Reference intervals for serum cystatin C and serum creatinine in an adult sub-Saharan African population

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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.

Gloria Ashuntantang

Cardiology and Nephrology Unit, Yaoundé General Hospital, Yaoundé, Cameroon.

Gloria Ashuntantang

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: jobertrichie_nansseu@yahoo.fr

ABSTRACT

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.

BACKGROUND

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

renalfunctionobtainedisquiteimprecise.

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

Reference intervals for serum cystatin C…

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.

Methods

Studydesignandsetting

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.

Descriptionofthestudypopulation

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).

Datacollection

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.

Biochemicalassays

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

Diagnostics, USA).

Statisticalanalysis

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.

Results

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

Jobert Richie Nansseu

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
BSA (m2) 1.68 [1.55–1.79] 1.70 [1.81] 1.65 [1.52–1.76] 0.002*
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 (1.10.1.10) < 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 (1.10.1.10)
[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 (1.10.1.20)

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)

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Reference intervals for serum cystatin C…

Discussion

In agreement with IFCC recommendations [11], 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 (1.29.1.35) < 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 (1.26.1.33)
[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 (1.22.1.32)
[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 (1.24.1.45)
≥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 (1.33.1.52)

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 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 [15]. 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 [16]. 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 [20]. 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 [24]. 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

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Reference intervals for serum cystatin C…

Table 4 Regression coefficients and p-values for the 25th, 50th and 75th percentiles quantile regression models

Serum cystatin C Serum creatinine
25th 50th 75th 25th 50th 75th
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
[12]. 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 [14]. 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
[33]. 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 [24]. 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 [33]. 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.
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