J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website http://www.jocmr.org

Original Article

Volume 12, Number 3, March 2020, pages 172-179

Serum Uric Acid, Serum Uric Acid to Serum Creatinine Ratio and Serum Bilirubin in Patients With Parkinson’s Disease: A Case-Control Study

Figure 1. Boxplot graph showing distribution of serum uric acid level (a), serum uric acid/creatinine ratio (b), serum total bilirubin (c) and serum indirect bilirubin (d) in the controls and in patients with Parkinson’s disease (according to Hoehn-Yahr stage). The analysis was performed by Fisher’s least significant difference (LSD) test and was controlled by age and co-morbidities. Data are expressed as median, 25-75 percentile and minimum-maximum.

**Table 1.** Demographic and Laboratory Findings Among Parkinson’s Disease Patients and Controls
	Parkinson’s disease (N = 61)	Controls (N = 135)	P value
Data are expressed as mean ± SD unless indicated otherwise. BMI: body mass index; CAD: coronary artery disease; H&Y: Hoehn-Yahr; UPDRS: unified Parkinson’s disease rating scale; SUA: serum uric acid; SCr: serum creatinine; SUA/SCr: serum uric acid/serum creatinine; AST: aspartate aminotransferase; ALT: alanine aminotransferase.
Sex, male, n (%)	34 (55.73)	68 (50.37)	0.486
Age, years	68.90 ± 6.95	66.78 ± 6.51	0.040
Co-morbidities
Hypertension, n (%)	25 (40.98)	2 (1.48)	< 0.001
Diabetes, n (%)	4 (6.56)	0	0.009
CAD, n (%)	3 (4.92)	1 (0.74)	0.090
Dyslipidemia, n (%)	14 (22.95)	2 (1.48)	< 0.001
BMI (kg/m²)	21.52 ± 3.94	21.06 ± 3.22	0.388
Disease duration (years)	5.62 ± 4.19	-	-
H&Y stage, n (%)		-	-
H&Y I	13 (21.31)
H&Y II	23 (37.70)
H&Y III	11 (18.03)
H&Y IV	11 (18.03)
H&Y V	3 (4.92)
UPDRS score
All	72.82 ± 47.31	2.04 ± 2.57	< 0.001
Non-motor (part I + II)	27.85 ± 19.36	1.35 ± 2.11	< 0.001
Motor (part III)	39.52 ± 26.68	0.69 ± 1.10	< 0.001
Motor (part IV)	5.44 ± 6.58	0 ± 0	< 0.001
Hemoglobin, g/L	124.23 ± 11.74	123.74 ± 15.01	0.806
SCr, µmol/L	74.63 ± 17.73	71.72 ± 13.76	0.257
SUA, µmol/L	304.22 ± 82.55	324.28 ± 77.66	0.102
SUA/SCr ratio	4.12 ± 0.90	4.59 ± 1.04	0.003
Albumin, g/L	41.75 ± 3.16	45.20 ± 32.58	0.076
AST, IU/L	25.13 ± 15.46	23.36 ± 7.70	0.853
ALT, IU/L	16.80 ± 15.62	18.00 ± 11.52	0.039
Total bilirubin, µmol/L	7.92 ± 3.67	6.59 ± 2.78	0.003
Direct bilirubin, µmol/L	3.39 ± 1.45	3.33 ± 1.16	0.592
Indirect bilirubin, µmol/L	4.52 ± 2.48	3.26 ± 1.82	< 0.001

Table 1. Demographic and Laboratory Findings Among Parkinson’s Disease Patients and Controls

Parkinson’s disease (N = 61)

Controls (N = 135)

P value

Data are expressed as mean ± SD unless indicated otherwise. BMI: body mass index; CAD: coronary artery disease; H&Y: Hoehn-Yahr; UPDRS: unified Parkinson’s disease rating scale; SUA: serum uric acid; SCr: serum creatinine; SUA/SCr: serum uric acid/serum creatinine; AST: aspartate aminotransferase; ALT: alanine aminotransferase.

Sex, male, n (%)

34 (55.73)

68 (50.37)

0.486

Age, years

68.90 ± 6.95

66.78 ± 6.51

0.040

Co-morbidities

Hypertension, n (%)

25 (40.98)

2 (1.48)

< 0.001

Diabetes, n (%)

4 (6.56)

0.009

CAD, n (%)

3 (4.92)

1 (0.74)

0.090

Dyslipidemia, n (%)

14 (22.95)

2 (1.48)

< 0.001

BMI (kg/m²)

21.52 ± 3.94

21.06 ± 3.22

0.388

Disease duration (years)

5.62 ± 4.19

H&Y stage, n (%)

H&Y I

13 (21.31)

H&Y II

23 (37.70)

H&Y III

11 (18.03)

H&Y IV

11 (18.03)

H&Y V

3 (4.92)

UPDRS score

All

72.82 ± 47.31

2.04 ± 2.57

< 0.001

Non-motor (part I + II)

27.85 ± 19.36

1.35 ± 2.11

< 0.001

Motor (part III)

39.52 ± 26.68

0.69 ± 1.10

< 0.001

Motor (part IV)

5.44 ± 6.58

0 ± 0

< 0.001

Hemoglobin, g/L

124.23 ± 11.74

123.74 ± 15.01

0.806

SCr, µmol/L

74.63 ± 17.73

71.72 ± 13.76

0.257

SUA, µmol/L

304.22 ± 82.55

324.28 ± 77.66

0.102

SUA/SCr ratio

4.12 ± 0.90

4.59 ± 1.04

0.003

Albumin, g/L

41.75 ± 3.16

45.20 ± 32.58

0.076

AST, IU/L

25.13 ± 15.46

23.36 ± 7.70

0.853

ALT, IU/L

16.80 ± 15.62

18.00 ± 11.52

0.039

Total bilirubin, µmol/L

7.92 ± 3.67

6.59 ± 2.78

0.003

Direct bilirubin, µmol/L

3.39 ± 1.45

3.33 ± 1.16

0.592

Indirect bilirubin, µmol/L

4.52 ± 2.48

3.26 ± 1.82

< 0.001

**Table 2.** Serum Uric Acid Level, Serum Uric Acid/Creatinine Ratio and Serum Bilirubin Levels According to Clinical Characteristics of Parkinson’s Disease
	Total cases (N)	SUA (µmol/L)	SUA/SCr ratio	Total bilirubin (µmol/L)	Indirect bilirubin (µmol/L)
Data are presented as mean ± SD and geometric mean (95% CI). The analysis was controlled by age and co-morbidities. PD: Parkinson’s disease; H&Y: Hoehn-Yahr; PIGD: postural instability/gait difficulty; SUA: serum uric acid; SUA/SCr: serum uric acid/serum creatinine. ^aP = 0.009 (total bilirubin; mild vs. severe disease); ^bP = 0.005 (total bilirubin, moderate vs. severe disease); ^cP = 0.012 (indirect bilirubin, mild vs. severe disease); ^dP = 0.008 (indirect bilirubin, moderate vs. severe disease). ^a-dAnalyzed by Fisher’s least significant difference (LSD) test.
PD disease severity (based on H&Y stage)
Mild (1 - 2)	36	315.74 ± 81.76	4.20 ± 0.88	7.65 (6.71 - 8.72)^a	4.28 (3.68 - 4.97)^c
Moderate (2.5 - 3)	11	269.82 ± 65.06	3.71 ± 0.80	8.72 (6.89 - 11.04)^b	4.93 (3.79 - 6.42)^d
Severe (4 - 5)	14	301.65 ± 93.94	4.24 ± 0.99	5.56 (4.46 - 6.94)	2.96 (2.20 - 4.00)
P value		0.222	0.271	0.010	0.014
PD disease duration (years)
< 2 years	9	321.85 ± 56.54	4.10 ± 0.45	7.70 (6.04 - 9.80)	4.08 (2.89 - 5.77)
≥ 2 years	52	301.17 ± 86.32	4.12 ± 0.96	7.21 (6.41 - 8.11)	4.03 (3.51 - 4.62)
P value		0.556	0.936	0.669	0.906
Motor symptom subtypes
PIGD	44	297.94 ± 89.27	3.99 ± 0.89	7.09 (6.33 - 7.93)	3.94 (3.44 - 4.50)
Tremor	10	321.19 ± 46.33	4.55 ± 0.82	8.96 (6.28 - 12.77)	4.81 (3.09 - 7.50)
P value		0.343	0.079	0.082	0.235

Table 2. Serum Uric Acid Level, Serum Uric Acid/Creatinine Ratio and Serum Bilirubin Levels According to Clinical Characteristics of Parkinson’s Disease

Total cases (N)

SUA (µmol/L)

SUA/SCr ratio

Total bilirubin (µmol/L)

Indirect bilirubin (µmol/L)

Data are presented as mean ± SD and geometric mean (95% CI). The analysis was controlled by age and co-morbidities. PD: Parkinson’s disease; H&Y: Hoehn-Yahr; PIGD: postural instability/gait difficulty; SUA: serum uric acid; SUA/SCr: serum uric acid/serum creatinine. ^aP = 0.009 (total bilirubin; mild vs. severe disease); ^bP = 0.005 (total bilirubin, moderate vs. severe disease); ^cP = 0.012 (indirect bilirubin, mild vs. severe disease); ^dP = 0.008 (indirect bilirubin, moderate vs. severe disease). ^a-dAnalyzed by Fisher’s least significant difference (LSD) test.

PD disease severity (based on H&Y stage)

Mild (1 - 2)

315.74 ± 81.76

4.20 ± 0.88

7.65 (6.71 - 8.72)^a

4.28 (3.68 - 4.97)^c

Moderate (2.5 - 3)

269.82 ± 65.06

3.71 ± 0.80

8.72 (6.89 - 11.04)^b

4.93 (3.79 - 6.42)^d

Severe (4 - 5)

301.65 ± 93.94

4.24 ± 0.99

5.56 (4.46 - 6.94)

2.96 (2.20 - 4.00)

P value

0.222

0.271

0.010

0.014

PD disease duration (years)

< 2 years

321.85 ± 56.54

4.10 ± 0.45

7.70 (6.04 - 9.80)

4.08 (2.89 - 5.77)

≥ 2 years

301.17 ± 86.32

4.12 ± 0.96

7.21 (6.41 - 8.11)

4.03 (3.51 - 4.62)

P value

0.556

0.936

0.669

0.906

Motor symptom subtypes

PIGD

297.94 ± 89.27

3.99 ± 0.89

7.09 (6.33 - 7.93)

3.94 (3.44 - 4.50)

Tremor

321.19 ± 46.33

4.55 ± 0.82

8.96 (6.28 - 12.77)

4.81 (3.09 - 7.50)

P value

0.343

0.079

0.082

0.235

**Table 3.** Comparison of Serum Total Bilirubin and Indirect Bilirubin Among PD Patients According to PD Disease Severity and Controls
	Total cases	Total bilirubin (µmol/L)	P value	Indirect bilirubin (µmol/L)	P value
Data are expressed as geometric mean (95% CI). All comparison were compared with control. The analysis was controlled by age and co-morbidities.
Control	135	6.07 (5.67 - 6.51)		2.78 (2.50 - 3.09)
PD disease severity (based on H&Y stage)
Mild (1 - 2)	36	7.65 (6.71 - 8.72)	0.025	4.28 (3.68 - 4.97)	0.001
Moderate (2.5 - 3)	11	8.72 (6.89 - 11.04)	0.018	4.93 (3.79 - 6.42)	0.004
Severe (4 - 5)	14	5.56 (4.46 - 6.94)	0.328	2.96 (2.20 - 4.00)	0.717

Table 3. Comparison of Serum Total Bilirubin and Indirect Bilirubin Among PD Patients According to PD Disease Severity and Controls

Total cases

Total bilirubin (µmol/L)

P value

Indirect bilirubin (µmol/L)

P value

Data are expressed as geometric mean (95% CI). All comparison were compared with control. The analysis was controlled by age and co-morbidities.

Control

135

6.07 (5.67 - 6.51)

2.78 (2.50 - 3.09)

PD disease severity (based on H&Y stage)

Mild (1 - 2)

7.65 (6.71 - 8.72)

0.025

4.28 (3.68 - 4.97)

0.001

Moderate (2.5 - 3)

8.72 (6.89 - 11.04)

0.018

4.93 (3.79 - 6.42)

0.004

Severe (4 - 5)

5.56 (4.46 - 6.94)

0.328

2.96 (2.20 - 4.00)

0.717

**Table 4.** Correlation Between Serum Uric Acid, Serum Uric Acid/Serum Creatinine Ratio and Serum Total Bilirubin, Indirect Bilirubin
	Parkinson’s disease (n = 61)	Controls (n = 135)	Parkinson’s disease, r (P value) for SUA	Controls, r (P value) for SUA	Parkinson’s disease, r (P value) for SUA/SCr ratio	Controls, r (P value) for SUA/SCr ratio
Data are expressed as mean ± SD. SUA: serum uric acid; SUA/SCr: serum uric acid/serum creatinine.
Total bilirubin, µmol/L	7.92 ± 3.67	6.59 ± 2.78	0.112 (0.391)	0.118 (0.171)	0.164 (0.208)	0.025 (0.773)
Indirect bilirubin, µmol/L	4.52 ± 2.48	3.26 ± 1.82	0.096 (0.460)	0.125 (0.149)	0.204 (0.114)	0.060 (0.493)
SUA, µmol/L	304.22 ± 82.55	324.28 ± 77.66
SUA/SCr ratio	4.12 ± 0.90	4.59 ± 1.04

Table 4. Correlation Between Serum Uric Acid, Serum Uric Acid/Serum Creatinine Ratio and Serum Total Bilirubin, Indirect Bilirubin

Parkinson’s disease (n = 61)

Controls (n = 135)

Parkinson’s disease, r (P value) for SUA

Controls, r (P value) for SUA

Parkinson’s disease, r (P value) for SUA/SCr ratio

Controls, r (P value) for SUA/SCr ratio

Data are expressed as mean ± SD. SUA: serum uric acid; SUA/SCr: serum uric acid/serum creatinine.

Total bilirubin, µmol/L

7.92 ± 3.67

6.59 ± 2.78

0.112 (0.391)

0.118 (0.171)

0.164 (0.208)

0.025 (0.773)

Indirect bilirubin, µmol/L

4.52 ± 2.48

3.26 ± 1.82

0.096 (0.460)

0.125 (0.149)

0.204 (0.114)

0.060 (0.493)

SUA, µmol/L

304.22 ± 82.55

324.28 ± 77.66

SUA/SCr ratio

4.12 ± 0.90

4.59 ± 1.04