Bertille Elodie Edinga-Melenge Suzanne Belinga, Eric Minkala, Prisca Armel Noudjeu, Michel Ondhoua, Samuel Walter Kokola, and Catherine Bilong
Department of Biochemistry, Centre Pasteur of Cameroon, Yaoundé, Cameroon.
Bertille Elodie Edinga-Melenge and Vicky Joceline Ama Moor
Department of Physiological Sciences and Biochemistry, Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, Cameroon.
Adrienne Tchapmi Yakam
Ebebda District Hospital, Centre Regional Delegation, Ministry of Public Health, Ebebda, Cameroon.
Jobert Richie Nansseu
Department for the Control of Disease, Epidemics and Pandemics, Ministry of Public Health, Yaoundé, Cameroon.
Jobert Richie Nansseu
Department of Public Health, Faculty of Medicine and Biomedical Sciences of the University of Yaoundé I, PO Box 1364, Yaoundé, Cameroon.
Vicky Joceline Ama Moor
Laboratory of Biochemistry, Yaoundé University Teaching Hospital, Yaoundé, Cameroon.
Cardiology and Nephrology Unit, Yaoundé General Hospital, Yaoundé, Cameroon.
Department of Internal Medicine and Specialties, Faculty of Medicine and Biomedical Sciences of the University of Yaoundé I, Yaoundé, Cameroon.
All Correspondences to: Jobert Richie Nansseu E-mail: firstname.lastname@example.org
Background: Serum cystatin C (SCysC) and serum creatinine (SCr) are two biomarkers used in common practice to estimate the glomerular filtration rate (GFR). For SCysC and SCr to be used in a given population, normal values need to be determined to better assess patients. This study aimed to determine SCysC and SCr reference intervals (RIs) in a Cameroonian adult population and factors susceptible of influencing them. Methods: We carried-out a cross-sectional study from November 2016 to May 2017 in Yaoundé, Cameroon. Participants were Cameroonians aged 18 years and above, residing inside the country and found in good health at study inclusion. SCysC and SCr were determined by particle-enhanced turbidimetric immunoassay standardized against the ERM-DA471/IFCC reference material and by the IDMS reference modified Jaffe kinetic method, respectively. RIs were determined using the 2.5th and 97.5th percentiles and their respective 90% confidence intervals (CIs). The quantile regression served to identify potential factors likely influencing SCysC and SCr values. Results: We included 381 subjects comprising 49.1% females.. RIs for SCysC varied between 0.57 (90%CI: 0.50–0.60) and 1.03 mg/L (90%CI: 1.00–1.10) for females, and from 0.70 (90%CI: 0.60–0.70) to 1.10 mg/L (90%CI: 1.10–1.20) for males. Concerning SCr, its RIs ranged from 0.58 (90%CI: 0.54–0.61) to 1.08 mg/dL (90%CI: 1.02–1.21) for females, and from 0.74 (90%CI: 0.70–0.80) to 1.36 mg/dL (90%CI: 1.30–1.45) for males. Men had significantly higher SCysC and SCr values than women (p < 0.001). Likewise, subjects aged 50 years and above had higher SCysC values in comparison to younger age groups (p < 0.001), which was not the case for SCr values (p = 0.491). Moreover, there was a positive and significant correlation between SCysC and SCr in women (ρ = 0.55, p < 0.001), in men (ρ = 0.39, p < 0.001) and globally (ρ = 0.58; p < 0.001). Furthermore, the sex influenced both biomarkers’ values across all quantile regression models while age and body surface area (BSA) influenced them inconsistently. Conclusion: This study has determined serum cystatin C and serum creatinine reference intervals in an adult Cameroonian population, whose interpretations might take into account the patient’s sex
and to a certain extent, his/her age and/or BSA.
Keywords: Reference interval, Cystatin C, Creatinine, Yaoundé, Cameroon.
Glomerularfiltrationrate(GFR)iswidelyacceptedas the mostusefuloverallindexofkidneyfunctionin healthand disease(1).It is best evaluated by clearance measurement ofexogenousmarkerssuchasinuline,but thecomplex proceduresofthesemeasureslimittheir routineuse(2,3). GFR is therefore commonly estimated fromserumlevelof endogenousfiltrationmarkers.The mostwidelyusedand recommendedendogenousmarker forinitialassessment ofGFRisserumcreatinine(4).
Despitethecheapestcostandthesimpleuseof creatinine-basedmeasurementsofGFR,estimationof thelevelof
Indeed, the steady-state serum creatinine level is determined byfactorsthatincludeleantissuemass; hence, it mayvarywithsex,age,weightandheight(3,5,6).
Asaresultoftheselimitations,alternativeendogenous markersforGFRsuchasserumcystatinChavebeen proposed.CystatinCisabiomarkerformedataconstant rate by all nucleated cells of the body which do not correlate with lean tissue mass (5). Evidence has demonstrated improved accuracy and sensitivity of cystatinC comparedtocreatinine(7).
For an accurate interpretation of biomarkers levels,
Nigerian Biomedical Science Journal Vol. 16 No 3 2019 49
referenceintervalsspecifictoapopulationneedtobe established.Intriguinglyandalthoughserumcreatinine is widely used in Cameroon, no previous study had yet focused at determining its reference intervals, interpretations relying on western countries’ data. Moreover consideringthegrowingimportanceofcystatin Casa prospectivemarkertoassesstherenalfunction,itis obvious thatthismarkerwouldbeintroducedinroutine clinicalpracticeinCameroonverysoon.Therefore,we conductedthepresentstudytodeterminethereference valuesofserumcreatinineandcystatinCinahealthy adult Cameroonianpopulationlivinginsidethecountry. Besides, weaimedtoidentifypotentialfactorslikely influencing thesereferenceintervals.
This was a population based cross-sectional study conducted betweenNovember2016andMay2017in Yaounde’thecapitalcityofCameroon.Participantswere recruitedfromthe4mostpopulatedhealthdistrictsout of the6thatconstitutesthecity,namely:Yaounde’1,2,4 and 7
(8). Biological analyses were performed at the Centre PasteurofCameroun.
ParticipantswereadultCamerooniansresidinginsidethe country,aged18yearsandabove,foundingoodhealthat studyinclusion-afterageneralexaminationincludinga briefmedicalinterview,urinalysisandmeasurementof bloodpressureandglycaemia-withnoevidenceofany acuteorchronicillnesssusceptibleofaffectingcreatinine orcystatinClevels.Weexcludedknownorsuspected hypertensives,thosewithanimpairedglucosemetabolism
(pre-diabetes or diabetes mellitus) or an abnormal dipstick urinetest.Pregnantandbreastfeedingwomenwerealso excluded, as well as drug users. No special dietary recommendations were required. Participants were consecutively recruited during the study period and a minimumof 120 participantswasrequiredforeachsex group,inline withtheInternationalFederationofClinical Chemistry’s (IFCC) recommendations (9).
Participants were mostly recruited in churches, sc hools/universities/collegesandmosques.Onthedaysof recruitment,eachpotentialparticipantwasrequiredto sign aconsentformasthetestimonyofhis/hervolunteering participation. Subsequently, he/she underwent a brief interview using a preconceived, standardized and pre-testedquestionnaire(Additionalfile 1);then a summary physicalexaminationwasconducted,duringwhich blood pressurewasmeasured.Weusedthesimplified calculation procedurefromMostellerRDtoderiveeach participant’s bodysurfacearea(BSA)(10).In addition, a urinesample wascollectedfordipstickurineanalysis andacapillary glycaemiawasperformedusinga OneTouch*analyzer.
Ten milliliters of venous blood were collected by
venipuncture in 2 dry tubes of 5ml each. Serum was separatedbycentrifugationat3000rpmwithin10min. Biochemical assays were conducted using the autoanalyzer CobasC501/6000,RocheDiagnostics,USA. Serum cystatinCwasmeasuredinincrementsof0.1mg/L by particle-enhanced turbidimetric immunoassay using Tina-quant*CystatinCreagentkits(RocheDiagnostics, USA).Themethodappliedwasstandardizedagainstthe ERM-DA471/IFCCreferencematerial.Meanwhile, serum creatininewasdeterminedbytheIsotopeDilution Mass Spectrometry (IDMS) reference modified Jaffe kinetic methodusingCreatinineJaffeCobas*reagentkits (Roche
DatawerecodedandenteredusingtheCensusand Survey ProcessingSystemversion7.1.Statisticalanalysis was performed using the Statistical Package for Social Sciencesversion23.0(IBMSPSSInc.,Chicago,Illinois, USA) and STATA version 12.0(STATACORP, Texas, USA).Categoricalvariablesarepresentedusingfrequency (percentage) while continuous variables are summarized withtheirmedian(interquartilerange,[IQR].
Edinga-Melengeetal.BMCClinicalPathology (2019) 19:4Page2 of 9
TheKolmogorovSmirnovtestwasusedtoassessthe normality of continuous variables’ distributions. Reference intervals(RIs) were determined by the nonparametric methodasdescribedintheIFCCguidelines (11).
This method was used to determine the 2.5 and 97.5 percentilesandtherespective90%confidenceintervals (CI) around these estimates. The Mann–WhitneyU-test and the Kruskal-Wallis H-test were used for bivariate analyses, to compare the distributions of continuous variables, consideringthatthesevariablesdidnotfollowa
Gaussianshape.Forthesamereason,itistheSpearman correlationtest(withitsrho(ρ)coefficient) that was used
to investigate existence of any correlation between continuousvariablesincludingserumcystatinC,serum creatinineandage.Furthermore,weuseda25th,50th and 75thpercentilequantileregressionanalysistoidentify any factor likely influencing serum cystatin C or serum creatininereferenceintervalsinamodelincluding theage, sex,andBSA.Statisticalsignificancewasset atap-value
lower than 0.05.
Atotalof 485healthysubjectswerescreenedofwhom 104 wereexcludedbecauseofunderlyingdiabetesmellitus, pre-diabetes,hypertensionorabnormaldipstick urinetest. Thereferencepopulationcomprised 381 healthyadults (including49.1% females)agedbetween 18and71years oldwithamedianageof28years[IQR 23-40].Therewere nodifferencesinthedistributionof agebetweenmaleand femaleparticipants(p=0.290).By contrast,maleshad significantlyhigherBSAvaluesthan females:p=0.002 (Table 1).
Thenon-parametricreferenceintervalsforserum cystatin Cwere0.57-1.03mg/Lforwomenand0.70-1.10mg/Lfor
50 Nigerian Biomedical Science Journal Vol. 16 No 3 2019
men; the reference intervals for the whole studypopulation were0.60 -1.10mg/L(Table 1).For serumcreatinine,these intervalswere0.58-1.08mg/dL forwomen,0.74-1.36 mg/dLformen,and0.61-1.30 mg/dLforallsubjects (Table1).As compared to women,menhadsignificantly highertitersofserum cystatinC(median0.90vs.0.80 mg/L; p<0.001;Table 1) thanwomen,exceptforthose aged50yearsandabove (p=0.125;Table 2).Similarly, men had significantly higher serum creatinine values (median1.06vs.0.79mg/dL; p<0.001;Table 1)than women, this tendency being thesameinallagegroups (Table3).
Additionally, serum cystatin C levels were higher in persons aged 50 years and above compared to their counterparts agedlessthan50yearsold(p<0.001;Table 2);on thecontrary,thisdifferencewasnotobservedwith serum creatininevalues(p=0.491;Table 3).Moreover, we found apositiveandsignificantcorrelationbetweenserum cystatinCandserumcreatininebothinfemales(p = 0.55; p
<0.001),in males(p =0.39 < 0.001) and in the total study population(p = 0.58;p<0.001).
Furthermore,thecorrelationbetweenserumcystatin C logarithmically-transformedvaluesandagewasweak and non-significantinmales(p=- 0.006,p=0.930;Fig. 1 a),but becamesignificantinfemales(p= 0.265, p< 0.001;Fig. 1b. Contrariwise,thecorrelationbetween serumcreatinine logarithmically-transformed values and age was significantinmales(p = 0.162, p=0.023;Fig. 2a),but insignificantinfemales(p = 0.127, p=0.082; Fig.2b).On theotherhand,resultsofthequantile regressionwhichare presentedinTable4showed thatacrossthevariousmodels, thesexremainedthe onlyfactorlikelyinfluencingboth serumcystatinC andserumcreatininevalues.Theage seemedtocontribute inexplainingserumcystatinCvalues inthe 75thpercentilequantileregressionmodel,which was identicalforserumcreatininevalues.TheBSAwas contributiveinexplainingserumcreatininevalues onlyin the50thpercentilequantileregressionmodel (Table 4).
Table 1 Reference intervals for serum cystatin C and serum creatinine according to sex
|Parameter||All (n = 381)||Males (n = 194)||Females (n = 187)||p*|
|Age (years)||28 [23–40]||28 [24–40]||26 [22–43]||0.290|
|Serum cystatin C (mg/L)|
|Median [IQR]||0.80||[0.70–0.90]||0.90||[0.80–1.00]||0.80||[0.70–0.90]||< 0.001|
|2.5th percentile (90%CI)||0.60||(0.60–0.61)||0.70||(0.60–0.70)||0.57||(0.50–0.60)|
|97.5th percentile (90%CI)||1.10||(1.10–1.11)||1.10||(1.10–1.20)||1.03||(1.00–1.10)|
|Serum creatinine (mg/dL)|
|Median [IQR]||0.92||[0.77–1.06]||1.06||[0.96–1.14]||0.79||[0.71–0.88]||< 0.001|
|2.5th percentile (90% CI)||0.61||(0.59–0.64)||0.74||(0.70–0.80)||0.58||(0.54–0.61)|
|97.5th percentile (90% CI)||1.30||(1.28–1.35)||1.36||(1.30–1.45)||1.08||(1.02–1.21)|
BSA body surface area, CI confidence interval, IQR interquartile range, SCysC serum cystatin C, SCr serum creatinine; †The Mann-Whitney U-test was used for variable comparisons; *p < 0.05
Table 2 Reference intervals for serum cystatin C by age and sex
|Age||N=381||Serum cystatin C (mg/L)|
|(years)||Median (IQR)||2.5th percentile (90%CI)||97.5th percentile (90%CI)||p„©|
|< 20||Male:||9 0.9 (0.85.1.05)||0.7 (0.70.0.90)||1.1||0.003|
|Female:||14||0.75 (0.70.0.80)||0.6 (0.60.0.70)||0.9|
|All: 23||0.8||(0.70.0.90) 0.6||(0.60.0.70)||1.1|
|[20.30]||Male: 95||0.9||(0.80.1.0)||0.6 (0.60.0.70)||1.1||(22.214.171.124)||< 0.001|
|Female:||89||0.7 (0.70.0.80)||0.6 (0.50.0.60)||1.0||(0.90.1.00)|
|All: 184||0.8||(0.70.0.90)||0.6 (0.60.0.60)||1.1||(126.96.36.199)|
|[30.40]||Male: 40||0.9||(0.80.0.90)||0.7 (0.70.0.80)||1.0||(1.00.1.00)||0.001|
|Female:||31||0.8 (0.60.0.80)||0.5 (0.50.0.50)||1.0|
|All: 71||0.8||(0.80.0.90)||0.5 (0.50.0.58)||1.0||(1.00.1.00)|
|[40.50]||Male: 32||0.9||(0.80.0.98)||0.7 (0.70.0.70)||1.1||0.002|
|Female:||21||0.8 (0.70.0.90)||0.6 (0.60.0.70)||1.0|
|All: 53||0.8||(0.80.0.90)||0.6 (0.60.0.70)||1.0||(1.00.1.00)|
|50||Male: 18||1.0||(0.88.1.0)||0.7 (0.70.0.80)||1.2||0.125|
|Female:||32||0.9 (0.80.0.90)||0.6 (0.60.0.80)||1.1|
|All: 50||0.9||(0.80.1.00)||0.7 (0.60.0.73)||1.2||(188.8.131.52)|
CI confidence interval, IQR interquartile range. Some 90% confidence intervals are not presented due to the small number of participants in corresponding age groups. ┼ The Mann-Whitney U-test was used to compare the distribution of serum cystatin C values between males and females. The difference between agegroups was significant when using the Kruskal-Wallis H-test (p < 0.001)
Nigerian Biomedical Science Journal Vol. 16 No 3 2019 51
In agreement with IFCC recommendations , the reference intervals for serum cystatin C and serum creatinine were determined in the present study among a healthy Cameroonian adult population. Our results revealed that the reference intervals for serum cystatin C
varied between 0.6 and 1.1 mg/L, with men having higher values than women (p < 0.001), except in the 50+ years age group. Concerning serum creatinine, the reference intervals ranged from 0.6 to 1.3 mg/dL; similarly, men had significantly higher levels than women (p < 0.001) across all age groups. Participants
Table 3 Reference intervals for serum creatinine by age and sex
|Age||N=381||Serum creatinine (mg/dL)|
|(years)||Median (IQR)||2.5th percentile (90%CI) 97.5th percentile (90%CI)||p„©|
|< 20||Male: 9||1.09 (1.00.1.15)||0.80 (0.80.1.04)||1.18||< 0.00|
|Female: 14||0.76 (0.72.0.79)||0.66 (0.66.0.70)||0.88|
|All: 23||0.79 (0.75.1.08)||0.66 (0.66.0.70)||1.18|
|[20.30]||Male: 95||1.03 (0.94.1.12)||0.80 (0.70.0.85)||1.30 (184.108.40.206)||< 0.001|
|Female: 89||0.79 (0.71.0.87)||0.60 (0.54.0.61)||1.07 (1.01.1.28)|
|All: 184||0.91 (0.78.1.05)||0.61 (0.59.0.65)||1.30 (220.127.116.11)|
|[30.40]||Male: 40||1.06 (0.95.1.13)||0.75 (0.69.0.81)||1.29||< 0.001|
|Female: 31||0.73 (0.65.0.83)||0.57 (0.57.0.60)||1.26|
|All: 71||0.94 (0.74.1.08)||0.58 (0.57.0.62)||1.27 (18.104.22.168)|
|[40.50]||Male: 32||1.08 (0.99.1.17)||0.68 (0.68.0.74)||1.45||< 0.001|
|Female: 21||0.74 (0.69.0.90)||0.51 (0.51.0.66)||1.02|
|All: 53||0.99 (0.74.1.10)||0.61 (0.51.0.66)||1.38 (22.214.171.124)|
|≥50||Male: 18||1.17 (0.99.1.30)||0.79 (0.79.0.96)||1.52||< 0.001|
|Female: 32||0.85 (0.79.0.93)||0.60 (0.60.0.65)||1.05|
|All: 50||0.93 (0.81.1.06)||0.64 (0.60.0.66)||1.43 (126.96.36.199)|
CI confidence interval, IQR interquartile range. Some 90% confidence intervals are not presented due to the small number of participants in corresponding age groups. ┼ The Mann-Whitney U-test was used to compare males and females; the difference in the distribution of serum creatinine values between age-groups was not significant with the Kruskal-Wallis H-test (p = 0.491)
Fig. 1 a Relationship between serum cystatin C (log) values and age in males [(n = 194); y = 0.0009x – 0.0114, ρ = 0.162 (p = 0.024)]. b Relationship between serum cystatin C (log) values and age in females [(n = 187); y = 0.0016x – 0.164, ρ = 0.265 (p < 0.001)]
52 Nigerian Biomedical Science Journal Vol. 16 No 3 2019
aged 50 years and above had higher serum cystatin C values than those aged less than 50 years (p < 0.001), which was not the case for serum creatinine values (p = 0.491). Moreover, the correlation between serum cystatin C and serum creatinine was positive and significant (ρ = 0.58; p < 0.001) and the quantile regression pointed mostly the sex, and to a certain extent the age and BSA as independent factors susceptible of influencing serum cystatin C and/or serum creatinine values. Reference intervals for serum cystatin C obtained in this study (0.60–1.10 mg/L) are in compliance with those from previous studies which have also used turbidimetric assay. For instance, Köttgen et al. recorded in a US population a reference interval varying between 0.61– 1.04 mg/L; Okonkwo et al. in a Nigerian population recorded a reference interval ranging between 0.64–1.12mg/L and Li et al. in a Chinese population recorded a reference interval varying from 0.60 to 1.08 mg/L [12–14]. By contrast, the reference intervals for serum creatinine obtained in this study (0.61–1.3 mg/dL)
Jobert Richie Nansseu
seem to differ from that of Caucasians. Indeed, Pottel et al. found reference intervals around 0.48–0.93 mg/dL in women and 0.63–1.16 mg/dL in men within a healthy adult Caucasian population . These intervals concur with those of Ceriotti et al. obtained in a multicenter analysis of three studies based on Caucasian adults. In this study indeed, the reference intervals for serum creatinine varied between 0.45–0.92mg/dL in women and 0.59–1.05mg/dL in men . These differences could be explained by the fact that the measurement of serum creatinine used enzymatic methods in the two studies just cited, which could give slightly lower values than colorimetric assays that were used in our study. Additionally, evidence has accumulated that black people have a more important lean tissue mass and a lower GFR compared to Caucasians [3, 17]. However, our results corroborate those from other African authors such as Sakande et al. in Burkina Faso and Dosoo et al. in Ghana. Indeed, Sakande et al. reported reference intervals ranging between 0.63–1.41 mg/dL in
Fig. 2 a Relationship between serum creatinine (log) values and age in males [(n = 194); y = 0.0009x – 0.0114, ρ = 0.162 (p = 0.024)]. b Relationship between serum creatinine (log) values and age in females [(n = 187); y = 0.0007x – 0.129, ρ = 0.127 (p = 0.082)]
men and 0.45–1.24 mg/dL in women; reference intervals obtained by Dosoo et al. were 0.63–1.35 mg/dL in men and 0.60–1.20mg/dL in women [18, 19]. Furthermore, Lim et al. conducted a study among afro-Americans and found similar results with men having serum creatinine reference intervals around 0.73–1.45 mg/dL and women, around 0.52–1.15 mg/dL . The sex-related differences in the non-parametric reference intervals for serum creatinine are in line with previous studies and reinforced by results of our quantile regression analysis indicating that the sex influenced serum creatinine values across all models, while adjusting for age and BSA. Indeed, muscular mass is
higher in men compared to women [3, 5, 6, 21]. Concurring with previous findings, our results indicate that serum cystatin C levels seem to be slightly affected by factors such as sex and age [22–24]. Pottel et al. showed for instance that cystatin C increases with age, after the age of 70 years old . The influence of sex on serum cystatin C levels is still unclear. In fact, some studies have reported that serum cystatin C levels are independent of sex unlike other studies have claimed that sex influences significantly serum cystatin C values [13, 23, 25–28]. In our study for instance, we found that the sex constituted one independent explanatory factor for serum cystatin C values, whatever
Nigerian Biomedical Science Journal Vol. 16 No 3 2019 53
Table 4 Regression coefficients and p-values for the 25th, 50th and 75th percentiles quantile regression models
|Serum cystatin C||Serum creatinine|
|Sex||-0.1 (< 0.001)*||– 0.1 (< 0.001)*||-0.09 (< 0.001)*||-0.24 (< 0.001)*||-0.28 (< 0.001)*||-0.27 (< 0.001)*|
|Age||7.67e-19 (1.000)||– 3.36e- 18 (1.000)||0.003 (0.001)*||0.0007 (0.171)||0.001 (0.162)||0.002 (0.031)*|
|BSA||9.39e-17 (1.000)||7.35e-16 (1.000)||0.038 (0.475)||0.08 (0.072)||0.15 (0.001)*||0.127 (0.073)|
|*p < 0.05|
|the quantile regression model considered; additionally,||perhaps because they used the Pearson correlation test and|
|serum cystatin C levels were 11% higher in men than in||rescaled their biomarkers. The inconsistent influence of|
|women (0.90 mg/L vs 0.80 mg/L; p < 0.001). These results||age on both serum cystatin C and serum creatinine values|
|corroborate those from Köttgen et al. in the US who||was observed after applying the quantile regression|
|reported a difference of 8% between males and females||analysis. Indeed, we found that age influenced|
|. However, Al Wakeel et al. in a Saudi adult population||significantly both serum cystatin C and serum creatinine|
|reported lower serum cystatin C levels in men compared to||values only at the 75th percentile quantile regression|
|women (0.72 mg/L vs 0.77 mg/L; p < 0.001) as well as Li et||model, the estimator being insignificant at the 25th and|
|al. in China (0.84 mg/L vs 0.85 mg/L; p < 0.05) [14, 29]. In||50th percentile models. We need further well-designed|
|the Saudi study, women had higher body mass index that||studies to better investigate the influence of age (and BSA)|
|men and the positive correlation between serum cystatin C||on serum cystatin C and serum creatinine values in our|
|and body mass index could have explained the higher||context. However, our findings need to be interpreted in the|
|serum cystatin C levels in women [13, 29, 30]. In Li et al.’s||context of some limitations, mainly occurring from the|
|study, the sex difference was observed only between 30||non-random sampling method used and single|
|and 60 years . Likewise, we found in our study that||measurement of serum cystatin C and serum creatinine. In|
|from 50 years old and beyond, differences of serum||fact, the representativeness of our study population and|
|cystatin C levels between men and women became non-||generalization of our results to the entire Cameroonian|
|significant (median 1.00 vs 0.90 mg/L; p = 0.125) while the||population would have been better obtained with|
|difference persisted for serum creatinine levels (median||randomization. Nevertheless, we selected the most|
|1.17 vs 0.85 mg/dL; p < 0.001). Actually, the influence of||populated health districts among the 6 that compose|
|sex on serum cystatin C levels seems non-significant with||Yaoundé, the cosmopolitan capital city of Cameroon. On|
|increasing age, suggesting a physiological or pathological||the other hand, participants were selected on the basis of|
|condition which should be more investigated in elderly.||their normal renal function which could be attested only by|
|Further studies are warranted in this respect. On the other||measurement of GFR by the gold standard (inuline).|
|hand, subjects aged 50 years and over had 11% higher||Nonetheless, the absence of risk factors for kidney disease|
|serum cystatin C levels compared to lower age groups||and the normal clinical and biological tests performed|
|(0.90 vs. 0.80; p < 0.001). Concurring with these results,||among our participants could be some indirect indicators|
|several other studies have demonstrated an increase in||of normal kidney function. Furthermore, we used rigorous|
|cystatin C values above a threshold age varying from 40 to||statistical procedures and applied the IFCC guidelines to|
|70 years [12, 14, 24, 29–32]. The higher levels of serum||depict our estimates. Notwithstanding and to the very best|
|cystatin C in older subjects could be due to the||of our knowledge, this is the first|
|physiological decrease in GFR which starts from 40 years||study providing the reference values for serum cystatin C|
|. Serum creatinine levels are also expected to increase||and serum creatinine in Cameroon, which could be|
|around the same age (≥50 years); however, we observed||translatable to similar sub Saharan African populations.|
|that the distributions of serum creatinine values were||Conclusion|
|similar across the various age groups (p = 0.491).|
|Likewise, Pottel et al. using a Caucasian population||This study depicted serum cystatin C and serum creatinine|
|noticed that between 20 and 70 years old, the mean serum||reference intervals in a healthy adult Cameroonian|
|creatinine level was stable . This could be explained by||population. Men had significantly higher levels of both|
|the drop in creatinine rate production due to reduction in||biomarkers compared to women. Subjects aged 50 years|
|the muscle mass which appears concomitantly with the||old and above had significantly higher serum cystatin C|
|decrease in GFR . The physiological increase in||values than those aged less than 50 years old. Therefore,|
|creatinine levels will be therefore lately observed around||the interpretation of both biomarkers should probably take|
|65–70 years [3, 15]. We found a positive and significant||into account the patient’s sex and to a certain extent, his/her|
|correlation between serum cystatin C and serum||age (and/or body surface area) for an appropriate diagnosis|
|creatinine, both in males (ρ = 0.39, p < 0.001), in females (ρ||of a renal disease. Moreover, it is hoped that our data|
|= 0.55, p < 0.001) and in the total population (ρ = 0.58; p <||stimulate further research on a larger population that will|
|0.001). These findings mirror those from Pottel et al. who||be more representative of the whole country’s diversity.|
|reported a positive correlation between these two||REFERENCES|
|biomarkers in a Caucasian population of 8584 subjects (r =|
|0.87; p < 0.0001) . Potter et al.’s correlation coefficient||1. Kellum JA, Lameire N, Aspelin P, Barsoum RS,|
|was higher than ours,||Burdmann EA, Goldstein SL, et al. KDIGO AKI|
54 Nigerian Biomedical Science Journal Vol. 16 No 3 2019
guidelines. Kidney Int. 2012;2:1.
- Agence Nationale d’Accréditation et d’Evaluation en Santé. Diagnostic del’insuffisance rénale chronique chez l’adulte. Paris: ANAES; 2002.
- Tournois-Hirzel C, Canivet E. Marqueurs de l’insuffisance rénale et prise en charge des patients en insuffisance rénale chronique, dialysés et transplantés. In: Beaudeux JL, editor. dir Biochimie médicale: marqueurs actuels et perspectives. 2nd ed. Cachan: Lavoisier; 2011. p. 343–56.
- Kidney Disease: Improving global outcomes (KDIGO) CKD work group. KDIGO 2012 clinical practice guideline for the evaluation and Management of Chronic Kidney disease. Kidney Int Suppl. 2013;3(1):1–150.
- Vinge E, Lindergård B, Nilsson-Ehle P, Grubb A. Relationships among serumcystatin C, serum creatinine, lean tissue mass and glomerular filtration rate in healthy adults. Scand J Clin Lab Invest. 1999;59:587–92.
- Delanaye P, Cavalier E, Maillard N, Krzesinski J-M, Mariat C, Cristol J-P, et al. La créatinine: d’hier à aujourd’hui. Ann Biol Clin. 2010;68:531–43.
- Roos JF, Doust J, Tett SE, Kirkpatrick CMJ. Diagnostic accuracy of cystatin C compared to serum creatinine for the estimation of renal dysfunction in adults and children—a meta-analysis. Clin Biochem. 2007;40:383–91.
- Bureau Central des Recensements et des Etudes de Population. Etat et structures de la population. BUCREP; 2005. Report No: 3.
- Henny J. Établissement et validation des intervalles de référence au laboratoire de biologie médicale. Ann Biol Clin (Paris). 2011;69:229–37.
- Mosteller RD. Simplified calculation of body-surface area. N Engl J Med.1987;317(17):1098.
- Solberg HE. Approved recommendation on the theory of reference values. Part 5. Statistical treatment of collected reference values. Determination of reference limits. Clin Chim Acta. 1987;170:S13–32.
- Köttgen A, Selvin E, Stevens LA, Levey AS, Van Lente F, Coresh J. Serumcystatin C in the United States: the third National Health and nutrition examination survey (NHANES III). Am J Kidney Dis. 2008;51:385–94.
- Ijoma C, Ijoma U, Okonkwo I, Ogbu I, Ulasi I. Reference intervals for serumcystatin C and creatinine of an indigenous adult Nigerian population. Niger J Clin Pract. 2015;18:173.
- Li D-D, Zou M-N, Hu X, Zhang M, Jia C-Y, Tao C-M,
Jobert Richie Nansseu
et al. Reference intervals and factors contributing to serum cystatin C levels in a Chinese population: reference intervals of cystatin C. J Clin Lab Anal. 2012;26:49–54.
- Pottel H, Vrydags N, Mahieu B, Vandewynckele E, Croes K, Martens F. Establishing age/sex related serum creatinine reference intervals from hospital laboratory data based on different statistical methods. Clin Chim Acta. 2008;396:49–55.
- Ceriotti F, Boyd JC, Klein G, Henny J, Queraltó J, Kairisto V, et al. Reference intervals for serum creatinine concentrations: assessment of available data for global application . Clin Chem . 2008;54:559–66.
- Wang X, Xu G, Li H, Liu Y, Wang F. Reference intervals for serum creatinine with enzymatic assay and evaluation of four equations to estimate glomerular filtration rate in a healthy Chinese adult population. Clin Chim Acta Int J Clin Chem. 2011;412:1793–7.
- Sakande J, Coulibaly J, Njikeutchi F, Bouabre A, Boukary A, Guissou I-P. Etablissement des valeurs de référence de 15 constituants biochimiques sanguins chez l’adulte burkinabé à Ouagadougou – Burkina Faso. Ann Biol Clin (Paris). 2004;62:229–34.
- Dosoo DK, Kayan K, Adu-Gyasi D, Kwara E, Ocran J, Osei-Kwakye K, et al. Haematological and biochemical reference values for healthy adults in the Middle Belt of Ghana. PLoS One. 2012;7:1–9.
- Lim E, Miyamura J, Chen JJ. Racial/ethnic-specific reference intervals for common laboratory tests: a comparison among Asians, blacks, Hispanics, and white. Hawaii J Med Public Health. 2015;74:302–10.
- Marieb E. Muscles et tissu musculaire. Anatomie et physiologie humaines. 4th ed: DeBoeck Université; 2010. p. 300.
- Flamant M, Boulanger H, Azar H, Vrtovsnik F. Mesure et estimation du débit de filtration glomérulaire : quels outils pour la prise en charge de la maladie rénale chronique ? Presse Med . 2010;39:303–11.
- Delanaye P, Chapelle J-P, Gielen J, Krzesinski J-M, Rorive GL. intérêt de la cystatine C dans l’évaluation de la fonction rénale. Néphrologie. 2003;24:457–68. Edinga-Melenge et al. BMC Clinical Pathology (2019) 19:4 Page 8 of 9
- Pottel H, Delanaye P, Schaeffner E, Dubourg L, Eriksen BO, Melsom T, et al. Estimating glomerular filtration rate for the full age spectrum from serum creatinine and cystatin C. Nephrol Dial Transplant Off Publ Eur Dial Transpl Assoc – Eur Ren Assoc. 2017;32(3):497–507.
Nigerian Biomedical Science Journal Vol. 16 No 3 2019 55
- Wasén E, Suominen P, Isoaho R, Mattila K, Virtanen A, Kivelä S-L, et al. Serum cystatin C as a marker of kidney dysfunction in an elderly population. Clin Chem. 2002;48:1138–40.
- Uhlmann EJ, Hock KG, Issitt C, Sneeringer MR, Cervelli DR, Gorman RT, et al. Reference intervals for plasma cystatin C in healthy volunteers and renal patients, as measured by the Dade Behring BN II system, and correlation with creatinine. Clin Chem. 2001;47:2031–3.
- Erlandsen EJ, Randers E, Kristensen JH. Reference intervals for serum cystatin C and serum creatinine in adults. Clin Chem Lab Med. 1998;36:393–7.
- Parildar Z. Age and gender associated changes in cystatin C and b 2 -microglobulin. Turk J Med Sci. 2002;32:317–21.
- Al Wakeel JS, Memon NA, Chaudhary A, Mitwalli AH, Tarif N, Isnani A, et al. Normal reference levels of serum cystatin C in Saudi adults. Saudi J Kidney Dis Transplant Off Publ Saudi Cent Organ Transplant Saudi Arab. 2008;19:361–70.
- Galteau MM, Guyon M, Gueguen R, Siest G. Determination of serum cystatin C: biological variation and reference values. Clin Chem Lab Med. 2001;39:850–7.
- Ognibene A, Mannucci E, Caldini A, Terreni A, Brogi M, Bardini G, et al. Cystatin C reference values and aging. Clin Biochem. 2006;39:658–61.
- Croda-Todd MT, Soto-Montano XJ, Hernández-Cancino PA, Juárez-Aguilar E. Adult cystatin C reference intervals determined by nephelometric immunoassay. Clin Biochem. 2007;40:1084–7.
- Lindeman RD. Assessment of renal function in the old.
S p e c i a l c o n s i d e r a t i o n s . C l i n L a b M e d .
- Pottel H, Dubourg L, Schaeffner E, Eriksen BO, Melsom T, Lamb EJ, et al. Data on the relation between renal biomarkers and measured glomerular filtration rate. Data Brief. 2017;14:763–72.