Variation of Serum Uric Acid with Renal Function, Fasting Blood Glucose and Blood Pressure in Northern Cameroonians with Essential Hypertension

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1 Oiginal Aticle Vaiation of Seum Uic Acid with Renal Function, Fasting Blood Glucose and Blood Pessue in Nothen Cameoonians with Essential Hypetension Macel Tangyi Tamanji 1,2 *, Divine Amagho Ngwakum 3, Olivie Pancha Mbouemboue 3,4 1 Faculty of Science, Univesity of Buea, Cameoon, 2 Medical Laboatoy Sevice, Regional Hospital Ngaoundéé, Cameoon, 3 Depatment of Biomedical Sciences, Univesity of Ngaoundéé, Cameoon, 4 Geneal Medicine Sevice, Regional Hospital Ngaoundéé, Cameoon Coesponding autho: Macel Tangyi Tamanji, Faculty of Science, Univesity of Buea, Cameoon, Tel: ; macelnanji@gmail.com Abstact Aim/Backgound: Hypeuicemia has been pupoted to be associated with enal and cadiovascula events as well metabolic syndome. We aimed at investigating the elationship between seum uic acid levels and enal function makes in hypetensive patients. Methods: Individuals diagnosed with hypetension wee consecutively ecuited into this coss-sectional study ove a peiod of fou months commencing Febuay Fasting whole blood samples and blood pessue measuements wee collected, and data wee analysed using the SPSS vesion 20.0 (IBM copoation, USA) softwae with statistical significance consideed at P<0.05. Results: Among 100 paticipants, 20% had aised seum uic acid levels. While uic acid levels coelated with seum ceatinine (=0.37; P<0.001) and uea(=0.31; P<0.01), and invesely vaied with glomeula filtation ate(= -0.24; P=0.02), no significant associations wee obseved between uic acid levels and blood pessue. Futhemoe, the mean ceatinine level was significantly highe in male paticipants with elevated uic acid levels compaed to those with nomal levels [1.67(0.74) mg/dl vesus 1.44(0.80) mg/dl; P<0.001). Although male hypetensive paticipants demonstated significantly highe mean uic acid level compaed to females [7.37(2.51) vs. 6.21(1.57); P<0.01], the pevalence of aised SUA levels was significantly highe women compaed to men (50.8% vs..2%; P<0.001). Conclusion: Seum uic acid level is associated with kidney function capacity in hypetensive pesons, especially in the male gende, and may epesent an accessoy teatment taget in etading the pogession of enal complications. Keywods: Uic Acid; Blood glucose; Renal Function; Essential Hypetension Intoduction Uic acid is a waste poduct of endogenous puine and ATP metabolism in humans, which is exclusively exceted by the kidneys in a less soluble fom owing to the absence of the enzyme uicase in humans. [1,2] which catalysis uic acid beakdown endeing it moe soluble and easy to excete. [3] Plasma uic acid levels theefoe depend almost entiely on enal excetoy capacity as a function of the ate of uic acid poduction and dietay intake as well as excess alcohol consumption and pathologies involving incease cell tunove such as in leukemias, lymphomas, solid tumos and a vaiety of cell lysis pocesses. [4] Since the inception of the phenomenon of the involvement of elevated plasma uic acid levels in the occuence of gout in the 1800s, [5] seveal studies have suggested hypeuicemia as a possible independent and modifiable isk facto in the occuence and pogession of gout, [6,7] obesity, [8] type 2 diabetes, [9,10] metabolic syndome, [-13] cadiovascula, [14] and enal events, [15-17] while othes potay it to be a teatment taget in cadiovascula and kidney disease states. [18-20] Futhemoe, vaious authos have epoted hypeuicemia to at best pecede hypetension and chonic kidney disease (CKD) o at least occu moe fequently among pesons with these diseases. [21,22] Seveal animal studies have demonstated that inceasing plasma uic acid independently inceases the isk of hypetension, chonic kidney disease, and the pogession of enal and cadiovascula events. Moeove, as poposed by many animal and human studies, hypeuicemia esults in a depeciation of cadiovascula and enal function by loweing endothelial nitic oxide levels and educing neuonal nitic oxide synthase in the macula densa of the kidney thus ae stimulating the eninangiotensin system. Also it may induce an inflammatoy eaction, pobable glomeula damage, tubula ischaemia, endothelial dysfunction, and the development of enal micovascula disease owing to the stimulation of vascula smooth muscle cell polifeation thus the installation of enal and systemic hypetension. [2,23-26] Although not yet globally acknowledged as an independent cadiovascula and enal disease isk facto, This is an open access aticle distibuted unde the tems of the Ceative Commons Attibution NonCommecial ShaeAlike 3.0 License, which allows othes to emix, tweak, and build upon the wok non commecially, as long as the autho is cedited and the new ceations ae licensed unde the identical tems. How to Cite this Aticle: Tamanji MT, et al. Vaiation of Seum Uic Acid with Renal Function, Fasting Blood Glucose and Blood Pessue in Nothen Cameoonians with Essential Hypetension. Ann Med Health Sci Res. 2017; 7: Annals of Medical and Health Sciences Reseach

2 [27-32] hypeuicaemia indeed occupies a vital position owing to its supposed involvement in the initiation and wosening of cadiovascula and enal function, making it an indispensable facto in the management of patients with hypetension and CKD in view of slowing down disease pogession and cubing cadiovascula and enal mobidity and motality. We set out thus to investigate the elationship between seum uic acid levels, blood pessue, and kidney function paametes among hypetensive patients in noth Cameoon. Patients and Methods Study design and sample collection Paticipants wee pogessively enolled duing the fist 4 months of this desciptive coss-sectional study caied out at the Geneal Medicine Sevices of the Ngaoundee Regional and Potestant Hospitals, commencing fom Febuay 2015 and spanning a total peiod of 6 months. Hypetension was defined as blood pessue (BP) >140/90mmHg and paticipants wee excluded fo pegnancy, diabetes, HIV/AIDS, dyslipidemias, cance and efusal to consent to the study. Subsequently, they wee funished with extensive infomation on the usefulness and inconveniences of the study, and a witten consent to paticipate obtained. A stuctual questionnaie was used to collect infomation on socio-demogaphy, medical and family histoy, with communication pincipally in the Fench, English and local languages. BP and weight measuements wee pefomed and 5ml of fasting whole blood was collected and immediately analyzed fo fasting whole blood suga (FBS) and the est left to clot in dy tubes on bench-top. The clotted blood samples wee centifuged at 2000pm fo 3 minutes with the esulting seum decanted into Eppendof tubes and stoed at -20 C pio to weekly badge analyses fo uic acid, ceatinine and uea levels. Glomeula filtation ate (GFR) was estimated using the Modification of Diet in Renal Disease (MDRD) and Cockcoft-Gault (CG) fomulas. All pocedues wee pefomed following standad opeating pocedues. Clinical and biochemical measuements Blood pessue An electonic blood pessue machine (OMRON-HEM- 712CN2, Seial numbe: LF, USA) was used to measue esting BP. Patients wee equied to est fo at least 15 minutes upon aival and BP measuements wee obtained fom both the ight and left ams pe patient within an aveage time lapse of 2-3 minutes, and the mean systolic and diastolic pessues between both ams calculated and ecoded. Biochemical paametes Blood suga measuements wee caied out on fasting whole blood samples using a glucomete (EasyTouch ET-101 Seial numbe: 1012A0029, Bioptik Technology Inc, Taiwan) having efeence ange as 75 5 mg/dl. Seum uic acid (SUA), ceatinine and uea levels wee measued using a Semi- Auto Chemisty Analyse (Minday BA-88, Seial numbe: BH7AB2710, China) based on enzyme coloimety (Uicase- TBHBA), Jaffe and Bethelot methods espectively, with nomal values stated at mg/dl, mg/dl and mg/dl fo males and mg/dl, mg/dl, and fo females espectively. GFR was estimated using both the Modification of Diet in Renal Disease [33] and the Cockcoft- Gault [34] fomulas. Quality assuance All pe-analytic pocesses made use of appopiate glass and plastic wae, specimen tanspot and stoage pocedues. Method calibation was ensued by the use of a Calimat multipaamete calibato (Refeence: 62321, Lot: , Bioméieux, Fance). The quality of biochemical analyses was veified and esults validated using a LYOTROLTMN contol seum (Refeence: 62373, Lot: , Bioméieux, Fance). Measuements of biochemical paametes fo the fist 10 paticipants wee eplicated using a second semiautomated spectophotomete (SECOMAM Basic/70V B0358, SN: 1790) to check fo epoducibility of esults and evaluate analytical pefomance. Likewise, automated BP measuements wee compaed with those obtained using a manual sphygmomanomete. Ethical consideations This study obtained ethical cleaance fom the Ngaoundee Regional Hospital Ethical Committee (Ref: 1227/L/RC/RA/ DSP/HR/NGD/CLE). Individuals wee eseved the ight to feely paticipate and teminate paticipation without any sanctions. Paticipant s infomation was stictly confidential and efeals to a nephologist wee done by the investigating cadiologist in cases of abnomal esults. Data management and analysis Micosoft Excel speadsheets wee used to ecod and clean data pio to analysis with the statistical package fo social sciences (SPSS) vesion 20.0 (IBM copoation, USA). Pimaily, subdata sets wee tested fo nomality using the Kolmogoov- Sminova and Shapio-Wilk tests of nomality. Coelations between paametes wee investigated using the Peason and Speaman coelation coefficients while the equality of means was tested using the ANOVA and Mann-Whitney U tests. Statistical significance was stated at P<0.05. Results 100 paticipants matched ou inclusion citeia among which wee 31 men and 69 women, anging in age fom 17 to 93 yeas old and having a mean age of 56.1(15.5) yeas. The mean systolic BP, diastolic BP, SUA, ceatinine and uea levels wee 163.7(30.1) mmhg, 96.8(19.9) mmhg, 6.7(2.1) mg/dl, 1.6(2.1) mg/dl, 53.8(39.9) mg/dl espectively. Raised uic acid levels wee obseved in 20% (20/100) of the study paticipants. SUA levels demonstated a diect elationship with seum ceatinine and uea measuements, and futhe coelated negatively with estimated GFR (C-G) in the geneal study population, but ecoded no significant elationship with both systolic and diastolic BP [Table 1]. In addition to the afoementioned elationships obseved in the geneal study population (with the exception of the SUA- Uea elationship), gende-based analyses evealed a significant positive elationship between SUA levels and FBS in male paticipants but not in thei female countepats [Table 1]. 82

3 Table 1: Coelation between SUA and selected clinical and biochemical paametes in the geneal study population, male and female paticipants. Categoy Paametes SBP DBP FBS Ceatinine Uea GFR-CG GFR-MDRD All Paticipants Male Paticipants Female Paticipants * * < * * * * We went on to compae the means of selected paametes between nomouicemic and hypeuicemic paticipants between who no significant diffeences wee ecoded in the geneal study population. It was obseved that the mean seum ceatinine was significantly highe in hypeuicemic compaed to nomouicemic male paticipants (but not in females). Both systolic and diastolic BP failed to demonstate statistical diffeences between nomouicemic and hypeuicemic paticipants [Tables 2 and 3]. Table 2: Compaison of means of selected paametes between nomouicaemic and hypeuicaemic in male paticipants. Paametes SUA level n Mean ± SD P-value Age (yeas) Weight (Kg) SBP (mmhg) DBP (mmhg) FBS (mg/dl) Ceatinine (mg/dl) Uea (mg/dl) ± ± ± ± ± ± ± ± ± ± ± ± ± ± * Table 3: Compaison of means of selected paametes between nomouicemic and hypeuicemic in female paticipants. Paametes UA 1 level n Mean±SD P-value Age (yeas) ± ± Weight (Kg) ± ± SBP (mmhg) ± ±.52 DBP (mmhg) ± ± FBS (mg/dl) ± ± Ceatinine (mg/dl) ± ± 0.74 Uea (mg/dl) ± ± Compaing the mean SUA level between gende, male compaed to female paticipants ecoded significant highe levels [7.4(2.5) vs. 6.2(1.6); P<0.01), although a geate popotion of women had aised SUA levels compaed to men [50.8% (31/61) vs..2% (/39); P<0.001]. Discussion Hypeuicemia has peviously been epoted by seveal authos to be associated with both enal impaiment [23,35] and cadiovascula events. [36-38] In this study caied out on 100 hypetensive pesons, the pevalence of aised SUA was estimated at 20%, esults which diffe fom the inceased ates of 46.1% epoted by Ofoi and Odia among newly diagnosed, unteated hypetensive Nigeians. [39] In an ealie study, hypeuicaemia was estimated in 25% of hypetensive patients without teatment, 50% of patients on diuetic theapy, and in moe than 75% of patients with malignant hypetension. [40] A ecent study epoted a 30.6% hypeuicaemia ate in patients with essential hypetension compaed to 10.6% in healthy contols. [41] These dispaities may be a diect consequence of the quality of ou paticipants, being a composition of both newly diagnosed and known hypetensive patients, 91(91%) of whom wee on antihypetensive phamacotheapy with vaying duations of teatment. This study demonstates an incease in SUA levels with inceasing seum uea, ceatinine, and deceasing GFR among hypetensive paticipants in geneal and futhe with inceasing blood glucose levels in males. In line with epots of pevious authos, this may be a esult of a pogessing glomeula damage, endothelial dysfunction, enal micovascula disease and tubula ischaemia [38,42-45] and the pedictive natue of hypeuicaemia to diabetes. [9,10] Paadoxically a pevious animal study by Kosugi and co-wokes hold that diabetes could be a pedisposing facto to hypeuicaemia as they obseved that diabetic ats wee moe likely to develop hypeuicaemia compaed to the non-diabetic. [46] Elevated uic acid levels have been pupoted to pedict pogession of CKD, [47-49] and as GFR falls, SUA levels incease, with about 50% of such patients becoming hypeuicemic pio to the commencement of dialysis. [50] Futhemoe, the mean SUA level was significantly highe in males than in females (P=0.005), suppoting pevious findings, [42-45] pobably being a esult of the inceased vulneability of males to hypeuicaemia than females, although Luk and Simkin ealie epoted that with inceasing age such diffeences tend to dampen. [51] Convesely, Ofoi and Odia obseved highe mean SUA levels in female hypetensives compaed to thei male countepats. We also noted that the popotion of female paticipants with aised SUA levels was significantly highe compaed to the male paticipants (50.8% vs..2%; P<0.001). Emokpae et al. epoted 62% and 59% aised SUA in females and males espectively, which was pupoted to be associated with the complex inteplay of sex homones in women. [44] Limitations This study was a coss sectional suvey to examine the association between seum uic acid, ateial blood pessue and enal function makes, and thus did not pemit the establishment 83

4 of a cause and effect elationship. Hindeing enough was the fact that ove 60% of ou study paticipants wee on at least a single antihypetensive medication and with the absence of a contol population, it was difficult to ule out the concomitant effect of antihypetensive phamacotheapy on ateial blood pessue as a confounde Conclusion This study demonstated a diect elationship between seum uic acid concentation, and seum ceatinine and uea levels; and also indicated that as glomeula filtation ate falls, uic acid levels incease as well. Moeove, seum ceatinine levels wee significantly highe in hypetensive males with aised SUA levels. Futhemoe, seum uic acid levels vaied diectly with fasting blood suga among male hypetensive paticipants. Accoding to ou findings, it could be suggested that seum uic acid levels may eithe modify enal function o itself be modified by enal impaiment in hypetensive patients. Futhe Reseach and Pespectives The paadoxical elationship between uic acid and taget ogan pathologies epesents an aea fo contempoay opeational eseach following pevious epots on thei association fom studies eplicated in seveal ethnic populations, and also following the non-univesal acceptance and inclusion of hypeuicaemia as pat of cadiovascula disease isk factos. Few studies in this line have been caied out in Cameoon in paticula and Afica as a whole, thus the validity o nonvalidity of such associations cannot be undoubtedly ascetained, hence the need fo extensive, longitudinal, and multidisciplinay studies to investigate pevious claims and hypotheses. Autho s Contibutions MTT and OPM conceived the study, defined the expeimental design and intellectual content, and pepaed and edited the manuscipt. MTT caied out laboatoy expeiments while OPM and DAN pefomed clinical studies. MTT and DAN pefomed the liteatue seach, and all authos paticipated in data acquisition and analysis, poof eading and appoval of the final manuscipt. Acknowledgements This wok would not have been successful without the immense contibutions fom the data management team and local language tanslatos. We also commend the collaboative effots of the administative, clinical and laboatoy staff of the Ngaoundee Regional and Potestant hospitals. Conflict of Inteest All authos disclose that thee was no conflict of inteest. Refeences 1. Heinig M and Johnson RJ. Role of uic acid in hypetension, enal disease, and metabolic syndome. Cleve Clin J Med. 2006; Johnson RJ, Nakagawa T, Sanchez-Lozada LG, Kang D, Ritz E. Uic acid and chonic kidney disease: Which is chasing which? Nephol. Dial. Tansplant. 2013; : Sautin YY, Johnson RJ. Uic acid: The oxidant antioxidant paadox. Nucleosides Nucleotides Nucleic Acids. 2008; 27: Kutzing MK, Fiestein BL. Alteed uic acid levels and disease states. 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