Introduction
Methods
Study setting and design
Definitions
Laboratory methods
Statistical analysis
Results
Baseline characteristics
All (n = 681) | Nephrotic range proteinuria (n = 183) | Non-nephrotic range proteinuria (n = 491) | P | |
---|---|---|---|---|
Age (yrs) | 12.2 (3.3) | 12.8 (3.2) | 11.9 (3.4) | 0.003 |
Sex (% boys) | 448 (65.8%) | 116 (63.4%) | 329 (67.0%) | 0.378 |
Caucasian ethnicity | 611 (89.7%) | 163 (89.1%) | 441 (89.8%) | 0.778 |
Primary kidney diagnosis | < 0.001 | |||
CAKUT | 470 (69.0%) | 113 (63.7%) | 354 (72.1%) | |
Glomerular | 57 (8.4%) | 33 (18.0%) | 24 (4.9%) | |
Other | 154 (22.6%) | 37 (20.2%) | 113 (23.0%) | |
Pubertal status-pubertal | 303 (44.9%) | 94 (51.6%) | 204 (42.0%) | 0.025 |
Height (cm) | 140.9 (20.2) | 142.9 (19.5) | 140.1 (20.4) | 0.110 |
SDS | − 1.35 (1.36) | − 1.51 (1.25) | − 1.29 (1.39) | 0.061 |
BMI (kg/m2) | 18.4 (3.9) | 18.6 (3.6) | 18.4 (4.0) | 0.552 |
SDS | 0.10 (1.28) | 0.15 (1.24) | 0.09 (1.29) | 0.621 |
Obese (%) | 36 (5.3%) | 10 (5.5%) | 26 (5.3%) | 0.940 |
Overweight (%) | 125 (18.4%) | 33 (18.0%) | 91 (18.5%) | 0.881 |
Waist-to-hip ratio | 0.92 (0.12) | 0.90 (0.11) | 0.93 (0.12) | 0.005 |
Waist-to-height ratio | 0.48 (0.07) | 0.48 (0.07) | 0.49 (0.07) | 0.259 |
eGFR (ml/min/1.73 m2) | 26.9 (11.6) | 22.1 (9.5) | 28.7 (11.8) | < 0.001 |
Time since CKD stage II (years) | 6.1 (4.6) | 5.3 (4.1) | 6.4 (4.7) | 0.010 |
Bicarbonate (mmol/l) | 21.3 (3.6) | 20.7 (4.2) | 21.5 (3.4) | 0.010 |
CRP (mg/dl) | 0.55 (1.99) | 0.60 (2.6) | 0.54 (2.0) | 0.400 |
Hemoglobin (g/dl) | 11.7 (1.6) | 11.5 (1.7) | 11.8 (1.6) | 0.025 |
Serum albumin (g/l) | 40.0 (5.5) | 35.0 (6.9) | 40.5 (3.9 g) | < 0.001 |
UACR (g/g) | 0.33 (1.14) | 2.29 (1.93) | 0.17 (0.38) | < 0.001 |
Systolic BP SDS | 0.80 (1.35) | 1.07 (1.50) | 0.71 (1.29) | 0.002 |
Diastolic BP SDS | 0.69 (1.08) | 1.0 (1.17) | 0.58 (1.03) | < 0.001 |
Physical activity | < 0.001 | |||
< 1 h per week | 159 (23.8%) | 61 (33.7%) | 95 (19.8%) | |
1–4 h per week | 228 (34.2%) | 52 (28.7%) | 172 (35.9%) | |
> 4 h per week | 280 (42.0%) | 68 (37.6%) | 212 (44.3%) |
A. All patients | ||||
All (n = 681) | Nephrotic range proteinuria (n = 183) | Non-nephrotic range proteinuria (n = 491) | p-value | |
Total cholesterol | ||||
Mean (SD) | 180 (48) | 199 (62) | 172 (37) | < 0.001 |
Median (IQR) | 173 (55) | 185 (72) | 171 (50) | |
HDL cholesterol | ||||
Mean (SD) | 48 (14) | 49 (16) | 48(14) | 0.676 |
Median (IQR) | 46 (19) | 46 (20) | 46 (18) | |
LDL cholesterol | ||||
Mean (SD) | 98 (39) | 113 (51) | 92 (30) | < 0.001 |
Median (IQR) | 93 (46) | 100 (53) | 91 (42) | |
Triglycerides | ||||
Mean (SD) | 147 (86) | 170 (101) | 138 (78) | < 0.001 |
Median (IQR) | 126 (84) | 142 (107) | 119 (78) | |
B. Fasting patients | ||||
All (n = 265) | Nephrotic-range proteinuria (n = 85) | Non-nephrotic range proteinuria (n = 177) | p-value | |
Total cholesterol | ||||
Mean (SD) | 180 (54) | 198 (68) | 169 (38) | < 0.001 |
Median (IQR) | 172 (58) | 182 (67) | 169 (52) | |
HDL cholesterol | ||||
Mean (SD) | 48 (15) | 48 (16) | 47 (14) | 0.749 |
Median (IQR) | 46 (19) | 45 (22) | 46 (18) | |
LDL cholesterol | ||||
Mean (SD) | 100 (44) | 115 (55) | 91 (31) | < 0.001 |
Median (IQR) | 94 (47) | 102 (50) | 90 (40) | |
Triglycerides | ||||
Mean (SD) | 137 (75) | 154 (83) | 129 (70) | 0.015 |
Median (IQR) | 123 (80) | 135 (96) | 115 (74) |
Abnormal lipid levels, types, and frequency of dyslipidemia
All | CKD stage 3 | CKD stage 4 | CKD stage 5 | *p-value | |
---|---|---|---|---|---|
Total cholesterol (n) | 679 | 249 | 322 | 108 | |
Mean (± SD; mg/dl) | 180 (48) | 177 (45) | 183 (49) | 178 (52) | 0.294 |
Normal (n, %) | 495 (72.9%) | 181 (72.7%) | 233 (72.4%) | 81 (75.03%) | 0.863 |
Abnormal (n, %) | 184 (27.1%) | 68 (27.3%) | 89 (27.6%) | 27 (25.0%) | |
HDL cholesterol | 681 | 249 | 324 | 108 | |
Mean (± SD; mg/dl) | 48 (14) | 49 (14) | 47 (15) | 46 (16) | 0.088 |
Normal | 464 (68.1%) | 188 (75.5%) | 207 (63.9%) | 69 (63.9%) | 0.007 |
Abnormal | 217 (31.9%) | 61 (24.5%) | 117 (36.1%) | 39 (36.1%) | |
LDL cholesterol | 678 | 249 | 322 | 107 | |
Mean (± SD; mg/dl) | 98 (39) | 96 (37) | 101 (40) | 96 (41) | 0.217 |
Normal | 575 (84.8%) | 211 (84.7%) | 268 (83.2%) | 96 (89.7%) | 0.269 |
Abnormal | 103 (15.2%) | 38 (15.3%) | 54 (16.8%) | 11 (10.3%) | |
Triglycerides | 680 | 249 | 324 | 107 | |
Mean (± SD; mg/dl) | 147 (86) | 134 (78) | 154 (89) | 154 (92) | 0.015 |
Normal | 308 (45.3%) | 130 (52.2%) | 135 (41.7%) | 43 (40.2%) | 0.022 |
Abnormal | 372 (54.7%) | 119 (47.8%) | 189 (58.3%) | 64 (59.8%) |
All | HDL-C low | HDL-C normal | p-value | |
---|---|---|---|---|
A. Total study population | ||||
High vs. normal TG (n; %) | ||||
Normal | 308 ( 45.3%) | 64 ( 29.5%) | 244 ( 52.7%) | < 0.001 |
Abnormal | 372 ( 54.7%) | 153 ( 70.5%) | 219 ( 47.3%) | |
Missing | 1 | 0 | 1 | |
B. Patients with nephrotic range proteinuria | ||||
High vs. normal TG (n; %) | ||||
Normal | 65 ( 35.5%) | 14 ( 23.0%) | 51 ( 41.8%) | 0.012 |
Abnormal | 118 ( 64.5%) | 47 ( 77.0%) | 71 ( 58.2%) | |
C. Patients without nephrotic range proteinuria | ||||
High vs. normal TG (n; %) | ||||
Normal | 240 ( 49.0%) | 50 ( 32.5%) | 190 ( 56.5%) | < 0.001 |
Abnormal | 250 ( 51.0%) | 104 ( 67.5%) | 146 ( 43.5%) | |
Missing | 1 | 0 | 1 |
All (n; %) | CKD stage 3 | CKD stage 4 | CKD stage 5 | p-value | |
---|---|---|---|---|---|
Dyslipidemia | |||||
No dyslipidemia | 190 (27.6%) | 81 (32.5%) | 77 (23.8%) | 32 (29.4%) | 0.102 |
Dyslipidemia | 489 (71.8%) | 168 (67.5%) | 246 (75.9%) | 75 (64.4%) | |
Isolated vs. multiple dyslipidemia | |||||
No dyslipidemia | 190 (27.9%) | 81 (32.5%) | 77 (23.8%) | 32 (29.6%) | 0.312 |
Isolated dyslipidemia | 220 (32.3%) | 79 (31.7%) | 110 (34.0%) | 31 (28.7%) | |
Abnormal lipid | |||||
Isolated high Chol | 28 (12.7%) | 14 (17.7%) | 12 (10.9%) | 2 (6.5%) | 0.242 |
Isolated low HDL-C | 59 (26.8%) | 19 (24.1%) | 34 (30.9%) | 6 (19.4%) | |
Isolated high TG | 133 (60.5%) | 46 (58.2%) | 64 (58.2%) | 23 (74.2%) | |
Isolated high LDL-C | 0 | ||||
Multiple dyslipidemia | 268 (39.4%) | 89 (35.7%) | 135 (41.7%) | 44 (40.7%) | |
Number of abnormal lipids: multiple dyslipidemia | |||||
2 | 170 (63.4%) | 63 (70.8%) | 80 (59.3%) | 27 (61.4%) | 0.264 |
3 | 77 (28.7%) | 23 (25.8%) | 42 (31.1%) | 12 (27.3%) | |
4 | 21 (7.8%) | 3 (3.4%) | 13 (9.6%) | 5 (11.4%) |
Factors associated with lipid levels and dyslipidemia at baseline
Cholesterol (n = 630) | LDL cholesterol (n = 629) | HDL cholesterol (n = 632) | Triglycerides (n = 631) | |||||
---|---|---|---|---|---|---|---|---|
Beta [95%CI] | p-value | Beta [95%CI] | p-value | Beta [95%CI] | p-value | Beta[95%CI] | p-value | |
Age (yrs) | − 1.77 [− 2.79, − 0.76] | 0.0007 | − 1.21 [− 2.06, − 0.38] | 0.0046 | − 0.77 [− 1.03, − 0.44] | < 0.0001 | n.i | |
Sex (ref male) | n.i | n.i | 3.82 [1.50, 6.11] | 0.0013 | − 14.02 [− 27.60, − 0.45 | 0.0429 | ||
Glomerular disease (ref CAKUT) | 38.19 [25.34, 51.05] | < 0.0001 | 28.27 [17.67, 38.85] | < 0.0001 | n.i | 37.92 [14.07, 61.79] | 0.0019 | |
Other diagnosis (ref CAKUT) | 12.13 [3.98, 20.28] | 0.0036 | 8.83 [2.12, 15.54] | 0.0100 | n.i | 2.18 [− 13.49, 17.86] | 0.7846 | |
eGFR (ml/min/1.73 m2) | n.i | n.i | 0.15 [0.05, 0.25] | 0.0040 | − 0.74 [− 1.28, − 0.20] | 0.0075 | ||
Time since CKD2 (years) | n.i | n.i | 0.54 [0.29, 0.79] | < 0.0001 | − 1.30 [− 2.78, 0.18] | 0.0861 | ||
Log UACR | 6.20 [4.11, 8.29] | < 0.0001 | 4.39 [2.67, 2.11] | < 0.0001 | 1.41 [0.70, 2.12] | 0.0001 | n.i | |
Log hsCRP | − 2.74 [− 4.87, − 0.60] | 0.0120 | − 1.38 [− 3.14, 0.38] | 0.1232 | − 1.34 [− 2.02, − 0.66] | 0.0001 | − 5.52 [− 9.52, − 1.53] | 0.0068 |
BMI-SDS | 3.89 [1.26, 6.52] | 0.0038 | 2.21 [− 0.05, 4.39] | 0.0449 | n.i | 10.59 [5.61, 15.57] | < 0.0001 | |
Serum albumin | − 1.22 [− 1.93, − 0.50] | 0.0009 | − 1.05 [− 1.64, − 0.47] | 0.0005 | 0.49 [0.27, 0.71] | < 0.0001 | − 3.68 [− 4.92, − 2.45] | < 0.0001 |
Diastolic BP SDS | n.i | n.i | n.i | 8.31 [2.50, 14.12] | 0.0052 | |||
Lack of physical activity (ref at least 1 h per week) | 9.89 [1.88, 17.89] | 0.0156 | 7.46 [0.87, 14.06] | 0.0267 | n.i | n.i | ||
Serum bicarbonate | 1.66 [0.71, 2.60] | 0.0006 | 1.35 [0.56, 2.14] | 0.0008 | 0.26 [− 0.05, 0.56] | 0.0966 | n.i | |
Serum hemoglobin | n.i | n.i | n.i | n.i | ||||
Non-fasting status (ref fasting) | − 0.52 [− 7.47, 6.43] | 0.8831 | − 3.02 [− 8.75, 2.72] | 0.3020 | − 0.90 [− 3.12, 1.31] | 0.4238 | 17.78 [4.87, 30.68] | 0.0070 |
High cholesterol (n = 630) | High LDL cholesterol (n = 629) | Low HDL cholesterol (n = 632) | High triglycerides (n = 631) | |||||
---|---|---|---|---|---|---|---|---|
OR [95%CI] | p-value | OR [95%CI] | p-value | OR [95%CI] | p-value | OR [95%CI] | p-value | |
Age (yrs) | 0.93 [0.88, 0.99] | 0.0137 | 0.91 [0.84, 0.98] | 0.0100 | 1.09 [1.03, 1.15] | 0.0025 | 0.87 [0.82, 0.91] | < 0.0001 |
Sex (ref male) | n.i | n.i | 0.43 [0.29, 0.65] | < 0.0001 | n.i | |||
Glomerular disease (ref CAKUT) | 5.02 [2.65, 9.49] | < 0.0001 | 5.07 [2.47, 10.42] | < 0.0001 | n.i | 1.80 [0.90, 3.59] | 0.0956 | |
Other diagnosis (ref CAKUT) | 1.43 [0.90, 2.26.] | 0.1262 | 1.36 [0.76, 2.45] | 0.3056 | n.i | 0.75 [0.49, 1.14] | 0.1790 | |
eGFR (ml/min/1.73 m2) | 1.02 [1.00, 1.04] | 0.0595 | n.i | 0.97 [0.95, 0.99] | 0.0007 | 0.98 [0.97, 0.99] | 0.0293 | |
Time since CKD2 (years) | n.i | n.i | 0.92 [0.88, 0.96] | 0.0002 | 0.94 [0.91, 0.99] | 0.0076 | ||
Log UACR | 1.38 [1.22 1.57] | < 0.0001 | 1.22 [1.04, 1.43] | 0.0159 | 0.84 [0.74, 0.94] | 0.0032 | n.i | |
Log hsCRP | 0.85[0.74, 0.96] | 0.0109 | n.i | 1.24[1.11, 1.39] | 0.0002 | n.i | ||
BMI-SDS | 1.26 [1.07, 1.48] | 0.0057 | 1.21 [0.99, 1.49] | 0.0577 | n.i | 1.20 [1.05, 1.37] | 0.0090 | |
Serum albumin | n.i | 0.95 [0.91, 0.99] | 0.0274 | 0.93 [0.89, 0.96] | 0.0001 | 0.95 [0.92, 0.99] | 0.0078 | |
Diastolic BP -SDS | n.i | n.i | n.i | 1.25 [1.06, 1.48] | 0.0069 | |||
Lack of physical activity (ref ≥ 1 h per week) | n.i | 1.84 [1.00, 3.36] | 0.0487 | n.i | 1.44 [0.95, 2.18] | 0.0825 | ||
Serum bicarbonate | 1.05 [1.00, 1.11] | 0.0702 | n.i | 0.94 [0.89, 0.99] | 0.0172 | n.i | ||
Serum hemoglobin | n.i | n.i | n.i | n.i | ||||
Non-fasting status (ref fasting) | 1.19 [0.80, 1.78] | 0.3884 | 1.28 [0.79, 2.07] | 0.3223 | 0.94 [0.65, 1.37] | 0.7611 | 0.90 [0.64, 1.28] | 0.5555 |