Table 1.
Baseline clinical characteristics of the CKD population at index date (1st January 2015) and according to the presence of type 2 diabetes and CKD stage
| Diabetes status | CKD stage | Total (n = 44,214; 100%) | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Non T2D (n = 24,229; 54.8%) | T2D (n = 19,985; 45.2%) | p | Stage 1 (n = 2159; 4.9%) | Stage 2 (n = 7386;16.7%) | P2 vs 1 | Stage 3a (n = 14,065; 31.8%) | P3a vs 1 | Stage 3b (n = 12,203; 27.6%) | P3b vs 1 | Stage 4 (n = 3537; 8.0%) | P4 vs 1 | Stage 5 (n = 1592; 3.6%) | P5 vs 1 | Unspecified (n = 3272; 7.4%) | PUnsp. vs 1 | ||
| Biodemographic data | |||||||||||||||||
| Age, years | 76.4 ± 14.1 | 75.8 ± 14.0 | 0.001 | 69.8 ± 14.7 | 74.5 ± 13.9 | < 0.001 | 76.8 ± 14.2 | < 0.001 | 78.1 ± 14.3 | < 0.001 | 79.2 ± 14.5 | < 0.001 | 79.8 ± 14.6 | < 0.001 | 65.1 ± 11.4 | < 0.001 | 76.4 ± 14.3 |
| Sex, Female, n (%) | 11,892 (49.1) | 9773 (48.9) | < 0.001 | 1105 (51.2) | 3545 (48.0) | < 0.001 | 6779 (48.2) | < 0.001 | 5992 (49.1) | 0.072 | 1680 (47.5) | < 0.001 | 876 (55.0) | < 0.001 | 1688 (51.6) | 0.773 | 21,665 (49.0) |
| Physical examination and laboratory tests | |||||||||||||||||
| BMI, Kg/m2 | 28.4 ± 5.2 | 29.3 ± 5.0 | < 0.001 | 29.3 ± 5.0 | 29.2 ± 5.0 | 0.307 | 28.6 ± 5.2 | < 0.001 | 28.5 ± 5.1 | < 0.001 | 28.1 ± 5.0 | < 0.001 | 27.8 ± 4.9 | < 0.001 | 29.6 ± 5.1 | 0.007 | 28.7 ± 5.1 |
| SBP, mmHg | 136.2 ± 20.2 | 138.3 ± 20.3 | < 0.001 | 135.9 ± 20.1 | 138.2 ± 20.6 | < 0.001 | 138.3 ± 20.6 | 0.194 | 138.6 ± 20.4 | 0.148 | 137.5 ± 20.7 | 0.392 | 135.2 ± 20.5 | 0.791 | 137.8 ± 20.0 | 0.392 | 137.1 ± 20.2 |
| UACR, mg/g | 347.4 ± 172.3 | 391.3 ± 189.4 | < 0.001 | 106.8 ± 49.8 | 126.9 ± 53.5 | < 0.001 | 250.3 ± 120.1 | < 0.001 | 252.1 ± 120.9 | < 0.001 | 1602.4 ± 782.6 | < 0.001 | 1642.3 ± 769.2 | < 0.001 | 132.7 ± 60.2 | < 0.001 | 362.9 ± 176.8 |
| UACR A1, n (%) | 137 (0.56) | 80 (0.4) | < 0.001 | 0 | 0 | – | 0 | – | 0 | – | 0 | – | 0 | – | 217 (6.6) | – | 217 (0.5) |
| UACR A2, n (%) | 16,493 (68.1) | 9772 (48.9) | < 0.001 | 2159 (100) | 7386 (100) | – | 8650 (61.5) | < 0.001 | 7480 (61.3) | < 0.001 | 432 (12.2) | < 0.001 | 53 (3.3) | < 0.001 | 105 (3.2) | < 0.001 | 26,265 (64.5) |
| UACR A3, n (%) | 7599 (31.4) | 10,133 (50.7) | < 0.001 | 0 | 0 | – | 5415 (38.5) | < 0.001 | 4723 (38.7) | < 0.001 | 3105 (87.8) | < 0.001 | 1539 (96.7) | < 0.001 | 2950 (90.2) | < 0.001 | 17,729 (35.0) |
| eGFRa | 49.6 ± 11.3 | 47.5 ± 12.4 | < 0.001 | 93.8 ± 4.7 | 75.1 ± 5.0 | < 0.001 | 52.2 ± 4.9 | < 0.001 | 37.2 ± 5.0 | < 0.001 | 21.9 ± 4.5 | < 0.001 | 8.7 ± 4.3 | < 0.001 | – | – | 48.7 ± 13.2 |
| eGFR ≥90a,n (%) | 1324 (5.5) | 835 (4.2) | < 0.001 | 2159 (100) | 0 | – | 0 | – | 0 | – | 0 | – | 0 | – | 0 | – | 2159 (4.9) |
| eGFR 60–89a, n (%) | 4216 (17.4) | 3170 (15.9) | < 0.001 | 0 | 7386 (100) | – | 0 | – | 0 | – | 0 | – | 0 | – | 0 | – | 7386 (16.7) |
| eGFR 45–59a, n (%) | 7931 (32.7) | 6134 (30.7) | < 0.001 | 0 | 0 | – | 14,065 (100) | – | 0 | – | 0 | – | 0 | – | 0 | – | 14,065 (31.8) |
| eGFR 30–44a, n (%) | 6572 (27.1) | 5631 (28.2) | < 0.001 | 0 | 0 | – | 0 | – | 12,203 (100) | – | 0 | – | 0 | – | 0 | – | 12,203 (27.6) |
| eGFR 15–29a, n (%) | 1730 (7.1) | 1807 (9.0) | < 0.001 | 0 | 0 | – | 0 | – | 0 | – | 3537 (100) | – | 0 | – | 0 | – | 3537 (8.0) |
| eGFR < 15a, n (%) | 644 (2.7) | 948 (4.7) | < 0.001 | 0 | 0 | – | 0 | – | 0 | – | 0 | 1592 (100) | – | 0 | – | 1592 (3.6) | |
| HbA1c. % | 6.2 ± 1.2 | 7.7 ± 2.0 | < 0.001 | 6.4 ± 1.3 | 6.6 ± 1.4 | 0.001 | 6.9 ± 1.6 | 0.001 | 6.8 ± 1.5 | < 0.001 | 6.9 ± 1.6 | 0.001 | 7.0 ± 1.5 | 0.001 | 7.0 ± 1.6 | 0.389 | 6.9 ± 1.6 |
| Creatinine. g/dL | 1.3 ± 0.4 | 1.3 ± 0.5 | 0.759 | 0.6 ± 0.3 | 0.9 ± 0.4 | < 0.001 | 1.1 ± 0.5 | < 0.001 | 1.5 ± 0.8 | < 0.001 | 2.2 ± 0.8 | < 0.001 | 0.6 ± 0.2 | 0.999 | 1.0 ± 0.3 | < 0.001 | 1.3 ± 0.6 |
| Uric acid. g/dL | 6.0 ± 2.0 | 7.1 ± 1.2 | < 0.001 | 6.6 ± 1.5 | 6.8 ± 1.6 | 0.041 | 6.7 ± 1.6 | 0.001 | 6.6 ± 1.5 | 0.999 | 6.7 ± 1.6 | 0.284 | 6.6 ± 1.6 | 0.999 | 6.7 ± 1.7 | 0.229 | 6.6 ± 1.6 |
| Comorbidities, n (%) | |||||||||||||||||
| CKD stage 1 | 1324 (5.5) | 835 (4.2) | < 0.001 | 2159 (100) | 0 | < 0.001 | 0 | – | 0 | – | 0 | – | 0 | – | 0 | – | 2159 (4.9) |
| CKD stage 2 | 4216 (17.4) | 3170 (15.9) | < 0.001 | 0 | 7386 (100) | < 0.001 | 0 | – | 0 | – | 0 | – | 0 | – | 0 | – | 7386 (16.7) |
| CKD stage 3a | 7931 (32.7) | 6134 (30.7) | < 0.001 | 0 | 0 | – | 14,065 (100) | – | 0 | – | 0 | – | 0 | – | 0 | – | 14,065 (31.8) |
| CKD stage 3b | 6572 (27.1) | 5631 (28.2) | < 0.001 | 0 | 0 | – | 0 | – | 12,203 (100) | – | 0 | – | 0 | – | 0 | – | 12,203 (27.6) |
| CKD stage 4 | 1730 (7.1) | 1807 (9.0) | < 0.001 | 0 | 0 | – | 0 | – | 0 | – | 3537 (100) | – | 0 | – | 0 | – | 3537 (8.0) |
| CKD stage 5 | 644 (2.7) | 948 (4.7) | < 0.001 | 0 | 0 | – | 0 | – | 0 | – | 0 | – | 1592 (100) | – | 0 | – | 1592 (3.6) |
| CKD not staged | 1812 (7.5) | 1460 (7.0) | < 0.001 | 0 | 0 | – | 0 | – | 0 | – | 0 | – | 0 | – | 3272 (100) | – | 3272 (7.4) |
| CKD unspecified | 6844 (28.2) | 799 (4.0) | < 0.001 | 319 (14.8) | 1079 (14.6) | 0.629 | 2411 (17.1) | < 0.001 | 2173 (17.8) | 0.001 | 508 (14.4) | 0.678 | 237 (14.9) | 0.932 | 916 (28.0) | < 0.001 | 7643 (17.3) |
| Dialysis | 226 (0.9) | 430 (3.2) | < 0.001 | 0 | 0 | 0 | – | 0 | 0 | – | 656 (41.2) | – | 0 | – | 656 (1.5) | ||
| CVD | 3616 (14.9) | 4579 (22.9) | < 0.001 | 296 (13.7) | 1230 (16.7) | < 0.001 | 2643 (18.8) | < 0.001 | 2295 (18.8) | < 0.001 | 597 (16.9) | < 0.001 | 386 (24.3) | < 0.001 | 748 (22.9) | < 0.001 | 8195 (18.5) |
| Myocardial infarction | 3081 (12.7) | 3671 (18.4) | < 0.001 | 253 (11.7) | 916 (12.4) | 0.383 | 2255 (16.0) | < 0.001 | 1920 (15.7) | < 0.001 | 575 (16.3) | < 0.001 | 274 (17.2) | < 0.001 | 559 (17.1) | < 0.001 | 6752 (15.3) |
| Heart failure | 4078 (16.8) | 4782 (23.9) | < 0.001 | 253 (11.7) | 998 (13.5) | < 0.001 | 2768 (19.7) | < 0.001 | 2601 (21.3) | < 0.001 | 831 (23.5) | < 0.001 | 453 (28.4) | < 0.001 | 956 (29.2) | < 0.001 | 8860 (20.0) |
| Stroke | 2136 (8.8) | 2492 (12.5) | < 0.001 | 133 (6.2) | 716 (9.7) | < 0.001 | 1218 (8.7) | < 0.001 | 1536 (12.6) | < 0.001 | 398 (11.3) | < 0.001 | 216 (13.6) | < 0.001 | 411 (12.6) | < 0.001 | 4628 (10.5) |
| Atrial Fibrillation | 3508 (14.5) | 3306 (16.5) | < 0.001 | 253 (11.7) | 971 (13.2) | 0.067 | 2374 (16.9) | < 0.001 | 2000 (16.4) | < 0.001 | 609 (17.2) | < 0.001 | 278 (17.5) | < 0.001 | 329 (10.1) | 0.062 | 6814 (15.4) |
| Peripheral artery disease | 1003 (4.1) | 921 (4.6) | < 0.001 | 94 (4.4) | 295 (4.0) | 0.409 | 481 (3.4) | 0.019 | 653 (5.4) | 0.055 | 171 (4.8) | 0.487 | 81 (5.1) | 0.317 | 149 (4.6) | 0.728 | 1924 (4.4) |
| Diabetes | 775 (3.2) | 19,985 (100) | < 0.001 | 933 (43.2) | 3483 (47.2) | < 0.001 | 6604 (47.0) | < 0.001 | 5890 (48.3) | < 0.001 | 1643 (46.5) | 0.015 | 712 (44.7) | 0.360 | 1495 (45.7) | < 0.001 | 20,760 (47.0) |
| Medications, n (%) | |||||||||||||||||
| Antihypertensives | 17,518 (72.3) | 17,346 (86.8) | < 0.001 | 1625 (75.3) | 5628 (76.2) | 0.389 | 10,844 (77.1) | 0.065 | 9737 (79.8) | < 0.001 | 2975 (84.1) | < 0.001 | 1345 (84.5) | < 0.001 | 2849 (87.1) | < 0.001 | 33,337 (75.4) |
| RAAS inhibitors | 14,944 (61.7) | 16,427 (82.2) | < 0.001 | 1436 (66.5) | 5449 (73.8) | < 0.001 | 10,267 (73.0) | < 0.001 | 8490 (69.6) | < 0.001 | 2530 (71.5) | < 0.001 | 1156 (72.6) | < 0.001 | 2043 (62.4) | < 0.001 | 31,371 (71.0) |
| ACEi | 7198 (29.7) | 6789 (34.0) | < 0.001 | 711 (32.9) | 2539 (34.4) | 0.196 | 4286 (30.5) | < 0.001 | 3467 (28.4) | < 0.001 | 1265 (35.8) | 0.010 | 592 (37.2) | < 0.001 | 1127 (34.4) | 0.253 | 13,987 (31.6) |
| ACEi at maximal doses | 339 (1.4) | 401 (2.0) | < 0.001 | 88 (4.1) | 28 (0.4) | < 0.001 | 181 (1.3) | < 0.001 | 475 (3.9) | 0.659 | 30 (0.8) | < 0.001 | 27 (1.7) | < 0.001 | 33 (1.0) | < 0.001 | 740 (1.7) |
| ARBs | 8509 (35.1) | 10,960 (54.8) | < 0.001 | 874 (40.5) | 2953 (40.0) | 0.677 | 6446 (45.8) | < 0.001 | 5690 (46.6) | < 0.001 | 1675 (47.4) | < 0.001 | 684 (43.0) | < 0.001 | 1147 (35.1) | < 0.001 | 19,469 (44.0) |
| ARBs at maximal doses | 465 (1.9) | 736 (3.7) | < 0.001 | 22 (1.0) | 0 | – | 660 (4.7) | < 0.001 | 393 (3.2) | < 0.001 | 110 (3.1) | < 0.001 | 16 (1.0) | 0.999 | 0 | – | 1201 (2.7) |
| Aldosterone antagonists | 1471 (6.1) | 1469 (7.4) | < 0.001 | 155 (7.2) | 325 (4.4) | < 0.001 | 858 (6.1) | 0.049 | 1031 (8.4) | 0.061 | 288 (8.1) | 0.218 | 151 (9.5) | < 0.001 | 132 (4.0) | < 0.001 | 2940 (6.6) |
| Direct renin inhibitors | 170 (0.7) | 118 (0.6) | < 0.001 | 8 (0.4) | 26 (0.4) | 0.999 | 80 (0.6) | 0.252 | 84 (0.7) | 0.111 | 30 (0.8) | 0.068 | 12 (0.8) | 0.108 | 48 (1.5) | < 0.001 | 288 (0.7) |
| ARNI | 1124 (4.6) | 2581 (12.9) | < 0.001 | 202 (9.4) | 631 (8.5) | 0.192 | 1374 (9.8) | 0.560 | 914 (7.5) | 0.002 | 231 (6.5) | 0.001 | 143 (9.0) | 0.676 | 210 (6.4) | < 0.001 | 3705 (8.4) |
| Beta blockers | 8315 (34.3) | 7656 (38.3) | < 0.001 | 598 (27.7) | 2370 (32.1) | < 0.001 | 5186 (36.9) | < 0.001 | 4682 (38.4) | < 0.001 | 1434 (40.5) | < 0.001 | 685 (43.0) | < 0.001 | 1016 (31.1) | < 0.001 | 15,971 (36.1) |
| Diuretics | 8957 (37.0) | 9260 (46.3) | < 0.001 | 611 (28.3) | 2755 (37.3) | < 0.001 | 5802 (41.3) | < 0.001 | 5607 (45.9) | < 0.001 | 1592 (45.0) | < 0.001 | 785 (49.3) | < 0.001 | 1065 (32.5) | < 0.001 | 18,217 (41.2) |
| Thiazide diuretics | 906 (3.7) | 1347 (6.7) | < 0.001 | 33 (1.5) | 420 (5.7) | < 0.001 | 715 (5.1) | < 0.001 | 742 (6.1) | < 0.001 | 174 (4.9) | < 0.001 | 39 (2.4) | 0.045 | 130 (4.0) | < 0.001 | 2253 (5.1) |
| Loop diuretics | 7986 (33.0) | 7884 (39.4) | < 0.001 | 511 (23.7) | 2228 (30.2) | < 0.001 | 5063 (36.0) | < 0.001 | 4852 (39.8) | < 0.001 | 1552 (43.9) | < 0.001 | 724 (45.5) | < 0.001 | 940 (28.7) | < 0.001 | 15,870 (35.9) |
| Potassium sparing diuretics | 1112 (4.6) | 2457 (12.3) | < 0.001 | 110 (5.1) | 538 (7.3) | < 0.001 | 1387 (9.9) | < 0.001 | 1025 (8.4) | < 0.001 | 210 (5.9) | 0.203 | 175 (11.0) | < 0.001 | 124 (3.8) | 0.021 | 3569 (8.1) |
| CCB | 6280 (25.9) | 7913 (39.6) | < 0.001 | 596 (27.6) | 2457 (33.3) | < 0.001 | 4647 (33.0) | < 0.001 | 3761 (30.8) | < 0.001 | 1165 (32.9) | < 0.001 | 521 (32.7) | < 0.001 | 1046 (32.0) | < 0.001 | 14,193 (32.1) |
| Dihydropyridines | 6300 (26.0) | 6803 (34.0) | < 0.001 | 613 (28.4) | 2225 (30.1) | < 0.001 | 3910 (27.8) | 0.563 | 3716 (30.5) | 0.050 | 1135 (32.1) | < 0.001 | 490 (30.8) | < 0.001 | 1014 (31.0) | < 0.001 | 13,103 (29.6) |
| Non-dihydropyridines | 1265 (5.2) | 397 (2.0) | < 0.001 | 55 (2.5) | 246 (3.3) | 0.060 | 768 (5.5) | < 0.001 | 210 (1.7) | 0.010 | 198 (5.6) | < 0.001 | 39 (2.4) | 0.845 | 146 (4.5) | < 0.001 | 1662 (3.8) |
| Antidiabetics | 218 (0.9) | 16,685 (83.5) | < 0.001 | 814 (37.7) | 2968 (40.2) | < 0.001 | 4965 (35.3) | < 0.001 | 4596 (37.7) | 0.999 | 1552 (43.9) | < 0.001 | 816 (51.3) | < 0.001 | 1192 (36.4) | 0.331 | 16,903 (38.2) |
| Metformin | 0 | 9645 (48.3) | < 0.001 | 564 (26.1) | 1854 (25.1) | 0.347 | 2768 (19.7) | < 0.001 | 2454 (20.1) | < 0.001 | 1062 (30.0) | < 0.001 | 562 (35.3) | < 0.001 | 381 (11.6) | < 0.001 | 9645 (21.8) |
| Sulfonylurea | 0 | 2260 (11.3) | < 0.001 | 122 (5.7) | 477 (6.5) | 0.179 | 603 (4.3) | 0.003 | 602 (4.9) | 0.117 | 230 (6.5) | 0.224 | 144 (9.0) | < 0.001 | 82 (2.5) | < 0.001 | 2260 (5.1) |
| DPP4 inhibitors | 0 | 7682 (38.4) | < 0.001 | 323 (15.0) | 1288 (17.4) | < 0.001 | 2607 (18.5) | < 0.001 | 2178 (17.8) | < 0.001 | 556 (15.7) | 0.478 | 298 (18.7) | < 0.001 | 432 (13.2) | < 0.001 | 7682 (17.4) |
| SGLT-2 inhibitors | 0 | 401 (2.0) | < 0.001 | 23 (1.1) | 44 (0.6) | 0.015 | 82 (0.6) | 0.008 | 57 (0.5) | 0.001 | 135 (3.8) | < 0.001 | 44 (2.8) | < 0.001 | 16 (0.5) | 0.012 | 401 (0.9) |
| GLP-1 receptor agonists | 0 | 695 (3.5) | < 0.001 | 47 (2.2) | 104 (1.4) | 0.001 | 121 (0.9) | 0.001 | 223 (1.8) | 0.205 | 95 (2.7) | 0.242 | 53 (3.3) | 0.039 | 52 (1.6) | 0.107 | 695 (1.6) |
| Metiglinides | 0 | 2992 (15.0) | < 0.001 | 89 (4.1) | 390 (5.3) | < 0.001 | 1067 (7.6) | < 0.001 | 955 (7.8) | < 0.001 | 164 (4.6) | 0.373 | 69 (4.3) | 0.762 | 258 (7.9) | < 0.001 | 2992 (6.8) |
| Glitazones | 0 | 259 (1.3) | < 0.001 | 17 (0.8) | 5 (0.1) | 0.114 | 52 (0.4) | 0.010 | 68 (0.6) | 0.279 | 58 (1.6) | 0.010 | 33 (2.1) | 0.001 | 26 (0.8) | 0.999 | 259 (0.6) |
| Acarbose | 0 | 314 (1.6) | < 0.001 | 48 (2.2) | 53 (0.7) | < 0.001 | 36 (0.3) | < 0.001 | 75 (0.6) | 0.001 | 65 (1.8) | 0.290 | 35 (2.2) | 0.999 | 2 (0.1) | < 0.001 | 314 (0.7) |
| Insulin | 218 (0.9) | 4246 (21.2) | < 0.001 | 155 (7.2) | 719 (9.7) | < 0.001 | 1411 (10.0) | < 0.001 | 1256 (10.3) | < 0.001 | 376 (10.6) | < 0.001 | 213 (13.4) | < 0.001 | 334 (10.2) | < 0.001 | 4464 (10.1) |
| Statins | 11,160 (46.1) | 12,798 (64.0) | < 0.001 | 1140 (52.8) | 4014 (54.3) | 0.218 | 7734 (55.0) | < 0.001 | 6685 (54.8) | 0.006 | 1906 (53.9) | 0.419 | 879 (55.2) | < 0.001 | 1600 (48.9) | < 0.001 | 23,958 (54.2) |
| Warfarin | 2849 (11.8) | 3092 (15.5) | < 0.001 | 189 (8.8) | 921 (12.5) | < 0.001 | 1972 (14.0) | < 0.001 | 1728 (14.2) | < 0.001 | 504 (14.2) | < 0.001 | 205 (12.9) | < 0.001 | 422 (12.9) | < 0.001 | 5941 (13.4) |
| Low dose aspirin | 6045 (25.0) | 5499 (27.5) | < 0.001 | 446 (20.7) | 1792 (24.3) | < 0.001 | 3847 (27.4) | < 0.001 | 3198 (26.2) | < 0.001 | 1026 (29.0) | < 0.001 | 445 (28.0) | < 0.001 | 790 (24.1) | < 0.001 | 11,544 (26.1) |
| Receptor P2Y12 antagonists | 872 (3.6) | 1998 (10.0) | < 0.001 | 110 (5.1) | 469 (6.3) | 0.039 | 774 (5.5) | 0.446 | 919 (7.5) | < 0.001 | 274 (7.7) | < 0.001 | 171 (10.7) | < 0.001 | 153 (4.7) | 0.502 | 2870 (6.5) |
ACEi angiotensin-converting enzyme inhibitors, ARBs angiotensin receptor blockers, ARNI angiotensin receptor and neprilysin inhibition, BMI body mass index, CCB Calcium channel blockers; CVD: cardiovascular disease, CKD chronic kidney disease, DPP4 dipeptidyl peptidase 4, eGFR estimated glomerular filtration rate, a mL/min/1.73 m2, GLP-1 glucagon-like peptide-1, PAD peripheral artery disease, RAAS renin angiotensin system, SBP systolic blood pressure, SGLT-2 sodium-glucose Cotransporter-2, UACR Urine albumin-to-Creatinine Ratio