificity of salivary creatinine to diagnose CKD with glomerular filtration rate (GFR) < 60 mL/min/1.73 m2 was obtained.

Results

Serum creatinine values ranged from 46 μmol/L to 1581 μmol/L, with a median value of 134 μmol/L. Salivary creatinine values ranged from 3 μmol/L to 400 μmol/L, with a median of 11 μmol/L. There was a strong positive correlation (r = 0.82) between serum and salivary creatinine values. Linear regression analysis of serum and salivary creatinine for CKD patients was significant in all CKD stages, except for stage 1. Area under the curve for salivary creatinine was 0.839. A cut-off value of 8.5 μmol/L yielded a sensitivity of 78.3% and specificity of 74.0% for classifying patients as having CKD based on estimated GFR < 60 mL/min/1.73 m2.

Conclusions

The results support the potential of salivary creatinine as a non-invasive diagnostic tool for estimating GFR and identifying patients with CKD.
Literature
1.
go back to reference Ruggenenti P, Schieppati A, Remuzzi G. Progression, remission, regression of chronic renal diseases. Lancet. 2001;357:1601–8.CrossRef Ruggenenti P, Schieppati A, Remuzzi G. Progression, remission, regression of chronic renal diseases. Lancet. 2001;357:1601–8.CrossRef
2.
go back to reference Hill NR, Fatoba ST, Oke JL, Hirst JA, O’Callaghan CA, Lasserson DS, Hobbs FR. Global prevalence of chronic kidney disease–a systematic review and meta-analysis. PloS One. 2016;11(7):e0158765.CrossRef Hill NR, Fatoba ST, Oke JL, Hirst JA, O’Callaghan CA, Lasserson DS, Hobbs FR. Global prevalence of chronic kidney disease–a systematic review and meta-analysis. PloS One. 2016;11(7):e0158765.CrossRef
3.
go back to reference Eknoyan G, Lameire N. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl. 2013;3:1–150.CrossRef Eknoyan G, Lameire N. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl. 2013;3:1–150.CrossRef
4.
go back to reference ElHafeez SA, Bolignano D, D’Arrigo G, Dounousi E, Tripepi G, Zoccali C. Prevalence and burden of chronic kidney disease among the general population and high-risk groups in Africa: a systematic review. BMJ Open. 2018;8(1):e015069.CrossRef ElHafeez SA, Bolignano D, D’Arrigo G, Dounousi E, Tripepi G, Zoccali C. Prevalence and burden of chronic kidney disease among the general population and high-risk groups in Africa: a systematic review. BMJ Open. 2018;8(1):e015069.CrossRef
5.
go back to reference Stanifer JW, Jing B, Tolan S, Helmke N, Mukerjee R, Naicker S, et al. The epidemiology of chronic kidney disease in sub-Saharan Africa: a systematic review and meta-analysis. Lancet Glob Health. 2014;2(3):e174–81.CrossRef Stanifer JW, Jing B, Tolan S, Helmke N, Mukerjee R, Naicker S, et al. The epidemiology of chronic kidney disease in sub-Saharan Africa: a systematic review and meta-analysis. Lancet Glob Health. 2014;2(3):e174–81.CrossRef
6.
go back to reference Matsha TE, Yako YY, Rensburg MA, Hassan MS, Kengne AP, Erasmus RT. Chronic kidney diseases in mixed ancestry south African populations: prevalence, determinants and concordance between kidney function estimators. BMC Nephrol. 2013;14(1):75.CrossRef Matsha TE, Yako YY, Rensburg MA, Hassan MS, Kengne AP, Erasmus RT. Chronic kidney diseases in mixed ancestry south African populations: prevalence, determinants and concordance between kidney function estimators. BMC Nephrol. 2013;14(1):75.CrossRef
7.
go back to reference Adeniyi AB, Laurence CE, Volmink JA, Davids MR. Prevalence of chronic kidney disease and association with cardiovascular risk factors among teachers in Cape Town, South Africa. Clin Kidney J. 2017;10(3):363–9.PubMedPubMedCentral Adeniyi AB, Laurence CE, Volmink JA, Davids MR. Prevalence of chronic kidney disease and association with cardiovascular risk factors among teachers in Cape Town, South Africa. Clin Kidney J. 2017;10(3):363–9.PubMedPubMedCentral
8.
go back to reference Feher JJ. Quantitative human physiology: an introduction. Amsterdam: Academic Press; 2012.CrossRef Feher JJ. Quantitative human physiology: an introduction. Amsterdam: Academic Press; 2012.CrossRef
9.
go back to reference Ahmadi Motamayel F, Davoodi P, Dalband M, Hendi SS. Saliva as a mirror of the body health. DJH. 2010;2:1–5. Ahmadi Motamayel F, Davoodi P, Dalband M, Hendi SS. Saliva as a mirror of the body health. DJH. 2010;2:1–5.
10.
go back to reference John MA, Li Y, Zhou X, Denny P, Ho CM, Montemagno C, et al. Interleukin 6 and interleukin 8 as potential biomarkers for oral cavity and oropharyngeal squamous cell carcinoma. Arch Otolaryngol Head Neck Surg. 2004;130(8):929–35.CrossRef John MA, Li Y, Zhou X, Denny P, Ho CM, Montemagno C, et al. Interleukin 6 and interleukin 8 as potential biomarkers for oral cavity and oropharyngeal squamous cell carcinoma. Arch Otolaryngol Head Neck Surg. 2004;130(8):929–35.CrossRef
11.
go back to reference Gao K, Zhou H, Zhang L, Lee JW, Zhou Q, Hu S, et al. Systemic disease-induced salivary biomarker profiles in mouse models of melanoma and non-small cell lung cancer. PLoS One. 2009;4(6):e5875.CrossRef Gao K, Zhou H, Zhang L, Lee JW, Zhou Q, Hu S, et al. Systemic disease-induced salivary biomarker profiles in mouse models of melanoma and non-small cell lung cancer. PLoS One. 2009;4(6):e5875.CrossRef
12.
go back to reference Rao PV, Reddy AP, Lu X, Dasari S, Krishnaprasad A, Biggs E, et al. Proteomic identification of salivary biomarkers of type-2 diabetes. J Proteome Res. 2009;8(1):239–45.CrossRef Rao PV, Reddy AP, Lu X, Dasari S, Krishnaprasad A, Biggs E, et al. Proteomic identification of salivary biomarkers of type-2 diabetes. J Proteome Res. 2009;8(1):239–45.CrossRef
13.
go back to reference Zhang L, Farrell JJ, Zhou H, Elashoff D, Akin D, Park NH, et al. Salivary transcriptomic biomarkers for detection of resectable pancreatic cancer. Gastroenterology. 2010;138(3):949–57.CrossRef Zhang L, Farrell JJ, Zhou H, Elashoff D, Akin D, Park NH, et al. Salivary transcriptomic biomarkers for detection of resectable pancreatic cancer. Gastroenterology. 2010;138(3):949–57.CrossRef
14.
go back to reference Lee YH, Kim JH, Zhou H, Kim BW, Wong DT. Salivary transcriptomic biomarkers for detection of ovarian cancer: for serous papillary adenocarcinoma. J Mol Med. 2012;90(4):427–34.CrossRef Lee YH, Kim JH, Zhou H, Kim BW, Wong DT. Salivary transcriptomic biomarkers for detection of ovarian cancer: for serous papillary adenocarcinoma. J Mol Med. 2012;90(4):427–34.CrossRef
15.
go back to reference Bader RS, Kora MA, El-Shalakany AH, Mashal BS. Clinical significance of saliva urea and creatinine levels in patients with chronic kidney disease. Menoufia Med J. 2015;28(2):406.CrossRef Bader RS, Kora MA, El-Shalakany AH, Mashal BS. Clinical significance of saliva urea and creatinine levels in patients with chronic kidney disease. Menoufia Med J. 2015;28(2):406.CrossRef
16.
go back to reference Lasisi TJ, Raji YR, Salako BL. Salivary creatinine and urea analysis in patients with chronic kidney disease: a case control study. BMC Nephrol. 2016;17(1):10.CrossRef Lasisi TJ, Raji YR, Salako BL. Salivary creatinine and urea analysis in patients with chronic kidney disease: a case control study. BMC Nephrol. 2016;17(1):10.CrossRef
18.
go back to reference Tomás I, Marinho JS, Limeres J, Santos MJ, Araújo L, Diz P. Changes in salivary composition in patients with renal failure. Arch Oral Biol. 2008;53(6):528–32.CrossRef Tomás I, Marinho JS, Limeres J, Santos MJ, Araújo L, Diz P. Changes in salivary composition in patients with renal failure. Arch Oral Biol. 2008;53(6):528–32.CrossRef
19.
go back to reference Lloyd JE, Broughton A, Selby C. Salivary creatinine assays as a potential screen for renal disease. Ann Clin Biochem. 1996;33(5):428–31.CrossRef Lloyd JE, Broughton A, Selby C. Salivary creatinine assays as a potential screen for renal disease. Ann Clin Biochem. 1996;33(5):428–31.CrossRef
20.
go back to reference Brown Connolly NE. A better way to evaluate remote monitoring programs in chronic disease care: receiver operating characteristic analysis. Telemedicine e-Health. 2014;20(12):1143–9.CrossRef Brown Connolly NE. A better way to evaluate remote monitoring programs in chronic disease care: receiver operating characteristic analysis. Telemedicine e-Health. 2014;20(12):1143–9.CrossRef
21.
go back to reference Xia Y, Peng C, Zhou Z, Cheng P, Sun L, Peng Y, et al. Clinical significance of saliva urea, creatinine, and uric acid levels in patients with chronic kidney disease. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2012;37(11):1171–6.PubMed Xia Y, Peng C, Zhou Z, Cheng P, Sun L, Peng Y, et al. Clinical significance of saliva urea, creatinine, and uric acid levels in patients with chronic kidney disease. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2012;37(11):1171–6.PubMed
22.
go back to reference Renda R. Can salivary creatinine and urea levels be used to diagnose chronic kidney disease in children as accurately as serum creatinine and urea levels? A case–control study. Ren Fail. 2017;39(1):452–7.CrossRef Renda R. Can salivary creatinine and urea levels be used to diagnose chronic kidney disease in children as accurately as serum creatinine and urea levels? A case–control study. Ren Fail. 2017;39(1):452–7.CrossRef
23.
go back to reference Ladgotra A, Verma P, Raj SS. Estimation of salivary and serum biomarkers in diabetic and non diabetic patients-a comparative study. J Clin Diagn Res. 2016;10(6):ZC56–61. Ladgotra A, Verma P, Raj SS. Estimation of salivary and serum biomarkers in diabetic and non diabetic patients-a comparative study. J Clin Diagn Res. 2016;10(6):ZC56–61.
24.
go back to reference Briet M, Collin C, Karras A, Laurent S, Bozec E, Jacquot C, et al. Arterial remodeling associates with CKD progression. J Am Soc Nephrol. 2011;22(5):967–74.CrossRef Briet M, Collin C, Karras A, Laurent S, Bozec E, Jacquot C, et al. Arterial remodeling associates with CKD progression. J Am Soc Nephrol. 2011;22(5):967–74.CrossRef
25.
go back to reference Lakatta EG, Levy D. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: part I: aging arteries: a “set up” for vascular disease. Circulation. 2003;107(1):139–46.CrossRef Lakatta EG, Levy D. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: part I: aging arteries: a “set up” for vascular disease. Circulation. 2003;107(1):139–46.CrossRef
26.
go back to reference Hench PS, Aldrich M. A salivary index to renal function. JAMA. 1923;81(24):1997–2003.CrossRef Hench PS, Aldrich M. A salivary index to renal function. JAMA. 1923;81(24):1997–2003.CrossRef
27.
go back to reference Edelstein CL. Biomarkers in acute kidney injury. Adv Chronic Kidney Dis. 2008;15(3):222–34. Edelstein CL. Biomarkers in acute kidney injury. Adv Chronic Kidney Dis. 2008;15(3):222–34.
Metadata
Title
Salivary creatinine as a diagnostic tool for evaluating patients with chronic kidney disease
Authors
Dada Oluwaseyi Temilola
Karla Bezuidenhout
Rajiv Timothy Erasmus
Lawrence Stephen
Mogamat Razeen Davids
Haly Holmes
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Nephrology / Issue 1/2019
Electronic ISSN: 1471-2369
DOI
https://doi.org/10.1186/s12882-019-1546-0

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