Introduction
Materials and methods
Study participants and corresponding study designs
AHTKV-α calculations and measurements of HtTKV slopes
Statistical analyses
Results
TKV and eGFR measurements
Comparisons of repeatability between AHTKV-α and measured HtTKV slopes
Characteristics of MIC and classifications using baseline AHTKV-α and baseline-measured HtTKV slope
Correlations of biomarkers with relevant clinical features
A | B | C | D | E | P value | |
---|---|---|---|---|---|---|
Range of biomarkers | ||||||
MIC based on AHTKV-α (%/year) | < 1.5 | 1.5–3.0 | 3.0–4.5 | 4.5–6.0 | ≥ 6.0 | |
Baseline AHTKV-α (%/year) | < 2.59 | 2.59–3.47 | 3.47–4.34 | 4.34–5.27 | ≥ 5.27 | |
Baseline-measured HtTKV slope (%/year) | < − 2.05 | − 2.05–2.9 | 2.9–6.85 | 6.85–11.1 | ≥ 11.1 | |
Patient number (male/female) | ||||||
MIC based on AHTKV-α | 11 (3/8) | 69 (19/50) | 112 (42/70) | 80 (36/44) | 24 (13/11) | 0.0893 |
Baseline AHTKV-α | 59 (16/43) | 59 (15/44) | 60 (25/35) | 59 (27/32) | 59 (30/29) | 0.0107 |
Baseline-measured HtTKV slope | 59 (14/45) | 59 (22/37) | 60 (27/33) | 59 (22/37) | 59 (28/31) | 0.0721 |
Baseline age (year) | ||||||
MIC based on AHTKV-α | 55.9 (10.5) | 49.6 (14.8) | 49.7 (13.3) | 40.5 (10.3) | 33.6 (7.7) | < 0.0001 |
Baseline AHTKV-α | 51.4 (14.3) | 50.8 (14.1) | 49.0 (13.4) | 43.7 (9.4) | 35.8 (10.0) | < 0.0001 |
Baseline-measured HtTKV slope | 49.3 (13.1) | 48.4 (14.4) | 43.8 (12.9) | 47.7 (13.5) | 41.5 (13.1) | 0.0061 |
Baseline TKV (mL) | ||||||
MIC based on AHTKV-α | 485.2 (237.2) | 814.0 (94.7) | 1634.4 (74.3) | 2150.2 (88.0) | 2518.3 (160.6) | < 0.0001 |
Baseline AHTKV-α | 694.6 (251.5) | 1221.8 (506.3) | 1745.7 (800.9) | 2053.0 (884.8) | 2340.2 (1150.1) | < 0.0001 |
Baseline-measured HtTKV slope | 1672.2 (943.5) | 1628.1 (1023.8) | 1540.9 (997.7) | 1760.2 (1011.0) | 1457.3 (903.0) | 0.4954 |
Baseline HtTKV (mL/m) | ||||||
MIC based on AHTKV-α | 308.1 (52.0) | 512.1 (225.3) | 1004.8 (459.5) | 1296.5 (652.8) | 1503.2 (629.4) | < 0.0001 |
Baseline AHTKV-α | 435.6 (163.7) | 765.8 (331.8) | 1066.4 (498.9) | 1243.6 (541.7) | 1403.7 (712.5) | < 0.0001 |
Baseline-measured HtTKV slope | 1040.2 (591.5) | 1000.2 (618.2) | 944.6 (628.5) | 1062.5 (602.2) | 869.7 (528.3) | 0.4023 |
Age at ADPKD diagnosis (year) | ||||||
MIC based on AHTKV-α | 53.5 (10.8) | 42.7 (12.7) | 41.0 (12.6) | 32.5 (8.9) | 24.0 (7.9) | < 0.0001 |
Baseline AHTKV-α | 45.5 (13.1) | 42.7 (13.8) | 39.0 (11.7) | 35.4 (9.0) | 27.6 (8.8) | < 0.0001 |
Baseline-measured HtTKV slope | 38.4 (13.5) | 40.6 (13.6) | 36.8 (11.5) | 38.6 (14.9) | 36.4 (11.1) | 0.4773 |
Age at onset of disease manifestations (year) | ||||||
MIC based on AHTKV-α | 49.8 (12.2) | 41.9 (13.5) | 40.4 (11.7) | 31.4 (9.1) | 25.4 (8.2) | < 0.0001 |
Baseline AHTKV-α | 44.2 (13.0) | 42.6 (12.6) | 38.6 (12.1) | 33.6 (9.8) | 27.9 (8.7) | < 0.0001 |
Baseline-measured HtTKV slope | 40.1 (13.7) | 39.5 (12.7) | 36.3 (12.8) | 36.7 (12.4) | 43.4 (11.5) | 0.1260 |
Age at onset of HTN (year) (n = 194) | ||||||
MIC based on AHTKV-α | 47.8 (11.8) | 46.4 (11.5) | 43.2 (10.7) | 35.0 (7.8) | 29.2 (6.8) | < 0.0001 |
Baseline AHTKV-α | 48.2 (12.5) | 44.7 (10.0) | 42.3 (10.7) | 36.4 (8.0) | 31.9 (8.1) | < 0.0001 |
Baseline-measured HtTKV slope | 44.4 (12.5) | 41.4 (10.1) | 40.4 (12.7) | 38.6 (10.4) | 36.6 (9.0) | 0.0192 |
Hypertensive patients, % (n = 267) | ||||||
MIC based on AHTKV-α | 55.6 | 64.6 | 86.5 | 77.3 | 95.5 | 0.0015 |
Baseline AHTKV-α | 58.9 | 82.4 | 88.7 | 81.5 | 81.1 | 0.0021 |
Baseline-measured HtTKV slope | 85.7 | 73.1 | 70.4 | 83.3 | 78.4 | 0.2445 |
Correlations of eGFR slopes with biomarkers
A | B | C | D | E | P value | |
---|---|---|---|---|---|---|
Patient number (male/female) | ||||||
MIC based on AHTKV-α (%/year) | 11 (3/8) | 69 (19/50) | 107 (41/66) | 78 (39/39) | 24 (13/11) | 0.1428 |
Baseline AHTKV-α (%/year) | 57 (17/40) | 58 (12/46) | 58 (25/33) | 58 (30/28) | 58 (31/27) | 0.0041 |
Baseline-measured HtTKV slope (%/year) | 57 (15/42) | 58 (24/34) | 58 (24/34) | 58 (24/34) | 58 (28/30) | 0.1815 |
Baseline age (year) | ||||||
MIC based on AHTKV-α | 55.4 (3.8) | 48.6 (1.5) | 48.1 (1.2) | 39.4 (1.4) | 33.1 (2.5) | < 0.0001 |
Baseline AHTKV-α | 49.8 (1.6) | 50.6 (1.7) | 48.4 (1.6) | 41.7 (1.6) | 34.5 (1.6) | < 0.0001 |
Baseline-measured HtTKV slope | 47.4 (1.8) | 46.1 (1.8) | 43.9 (1.8) | 46.5 (1.8) | 41.5 (1.8) | 0.1390 |
Baseline eGFR (mL/min/1.73 m2) | ||||||
MIC based on AHTKV-α | 87.5 (6.2) | 75.1 (2.5) | 66.5 (2.0) | 56.3 (2.4) | 47.4 (4.3) | < 0.0001 |
Baseline AHTKV-α | 78.4 (2.8) | 72.4 (2.8) | 65.7 (2.7) | 59.1 (2.7) | 50.2 (2.9) | < 0.0001 |
Baseline-measured HtTKV slope | 65.8 (3.9) | 65.8 (3.9) | 66.9 (3.9) | 62.2 (3.9) | 68.8 (3.9) | 0.8249 |
eGFR slope (mL/min/1.73 m2/year) | ||||||
MIC based on AHTKV-α | − 1.18 (0.41) | − 1.40 (0.12) | − 1.70 (0.10) | − 2.11 (0.14) | − 2.92 (0.27) | < 0.0001 |
Baseline AHTKV-α | − 1.19 (0.21) | − 1.64 (0.20) | − 1.78 (0.22) | − 2.41 (0.24) | − 2.27 (0.16) | < 0.0001 |
Baseline-measured HtTKV slope | − 1.98 (0.23) | − 1.69 (0.21) | − 1.42 (0.22) | − 1.32 (0.21) | − 1.74 (0.15) | 0.0181 |
Effects of sex and age on eGFR slopes
Renal survival analyses according to classifications based on two biomarkers
Classification | Range | Unit | Subjects (n) | Cox proportional hazard analysis | ||
---|---|---|---|---|---|---|
Multivariate HR | 95% CI | FDR-adjusted P value | ||||
MIC by AHTKV-α* | ||||||
1A + 1B | < 3.0 | %/year | 80 | 1 | ||
1C | 3.0–4.5 | 112 | 1.31 | 0.03–2.58 | 0.0443 | |
1D + 1E | 4.5 ≤ | 104 | 3.36 | 2.00–4.71 | < 0.0001 | |
Three equally divided subgroups for baseline AHTKV-α | ||||||
A | < 3.175 | %/year | 100 | 1 | ||
B | 3.175–4.53 | 98 | 1.62 | 0.46–2.79 | 0.006 | |
C | 4.53 ≤ | 98 | 3.49 | 2.26–4.73 | < 0.0001 | |
Three equally divided subgroups for baseline-measured HtTKV slope | ||||||
A | < 1.748 | %/year | 98 | 1 | ||
B | 1.748–7.91 | 99 | 0.11 | − 0.71–0.92 | 0.799 | |
C | 7.91 ≤ | 99 | − 0.62 | − 1.66–0.41 | 0.361 |
PKD genic and PKD1 allelic influences on AHTKV-α
Demographic data of 88 patients with pathogenic PKD mutations | All |
PKD1
|
PKD2
| P value |
---|---|---|---|---|
N (male/female) | 88 (34/54) | 77 (30/47) | 11 (4/7) | 0.8686 |
Age at baseline TKV measurement (year) | 47.4 (13.6) | 45.6 (12.6) | 60.0 (14.3) | 0.0008 |
TKV observation period (year) | 4.9 (2.0) | 4.76 (2.01) | 6.07 (2.01) | 0.0462 |
Baseline TKV (mL) | 1851.7 (1042.7) | 1901.3 (1056.0) | 1503.9 (912.2) | 0.2392 |
Baseline HtTKV (mL/m) | 1135.6 (641.2) | 1165.2 (651.1) | 928.4 (548.9) | 0.2542 |
Baseline eGFR (mL/min/1.73 m2) | 60.9 (31.8) | 61.6 (32.6) | 56.1 (26.4) | 0.5931 |
PKD genic influences on HtTKV growth biomarkers | All |
PKD1
|
PKD2
| *P value |
---|---|---|---|---|
Baseline AHTKV-α (%/year) | 4.19 (1.31) | 4.39 (1.26) | 2.79 (0.78) | < 0.0001 |
Baseline-measured HtTKV slope (%/year) | 4.55 (8.92) | 4.61 (9.04) | 4.16 (8.40) | 0.9950 |
PKD1 allelic influences on HtTKV growth biomarkers | All | Truncating-type | Nontruncating-type | *P value |
---|---|---|---|---|
N (male/female) | 77 | 49 (22/27) | 28 (8/20) | |
Baseline AHTKV-α (%/year) | 4.39 (1.25) | 4.71 (1.14) | 3.84 (1.27) | 0.0300 |
Baseline-measured HtTKV slope (%/year) | 4.61 (9.04) | 5.49 (9.30) | 3.06 (8.51) | 0.5491 |