Background
Methods
Study participants and design
Study procedures and data collection
Outcome measurements
Sample size considerations
Statistical analysis
Results
Baseline characteristics
Variable | CKD+/MDD+ (n = 175) | Sertraline (n = 88) | Placebo (n = 87) | P-value |
---|---|---|---|---|
Age, years, mean ± SD | 58 ± 13 | 58 ± 13 | 58 ± 13 | 0.95 |
BMI, kg/m2, mean ± SD | 33.4 ± 17.2 | 31.4 ± 8.8 | 35.4 ± 22.7 | 0.13 |
Women, n (%) | 46 (26) | 24 (27) | 22 (25) | 0.77 |
African American, n (%) | 97 (55) | 50 (57) | 47 (54) | 0.78 |
Diabetes mellitus, n (%) | 103 (59) | 48 (55) | 55 (63) | 0.28 |
Proton pump inhibitor use, n (%) | 46 (26) | 21 (24) | 25 (29) | 0.46 |
Beta blocker use, n (%) | 116 (66) | 61 (69) | 55 (63) | 0.39 |
Statin use, n (%) | 109 (62) | 53 (60) | 56 (64) | 0.57 |
ACEI/ARB use, n (%) | 102 (58) | 53 (60) | 49 (56) | 0.60 |
eGFR, mL/min/1.73 m2, mean ± SD | 27 ± 13 | 28 ± 13 | 27 ± 13 | 0.74 |
Urine albumin-to-creatinine ratio, mg/g, median (IQR) | 337 (0.5–10,250) | 312 (0.5–7032) | 555 (9–7723) | 0.19 |
Hemoglobin, g/dL, mean ± SD | 12.4 ± 7.6 | 13.0 ± 10.4 | 11.9 ± 2.3 | 0.36 |
White blood cell count, K per μL, mean ± SD | 7 ± 3 | 7.0 ± 2.8 | 7.0 ± 2.7 | 0.92 |
Platelet count, K per μL, mean ± SD | 224 ± 72 | 223 ± 81 | 226 ± 61 | 0.80 |
Serum total cholesterol, md/dL, mean ± SD | 169 ± 47 | 168 ± 45 | 169 ± 49 | 0.85 |
Serum triglycerides, mg/dL, mean ± SD | 147 ± 88 | 139 ± 73 | 155 ± 102 | 0.25 |
Serum LDL, mg/dL, median (IQR) | 86 (14–284) | 89 (32–252) | 85 (14–287) | 0.88 |
Serum total bilirubin, mg/dL, mean ± SD | 1.0 ± 5.6 | 1.4 ± 8.0 | 0.5 ± 0.2 | 0.28 |
Hemoglobin A1c, %, mean ± SD | 7.0 ± 4.0 | 6.8 ± 1.7 | 7.3 ± 5.4 | 0.34 |
Serum albumin, g/dL, mean ± SD | 3.8 ± 0.6 | 3.8 ± 0.6 | 3.8 ± 0.5 | 0.93 |
Serum uric acid, mg/dL, mean ± SD | 8.3 ± 2.1 | 8.2 ± 2.4 | 8.3 ± 1.8 | 0.83 |
Serum calcium, mg/dL, mean ± SD | 9.1 ± 0.9 | 9.1 ± 0.8 | 9.1 ± 1.0 | 0.62 |
Serum phosphorus, mg/dL, mean ± SD | 4.1 ± 0.9 | 4.0 ± 0.8 | 4.2 ± 1.0 | 0.09 |
Serum parathyroid hormone, ng/L, median (IQR) | 127 (2–1629) | 125 (5–708) | 137 (20–1629) | 0.37 |
Serum 25-hydroxyvitamin D, pg/L, mean ± SD | 28 ± 15 | 30 ± 16 | 26 ± 13 | 0.09 |
QIDS-SR16 score, median (IQR) | 12 (10–21) | 12 (3–21) | 12 (10–18) | 0.15 |
Association between severity of depression, platelet function, and sertraline levels
Spearman correlation coefficient | P-value | |
---|---|---|
Depression Severity at baseline by QIDS-SR16 Scorea | N = 175 | |
WBPA to 0.5 mM arachidonic acid, Ω | − 0.05 | 0.55 |
WBPA to 0.25 mM arachidonic acid, Ω | − 0.06 | 0.46 |
WBPA to 20 μM ADP, Ω | − 0.16 | 0.06 |
WBPA to 10 μM ADP, Ω | − 0.11 | 0.16 |
WBPA to 2 μg/mL collagen, Ω | −0.10 | 0.18 |
ATP secretion to 0.5 mM arachidonic acid, nmoles | −0.04 | 0.63 |
ATP secretion to 0.25 mM arachidonic acid, nmoles | −0.02 | 0.79 |
ATP secretion to 2 μg/mL collagen, nmoles | −0.14 | 0.06 |
ATP secretion to 1 unit/mL thrombin, nmoles | −0.06 | 0.45 |
bPlasma P-selectin levels, pg/L | 0.06 | 0.61 |
bPlasma E-selectin levels, pg/L | 0.00953 | 0.93 |
cSerum Sertraline levels, pg/L | 0.21 | 0.01 |
cSerum N-desmethylsertraline levels, pg/L | 0.18 | 0.03 |
Serum Sertraline Levels in pg/L | ||
WBPA to 0.5 mM arachidonic acid, Ω | −0.0089 | 0.93 |
WBPA to 0.25 mM arachidonic acid, Ω | − 0.0650 | 0.51 |
WBPA to 20 μM ADP, Ω | −0.1092 | 0.35 |
WBPA to 10 μM ADP, Ω | 0.0341 | 0.7 |
WBPA to 2 μg/mL collagen, Ω | −0.0154 | 0.88 |
ATP secretion to 0.5 mM arachidonic acid, nmoles | −0.08725 | 0.38 |
ATP secretion to 0.25 mM arachidonic acid, nmoles | − 0.1472 | 0.14 |
ATP secretion to 2 μg/mL collagen, nmoles | − 0.1513 | 0.12 |
ATP secretion to 1 unit/mL thrombin, nmoles | −0.2200 | 0.03 |
bPlasma P-selectin levels, pg/L | −0.0946 | 0.50 |
bPlasma E-selectin levels, pg/L | −0.2076 | 0.14 |
Serum N-desmethylsertraline levels in pg/L | ||
WBPA to 0.5 mM arachidonic acid, Ω | − 0.0045 | 0.96 |
WBPA to 0.25 mM arachidonic acid, Ω | − 0.0553 | 0.59 |
WBPA to 20 μM ADP, Ω | −0.1063 | 0.37 |
WBPA to 10 μM ADP, Ω | 0.0510 | 0.60 |
WBPA to 2 μg/mL collagen, Ω | −0.0164 | 0.87 |
ATP secretion to 0.5 mM arachidonic acid, nmoles | −0.0789 | 0.43 |
ATP secretion to 0.25 mM arachidonic acid, nmoles | −0.1237 | 0.22 |
ATP secretion to 2 μg/mL collagen, nmoles | −0.1287 | 0.20 |
ATP secretion to 1 unit/mL thrombin, nmoles | −0.2012 | 0.04 |
bPlasma P-selectin levels, pg/L | −0.0554 | 0.40 |
bPlasma E-selectin levels, pg/L | −0.2166 | 0.12 |
Effect of sertraline treatment on platelet function in MDD+/CKD+ group
Sertraline, N = 88 | Placebo, N = 87 | P-value | |||||||
---|---|---|---|---|---|---|---|---|---|
Platelet function | Baseline | Week 12 | Median change from baseline to week 12 | Baseline | Week 12 | Median change from baseline to week 12 | Between-groups at baselinea | Between groups at Week 12b | Between groups for changec |
A. Whole blood platelet aggregation induced by agonist (in ohms) | |||||||||
0.5 mM arachidonic acid | 5 (0, 20) | 1 (0, 21) | −4.00 | 0 (0,10) | 0 (0, 10) | 0 | 0.08 | 0.04 | 0.14 |
0.25 mM arachidonic acid | 0 (0, 17) | 0 (0, 15) | 0 | 0 (0, 14) | 0 (0, 6) | 0 | 0.40 | 0.22 | 0.07 |
20 μM ADP | 10 (6, 14) | 8 (5, 12) | −2.00 | 11 (8, 14) | 11 (5, 15) | 0 | 0.82 | 0.22 | 0.10 |
10 μM ADP | 10 (5, 12) | 10 (6, 14) | 0 | 10 (7, 15) | 10 (7, 15) | 0 | 0.08 | 0.15 | 0.23 |
2 μg/mL collagen | 20 (14, 26) | 20 (15, 27) | 0 | 21 (14, 30) | 18 (13, 24) | −3.00 | 0.51 | 0.21 | 0.09 |
B. ATP secretion induced by agonist (in nmoles) | |||||||||
0.5 mM arachidonic acid | 0.35 (0, 0.76) | 0.23 (0, 0.68) | −0.12 | 0.26 (0, 0.72) | 0.14 (0, 0.52) | −0.12 | 0.50 | 0.27 | 0.16 |
0.25 mM arachidonic acid | 0.20 (0, 0.67) | 0.11 (0, 0.63) | −0.09 | 0.13 (0, 0.52) | 0 (0, 0.30) | −0.13 | 0.42 | 0.12 | 0.17 |
2 μg/mL collagen | 0.71 (0.43, 1.11) | 0.62 (0.35, 0.88) | −0.09 | 0.52 (0.29, 0.91) | 0.55 (0.33, 0.89) | 0.03 | 0.05 | 0.74 | 0.13 |
1 unit/mL thrombin | 1.17 (0.83, 1.73) | 0.87 (0.63, 1.15) | −0.30 | 1.02 (0.73, 1.43) | 0.90 (0.46, 1.37) | −0.12 | 0.09 | 0.71 | 0.39 |
C. Plasma levels of platelet activation markers (in pg/L) | |||||||||
P-selectin | 34.10 (23.47, 49.24) | 32.99 (23.92, 42.73) | −1.11 | 36.36 (29.60, 41.20) | 31.32 (27.41, 43.13) | −5.04 | 0.90 | 0.57 | 0.44 |
E-selectin | 42.06 (30.30, 59.95) | 40.35 (30.24, 60.30) | −1.71 | 43.53 (36.11, 51.33) | 44.38 (35.81, 56.05) | 0.85 | 0.97 | 0.41 | 0.34 |
Subgroup analysis
Variable | MDD+/CKD+ (n = 49) | MDD−/CKD+ (n = 28) | MDD−/CKD- (n = 15) | P-value |
---|---|---|---|---|
Age, years, mean ± SD | 53 ± 12 | 52 ± 10 | 49 ± 11 | 0.55 |
BMI, kg/m2, mean ± SD | 32.3 ± 9.9 | 32.0 ± 5.5 | 29.8 ± 4.9 | 0.56 |
Female, n (%) | 20 (41) | 16 (57) | 8 (50) | 0.38 |
African American, n (%) | 27 (55) | 15 (54) | 4 (25) | 0.14 |
Diabetes mellitus, n (%) | 27 (55) | 13 (46) | 7 (44) | 0.64 |
Proton pump inhibitor use, n (%) | 10 (20) | 1 (4) | 1 (6) | 0.07 |
Beta blocker use, n (%) | 31 (63) | 21 (75) | 0 (0) | < 0.01 |
Statin use, n (%) | 26 (53) | 19 (68) | 5 (31) | 0.06 |
ACEI/ARB use, n (%) | 24 (49) | 12 (43) | 5 (31) | 0.46 |
eGFR, mL/min/1.73 m2, mean ± SD | 22 ± 13a | 17 ± 7a | 101 ± 15b | < 0.01 |
Urine albumin-to-creatinine ratio, mg/g, median (IQR) | 432 (27–4962)a | 1282 (2–6469)b | 5 (0–87)c | < 0.01 |
Hemoglobin, g/dL, mean ± SD | 11.2 ± 2.1a | 11.2 ± 1.7a | 14.4 ± 1.7b | < 0.01 |
White blood cell count, K per μL, mean ± SD | 7 ± 3 | 8 ± 2 | 6 ± 2 | 0.25 |
Platelet count, K per μL, mean ± SD | 230 ± 80 | 232 ± 55 | 217 ± 55 | 0.77 |
Serum total cholesterol, mg/dL, mean ± SD | 179 ± 54 | 170 ± 42 | 180 ± 33 | 0.72 |
Serum triglycerides, mg/dL, median (IQR) | 131 (47–340) | 124 (35–275) | 112 (43–443) | 0.85 |
Serum LDL, mg/dL, mean ± SD | 92 ± 42 | 94 ± 38 | 102 ± 29 | 0.71 |
Serum total bilirubin, mg/dL, mean ± SD | 0.5 ± 0.7 | 0.4 ± 0.2 | 0.7 ± 0.6 | 0.20 |
Hemoglobin A1c, % | 6.4 ± 1.8 | 6.5 ± 1.5 | 6.2 ± 0.8 | 0.80 |
Serum albumin, g/dL, mean ± SD | 3.7 ± 0.6 | 4.0 ± 0.5 | 4.2 ± 0.4 | < 0.01 |
Serum uric acid, mg/dL, mean ± SD | 7.7 ± 2.0 | 8.9 ± 2.0 | 5.1 ± 1.8 | < 0.01 |
Serum calcium, mg/dL, mean ± SD | 8.9 ± 0.9 | 9.1 ± 0.8 | 9.3 ± 0.3 | 0.11 |
Serum phosphorus, mg/dL, mean ± SD | 4.6 ± 1.0a | 4.6 ± 1.1a | 3.3 ± 0.3b | < 0.01 |
Serum parathyroid hormone, pg/mL, median (IQR) | 184 (11–708)a | 170 (77–255)a | 42 (27–82)b | < 0.01 |
Serum 25-hydroxyvitamin D, ng/mL, mean ± SD | 27 ± 17 | 28 ± 14 | 29 ± 15 | < 0.01 |
QIDS-SR16 score, median (IQR) | 12 (5–19)a | 4 (0–8)b | 3 (0–9)b | < 0.01 |