jurnal gh tambunta

7262019 Jurnal GH Tambunta

httpslidepdfcomreaderfulljurnal-gh-tambunta 16

Original Article

Clinical implications and outcome prediction in chronic hemodialysispatients with lower serum potassium times uric acid product

Ming-Yan Jiang a Jyh-Chang Hwang ab Yi-Hua Lu a Charn-Ting Wang a

a Division of Nephrology Chi Mei Medical Center Tainan Taiwanb Department of Hospital and Health Care Administration Chia Nan University of Pharmacy and Science Tainan Taiwan

a b s t r a c ta r t i c l e i n f o

Article history

Received 20 May 2015Received in revised form 19 June 2015

Accepted 28 June 2015

Available online 20 August 2015

Keywords

Hypokalemia

Hyperuricemia

End-stage renal disease

Malnutrition

In1047298ammation

Chronic kidney disease

Background The aims of this study were to evaluate correlations between serum potassium (S[K]) and uric acid

(S[UA]) in hemodialysis patients and to determine whether lower levels of both S[K] and S[UA] were associatedwith poor long-term prognoses in these patients

Methods A cohort of 424maintenance hemodialysis patients (58 plusmn 13 years of age47 male 39 with diabetes)

from a single center were divided into tertiles based on the product of S[K] times S[UA] (K times UA) Group 1 low

KtimesUA n = 141Group2 medianK times UA n = 141andGroup3 highK times UA n = 142The longest observation

period was 60 months

Results S[K] showed a positivelinear correlation with S[UA] (r = 033 p b 0001) In multivariate logistic regres-

sion analysis Group 1 was characterized by hypoalbuminemia (odds ratio [OR] = 020 95 con1047297dence interval

(CI) = 011ndash035) and lower levels of normalized proteincatabolism [nPCR] (OR = 010 95CI = 005ndash022) and

phosphate levels (OR = 041 95CI = 033ndash051) In contrast Group 3 was associated with higher nPCR

(OR = 607 95CI = 293ndash1250) and albumin levels (OR = 212 95 CI = 212ndash700) Compared to the

reference (Group 1) the hazard ratio (HR) for long-term mortality was signi1047297cantly lower in Groups 2

(HR = 065 95CI = 043ndash099) and 3 (HR = 056 95CI = 036ndash089) In multivariate Cox proportional

analysis the risk of mortality decreased by 2 (HR = 098 95CI = 096 ndash099) per 1 unit increase in

K times UA product

ConclusionHemodialysis patientswith lower S[K] and [UA] levels were characterized by hypoalbuminemia

and lower nPCR and they were associated with a long-term mortality risk

copy 2015 European Federation of Internal Medicine Published by Elsevier BV All rights reserved

1 Introduction

Hyperkalemia is a potentially life-threatening condition for patients

with end-stage renal disease (ESRD) [1] Furthermore dialysate po-

tassium concentration hasbeenshown to have an impact on theout-

comes of hyperkalemic hemodialysis (HD) patients [2] Conversely

hypokalemia is usually overlooked as most patients are asymptom-

atic Severe hypokalemia increases the risk of ventricular arrhyth-

mias that can lead to cardiac arrest in patients with underlying

cardiac diseases [ 3] Chronic hypokalemic HD patients have also

been shown to be associated with a worse long-term prognosis [4]

The prevalence of hyperuricemia and gout has been reported to

increase with a decrease in glomerular 1047297ltration rate [5] However the

association of serum uric acid concentration (S[UA]) and mortality in

patients with ESRD is still controversial A population-based study

from the United States Renal Data System revealed that incidental

gout was associated with a 15-fold increase in the risk of mortality in

patients with ESRD [6] In contrast data from the Dialysis Outcomes

and Practice Patterns Study (DOPPS) showed that a higher S[UA] was

associated with a lower risk of all-cause and cardiovascular mortality

in HD patients A high S[UA] has also been reported to be related to a

higher normalized protein catabolic rate (nPCR) [7]

In patients with ESRD both potassium and UA homeostasis share a

common pathway by depending on oral intake dialytic removal and

adapted extra-renal excretion [89] Their serum levels are elevated as

renal function deteriorates In addition both serum potassium concen-

tration (S[K]) [24] and S[UA] [7] levels have been positively associated

with nPCR andplasmaalbumin levelwhichsuggeststhe linkage of both

parameters to protein nutritional status However few studies have in-

vestigated the association between S[K] and S[UA] although a high

S[UA] (uric acid N 82 mgdL) was found to be weakly associated with

a lower S[K] in the DOPPS study [7]

BothS[UA] and S[K] are routinely monitored for chronic HD patients

in clinical practice Therefore the aim of this study was to evaluate the

European Journal of Internal Medicine 26 (2015) 646ndash651

Corresponding author at 901 Zhonghua Rd Yongkang Dist Tainan City Taiwan

71010 Tel +886 6 2812811 ext 57475 fax +886 6 2816825

E-mail address alfonjchseednettw (J-C Hwang)

httpdxdoiorg101016jejim201506016

0953-6205copy 2015 European Federation of Internal Medicine Published by Elsevier BV All rights reserved

Contents lists available at ScienceDirect

European Journal of Internal Medicine

j o u r n a l h o m e p a g e w w w e l s e v i e r c o m l o c a t e e j i m



correlation between S[K] and S[UA] in HD patients We also com-

bined these two biochemical markers to investigate whether lower

levels of both S[K] and S[UA] were associated with a poor long-

term prognosis in these patients since both parameters are related

to protein nutrition

2 Patients and methods

21 Patient enrollment

This study was a cohort observational study of prospectively

collected data based on a database that was constructed for outcome

assurance from January 2004 to July 2008 at a single medical center

After excluding the patients who had received HD for fewer than 6

months (n = 18) those suspected of having acute renal failure

(n = 6) and those with the long-term use of diuretics and

potassium-reducing agents (n = 2) a total of 424 patients with

ESRD undergoing maintenance HD at our unit three times a week

for 4 hours per session in January 2004 were enrolled into this

study Based on the product of pre-dialysis(S[K] times S[UA]) as assessed

on the last mid-week dialysis session in January 2004 the patients

were categorized into tertiles Group 1 S[K] times S[UA] le 299 n = 141

Group 2 S[K] times S[UA] N 299 le 383 n = 141 and Group 3S[K] times S[UA] N 383 n = 142 The hollow-1047297ber dialyzers used in all

patients included FB210G (Nissho Corporation Osaka Japan) B3-

20 (Toray Industries Inc Tokyo Japan) Hemo1047298ow F10 HPS (Fresenius

Medical Care AG Bad Homburn Germany) and PSN-210 (Baxter

Healthcare Corporation McGaw Park IL USA) The formula of the dial-

ysate bath used at the initiation of thestudy was sodium 1400 mmolL

calcium 15 mmolL potassium 10 mmolL magnesium 05 mmolL

chloride 1045 mmolL acetate 40 mmolL dextrose 200 mgdL and

bicarbonate 35 mmolL (Renasolreg SB-1080 Renal System Minneapo-

lis MN USA) Due to concerns over cost we used another dialysate

(Hemodialysis Concentrate A-35 and BP-11 Chi Sheng Chemical

Corporation Hsinchu Taiwan) from July 2004 to the end of the

study The formula of this dialysate was sodium 1390 mmolL calci-

um 15 mmolL potassium 20 mmolL magnesium 05 mmolL

chloride 1065 mmolL acetate 40 mmolL dextrose 200 mgdL

and bicarbonate 39 mmolL No changes in potassium concentration

in the dialysate bath or dialysate sodium remodeling process were

applied throughout the study period For management of anemia

8000 unitsweek of Epoetinum alfa (EPREXreg Cilag AG Switzerland)

was subcutaneously injected after HD for patients with hemoglobin (Hg)

less than 85 gdL 6000 unitsweek for those with Hg between 85 gdL

and 10 gdL 4000 unitsweek for Hg between 10 gdL to 11 gdL and

2000 unitsweek for Hg between 11 and 12 gdL No patients received

allopurinol and diuretics in this study

22 Data collection

Blood samples were taken in the last mid-week of January 2004(the beginning of the study) and every six months thereafter until

September 2008 Pre-HD biochemical tests included serum albu-

min by means of bromocresol purple and potassium blood urea

nitrogen creatinine uric acid and phosphate concentrations were

measured using a Hitachi 7601ndash110 Automatic Analyzer (Tokyo

Japan) Residual renal function (R RF) was calculated by MDR D for-

mula Hematocrit was measured using a Beckman Coulter LH755-A

system (Fullerton CA USA) Levels of high sensitive C-reactive pro-

tein (hs-CRP) (CardioPhasereg Siemens Healthcare Diagnostics Prod-

ucts GmbH Germany) and pre-albumin (immunochemically

Dade Behring Marburg GmbH Germany) were also measured The

data of the patients who were transferred to other centers or who

died during the study were omitted on a monthly basis We also

evaluated KtV urea (Gotch formula) and nPCR for all patients at

the beginning of study to compare differences in dialysis dosage

and protein intake between the groups [10]

23 Comorbidity

Comorbidities were assessed according to the past history re-

corded in the medical charts at the beginning of study The diag-

nostic criteria for the various comorbid conditions were described

in our previous study [11] All patients recordsinformation wereanonymized and de-identi1047297ed prior to analysis The current study

was approved by the Ethics Committee of Chi Mei Medical Center

and was conducted in accordance with the guiding principles for

human experimentation of the Helsinki Declaration

3 Statistical analysis

Appropriateχ2 and ANOVA with post hocBonferroni tests were used

for comparisons between categorical and continuous variables between

Table 1

Basic demographic characteristics of the three groups of patients

Group 1 Group 2 Group 3

n = 141 n = 141 n = 142

Demographic factors

Diabetes mellitus 50 39 27b

Male 35 51a 54a

Age at study years 59 plusmn 14 58 plusmn 13 56 plusmn 12

HD vintag e months 504 plusmn 41 4 499 plusmn 439 432 plusmn 1183

Ultra1047297ltration Lsession 25 plusmn 08 26 plusmn 08 29 plusmn 08

nPCR gkgday 111 plusmn 031 127 plusmn 032de 137 plusmn 029d

KtV 145 plusmn 025 143 plusmn 026 140 plusmn 025

Residual renal function

mlmin173 m2

657 plusmn 218 533 plusmn 165de 475 plusmn 130d

Mean pre-HD blood pressure

mm Hg

98 plusmn 19 94 plusmn 17 92 plusmn 20c

BMI kgm2 216 plusmn 34 220 plusmn 34e 236 plusmn 38d

ACEI andor ARB 26 28 26

Karnofsky score 71 plusmn 17 77 plusmn 17

ce

83 plusmn 16

d

Clinical comorbidity

Coronary artery disease 21 15 20

Congestive heart failure 4 2 4

Peripheral vascular disease 7 7 6

Stroke 14 14 6

Neoplasm 12 6 6

Chronic lung disease 1 1 1

Liver cirrhosis andor hepatoma 4 5 1

Malnutrition 6 4 1

No comorbidity 46 57 65b

Mortality rate 37 29 23a

Laboratory data

hs-CRP mgL median 473 469 365

(1stndash3 rd qua rti le r anges) ( 156ndash133) (165ndash973) (150ndash859)

Pre-albumin mgdL 277 plusmn 86 342 plusmn 91d 367 plusmn 91d

Albumin gdL 37 plusmn 05 40 plusmn 04

d

41 plusmn 04

d

Sodium mmolL 1386 plusmn 30 1387 plusmn 23 1380 plusmn 24

Potassium mmolL 37 plusmn 06 45 plusmn 05df 52 plusmn 07d

Uric acid mgdL 64 plusmn 10 78 plusmn 09df 91 plusmn 15d

Potassium times uric aci d 238 plusmn 48 345 plusmn 24df 477 plusmn 88d

Uric acidpotassium ratio 18 plusmn 04 18 plusmn 0 4 1 8 plusmn 04

Phosphate mgdL 38 plusmn 12 49 plusmn 13df 56 plusmn 16d

BUN mgdL 57 plusmn 17 75 plusmn 16df 91 plusmn 20d

Creatinine mgdL 81 plusmn 21 100 plusmn 24df 111 plusmn 26d

Hemoglobin gdL 88 plusmn 16 92 plusmn 15 93 plusmn 15c

Abbreviations HD hemodialysis nPCR normalized protein catabolism rate ACEI

angiotensinogen converting enzyme inhibitor ARB angiotensin receptor blockade

hs-CRP high sensitivity C-reactive protein BUN blood urea nitrogen

Statistics

a p b 005 b p b 0001 vs group 1 (χ2 tests)

c p b 005 d p b 0001 vs group 1 (ANOVA with post hoc Bonferroni tests)

e p b 005 f p b 0001 vs group 3 (ANOVA with post hoc Bonferroni tests)

Gotch formula

647M-Y Jiang et al European Journal of Internal Medicine 26 (2015) 646 ndash651



the groups respectively as shown in Table 1 The relationship betweenS[K] and S[K] was assessed by Pearson correlation analysis in Fig 1

Levels of hs-CRP were compared among the three groups using

Kruskal-Wallis one-way analysis of variance To evaluate the factors

associated with S[K] times S[UA] nPCR albumin corrected sodium and

phosphate concentrations were included and analyzed by multiple

linear regression tests as shown in Table 2 Actuarial survival rates

of the three groups categorized by different S[K] times S[UA] products

were determined by the Kaplan-Meier method and log-rank tests

were used to compare different survival curves between groups

Cox proportional hazard analysis was also used to analyze the risk

factors associated with long-term mortality as shown in Table 3

With the exception of hs-CRP (median interquartile range) all

other data are expressed as mean plusmn standard deviation A p value

of less than 005 was considered to be signi1047297cant and all analyses

were performed with SPSS for Windows version 18 (SPSS Chicago

IL USA)

4 Results

41 Basic demographic characteristics of the three groups of patients

As shown in Table 1 Group 1 had a higher percentage of diabe-

tes mellitus (DM) and higher pre-HD blood pressure Group 1 was

also characterized by a signi1047297cantly lower nPCR body mass index

and Karnofsky score and fewer male patients Group 3 had a signif-

icantly higher percentage of male patients nPCR body mass index

Karnofsky score and hemoglobin level and a lower percentage of

DM and mean pre-HD blood pressure compared with Groups 1

and 2 There were no signi1047297cant differences in age at the initiation

of study HD vintage KtV ultra1047297ltration rate and the use of angio-

tensin converting enzyme inhibitor (ACEI) andor angiotensin

receptor blockade (ARB) among the three groups of patients

In the comparison of biochemical tests Group 3 had signi1047297cantly

higher levels of pre-albumin albumin potassium phosphate bloodurea nitrogen creatinine and uric acid Conversely lower levels of

serum pre-albumin albumin potassium phosphate blood urea

nitrogen creatinine and uric acid were found in Group 1 There were

no signi1047297cant differences in serum levels of hs-CRP S[UA]S[K] ratio

or sodium among the three groups

42 Correlation of serum uric acid and potassium levels

Fig 1A shows that the correlation performed in the whole group

of HD patients (N = 424) between S[K] and S[UA] was signi1047297cant

(r = 033 p b 0001) In the patients with a lower serum potassium

level (medium S[K] = 44 mmolL as a cut-off value) S[K] was still pos-

itively correlated to S[UA] (n = 215 r = 036 p b 0001) However this

positive correlation gradually reduced (n = 209 r = 013 p = 006) inthepatients with a higher serum potassium level(K N 44 mmolL) The

quotients of S[UA] divided by S[K] over the 5 years varied from approx-

imately 16ndash20 and were grossly constant (Fig 1B)

43 Comparison of long-term survival among the three groups divided by

S[K] times S[UA]

In Kaplan-Meier analysis Group 3 had a signi1047297cantly better cumula-

tive survival than Group 1 (p = 0001) and Group2 (p = 004) Group 1

had a poorer outcome compared to Groups 2 and 3 but there was no

statistically signi1047297cant difference between Groups 1 and 2 (p = 018)

(Fig 2A) After adjusting for DM gender HDduration and age at thebe-

ginning of the study as compared to the reference (Group 1 = 1) the

hazard ratios for mortality were signi1047297cantly lower in Groups 2

Fig 1 Correlation of serum uricacid (S[UA])and potassium (S[K]) levels (A) Thecorrela-

tion performedin thewholegroupof HDpatients (N= 424) between S[K] and S[UA]was

signi1047297cant (r= 033 p b 0001) (B) The quotients of S[UA] divided by S[K] concentration

over the 5-year study period varied from about 16 to 20

Table 2

Multiplelinearregression analysis forevaluating thefactors associatedwiththe productof

serum potassium and uric acid concentrations

95 CI

β Lower Upper p valuea

nPCR gkgday 017 314 835 b0001

Serum albumin gdL 012 080 523 0008

Serum sodium mmolL minus022 minus131 minus067 b0001

Serum phosphate mgdL 032 176 289 b0001

RRF mlmin173 m2minus031 minus242 minus131 b0001

Abbreviations nPCR normalized protein catabolism rate RRF residual renal functiona

Adjusted for age at the study diabetes mellitus gender and hemodialysis vintage

Table 3

Multivariate logistic regression analysis of the clinical associations of Groups 1 and 3

95 CI

OR Lower Upper p values

Group 1a

nPCR gkgday 010 005 022 b0001

albumin gdL 020 011 035 b0001

phosphate mgdL 041 033 051 b0001

Group 3b

nPCR gkgday 606 293 1250 b0001

albumin gdL 385 212 700 b0001


Abbreviations CI con1047297dence interval nPCR normalized protein catabolic rate HD

hemodialysisa Dependent variable Group 1 (n = 141) vs others (Groups 2 and 3 n = 283)b Dependent variable Group 3 (n = 142) vs others (Groups 1 and 2 n = 282) Adjusted for diabetes mellitus gender age at initiation of the study and HD vintage

648 M-Y Jiang et al European Journal of Internal Medicine 26 (2015) 646 ndash651



(HR = 065 95 CI= 043ndash099) and 3 (HR = 056 95 CI= 036ndash089)

(Fig 2B)

44 Factors associated with the product of S[K] times S[UA]

The product of S[K] times S[UA] showed a positive correlation to

nPCR serum albumin and phosphate levels but a negative correla-

tion to S[Na] and RRF in multiple linearregressionanalysis (Table 2)

After adjusting for DM gender age at the initiation of the study andHD vintage in multivariate logistic regression analysis Group 1 was

associated withlower nPCR albumin and phosphate concentrations

(Table 3) However Group 3 was associated with high levels of

nPCR albumin and phosphate

45 Long-term serum potassium UA and albumin concentration changes

over the 5-year study period

Fig 3 shows theserialchanges of serum albumin and theproducts of

S[K] times S[UA] throughout the study period The patients with a higher

S[K] times S[UA] at baseline had persistently higher values of S[K] times S[UA]

throughoutthe study period (Fig 3B) They also had consistently higher

serum albumin concentrations (Fig 3A)

46 Cox proportional analysis for the evaluation of risk factors related to

mortality

As seen in Table 4 a lower S[K] times S[UA] product DM and old age

were risk factors for mortality in univariate Cox proportional analysis

Fig 2 Long-term survival among the three groups divided by S[K] times S[UA] product

(A) Group 1 had a poorer outcome compared to Groups 2 and 3 but there was no statis-

tical difference between Groups 1 and 2 (p = 018) (B) After adjusting for diabetes

mellitus sex hemodialysis duration and age at the beginning of the study as compared

to the reference (Group 1 = 1) the hazard ratio for mortality was signi1047297cantly lower in

Groups 2 (HR = 065 95 CI = 043ndash099) and 3 (HR = 056 95 CI = 036ndash089)Fig 3 Serial changes in serum albuminand S[K]times S[UA] products (B)The patients with a

higher S[K] times S[UA] product at baseline had persistently higher S[K] times S[UA] values

(A) They also had consistently higher serum albumin concentrations

Table 4

Multivariate Cox proportional analysis to evaluate the effect of mortality of the S[K] times

S[UA] product

Model 1 Model 2

95 CI 95 CI

HR Lower Upper p HR Lower Upper p

S[K] times S[UA]

product unit

098 096 099 002 099 097 101 037

Age year 105 103 107 b000 1 1 0 4 1 0 2 106 b0001

HD vintage

month

100 100 101 008 100 100 101 006

Diabetes yes or

no

163 111 239 001 151 102 223 004

Male yes or no 141 098 202 007 155 107 224 002

Albumin gdL 045 029 072 b0001

Model 1 adjusted for age hemodialysis vintage diabetes mellitus and gender

Model 2 adjusted for age hemodialysis vintage diabetes mellitus gender and albumin

Abbreviations S[K] serum potassium concentration S[UA] serum uric acid concentra-

tion CI con1047297dence interval HD hemodialysis




After adjusting for DM sex age at the initiation of the study and HD

vintage in model 1 study a 2 increased risk of mortality for each unit

decline in S[K] times S[UA] product was shown by in multivariate Cox pro-

portional analysis (HR = 098 95 CI = 096ndash099) After incorporating

serum albumin in the model 2 analysis S[K] times S[UA] product lost the

power to predict long-term prognosis of chronic HD patients

5 Discussion

This study evaluated the combined effect and correlation of S[K] and

S[UA] on the long-term survival of chronic HD patients The main 1047297nd-

ing was that pre-HD S[K] in the HD patients was linearly correlated to

S[UA] especially in the hypokalemic patients The quotients of S[UA]

S[K] were constant across the 5 years ranging from 16 to 20 The pa-

tients with a lower S[K] times S[UA] product were characterized by hypoal-

buminemia and a lower nPCR level They were also associated with a

higher hs-CRP level and more comorbidities Lower levels of both

markers in the HD patients were shown to be an important predictor

for a high long-term mortality rate In contrast the HD patients with a

higher S[K] times [UA] product tended to have better outcomes

Hypokalemia has been shown to be associated with higher rates of

all-cause and cardiovascular mortality in chronic HD patients [24]

Predialysis hypokalemic patients have also been shown to have lower

levels of serum albumin creatinine phosphate and nPCR [24] Hypoal-

buminemia and lower nPCR are considered to be important risk factors

for mortality in patients with ESRD [12] After adjustments for case mix

and malnutritionndashin1047298ammationndashcachexia syndrome the associations

between hypokalemia andmortalityhave been reported to be mitigated

[2] Therefore pre-dialysis hypokalemia may be a surrogate marker of

protein-energy wasting in patients with ESRD which may predispose

to a higher mortality rate On the other hand Kovesdy et al reported

an association between hyperkalemia and higher all-cause and cardio-

vascular mortality rates in HD patients [2] That our patients used

a lower potassium bath (10 or 20 mmolL vs 35 or 40 mmolL)

throughout the whole course may explain the difference in our results

Hemodialysis patients witha lower S[UA] have alsobeen reported to

have higher all-cause [1013] and cardiovascular mortality rates [10] In

addition a lower S[UA] in HD patients has been proven to be associatedwith DM older agemore comorbidities and hypoalbuminemia [1013]

Such patients have also been reported to have lower levels of

phosphate body mass index and nPCR [10] Therefore a lower S[UA]

may also be regarded as a sign of malnutrition status in HD patients Aldquo J-shapedrdquo association between S[UA] and mortality risk has been re-

ported in several small sample size studies [1415] Moreover UA has

been reported to be an anti-oxidant agent [16] A higher S[UA] in HD

patients has been reported to be a marker for more protein intake and

betternutritionalstatus [10] Thus we speculate that the better progno-

sis among HD patients with higherS[UA] may be attributed to this com-

bined effect of adequate nutrition and anti-in1047298ammation

However in the Modi1047297cation of Diet in Renal Disease trial in non-

diabetic patients with stage 3ndash4 chronic kidney disease (CKD) hyper-

uricemia has been reported to be a risk factor for all-cause and cardio-vascular mortality [17] The Atherosclerosis Risk in Communities study

also showed an association between hyperuricemia and high mortality

in patients with CKD [18] This is in contrast to theresults in the studies

on HD patients We hypothesize that there are different clinical implica-

tions of a higher S[UA] in patients with CKD before HD and after main-

tenance HD A higher S[UA] has been demonstrated to indicate the

severity of metabolic syndrome in pre-dialysis patients with CKD [18]

and it may be equivalent to a lower malnutrition and in1047298ammation sta-

tus in chronic dialysis patients

S[K] was found to be linearly correlated with S[UA] in this study es-

pecially for a lower S[K] (K le 44 mmolL) This supports our hypothesis

that the higher mortality rate associated with pre-dialysis hypokalemia

and lower S[UA] is related to protein-energy wasting From the constant

values of the quotients of S[UA]S[K] across the 5 years of the study

period these two markers seemed to remain in close correlation We

suggest that a combination of S[K] and S[UA] can synergistically predict

the outcome of HD patients

In our previous study [4] hypokalemic HD patients had persistently

lower and hyperkalemic patients persistently higher S[K] The DOPPS

study also showed consistent S[UA] values in HD patients with a co-

ef 1047297cient of variation b20 [7] Asshownin Fig 3 thepatients with an

initially higher S[K] times S[UA] product consistently had the highest

level of S[K] times S[UA] in the following observation period Theserum albumin levels also consistently paralleled the S[K] times S[UA]

product throughout the study period This implies that HD patients

witha lower S[K] times S[UA] product share some intrinsic comorbidities

leading to a chronic and persistent malnutritionndashin1047298ammationndash

atheroscloerosis (MIA) syndrome which results in a poor outcome

To the best of our knowledge no previous studies have reported

on the impact of the combined effect of S[K] and S[UA] on the long-

term prognosis of chronic HD patients The strength of this study is

the 5-year longitudinal follow-up period However there are also

some limitations to this study First the analysis was based on single

potassium and UA values However the S[K] S[UA] and albumin con-

centrations of the remaining patients were continually monitored

throughout the 5-year observation period to evaluate the consistency

of trends in these parameters Second the protein intake was indirectly

calculated by PCR rather than by a direct dietary measurement More-

over the dialysate composition was changed shortly after baseline

whichalsomay have in1047298uencedthe results However this is notexpect-

ed to distort the deleterious impact of lower S[K] superimposed with

lower S[UA] on the long-term prognosis of HD patients

In conclusion our results demonstrated that HD patients with lower

levels of both S[K] and S[UA] were associated with poor cumulative sur-

vivalThey were alsoassociated with hypoalbuminemiaand lower nPCR

and phosphate levels Independent from the traditional risk factors in-

cluding DM age sex and HD vintage lower levels of both markers

could predict poor long-term outcomes of the HD patients On the

other hand the patients with higher levels of both S[K] and S[UA]

were found to have a better long-term prognosis This suggests that a

combination of S[K] and S[UA] can synergistically predict the outcomes

of chronic HD patients Although persistent malnutrition in1047298ammationstatusand more comorbidities in thepatients with a lower S[K] times S[UA]

product were suspected to be the main cause of a higher mortality rate

further studies are needed to clarify the actual mechanism

Ethical issues

The current study wasapproved by theEthics Committee of Chi Mei

Medical Center (IRB no 10402ndash007) and was conducted in accordance

with the guiding principles for human experimentation of the Helsinki

Declaration

Funding

None

Con1047298icts of interest

None of the authors has a 1047297nancial relationship with a commercial

entity that has an interest in the subject of this manuscript

References

[1] Krishnasamy R Badve SV Hawley CM McDonald SP Boudville N Brown FG et alDaily variation in death in patients treated by long-term dialysis comparison of in-center hemodialysis to peritoneal and home hemodialysis Am J Kidney Dis20136196ndash103

[2] Kovesdy CP Regidor DL Mehrotra R Jing J McAllister CJ Greenland S et al Serumand dialysate potassium concentrations and survival in hemodialysis patients Clin

J Am Soc Nephrol 20072999ndash

1007




[3] Abe S Yoshizawa M NakanishiN YazawaT Yokota K Honda M et al Electrocardio-graphic abnormalities in patients receiving hemodialysis Am Heart J 19961311137ndash44

[4] Hwang JC Wang CT Chen CA Chen HC Hypokalemia is associated with increasedmortality rate in chronic hemodialysis patients Blood Purif 201132254ndash61

[5] KrishnanE Reducedglomerularfunction and prevalence of gout NHANES 2009ndash10PLoS One 20127e50046

[6] Cohen SD Kimmel PL Neff R Agodoa L Abbott KC Association of incident gout andmortality in dialysis patients J Am Soc Nephrol 2008192204ndash10

[7] Latif W Karaboyas A Tong L Winchester JF Arrington CJ Pisoni RL et al Uric acidlevels and all-cause and cardiovascular mortality in the hemodialysis population

Clin J Am Soc Nephrol 201162470ndash

7[8] Choi HY Ha SK Potassium balances in maintenance hemodialysis Electrolyte BloodPress 2013119ndash16

[9] Murea M Advanced kidney failure and hyperuricemia Adv Chronic Kidney Dis201219419ndash24

[10] Depner TA Daugirdas JT Equations for normalized protein catabolic rate based ontwo-point modeling of hemodialysis urea kinetics J Am Soc Nephrol 19967780ndash5

[11] Hwang JC Jiang MY Wang CT Lower serum potassium combined with lowersodium concentrations predict long-term mortality risk in hemodialysis patientsBMC Nephrol 201314269

[12] Cooper BA Penne EL Bartlett LH Pollock CA Protein malnutrition and hypoalbu-minemia as predictors of vascular events and mortality in ESRD Am J Kidney Dis20044361ndash6

[13] LeeSM LeeAL Winters TJTamE JaleelM Stenvinkel P etal Low serumuricacidlevelis a riskfactor fordeath in incidenthemodialysis patients Am J Nephrol 20092979ndash85

[14] Suliman ME Johnson RJ Garciacutea-Loacutepez E Qureshi AR Molinaei H Carrero JJ et al J-shaped mortality relationshipfor uricacid in CKDAm J Kidney Dis 200648761ndash71

[15] Hsu SP PaiMF Peng YS Chiang CKHo TI Hung KYSerum uric acid levelsshowa lsquo J-shapedrsquo association with all-cause mortality in haemodialysis patients Nephrol DialTransplant 200419457ndash62

[16] Kandaacuter R Zaacutekovaacute P Muzaacutekovaacute V Monitoring of antioxidant properties of uric acid

in humans for a consideration measuring of levels of allantoin in plasma by liquidchromatography Clin Chim Acta 2006365249ndash56[17] Madero MSarnakMJ WangX Greene TBeckGJKusekJWet al Uricacidandlong-

term outcomes in CKD Am J Kidney Dis 200953796ndash803[18] Navaneethan SD Beddhu S Associations of serum uric acid with cardiovascular

events and mortality in moderate chronic kidney disease Nephrol Dial Transplant2009241260ndash6




correlation between S[K] and S[UA] in HD patients We also com-

bined these two biochemical markers to investigate whether lower

levels of both S[K] and S[UA] were associated with a poor long-

term prognosis in these patients since both parameters are related

to protein nutrition

2 Patients and methods

21 Patient enrollment

This study was a cohort observational study of prospectively

collected data based on a database that was constructed for outcome

assurance from January 2004 to July 2008 at a single medical center

After excluding the patients who had received HD for fewer than 6

months (n = 18) those suspected of having acute renal failure

(n = 6) and those with the long-term use of diuretics and

potassium-reducing agents (n = 2) a total of 424 patients with

ESRD undergoing maintenance HD at our unit three times a week

for 4 hours per session in January 2004 were enrolled into this

study Based on the product of pre-dialysis(S[K] times S[UA]) as assessed

on the last mid-week dialysis session in January 2004 the patients

were categorized into tertiles Group 1 S[K] times S[UA] le 299 n = 141

Group 2 S[K] times S[UA] N 299 le 383 n = 141 and Group 3S[K] times S[UA] N 383 n = 142 The hollow-1047297ber dialyzers used in all

patients included FB210G (Nissho Corporation Osaka Japan) B3-

20 (Toray Industries Inc Tokyo Japan) Hemo1047298ow F10 HPS (Fresenius

Medical Care AG Bad Homburn Germany) and PSN-210 (Baxter

Healthcare Corporation McGaw Park IL USA) The formula of the dial-

ysate bath used at the initiation of thestudy was sodium 1400 mmolL

calcium 15 mmolL potassium 10 mmolL magnesium 05 mmolL

chloride 1045 mmolL acetate 40 mmolL dextrose 200 mgdL and

bicarbonate 35 mmolL (Renasolreg SB-1080 Renal System Minneapo-

lis MN USA) Due to concerns over cost we used another dialysate

(Hemodialysis Concentrate A-35 and BP-11 Chi Sheng Chemical

Corporation Hsinchu Taiwan) from July 2004 to the end of the

study The formula of this dialysate was sodium 1390 mmolL calci-

um 15 mmolL potassium 20 mmolL magnesium 05 mmolL

chloride 1065 mmolL acetate 40 mmolL dextrose 200 mgdL

and bicarbonate 39 mmolL No changes in potassium concentration

in the dialysate bath or dialysate sodium remodeling process were

applied throughout the study period For management of anemia

8000 unitsweek of Epoetinum alfa (EPREXreg Cilag AG Switzerland)

was subcutaneously injected after HD for patients with hemoglobin (Hg)

less than 85 gdL 6000 unitsweek for those with Hg between 85 gdL

and 10 gdL 4000 unitsweek for Hg between 10 gdL to 11 gdL and

2000 unitsweek for Hg between 11 and 12 gdL No patients received

allopurinol and diuretics in this study

22 Data collection

Blood samples were taken in the last mid-week of January 2004(the beginning of the study) and every six months thereafter until

September 2008 Pre-HD biochemical tests included serum albu-

min by means of bromocresol purple and potassium blood urea

nitrogen creatinine uric acid and phosphate concentrations were

measured using a Hitachi 7601ndash110 Automatic Analyzer (Tokyo

Japan) Residual renal function (R RF) was calculated by MDR D for-

mula Hematocrit was measured using a Beckman Coulter LH755-A

system (Fullerton CA USA) Levels of high sensitive C-reactive pro-

tein (hs-CRP) (CardioPhasereg Siemens Healthcare Diagnostics Prod-

ucts GmbH Germany) and pre-albumin (immunochemically

Dade Behring Marburg GmbH Germany) were also measured The

data of the patients who were transferred to other centers or who

died during the study were omitted on a monthly basis We also

evaluated KtV urea (Gotch formula) and nPCR for all patients at

the beginning of study to compare differences in dialysis dosage

and protein intake between the groups [10]

23 Comorbidity

Comorbidities were assessed according to the past history re-

corded in the medical charts at the beginning of study The diag-

nostic criteria for the various comorbid conditions were described

in our previous study [11] All patients recordsinformation wereanonymized and de-identi1047297ed prior to analysis The current study

was approved by the Ethics Committee of Chi Mei Medical Center

and was conducted in accordance with the guiding principles for

human experimentation of the Helsinki Declaration

3 Statistical analysis

Appropriateχ2 and ANOVA with post hocBonferroni tests were used

for comparisons between categorical and continuous variables between

Table 1

Basic demographic characteristics of the three groups of patients

Group 1 Group 2 Group 3

n = 141 n = 141 n = 142

Demographic factors

Diabetes mellitus 50 39 27b

Male 35 51a 54a

Age at study years 59 plusmn 14 58 plusmn 13 56 plusmn 12

HD vintag e months 504 plusmn 41 4 499 plusmn 439 432 plusmn 1183

Ultra1047297ltration Lsession 25 plusmn 08 26 plusmn 08 29 plusmn 08

nPCR gkgday 111 plusmn 031 127 plusmn 032de 137 plusmn 029d

KtV 145 plusmn 025 143 plusmn 026 140 plusmn 025

Residual renal function

mlmin173 m2

657 plusmn 218 533 plusmn 165de 475 plusmn 130d

Mean pre-HD blood pressure

mm Hg

98 plusmn 19 94 plusmn 17 92 plusmn 20c

BMI kgm2 216 plusmn 34 220 plusmn 34e 236 plusmn 38d

ACEI andor ARB 26 28 26

Karnofsky score 71 plusmn 17 77 plusmn 17

ce

83 plusmn 16

d

Clinical comorbidity

Coronary artery disease 21 15 20

Congestive heart failure 4 2 4

Peripheral vascular disease 7 7 6

Stroke 14 14 6

Neoplasm 12 6 6

Chronic lung disease 1 1 1

Liver cirrhosis andor hepatoma 4 5 1

Malnutrition 6 4 1

No comorbidity 46 57 65b

Mortality rate 37 29 23a

Laboratory data

hs-CRP mgL median 473 469 365

(1stndash3 rd qua rti le r anges) ( 156ndash133) (165ndash973) (150ndash859)

Pre-albumin mgdL 277 plusmn 86 342 plusmn 91d 367 plusmn 91d

Albumin gdL 37 plusmn 05 40 plusmn 04

d

41 plusmn 04

d

Sodium mmolL 1386 plusmn 30 1387 plusmn 23 1380 plusmn 24

Potassium mmolL 37 plusmn 06 45 plusmn 05df 52 plusmn 07d

Uric acid mgdL 64 plusmn 10 78 plusmn 09df 91 plusmn 15d

Potassium times uric aci d 238 plusmn 48 345 plusmn 24df 477 plusmn 88d

Uric acidpotassium ratio 18 plusmn 04 18 plusmn 0 4 1 8 plusmn 04

Phosphate mgdL 38 plusmn 12 49 plusmn 13df 56 plusmn 16d

BUN mgdL 57 plusmn 17 75 plusmn 16df 91 plusmn 20d

Creatinine mgdL 81 plusmn 21 100 plusmn 24df 111 plusmn 26d

Hemoglobin gdL 88 plusmn 16 92 plusmn 15 93 plusmn 15c

Abbreviations HD hemodialysis nPCR normalized protein catabolism rate ACEI

angiotensinogen converting enzyme inhibitor ARB angiotensin receptor blockade

hs-CRP high sensitivity C-reactive protein BUN blood urea nitrogen

Statistics

a p b 005 b p b 0001 vs group 1 (χ2 tests)

c p b 005 d p b 0001 vs group 1 (ANOVA with post hoc Bonferroni tests)

e p b 005 f p b 0001 vs group 3 (ANOVA with post hoc Bonferroni tests)

Gotch formula



















IL USA)

4 Results





























S[K] times S[UA]












Table 2



95 CI


nPCR gkgday 017 314 835 b0001







Table 3


95 CI


Group 1a

nPCR gkgday 010 005 022 b0001

albumin gdL 020 011 035 b0001


Group 3b

nPCR gkgday 606 293 1250 b0001

albumin gdL 385 212 700 b0001








(Fig 2B)

















mortality











Table 4


S[UA] product

Model 1 Model 2

95 CI 95 CI


S[K] times S[UA]

product unit

098 096 099 002 099 097 101 037

Age year 105 103 107 b000 1 1 0 4 1 0 2 106 b0001

HD vintage

month

100 100 101 008 100 100 101 006

Diabetes yes or

no

163 111 239 001 151 102 223 004

Male yes or no 141 098 202 007 155 107 224 002

Albumin gdL 045 029 072 b0001














5 Discussion






























































































Ethical issues




Declaration

Funding

None




References




1007








































IL USA)

4 Results





























S[K] times S[UA]












Table 2



95 CI


nPCR gkgday 017 314 835 b0001







Table 3


95 CI


Group 1a

nPCR gkgday 010 005 022 b0001

albumin gdL 020 011 035 b0001


Group 3b

nPCR gkgday 606 293 1250 b0001

albumin gdL 385 212 700 b0001








(Fig 2B)

















mortality











Table 4


S[UA] product

Model 1 Model 2

95 CI 95 CI


S[K] times S[UA]

product unit

098 096 099 002 099 097 101 037

Age year 105 103 107 b000 1 1 0 4 1 0 2 106 b0001

HD vintage

month

100 100 101 008 100 100 101 006

Diabetes yes or

no

163 111 239 001 151 102 223 004

Male yes or no 141 098 202 007 155 107 224 002

Albumin gdL 045 029 072 b0001














5 Discussion






























































































Ethical issues




Declaration

Funding

None




References




1007


























(Fig 2B)

















mortality











Table 4


S[UA] product

Model 1 Model 2

95 CI 95 CI


S[K] times S[UA]

product unit

098 096 099 002 099 097 101 037

Age year 105 103 107 b000 1 1 0 4 1 0 2 106 b0001

HD vintage

month

100 100 101 008 100 100 101 006

Diabetes yes or

no

163 111 239 001 151 102 223 004

Male yes or no 141 098 202 007 155 107 224 002

Albumin gdL 045 029 072 b0001














5 Discussion






























































































Ethical issues




Declaration

Funding

None




References




1007































5 Discussion






























































































Ethical issues




Declaration

Funding

None




References




1007























jurnal gh tambunta

Documents