Association of Circulating Endothelial Nitric Oxide Synthase Levels with Phosphataemia in Patients on Haemodialysis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patients on HD
2.2. Controls
2.3. Study Design
2.4. Ethics Approval of Research
2.5. Clinical and Laboratory Methods
2.6. Statistical Analysis
3. Results
3.1. Comparison between the Entire HD Group and the Control Group
3.2. Comparison of Biochemical Parameters According to Plasma Phosphorus Tertiles in Patients on HD
3.3. Comparison of Plasma Levels of eNOS, Phosphate, and Other Parameters between Patients on HD with and without D
3.4. Comparison of Plasma Levels of eNOS, Phosphate, and Other Parameters in Controls with and without D
3.5. Comparison of Plasma Levels of eNOS, Phosphate, and Other Parameters between Patients on HD with and without Type 2 DM
3.6. Correlation Analysis of eNOS Levels and Other Parameters in Patients on HD and Controls
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
AGEs | Advanced glycation end products |
BH4 | Tetrahydrobiopterin |
BMI | Body mass index |
BPdias | Diastolic blood pressure |
BPsys | Systolic blood pressure |
Ca | Total calcium |
CI | Confidence interval |
CV | Coefficient of variation |
D | Dyslipidaemic |
DBW | Dry body weight |
DM | Type 2 diabetes mellitus |
EAS | European Atherosclerosis Society |
ECs | Endothelial cells |
EDTA | Ethylenediaminetetraacetic acid |
ELISA | Enzyme-linked immunosorbent assay |
eNOS | Endothelial nitric oxide synthase |
ESA | Erythropoietin stimulating agent |
ESC | European Society of Cardiology |
ESRD | End-stage renal disease |
F | Female |
FPG | Fasting plasma glucose |
HbA1c | Glycated haemoglobin |
HD | Haemodialysis |
HDL-chol | High-density lipoprotein cholesterol |
HgB | Haemoglobin |
HOMA-IR | Homeostasis model assessment of insulin resistance |
HP | Hyperphosphataemia |
hsCRP | High-sensitivity c-reactive protein |
Ht | Haematocrit |
K/DOQI | Kidney Disease Outcomes Quality Initiative |
LDL-chol | Low-density lipoprotein cholesterol |
M | Male |
MAP | Mean arterial pressure |
NO | Nitric oxide |
Non-HDL-chol | Non-high-density lipoprotein cholesterol |
P | Inorganic phosphorus |
PLT | Platelets |
PP | Pulse pressure |
PTH | Parathyroid hormone |
RBCs | Red blood cells |
Tchol | Total cholesterol |
TG | Triglycerides |
WBCs | White blood cells |
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Parameter | Controls n = 26 Median (Q1–Q3) | HD Patients n = 50 Median (Q1–Q3) | p Value |
---|---|---|---|
Age (years) | 69 (64–76) | 66 (60–74) | 0.061 |
Gender, M/F | 11/15 | 27/23 | - |
Dyslipidaemia, n (% of all) | 15 (57) | 26 (54) | 0.693 |
Cigarette smoking, n (% of all) | 1 (4) | 4 (8) | 0.837 |
Body mass index, kg/m2 | 27.2 (24.1–30.1) | 26.9 (23.6–29.2) | 0.660 |
ESA, IU/kg body weight/per week | - | 30.2 (12–104) | - |
Calcium-containing phosphate binders, n (%) | - | 38 (76) | - |
Non-calcium-containing phosphate binders, n (%) | 0 | 0 | - |
Alfacalcidol, n (%) | 0 | 24 (48) | - |
Cinacalcet, n (%) | 0 | 0 | - |
BPsys., mm Hg | 130 (120–140) | 120 (100–164) | 0.078 |
BPdias., mm Hg | 80 (75–90) | 70 (70–80) | 0.002 |
PP, mm Hg | 50 (45–55) | 50 (40–60) | 0.715 |
MAP, mm Hg | 66.7 (60–73.3) | 66.7 (77.7–67.1) | 0.714 |
Basal disease, n (% of subjects) | |||
Diabetic nephropathy | 0 | 25 (50) | - |
Chronic glomerulonephritis | 0 | 12 (24) | - |
Polycystic kidney disease | 0 | 5 (10) | - |
Chronic tubulointerstitial nephritis | 0 | 3 (6) | - |
Other/unknown | 0 | 5 (10) | - |
Parameter | Controls n = 26 Median (Q1–Q3) | HD Patients n = 50 Median (Q1–Q3) | p Value |
---|---|---|---|
eNOS, ng/mL | 1.46 (1.2–1.69) | 0.725 (0.380–1.870) | 0.004 |
P, mg/dL | 3.85 (2.96–4.43) | 5.4 (3.56–6.79) | 0.0027 |
Ca, mg/dL | 9.18 (8.92–9.74) | 8.43 (7.98–8.99) | 0.00001 |
Ca × P | 35.1 (26.7–41.4) | 45.2 (33.8–56.7) | 0.026 |
PTH, pg/mL | 27.4 (22.1–47.4) | 483 (324–740) | <0.0001 |
HgB, g/dL | 13.6 (12.8–14.3 | 11.6 (10.3–12.0) | 0.070 |
RBC | 4.6 (4.2–4.8) | 3.81 (3.42–3.96) | <0.000001 |
Tchol, mg/dL | 195.5 (178–234) | 170 (137–196) | 0.001 |
LDL-chol, mg/dL | 102.5 (89–139) | 91.5 (65–117) | 0.005 |
HDL-chol, mg/dL | 64.5 (52.0–79.0) | 38.0 (33.0–49.0) | 0.005 |
TG, mg/dL | 90 (72–112) | 161 (108–206) | <0.0001 |
hsCRP, mg/L | 4.8 (2.1–5.1) | 8.1 (4.0–18.4) | 0.050 |
HOMA | 2.31 (1.6–2.92) | 6.34 (2.62–9.52) | 0.0002 |
HbA1c | 5.4 (5.2–5.6) | 5.75 (5.0–7.0) | 0.130 |
Albumin, g/dL | 4.4 (4.2–4.6) | 3.7 (2.9–4.1) | <0.000001 |
HD Patients | n = 50 | |||
---|---|---|---|---|
T1 (n = 8) | T2 (n = 22) | T3 (n = 20) | p for Trend | |
Phosphorus, mg/dL | ≤3.4 Median (Q1–Q3) | 3.5–5.5 Median (Q1–Q3) | ≥5.6 Median (Q1–Q3) | |
eNOS, ng/mL | 3.75 (2.01–4.0) | 0.755 (0.380–1.85) | 0.570 (0.270–0.830) | 0.0008 |
HgB, g/dL | 11.4 (9.8–11.9) | 11.6 (10.2–12.2) | 11.8 (11.1–12.5) | 0.091 |
RBC, 106/µL | 3.82 (3.62–4.05) | 3.73 (3.33–3.87) | 3.86 (3.58–3.96) | 0.136 |
P, mg/dL | 2.6 (2.37–2.74) | 4.74 (3.78–5.4) | 7.0 (6.44–7.94) | <0.000001 |
Ca, mg/dL | 8.43 (8.31–8.83) | 8.82 (8.06–9.03) | 8.31 (7.89–8.98) | 0.218 |
Ca × P, mg2/dL2 | 22.2 (18.8–24.4) | 40.6 (33.8–44.6) | 58.3 (53.8–66.6) | 0.200 |
PTH, pg/mL | 538 (204–972) | 465 (252–662) | 500 (414–730) | 0.267 |
Tchol, mg/dL | 159 (128–195) | 174 (146–206) | 168 (139–191) | 0.395 |
LDL-chol, mg/dL | 85 (62–114) | 94.5 (76–117) | 92.5 (62.5–119) | 0.273 |
HDL-chol, mg/dL | 40 (33–57) | 38.5 (34–45) | 36.5 (31.5–50) | 0.252 |
TG, mg/dL | 134 (99–200) | 162 (99–235) | 161 (115–224) | 0.285 |
hsCRP, mg/L | 13.2 (6.75–23.6) | 6.9 (4.0–18.4) | 4.7 (4.0–20.7) | 0.301 |
HOMA | 3.37 (0.976–16.7) | 6.73 (3.19–9.5) | 5.61 (3.17–9.97) | 0.392 |
HbA1c, % | 5.6 (4.9–7.3) | 6.3 (5.3–7.2) | 5.4 (5.0–7.6) | 0.304 |
Age, years | 74 (67–79) | 65 (53–67) | 65.5 (61–74) | 0.307 |
BMI, kg/m2 | 24.6 (20.6–29.4) | 27.8 (24.8–29.2) | 25.5 (23.8–29.9) | 0.485 |
HD vintage, months | 50.4 (35.7–66.6) | 29.7 (15.1–47.4) | 22.9 (13–41.9) | 0.211 |
BPsys, mmHg | 120 (110–120) | 125 (110–130) | 130 (120–140) | 0.021 |
BPdias, mmHg | 70 (70–75) | 70 (70–80) | 80 (70–80) | 0.317 |
PP | 50 (40–50) | 50 (40–60) | 50 (40–60) | 0.091 |
MAP | 66.7 (53.3–66.7) | 66.7 (53.3–80) | 66.7 (53.3–80) | 0.370 |
Parameter | HD with D n = 26 Median (Q1–Q3) | HD without D n = 24 Median (Q1–Q3) | p Value |
---|---|---|---|
eNOS, ng/mL | 0.725 (0.400–2.63) | 0.700 (0.375–1.615) | 0.573 |
P, mg/dL | 5.16 (4.16–6.86) | 5.43 (3.44–6.44) | 0.830 |
Ca, mg/dL | 8.38 (8.06–8.85) | 8.70 (7.89–9.07) | 0.534 |
Ca × P | 43.9 (35.4–56.7) | 47.0 (29.3–56.9) | 0.808 |
PTH, pg/mL | 465 (275–740) | 502 (379–797) | 0.534 |
HgB, g/dL | 11.6 (10.2–12.4) | 11.8 (10.5–12.3) | 0.690 |
RBC, 106/µL | 3.80 (3.33–3.98) | 3.81 (3.57–3.93) | 0.688 |
Tchol, mg/dL | 194 (180–231) | 136 (125–154) | <0.0001 |
LDL-cholesterol, mg/dL | 116 (101–135) | 64.0 (52.5–79.0) | <0.0001 |
HDL-cholesterol, mg/dL | 38.0 (34.0–49.0) | 38.5 (31.5–54.0) | 0.953 |
TG, mg/dL | 204 (148–289) | 111 (87.0–162) | <0.0001 |
hsCRP, mg/L | 4.7 (4.0–18.0) | 9.45 (4.0–24.0) | 0.410 |
HOMA | 7.11 (2.99–9.52) | 5.55 (2.13–9.88) | 0.478 |
HbA1c, % | 6.1 (5.2–7.5) | 5.7 (5.0–7.2) | 0.748 |
Albumin, g/dL | 3.75 (3.5–4.0) | 3.6 (3.4–3.8) | 0.058 |
With D Median (Q1–Q3) | Without D Median (Q1–Q3) | p Value | With Type 2 DM Median (Q1–Q3) | Without DM Median (Q1–Q3) | p Value | |
---|---|---|---|---|---|---|
N subject | 26 | 24 | - | 25 | 25 | - |
Age (years) | 64.5 (60.0–72.0) | 66.5 (60.0–74.5) | 0.938 | 67.0 (59.0–73.0) | 65.0 (61.0–74.0) | 0.938 |
Gender (M/F) | 12/14 | 15/9 | – | 14/11 | 13/12 | - |
HD vintage, months | 31.3 (15.4–59.8) | 25.9 (11.1–46.3) | 0.084 | 28.3 (15.1–46.0) | 31.6 (15.3–67.7) | 0.097 |
BMI (kg/m2) | 26.9 (23.9–29.1) | 27.0 (20.9–29.6) | 0.742 | 28.4 (24.8–30.4) | 25.1 (23.5–28.0) | 0.235 |
BPsys (mmHg) | 120 (110–140) | 125 (115–135) | 0.588 | 120 (120–140) | 120 (110–140) | 0.169 |
BPdias (mmHg) | 70 (70–80) | 70 (70–80) | 0.824 | 70 (70–80) | 70 (70–80) | 0.651 |
PP | 50 (40–60) | 50 (40–60) | 0.725 | 50 (50–60) | 50 (40–60) | 0.133 |
MAP | 66.6 (53.3–80.0) | 66.6 (53.3–80.0) | 0.726 | 66.6 (66.6–80.0) | 66.6 (52.5–80.0) | 0.132 |
Parameter | HD with Type 2 DMn = 25 Median (Q1–Q3) | HD without DM n = 25 Median (Q1–Q3) | p Value |
---|---|---|---|
eNOS, ng/mL | 0.660 (0.420–1.70) | 0.750 (0.380–1.96) | 0.992 |
P, mg/dL | 5.0 (3.56–6.44) | 5.4 (3.8–6.8) | 0.648 |
Ca, mg/dL | 8.34 (7.88–9.03) | 8.81 (8.26–8.95) | 0.409 |
Ca × P | 42.3 (33.7–54.1) | 46.3 (35.4–58.0) | 0.497 |
PTH, pg/mL | 466 (283–662) | 515 (420–815) | 0.460 |
HgB, g/dL | 11.6 (10.3–12.2) | 11.6 (10.9–12.4) | 0.649 |
RBC, 106/µL | 3.8 (3.4–4.1) | 3.82 (3.46–3.91) | 0.586 |
Tchol, mg/dL | 166 (146–192) | 178 (135–196) | 0.763 |
LDL-cholesterol, mg/dL | 89.0 (63.0–104) | 100 (73.0–117) | 0.210 |
HDL-cholesterol, mg/dL | 39.0 (33.0–49.0) | 38.0 (34.0–47.0) | 0.719 |
TG, mg/dL | 162 (114–235) | 161 (92.0–202) | 0.547 |
hsCRP, mg/L | 8.7 (4.0–23.3) | 4.0 (4.0–18.3) | 0.240 |
HOMA | 9.5 (6.5–24.1) | 2.99 (1.11–4.34) | <0.0001 |
HbA1c, % | 7.2 (6.4–8.0) | 5.0 (4.8–5.3) | <0.00001 |
Albumin, g/dL | 3.7 (3.4–3.8) | 3.7 (3.5–3.9) | 0.703 |
Groups and Correlated Parameters | R | p Value |
---|---|---|
Whole HD group, n = 50 | ||
eNOS and P | −0.541 | <0.000049 b |
eNOS and Ca × P | −0.542 | 0.000049 b |
Controls, n = 26 | ||
eNOS and P | 0.373 | 0.059 |
eNOS and Ca | 0.469 | 0.015 a |
eNOS and Ca × P | 0.424 | 0.030 a |
Dyslipidemic HD group, n = 26 | ||
eNOS and BPsys | −0.401 | 0.042 a |
eNOS and BPdias | −0.440 | 0.021 a |
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Niepolski, L.; Malinowska-Loba, K. Association of Circulating Endothelial Nitric Oxide Synthase Levels with Phosphataemia in Patients on Haemodialysis. Biomedicines 2024, 12, 687. https://doi.org/10.3390/biomedicines12030687
Niepolski L, Malinowska-Loba K. Association of Circulating Endothelial Nitric Oxide Synthase Levels with Phosphataemia in Patients on Haemodialysis. Biomedicines. 2024; 12(3):687. https://doi.org/10.3390/biomedicines12030687
Chicago/Turabian StyleNiepolski, Leszek, and Kamila Malinowska-Loba. 2024. "Association of Circulating Endothelial Nitric Oxide Synthase Levels with Phosphataemia in Patients on Haemodialysis" Biomedicines 12, no. 3: 687. https://doi.org/10.3390/biomedicines12030687