Table 1.
Characteristics of recruits in the six groups at point of randomisation and after all rounds of HLA antibody re-screening.
| Group | DSA+ |
Non-DSA+ |
No HLA Ab |
Total (at Randomisation) | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Blinded (SC) |
Unblinded (BLC) |
Blinded (SC) |
Unblinded (BLC) |
Blinded (SC) |
Unblinded (BLC) |
||||||||
| A1a |
B1 |
A2 |
B2 |
C |
D |
||||||||
| Randomisation (N = 64) | Post-Screeningb (N = 92) | Randomisation (N = 71) | Post-Screening (N = 106) | Randomisation (N = 275) | Post-Screening (N = 391) | Randomisation (N = 280) | Post-Screening (N = 427) | Randomisation (N = 670) | Post-Screening (N = 526) | Randomisation (N = 677) | Post-Screening (N = 495) | ||
| Age (years) Mean (SD) | 49.5 (12.0) | 48.1 (13.7) | 47.0 (14.6) | 46.8 (14.0) | 50.0 (11.9) | 49.4 (12.7) | 50.6 (12.6) | 50.3 (12.6) | 50.3 (13.30) | 51.1 (12.7) | 50.5 (13.2) | 51.0 (13.3) | 50.2 (13) |
| Male (%) | 66% | 72% | 80% | 81% | 56% | 61% | 59% | 59% | 73% | 72% | 72% | 75% | 69% |
| Ethnicity (%) | |||||||||||||
| Asian | 9.4% | 9.9% | 14% | 12% | 13% | 12% | 13% | 14% | 11% | 11% | 13% | 13% | 12% |
| Black | 19% | 16% | 14% | 12% | 7.6% | 10% | 11% | 12% | 11% | 9.5% | 9.7% | 8.7% | 10% |
| White | 69% | 72% | 70% | 74% | 76% | 74% | 72% | 71% | 75% | 76% | 75% | 76% | 74% |
| Mixed | 1.1% | 1.1% | 0% | 0% | 1.5% | 1.5% | 1.4% | 0.9% | 0.6% | 0.4% | 0.1% | 0.2% | 0.7% |
| Other | 1.6% | 1.1% | 1.4% | 1.9% | 2.5% | 2.0% | 1.8% | 1.9% | 2.4% | 2.9% | 2.5% | 2.6% | 2.3% |
| Site [N (%)]c | |||||||||||||
| Leeds | 8 (2.7%) | 11 (3.8%) | 8 (2.7%) | 12 (4.1%) | 41 (14%) | 70 (24%) | 40 (14%) | 76 (26%) | 96 (33%) | 64 (22%) | 98 (34%) | 58 (20%) | 291 (14%) |
| Royal London | 6 (4.6%) | 8 (6.2%) | 5 (3.8%) | 8 (6.2%) | 11 (8.5%) | 17 (13%) | 12 (9.2%) | 18 (14%) | 48 (37%) | 40 (31%) | 48 (37%) | 39 (30%) | 130 (6.4%) |
| Guy's | 21 (4.0%) | 32 (6.0%) | 24 (4.5%) | 34 (6.4%) | 69 (13%) | 105 (20%) | 72 (14%) | 121 (23%) | 170 (32%) | 123 (23%) | 173 (33%) | 114 (22%) | 529 (26%) |
| Manchester | 8 (2.6%) | 12 (3.8%) | 8 (2.6%) | 9 (2.9%) | 44 (14%) | 50 (16%) | 47 (15%) | 54 (17%) | 103 (33%) | 93 (30%) | 102 (33%) | 94 (30%) | 312 (15%) |
| Birmingham | 3 (1.4%) | 5 (2.3%) | 2 (0.9%) | 12 (5.5%) | 31 (14%) | 47 (22%) | 27 (12%) | 42 (19%) | 77 (36%) | 59 (27%) | 77 (36%) | 52 (24%) | 217 (11%) |
| King's College Hospital | 6 (4.2%) | 8 (5.6%) | 4 (2.8%) | 5 (3.5%) | 21 (15%) | 29 (20%) | 21 (15%) | 28 (20%) | 44 (31%) | 34 (24%) | 47 (33%) | 39 (27%) | 143 (7.0%) |
| York | 2 (3.8%) | 4 (7.5%) | 2 (3.8%) | 4 (7.5%) | 6 (11%) | 9 (17%) | 7 (13%) | 16 (30%) | 18 (34%) | 13 (25%) | 18 (34%) | 7 (13%) | 53 (2.6%) |
| Coventry | 0 (0.0%) | 0 (0.0%) | 1 (1.9%) | 2 (3.8%) | 6 (11%) | 8 (15%) | 7 (13%) | 12 (23%) | 18 (34%) | 16 (30%) | 21 (40%) | 15 (28%) | 53 (2.6%) |
| Preston | 1 (1.5%) | 2 (3.1%) | 4 (6.2%) | 5 (7.7%) | 11 (17%) | 13 (20%) | 8 (12%) | 12 (19%) | 21 (32%) | 18 (28%) | 20 (31%) | 15 (23%) | 65 (3.2%) |
| Salford | 1 (1.9%) | 1 (1.9%) | 1 (1.9%) | 1 (1.9%) | 6 (12%) | 8 (15%) | 8 (15%) | 8 (15%) | 19 (37%) | 17 (33%) | 17 (33%) | 17 (33%) | 52 (2.6%) |
| Bradford | 3 (6.2%) | 3 (6.2%) | 5 (10%) | 7 (15%) | 8 (17%) | 8 (17%) | 9 (19%) | 12 (25%) | 12 (25%) | 12 (25%) | 11 (23%) | 6 (13%) | 48 (2.4) |
| Royal Free | 5 (4.0%) | 5 (4.0%) | 6 (4.8%) | 6 (4.8%) | 18 (14%) | 24 (19%) | 19 (15%) | 22 (18%) | 38 (30%) | 32 (26%) | 39 (31%) | 36 (24%) | 125 (6.1) |
| St Helier | 0 (0.0%) | 1 (5.3%) | 1 (5.3%) | 1 (5.3%) | 3 (16%) | 3 (16%) | 3 (16%) | 6 (32%) | 6 (32%) | 5 (26%) | 6 (32%) | 3 (16%) | 19 (0.9%) |
| Cause of renal failure [N (%)] | |||||||||||||
| DM | 4 (6.9%) | 5 (6.0%) | 2 (3.4%) | 7 (8.0%) | 7 (2.9%) | 17 (5.1%) | 13 (5.4%) | 22 (5.9%) | 38 (6.7%) | 27 (6.0%) | 40 (6.8%) | 26 (6.1%) | 104 (6.0%) |
| GN | 22 (38%) | 28 (34%) | 19 (33%) | 30 (34%) | 93 (39%) | 128 (38%) | 94 (39%) | 147 (40%) | 216 (38%) | 175 (39%) | 224 (38%) | 160 (38%) | 668 (38%) |
| PKD | 7 (12%) | 10 (12%) | 9 (16%) | 12 (14%) | 32 (13%) | 45 (14%) | 34 (14%) | 54 (15%) | 105 (19%) | 89 (20%) | 100 (17%) | 77 (18%) | 287 (16%) |
| Hypertension | 6 (10%) | 7 (8.4%) | 6 (10%) | 7 (8.0%) | 20 (8.3%) | 28 (8.4%) | 22 (9.2%) | 34 (9.2%) | 43 (7.6%) | 34 (7.6%) | 47 (8.0%) | 34 (8.0%) | 144 (8.2%) |
| Congenital | 7 (12%) | 13 (16%) | 7 (12%) | 10 (11%) | 31 (13%) | 41 (12%) | 22 (9.2%) | 34 (9.2%) | 66 (12%) | 50 (11%) | 47 (8.0%) | 32 (7.6%) | 180 (10%) |
| Obstructive | 8 (14%) | 12 (15%) | 10 (17%) | 16 (18%) | 38 (16%) | 50 (15%) | 34 (14%) | 48 (13%) | 54 (9.5%) | 38 (8.5%) | 80 (14%) | 60 (14%) | 224 (13%) |
| Other | 4 (6.9%) | 8 (9.6%) | 5 (8.5%) | 6 (6.7%) | 19 (7.8%) | 25 (7.5%) | 20 (8.3%) | 31 (8.4%) | 45 (8.1%) | 35 (7.7%) | 46 (7.9%) | 34 (7.9%) | 139 (8.1%) |
| Previous transplants [N (%)] | |||||||||||||
| 0 | 48 (76%) | 71 (78%) | 52 (73%) | 85 (80%) | 193 (71%) | 301 (77%) | 198 (71%) | 337 (79%) | 613 (92%) | 482 (92%) | 633 (94%) | 461 (94%) | 1737 (86%) |
| 1 | 12 (19%) | 17 (19%) | 18 (25%) | 20 (19%) | 71 (26%) | 79 (20.%) | 65 (23%) | 73 (17%) | 55 (8.2%) | 42 (8%) | 35 (5.2%) | 25 (5.1%) | 256 (12%) |
| 2 | 3 (4.8%) | 3 (3.3%) | 1 (1.4%) | 1 (0.9%) | 8 (2.9%) | 8 (2.1%) | 13 (4.7%) | 13 (3.1%) | 0 (0%) | 0 (0%) | 5 (0.7%) | 5 (1.0%) | 30 (1.5%) |
| 3 | 0 (0%) | 0 (0%) | 0 (0%) | 9 (0%) | 1 (0.4%) | 1 (0.3%) | 3 (1.1%) | 3 (0.7%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 4 (0.2%) |
| Time (years) since Tx Median (IQR) |
6.6 (3.0–12.0) | 5.9 (3.0–11.9) | 9.7 (3.9–14.3) | 6.7 (3.0–12.4) | 5.7 (2.2–10.9) | 5.4 (2.2–9.8) | 4.9 (2.3–11.2) | 5.1 (2.4–10.8) | 5.4 (2.4–9.2) | 5.4 (2.4–9.6) | 5.1 (2.4–9.7) | 5.1 (2.4–9.8) | 5.4 (2.4–10.3) |
| Immunosuppression | |||||||||||||
| CsA [N (%)] | 17 (27%) | 26 (28%) | 18 (25%) | 22 (21%) | 49 (18%) | 69 (18%) | 49 (18%) | 74 (17%) | 121 (18%) | 90 (17%) | 120 (18%) | 89 (18%) | 374 (18%) |
| Mean Dose [mg (SD)] | 170.3 (49.8) | 187.3 (62.8) | 199.4 (68.5) | 199.6 (63.6) | 168.6 (65.0) | 174.4 (62.5) | 168.7 (60.4) | 160.6 (58.9) | 180.7 (67.9) | 176.3 (67.8) | 168.7 (63.0) | 174.7 (62.9) | 174.1 (64.4) |
| Mean trough level [μg/L (SD)] | 72.3 (34.8) | 89.3 (56.2) | 80.9 (55.3) | 80.7 (51.5) | 102.8 (84.8) | 101.2 (79.8) | 88.6 (56.1) | 87.3 (52) | 100 (71.4) | 91.9 (52.3) | 109.6 (88.5) | 116.4 (97.2) | 99.9 (76) |
| Tac [N (%)] | 39 (61%) | 56 (64%) | 41 (58%) | 67 (64%) | 205 (75%) | 296 (76%) | 205 (73%) | 313 (73%) | 499 (74%) | 392 (75%) | 501 (74%) | 366 (74%) | 1490 (73%) |
| Mean dose [mg (SD)] | 6.14 (6.72) | 6.18 (5.97) | 4.01 (2.24) | 4.62 (3.33) | 5.08 (3.51) | 5.14 (3.66) | 5.60 (4.60) | 5.41 (3.73) | 5.50 (4.12) | 5.44 (4.13) | 4.89 (3.65) | 4.70 (3.15) | 5.23 (4.02) |
| Mean trough level [μg/L (SD)] | 6.49 (2.64) | 6.56 (2.86) | 5.65 (2.06) | 5.83 (2.18) | 6.95 (2.93) | 6.88 (2.74) | 6.86 (2.29) | 6.68 (2.21) | 6.91 (2.31) | 6.93 (2.26) | 6.71 (2.47) | 6.72 (2.52) | 6.79 (2.46) |
| MMF [N (%)] | 40 (63%) | 59 (64%) | 41 (58%) | 62 (59%) | 177 (64%) | 254 (65%) | 176 (63%) | 271 (63%) | 460 (69%) | 361 (69%) | 471 (70%) | 351 (71%) | 1365 (67%) |
| Mean dose [mg (SD)] | 1156 (476) | 1165 (482) | 1098 (422) | 1145 (399) | 1131 (450) | 1134 (457) | 1117 (483) | 1112 (472) | 1155 (490) | 1147 (495) | 1136 (466) | 1136 (473) | 1138 (473) |
| Aza [N (%)] | 15 (2.0%) | 19 (2.0%) | 19 (7.0%) | 26 (25%) | 52 (19%) | 66 (17%) | 39 (14%) | 61 (14%) | 90 (13%) | 71 (13%) | 94 (14%) | 69 (14%) | 309 (15%) |
| Mean dose [mg (SD)] | 88.3 (45.2) | 90.8 (43.5) | 69.7 (33.9) | 76.9 (32.3) | 76.7 (43.3) | 78.2 (40.8) | 86.5 (39.3) | 88.5 (39.4) | 85.3 (34.7) | 85.2 (33.4) | 85.1 (35.1) | 83.6 (35.9) | 83.1 (37.5) |
| Sirolimus [N (%)]d | 2 (3.1%) | 2 (2.2%) | 5 (7.0%) | 6 (5.7%) | 10 (3.6%) | 10 (2.6%) | 4 (1.4%) | 6 (1.4%) | 17 (2.5%) | 16 (3.0%) | 25 (3.7%) | 18 (3.6%) | 63 (3.1%) |
| Mean dose [mg (SD)] | 2.5 (0.71) | 2.5 (0.71) | 1.6 (0.55) | 1.5 (0.55) | 2 (0.82) | 2 (0.82) | 2 (0.82) | 2 (0.89) | 1.65 (0.70) | 1.62 (0.72) | 2 (0.91) | 2.06 (0.8) | 1.89 (0.81) |
| Prednisolone [N (%)] | 37 (58%) | 53 (58%) | 38 (54%) | 62 (59%) | 153 (56%) | 210 (54%) | 154 (55%) | 227 (53%) | 369 (55%) | 295 (56%) | 372 (55%) | 274 (55%) | 1123 (55%) |
| Mean dose [mg (SD)] | 4.97 (1.72) | 5.16 (1.81) | 4.97 (2.13) | 5.1 (1.87) | 4.99 (1.45) | 5.01 (1.39) | 4.99 (1.62) | 5.13 (1.53) | 5.08 (1.67) | 5.11 (1.75) | 5.2 (1.62) | 5.11 (1.43) | 5.08 (1.57) |
| Taking Tac/MMF/Pred [N (%)] | 13 (20%) | 19 (21%) | 13 (18%) | 24 (23%) | 82 (30%) | 114 (29%) | 70 (25%) | 106 (25%) | 192 (29%) | 152 (29%) | 189 (28%) | 139 (28%) | 559 (23%) |
| Renal function Creatinine (μmol/L) [Mean (SD)] |
128.97 (40.32) | 129.09 (39.30) | 124.96 (37.29) | 126.06 (38.25) | 123.23 (35.42) | 124.08 (35.23) | 122.61 (35.81) | 121.17 (35.25) | 126.17 (38.78) | 126.02 (39.71) | 126.73 (36.76) | 129.07 (36.96) | 125.52 (37.26) |
| eGFR (mls/min/1.73 m2) [Mean (SD)] | 52.31 (15.36) | 52.93 (15.23) | 56.27 (17.70) | 56.16 (18.01) | 52.12 (16.54) | 52.80 (16.39) | 52.89 (16.32) | 54.12 (17.30) | 53.77 (15.90) | 53.59 (15.95) | 53.76 (17.26) | 52.82 (16.57) | 53.46 (16.55) |
| PCRe (mg/mmol) [Median (IQR)] | 26.50 (15.50–48.25) | 26.50 (13.75–49.75) | 16.50 (10.75–39.25) | 23.50 (13.00–49.50) | 18.00 (8.00–37.25) | 18.00 (8.00–38.00) | 20.00 (9.00–42.50) | 19.00 (9.00–37.25) | 17.00 (9.00–41.25) | 17.00 (9.00–39.00) | 21.00 (10.00–41.00) | 21.00 (10.00–43.00) | 19.00 (9.00–41.00) |
| ACR (mg/mmol) [Median (IQR)] | 1.90 (1.40–1.95) | 2.00 (1.90–45.60) | 5.30 (2.75–7.85) | 2.30 (0.80–8.00) | 2.80 (1.30–6.30) | 2.80 (1.20–7.70) | 7.05 (3.13–15.10) | 6.40 (2.82–20.10) | 3.20 (1.20–9.22) | 3.20 (1.35–9.22) | 3.30 (0.95–10.20) | 2.55 (0.90–8.75) | 3.30 (1.30–9.60) |
DSA = donor specific antibody; HLA = human leukocyte antigen; Ab = antibody; SC = standard care; BLC = biomarker led care; SD = standard deviation; GSTT = Guy's & St Thomas' NHS Foundation Trust; DM = Diabetes mellitus; GN = glomerulonephritis; PKD = polycystic kidney disease; IQR = interquartile range; CsA = ciclosporin; Tac = tacrolimus; MMF = mycophenolate mofetil; Aza = azathioprine; eGFR = estimated glomerular filtration rate (by 4 value Modification of Diet in Renal Disease formula); PCR = urinary protein creatinine ratio; ACR = albumin creatinine ratio.
a
Group nomenclature refers to Supplementary Fig. S1.
b
Post-screening refers to status following movement from HLA Ab-negative to the HLA Ab+ groups; with reference to the immunosuppression data for groups B1 and B2, this table shows values prior to optimization.
c
For full names of recruiting NHS trusts see Supplementary File.
d
Three patients in the blinded SC group were taking Everolimus, with a mean ± SD dose of 2.33 ± 0.58 mg/L. These patients are not included here.
e
According to centre preference, patients had either PCR or ACR measured, not both.